Charcot arthropathy secondary to amyloid neuropathy.

Neuropathic (Charcot) ankle joints developed in a 50-year-old patient with end-stage renal disease from primary, nonfamilial amyloidosis. Sensory neuropathy in the legs had been noted three years before the onset of uremia and had porgressed. Sural nerve, but not synovial biopsy specimen, showed amyloid in and around arteriolar walls by light and electron microscopy. Since Charcot joints are only rarely associated with amyloid neuropathy, it is possible that uremic neuritis, or prolonged survival by dialysis, contributed to progression of the neuropathy, allowing subsequent joint degeneration.


Hemodialysis in the treatment of severe hypercalcemia.

Severe hypercalcemia is a life-threatening problem that requires prompt therapy. With the exception of diuresis, most forms of therapy are either ineffective, slow in action, or have major serious disadvantages. In some instances diuresis is relatively ineffective. As shown in this case report, hemodialysis with a dialysate low in calcium is rapidly effective in such instances and should be considered for patients with severe hypercalcemia while they are being prepared for surgery or while diagnostic studies are being performed.


Subacute constrictive uremic pericarditis. Survival after pericardiectomy.

Uremic pericarditis progressed to subacute constriction despite intensive medical treatment in two patients with concomitant metabolic stress of surgery and infection. Total pericardiectomy was successful and should be done as soon as medical measures fail to resolve the pericarditis.


Phenformin and lactic acidosis.

All patients admitted with severe lactic acidosis to a university teaching hospital during a 17-month period were taking phenformin hydrochloride. Serum phenformin concentration was measured in one patient and found to be four to nine times the usual therapeutic concentration. Prerenal azotemia was present at the time of admission in all but one of these patients, but renal function was normal at the time of discharge in those patients with phenformin-associated lactic acidosis who survived. Phenformin-associated lactic acidosis accounted for 7% of the episodes of metabolic acidosis and 27% of deaths due to metabolic acidosis in diabetics.


Systemic mastocytosis associated with presence of rheumatoid factor.

We encountered a case of systemic mast cell disease associated with rheumatoid factor; to our knowledge, this has not been reported in the literature. Rheumatoid arthritis as an unrelated second disease cannot be excluded, but there is support for a relation between joint symptoms, rheumatoid factor, and the mast cell disease.


Neuroblastoma in father and son.

A growing literature supports the concept that some cases of neuroblastoma are hereditary. To this we add the first known case, to our knowledge, of neuroblastoma in a parent and child. Various factors, such as the remarkable tendency for this tumor to regress spontaneously, as well as its frequent fatal outcome, have reduced the number of observed familial cases. It is important that siblings and progeny of patients with neuroblastoma be examined to detect possible subclinical neuroblastoma.


Respiratory failure in neuromuscular disease. Management in a respiratory intensive care unit.

Patients with neuromuscular disease frequently experience acute respiratory failure. Most require endotracheal intubation or tracheostomy and mechanical ventilation because of paralysis and inability to maintain adequate spontaneous respiration. The prognosis is usually excellent if ventilatory management is successful.


Leukopenia after postmastectomy irradiation.

Significant peripheral white blood cell depression was noted in 75% of postmastectomy patients receiving chest wall and nodal irradiation and in 50% of patients receiving only peripheral nodal irradiation. Leukopenia was documented for as long as 36 months following therapy. With the current trend to earlier institution of chemotherapy, the routine use of postoperative irradiation must be reevaluated.


Cardiovascular risk and use of estrogens or estrogen-progestagen combinations. Stanford three-community study.

Cardiovascular risk factors were assess in 986 women residing in three northern California communities. Women who reported current use of oral contraceptives had higher plasma triglyceride levels and systolic and diastolic blood pressures compared with women not using these agents, after adjusting for age and for the greater relative leannes of oral contraceptive users. Similar increases, albeit of lesser magnitude, were observed in women who used pure estrogens. Mexican-American women appeared to be more susceptible to the effects of estrogens, perhaps as a consequence of their greater degree of obesity.


The role of the intermediate cardiac care unit.

After the introduction of a 22-bed, monitored intermediate cardiac care unit (ICCU), cardiac care unit admissions increased by 15.7%. A further increase in patient admissions of 37% was permitted by direct admissions to the ICCU from the emergency room. The duration of the hospital stay of patients with acute myocardial infarct was shortened by three days. The success rate of cardiac resuscitation improved, and potentially serious arrhythmias were treated more promptly. Hospital costs were substantially reduced by the use of a convalescent unit for patients whose ICCU stay was uncomplicated. Concentration of cardiac patients and specialized staff and equipment permitted more efficient care.


Selective coronary arteriography. Risk in a community hospital.

Over a 33-month period, selective coronary arteriography was performed in 627 consecutive patients in a 385-bed, non-university-affiliated community hospital. Mortality was 0.16% (one death); there was also one nonfatal myocardial infarction. No deaths or myocardial infarctions occurred in the last 369 consecutive patients in this series when routine systemic heparinization was introduced. Substantially greater risk of mortality (2.6%) and nonfatal myocardial infarction (2.6%) was encountered in an earlier series of 78 consecutive patients for whom a different protocol was used. It included extensive exercise hemodynamic studies with the use of percutaneous arterial angiographic catheters, without systemic heparinization. This indicates that coronary arteriography can be carried out with acceptable risk in a community hospital. Protocols should be designed to minimize the time that catheters are in the arterial system. Systemic heparinization may reduce the risk of procedure-related death and myocardial infarction.


Variant angina pectoris. Pain and arrhythmias controlled after postoperative myocardial infarction.

A 30-year-old man with variant angina pectoris and ventricular arrhythmias had an angiographically demonstrable 60% obstructive lesion of the proximal left anterior descending coronary artery that was observed to progress to 100% during spasm. Control of pain and arrhythmia by pharmacologic means was unsuccessful. Aortocoronary saphenous vein-internal mammary coronary bypass was associated with an anteroseptal wall myocardial infarction and relief from both angina pectoris and arrhythmias. It is suggested that infarction of the ischemic myocardium played a role in the successful management of this case.


Death from myocardial infarction after exercise test with normal result.

Death from acute myocardial infarction immediately followed a submaximal exercise test with a normal result in a 56-year-old man. Hemorrhage into an intimal atherosclerotic plaque with superimposed, intraluminal clot formation was the cause of coronary artery occlusion. It is probable that the exercise precipitated  an intramural capillary rupture and intimal hemorrhage or caused further hemorrhage into a preexisting intimal hematoma. The resulting luminal narrowing and intimal rupture with superimposed clot formation caused coronary artery occlusion.


Amelioration of insulin lipoatrophy by dexamethasone injection.

Widespread subcutaneous lipoatrophy occurred in a 47-year-old woman after subcutaneous injections of isophane insulin suspension for five months. Subsequent systemic treatment with a dexamethasone (0.08 mg/day) insulin mixture injected subcutaneously into the depressed areas resulted in an impressive return of subcutaneous tissue after eight months of continuous therapy.


Release of protein and cations from the lens in the presence of different antigen-antibody interactions.

Rabbit lenses exposed to unrelated Ag/Ab interactions and to heterologous anti-lens and anti-uveo-retinal antibodies show alterations of their permeability with loss of Rb+ followed by efflux of macromolecular intracellular constituents; these phenomena take place also without complement when the ratio of the unrelated Ag/ab is in Ag excess, while complement is strictly required for the action of anti-tissue antibodies. The possible role of these findings as regards the pathogenesis of complicated cataracts in uveitis and the self-maintenance of recurrent uveitis is briefly discussed.


Antecedent events in amyotrophic lateral sclerosis.

To identify antecedent events contributing to the development of amyotrophic lateral sclerosis, we studied 25 amyotrophic lateral sclerosis patients in whom we tabulated the incidence of factors previously associated with motor neuron disease and compared the incidences with those found in 25 hospitalized patients and 25 normal people. More amyotrophic lateral sclerosis patients reported exposure to lead and mercury, participation in athletics, and consumption of large quantities of milk. Exposure to lead and mercury, athletic participation, and milk ingestion are possible risk factors that may predispose to the development of amyotrophic lateral sclerosis.


Computed tomography in Graves' ophthalmopathy.

The CT scan with the 160 x 160 matrix demonstrated both the normal orbital anatomy and the abnormal orbital anatomy of Graves' ophthalmopathy in great detail. In Graves' ophthalmopathy, the cardinal pathologic feature of extraocular muscle enlargement was accurately reflected on the CT scan and was a distinctive, diagnostically reliable finding. Enlargement of the medial and lateral rectus muscles and of the apex of the muscle cone were the most consistent findings. The severity of the CT scan abnormalities correlated well with clinical severity. Because muscle cone abnormality was observed characteristically in those patients with sight loss, we suggest that pressure by the extraocular muscles on the optic nerve may contribute to visual acuity loss in this disease.


Food antibodies in patients with dermatitis herpetiformis and adult coeliac disease - relationship to jejunal morphology.

Serum antibodies to a variety of dietary proteins were investigated in 26 patients with adult coeliac disease (ACD, 14 untreated and 17 treated with a gluten-free diet) and 38 patients with dermatitis herpetiformis (DH) with varying small bowel abnormalities. The incidence of one or more positive tests was highest in untreated ACD (73.4%) and DH with subtotal villous atrophy (57.4%). This incidence fell with morphological improvement, being 56.4% in treated ACD patients with partial villous atrophy (PVA), and 33.4% in DH with PVA, and 0% in DH with normal biopsies. The height of the serum antibody titre also fell with morphological improvement. These results show that there is an abnormally high incidence of dietary antibodies in patients with DH, and this correlates with the degree of small bowel damage.


Diffuse lymphosarcomatous infiltration in the central nervous system.

Massive lymphosarcomatous infiltration, confirmed at autopsy, occurred in a 46-year-old man with neurological signs rapidly progressing to total paralysis of peripheral as well as cranial nerves. These signs set in at a time when the malignant systemic disease seemed to be otherwise in remission, and indeed they gave rise to great differential diagnostic difficulties.


Carcinoma in situ of the cervix uteri in pregnancy.

After reviewing the charts of patients at the Tulane Unit of Obstetrics and Gynecology of Charity Hospital between the years 1950 and 1970, 25 patients were noted to have carcinoma in situ of the cervix uteri associated with pregnancy. Twenty-two patients had positive Papanicolaou smears. Subsequently, 20 patients had conization of the cervix uteri to exclude an invasive lesion. Vaginal delivery was accomplished in 17 of the patients. After complete re-evaluation, definite treatment was done six to eight weeks post partum, and there were no recurrences or deaths from the disease.


