Controlled overpressure cisternography to localize cerebrospinal fluid rhinorrhea. Cerebrospinal fluid (CSF) rhinorrhea is often intermittent, thus complicating the cisternographic localization of the leakage. In four patients studied, this difficulty was overcome by lumbar infusion of artificial CSF to which a bolus of radionuclide was added. The tracer was moved in bulk to the basal cisterns, and the rise in CSF pressure elicited a profuse rhinorrhea. Sequential imaging was started during the infusion, and prompt identification of the site of leakage was easily obtained. Special precautions must be followed when this technique of overpressure is used.


Analysis of homatropine methylbromide dosage forms. A stability-indicating method of analysis of homatropine methylbromide in pharmaceutical formulations was developed. This method is based on the formation of a picric acid-quaternary ammonium complex, which is adsorbed on acid-washed diatomaceous earth in alkaline media followed by on-column chloroform extraction. The picrate complex is measured spectrophotometrically at 365 nm. The method was selective for homatropine methylbromide in that there was no interference from its major hydrolytic decomposition products, tropinium methylbromide and mandelic acid.


Invasion of lymphosarcoma cells into the perfused mouse liver. Liver of (C57BL X DBA)F1 mice were perfused in situ with a synthetic hemoglobin-free medium, to which murine lymphosarcoma cells were added. All cells were arrested. They were only found in the sinusoids, predominantly in periportal areas. Many lymphosarcoma cells penetrated the walls of the sinusoids with protrusions that extended into and through the endothelial cells. The protrusions often also invaded hepatocytes, and some cells migrated out of the sinusoids. The percentage of the cells that penetrated endothelium was constant and reproducible (68 +/- 4%) in experiments lasting longer than 90 minutes, but the percentage of these cells that also invaded hepatocytes varied greatly. Parellel experiments in vivo yielded similar results, except that the number of cells that invaded hepatocytes was generally much lower. The advantages of the perfused liver as a model for experimental study of the invasion mechanism were evaluated.


Detection of breast cancer in young women. The method of discovery of breast tumors in young women was determined for 106 patients less than 45 years of age treated for breast cancer from 1967 through 1975. The patients detected 84% of the tumors themselves. Physical examinations by physicians detected 14% of the tumors. Two percent were noted on mammography in the absence of clinical findings. Fifty-two patients had roentgenographic examination of their breasts prior to biopsy. Sixty-three percent of these examinations failed to demonstrate the cancer. The report of a normal roentgonogram contributed to a decision to defer surgical treatment in 15 instances. These 15 patients had more advanced tumors at operation.


The breast cancer controversy. A natural experiment. The number and types of breast lesions treated surgically at the Flower and Fifth Avenue Hospitals during the period from November 1974 through February 1976, increased sharply in monthly incidence as compared with the period from January 1973 through October 1974. This increase was attributable to public awareness of breast cancer because of the publicity given to its occurrence in the wives of the President and Vice-President. However, the consequent increase in mammography and breast surgery was not accompanied by any improvement in the stage characteristics of the breast cancers treated. The proportion of prognostically unfavorable stage II cases with involvement of four or more axillary nodes was undiminished, while the proportion of stage 0 and stage I cases was not increased among breast cancers diagnosed since Nov 1, 1974.


An appraisal of the criteria of cerebral death. A summary statement. A collaborative study. Based on the findings in a collaborative study of 503 comatose and apneic patients, the establishment of cerebral death requires (1) that all appropriate examinations and therapeutic procedures have been performed, (2) that cerebral unresponsivity, apnea, dilated pupils, absent cephalic reflexes, and electrocerebral silence be present for 30 minutes at least six hours after the ictus, and (3) that if one of these standards is met imprecisely or cannot be tested, a confirmatory test be made to demonstrate the absence of cerebral blood flow. This would allow the diagnosis of a dead brain to be made in patients with small amounts of sedative drugs in the blood, In patients undergoing therapeutic procedures that make examination of one or more of the cranial nerves impossible, and in patients otherwise meeting the criteria whose pupils are small.


Decline in duodenal ulcer surgery.

Decline in duodenal ulcer surgery. The number of perforated duodenal ulcers at five Seattle-area hospitals and all duodenal ulcer operations performed at three Seattle-area hospitals were studied. In the past ten years, a decline of 35% in both perforated duodenal ulcers and all duodenal ulcer surgery indicates a similar decline in the overall incidence of duodenal ulcer. These data are supported by articles in the literature, which report a declining incidence of duodenal ulcer beginning around 1955 and continuing for 20 years. This decline challenges the idea that duodenal ulcer results chiefly from the stresses of urbanization.


Prednisone-responsive congenital erythroid hypoplasia. A 24-year-old woman had congenital hypoplastic anemia (Blackfan-Diamond syndrome). Anemia was discovered at the age of 12 months and persisted thereafter. The patient had associated congenital abnormalities of urethral stricture, hypoplastic thumb, and absent radial pulse. Her erythroid hypoplasia responded favorably to treatment with prednisone.


Legal abortion mortality in the United States. Epidemiologic surveillance, 1972-1974. As determined by the Center for Disease Control's epidemiologic surveillance of abortion mortality, the death-to-case rate for legal abortion in the United States for the three years 1972 to 1974 was 3.9/100,000 procedures. This mortality compares favorably with that from other commonly performed surgical procedures. Women who were older, were of nonwhite races, had the procedure in their state of residence, were at later gestational age, and who underwent intrauterine instillation or major abdominal surgery had the highest mortality. Duration of pregnancy proved to be the most important determinant of risk. Compared to mortality from pregnancy and childbirth, legal abortion in the first trimester was almost nine times safer.


Type B botulism outbreak caused by a commercial food product. West Virginia and Pennsylvania, 1973. In the week of May 7, 1973, seven persons contracted botulism after eating together. The most common symptoms were vomiting, constipation, dry mouth, dysphagia, and dysphonia. All were treated with trivalent botulinal antitoxin, and none died. Serum specimens obtained from all seven patients were negative for botulinal toxin, but stool specimens from three patients were positive for type B toxin. Electromyographic studies performed on five patients documented the neurophysiologic abnormalities of botulism. Commercially canned peppers in oil were implicated epidemiologically, and type B toxin was identified in leftover peppers. The processor voluntarily recalled the pepper product, and no further cases were reported.


Volvulus of the spleen.

Volvulus of the spleen. Volvulus of the spleen in absence of malarious splenomegaly is rare. Most reported instances occur in young and middle-aged women and are related to a congenital abnormality of the mesogastrium, pregnancy, and multiparity. In this reported case of splenic volvulus in a young, multiparous woman, posterior mesogastrium malformation was the cause. Certain preoperative findings could suggest this infrequent diagnosis in future cases.


Patient survival and instrument performance with permanent cardiac pacing. Among 313 patients who received cardiac pacemakers between 1961 and 1973, there was a 65% survival rate after five years, a progressive decrease in premature pulse generator failures, and a low, stable incidence of electrode malfunction. Decreased survival among more recently paced patients was attributed to an evolution of the selection for pacing that favored older patients with associated diseases. Death due to unexpected pacing failure was extremely rare. Premature pulse generator failures decreased from 0.8 per 100 pacing months among early units to 0.06 per 100 months among units implanted during 1971 to 1973, when a prophylactic replacement policy was in effect. Electrode revisions were required at a frequency of 0.5 to 0.8 per 100 months in both epicardial and endocardial systems. Electrode failures may limit the predictive value of surveillance systems, since these rely on a change of pacing frequency or pulse width to indicate battery depletion.


Amikacin therapy for serious gram-negative infection. Amikacin sulfate was administered to 18 patients for the treatment of 19 severe infections. Seventeen infections were caused by gentamicin-resistant Gram-negative bacilli, and 13 patients were bacteremic. Bacteriologic cure was attained in all but one instance, and effective serum, bile, and pleural fluid drug levels were demonstrated. Drug-related fever occurred in one patient, and another experienced a maculopapular rash and monilial intertrigo. In three patients, reversible renal toxicity developed, but none had clinical evidence of ototoxicity. Amikacin sulfate in a dose of 15 mg/kg/day is an effective antibiotic for the treatment of serious Gram-negative infections, particularly those due to gentamicin-resistant organisms.


Changing social-sexual patterns in gynecologic practice. One hundred randomly selected patients from the outpatient Gynecology Unit of the University of California at San Francisco Medical Center were interviewed to determine current attitudes toward reproductive and sexual roles. Major areas of change apparent in the younger population were a substantial decrease in formal marriage, a reduction in the wish for children, a movement away from oral contraception back to mechanical barrier methods, and an attitudinal shift toward acceptance of a bisexual adaptation. It is important for the practicing physician to be responsive to the life-style pattern present in the new generation of women patients.


Unsuccessful treatment of staphylococcal endocarditis with cefazolin. Two patients with staphylococcal endocarditis were treated unsuccessfully with cefazolin sodium. One patient relapsed after 52 days of therapy. The second patient had concomitant central nervous system infection and failed to respond to cefazolin therapy. Both patients recovered with methicillin sodium or nafcillin sodium therapy. Other studies report unsuccessful therapy of staphylococcal endocarditis with cefazolin.


Insulin in the management of the diabetic surgical patient: continuous intravenous infusion vs subcutaneous administration. A prospective randomized study comparing constant intravenous infusion of regular, low-dose insulin versus conventional subcutaneous administration of neutral protein Hagedorn (NPH) insulin in insulin-requiring patients undergoing orthopedic procedures under general anesthesia was undertaken. The degree of diabetic control was better in those receiving constant 2 units/hour of regular insulin than in those receiving two thirds of daily maintenance doses of NPH insulin. However, in two of eight patients receiving 2 units/hour, decreased insulin infusion rates and increased dextrose infusion rates were required to avoid hypoglycemia. Preoperative NPH insulin and 1 unit/hour insulin administration resulted in equivalent diabetic control.


One-view follow-up mammogram. Efficacy in screening for breast cancer. To determine whether one-view mammography would be sufficiently diagnostic, 106 cases of breast cancer diagnosed by film mammography or xeromammography were reviewed independently by two radiologists. Detection rates were analyzed for the lateral view, the craniocaudal view, and then both views combined. The lateral projection resulted in an accuracy rate of 97%. Errors in false-negative reports in either projection were traced to their source.


