Effects of prostaglandins on the smooth muscle of the urinary tract.

A short review is given of the effects of prostaglandins on the smooth muscle of the bladder, urethra and ureter. In several animal species and in man, prostaglandins of the E and F types contract the detrusor. The contractions develop slowly and are not affected by tetrodotoxin, phenoxybenzamine, or atropine, suggesting a direct effect on the smooth muscle cell. However, evidence is also available suggesting a role of the prostaglandins as modulators of transmitter release in the bladder. In animals as well as in man, urethral smooth muscle is contracted by prostaglandin F2alpha, but relaxed by prostaglandins E1 and E2. The smooth muscle of the ureter seems to react similarly, but published results vary. The detailed mode of action, and the role of prostaglandins in the control of activity in urinary tract smooth muscle remain to be established.


Bioavailability of four different pharmaceutical preparations of carbamazepine.

The bioavailabilities of two tablet brands carbamazepine (CBZ) (Tegretol, A; Neurotol, B) were compared with two new experimental preparations (C,D). Formulation A showed a more sustained release nature than did the other formulations. The AUCs0 leads to infinity gave no significant differences between treatment A and three other treatments. However, if AUC0 leads to 72 was calculated instead of AUC0 leads to infinity, the preparation A gave the significantly lower bioavailability than the other compounds. Formulations A and B are marketed as generically equivalent preparations in Finland. However, their pharmacokinetic parameters after a single dose were different.


Different effects of the ionophore A-23187 and D-glucose on 45Ca2+ fluxes in isolated islets of ob/ob-mice.

Fluxes of 45Ca2+ were studied in beta-cell rich islets of non-inbred ob/ob-mice, using LaCl3 to wash out extra-cellular and superficially bound 45Ca2+. The ionophore A-23187 (10 microM) increased the 45Ca2+ uptake in islets both at 3 and 20 mM D-glucose, the effect being more pronounced after 10 min than after 120 min of incubation. In incubations for 120 min, 20 mM D-glucose induced a higher uptake of 45Ca2+ than did A-23187. The ionophore enhanced the unidirectional efflux of 45Ca2+ from preloaded islets. Pretreatment of islets with 20 mM D-glucose in non-radioactive medium inhibited the subsequent D-glucose-induced 45Ca2+ uptake. Similar pretreatment with A-23187 increased the subsequent ionophore-induced 45Ca2+ uptake. The results suggest that A-23187 acts by catalyzing Ca2+ fluxes across the beta-cell plasma membrane. The different effects of D-glucose and A-23187 on 45Ca2+ fluxes suggest that the two agents act through different mechanisms in the beta-cells.


Localization of kallikrein and its relation to other trypsin-like esterases in the rat pancreas. A comparison with the submandibular gland.

Kallikrein was located by the direct immunofluorescence technique to the granule-containing luminal portion of pancreatic acinar cells. For the demonstration of the intracellular distribution of pancreas kallikrein, in vivo fixation of the gland was necessary. No kallikrein was found in the duct cells or in the islets of Langerhans. Quantitation by single radial immunodiffusion showed that the concentration of kallikrein in the presence was 1.32 +/- 51 microgram/g wet weight, i.e. 1/91 that of the rat submandibular gland. Bz-Arg-OEt-esterases were in the pancreas found as pro-enzyme but as active enzyme in the submandibular gland. Trypsin-like esterases, hydrolyzing epsilon-amino caproic acid naphtol-AS-D.HBr (ACA), were found in the active form in both submandibular gland and pancreatic homogenates. The submandibular gland contained per g wet weight 6 times as much ACA-esterase activity as the pancreas. In the submandibular gland, kallikrein and ACA-esterase activity were found together in practically all granular tubular cells. Thus, the granular tubular cell contains kallikrein as well as other trypsin-like enzymes like the ACA-esterase, and is in this way comparable to the pancreatic acinar cell. An extraglandular function of kallikrein is suggested for the pancreas in contrast to other kallikrein-containing exocrine organs.


Suppresion of autonomic postganglionic discharges by pentobarbital in dogs, with or without endotoxemia.