Genetic counseling. An evaluation of public health genetic clinics.

The geographic distribution of County Health Department clinic facilities in the state of California has made it readily possible to establish a regionalized program for genetic counseling services, using public health nurses as a major source of case-finding. From both consumer and health professional standpoints, regionalized satellite genetic counseling clinics have been successful, and in particular, the effectiveness of public health nurses in identifying clinical genetic problems is readily apparent.Long-term follow-up reinforcement of genetic counseling appears to be an important conclusion from these studies. It is our suggestion that reinforcement of counseling would best be accomplished through the health team member (physician, nurse and so forth) following the patient or family rather than through the consulting geneticist.


Growth hormone and somatomedin behaviour in the newborn.

Human growth hormone (HGH) and somatomedin (Sm) concentrations have been studied in a group of newborns. Plasma HGH values were 41.17 +/- 24.26 (SD) ng/ml (14.00-90.00 ng/ml) and the Sm value was 0.59 +/- 0.43 (SD) U/ml (0.18-1.8 U/ml); the difference between these values and the ones observed in normal adults (2.45 +/- 2.53 (SD) ng/ml and 1.16 +/- 0.28 (SD) U/ml respectively) were statistically significant. While growth hormone values were higher than in normal adult controls, somatomedin was significantly decreased. It is possible that the dissociation between human growth hormone and somatomedin in newborn could reflect a reduced biosynthesis of the somatomedin-generating system and consequently a lack of a feed-back control on GH exerted by somatomedin.


Inhibition of mid-cycle gonadotrophin release in healthy women by pimozide and fusaric acid.

The effects of pimozide, a drug blocking dopamine receptors, and fusaric acid, an inhibitor of dopamine beta-hydroxylase, on mid-cycle release of FSH and LH were studied in 8 healthy women 20-25 years of age. None had used contraceptive drugs for the preceding 10 months. From the menstrual history and serum LH determinations during the normal cycle, mid-cycle gonadotrophin bursts were predicted for the following three cycles. Two days before and after the expected gonadotrophin surge were regarded as sufficient for the drug tests. Pimozide (initially 2 mg, then 1 mg/day) and fusaric acid (600 mg/day) were administered in a randomized cross-over study. The mid-cycle LH values were reduced from the control level of 56 +/- 10 mIU/ml (mean +/- SE) to 22 +/- 4 mIU/ml by pimozide (P less than 0.001) and to 17 +/- 5 mIU/ml by fusaric acid (P less than 0.001). The serum FSH level was 9 +/- 2 mIU/ml on the day of the LH surge and did not change significantly during treatment with either drug. The LH and FSH responses to synthetic LRF (100 mug iv) were not changed by pimozide or fusaric acid. The rise of basal temperature associated with ovulation was not affected by the drugs. These results suggest that suprapituitary noradrenergic and dopaminergic neurotransmitters are involved in the regulation of mid-cycle gonadotrophin secretion in women.


Heterologous radioimmunoassay for bovine follicle-stimulating hormone and its application during the oestrous cycle in cattle.

A specific heterologous radioimmunoassay for bovine follicle-stimulating hormone (bFSH) has been developed using guinea pig antiserum to ovine FSH with radio-iondinated ovine FSH. Slight cross-reactions with bovine TSH and LH could be eliminated by adding bovine TSH and LH to each tube during the assay. The labelling method with lactoperoxidase turned out to be more useful than the chloramine-T method. Inhibition curves obtained with male and female bovine plasma were parallel to those obtained with the bovine standard preparation. Exogeneous bFSH could be quantitatively recovered from 200 mul of plasma or serum with a mean of 101.7 +/- 7.7%. The intra-assay coefficient of variation (CV) was less than or equal to 6%. The inter-assay CV was 13.5%. Sensitivity was 70 ng/ml NIH-FSH-B1. Mean plasma concentrations of FSH (NIH-FSH-B1) during the oestrous cycle were 303 +/- 101 ng/ml. When plasma samples were collected in 6 h intervals from 17 oestrous cycles from 13 regularly cycling heifers and cows, a significant FSH peak occurred just before and during oestrus and coincided with the preovulatory LH peak. Further FSH elevations could be measured on day 4, 8 and 12 after ovulation and 5 and 3 days before ovulation and showed a rhythmic pattern of four day intervals approximately.


In vivo activation of synthetic hormonogens of lysine vasopressin: Na-glycyl-glycyl-glycyl-[8-lysine]vassopressin in the cat.

The urine and plasma levels of vasopressin-like immunological activity and of antidiuretic activity were examined following injection of Na-glycyl-glycyl-glycyl-[8-lysine]vasopressin (triglycylvassopressin, TGLVP) in 3 cats. The plasma levels of immunoreactive material were initially high, and fell rapidly. The levels of antidiuretic activity showed considerable variation; the overall pattern was strikingly different from that demonstrated by radioimmunoassay, and all 3 animals showed a rise in plasma antidiuretic activity in the early part of the experiment. Following injection of lysine vasopressin (LVP) the pattern of disappearance of both biological and immunological activity was similar. The total amount of immunoreactive material found in the urine was greater than the amount of antidiuretically active material. These results clearly demonstrate that the antidiuretic activity of TGLVP is mainly due to its conversion to LVP in vivo.


The degree of bone mineralization in hyperthyroidism estimated from the phosphorus to hydroxyproline ratio in bone.

The proportion between mineral and collagen in bone tissue, "the degree of mineralization", can be evaluated from the phosphorus to hydroxyproline ratio (P/Hypro ratio), determined in bone biopsies. The ratio was measured in 27 unselected hyperthyroid patients. No significant correlation was found between the P/Hypro ratio and the age of the patient, the duration of the disease or the value of serum thyroxine. The mean value of the P/Hypro ratio for the group studied was not significantly different from the normal mean. The results of the study indicate a normal degree of mineralization in the bone of patients with hyperthyroidism.


Rapid simultaneous radioimmunoassay for the measurement of triiodothyronine and thyroxine in unextracted human serum.

A rapid simultaneous radioimmunoassay for the measurement of triiodothyronine and thyroxine in unextracted human serum is described. The method requires 25 mul serum. Approximately 150 human sera can be tested for triiodothyronine and thyroxine levels in one day by one technical assistant. The triiodothyronine levels in peripheral venous blood in euthyroid subjects and in patients with various thyroid diseases are as follows: euthyroid (50) 115 +/- 22 (mean +/- SD) ng/100 ml, hypothyroid (20) 33 +/- 35 (mean +/- SD) ng/100 ml and hyperthyroid (20) 411 +/- 142 (mean +/- SD) ng/100 ml. The corresponding levels for thyroxine are: 6.9 +/- 1.3, 2.0 +/- 1.4 and 21.4 +/- 5.2 mug/100 ml. The levels of triiodothyronine in the thyroid venous blood are higher (P less than 0.05) than in the peripheral venous blood. The levels of thyroxine in the thyroid venous blood was not significantly higher than in peripheral venous blood.


Inhibition of thyroglobulin biosynthesis and degradation by excess iodide. Synergism with lithium.

Lithium and excess iodide inhibit the release of thyroid hormone from preformed stores. We thus tested the hypothesis that this was due to an inhibition of thyroglobulin breakdown. Rats were pre-treated with propyl-thiouracil (PTU) for 3 weeks in order to deplete their thyroids of thyroglobulin. While the PTU was continued, lithium chloride (0.25 mEq./100 g weight) or potassium iodide (3 mg per rat) were injected every 12 h for d days. Thereafter the thyroglobulin content in thyroid gland homogenates was measured. PTU pre-treatment lowered the thyroglobulin content from 4.21 to 0.22 mg/100 mg gland. Lithium caused a marked re-accumulation of thyroglobulin to 0.60 mg/100 mg within 3 days. While iodide alone had only a borderline effect, it markedly potentiated the action of lithium and a combination of the two drugs increased the thyroglobulin content to 1.04 mg/100 mg. Thyroxine was injected into similarly pre-treated animals to suppress secretion of thyrotrophic hormone. This markedly inhibited the proteolysis of thyroglobulin and 1.3 mg/100 mg gland accumulated after 3 days. Excess iodide, given in addition to thyroxine, decreased the amount of thyroglobulin accumulated to 0.75 mg/100 mg gland. To study whether this could be explained by an inhibitory action of iodide on thyroglobulin biosynthesis, thyroid glands from animals treated with excess iodide were incubated in vitro in the presence of 0.2 mM iodide for 3 h. Iodide decreased the incorporation of radioactive leucine into total thyroidal protein and into thyroglobulin by 25 and 35% respectively. Iodide did not inhibit protein synthesis in the kidney, liver or muscle tissue. Thus, large doses of iodide selectively inhibit thyroglobulin biosynthesis.


Effect of somatostatin on basal and glucose induced insulin release in five patients with hyperinsulinaemia.

Somatostatin in a dose of 490 mug over 90 min inhibited basal insulin release in one subject with hyperplasia of the pancreatic islets and in two with benign insulin secreting adenomas. These three subjects also showed a marked insulin response to glucose infusion. No inhibitory effect of somatostatin was observed in two patients with benign insulinomas who demonstrated only a minor response to glucose. In the patient with islet hyperplasia and in one of the adenoma patients, who had an exaggerated insulin response to glucose (maximal response 10-30 times the basal insulin value), somatostatin also suppressed glucose induced insulin release. Our data suggest a beneficial therapeutic effect of somatostatin in patients with spontaneous hyperinsulinism with a pronounced insulin response to glucose.


Ultramorphometric studies of the adrenal cortex of adult rats after neonatal administration of sex steroids.

The outer zona fasciculata of 28 Sprague-Dawley rats, 8 weeks old, was studied by means of ultramorphometry. Four males and 4 females each received 1250 mug of testosterone proprionate (TP) or 300 mug oestradiol benzoate (OeB) on the second day of life. Four males and 4 females in oestrus or dioestrus served as controls. The controls showed both sex and cyclic differences: in comparison to the males, females displayed a finely dispersed lipoid pattern; enlargement of the nucleus and an increase in the amount of smooth endoplasmic reticulum (SER) indicated an increased stimulation of the cortex during oestrus. Neonatal administration of TP in females causes a distinct enlargement of cells with an increase in the volumes of nucleus, mitochondria, liposomes, SER and liposomes. The mitochondria and liposomes show a small-dispersed pattern of distribution. All these function-specific morphometric parameters point to an increased activity of the individual cell. The changes are less pronounced after OeB than after TP. In the male, neonatal administration of sex steroids results in an alteration of the sizes of the mitochondria and liposomes. The liposomes are distributed finely dispersed. At the same time there is an increase in the lipoid content. According to these parameters, fasciculata cells fulfil the morphological conditions that are a prerequisite for an elevated functional reaction. This change is more marked following OeB than TP. Sex dimorphism is preserved following neonatal application of sex steroids since the alterations are much more pronounced in females than in males.