A diagnostic index of clinical practice. In this method of accural of medical data by clinicians, entry and retrieval of information is facilitated by directly recording patient data in diagnostic categories according to the familiar anatomical organ system classification instead of a numerical code. The diagnostic index is kept in looseleaf form, with tabulation of the patient's name, chart number, diagnosis, and other conditions present. Certain diagnoses are frequent enough to warrant insertion in a separate column of the page or on a separate page under the appropriate organ system. Special pages are used for diagnostic procedures, deaths, perplexing problems, and complaints, making it possible to assemble all pertinent data derived from ambulatory or hospital practice. This system allows any physician access to his own clinical experiences with minimal effort.


Surfing injuries At waikiki.

Surfing injuries At waikiki. A 56-month survey of 36 hospitalized patients injured while surfing off Oahu, Hawaii, indicated that 34% of the injuries involved the head and spine. Bodysurfing involves a considerable risk of craniospinal injury if the head is driven into the sand. The most frequent injury in surfboarding is being hit by a loose board. Risk of injury in surfboarding is approximately one per 17,500 surfing days--an incidence far below most sports.


Cancer and the coroner.

Cancer and the coroner. There exist few reports concerning cancer presenting in forensic autopsies. This study of 1,300 consecutive forensic autopsies yielded 22 cases of single cancers (1.7%) of multiple primary sites and histologic types. The forensic autopsy affords unique opportunity to study not only diagnosed and treated trauma, disease, and cancer, but the natural evolution of untreated cancer as well. Clinically occult cancer is not uncommon and may eventually present clinically or at autopsy in unusual fashion. Advanced cancer may, sometimes on initial presentation, be responsible for sudden unexpected death. Persons with cancer, even in an advanced state, uncommonly commit suicide. Conversely, those committing suicide ostensibly because of known cancer infrequently prove to have cancer at autopsy. Through these autopsy studies, the forensic pathologist gains information invaluable for statistical, clinical, and medicolegal purposes, truly fulfilling his role of "community pathologist".


Tuberculosis transmission in a large urban jail. Following diagnosis of moderately advanced tuberculosis in an inmate of Cook County Jail, tuberculin testing was performed to assess the degree of transmission of tuberculosis within the jail. Twenty-three percent of inmates exposed to the index patient were initially found to be tuberculin positive. Subsequent tuberculin testing three months later demonstrated a 71% rate of skin-test conversion in previously tuberculin-negative inmates exposed to the index patient. The rate of infectivity of tuberculosis within a jail is analogous to a household situation. Despite major obstacles, modern programs of tuberculosis screening and treatment are essential in correctional institutions.


Room humidifiers as the source of Acinetobacter infections. Twenty-four patients contracted systemic infections with Acinetobacter calcoaceticus during a four-month period. Unheated room humidifiers at the patients' bedsides were implicated as the source of infection in six. The outbreak was terminated with the removal of the humidifers.


Hereditary spherocytosis and glucose-6-phosphate dehydrogenase deficiency. The first reported case of hereditary spherocytosis (HS) and glucose-6-phosphate dehydrogenase deficiency in a black is presented. The recent literature is reviewed, with emphasis on the frequency of multiple inherited RBC defects in this ethnic group. Despite a coexisting hemoglobinopathy or enzyme deficiency, HS can be diagnosed in most cases by the peripheral blood smear, osmotic fragility curve, and family history. The implications of the double RBC abnormality are discussed, stressing the importance of splenectomy in relieving the hemolytic component due to spherocytosis.


Coagulation abnormalities in women taking oral contraceptives. Thirteen asymptomatic women taking oral contraceptives (OCs) were compared with normal subjects. Platelet aggregation and serotonin (tagged with carbon 14) release with adenosine diphosphate, epinephrine, and collagen did not differ from controls. Activation of the intrinsic coagulation pathway was evaluated by measurements of factor XII, prekallikrein, and kallikrein inhibitors. Women taking OCs had normal factor XII levels, moderately elevated prekallikrein levels, and decreased kallikrein inhibitor levels, a pattern not consistent with activation of the intrinsic pathway. The concentration of heavy molecular weight fibrinogen derivatives (HMWFD) was significantly elevated (P less than .001). In contrast, fibrin and fibrinogen degradation products in serum were lower than normal (P less than .05). The increased HMWFD concentration may reflect activation of the coagulation system not mediated by factor XII activation nor potentiated by decreased antithrombin III. Thus, plasma coagulation abnormalities rather than platelet changes may be the factor that predisposes women taking OCs to thromboembolic disorders.


Drug-related deaths among medical inpatients. Among 26,462 carefully monitored medical inpatients, 24, or 0.9 per 1,000, were considered to have died as a result of a drug or group of drugs. Most of the patients were seriously ill prior to the event that caused death. Six of the deaths-five from fluid overload and one from excessive potassium therapy-may have been preventable.


Cooperative study of hospital frequency and character of transient ischemic attacks. I. Background, organization, and clinical survey. To better understand transient ischemic attacks (TIA), all patients (1,328) with TIA-like symptoms were identified at six participating institutions representing known variations in geography, referral patterns, and socioeconomic status. A total of 954 patients were observed for a mean of 14.3 months. Problems in diagnosis are defined, demographic information is summarized, and features of the histroy, examination, tests, and treatments are noted.


Multiphasic screening. Case-finding tool in a Teaching Hospital Medical Clinic. Multiphasic screening as a case-finding tool was evaluated in a randomized, controlled study. For each of 112 physicians, a patient was assigned to one of three groups: multiphasic screening group (SG), chart abstract group (AG), or chart review group (RG). Medical problem lists constructed before and after receiving additional information were compared. Physicians for 36 SG patients identified considerably more new medical problems, both total (77) and ones they considered important (25), than 40 AG physicians (14 and 8) and 36 RG physicians (4 and 0). One year later, 38 of the 95 newly identified problems had been acted on, 31 in the SG. Medical care was affected in nine patients: six in SG, two in AG, and one in RG. Multiphasic screening may help physicians identify new medical problems in clinic patients.


Retropsoas and subgluteal abscesses following paracervical and pudendal anesthesia. Retroperitoneal abscesses are uncommon in obstetrics and gynecology. Recently, seven reported cases of retropsoas-subgluteal abscesses following paracervical-pudendal anesthesia have been reported, and we have seen two additional cases. The infrequent occurrence and diagnostic difficulties make these abscesses especially dangerous. They can result in substantial patient morbidity and mortality. They must be suspected in patients receiving paracervical-pudendal anesthesia prior to vaginal delivery in whom hip pain subsequently develops. Therapy consists of prompt surgical exploration and drainage and appropriate antibiotic therapy.


Expansion pattern of terminal air-spaces in the premature rabbit lung after tracheal deposition of surfactant. The expansion pattern of the lungs of full-term and premature newborn rabbits was evaluated by direct observation of the lung surface during an inflation-deflation cycle, with particular reference to the effect of tracheal deposition of surfactant before the first breath. In non-treated premature fetuses, aeration of alveoli was initiated at an endotracheal pressure of 35 cm H2O; the mean corresponding 'opening pressure' was 25 cm H2O in both full-term and surfactant-treated premature animals. The process of alveolar aeration was asynchronous in all groups but at maximal inflation pressure (35 cm H2O) the expansion pattern was uniform in full-term and surfactant-treated premature fetuses; these animals also developed residual volume. In non-treated premature animals aeration was patchy, even at maximal inflation, and the lungs emptied at the end of deflation.


[The 2nd saccoradiculography: changes in the post-radiculographic and postoperative radiological morphology (340 cases apropos of 2,292 files)]. A study was made of the files 2292 patients examined by sacco-radiculography with watersoluble contrast medium, of whom 340 had been subjected to a second examination. 284 of these had undergone surgery with good results during the interval between the two examinations. In 56 cases, repeat sacco-radiculography was carried out but no operation performed. In both groups of patients a semiological study was made of the radiological appearances to determine which were the effects of the contrast medium and which could be attributed to the operation. The paper concludes with  a discussion of the problem of genuine and false albuminoachies of sacco-radiculography using meglumine locarmate (dimer-X).


[Taxonomic studies on aeromonads of milk, water and minced meat (author's transl)]. 365 aeromonads isolated from milk, water and minced meat were tested in 24 biochemical characters. By application of a numerical method the material was devided into two subgroups. The properties of these subgroups are not in accordance with the definitions of species and subspecies of the taxonomical system of Aeromonas as it is accepted at present. With regard to the priority of the name A. punctata it is suggested to make use of only this name till the real combinations of characters and the resulting arrangement of groups are cleared to a better degree.


Prolactin levels in the insulin tolerance test with and without pre-treatment with dexamethasone. The serum prolactin response to insulin-induced hypoglycaemia was studied in 20 healthy volunteers. The results of insulin tolerance tests performed after pre-treatment with dexamethasone in a dose of 0.5 mg (0.5-DEX-ITT) and 1.0 mg (1.0-DEX-ITT) were compared with those of a similar control insulin tolerance test (ITT). The serum prolactin levels increased in all but 3 ITT's. In the ITT and 0.5-DEX-ITT the prolactin responses were significantly greater in women than in men. After pretreatment with dexamethasone the basal serum prolactin levels and the prolactin response to hypoglycaemia were significantly decreased compared with those in the ITT. The prolactin response both to insulin-induced hypoglycaemia and to dexamethasone showed such a large individual variation that this type of response seems unsuitable for evaluation of the hypothalamo-pituitary function.


Progesterone treatment increases pituitary oestradiol retention in the ovariectomized normal female rat but not in the male nor in the androgen- or oestrogen-sterilized female rat. Pituitary retention of [3H] oestradiol in ovariectomized rats was measured following in vivo progesterone pre-treatment and found to be significantly increased after 48, 72, 96 and 120 h of pre-treatment. Increased [3H]-oestradiol retention was also observed for at least up to 72 h after removal of the progesterone pre-treatment source. This retention was measured as DPM per mg dry tissue weight. [3H] Oestradiol retention was also measured in the  nuclear fraction of tissues incubated with [3H]-oestradiol in vitro. Following 72 h of in vivo progesterone pre-treatment, the nuclear fraction from the pituitary was found to retain significantly more [3H]oestradiol than corresponding fractions from non-treated animals. In contrast to ovariectomized females, no increase in [3H]oestradiol retention was found in the pituitary of orchidectomized males pre-treated with progesterone for 72 h. [3H]Oestradiol retention by pituitaries of ovariectomized rats injected on the day of birth with 200 mug oestradiol benzoate (OeB) or 500 mug testosterone propionate (TP) was significantly decreased in comparison to control animals. When the rats were pre-treated in vivo with oestradiol for 6 or 72 h and [3H]oestradiol retention was measured 6 or 24 h after this pre-treatment, the OeB and TP treated animals retained significantly less [3H]oestradiol under most treatment conditions. Progesterone pre-treatment for 24 or 72 h in vivo followed by measurement of [3H]oestradiol retention immediately or 6 or 24 h later resulted in a significant increase in [3H]oestradiol retention for the control animals. In contrast, the neonatally OeB or TP treated animals differed significantly by not showing increased retention. When [3H]oestradiol retention of the pituitary was measured in vitro following homogenization at 0 degrees C and incubation at 37 degrees C for 1 h, the nuclear fraction from both OeB and TP treated animals was found to retain less hormone per unit DNA; however, this decrease was significant only for the TP animals. Thus, males and androgen- or oestrogen-sterilized females have an altered and reduced augmentation of pituitary oestradiol retention in response to both oestrogen and progesterone pre-treatments.