Initial effects of pentobarbital (8 mg/kg) on autonomic efferent and afferent discharge rates were studied in 26 dogs under morphine-chloralose anesthesia. Half of the dogs were given endotoxin E. coli (1 mg/kg) before pentobarbital. The postganglionic cervical vagal efferentation of all the dogs decreased as did the postganglionic cardiac sympathetic efferentation. The heart rate of the dogs given endotoxin decreased, while an increase in heart rate with abolition of respiratory arrhythmia, was observed in dogs without endotoxin. The aortic pressure of the former dogs dropped while it fell only slightly in the latter ones. The aortic arch baroreceptor activity decreased while the changes of left atrial B-type receptor activity were not significant. The changes of the left atrial and central venous pressures were slight but those of the pulmonary arterial pressure generally paralleled the changes  in the aortic pressure. Pentobarbital, accordingly, seems to exert both sympatholytic and vagolytic effects. These explain the heart rate changes, as well as the impaired cardiac contractility it evokes. The obvious impairment of cardiovascular control mechanisms by pentobarbital should be seriously considered in investigations into the cardiovascular control.


Plasma vasopressin in ethanol intoxication and hangover.

The effect of ethanol intoxication and hangover on immunoreactive plasma arginine vasopressin (AVP) concentration was studied in 7 healthy supine men in controlled clinical conditions. In 6 subjects plasma AVP increased above control values at the time of maximal blood ethanol concentration. The highest AVP values were observed in the subjects having nausea and vomiting and the worst hangover symptoms. During hangover plasma AVP values were higher than the controls and the response of plasma AVP to upright posture was exaggerated. The dissociation of plasma AVP concentration and ethanol diuresis suggested that the suppression of AVP release is not the sole determinant of ethanol diuresis. The study may indicate that the toxic effects of ethanol and the severity of hangover symptoms are associated with the state of hydration and individual sensitivity of AVP triggering mechanisms.


Reflex adrenergic control of endocrine pancreas evoked by unloading of carotid baroreceptors in cats.

The effects of unloading of the carotid baroreceptors on arterial plasma glucose concentration as well as on portal plasma immunoreactive glucagon (IRG) and insulin (IRI) concentrations were studied in anestethized, vagotomized cats either by sectioning the sinus nerves or by lowering the pressure in the isolated carotid sinuses. Complete elimination of the carotid baroreceptor discharge by cutting the sinus nerves caused an increase in the arterial plasma glucose concentration by 100% and an increase in the portal IRG level by about 200%, whereas the portal IRI concentration decreased to 50% of its basal value. These baroreceptor-induced changes of the plasma IRG and IRI levels seemed to be graded in relation to the drop in carotid blood pressure and they were clearly detectable when the pressure was lowered from 120 to 90 mmHg in the isolated carotid sinus preparation. The described reflex hyperglycemia, hyperglucagonemia and hypoinsulinemia were mediated to the pancreas and liver mainly by the sympatho-adrenal system, since cutting the splanchnic nerves above the adrenal glands abolished the hyperglycemia and hypoinsulinemic responses and markedly depressed the magnitude of the hyperglucagonemic response. In adrenalectomized cats, complete unloading of the baroreceptors evoked both hyperglucagonemia and hypoinsulinemia although the magnitude of the hormonal responses was diminished. In animals where the pancreas and liver were sympathectomized but the adrenal glands left intact, cutting the sinus nerves evoked a doubling of the IRG level and a slight increase in plasma glucose, but no significant change of the IRI level. I.v. infusion of adrenaline (1 microgram/kg X min) or noradrenaline (5 microgram/kg X min) caused pronounced increases in IRG and plasma glucose and a clear-cut reduction of IRI. We conclude that the function of the endocrine pancreas in the cat can be influenced by variations in the blood pressure by means of a reflex control which originates from arterial baroreceptors. This reflex adjustment of the endocrine pancreas is mediated chiefly by two links of the sympatho-adrenal system, namely by catecholamine-release from the adrenal medulla and, more importantly, by a direct adrenergic nerve fibre influence on the alpha- and beta- cells.


Cis(Z)-clopenthixol and clopenthixol (Sordinol) in chronic psychotic patients. A double-blind clinical investigation.