Sialic acid and sialidase activity in human endometrial tissue, uterine fluid and plasma under different conditions of uterine dysfunction.

Sialic acid content in endometrial tissue and sialidase activity in the endometrium, uterine fluid and plasma has been measured in normal and in conditions of uterine dysfunctions. It has been observed that an antagonistic effect exists between endometrial sialidase and sialic acid content, but in all the cases of uterine dysfunctions, the sialidase activity in uterine fluid and plasma decreases, whereas it increases during pregnancy.


RNA metabolism in chick oviduct during oestrogen stimulation.

The amount and the labelling of RNA were studied in chick oviduct after secondary stimulation of pre-treated chicks with oestrogen. The weight of the oviduct increases over 2 fold in 20 h of oestrogen action using a dose of 1 mg. During the hormonal treatment the amount of cytoplasmic and nuclear RNA increases about 3 and 1.5 fold, respectively. The amount of poly(A) containing RNA increases somewhat less than that of RNA lacking poly(A). The proportion of poly(A) containing species of the total cytoplasmic and nuclear RNA decreases from 5.8% to 4.4% and from 7.8% to 6.3%, respectively. Hydroxyurea largely prevents the effect of oestrogen in increasing the amount of RNA. Incorporation of [3H]uridine in RNA in vitro is stimulated about 2.5 fold in cytoplasmic RNA lacking poly(A) and only 1.2 fold in RNA containing poly(A) in 20 h of oestrogen action. In nuclear RNA the labelling of the two species is stimulated about 1.7 fold. Hydroxyurea fails to interfere with the oestrogen-induced stimulation in the labelling of RNA. Cytoplasmic and nuclear RNA containing poly(A) is distributed in a peak of about 20 S in agarose-acrylamide gels.


Translation of avidin mRNA from chick oviduct in the oestrous mouse uterus.

Oestrogen-primed immature chicks were injected with 5.0 mg of progesterone. Twenty hours after progesterone avidin mRNA was isolated and purified by a method including an antibody precipitation of the avidin polysomes, phenol extraction and nitrocellulase trapping. A water solution of mRNA (1 mug) with [14C]amino acids was instilled into the uterine horn of oestrous or dioestrous mice. Saline and [14C]amino acids were injected into the opposite control uterine horn. Avidin was assayed by an antibody method. A clear-cut avidin synthesis was found in the oestrous uterus, whereas the dioestrous showed only a slight avidin synthesis. This suggest that there are no absolute species-specific factors required at the translational level of uterine protein synthesis and that the mammalian uterus can translate foreign hormone-specific proteins at a rate dependent on the endogenous protein synthesis.


Differences in urinary excretion of steroid 21-deoxyketols by women pregnant with a normal or an anencephalic foetus.

During late pregnancy the urinary excretion of steroid 21-deoxyketols, which contain the CH3-CO-C(OH)less than side chain, was 1.16 +/- 0.50 mg/24 h (mean +/- SD n = 9). The mean excretion of these metabolites in 8 pregnancies with an anencephalic foetus showed a significant reduction (P less than 0.01, t-test) to 0.42 +/- 0.18 mg/24 h. Six untreated non-pregnant women and 7 taking oral contraceptives which contain oestrogen had steroid 21-deoxyketol excretions of 0.26 +/- 0.09 mg/24 h and 0.19 +/- 0.09 mg/24 h respectively. These results imply that the adrenal of the normal foetus makes a contribution to the secretion of those steroids which are ultimately excreted by the mother as 21-deoxyketols.


Comparison of the methods for measuring human chorionic gonadotrophin after hydatidiform mole.

Six patients who had hydatidiform mole and who subsequently developed clinical choriocarcinomas were studied. Serial plasma samples were assayed for HCG content by (i) haemagglutination-inhibition test (HI test), (ii) a non-specitic radioimmunoassay and (iii) a specific radioimmunoassay developed against the beta-sub unit of HCG. When levels of HCG were high all three assays gave results which parallelled each other. However, the radioimmunoassays were able to detect the presence of HCG several weeks after the HI test became negative. Luteinizing hormone cross-reacted in the non-specific radioimmunoassay of HCG and may lead to false positive results. The present study indicated that it is important to employ the radioimmunoassay against the beta-sub unit of HCG to permit a specific assessment of HCG activity and thereby provide a reliable monitoring of patients following hydatidiform mole or with choriocarcinoma.


Diurnal testosterone and 17alpha-hydroxyprogesterone in peripheral plasma of young post-pubertal bulls. A study by frequent sampling.

Testerone and 17alpha-hydroxyprogesterone were measured in the peripheral plasma of 6 young post-pubertal bulls of 1 year of age, by separate radioimmunoassays. Samples were collected every hour for 25 h at the beginning of each of four seasons. On a separate occasion blood samples were collected from one bull every 10 min for 2 h. As a result of the study, testosterone and 17alpha-hydroxyprogesterone appeared to be secreted episodically. These two steroid peaks showed good correlation. Each 24 h period showed its own characteristic pattern of pulsatile changes. Episodic secretion seems to be progressive rather than rapid and short lived. No real circadian rhythm was observed but at about 10.00 a.m. a trough in these steroid secretions occurred. This was followed by an increase in peripheral plasma concentration. These troughs occurred at all seasons after the morning feed and while semen was being collected in the performance test station.


Effect of synthetic gonadotrophin-releasing hormone (Gn-RH) on circulating luteinizing hormone (LH) and testosterone in young post-pubertal bulls.

The reproducibility of LH and testosterone responses after Gn-RH treatment in young post-pubertal bulls was tested. Ten bulls were injected im (250 mug) twice with an interval of 4 weeks. Blood samples were collected every 15 min for 21/2 h and then on the second occasion, every hour. LH increases very rapidly and reaches an initial peak by 30 min after Gn-RH injection. This increase over basal level was 25 to 30-fold. After a plateau of high levels lasting 40 to 50 min, a second peak of LH concentration occurs. LH then decreases and returns to basal levels by 6 to 7 h after treatment. The increase of plasma testosterone was more prolonged and of smaller magnitude than that of LH: 3 to 4-fold. There was a large and significant variation between bulls; but with LH, a given individual responded in a consistent manner on the two separate occasions. It is concluded that LH response to Gn-RH treatment might be useful and should be tested as a diagnostic value for clinical or breeding purposes. The testosterone response does not seem to be as valuable and reliable as that of LH.


The effects of castration on body composition, adipose tissue cellularity and lipid and carbohydrate metabolism in adult male rats.

Gonadal hormones affect body composition, food intake, weight gain and serum lipids in numerous species including man. In this study, mature male Sprague-Dawley rats were castrated or sham-operated at 16 weeks of age. During the 6-week observation period with weekly records of food intake and weight gain, these parameters were significantly lower in the castrated group. The decrease in food intake in this group could not account for the difference in body weight between the groups, indicating a lower feed utilisation in the castrates. At sacrifice accessory reproductive organs, the levator ani muscle, thymus and adrenals were dissected for determination of organ weight and histology, revealing significant reductions in the accessory reproductive organs and levator ani of the castrates. The thymus was significantly heavier in the castrated animals. No differences were found in the adrenals. Two of the sham-operated animals had signs of accidental functional castration. The proportion of body cell mass and total lipid of the carcass was the same in both groups. Significant reductions in adipocyte weights were found in the epididymal depots of the castrated rats. Blood samples taken at sacrifice in pentobarbital anaesthesia were analysed for glucose, insulin, triglycerides, cholesterol, FFA, glycerol and protein. Statistically significant reductions in triglycerides and protein were recorded in the castrated animals without any significant changes in the other parameters studied. The results are discussed with reference to the age of castration and the importance of the reduced food intake in castrated animals.


Radioimmunoassay of oestrone in plasma. A comparison of different methods with respect to the relation between assay specificity, sample purification and antibody specificity.

A radioimmunoassay (RIA) for oestrone (Oe1) in plasma was developed using an ether extraction, a partition between NaOH and light petroleum, and a TLC as sample purification and an antiserum cross-reacting with Oe2 for the final assay (Method A1). The reliability criteria are given in detail. In order to simplify this method a highly specific antiserum was developed by using Oe1-3-hemisuccinate-BSA as an antigen. Using this antiserum for the final assay but omitting the TLC (Method B) the Oe1 concentration in male plasma was 76% overestimated (Method B compared with Method A1). In pregnancy plasma Oe1 could specifically be determined after a simple ether extraction (Method C). It was concluded that the use of a highly specific antiserum (as determined by cross-reaction studies) for the final assay does not necessarily imply that a chromatographic sample purification can be omitted without loss in assay specificity. This appears to be true mainly in cases where the steroid concentration of the sample is low. Normal values of Oe1 from 80 healthy adult males were ascertained by Method A1. Age group I (22-61 years, n = 48) ranged from 1.22-5.60 ng/100 ml, median 2.81; age group II (67-90 years, n = 32) from 1.55-6.40, 100 median 3.41. The small increase of Oe1 with age was highly significant.


Melanotropic drugs and retinal functions. I. Effects of quinine and chloroquine on the sheep ERG.

The present work is the first in a series of investigations on the effects of melanotropic drugs on retinal function. Teh changes in the conventional ERG of the dark-adapted, intact sheep eye were studied after iv administrations of quinine and chloroquine. Both drugs influenced the ERG in principally the same way. Small doses changed only the c-wave amplitude which began to oscillate after a delay of about 1 hour. Larger doses had an immediate effect on both the b- and c-waves. The b-wave amplitude dropped and the c-wave showed an initial peak followed by oscillatory changes about 1 h later. These late changes were similar to those observed after administration of small doses of the drugs. The present results indicate that small doses of quinine and chlorquine have a delayed effect on the pigment epithelial cells, while larger doses exert a more immediate and general retinotoxic effect.


Melanotropic drugs and retinal functions. II. Effects of phenothiazine and rifampicin on the sheep ERG.