Secretion of thyroxine, 3,5,3'-triiodothyronine and 3,3'5'-triiodothyronine in euthyroid man. The secretion of iodothyronines from the normal human thyroid gland was assessed by radioimmunoassay analyses of the concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (reverse T3, rT3) in thyroid venous and peripheral venous blood. The subjects studied were euthyroid patients undergoing parathyroid surgery. Measurements were carried out both under apparently normal conditions, following peroral T3 pre-treatment, and before and after acute administration of TSH into a thyroid artery. In the control subjects, significant gradients between thyroid venous and peripheral venous concentrations were recorded both for T4, T3 and rT3, suggesting that all three iodothyronines are secreted by the normal human thyroid. T3 pre-treatment seemed to reduce this secretion, and acute administration of TSH promoted rapid, marked, and concomitant increments in the thyroid venous concentrations of all three iodothyronines. Hence, it appears that not only T4 but also T3 and rT3 are secreted by the normal human thyroid gland, and that TSH stimulates the secretion of all three iodothyronines. On the other hand, calculations of the relative secretion rates uielded the relation T4:T3:rT3 as 85:9:1. This indicates that, in euthyroid subjects, most of T3, and almost all of rT3, is produced by extrathyroidal conversion of T4 and not by direct thyroidal secretion.


Effect of increased iodide intake on thyroid function in subjects on chronic lithium therapy. Thyroid function tests were obtained in 10 patients on chronic lithium therapy before and after the administration of potassium iodide 250 mg q.i.d. Mean serum TSH rose by 8.9 muU/ml and mean serum T3 rose from 70 to 101 ng/dl. Two patients became hypothyroid; a third showed a rise in TSH without any change in T3 or T4. A fourth patient developed hyperthyroidism probably secondary to the Jod-Basedow phenomenon. Pharmacologic doses of iodine should be administered with caution to patients on chronic lithium therapy.


A microgel electrophoretic analysis the colloid in single rat thyroid follicles during thyroxine suppression. A sequential study of the effect of thyroxine (T4) on the protein composition of the colloid in the rat thyroid gland has been carried out in 24 rats. Daily ip injections of 20 mug thyroxine were given and the colloid was analyzed after 1, 2, 3 and 4 days and 1, 2 and 3 weeks. The protein constituents were separated by microgel electrophoresis and measured by microdensitometry. The incorporation of [3H]leucine into the thyroglobulin fraction and into the albumin-like protein in the homogenate of the gland was analyzed after T4 suppression for 2 days. The 2 h thyroidal iodine uptake was analyzed during the first week of T4 administration. During the second and the third day of T4 administration, the amount of 27S and larger complexes of thyroglobulin was reduced by 30-40 per cent and the amount of the albumin-like protein was significantly increased and present in almost all samples. Preliminary data indicated that during the same period the relative amount of [3H]leucine activity was increased in the albumin-like protein fraction compared to the thyroglobulin fraction in the thyroid. It is concluded that the exocytotic vesicles contain the albumin-like protein. The results further indicate that the administration of T4 temporarily changes the relative rates of formation of thyroglobulin and of the albumin-like protein in the follicle.


Bone mineralization and bone mineral content in primary hyperparathyroidism. The degree of bone mineralization and the bone mineral content (BMC) was evaluated in 6 patients with primary hyperparathyroidism. The degree of bone mineralization was estimated as the phosphorus/hydroxyproline ratio (P/Hypro) in bone biopsies; BMC was estimated by photon absorptiometry on both forearms. The mena values of both parameters were significantly lower than normal (P less than 0.001 for P/Hypro; P less than 0.02 for BMC). As no significant correlation was found between P/Hypro and BMC in hyperparathyroidism, the findings of low values of P/Hypro and of BMC in patients with elevated serum calcium point to primary hyperparathyroidism.


The plasma concentrations of testosterone and LH during the ovulation cycle of the hen (Gallus domesticus). The plasma concentrations of testosterone and luteinizing hormone (LH) were measured by radioimmunoassay during the ovulation cycle of the hen. The baseline concentrations of testosterone were 100 to 250 pg/ml and the maximum concentration of 904 pg/ml was observed 6 h before ovulation. The possibility that testosterone is the ovarian excitation hormone which initiates the ovulation-inducing surge of LH is discussed.


Anti-oestrogen action: uterine nuclear retention of the CI-628 anti-oestrogen receptor complex in vitro. Experiments were performed in vitro which compared the nuclear retention of the anti-oestrogen receptor complex formed by CI-628 and the nuclear retention of the oestrogen receptor complex formed by oestradiol-17beta. Uterine nuclei retained the CI-628 receptor complex regardless of whether uterine incubations were carried out in the continued in fresh medium. However, for oestradiol-17beta there was a rapid decrease in the amount of receptor complex retained in the nucleus with time. When extractions using KCI were performed on nuclei after maximal accumulation of receptor complex by oestradiol-17beta or CI-628 the oestrogen receptor complex was found to have a higher relative nuclear affinity than did the CI-628 receptor complex. These studies suggest different nuclear binding sites for these complexes.


Mammotrophic activity in rat amniotic fluid. Mammotrophic activity was present in rat amniotic fluid collected on days 13, 15 and 19 of pregnancy. The mammotrophic activity in the fluid was equivalent to that in the maternal serum on day 15, but is was lower on day 19. The effect of tha amniotic fluid was similar to that of human placental lactogen on the rat mammary gland in vitro. The prolactin concentration in the amniotic fluid was low (approximately 1 ng/ml).


Prevention by melatonin of short day induced atrophy of the reproductive systems of male and female hamsters. Male and female hamsters were exposed to natural photoperiodic and temperature conditions beginning on November 13 and groups of hamsters were necropsied either on January 15 or on April 10. Throughout the study, half of the hamsters (control hamsters) received subcutaneous implants of beeswax (25 mg) every other week while the other half received beeswax pellets containing 1 mg melatonin. Control beeswax-treated males necropsied in January had atrophic testes and accessory sex organs while the uteri of the control females were infantile in appearance. Melatonin treatment prevented the atrophic responses of the testes and accessory sex organs in males and the uteri in females. Melatonin-treated hamsters killed in January also had higher plasma levels of immunoreactive LH while in females both pituitary and plasma levels of LH were elevated after melatonin treatment. By April 10, the testes and accessory organs of control males and the uteri of control females had regenerated to the adult condition and these organs were comparable in size to those in melatonin-treated hamsters. The pituitary glands of control males contained slightly more LH and much more FSH than the pituitaries of melatonin-treated males. Melatonin-treated females necropsied in April had pituitary and plasma levels of LH and FSH similar to those in beeswax-treated females killed at the same time. The data show that chronic melatonin treatment prevents atrophy of the reproductive organs of male and female hamsters which is associated with the shortened days of the winter.


Michaëlis--Menten kinetics of phenazone elimination in the perfused pig liver. The purpose of the present study was to define the elimination kinetics of phenazone (NFN) in the isolated perfused pig liver. In five experiments phenazone was administered as constant infusion to obtain steady-state periods over a wide range of concentrations. The elimination of phenazone followed saturation kinetics (concentrations 0.1-12 mmol x 1(-1) and the maximal elimination rate (Vmax) was on average 102 mumol x min-1 x kg-1 liver and the Michaëlis-constant (Km) of 2.6 mmol x 1(-1). Estimates of Vmax and Km for the microsomal phenazone hydroxylase activity measured in liver biopsies found to be considerably lower than in the perfused liver. The hepatic elimination of phenazone during perfusion of pig liver at phenazone concentrations corresponding to human therapeutic doses follows first-order kinetics.


The influence of lithium on water binding ability, consistency and macromolecules in the rat brain. Wistar male rats were treated with lithium for 50, 80, and 120 days, respectively. Lithium was added to the diet (40 mmol/kg of diet), the plasma lithium concentration being in the range of 0.55-0.70 mmol/1 of plasma. The treatment caused a significantly more rigid consistency of the brain tissue. The water content and water binding ability in various parts of the brain - measured by a drying course - was unchanged. The content of hexosamine and protein in total brains was significantly decreased (about 10 per cent) after the treatment. The content of chondroitin sulphate in various parts of the brain was unchanged, whereas the content of hyaluronic acid was significantly increased in the cerebellum (25 per cent) and in the thalamic area (20 per cent). The results suggest an influence of lithium on the macromolecules from the extracellular space, causing an alteration of the neuronal function.


Effect of a low-protein diet on acetaldehyde metabolism in rats. The effect of dietary changes on liver alcohol and aldehyde dehydrogenase activities as related to effects on ethanol and acetaldehyde metabolism was investigated. Feeding rats for 8 weeks on diets rich in carbohydrate or fat, but with normal protein content, induced minor changes relative to giving a balanced diet. A low-protein, high-carbohydrate diet (5 per cent and 80 per cent of calory content, respectively) caused a significant reduction of both alcohol and aldehyde dehydrogenase activities in the liver. The activity of the high-Km aldehyde dehydrogenase in the microsomal and soluble fractions appeared to be more reduced than that of the low-Km enzyme in the mitochondrial fraction. The tail blood acetaldehyde was significantly higher in rats on the protein deficient diet in spite of their reduced ethanol elimination rates. The results suggest that protein deficiency deranges acetaldehyde metabolism and may thus increase the possible contribution of acetaldehyde to the effects caused by ethanol metabolism.