The clinical effect of cis(Z)-clopenthixol has been compared with that of clopenthixol, which is a mixture of the pharmacologically active cis(Z)-isomer and the inactive trans(E)-isomer. In the 2-month double-blind trial were included 57 psychotic patients, mainly schizophrenics. Ratings evaluating severity of illness, therapeutic effect, possible interference of side effects with the patient's functioning, as well as any individual side effects were done at months 0, 1, and 2. The antipsychotic effect of cis(Z)-clopenthixol was found equal to that of clopenthixol whereas the cis(Z)-isomer on a mg/mg basis was twice as active as clopenthixol. Apart from the finding that the unspecific sedative effect appeared to be less marked with cis(Z)-clopenthixol, the type, degree, and frequency of side effects were the same in the two groups of patients. More than half of the patients experienced no side effects.


Addition of L-tryptophan to electroconvulsive treatment in endogenous depression. A double-blind study.

The combination of electroconvulsive treatment (ECT) and i.v. L-tryptophan (T) was compared with ECT and saline in double-blind study comprising 20 patients with endogenous depression. No significant difference was found with regard to the number of ECT given nor in the rate of reduction of depressive symptoms. Except for a slight decrease of plasma total tryptophan in the palcepo group, no difference were found in plasma total and free tryptophan nor in the concentration of total tryptophan in the cerebrospinal fluid.


Cisternal changes produced by experimental balloon tumours in the posterior cranial fossa. A post-mortem investigation.

Post-mortem cisternography before and after stereotactic introduction of balloon tumours to predetermined positions in the posterior fossa was carried out. Radiography in situ as well as radiography and inspection of plastic casts of the cisterns were used for the systematic analysis of the appearances of the cisterns.


Radiologic appearance of complete gastric erosions.

At gastroscopy of 656 patients, complete gastric erosions were found in 58 (11%). Radiography performed in 46 of these demonstrated erosions in 21 of 33 with a time span less than one month between radiography and gastroscopy but in only 4 of 13 with a time span of one to 3 months. Double contrast technique supplemented with films of compressed barium-filled antrum demonstrate the lesions best. Complete erosions have often appearances simulating gastric polyps or large mucosal folds and are often found together with ulcers.


Time-blind evaluation of psychopathology in drug research.

Before the development of audiovisual techniques, it was impossible to avoid two time-related biases in drug evaluation: rating on different occasions, i.e. in different mood states as regards the rater (the so-called time-gap); knowledge by the rater of the sequence of his ratings. In order to make a time-blind evaluation possible, the author has worked out the following steps: tape-recording of the interviews, standardization of the interview, elimination of questions endangering a time-blind analysis, evaluation of the different interviews of the same patient on different rating sessions. The author summarizes his first three drug trials analyzed according to the time-blind procedure, and concludes that this procedure is a definite progress regarding the validity of drug research.


Disturbances in acid-base balance during hypophosphatemia and phosphate depletion.

Phosphate depletion leads to bone resorption, resulting in the accession of alkali to the blood and urine. There may also be a release of lactic acid from liver, resulting from ATP depletion and intracellular alkalosis. In general, the net result of these tissue effects is an alkali load discharged into the extracellular fluid. In the kidneys, phosphate depletion causes impaired proximal tubular reabsorption of bicarbonate, and perhaps other substrates, owing in all likelihood to both intracellular alkalosis and depletion of ATP. This impaired proximal capacity to reclaim bicarbonate results in hyperchloremic acidosis. The distal nephron may contribute to acidosis by virtue of inability to produce titratable acid (phosphate-free urine) and perhaps impaired ammonia production. Severe phosphate depletion, therefore, tends to produce hyperchloremic acidosis as a result of a diminished capacity for bicarbonate reclamation in the proximal tubule and probably some impairment of bicarbonate regeneration in the distal nephron. These effects, when marked, ultimately outweigh the contribution of alkali coming from bone breakdown. In the liver, phosphate depletion may stimulate lactic acid production by reducing hepatic ATP stores (Pasteur effect) and producing intracellular alkalosis. ATP depletion may also limit hepatic uptake of lactate. Finally, in muscle cells ATP depletion, resulting from either profound hypophosphatemia or the metabolism of massive fructose loads, may eventuate in frank rhabdomyolysis.


Physiological and pharmacological aspects of 24,25-dihydroxycholecalciferol in man.