The acute effects of chlorpromazine, promethazine and rifampicin on the a-, b- and c-waves of the conventional electroretinogram (ERG) were studied in sheep. Iv administration of chlorpromazine and promethazine resulted in a b-wave amplitude decrease and an initial c-wave amplitude decrease, followed by cyclic amplitude changes resembling damped oscillations. Iv injections of rifampicin, however, resulted in cyclic changes of the c-wave amplitude without initial concomitant b-wave changes. The results of the present study indicate that rifampicin has a selective influence on the pigment epithelial cells, while chlorpromazine and promethazine seem to have more generalized retinal effects on both the neuroretina and the pigment epithelial cells.


Blood-aqueous barrier in newborn and young rabbits. An electron microscopic study.

Distribution of intravenously injected horseradish peroxidase (HRP) in the ciliary body of newborn and young (2 weeks old) rabbits was studied with the electron microscope. The reaction product was localized in all animals in the lumen of the blood vessels, in the perivascular area, in the surrounding connective tissue stroma and also in the epithelial cell layers. The peroxidase penetrated through the intercellular junctions of the pigmented cells to the intercellular space between the apical membranes of the two epithelial cell layers. In young rabbits peroxidase penetrated between the apical intercellular clefts of the non-pigmented cells in small quantities only, whereas in the newborn animals the clefts were filled with peroxidase. This reflects differences in the blood-aqueous barrier mechanism between the two studied groups and is evidently due to developmental stages of the eyes.


Resemblance between tonometer readings on relatives and spouses.

The resemblance between tonometer readings on relatives and spouses was studied in a material derived from a population survey and consisting of 1042 unique individuals forming 365 nuclear families and 1333 pairs divided into groups with different sex-composition and type of connection. Persons in whom glaucoma was suspected were excluded. The general level of resemblance in the present study was similar to that in previous studies. Differences between groups with different sex-composition conformed to a pattern expected from environmental effects. The resemblance between husbands and their wives was highly significant and of the same order of magnitude as that in relatives sharing a common genetic background. We concluded that a common environment contributes materially to the resemblance between tometer readings on relatives. The possibility of a cumulative environmental effect was suggested by an increase in resemblance with age.


The "Knapp-Ronne" type of malignant melanoma of the choroid. A haemangioma-like melanoma with a typical clinical picture. So-called "preretinal malignant choroidal melanoma".

Five cases of a rare type of malignant melanoma of the choroid with a typical clinical and histopathological picture are reported. This tumour is characterized by it location near the optic disk,its early growth through the retina, its structure with bloodless and blood-filled cavernous spaces, and its manifestation by a massive haemorrhage into the vitreous. "Historical" cases are mentioned, showing that this rare tumour, occurring in about 1:250 of malignant melanomas of the choroid, has a Scandinavian tradition. The clinical and histopathological details are discussed.


Chorio-retinal resection of a neoplasm from the human eye.

An epithelioma was removed from the iris and ciliary body of a six-year-old girl by a partial irido-cyclectomy. Three months later recurrence of the tumour was seen in the equatorial zone of the fundus. Three weeks after application of transscleral cryotherapy around the neoplasm, a chorio-retinal resection of the tumour area in the fundus was performed. The postoperative healing was satisfactory. Re-examination 16 months later revealed a healthy eye. The results indicate that a circumscribed tumour can successfully be resected from the fundus.


Prognosis of primary rhegmatogenous retinal detachments. 2. Accounting for and predicting final visual acuity in surgically reattached cases.

Multiple linear regression-analysis of variance was used to define relationships between final visual acuity and several parameters in 31 patients with reattached primary rhegmatogenous retinal detachments. Older patient age, preoperative macular detachment, clinically visible macular lesions, greater detachment duration and extent, and higher subretinal fluid butyrylcholinesterase activity were all inversely related to final acuity. The relationship of each parameter to final acuity, in conjunction with and apart from all the other parameters, was defined. Collectively the parameters accounted for 85% of the variation about the mean of the clinically observed finally acuities. The parameters could be weighted to give a generally, reasonably accurate prediction of final acuity at the time of surgery. The findings are consistent with a pathophysiological sequence involving alterations in the choroidal circulation and the blood-ocular barrier of the posterior segment.


Sympathetic nerves to the rat cornea.

The adrenergic innervation of the rat cornea was investigated by using the formaldehyde induced fluorescence (FIF) technique. The fluorescent nerves were observed mainly in the corneal stroma. Either cervical sympathectomy or pre-treatment with reserpine completely abolished the fluorescence of the adrenergic nerves of the cornea. After a stereotactic coagulation of the ophthalmic division of the trigeminal nerve, no adrenergic fibres were visible in the cornea and the number of the fluorescent iridic nerves was also reduced to a marked extent. On the other hand, ciliary ganglionectomy seemed to have no effect on the adrenergic fibres of the cornea. When the rats had been pre-treated with a monoamine oxidase inhibitors, nialamide, and noradrenaline, not only was there an increase in the intensity of the specific fluorescence, but also in the number of adrenergic nerves in the cornea. The epithelium was also shown to contain adrenergic nerves by administering high doses of nialamide combined with noradrenaline, both intravenously as well as topically on the cornea, under the protection of propranolol. It may be concluded that the rat cornea receives its adrenergic innervation along the posterior ciliary nerves. The short ciliary nerves do not appear to carry sympathetic nerves to the cornea.


Effects of denervations on the acetylcholinesterase-containing and fluorescent nerves of the rat iris.

The thiocholine method for the demonstration of AChE-containing fibres and the formaldehyde-induced fluorescence technique for the visualization of adrenergic fibres were employed to study the innervation of the albino rat iris. The following denervations were performed in order to verify the origins of different nerve types: (1) extirpation of the ciliary ganglion, (2) extirpation of the superior cervical ganglion, (3) stereotactic coagulation of the ophthalmic division of the trigeminal nerve, and (4) all possible combinations of the above-mentioned procedures. The denervations disclosed three main types of AChE-containing nerves in the iris: (1) nerve fibres degenerating after ciliary ganglionectomy, (2) thick nerve bundles in the dilator region disappearing after trigeminal neurotomy, and (3) fibres remaining intact after any type of denervation. Cervical sympathectomy had no effect on AChE-positive fibres. Under electron microscope AChE activity could be seen in the axolemma both in unmyelinated and in myelinated fibres. All fluorescent fibres vanished after ipsilateral cervical sympathectomy. Most of these fibres also disappeared after trigeminal neurotomy and the remaining fibres degenerated after subsequent ciliary ganglionectomy. On the basis of the present findings, the following conclusions can be drawn: (1) Most AChE-containing fibres of the rat iris originate in the ciliary ganglion. (2) The majority of the myelinated sensory fibres of the rat iris also contain AChE. (3) There is no AChE in the adrenergic fibres of the rat iris. (4) All adrenergic fibres of the rat iris originate in the ipsilateral superior cervical ganglion, and (5) these fibres enter the iris along with both the long and short ciliary nerves.


The nature of capsular inclusions in lenticular chalcosis. Report of a case.

A case of lenticular chalcosis has been studied where the accidentally implanted brass fragment had been removed 2 years prior to extraction of the lens. Characteristic capsular inclusions were found which did not contain copper. The inclusions probably consisted of a lipoid material.


Relationship of lactose intolerance to milk intolerance in young children.

The prevalence of lactose intolerance as revealed by the standard lactose tolerance test was compared with the occurrence of intolerance to graded amounts of milk in 69 black and 30 white children. Of the black children studied, 11% of those 4 to 5 years old, 50% of those 6 to 7 years old, and 72% of those 8 to 9 years old were found to be lactose-intolerant, yet no child was intolerant to 240 ml of milk. Symptom responses to greater amounts of milk did not suggest that the frequency of primary lactose intolerance might be a reason for limiting existing milk programs for young children. No significant differences were found between the milk intakes of black lactose-tolerant and black lactose-intolerant children, nor between milk intakes of 6- and 7-year-old black and white children in Boston. However, 8- to 9-year-old black children drank significantly less milk than 8- to 9-year-old white children did. The blood glucose response at 0, 20, and 45 min after the ingestion of 2 g lactose/kg (maximum 50 g) was unreliable as an indicator of an individual's symptomatic response to lactose.


Congenital graves disease. Four familial cases with long-term follow-up and perspective.

Congenital Graves disease has been described as a transient disorder in which the mother has or has had hyperthyroidism. Experience with four affected children to ages 5 to 9 years and a review of published cases led us to conclude that long-acting thyroid stimulator (half-life, six days) is not the cause of the disease. This disease occurs in infants from families with a high incidence of Graves disease, and, in many, hyperthyroidism persists for months or years. The pathogenesis of Graves disease is unknown, and the simplistic maternal-to-fetal humoral theory is not a suitable explanation for congenital Graves disease. If Graves disease is considered in the larger perspective than the maternal-fetal unit, a pattern of inheritance is apparent, ie, an autosomal-dominant trait with a predilection for the female individual.


Ultrasonic examination of the thyroid gland. Possibilities and limitations.

In 440 patients with various thyroid disorders scintiphotography and ultrasonography were carried out. For ultrasonic examination both the A-mode and B-mode display technics were employed, included in the study were 324 patients with hypofunctioning solitary nodules; a histopathologic diagnosis could be obtained in 151 of these. The method proved to be especially valuable for differentiating between solid and cystic nodules. This is of practical importance because completely cystic nodules are nearly always benign and may be treated by thin needle puncture with aspiration of the cyst fluid. In addition, ultrasonography is of some value in making a better functional classification of nodules, better estimating the size of the thyroid and in the follow-up of patients with various thyroid disorders who are under treatment or untreated. Differentiating between benign and malignant solid nodules was not possible with the technic used. The examination can be safely carried out in pregnancy. The limitations of the technic are discussed.


Minimal hepatic changes in rats fed alcohol and a high casein diet.

This study was designed to determine whether prolonged ingestion of alcohol in combination with a nutritious diet can produce hepatic cirrhosis in the rat. Male Wistar-strain rats were fed a high protein liquid diet in which alcohol comprised 35.5% of total calories. Rats maintained on this diet for 19 months had normal growth. There was no evidence of cirrhosis after 19 months. Histological examination showed no hepatocellular necrosis, inflammation, or increased connective tissue. Ultrastructural study showed no substantial changes, except for occasional mitochondrial enlargement in cells containing increased lipid. Biochemical analyses at 19 months showed moderate increase in hepatic triglyceride levels and slight increase in hepatic collagen content in the experimental groups.


Glucose-6-phosphate dehydrogenase deficiency and lobar pneumonia. Fine structure of the liver.