Quantitative gas-liquid chromatographic determination of clonidine in plasma. A highly sensitive gas-liquid chromatographic method with electron capture detection of clonidine in plasma is described. The alkaline samples (100-200mul) are extracted into cyclohexane-butanol (9:1), re-extracted into 0.1 N sulphuric acid, made alkaline and back-extracted into cyclohexane-butanol. The pentafluorobenzyl derivatives of clonidine and the internal standard 2,-(2,4-dichlorophenylamino)-2-imidazoline are then formed, and excess of reagent is removed by solvent extractions. The minimum detectable quantity (MDQ) of clonidine and the internal standard are 2.5.10(-16) mol/sec. (3.3 picogram) and 2.8.10(-16) mol/sec (5.9 picogram), respectively. The smallest amount of clonidine which can be determined in plasma samples with a precision of less than 20 per cent S.D. is 200 picogram. The time course of clonidine in plasma after intravenous administration of 500 mug/kg to rats revealed that the data best fit a three-compartment open model.


On the absorption of proscillaridin A after single oral doses to normal and achlorhydric subjects. Proscillaridin A was given in single oral doses (1.5-2.5 mg) to normal and achlorhydric subjects. Plasma activities of the glycoside were analysed by 86Rb-technique. The absorption pattern was similar in both groups. A marked first peak of proscillaridin activity was seen after about 30 min. After a first minimum, a second peak of activity was registered within 6-12 hrs. An estimate of the amount of active glycoside absorbed during the first 12 hrs after the administration was obtained by calculating the areas under the plasma activity curves (AUC). When corrected for differences in dose per kg body weight, the mean AUC in the achlorhydric group was about 60 per cent greater than in the normal group. The results suggest that proscillaridin is rapidly absorbed; gastric acidity seems to contribute to inter-individual differences in the bio-availability of the glycoside.


Chronic copper poisoning in sheep. I. The relationship of methaemoglobinemia to Heinz body formation and haemolysis during the terminal crisis. The values of haematocrit, total haemoglobin in plasma, methaemoglobin percentages in erythrocytes and plasma, the osmotic fragility of the erythrocytes, and the occurrence of Heinz bodies were investigated during the terminal crisis in 4 cases of experimental chronic copper poisoning in sheep. At the beginning of the crisis, which lasted for well over one day, 10-20 per cent methaemoglobin was detected in the erythrocytes, before any haemolysis occurred. Later on severe haemolysis developed, and maximum levels of haemoglobin in the plasma were close to 2.5 g/100 ml. During the haemolytic stage both methaemoglobin and haemoglobin were detected in the plasma at approximately the same proportions as in the erythrocytes. No changes were observed in the osmotic fragility of the red cells until the onset of the haemolysis. It is concluded that the methaemoglobin formation is mainly an intra-corpuscular process and that most of the methaemoglobin detected in plasma in chronic copper poisoning in sheep, comes from the erythrocytes.


Chronic copper poisoning in sheep. ii. The distribution of soluble copper-, molybdenum-, and zinc-binding proteins from liver and kidney. The concentrations of copper, molybdenum, and zinc in the soluble protein fraction from sheep liver and kidney were determined after gel filtration. Samples from grazing sheep as well as from copper poisoned sheep were tested. In normal sheep the copper-binding proteins were separated into 3 different fractions. In copper poisoned sheep, as well as in grazing sheep with high copper concentrations, only 2 main fractions were seen. Molybdenum was only found in the high molecular weight protein fraction. The distribution of the zinc-binding proteins varied according to the degree of copper accumulation. The low molecular weight zinc-binding protein fraction was only seen in sheep with liver copper concentrations lower that 40 mug/g wet weight. In copper poisoned sheep a major part of the kidney copper was found in the low molecular weight protein fraction. At post mortem the bile copper concentrations in the copper poisoned sheep were only 2-4 times higher than those of the control animals.


Metabolic actions of some sympathomimetic amines and their acetyl derivatives in the rabbit. To study how acetylation affects the activity of sympathomimetic amines the effects of tyramine, amphetamine, ephedrine, phenylephrine, orciprenaline and salbutamol and of their O- and N-acetyl derivatives on blood glucose and free fatty acid concentrations were studied in the rabbit. Hyperglycemia was induced by all parent compounds except amphetamine which tended to have a weak hypoglycaemic action. Hyperlipaemia in the doses used was induced by ephedrine and orciprenaline but not by the other parent compounds. Usually acetylation decreased the metabolic effects of the compounds but O-acetylation of tyramine and salbutamol caused hyperlipaemia and O-acetylation of ephedrine increased its fatty acid-mobilizing action, perhaps as a consequence of increased lipid solubility of the compounds. The ultimate effects of the O-acetyl derivatives were probably at least partly due to deacetylation at their sites of action. However O-acetylation of sympathomimetics could perhaps be used to induce drug latentiation.


Effect of acetylated derivatives of some sympathomimetic amines on the isolated auricles and tracheal chain of the guinea-pig. The effects of acetylation of sympathomimetic amines, tyramine, amphetamine, ephedrine, phenylephrine, orciprenaline, and salbutamol, and their O- and N-acetyl derivatives and the effects of reserpine or physostigmine pretreatment on the isolated auricles and tracheal chain of guinea-pigs have been studied. All the parent drugs relaxed the tracheal chain and had a positive inotropic and chronotropic effect on the isolated auricles; only amphetamine, on the contrary, contracted the tracheal chain. O-acetylation of these sympathomimetic amines generally decreased less chronotropic than iontropic action on the isolated auricles. O-acetylation of tyramine however: actually increased the positive chronotropic activity of drug. As a rule, O-acetylation also decreased the beta-adrenergic effect of these compounds on the tracheal chain, but not so markedly as on the isolated auricles. N-acetylation generally abolished the adrenergic effects of these sympathomimetic amines on the isolated auricles and decreased those effects on the tracheal preparation. N,O-triacetylation of salbutamol abolished the stimulating effect of the parent drug on the auricles but increased the relaxant activity on the trachea. Physostigmine antagonized the effects of O-acetyltyramine and O-triacetylorciprenaline but not those of tyramine and orciprenaline on the trachea preparation. It is concluded that among the sympathomimetic amines acetylation may be utilized for the development of specific bronchodilators and O-acetylation for inducing drug latentiation.


Pharmacodynamics of a new selective beta2-adrenergic bronchodilator 3-(4-methoxybenzylamino)-4-hydroxy-alpha-(tert. butylaminomethyl)-benzyl-alcohol, HCl (QH25). The bronchodilator effect of QH25 (3-(4-methoxybenzylamino)-4-hydroxy-alpha-(tert. butylaminomethyl)benzylalcohol, HCl) a new beta2-adrenergic bronchodilator has been investigated in conscious guinea pigs and in anaesthetized guinea pigs and cats and compared to that of salbutamol and isoprenaline. In anaesthetized guinea pigs QH25 and isoprenaline were equipotent after intravenous administration, whereas salbutamol was four times less active. The same difference between QH25 and salbutamol was observed after intraduodenal administration. After oral administration in conscious guinea pigs QH25 was eight and five times more potent than salbutamol and isoprenaline respectively, whereas no difference was observed when the agents were administered as aerosols. The bronchodilator action of QH25 was apprxomately three times that of salbutamol in egg-albumine sensitized guinea pigs after oral administration. In anaesthetized cats the bronchodilator potency of QH25 was three times that of salbutamol and the same or slightly higher than that of isoprenaline. A half-life of 4 hours for the bronchodilator action in guinea pigs was determined for both QH25 and salbutamol after oral administration. The effect of QH25 and salbutamol on cardiovascular parameters i.e. chrono- and inotropic action and blood pressure decreasing effect in guinea pigs, cats and dogs was essentially the same whereas isoprenaline was from 5 to 30 times more potent. The potential tremorogenic action of QH25 estimated on the cat soleus muscle was eight times less than that of isoprenaline and the same or slightly less than that of salbutamol. From the experimental data it is concluded that QH25 has the same potency as isoprenaline as a bronchodilator agent but is more potent than salbutamol. Taking into account that isoprenaline is considerably more active on cardiovascular parameters and on the cat soleus muscle than QH25 which has the same or less effect than salbutamol on these parameters the data suggest that QH25 is a more selective bronchodilator agent than both isoprenaline and salbutamol.


Absorption and elimination kinetics of 32P malathion in the hen. A method for the separation of urine and faeces in the hen was developed and the biological fate of 32P malathion, following a single oral dose of 262.40 mg/kg body weight was studied. The results suggested that the compound was rapidly absorbed from the gastrointestinal tract; significant quantities being detected in the plasma and whole blood 1/2 hr after ingestion. Total 32P was eliminated in the urine by apparent first order kinetics with an average half-life of 5.7 hrs. The cumulative urinary and faecal data revealed that 93% of the 32P is excreted via the urine within 48 hrs, thus indicating that the compound is almost completely absorbed. It is therefore concluded that accumulation in the system is unlikely.


Influence of various anaesthetics on the cardiovascular responses to noradrenaline in rats before and after guanethidine. The influence of surgical anaesthesia induced by ketamine, pentobarbital, pentobarbital-xylazine, or chloralose-urethane on blood pressure and heart rate was studied, and the effects were compared with results in conscious and pithed rats. The blood pressure was significantly decreased by pentobarbital-xylazine. The heart rate increased in all groups except in pentobarbital-xylazine anaesthetized rats. Generally, a fall in heart rate and blood pressure was observed during a two hours lasting anaesthesia as compared to the initial values. The blood pressure response to noradrenaline was significantly lowered by ketamine, pentobarbital and chloralose-urethane. Guanethidine 5 mg/kg intravenously significantly lowered the blood pressure in the ketamine, pentobarbital, and chloralose-urethane anaesthetized groups. The guanethidine induced potentiation of the haemodynamic effects of noradrenaline was considerably influenced by the anaesthetic, the augmentation being greatest in pentobarbital and chloralose-urethane anaesthetized rats. Chloralose-urethane is considered a suitable anaesthetic in rats when studying the effects of noradrenaline and guanethidine. Following a single intraperitoneal injection a surgical anaesthesia of more than two hours' duration was obtained, and the variance of the parameters studied was less than that following administration of the other anaesthetics. It is emphasized that various effects of anaesthetics unrelated to their anaesthetic properties may obscure or even invalidate results obtained with drugs acting on the peripheral sympathetic nervous system.