The present study describes the response to small oral doses (1--10 microgram/day) of 24,25-DHCC in man. Contrary to expectation, 24,25-DHCC was as potent as 1,25-DHCC in increasing intestinal absorption of calcium both in normal persons and in patients with a variety of disorders of calcium metabolism. Despite this increase in intestinal absorption, plasma and urine calcium did not increase after 24,25-DHCC as they did after 1,25-DHCC. Metabolic balance studies showed calcium balances to increase by 1.6 to 11.5 mmoles/day in 5 of the 6 patients studied. 24,25-DHCC increased intestinal absorption of calcium equally well in anephric patients, suggesting that conversion of 24,25-DHCC to 1,24,25-trihydroxycholecalciferol by the kidney cannot be the sole mechanism by which 24,25-DHCC expresses biological activity, even though in vitamin D deficient rats nephrectomy does abolish the ability of large doses of 24,25-DHCC to increase calcium absorption. It is concluded that 24,25-DHCC may be a calcium-regulating hormone in man. In view of the effects demonstrated here and its relatively high concentration in plasma and slow turnover rate, 24,25-DHCC has the properties that might be ideal for a long-acting stimulator of bone mineralisation. Further work is needed to explain why 24,25-DHCC has effects in man which are not readily seen in other species.


Renal handling of magnesium.

In summary, magnesium reabsorption occurs throughout the proximal and distal segments of the nephron. The proximal tubule is less permeable to magnesium than calcium and sodium with most of the filtered load being reclaimed in the ascending loop of Henle. In contrast to calcium and sodium a tubular reabsorptive maximum has been demonstrated for magnesium and under certain circumstances secretion has been demonstrated in the terminal nephron segments. Although many factors are known to affect magnesium reabsorption the mechanism of the renal homeostasis remains to be determined.


Clinical correlants of changes in nasal flow/resistance (Rn) measurements.

It has been suggested that changes in nasal airways flow/resistance imply clinical betterment and increased nasal patency, and that patients with congestion sense relief when treatment improves their Rn values by 20% or more, speculations supported by inferences from lower airways dynamics. This hypothesis was tested in a double-blind study of the nasal decongestant potency of phenylpropanolamine/aromatic oil, phenilpropanolamine, aromatic oil and placebo syrups given to 80 patients with common colds who were followed for 6 hours. Rn was determined by electronic posterior rhinometry; patients estimated their degree of nasal congestion with a 6-ranked subjective scale. Statistical techniques included paired and unpaired t-tests, chi-square analysis, analysis of covariance to determine comparisons of within-group differences, differences between drug and placebo groups, and determination of the number in each group improving 20% or more from control Rn. Correlation coefficients relating Rn values to subjective responses were determined by pairing these for each patient and applying standard regression analysis. Despite a strong placebo effect, mean Rn changes ranked the efficacy of the 4 test mixtures, with the 20% improvement criterion allowing the sharpest separation of active mixtures from inactive. In regression analysis the correlation coefficient of 0.56 and the regression slope of 0.66 were both significant (p = 0.01 or better); the latter figure implied that a 1 unit difference on the subjective scale corresponded to a 0.66 unit difference on the Rn scale. With an average objective reading of 3.77 a 1 unit change n the subjective rating perceptible to the subject as a difference in the state of his nasal congestion was equivalent to a mean Rn change of 17.5%. This supports our prior assumption, indicating that a 17.5% to 20% improvement in Rn is experienced as clinical relief. Further, subjective rating scales appear to be statistically sound as a means of assessment of the status of the nasal airways.


Results of a clinical trial with a Dermatophagoides pteronyssinus tyrosine adsorbed vaccine.