Ultrastructural changes appeared in liver biopsy specimens from eight patients with glucose-6-phosphate dehydrogenase deficiency who developed jaundice during the course of lobar pneumonia. The observed changed indicate that the hyperbilirubinemia and jaundice that develop in patients with glucose-6-phosphate dehydrogenase deficiency with lobar pneumonia are caused partly by hemolysis and partly by intrahepatic cholestasis. The cholestasis may be caused by a genetic predisposition in enzyme-deficient individuals; the hemolysis may be induced by pulmonary infection in individuals with an enzyme deficiency.


Hepatic infarction. A clinicopathologic study of seven cases.

Five of the seven cases of hepatic infarction that compose this study were encountered in a series of 442 consecutive autopsies, giving an incidence of one in 88 autopsies. The clinical and laboratory features were suggestive of hepatocellular dysfunction, although in only three cases was the diagnosis considered prior to death. Morphologically, in four of the seven patients, the infarcts were regarded as massive or of submassive proportions and were directly responsible for the patients' death. The majority of infarcts were of recent origin, with the estimated ages ranging from 18 to 72 hours. One was of about two weeks' duration and was the only example in this series associated with cirrhosis.


Articular cartilage of diabetic Chinese hamsters.

Investigations were carried out in order to determine whether animals with spontaneous diabetes are prone to develop skeletal lesions comparable to those found in diabetic human subjects. The present report deals with the ultrastructure of the cartilage of the hip joint of diabetic Chinese hamsters and nondiabetic control animals. In the diabetic animals, chondrocytes of the femoral head showed atrophy of the endoplasmic reticulum, bizarre mitodhoncria, and huge lipid inclusions, which are changes suggestive of disturbed function.


The gay bowel syndrome: clinico-pathologic correlation in 260 cases.

The clinical and pathological findings in a group of 260 homosexual men comprising 10% of a private proctologic practice are reviewed. A clinical pattern of anorectal and colon diseases encountered with unusual frequency in these homosexual patients is termed the gay bowel syndrome. The clinical diagnoses in decreasing order of frequency include condyloma acuminata, hemorrhoids, nonspecific proctitis, anal fistula, perirectal abscess, anal fissure, amebiasis, benign polyps, viral hepatitis, gonorrhea, syphilis, anorectal trauma and foreign bodies, shigellosis, rectal ulcers and lymphogranuloma venereum. 60 anorectal and sigmoid biopsies from 51 patients failed to disclose evidence of specific infection other than condyloma acuminata. Of 21 patients with biopsy diagnosis of nonspecific proctitis, 8 had a specific infection which was detected by other means,--5 cases of shigellosis and one case each of gonorrheal proctitis, amebiasis and lymphogranuloma venereum. In evaluating proctologic problems in the gay male, all of the known sexually transmitted diseases should be considered. Shigellosis, amebiasis and viral hepatitis should be included. Microbiological evaluation is essential. Concurrent infections with 2 or more pathogens should be anticipated. Chlamydia trachomatis, an important cause of nonspecific urethritis in the general population, is high on the list of possible causes of the nonspecific proctitis present in 31 of the 260 patients.


Postmortem delineation of infarcted myocardium. Coronary perfusion with nitro blue tetrazolium.

Perfusion of hearts with nitro blue tetrazolium resulted in gross formazan staining of intact myocardium, while infarcted zones and scars were unstained or were poorly stained. Subsequent perfusion with 3.7% formaldehyde solution provided a rigid specimen with well-preserved anatomical structures and landmarks suitable for detailed correlation of three-dimensional infarct distribution with clinical data. Specimens are particularly amenable to further gross dissection of mapping of lesions from interval slices, or both.


Microsomal enzyme inducers and hypervitaminosis A in rats.

Pretreatment of rats with pregnenolone-16alpha-carbonitrile (PCN) completely prevented the osseous lesions produced by vitamin A overdosage, whereas pretreatment with phenobarbital or with phenytoin (diphenylhydantoin) provided only partial prophylaxis. These microsomal enzyme inducers also decreased vitamin A concentration in the liver and seemed to protect against hypervitaminosis A by enhancing the metabolism of the vitamin. Electron microscopy of the liver showed large, vitamin A-storing perisinusoidal cells. The number, size, and lipid content of these cells were decreased in rats treated simultaneously with vitamin A and PCN, but not in rats pretreated with phenobarbital or phenytoin. Vitamin A, given alone, produced moderate accumulation of smooth endoplasmic reticulum (SER) in hepatocytes, without accelerating microsomal drug-metabolizing enzyme activity; phenobarbital, phenytoin, and PCN also elicited SER accumulation, particularly when administered with vitamin A.


Primary causes of perinatal mortality. Autopsy study of 100 cases.

Many previous reports on perinatal mortality mix primary and secondary causes of death, exclude such important causes as necrotizing enterocolitis and intrauterine growth retardation, and do not break down causes of extrinsic perinatal hypoxia. To avoid these criticisms, a slight modification was made of the list of causes of death used by the Perinatal Mortality Committee of Quebec Province, Canada. The methodology and results of 100 consecutive autopsies are described. Respiratory distress syndrome (31%), congenital anomalies (28%), and extrinsic perinatal hypoxia (17%) were the three commonest causes. Maternal, placental, or labor and delivery problems were associated with about half the cases of extrinsic perinatal hypoxia. In one case of unexplained death, sudden infant death syndrome may be considered as a possibility.


Lack of amyloidosis and renal disease in A strain mice.

Amyloid deposition in two sublines of the A strain mouse, a reputedly reliable murine model of spontaneous amyloidosis, was reevaluated using combined green polarization birefringence after Congo red staining and a fibrillar ultrastructure for amyloid identification. Both sublines were found to be devoid of amyloid at an age when the A strain mouse had been reported to have a high incidence of papillonephritis, amyloidosis, and death. This finding indicates a need for reassessment of this and other traditional models of spontaneous amyloidosis.


Cartilage in hemophilic arthropathy. Ultrastructural and microanalytical studies.

The presence of iron in articular cartilage was investigated in five human and two canine cases of factor VIII-deficiency hemophilic arthropathy. The lesions were mild in three cases. Advanced destruction of the cartilage was present in four cases, in one of which sufficient cartilage was preserved to permit recognition of hemosiderin in chondrocytes. The Fe was present in the form of siderosomes and ferritin granules free in the cytoplasm. Iron and phosphorus were demonstrated in the siderosomes by energy dispersion analysis of x-rays; but no Fe was identified by this means or by light or transmission electron microscopy in chondrocytes from the three subjects in an early stage of the disease or in the matrix from any of the seven subjects. The findings lend no support to the hypothesis that salt formation or chelation of Fe ions by matrix proteoglycans is responsible for destruction of cartilage in hemophilic or other chronic hemarthroses. A second, nonferruginous, bilirubin-like pigment (hematoidin) was present in the matrix at the surface of the cartilage in two specimens.


Arterial cell renewal after experimentally induced thrombosis.

Thrombosis was experimentally induced in one common carotid artery in 40 rats. One hour to 180 days afterward, the cell renewal in the arterial wall was studied by tritiated thymidine autoradiography. An increased number of labeled cells were observed, especially in the early developmental phase of the thrombosis and mainly in the tunica media. These findings seem to accord best with the hypothesis that the thrombi are mainly organized by smooth muscle cells from the tunica media, which are partly dedifferentiated toward fibroblast-like cells.


Spontaneous calcific emboli from calcific mitral annulus fibrosus.

Clinically important complications resulting from calcific mitral annulus fibrosus (CMAF) are unusual. They include mitral regurgitation, mitral stenosis, and complete heart block. In one patient with massive CMAF associated with multiple systemic calcific emboli originating from the mitral valve, the emboli were the cause of multiple brain infarcts and a clinical course of unexplained neurological deterioration. We believe that this is the first report of such a complication occurring with CMAF.


Acute cholecystitis and persistent liver necrosis in mice provoked by isothiocyanate.

Two known cholangiotoxic agents, alpha-naphthylisothiocyanate (ANIT) and p-phenylenediisothiocyanate (PDT), were administered in single doses to mice to study their effects on the gallbladder. Both compounds caused maximal bile duct necrosis and periportal hepatocytic necrosis at 24 hours. In contrast, the gallbladders were edematous but not necrotic at 24 hours after treatment. At 48 hours, and in some animals up to four days, severe cholecystitis was present, while bile ducts revealed progressive regeneration. The delay in the onset of gallbladder lesions was assumed to be the result of the toxic agent concentration in gallbladder bile after hepatic bile secretion was suppressed for 24 hours. The lesions provoked by PDT were similar to those induced by ANIT, except for a hemorrhagic component.


Methyldopa-induced liver injury. Rapid progression to fatal postnecrotic cirrhosis.

A 55-year-old woman developed symptoms suggestive of hepatitis 12 weeks after first receiving methyldopa for hypertension. Liver biopsy showed chronic aggressive hepatitis with subacute hepatic necrosis. Methyldopa was discontinued, but after exhibiting transient clinical improvement, the patient's condition progressively deteriorated until she died of hepatic failure, in spite of therapy with massive doses of corticosteroids and other nonspecific measures. During the terminal stage, a considerable decrease in the size of the liver was observed. At autopsy, the liver was found to be small, shrunken, and scarred; histological sections demonstrated postnecrotic cirrhosis. Such a rapid and relentless progression of methyldopa-induced liver injury is undoubtedly rare, but it may be prevented by careful supervision of patients who exhibit liver function abnormalities early in the course of therapy.


Pulmonary yellow hyaline membrane disease. New variant in premature infants with intrahepatic cholestasis.

Two premature female infants with a new variant of pulmonary hyaline membrane disease had both received assisted ventilation with high oxygen concentrations. Postmortem examination showed straw-yellow hyaline membranes lining the terminal bronchioles and alveoli. Pneumonocytes and macrophages also contained straw-yellow pigments in the cytoplasm. These yellow membranes and pigments in pneumonocytes and in macrophages stained positively for bile and negatively for iron. Both infants had severe intrahepatic cholestasis. Cholestasis and pulmonary changes due to oxygen toxicity are believed to be the main features leading to this curious entity.


Epithelial and surfactant changes in influenzal pulmonary lesions.

Pulmonary epithelial cell destruction in mice infected with PR8-A influenza virus has been studied with light and electron microscopy and enzyme histochemistry, and correlated with pulmonary surfactant activity. All epithelial cell types were infected by the virus, resulting in destruction, pneumonitis, and atelectasis by seven to ten days. Pulmonary surfactant activity decreased progressively following onset of infection, and was minimal by seven to ten days. Before types 1 and 2 alveolar pneumocytes regenerated, the regenerating bronchial cells grew peripherally into some of the denuded alveolar ducts and alveoli to form epithelial nodules. Eventually the types 1 and 2 pneumocytes regenerated to cover the alveolar surfaces that were not invaded by bronchial epithelium. This regeneration was associated with increased surfactant activity in the postinfluenzal lesions, suggesting that the type 2 pneumocytes are a source of surfactant.