Evoked efflux of 3H-bretylium by sympathomimetic amines from the rat vas deferens in vitro. The efflux of 3H-bretylium in rat vas deferens in vitro evoked by a number of sympathomimetic amines was examined. The tissue was preloaded with 3H-bretylium (2 x 10(-7) M) and the efflux of bretylium to the incubation medium in the presence of the amines during 20 min, was determined. The efflux evoked by (+)-amphetamine was almost abolished at 0 degrees and by desipramine. The dose response curves showed that some of the amines at high concentrations markedly antagonized their own effect. It could be demonstrated that (+)-amphetamine and N-methylamphetamine at a high concentration also antagonized the efflux evoked by low external Na+ concentrations and it is suggested that this effect is produced by inhibition of the outward transport of bretylium through the neurone membrane. The structure activity relationship obtained shows that the non-hydroxylated amines are most potent in evoking bretylium efflux and that the potency diminished with the number of hydroxyl groups. The tertiary amine analogue of amphetamine is less active and the quaternary derivative much less active than amphetamine and N-methylamphetamine. A hydroxyl group at 3-position gives a somewhat higher potency than that at 4-position. This structure activity relationship is similar to that previously reported for the sympathomimetic amines in reversing the adrenergic neurone blockade for bretylium and it is proposed that this reversal is induced by the reduction of the intraneuronal concentration of bretylium as a result of the evoked efflux.


Interaction of perphenazine with the kinetics of nortriptyline. The kinetics of nortriptyline in four patients were investigated before and during treatment with perphenazine (24-36 mg/day) by administering 57 mg nortriptyline hydrochloride as an intravenous infusion and evaluating the resulting plasma concentration data according to a two compartment open model. In all patients an increased biological half-life as well as a decreased systemic clearance and rate of metabolism were found in the perphenazine-period, thus confirming the inhibitory effect of perphenazine on the metabolism of nortriptyline found in earlier studies. Some interaction with distribution parameters was also indicated, but on the whole the model parameters did not provide much further information about the interaction. Although the most pronounced changes were found with the patient getting the highest dose of perphenazine, the dose-effect relationship remains obscure.


Osmolalities of infant formulas.

Osmolalities of infant formulas. The osmolalities of breast milk and of 36 products that may be fed to infants were determined by the freezing-point depression method. A wide range of osmolality was observed among formulas that provide 67 kcal/100 ml, and many have osmolalities greater than 400 mOsm/kg of water. Reconstituted powdered formulas have osmolalities that are widely varied from batch to batch, are greater when prepared by scoop measures when the osmolalities of corresponding ready-to-feed formulas, and are greater than the osmolalities of the formulas prepared by weighed measures from the manufacturer's formulation. The osmolality of products for oral consumption should be considered in the selection of formulas for preterm infants.


Neonatal hyperthyroidism and heart failure. A differential approach. Congestive heart failure in neonatal thyrotoxicosis is attributed to sympathetic overstimulation of the myocardium with resulting high-output cardiac failure. An additional case of neonatal thyrotoxicosis with congestive heart failure is discussed; three possible causes (thyrotoxicosis, maternal propranolol therapy, and ventricular septal defect) were present. Along with the usual procedures, the echocardiogram is of value in separating these factors. In addition, we discuss the potential dangers to the newborn of a mother receiving long-term propranolol hydrochloride therapy during pregnancy.


Hypothyroid Graves' disease.

Hypothyroid Graves' disease. Graves' disease has recently been shown to exist in a euthyroid form in untreated patients. Sporadic reports of a hypothyroid form are beginning to emerge, thus illustrating the multifaceted nature of this disorder, with thyrotoxicosis at one end of the spectrum and hypothyroidism at the other. Three patients with nonthyrotoxic Graves' disease and concomitant hypothyroidism were seen at Emory University Hospital in one year, and deatailed studies were made to help elucidate the nature of this unusual combination. Results of these studies are reported and briefly discussed. It is suggested that, until more is known about this intriguing aspect of the Graves' disease spectrum, the label "hypothyroid Graves' disease" is justifiable.


The effects of fetal thyroidectomy in the ovine fetus. Cerebral function and metabolism, morphology and histology of the nervous system, and lung maturity in terms of surfactant production were studied at term in five sheep fetuses thyroidectomized at gestational ages ranging from 104 to 111 days. Compared to age-matched controls, body weight (thyroidectomized animals, 2.8 +/- 0.11 kilograms; controls, 3.9 +/- 0.2 kilograms; P less than 0.0005) and brain weight (thyroidectomized animals, 43.51 +/- 1.38 grams; controls, 48.49 +/- 1.75 grams; P less than 0.05) were significantly reduced. In the nervous system, morphology, histology, brain function, and metabolism were not significantly different from those of the controls. Lung weight was less, but not significantly, and surfactant production was not deficient as compared to that of age-matched controls. The failure to find any disturbance of maturation in the brain and lungs of fetuses thyroidectomized at 104 to 111 days may be related to the relative maturity of the sheep fetus at this age.


Bromocryptine therapy in cases of amenorrhea-galactorrhea. Of 28 patients presenting with amenorrhea-galactorrhea, pituitary tumors were confirmed in eight. Six patients had occult hypothyroidism and the rest had an endocrine profile suggestive of pituitary tumor or of an idiopathic etiology. Treatment with bromocryptine resulted in suppression of the inappropriate lactation and restoration of regular menstrual function. In five cases, however, the galactorrhea was only diminished and in four of these cases, normal ovarian function did not return. Of the 19 patients that were seeking fertility and continued the medication for at least 20 days, nine pregnancies resulted. A similar response to bromocryptine was observed regardless of the underlying cause of the amenorrhea-galactorrhea.


The lecithin/sphingomyelin ratio in cases associated with fetomaternal disease. The efficacy of correlating the L/S ratio in the amniotic fluid with fetal lung maturity has been substantiated in normal pregnancies. In gestations complicated by fetomaternal diseases, however, the assay is less reliable. This study involves 555 pregnancies in which there was a significant maternal, fetal, or placental disorder. The L/S ratio was related to fetal respiratory maturity as measured by Dubowitz criteria and the occurrence of RDS. The results show that pre-eclampsia, chronic hypertension, diabetes (Class D, E, F), significant cardiovascular disease, severe hemoglobinopathies, various congenital anomalies, chronic placental insufficiency, and prolonged ruptured membranes accelerated the L/S ration. Conversely, mild diabetes (Class B, C), intrinsic renal disease, hepatitis, collagen disease, hydrops fetalis, syphilis, and toxoplasmosis were associated with a delay in the L/S ratio. A significant increase in erroneous responses was noted in these patients when the L/S ratio was correlated to infant maturity and to the incidence of RDS. Possible mechanisms for these findings are discussed.


A syndrome of immunoglobulin A deficiency, diabetes mellitus, malabsorption, a common HLA haplotype. Immunologic and genetic studies of forty-three family members. Three persons in a kindred of 43 had variable expression of a syndrome consisting of immunoglobulin A deficiency, diabetes mellitus, malabsorption, and a common HLA haplotype. Findings from the proband included life-threatening malabsorption; idiopathic intestinal mucosal atrophy with infalmmation; IgA deficiency and antibodies to multiple endocrine organs; insulin-dependent diabetes mellitus; and the major histocomptability antigens HLA-A2, B8, and DW3. In addition to the described syndrome other conditions present in the family include Graves' disease, vitiligo, hypocomplementemia, rheumatic fever, multiple sclerosis, and a high frequency of antibodies to endocrine tissue. Since Graves' disease, diabetes mellitus, and idiopathic Addison's disease have all been described in association with HLS-B8 and DW3, we believe that the occurrence of these diseases in this family suggests that a single immune response gene or gene complex is linked with HLA-B8 and DW3.


Painless thyroiditis and transient hyperthyroidism without goiter. Eight women had painless thyroiditis, transient thyrotoxicosis, and low radioactive iodine uptakes but were without goiter; they constituted 15% of all thyrotoxicosis cases that we saw during the past year. Standard antithyroid antibody tests by tanned erythrocyte hemagglutination, complement fixation, and colloid and microsomal fluorescence, if present initally, were only weakly psotivie and became negative by 9 months. However, human antithyroglobulin antibody levels by a sensitive radioimmunoassay were elevated initially in all patients. In general, these radioimmunoassayable antibody levels fell, but they had not returned to normal by 9 months. Serial thyroid function tests and standard antithyroid antibody tests were most compatible with subactue thyroidtis. However, the persistence of radioimmunoassayable antithyroblobulin antibodies and recent reports of histologic evidence of lymphocyte thyroiditis in similar patients with goiter leaves open the possibility that this is a previously unrecognized presentation of chronic lymphocytic thyroiditis. Neither the cause nor the ultimate course of this syndrome is known.


Inflammatory pseudotumor of the orbit.

Inflammatory pseudotumor of the orbit. The history and confusing terminology regarding reports of inflammatory pseudotumor of the orbit are reviewed. The wide clinical spectrum and variety of associated conditions is emphasized. Twenty-seven patients from the Wills Eye Hospital with clinical records and histopathologic material consistent with orbital pseudotumor were reviewed and an attempt was made to correlate the histopathologic findings with clinical presentation, response to steroids, and final outcome. Adequate follow-up averaging 3.6 years was obtained in 17 cases. Most cases in the series had a favorable outcome, and patients demonstrating the acute and subacute stages of Type II patterns responded to systemic steroids. Repeated and extensive surgical intervention appear to be harmful.


Milk bolus obstruction in the neonate.

Milk bolus obstruction in the neonate. Seventeen cases of neonatal intestinal obstruction due to inspissated milk curds were seen at this hospital in the 9 years 1964-1972. The obstruction started on the 2nd to 10th day of life. Half the babies passed blood from the rectum and in most the x-rays were diagnostic. All survived, 14 after operation and 3 after medical treatment with a Gastrografin enema. Incomplete absorption of solids, particularly the fat from cows' milk feeds, is suggested as the cause.


Differences in subcutaneous fat in breast- and formula-fed infants. During the first 6 weeks of life, 87 breast-fed infants had a significantly greater increase in skinfold thickness than 173 infants fed only with artificial milk formulae. The two groups were similar in respect of racial origin, gestational age, birthweight, and weight gain in the first 6 weeks of life. These findings show that formula-fed infants have a different distribution of body fat from breast-fed infants.