Twenty-eight patients were included in a double-blind placebo-controlled study of a vaccine containing tyrosine-adsorbed Dermatophagoides pteronyssinus antigen (Migen(R)). The aim of the trial was to show the efficacy and safety of Migen as a 6-injection course, with or without a follow-up course of 6 maintenance doses, for the treatment of bronchial asthma. The patients selected had suffered from perennial asthma for at least 2 years and gave a strong skin reaction to house dust mite. The subjects in the study were divided into two groups: one of twelve patients receiving only a standard course of six graded injections at weekly intervals and the other of sixteen patients receiving the same course followed by a maintenance course comprising six injections of the highest strength (400 N.U.). Approximately half the patients in each of these groups were on placebo. Assessment was based on the patient's and doctor's impression of the response to the treatment using a daily symptom record card and clinical observation of the patient at regular intervals. The overall assessment was graded in accordance with the following four point scale: very good, good, same and worse. Results showed that the pa tients receiving Migen as a 6-injection course responded better than patients receiving placebo; moreover, patients who received 6 maintenance injections of Migen gave a very good or good response compared to those who were submitted to 12 injections of placebo and also compared to those receiving the standard course. Particular notice was taken of the side effects of the vaccine. Migen proved to be a good and and safe method of treating bronchial asthma due to house dust mite (D. pteronyssinus).


Diet and breast cancer: a review.

Diet may promote or inhibit human breast cancer through its effects on hormonal systems. In this paper, risk factors with potential dietary components, geographic variations related to diet, experimental studies on diet and mammary tumors, and hormonal hypotheses are reviewed. The associations of early menarche with higher risk, and of early first pregnancy with lower risk suggest that events during teenage years may be determinants of breast cancer. Although data on the association between obesity and mammary cancer are not entirely consistent, it does seem clear that body fatness at menarche and during postmenopausal years may influence hormonal synthesis and metabolism. Published reports based on the Food and Agricultural Organization's food availability data or frequencies of individual foods are inadequate for associating diet with breast cancer incidence or mortality. Also, diets and susceptibility to breast cancer vary among species, and therefore results from rodent experiments should not be extrapolated to humans. Circumstantial evidence suggests that patterns of hormone metabolism in early years of life may be determinants of breast cancer risk. Research concerning the relationship of androgens, prolactin, estrogens, and possibly other hormones to risk factors should be continued. Further, there is a need for data relating dietary factors to hormone synthesis and metabolism. Epidemiological studies among young women in low- and high-risk countries are recommended. Comparisons of diet, body fatness, and hormonal levels could provide further insight about the relationship of diet to breast cancer risk. These same factors should be measured in case-controls studies, along with qualitative estimates of previous diet and possibly weight and height during adolescence. Dietary indices associated with early menarche may be the same as those related to breast cancer. Results of these investigations may provide valuable leads for preventive health programs.


Breast-feeding: main promoter of infant health.

Unique immunological factors in breast milk are responsible for the protection it affords infants against pathogenic agents. This protection is particularly effective against the infectious agents which invade or colonize the small and large intestine. Factors interfering with enterotoxigenic and enteroinvasive bacteria, and with entero- and rotaviruses, have already been detected in colostrum and mature human milk. Moreover, the biochemical composition of human milk makes it the best infant food during the first 6 months of life, and with supplementation, for months thereafter. At the same time, optimal maternal-infant interactions are effected during breast-feeding which strengthen infant care in health, in illness and during convalescence. The low cost of breast-feeding when compared to other types of alimentation, coupled with its unparalleled nutritive, anti-infectious, and behavior stimulating properties makes it the main promoter of infant health. There remains a need for investigation of the factors that have brought about a reduction in breast-feeding throughout the world. New methodologies to increase the incidence of breast-feeding, particularly in the developing nations, are critical. The availability of such methodologies could facilitate delivery of other health interventions ideally delivered by the mother, the most important agent for improving the health of infants and children.


Bone marrow aspiration and trephine biopsy. An approach to a thorough study.

Recent advances in the treatment of hematologic malignancies have been paralleled by renewed interest on the part of pathologists and hematologists in methods of obtaining and preparing bone marrow for diagnostic studies. A thorough bone marrow morphologic study involves examination of peripheral blood smears, direct, particle, and buffy coat bone marrow smears, trephine biopsy imprints, particle and trephine biopsy sections, and marrow volumetric data. The information obtained from the study of these various specimens is complementary. Frequently it is a combination of clues gathered from examination of several different preparations that leads to a correct diagnosis. Utilization of biopsy material by the methods described provides complete, accurate and reproducible information and minimizes the necessity for repeating a biopsy for morphologic diagnosis or ancillary studies.


Preparation and light-microscopic examination of fixed hematopoietic cells in soft agar.