Toxic effects of hydroperoxide injections on rat lung. A light microscopical and ultrastructural study.

Intravenous administration of methyl linoleate hydroperoxide (MLH) uniformly resulted in extensive damage to septal wall components of the rat lung; the severity of these changes paralleled the administered dosage. The target cell of injury appeared to be the capillary endothelial cell. Destructive changes within the plasma membrane suggested that the major toxic effect of MLH was directed against membranous structures. Ultrastructural analysis showed that these effects were more severe in the vitamin E-deficient animals. Secondary changes were characterized by interstitial and alveolar edema, and degenerative changes within alveolar pneumocytes. Reparative proliferation of type 2 pneumocytes first became evident in animals that survived two days. These observations provide an insight into the susceptibility and sequential damage to pulmonary tissue by hydroperoxides and serve as a guide for investigations of the toxic effects of other oxidants on lung.


The excretion and distribution of inorganic mercury in the rat as influenced by several chelating agents.

Among 15 chelating agents tested, sodium-2,3-dimercaptopropane 1 sulfonate (DMPS), 2,3-dimercaptopropanol (BAL), sodium-mercaptoethyliminodiacetate (MEIDA), and D-penicillamine (PA) exerted an influence on the excretion of Hg and its distribution in the organs. The excretion pattern however, is different for these compounds, and, from the practical point of view, a favourable effect is exhibited only by DMPS which enhances the urinary excretion rate and lowers the Hg-concentration in all organs.


The kinetics of methylmercury administered repeatedly to rats.

Female rats (65-75 days old) were given orally 0.84 or 3.36 mg Hg/kg as methylmercury chloride (MeHgCl) 5 times a week for 13 and 3 weeks, respectively. The proportion of inorganic to total mercury remained as low as 6% in whole animal though it increased to above 40% in the kidneys. Differences in organ half times and the negative correlation with time for blood to liver, brain and kidney mercury ratios indicated more than one compartment for MeHg+. Brain had 26 days half time with a 32% final equilibrium concentration in relation to the body concentrations. Brain concentrations of mercury reported on rats dosed repeatedly with MeHg+ agreed with these values which justifies their use when experiments are planned to give a certain brain MeHg+ concentration. Half time for the whole body was 34 days but patholgical changes-weight loss, tubular damage, slow gastrointestinal passage-disturbed the accumulation curves in the higher dose group. Blood to kidney ratio and uptake of MeHg+ by kidneys also changed significantly.


Effect of pregnancy on hepatic microsomal drug metabolism in rabbits and rats.

In Dutch-belted rabbits, pregnancy caused several-fold decrease of in vitro hepatic microsomal aminopyrine, benzphetamine, and hexobarbital biotransformations. In pregnant Sprague-Dawley rats, various kinds of expressing the in vitro rates of hexobarbital biotransformation (per mg of microsomal protein, g of liver, 100 g of body weight) indicated unchanged or slightly elevated microsomal enzyme activity. In vivo, the course of hexobarbital blood levels after i.p. hexobarbital sodium, 100 mg/kg, indicated that the fate of hexobarbital was not primarily determined by the small changes of microsomal enzyme activity but, rather, by changed hexobarbital distribution. Different ways of expressing in vitro rates of aniline biotransformation showed decreased or unchanged enzyme activity during pregnancy and in vivo experiments indicated that these changes did not affect aniline metabolism in living rats. The results pointed out marked species differences in the effect of pregnancy on drug metabolism. Interpretation of in vitro biotransformation data for living animals suggested that with different substrates, microsomal enzyme activity and distribution, respectively, may exert different effects playing either significant or apparently minor role in drug disposition.


Acute cardiovascular toxicity of thallium (I) ions.

The acute cardiovascular toxicity of thallium (I)-ions was studied in anesthetized rats and also in some isolated preparations. In pentobarbital-anesthetized rats, intravenously applied Tl2SO4 (range 3 to 100 mg/kg) caused a significant, dose-dependent decrease in mean arterial blood pressure and heart rate. In spontaneously beating guinea pig isolated atria, thallium (I)-ions (10(-5) to 10(-3) M) caused a concentration-dependent decrease in frequency, which was not influenced by atropine, cocaine, or by considerable changes in the potassium concentration of the medium. A direct influence of Tl+ on the sinus node is presumed. Thallium decreases contractile force probably as a result of its negative chronotropic properties, since the amplitude of contraction remained uninfluenced in electrically driven atria. Thallium (I)-ions were readily taken up by the guinea pig isolated atria. At a bath concentration of 5 times 10(-5) M Tl+ a tissue/medium ratio of approximately 45 was achieved. Probably, an exchange against cellular potassium takes place. Relaxation of vascular smooth muscle by Tl+ was demonstrated both in isolated aortic strips (rabbit) and in the isolated perfused rabbit ear preparation. Both the vascular smooth muscle relaxation and the decrease in heart rate would explain the acute hypotensive effect of thallium.


Teratology study of two isoglutamine derivatives.

The embryotoxicity and teratogenicity of N-phthalyl isoglutamine (2), a metabolite of thalidomide, and of "K-2004-1c", 2-(bicyclo[2.2.1]heptane-2-endo-3-endo-dicarboximido)-glutaric acid 1-amide (4), the main metabolite of the test compound "K-2004" (proposed generic name: biglumide), a nonteratogenic congener of thalidomide, have been investigated in mice and rats. Whereas 2 proved to be highly teratogenic and embryotoxic, 4 showed none of these activities in the dose range from 50 to 400 mg/kg.


The syndrome of ankyloblepharon, ectodermal defects and cleft lip and palate: an autosomal dominant condition.

Seven patients from four families are reported who had an inherited condition of which the main features were ankyloblepharon, ectodermal defects and cleft lip and palate. The ectodermal defects were partial or complete hair loss, absent or dystrophic nails, pointed widely spaced teeth and partial anhidrosis. Associated anomalies included lacrimal duct atresia, supernumerary nipples, syndactyly and auricular deformities. The inheritance of this abnormality was consistent with that of an autosomal dominant trait. The relationship between this and similar syndromes is discussed.


Erythrocyte vitamin B12 activity in healthy Indian lactovegetarians.

Plasma and erythrocyte vitamin B12 was measured in apparently healthy Indian lactovegetarians and compared with the healthy non-vegetarians from the same population. Comparison of the mean values for routine haematological parameters revealed no significant difference in various dietetic groups. The plasma vitamin B12 levels were distinctly lower in the lactovegetarians than in the non-vegetarians. However, the mean erythrocyte vitamin B12 levels in different dietetic groups showed no significant difference.


Bone marrow involvement in non-Hodgkin's lymphoma: implications for staging and therapy.

We evaluated the incidence of bone marrow involvement in 121 patients with non-Hodgkin's lymphoma who were seen prior to the institution of definitive therapy. Involvement of the marrow was found to be dependent on both histologic type and the extent of extramedullary disease. It was observed most frequently in patients with poorly differentiated lymphocytic lymphoma (60%), but was not observed in 36 patients of all histologic types whose clinical evaluation and/or laparotomy revealed disease in stage I or II. Among 56 patients with poorly differentiated lymphocytic lymphoma in stage III or IV exclusive of marrow involvement, disease was observed in the marrow in 40 patients, or 71%. These observations, together with the results of previously reported therapeutic trials, suggest that staging laparotomy and total nodal radiotherapy alone may be of limited value in patients with poorly differentiated lymphocytic lymphoma when clinical evidence of stage III or IV disease is present.


The effect of prolactin on kidney structure of the euryhaline teleost Gasterosteus aculeatus during adaptation to fresh water.

The effect of injections of ovine prolactin on kidney structure was examined in the first 10 days following transfer of seawater sticklebacks to fresh water. In hormone injected animals as well as in controls the glomeruli increase slightly in size after transfer. The podocytes intensify the secretion of mucopolysaccharides, which is indicative of increased turnover of the components of the glomerular basal lamina. The nuclei of the podocytes become enlarged, while those of the juxtaglomerular cells decrease in size. These changes are related to the well known rise of the glomerular filtration rate following transfer to fresh water. Structural indications that prolactin is involved in the control of glomerular filtration were not found. The epithelial cells of the three nephronic segments and of the ureter become considerably better developed after transfer to fresh water. Cell height, nuclear and mitochondrial volume, and surface of the membranes of the basal labyrinth increase in all tubular epithelia, although not to the  same extent. Increases are moderate in the first proximal segment, but increasingly higher for the second proximal segment, collecting duct and the ureter. Especially the growth of membrane surface of the basal labyrinth, site of ion transport mechanisms, is impressive. In controls, values characteristic for freshwater fishes are reached in 6 to 9 days for all parameters for cellular development. Prolactin injections greatly stimulate growth rates in all tubular epithelia: freshwater values are reached within 3 days. No further increase was found, however.


Cartilage fibrillation on the lateral tibial plateau in Liverpool necropsies.

A study has been made of the state at necropsy of the hyaline articular cartilage of the left tibial plateaux, with particular reference to the lateral plateau, in 47 adult white Europeans (24 men; 23 women) aged 21-88 years. The surface morphology and topographical distribution of the lesions is described for the bare area of the lateral plateau and its meniscus-covered segments, and quantitative point-counting data are presented for the amount, according to age, of overt fibrillation on the bare area. A variety of cartilage lesions was encountered: macroscopically apparent ' parallel linear' minimal fibrillation; other patterns of minimal fibrillation; 'ravines'; overt fibrillation; localized incomplete defects of the cartilage; and full-thickness cartilage loss with bone exposure. Sites of superficial fraying and splitting of the hyaline articular cartilage are a normal finding on adult human tibial plateaux. Especially in younger adults, such sites are often accompanied by large areas of cartilage surface which are still intact. On the lateral plateau, the bare area and the meniscus-covered posterior segment are more susceptible to overt fibrillation than are the meniscus-covered lateral and anterior segments. In contrast to the findings in other synovial joints, the peripheral rim of the upper tibial cartilage sheet is not particularly susceptible to overt fibrillation. Tangential extension of the changes on the lateral plateau leads to widespread involvement of the bare area and the meniscus-covered posterior segment in older subjects. However, vertical progression of the changes, sufficient to give full-thickness cartilage loss with tibio-femoral bone exposure, was seen in only a minority of persons aged over 80 years.