Infectious syphilis mimicking neoplastic disease. Five patients who were initially evaluated for malignant neoplasm actually had infectious syphillis (one primary, two secondaries, two secondaries with persistence of primary). Two patients were considered for radical surgery and one for extensive radiation and/or chemotherapy. In four patients an elevated routine admission VDRL was the first indication of the correct diagnosis. Dark-field examination is the most important laboratory test in the diagnosis of primary syphillis; VDRL and FTA-ABS are most important in confirming secondary syphillis. Penicillin remains the drug of choice for therapy. At a time when the incidence of sexually transmitted diseases is increasing, it is extremely important to develop adequate educational programs for medical students and physicians.


Limitations of visualization of the entire fetus by means of second-trimester fetoscopy. Fetoscopy with rigid fiber optics was performed under general anesthesia in 9 patients scheduled for therapeutic abortion by hysterotomy with a duration of pregnancy between 12 and 18 weeks. Visualization of fetus and placenta was found to be at random chance and incomplete, and could not be improved by internal or external manipulation. Skin biopsies were obtained in 5 cases. The cord could be recognized in all cases. It is concluded that the haphazard and incomplete visualization of the uterine contents at present precludes the application of second-trimester fetoscopy for early detection of visible congenital fetal abnormalities.


[Fetal causes of the onset of labour. A kybernetic model (author's transl)]. The question of initiation of labour is not yet solved. A fetal fixing of the date would be ingenious. On the one hand the fet is endangered by prematurity, on the other hand by placental insufficiency in postmaturity. Fetuses with comparatively lighter placenta remain in average shorter in utero until spontaneous initiation of labour than those with comparatively heavier placenta. This fact leads to the assumption of a relative placental insufficiency as a determining factor of the onset of labour. A further inquiry demonstrates, that babies born after premature termination of pregnancy about the term - either by induction of labour or by primary sectio caesarea - are heavier and longer than those born after spontaneous labour. This leads to the assumption of a prenatal weight loss of the infant before spontaneous initiation of labour. This weight loss is caused by diminution of water content and relative placental insufficiency. This relative placental insufficiency also leads to a diminution of amniotic fluid, which is swallowed by the "hungry" fet in a greater amount. Altogether a diminution of uterine volume is resulting, which is accomplished by a diminution of uterine wall tension. The coordination of uterine activity, which precedes delivery, is combined with the ripening of the cervix. The ripening of the cervix also leads to a retraction of myometrium and thus to a further diminution of uterine wall tension. It is concluded, that a diminution of uterine volume, causes by fetal weight loss and diminution of amniotic fluid, leads to a reduction of uterine wall tension, which is supported by the ripening of the cervix. This reduction of uterine wall tension is the precondition of the increasing coordination of activity, which precedes delivery.


[Light- and electronmicroscopic examinations on granulosa and theca of primordial-, primary-, secondary- and resting tertiary follicles of human ovaries (author's transl)]. Light- and electromicroscopic examinations were performed on granulosa and theca of primordial-, primary-, secondary- and resting tertiary follicles of human ovaries. These examinations were intended to clarify how far correlation exist between the structural components of the different tissue formations of the follicles and their determined functions. Remarkably many intraplasmatic filaments were found in the cytoplasm of granulosa cells of primordial-, primary- and secondary follicles. In the resting tertiary follicles the electronmicroscopy defines the majority of the follicle granulosa cells as proteinsynthetic active cells with abundant rough endoplasmatic reticulum. Most of the nuclei contain several nucleoli. An interesting finding compared with the granulosa cells of earlier developing stages of the follicle is the presence of single or grouped fat droplets in the cytoplasm, whereas metaplastic structures like filaments and/or microtubules are rare. The theca cells aroung the primordial-, primary- and secondary follicle were characterized by electromicroscopy as typical stroma cells. These cells of the resting tertiary follicles in the theca interna and externa show characteristic submicroscopic criteria of active steroidbiosynthesis. Their cytoplasm is especially rich of smooth endoplasmatic reticulum about from that there are tubular mitochondria and diffus fat droplets. Regarding the functional meaning of the different tissue formation of the follicles the existence of filamentous material in the membrana granulosa of primordial-, primary- and secondary follicles demonstrates an important finding. Apparently the presence of these metaplastic structures in the follicle granulosa cells play a role in the formal development of the zona pellucida and the Call-Exner-bodies. The structural organisation of the granulosa cells of resting tertiary follicles shows a high proteinsynthetic activity which plays a role in the metabolism of oocyte and the follicular fluid production. So far there are no definite submicroscopic criteria for steroidbiosynthesis. The structural differentiation of the normal stroma cells around primordial-, primary- and secondary follicles leads to definite submicroscopic steroidcells in the resting tertiary follicle. According to our results the process of the transformation of follicular granulosa cells in steroidbiosynthetic active cells in the resting tertiary follicle is not complete.


[Isolation and characterization of a new tissue protein (pp7) from human placentae (author's transl)]. The isolation and characterization of a new tissue protein (PP7) from human placentae is described. The placental protein PP7 is not specific for the placenta; it is found in relative high concentrations in other human tissues as well. Trace amounts of PP7 occur in erythrocytes, too. In sera this protein could not be detected with the gel diffusion test of Ouchterlony nor with the electroimmunoassay technique. PP7 has a molecular weight of around 40,000 daltons and is composed of two identical subunits which are non-covalently linked. In the ultracentrifuge PP7 sediments with 3.5 S. The isoelectric point was found to be 4.9. Electrophoretically the protein migrates in the range between alpha 2 and beta1-globulins. PP7 is a glycoprotein; its carbohydrate content amounts to 5.4% (hexoses 3.0%, Hexosamine 1.2%, Fucose 0.2%, sialic acid 1.0%). The amino acid composition of the protein is reported, too.


[Glomus structures in axillary lymph nodes and the demarcation against metastases of mammary carcinoma (author's transl)]. A report is presented on the demonstration of epithelioid cell clusters within the axillary lymph node group, which could be taken for micrometastases of a mammary carcinoma. The lymph node material from 400 extensively excised mammary carcinomas with obligatory lymphonodectomy was available for this study. Metastases of mammary carcinoma were found in 264 cases (66%). Therewithal a procedure with microscopic inspection of successive sections at 100 mu intervals of all lymph nodes led to the discovery of epithelioid cell clusters in 18 out of the 400 cases examined. As regards their appearance and structural peculiarities, with direct allocation to the local vascular stroma, these clusters must be regarded as glomus-like structures. From a clinical point of view, their fundamental significance consists in the necessary differentialdiagnostic demarcation against micrometastases of carcinoma in the region of origin of the lymph.


[Major gynecological operations on women of 80 years of age or more (author's transl)]. Because of the greater life expectancy of women, the length of the post-menopausal period has also been constantly increasing. Since there is no generally accepted definition of the late post-menopause and senium in women, we submit a suggestion of how these periods of life may be deliminated. During the years 1960--1969 6662 female patients aged 60 years or more, were operated on in 17 different Westberliner departments of gynecology. Of these 3.9% (i.e. 261 cases) were major gynecological operations on women of 80 years or more: 155 were malignant and 37 benign tumors, 59 were due to displacement of the uterus (11 cases of minor descended uterus and 48 cases of fully prolapsed uterus) and 10 other diseases. The postoperative death rate was 13.4% (36 cases). In spite of such mortality these major operations were generally considered necessary and beneficial in women of this age group. Among other reasons, cancer-screening examinations of old women should be done more regularly than at present because of the multi-morbidity occurring at this age.


Ferritin phagocytosis.

Ferritin phagocytosis. The in vitro events of phagocytosis of ferritin and of cationized ferritin by normal eosinophils and the eosinophilic cells of two patients with hypereosinophilic syndrome are described. After one minute of incubation, the cells showed a noticeable pseudopod formation, while after five minutes, ferritin-containing vacuoles were seen in both the normal and the patients' eosinophils. No alterations of the specific granules were observed in cells incubated for 90 minutes or less. Ferritin was observed in the membrane-bound vacuoles, but not in the specific granules of the cells. There was no difference in phagocytic activity of the patients' eosinophils as compared with the normal eosinophils, as well as between phagocytosis of ferritin and of cationized ferritin.


Phenytoin inhibition: failure to inhibit periosteal responses to lathyrogen. beta-Aminopropionitrile (BAPN) administered to rats has caused exostosis formation at sites of muscle attachment and also caused delay in the healing of soft tissue wounds and of bone fractures. Since phenytoin sodium has an opposite effect on wound healing, bone fractures, and the tensile strength of connective tissues, an experiment was performed to determine whether or not BAPN could produce periosteal exostoses in the presence of phenytoin. Rats that were given both BAPN and phenytoin produced similar exostoses as rats that were given BAPN alone. This indicates that phenytoin does not prevent inhibition of lysyl oxidase by BAPN, does not promote increased tensile strength of connective tissues in the presence of BAPN, and does not facilitate the detoxification of BAPN. Further, no evidence for an increased cellular response with phenytoin was observed. The mechanism by which phenytoin promotes wound healing is still unknown.


Nonbacterial thrombotic endocarditis (NBTE) and disseminated intravascular coagulation (DIC): autopsy study of 36 patients. A pathogenetic relationship between nonbacterial thrombotic endocarditis (NBTE) and disseminated intravascular coagulation (DIC) was sought by reviewing autopsies from a recent 12-year period. Of 4,783 autopsies, 36 patients were found to have NBTE. The histopathologic diagnosis of DIC in patients with NBTE was dependent on the observation of thrombi in vasa recta and central glomerular capillaries of the kidneys and in sinusoids, arterioles, capillaries, venules, and medium-sized veins of the major viscera. Morphologic evidence of DIC was found in 18 (50%) of the 36 patients with NBTE. In addition, venous and arterial thromboses were found in 13 patients (36%) and pulmonary thromboembolism in 17 (47%). These findings support the view that NBTE and DIC may be pathogenetically related and result from a hypercoagulable state.


Aortic lesion in Marfan syndrome: the ultrastructure of cystic medial degeneration. Areas of medial alteration (Erdheim cystic medionecrosis) in an aortic root aneurysm surgically removed from a patient with Marfan syndrome were studied with an electron microscope. The single striking morphologic abnormality was the disorganized, haphazard architecture of the media in these areas. This lesion is interpreted as being an abortive reparative response to hemodynamic stress in a condition with a molecular defect in the structural proteins of connective tissue.


Diffuse rhabdomyomatosis of the heart.