Hematopoietic cells from the blood or bone marrow (of leukemic and nonleukemic patients) grown in vitro using soft agar tissue-culture technics may be fixed in formalin, embedded in paraffin, sectioned, and mounted on glass slides. Light microscopic examination of these sections stained with hematoxylin and eosin and with other histologic stains provides information useful in investigative and diagnostic hematology. Morphologic interpretation of the characteristics of cultured cells is within the capability of pathologists and clinical hematologists. The slides provide a permanent record of growth in vitro.


Immunofluorescent localization of Staphylococcos aureus antigen in acute bacterial endocarditis nephritis.

A 75-year-old man with Staphylococcus aureus endocarditis in whom acute diffuse proliferative glomerulonephritis developed is described. The light- and electron-microscopic changes of the glomeruli in this case were identical to those of acute poststreptococcal glomerulonephritis. Immunofluorescence revealed deposition of immunoglobulins and complement in the glomeruli. In addition, bacterial antigenic material was demonstrated in the glomeruli by indirect immunofluorescence. These observations further support the hypothesis of an immune-complex pathogenesis in this form of glomerulonephritis.


Pediatric clinical pharmacology. A practical review.

Significant differences exist between children and adults in their handling of a large number of therapeutic agents. The relative immaturity of the pediatric patient and the continuous state of development of body and organ functions influence both drug effects and drug disposition. Daily dosage requirements vary with age. For many drugs, children require and tolerate much more of a drug, relative to their size, for the same effect. Newborns may need more or less of a drug for a comparable effect. A conceptual framework is provided to aid in understanding the individuality of the pediatric patient's drug disposition processes based on differences in physiologic functions affecting drug absorption, distribution, metabolism, and excretion. Additional data are needed on drug disposition in children of all ages to maximize therapeutic drug usage with avoidance of toxicity.


Trimethoprim-sulfamethoxazole vs sulfamethoxazole for acute urinary tract infections in children.

A total of 118 children between 6 months and 10 years of age with acute urinary tract infection were treated in a random; double-blind manner with 12 mg/kg/day of trimethoprim-sulfamethoxazole (61 patients) or 50 mg/kg/day of sulfamethoxazole (57 patients) for ten days. Mean trimethoprim and sulfamethoxazole susceptibilities of Escherichia coli isolated from these patients were 1.2 and 0.6 microgram/ml, respectively. Mean serum concentrations of trimethoprim and sulfamethoxazole were 1.8 and 62 microgram/ml, respectively, one hour after the dose. Of the children who completed the ten days of prescribed medication, clinical and bacteriological cure was confirmed immediately after treatment for all but one patient in each group. Most patients in each treatment group with recurrent infections had underlying urological abnormalities. Severe hematological, renal, or hepatic toxicity requiring interruption of treatment was not encountered. No advantage of trimethoprim-sulfamethoxazole over sulfamethoxazole alone for acute urinary tract infection was demonstrated.


Respiratory syncytial virus infection. Rapid diagnosis in children by use of indirect immunofluorescence.

Specimens of 387 nasopharyngeal suction smears obtained from 354 children hospitalized with acute respiratory infections during an eight-month period were examined for the presence of respiratory syncytial (RS) virus by the indirect immunofluorescence antibody technique (IFAT) and by conventional tissue culture infectivity techniques. Respiratory syncytial virus was identified in nasopharyngeal suction smear specimens from 123 of these specimens (32%) with the use of both techniques. Of the specimens positive on tissue culture 92% were also positive for RS virus by IFAT. However, eight specimens positive for RS virus by tissue culture were negative by IFAT, although three of the specimens were technically unsuitable. Six percent of the specimens negative for RS virus by tissue culture were positive for RS virus antigen when tested by IFAT. Using IFAT, identification of RS virus could be accomplished within four to six hours, whereas isolation by tissue culture took an average period of ten days. These data suggest that IFAT is a reliable means for the rapid diagnosis of RS virus infection in infants and children.


Urolithiasis in adolescents.