Relation between prolactin and gonadotrophin secretion in post-partum lactating rats.

In post-partum lactating rats, sucking by the young was associated with high prolactin release and maintenance of lactation but severe inhibition of LH and FSH release and suspension of oestrous cycles. Shortly after the pups were removed on day 22 post partum LH and FSH release returned to normal and oestrous cycles resumed. Twice-daily injections of ergocornine methanesulphonate (ERG) into mothers beginning at 5 or 7 days post partum, resulted in sustained inhibition of prolactin release and diminished mild secretion. By frequent exchange of pups between control and ERG-treated mothers, it was possible to maintain vigorous sucking and almost normal pup growth despite low serum prolactin levels and diminished lactation. In these rats, serum levels of LH remained low during 11 or more days of treatment with ERG, but serum FSH was consistently higher than in untreated control mothers. After 11 or more days of ERG treatment, most rats showed a return to normal LH and FSH release and resumption of oestrous cycles. These results suggest (a) that the sucking stimulus rather than high prolactin levels in the circulation is mainly responsible for inhibition of LH and FSH release during the first 11 days post partum, (b) that the sucking stimulus acts to increase prolactin and inhibit LH release by separate hypothalamic mechanisms, and (c) that administration of ERG results in diminished prolactin release and lactation, and in increased release of FSH and subsequently of LH with earlier resumption of oestrous cycles.


[A critical study of arteriography of tumours of soft tissue of the extremities (author's transl)].

We feel that arteriography occupies at the present time an indispensable and irreplaceable role in the pre-therapeutic assessment of a soft tissue tumour of the extremities. It obviously cannot provide a definite diagnosis in all cases with regard to the benign or malignant nature of the lesion. However careful analysis of the various features of the images obtained, leading to a radiological classification of the tumour into one of three groups (LEVIN, WATSON and BALTAXE), makes possible, in groups I and III, to predict the nature with a high probability of accuracy. Only in type II (35% of our cases) is it impossible to make such a deduction. The value of arteriography is not limited to diagnosis. It also provides information on the extent and arterial supply of the tumour which are essential to the surgeon and which cannot be supplied by any other investigation.


Amniotic fluid and fetal maturity.

The lecithin/sphingomyelin ratio in amniotic fluid is a method of predicting fetal lung maturity. The L/H ratios in certain high risk pregnancies are poorly correlated with the shake test. The L/S ratios in drug addiction methadone pregnancies and diabetic pregnancies do not have a high degree of correlation with normal L/S ratios after 36 weeks of gestation and are often low.


Registry of experimental cancers of the National Cancer Institute.

This report describes the organization and functions of the Registry of Experimental Cancers and gives the chronology of events that led to its establishment. Currently 21,500 accessions have been coded; the vast majority are spontaneous and induced cancers, chiefly of rodents, and also a wide variety of nonneoplastic diseases. Accessions are accepted from contributors working in laboratories in this country and abroad. The material is available for study by responsible scientists, and a limited number of study sets is available for loan on request.


Fetal alcohol syndrome. Experience with 41 patients.

Forty-one patients with the fetal alcohol syndrome, including 11 whose cases were previously reported, were studied. These children have a pattern of defects including prenatal and postnatal growth deficiency, small head size with mental subnormality, and facial abnormalities allowing for recognition of the disorder in infancy. The same pattern of abnormalities has been independently reported from France in a series of 127 offspring of chronic alcoholics.


Industrial hypertension control program in a rural state.

Many problems remain in attempting to improve the detection and management of hypertension in the United States. This study applied a previously established model community hypertension program to a wide geographic area in a rural state. In 47 industries in 18 communities, 15,689 subjects were screened for the presence of hypertension. Eight hundred five subjects were found to have an elevated blood pressure on three separate occasions and were classified for further management. Follow-up showed that 76% visited their physicians within six months, and of these 81% were being observed. Sixty-seven percent of the subjects who saw their physicians were receiving antihypertensive drug therapy. The cost of finding each subject with an elevated blood pressure was $80 and of identifying a subject who received drug therapy, $160.


Single subcutaneous injection of iothalamate sodium I 125 to measure glomerular filtration rate.

The renal clearance of iothalamate sodium I 125, identical to that of inulin, permits measurement of glomerular filtration rate with a single injection in varying degrees of renal failure.


Diagnosis of Meckel diverticulum by sodium pertechnetate Tc 99m scan.

Meckel diverticulum was diagnosed preoperatively as the cause of recurrent rectal bleeding in a 2-year-old child by means of a sodium pertechnetate Tc 99m scan. Although false-negative scans have been reported to occur in approximately 50% of all cases of Meckel diverticulum, the procedure should be considered in any case of unexplained, painless rectal bleeding, especially in pediatric patients.


Adjunct hospital emergency toxicology service. A model for a metropolitan area.

A feasibility demonstration with a gas chromatograph/mass spectrometer/computer system (GC/MS) was initiated to provide a 24-hour (seven days/week) adjunct emergency toxicology service to the hospitals in the tricounty area comprising Metropolitan Detroit. During June 1, 1974, to April 1, 1975, more than 85 different drugs and other agents were identified in the body fluids of approximately 1,000 victims of accidental or deliberate poisonings. At least one toxic substance was identified in 57% of the cases, and the presence of two or more drugs was established in one of five (19%) of the victims. This study indicates that a centrally located GC/MS/computer system can provide an effective adjunct emergency toxicology service for an entire metropolitan community and thereby provide guidelines for a prompt and rational therapy.


Cervical analgesic discography. A new test for the definitive diagnosis of the painful-disk syndrome.

The cervical discogenic (painful-disk) syndrome consists of scapular pain radiating into the head, shoulder, and upper arm, often associated with paresthesias but without neurologic deficit. Plain roentgenograms or myelograms are normal or show degenerative changes. Positive-contrast discography has been useful but is subject to a high percentage of false-positive results roentgenographically and nonspecific pain patterns clinically. Analgesic discography more precisely confirms the diagnosis and more accurately locates the pain-producing disk. Injection of a local anesthetic into a painful disk produces transient symptomatic relief and full neck mobility. Its use during a two-year period in 71 consecutive discogenic patients followed by anterior cervical fusion resulted in a 93% excellent or good recovery rate. Analgesic discography is the most effective test for diagnosis and location in the painful-disk syndrome.


Intrauterine devices and acute pelvic inflammatory disease.

One of the most serious problems among women using the intrauterine device (IUD) has been pelvic inflammatory disease (PID). Subjects for the present investigation were chosen from 15- to 44-year-old women seeking emergency medical attention at a large city hospital. Febrile and afebrile patients with PID and appropriate controls were asked to complete a self-administered questionnaire concerning their demographic, reproductive, and contraceptive histories. Results showed a significantly higher proportion of IUD users among febrile cases of PID (38%) than among controls (11%). This implies that febrile PID is five times as likely to develop in an IUD user as in a nonuser.


Bacteriuria localization and response to single-dose therapy in women.

One hundred women with bacteriuria had the infection localized by the "bladder-washout" technique. Thirty-six of the 39 with infection confined to the bladder were cured with a single intramuscular injection of 500 mg of kanamycin sulfate, whereas 47 of the 65 patients with infection originating from their upper tract relapsed almost immediately. None of the seven patients with abnormal pyelograms and associated upper tract infection was cured with kanamycin. These results suport the hypothesis that bladder infections in women can be readily cured with a very short course of therapy. Women who relapse after a single injection of kanamycin almost always have renal infection.


Acute enteritis associated with reovirus-like agents.

In Atlanta, from January to April 1975, reovirus-like agents (RLAs) were detected by a simplified electron-microscopic technique in the stools of 16 of 29 children with acute enteritis. Complement fixation tests with purified RLA antigens demonstrated antibody titer rises in seven children with RLA in their stools and in two mothers (one symptomatic) from whom acute and convalescent sera were available. Complement fixation tests performed on 207 individuals of varying ages and 60 laboratory workers indicated a high frequency of past infection with RLA, the highest frequency being in children 6 months to 4 years of age. These results corroborate the high rate of RLA detection in the stools of children with acute enteritis in other parts of the world and suggest that such infections can also occur in adults.


Pharmacokinetics in clinical practice. I. Concepts.

Important concepts of pharmacokinetics, such as the biologic half-life, clearance, and bioavailability of drugs, can be utilized to describe and predict the time course of drug concentrations in plasma as a function of dose and frequency of drug administration. In quantitative terms, they can serve to characterize the individuality of the patient, including the effects of disease, with respect to drug absorption, distribution, excretion, and metabolism.


Scurvy and hemarthrosis.

Scurvy developed in a 56-year-old man with poor dietary intake and was associated with knee hemarthroses and synovial thickening. The synovial membrane showed interstitial hemorrhage and many large fibroblasts but little collagen and some disarray of vascular basement membrane. Hemarthroses and all knee symptoms completely resolved on a normal diet. To our knowledge, these are the first electron-microscopic studies of synovial membrane in human scurvy, and our findings support a defect in collagen synthesis as a factor in etiology.


Prevention of venous thrombosis with small, subcutaneous doses of heparin.

The effect of low-dose heparin prophylaxis on venous thrombosis and bleeding after major elective surgery was studied in a prospective controlled study of 820 patients. The total incidence of venous thrombosis detected with leg-scanning using fibrinogen labeled with radioactive iodine (125I) was reduced from 16.0% in the control group to 4.2% in treated patients. More important, the incidence of popliteal or femoral vein thrombosis was reduced from 2.9% to 1.0%. Prophylaxis resulted in a slight increase in bleeding-minor wound hematoma, mean volume of blood transfused, and a post-operative hematocrit fall in treated patients. However, increased bleeding was clinically minor, and prophylaxis was well tolerated.


Clinical experience with theophylline. Relarionships between dosage, serum concentration, and toxicity.

Relationships between theophylline dosage, serum theophylline concentration, and theophylline toxicity were evaluated retrospectively in 47 hospitalized adults. The amount of theophylline administered daily varied more than sixfold, from 6 to 38 mg/kg. The serum theophylline concentrations, however, varied 24-fold from 2 to 49 mug/ml. The relationship between daily dosage and serum concentration was unpredictable in an individual patient. Fourteen patients (30%) had a toxic reaction to theophylline. Toxic symptoms, which were not always gastrointestinal, occurred commonly with serum concentrations over 25 mug/ml but were not noted with concentrations below 15 mug/ml. High serum theophylline concentrations and a toxic reaction developed just as often with the oral route as when the drug was given intravenously. In six patients, measurement of serum theophylline concentration disclosed subtherapeutic concentrations. Serum theophylline determination appears to be important clinically in guiding effective and safe usage of theophylline.