Diffuse rhabdomyomatosis of the heart. The myocardium of a 13-year-old boy was infiltrated with cells like those of classical congenital rhabdomyoma. In contrast to the latter condition, in which distinct nodules are present, our patient had an infiltrated myocardium without a distinct tumor formation. The condition is similar to that reported earlier and may be designated as diffuse rhabdomyomatosis.


Short left circumflex artery.

Short left circumflex artery. There was evidence of posterior infarction in 61 of 212 hearts studied. The condition was associated with a relatively short circumflex branch of the left coronary artery (LCX) in 24 hearts and with a longer LCX in 37 hearts. Total occlusion of LCX was found in two (8%) hearts with a shorter circumflex branch and in 27 (73%) hearts with a longer circumflex branch. The right coronary artery (RCA) was occluded in nearly all hearts with posterior infarction. In those hearts with a shorter LCX, occlusion of RCA appeared to be the major factor in the pathogenesis of posterior myocardial infarction.


Regional myocardial infarction of low-flow type in a neonate with tricuspid atresia. Clinical and anatomical data are presented on a neonate with tricuspid atresia, who died at 16 hours with a regional, nontransmural myocardial infarcti after clinical documentation of akinesis. A partially occlusive intimal lesion associated with acute angulation of the right coronary artery was noted in an area of fibrosis that included the atretic tricuspid valve. Low-flow myocardial infarction was found in the posterior part of the left ventricle in an area supplied by the right coronary artery distal to the arterial lesion.


Lead cardiomyopathy in mice: a correlative ultrastructural and blood level study. This is a correlative study of ultrastructural changes in the myocardium and the blood lead levels (BLLs) in acute lead toxicity in mice. No substantial ultrastructural changes were observed with BLLs of less than 20 mug/100ml. Blood lead levels of 20 mug/100ml and above were associated with nuclear chromatin clumping and nucleolar disorganization. Sarcotubular dilation and mitochondrial changes characterized by mitochondrial enlargement, cristal disorientation, and an increase in intramitochondrial matrix were observed with BLLs of 40 mug/100ml and over. Blood lead levels of 60 mug/100 ml and above were associated with local myofibrillar degeneration, focal intercalated disk disjunction, and interstitial cell changes characterized by prominent endoplasmic reticulum and the appearance of cytoplasmic lysosome-like dense bodies. Our findings indicate a differential sensitivity of various myocardial cell organelles to lead and suggest that the changes observed are directly related to the BLLs.


Retrolental Fibroplasia. II. Pathologic correlation. Retinas of 142 eyes from 71 premature infants on whom autopsies had been done were studied by gross observation and by using PAS-stained whole mount, trypsin-digest, and conventional histological techniques. With these techniques, vascular pathologic condition was correlated with fluorescein angiograms in living infants with acute retrolental fibroplasia. The specific lesions seen in acute phase were a major arteriovenous shunt in the eye, microvascular changes including tufting, and obliteration of capillaries around arteries and veins. Regression occurred by vascular budding from the anterior edge of the shunt. Observations on vascularization in the normal indicated a variability of the level of maturation of the retinal vasculature, only roughly correlated with gestational age.


Acute retrolental fibroplasia.

Acute retrolental fibroplasia. Three hundred eighty-four premature infants were examined by indirect ophthalmoscopy in a period of 38 months. Sixty-eight were found to have some degree of retrolental fibroplasia. Most pathologic changes resolved spontaneously to normal or near normal. A classification was formulated, based on peripheral vascular changes, to enable observers to interpret and quantitate the amount of disease present. The role of the ophtalmologist in the perinatal intensive care nursery is not to dictate the amount of oxygen administration during the acute phase of respiratory distress syndrome but to monitor peripheral fundus and posterior vascular changes of infants of low birth weight, or who have received oxygen, or both, at a time that is not detrimental to the health of the infant. To evaluate the possible indications and efficacy of surgical intervention, an understanding of the natural course of the disease process is mandatory.


Retrolental fibroplasia: I. Clinical observations. The changes occurring in retrolental fibroplasia were studied in 97 premature infants with fundus photography and fluorescein angiography. The macrovascular lesion of proliferative retrolental fibroplasia was identified as a functioning arteriovenous shunt. The microvascular abnormalities were capillary tufts, collaterals, capillary-free zones, and neovascular membranes. Regression was signaled by the ingrowth of capillaries from the shunt into the avascular retina. Cicatrization was characterized by persistence of the vascular abnormalities of the proliferative phase and organization of the avascular retina into a contracting scar.


[Injury of the semilunar cartilages of the knee-joint in childhood (author's transl)]. In the paper, 30 patients at the age of 5 till 14 with injuries of the semilunar cartilages of the knee-joint, are presented. All the children were subjected to surgery, and 20 of them underwent same examinations performed in a delay of 1 to 12 years after they had been operated. Both etiology and the injury mechanism subjects are hadled together with the clinical pictures, specific to the age of the young patients. Basing of the clinical and X-ray examinations, the state of the morphological and functional condition of the knee of a child after semilunar cartilage had been removed, was considered and estimated.


The reliability of averaging technique in registration of slow auditory evoked potentials in man. The authors studied the application of arithmetic averaging in the registration of auditory evoked potentials (AEP). Fourier analyses of averaged potentials show a typical shape of both amplitude and phase spectra in the region of the AEP. The maximum of the amplitude spectra diminishes with lower sound intensities and shifts to lower frequencies. The enhancement of the mean power of the EEG  in the region of the AEP demonstrates the suitability of the arithmetic averaging technique in the Electric Response Audiometry. For clinical practice the simultaneous registration of the arithmetic mean and the mean square value along with the standard deviation is useful to detect artifacts or amplitude and latency shifts of the AEP components.


[High frequency cinematographic investigations of the mode of operation of common grinding instruments on bone and cartilage (author's transl)]. The mode of operation of grinding faces, rod diamonds and diamond grinding heads which are expecially employed in oto-surgery was investigated in slow motion pictures with the aid of high frequency cinematography. The R.P.M. ranged between 5,000-80,000, the picture frequency was usually 6,000 pictures per second. Full efficiency of the diamond grinding heads (DS) is only guaranteed by adequate flushing. Water stream flushing and drop flushing (drop sequence depending on R.P.M.) must be centered on the grinding head, as increased soiling due to filling of the diamond surface occurs otherwise. Because of the fixed mounting of the spray tube in the direction of the shaft, spray flushing is most useful, although not unsable for diamond faces. Due to its very fine-rough surface, the DS produces grinding dust by abrasion from the bone or cartilage which is readily distributed in the airspace over the whole working area. The same does also apply to finely atomized fluid sprays. Cutting is performed tangentially. The percussing DS touches the bone only with a small part of its surface and easily gets soiled. Depending on the R.P.M., the cutting speed was 10,000-80,000 R.P.M. These values also apply for the fluid dropping rate. Contrary to the rose bit or the surgical fraises, the DS got soiled more easily and produced definitely finer cuts.


Vascular supply to the organ of corti in man. The capillary distribution in the basilar membrane and the osseous spiral lamina was studied in 40 human temporal bones. The capillaries were made visible using a histochemical technique for demonstrating alkaline phosphatase activity. High tone sensorineural hearing loss can be explained by capillary distribution, length of a segment in the outer spiral vessel and the distance between the inner and the outer spiral vessels in different cochlear turns.


[Pathogenesis and clinical observations of papillomatous diseases of the skin and of the mucous membranes (author's transl)]. In the certain skin-warts, condylomata acuminata, oral-, laryngeal- and bronchial papillomas a morphologically identic virus is often seen. This virus belongs to the papova-virus-group and causes papillomas: Independant of their localization their clinical behaviour is very similar. Using cytophotometric methods we tried to find out if there are any signs which allow to reveal malignancy in continous reappearing papillomas.


Basic study of nasal provocative test first report: side, site of the nose, size of site and allergen amount. The methodology of the provocative nasal test has varied according to the investigators. In order to establish a standard method of this test quantification of the nasal challenge, including the amount of the allergen, nasal site, side and size of allergen deposition, was studied. From the results obtained it is preferable to use the end point test and to apply allergen to the anterior part of the inferior turbinate in a 7mm2 size of surface area, bilaterally. An alternative test is to use a fixed amount of allergen (500 mug house dust in house dust allergy).


Caloric diagnosis maximum stimulus and suppression of habituation effects. The relation between randomized caloric stimuli of 30 degrees - 5 degrees C to the parameters: duration, maximum frequency and maximum intensity was electronystagmographically examined on 25 persons. The duration and the maximum frequency showed only a slight correlation to the stimulus. There was a linear correlation to the maximum intensity and the stimulus between 30 degrees and 15 degrees C. But with temperatures below 15 degrees C the reaction did not increase. So the maximum intensity corresponds best to the characteristics of the temperature wave in the petrous bone and thus to the cupula deviation. By mathematical correction of the randomized stimulus sequence it was possible to show that habituation effects can be suppressed by certain test conditions, e.g. a constant degree of alertness of the subject and free head movements in the intervals. It is recommended to replace the 30 degrees C stimulus by a 17 degrees C stimulus: by this strong stimulus extra-vestibular interference and the influence of a latent spontaneous nustagmus are relatively suppressed and hypoexcitability is more accurately determined. Temperatures below 15 degrees C are not recommendable: the vestibular stimulus is not stronger but more painful and pseudocaloric effects are accentuated. When ascertaining correctly a spontaneous nystagmus we propose to refrain from the determination of directional preponderance, the value of which seems questionable.


[Diagnostic and therapeutic aspects of solitary extramedullary plasmacytomas (author's transl)]. The rare solitary extramedullary Plasmacytoma is discussed and compared to the more common disseminated form. Based upon the pertinent literature, some diagnostic problems, clinical and pathological features as well as prognostic and therapeutic aspects of the solitary lesion in the ENT field are reviewed. In connection to one personal case, the authors analyze Trotter's Median Labiomandibular Glossotomy.


Inner ear malformations with oto-liquorrhea. Tomographic findings in three cases with a mixed hearing impairment. The paper deals with three boys suffering from a mixed hearing loss. They were all referred to tomography of the temporal bones in order to find some middle ear malformation amenable to surgery. The tomograms revealed identical malformations of the inner ear; the lumen of the labyrinth are found irregularly dilated and the internal acoustic meatus is widened. Its course in the lateral end is abnormal with a downwards turn towards the basal coil of the cochlea. Explorative tympanotomy in one of the patients revealed a severe otoliquorrhea during an attempt to perform a stapedectomy, and this may serve as a warning against operation in patients presenting the mentioned tomographic changes which, once seen, are easily recognized.