Pharmacokinetics in clinical practice. 2. Applications.

The pharmacokinetic concepts introduced and defined in a preceding article are now applied to the management of drug therapy for the individual patient. The factors that affect the time course of drug concentrations in plasma produced by repetitive administration include the dosing rate, total clearance, biologic half-life, and systemic availability of the drug. A clinical pharmacokinetics service can monitor drug concentrations in biologic fluids, design individualized drug-dosing regimens, and carry out pharmacokinetic diagnostic work-ups to help determine the reasons for a patient's unusual response to drug therapy.


Reduction of amphotericin B nephrotoxicity with mannitol.

Amphotericin B in combination with mannitol was given to a patient who had mucocutaneous candidiasis and moderate renal insufficiency. Previously, amphotericin B alone had induced an abrupt increase in serum creatinine and urea nitrogen, but when mannitol was given concurrently there was no worsening of renal function. Thus, amphotericin B with mannitol appears to offer a less nephrotoxic but equally candicidal therapeutic regimen in the renal compromised patient requiring parenteral candicidal therapy.


Lymphedema tarda.

The clinical recognition and evaluation of congenital lymphedema of the lower extremities with abrupt onset in a 51-year-old man are reviewed. A rational, systematic approach is outlined and exemplifies the use of an interdisciplinary effort to achieve accurate diagnosis through readily available diagnostic procedures.


The serious suicide attempt. Five-year follow-up study of 886 patients.

A five-year follow-up study was undertaken of a previously reported 1968 cohort of 886 people who had attempted suicide. The working hypothesis that those who had seriously attempted suicide (21%) would have a higher suicide rate on long-term follow-up was confirmed. During the five-year follow-up period, a total of 34 suicides were found, which represented 3.84% of the total number at risk. Of those who had seriously attempted suicide, 12 (6.45%) of 186 succeeded later; of the other (nonserious or less serious) attempters, 22 (3.1%) of 700 succeeded. The serious-attempter suicide rate was 2.1 times that of the others, and this difference was statistically significant (P less than .05). In addition, patients who made attempts that were judged serious on medical but not on psychiatric grounds were found to have a suicide rate significantly higher (P less than .05) than patients who had made suicide attempts that were not a serious medical threat.


Intravenous aminophylline dosage. Use of serum theophylline measurement for guidance.

A practical method for monitoring serum theophylline concentrations has been used to investigate intravenous aminophylline dosage requirements. Initial serum theophylline concentrations were found to vary widely and correlate poorly with drug history. Aminophylline loading doses determined from these values more frequently resulted in drug concentrations in the therapeutic range (10 mug to 20 mug/ml) than when therapy was given without knowledge of serum theophylline concentrations. Continuous intravenous aminophylline therapy administered in a standardized dosage (0.9 mg/kg/hr in adults and 1.0 mg/kg/hr in children) produced variable and often excessive serum concentrations. This resulted from variable drug clearance rates, which in adults averaged 0.64 +/- 0.38 ml/kg/min (mean +/- SD), only half that previously reported. These observations suggest that it is not possible to achieve optimal therapeutic aminophylline dosage without monitoring serum theophylline concentrations.


Myasthenia gravis associated with wasp sting.

A clinical picture indistinguishable fro, but not therefore identical with, myasthenia gravis (ocular form) developed within 24 hours of a wasp sting. Because of the close temporal association of events, operative mechanisms may be either an immediate hypersensitivity reaction to some components of wasp venom or a direct toxic effect of these substances on acetylcholine synthesis, release, or degradation. Theoretical considerations from the literature and the lack of immunologic abnormalities in the patient suggest that the latter may be correct. Unique host conditions must have been present at the time of the sting, implying latent or subclinical myasthenia gravis.


Aspergillus oryzae meningitis.

In a patient with only meningitis, a septate hypha was seen in a Langhans giant cell, and the rarely pathogenic Aspergillus oryzae was cultured from the cerebrospinal fluid. Serologic results confirmed the diagnosis. The patient responded to therapy with amphotericin B and flucytosine.


[Distribution of probon in various organs in acute poisoning].

Toxicological analysis of a Hungarian analgetics - Probon - of new chemical structure was carried out in experiment. A new technique was developed for quantitative analysis of the drug and its main metabolits in biological material. Distribution of Probon in various organs, grade of the metabolization in acute intoxication was also studied.


An inhibitor of macrophage chemotaxis produced by neoplasms.

The accumulation of macrophages at neoplastic sites may be an important event in immunologically mediated tumor killing. The implantation of syngeneic neoplasms in mice, however, was found to depress the animal's ability to localize macrophages at inflammatory sites. A low-molecular-weight (6,000 to 10,000) factor released by growing neoplasms that inhibits the accumulation of macrophages in vivo and chemotactic responsiveness in vitro was identified. The factor is active in the inhibition of macrophages and is ineffectual at retarding the migration of polymorphonuclear leukocytes. Neoplastic cells may thus abrogate immunosurveillance by releasing products that prevent potentially tumoricidal macrophages from accumulating at sites of developing malignancies.


Enzootic leucosis in a flock of sheep in Rhodesia.

Fourteen cases of lymphosarcoma occurred in a small experimental flock of sheep in Rhodesia. There appeared to be horizontal spread and the ages of the affected animals varied from one to more than 10 years. Thirteen of the cases so far diagnosed were leucaemic with a high lymphocyte count. Eleven of the sheep demonstrated multicentric lesions and two alimentary mesenteric; the remaining animal is still alive. Transmission attempts in four neonates resulted in one showing a high white cell count after 25 months. Electron microscope studies failed to demonstrate C-type virus-like particles. This appears to be the first recorded example of an outbreak of lymphosarcoma in a flock of sheep in Southern Africa and the descriptive term "enzootic leucosis" has been adopted.


Inconsistency of the tibia test for estimating growth hormone in crude pituitary extracts.

The complement fixation immunoassay (CFIA) was used for quantitating growth hormone (GH) in crude anterior pituitary extracts from rats subjected to thyroidectomy with or without cortisol and exogenous GH administration. The results obtained from this study were compared with pertinent bioassay (tibia test) results or correlated with the pituitary acidophil cell counts. Whereas it has been reported that pituitary GH levels are normal by the tibia test at 2 weeks after thyroidectomy, the highly specific CFIA method showed an actual 87% decrement which correlated well with the reduction in acidophilis. In addition, the apparently normal content of GH after cortisol administration to thyroidectomized rats, as measured by the tibia test, was contradictory to the very low acidophil population and to the marked reduction in pituitary GH content as measured by the CFIA. Furthermore, theoretical tibia responses illustrate the inconsistency of the bioassay in different experimental conditions. If, as previously suggested, the content of thyrotrophin (TSH) in the crude pituitary extracts renders the bioassay of GH a dubious procedure, then the superiority  of immunoassay is obvious.


Acid phosphatase activity in the rat neurohypophysis during increased levels of gonadothrophic hormones, in diabetes insipidus (Bratteboro strain) and after water loading.

The acid phos phatase activity of the rat neurohypophysis was measured during increased gonadotrophic hormone levels, in diabetes insipidus (DI) (Brattleboro strain) and after water loading, i.e. conditions that interfere with the function of the hypothalamo-neurohypophyseal system (HNS). In addition determination of tissue protein, lipid and DNA and of water metabolism were performed. Neurohypophyseal acid phosphatase activity expressed on a dry weight basis increased under all conditions. For gonadectomized females, Brattleboro rats and water loaded males an increased water metabolism was observed. The increased acid phosphatase activity is interpreted as being related to disposal of release residues during stimulation of the HNS (increased gonadotrophic hormone levels and DI) and to disposal of neurosecretory material during inhibition (water loading).


The diurnal variation in renal iodide excretion rate in rabbits.

The diurnal variation in renal iodide excretion rate was determined in unrestrained female rabbits by means of either a conventional clearance technique or a continuous monitoring of the whole body disappearance of iv injected 125I-iodide using an implanted Geiger-Muller detector. A distinct diurnal rhythm was detected in the disappearance rate of 125I-iodide. A slow disappearance rate occurred from 12 p.m. to 6 a.m. (darkness from 5 p.m. to 5 a.m.). The values of iodide excretion rate obtained by both methods were consistent like in humans with an excretion fraction of 0.3 for iodide in rabbits. In rabbits weighing 3-4 kg the renal iodide excretion rates were 5-7 ml/min during the rapid phase and 3-4 ml/min during the slow phase.


Association between subcellular proliferating membranes and mitochondria in dog thyroid follicular cells induced by synthetic double-stranded RNA administration.

The administration of polyriboinosinic-polyribocytidylic acid [poly(rI:rC)], an interferon inducer and antitumour agent, induced proliferating intracellular membranes as well as a characteristic association between those membranes and mitochondria. The membrane-mitochondrion association was most often observed in small mitochondria lying close to the basal cell membrane. Although the meaning of this differential response is not known, these findings might be explained by an actual biogenesis of the mitochondria from subcellular membranes induced by poly (rI:rC), either directly or secondary to its toxic effects.


Diminished sensitivity of the insulin response to glucose following growth hormone influsion in man.

The acute effect of growth hormone (GH) administration on the dose-kinetics of glucose-stimulated insulin release was investigated in eight healthy, non-obese male subjects. The glucose-insulin dose-response relationship in these subjects was established by performing glucose infusions at three different dose levels. In a second series of experiments, the glucose infusions were preceded by a 30 min infusion of GH (40 mug/kg body weight), terminated 60 min before administration of glucose. GH induced small but significant reductions in the basal levels of blood glucose and plasma insulin. The glucose tolerance (k-value) was diminished after GH at all glucose doses. Both the initial late phases of insulin response to glucose were impaired following GH treatment. This effect was most pronounced when the intermediary glucose dose (eliciting a blood glucose level around 300 mg/100 ml) was used. Thus, the insulinogenic index (whole period of stimulation) was reduced by GH to 88.9 +/- 7.6, 60.4 +/- 7.1 and 74.3 +/- 11.0% of the respective controls when the smallest, the intermediate, and the largest glucose loads, respectively, were given. The blood glucose-plasma insulin dose-response curves were shifted to the right of the control ones when glucose infusion was preceded by GH. These findings suggest that GH diminishes the sensitivity of the islet for the insulin releasing action of glucose. Some possible mechanisms by which GH may modify insulin release are discussed.