Inefficiency of cynarin as therapeutic regimen in familial type II hyperlipoproteinaemia. Seventeen ambulant outpatients with familial Type IIa or Type IIb hyperlipoproteinaemia were treated with Cynarin, the 1,5-dicaffeyl ester of quinic acid, the constituent of the artichoke (Cynara scolymus). The dose tested was 250 mg and 750 mg daily. The mean serum cholesterol and triglyceride concentrations were not significantly changed within 3 months. Cynarin, administered per os, has no hypolipidaemic effect in familial Type II hyperlipoproteinaemia.


Sodium dodecyl sulfate-disc gel electrophoresis patterns of bovine lung surfactant. Bovine lung surfactant material, isolated by three steps of centrifugation from lung washings, had a phospholipid: protein ration of 4.98+/-S.D. 0.62 mumol/mg. Sucrose continuous density gradient centrifugation showed only one visible band at a density of 1.081 g/ml. Sodium dodecyl sulfate-disc gel electrophoresis patterns of the apoprotein extracted from this material revealed that the main component (70-80%) of the protein subunits of bovine lung surfactant material has a molecular weight of 36 000. It was suggested that the apoprotein of bovine lung surfactant material exists as a combination of a few protein subunits, most of which have a molecular weight of 36 000.


Tuftsin and some analogs: synthesis and interaction with human polymorphonuclear leukocytes. The phagocytosis-stimulating tetrapeptide tuftsin, L-threonyl-L-lysyl-L-prolyl-L-arginine, was synthesized by both conventional and polymeric-reagent approaches. Using a combination of the two methods several analogs were prepared, including: [Ala1]tuftsin, [Lys1]tuftsin, [Ser1]tuftsin, [Val1]tuftsin, acetyl-tuftsin, p-aminophenylacetyl-tuftsin and tyrosyl-tuftsin. [Des-Thr1]tuftsin and [omega-NO2(4)]tuftsin were synthesized using a conventional procedure. The effects of synthetic peptides on the phagocytosis of heat-killed yeasts and on the reduction of the dye nitroblue tetrazolium by normal human polymorphonuclear leukocytes were investigated. Tuftsin and to a lesser extent [Lys1]tuftsin and [Ser1]tuftsin were found to stimulate phagocytosis, whereas the other analogs synthesized as well as [Ser1]tuftsin exhibited inhibitory effects to tuftsin's action. Tuftsin alone has stimulated nitroblue tetrazolium reduction; [Des-Thr1]tuftsin and [Ala1]tuftsin repressed this stimulation, while the other peptides showed no effect.


Ophthalmic Graves's disease: natural history and detailed thyroid function studies. Of 27 patients with ophthalmic Graves's disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH.


[Feeding of low-birth-weight infants].

[Feeding of low-birth-weight infants]. A child with low birth-weight is defined. Physiological and biochemical bases for the nutrition of these babies are given. Breast-feeding is recommended describing advantages and disadvantages compared with other milk formulas. Some artificial milk formulas in the national market are analyzed and modified milk or protein-modified milk are recommended as substitutes for mother's milk.


A gas-liquid chromatographic method for the determination of butriptyline in serum. 1. A gas-liquid chromatographic (GC) method for the analysis of butriptyline in serum has been development. Quantitation is based on the peak height ratio between butriptyline and promazine used as internal standard. A triple partition provides a "clean" extract. A detection limit of 10 ng/ml is achieved. 2. The usefulness of the method has been demonstrated in bioavailability studies in dogs.


Greater bioavailability of digoxin solution in capsules. Studies in the postprandial state. A liquid concentrate of digoxin administered as a capsule has recently been found to be better absorbed by normal subjects in the fasting state than a standard tablet or even a solution as such. It was not known whether the enchanced bioavailability of the encapsulated digoxin solution could also be demonstrated when given postprandially. In a crossover study single 0.4 mg doses of digoxin solution in a capsule, a solution in 10% ethanol as such, and a standard tablet were given to 12 normal volunteers immediately following a high-fat breakfast. The mean area under the serum concentration-time curve (AUC) and 6-day cumulative urinary glycoside excretion (CUE) were greater after the capsule than that of either the solution or the tablet. The latter two preparations appeared to be bioequivalent. Intersubject variability in the CUE was less than with the AUC, but did not differ when the three drug formulations were compared. The bioavailability of an encapsulated liquid digoxin concentrate was thus also found to be enhanced when administered postprandially.


On the competition between protamines and histones: studies directed towards the understanding of spermiogenesis. Specific contacts between the crossinteracting histones effectively prevent their protamine-mediated displacement from nucleoproteins revealing a complex competition pattern not expected from their relative affinities to DNA. Histone H1 is the only species freed under a variety of conditions if native chromatin is used; the results found with chromatins obtained by conventional methods reflect the extent to which histone redistribution has occurred. It is concluded that the events occurring during spermiogenesis must be apt to disrupt histone interactions found in the nucleosomes. The possible role of a protamine phosphorylation/dephosphorylation mechanism is discussed on the basis of comparative experiments with protamines phosphorylated to different extents.


Diet therapy of peptic ulcer disease.

Diet therapy of peptic ulcer disease. Information from 326 dietitians representing 50 states and Puerto Rico on the diet therapy of peptic ulcer disease (PUD) in their hospitals was analyzed. There were 74 teaching, 65 teaching/private, 46 private, 120 Veterans Administration, and 21 miscellaneous hospitals. A bland diet was the most commonly used diet for PUD in 250 (77%) of the hospitals. Of the 161 providing information on the type of bland diet, 72% used a bland I or II. Milk was given routinely or usually in 55% of the 326 hospitals. On discharge, dietitians in one-half of the hospitals instructed patients on a bland diet, usually a bland IV, whereas the remaining dietitians instructed their patients on a regular or modified regular diet. Outpatient PUD instruction was similar. Review of bland diets in 105 manuals revealed marked variation in nomenclature and composition of even supposedly similar diets. Uniformity would benefit patients, dietitians, and physicians.


Analysis of 100 patients with anterolateral rotatory instability of the knee. Of 100 consecutive patients with anterolateral rotatory instability analyzed, 84 were males and the average age was 27.4 years. Over 50 per cent were injured while participating in athletics and 40 per cent were injured during daily activities. The group averaged 1.2 operations prior to diagnosis. The most frequently performed procedures were medial meniscectomy, pes anserinus transfer and medial capsular reefings. Eighty-four of 100 patients underwent surgery during the study period. Seventy-one had combined rotatory instability and 13 had anterior lateral rotatory instability alone. Sixty-six patients had articular cartilage damage. Before treating the anterolateral rotatory instability, it is necessary to identify and treat other commonly associated abnormalities.


Plasma clofibric acid (CPIB) levels induced by three marketed compounds releasing clofibric acid, in volunteers. The very low plasma clofibric acid levels achieved in normolipemic volunteers during 96 h by a single dose of alufibrate (basic aluminum salt of clofibric acid) as 4 x 360 mg tablets, have been confirmed. With a crossover study in healthy volunteers receiving therapeutic doses of clofibrate as 2x500 mg capsules, clofibride as 2x450 mg capsules, twice daily for ten days, the plasma clofibric acid concentrations were already found in the therapeutic range after two days and remained above 80 mug/ml at the tenth day. On the other hand, the plasma clofibric acid concentrations measured during a ten-day administration of alufibrate as 2x360 mg tablets twice daily, were regularly found to be much lower at each time; they did not reach levels exceeding 60 mug/ml.


Hormonal changes induced by bromocriptine (CB-154) at the early stage of treatment. Fifteen female patients with amenorrhea and hyperprolactinemia were studied 1 to 3 times daily during the first 4 days of treatment with bromocriptine (2.5 mg b.i.d). Normal PRL levels were reached within one day in 12 while the mean value for the whole group showed no further significant decrease. Estradiol, LH and FSH levels did not vary significantly at this stage even in those 10 patients who subsequently resumed menstruation.


Phloretin-induced changes in ion transport across lipid bilayer membranes. Phloretin, the aglucone derivative of phlorizin, increases cation conductance and decreases anion conductance in lipid bilayer membranes. In this paper we present evidence that phloretin acts almost exclusively by altering the permeability of the membrane interior and not by modifying the partition of the permanent species between the membrane and the bulk aqueous phases. We base our conclusion on an analysis of the current responses to a senylborate, and the cation complex, peptide PV-K+. These results are consistent with the hypothesis that phloretin decreases the intrinsic positive internal membrane potential but does not modify to a great extent the potential energy minima at the membrane interfaces. Phloretin increases the conductance for the nonactin-K+ complex, but above 10(-5) M the steady-state nonactin-K+ voltage-current curve changes from superlinear to sublinear. These results imply that, above 10(-5) M phloretin, the nonactin-5+ transport across the membrane becomes interfacially limited.


Correlation of cell kinetic findings with morphology of non-Hodgkin's malignant lymphomas. Kinetic studies were carried out on 6 benign and 37 malignant lymph nodes from patients with non-Hodgkin's malignant lymphomas (ML). The labeling index, DNA content, and cell distribution through the cell cycle were analyzed in the ML, which were classified according to the Kiel classification. Approximately 90% of the ML studied showed a clear diploidy; the only cases of polyploidy were limited to some centroblastic-centrocytic ML with more than 30% malignant centroblasts and to be single centroblastic ML. The labeling indexes ranged from 0.05 to 33%. No correlation was found between the proliferative rate and the degree of ploidy, while a grading of labeling index was found in relation to the three main DNA distribution patterns observed (i.e., G1 peak, S accumulation, and bimodal distribution through the cell cycle). From a kinetic point of view, the most heterogeneous groups were the lymphoplasmacytoid (subtype polymorphous) and centroblastic-centrocytic ML, where the degree of proliferation increased as the mixture of cell type (relative to the former group) and the malignant centroblastic component (relative to the latter group) increased.


Annulate in four cases of diffuse lymphocytic lymphoma. Annulate lamellae were observed in 4 cases of diffuse lymphocytic lymphoma. Two lymphomas were well differentiated and 2 were of intermediate differentiation. These lymphomas had additional abnormalities of membranes: specifically, excessive blebbing of nuclear membranes and lattice-like formations of tubular endoplasmic reticulum.