The characteristics of 31 adolescent patients aged 11 to 20 years with urolithiasis were examined by means of a ten-year retrospective chart review. The majority of stones were found to be secondary to preexisting conditions, with the most common being bladder dysfunction (neurogenic or exstrophy). Exogenous corticosteroid therapy appeared to play a role in lithogenesis in five patients and was the only apparent contributing factor in an 11 1/2-year-old girl. Childhood inborn errors of metabolism accounted for the stones in four of the teenagers. An additional four adolescents did not have any definable biochemical, genetic, or anatomic abnormalities and, therefore, no obvious etiology.


Avascular necrosis of bone after renal transplantation.

Avascular necrosis (AN) of bone developed in 11 of 100 children who received renal transplants from 1964 to 1977. Bones involved were femoral heads, 14; femoral condyles, 12; tall, two; and carpal naviculars, two. Seven children with symptomatic AN of the femoral heads were treated with limited weight bearing; three subsequently required arthroplasty, and degenerative joint disease developed in one. The AN at other joints healed clinically but not roentgenographically. Although the prevalence of AN decreased after 1967 coincident with a decrease in prednisone dose, children with AN received the same cumulative prednisone dose as children in a control group. Serum phosphorus levels were different in the AN and control groups, but other indexes of hyperparathyroidism were similar. The relative contributions of prednisone therapy and hyperparathyroidism to the development of AN could not be delineated.


Strongyloidiasis in childhood.

Strongyloides stercoralis is an intestinal nematode of man that is still regularly encountered in many parts of the United States. Strongyloidiasis should be considered in any child with unexplained eosinophilia, steatorrhea, protein-losing enteropathy, or chronic diarrhea, especially if associated with weight loss, growth failure, or recurrent upper abdominal pain. This parasite should be ruled out in any patient from an endemic region who is to be treated with corticosteroids of immunosuppressive agents. Microscopical examination of duodenal fluid, Baermann's fecal extraction technique, or the Haradi-Mori stool culture method may be required to make a diagnosis because the organism is not routinely found in concentrated feces even after multiple examinations in some infected individuals. A diagnosis of strongyloidiasis is important because the disease is curable.


Oral gentamicin therapy in the prevention of neonatal necrotizing enterocolitis. A controlled double-blind trial.

The value of prophylactic oral gentamicin sulfate therapy in the prevention of necrotizing enterocolitis (NEC) was evaluated in a group of 42 high-risk neonates over a four-month period in a randomized, double-blind controlled trial. Twenty babies in the treatment group received 2.5 mg/kg of gentamicin sulfate every six hours for one week after birth, and 22 babies received dextrose-and-water placebo in an equivalently small volume. None of the 20 gentamicin-treated babies developed NEC. Four of the control babies did. Two of these babies died, and their diagnosis was pathologically confirmed. This difference in the incidence of NEC between the treatment and control group was significant at the .05 level. These results support the prophylactic use of orally given gentamicin for selected babies at high risk for NEC, particularly those born prematurely and those who have a history of perinatal asphyxia or umbilical artery catheterization or both. Continued surveillance for changes in antimicrobial sensitivity patterns is recommended.


Cell-mediated immunity to acetaldehyde in alcoholic liver disease demonstrated by leukocyte migration test.

To determine whether a sensitization to ethanol metabolites occurs in alcoholic liver disease, reactivity of lymphocytes to nontoxic amounts of acetaldehyde was studied by direct elaboration of migration inhibitory factor (MIF) production. Eighteen alcoholics with various degrees of biopsy-proven liver damage showed increased MIF production in response to acetaldehyde; the mean value of the group differed significantly from 15 healthy controls, 15 subjects with nonalcoholic liver disease, and 15 alcoholics without liver involvement (P less than 0.001, P less than 0.001, P less than 0.02, respectively). Among the alcoholics with liver disease, none individuals (50%) with histological signs of advanced alcoholic hepatitis showed the highest percentage of inhibition of migration; the value differed significantly from the remaining patients with lesser degrees of hyaline necrosis in liver biopsies (P less than 0.005). These results indicate that acetaldehyde is involved in the pathogenesis of alcoholic hepatitis. Clinically, this test might facilitate the selection of patients with alcoholic hyaline necrosis.


Failure of cyanoacrylate tissue glue (Flucrylate, MBR4197) to stop bleeding from experimental canine gastric ulcers.

A plastic tissue adhesive, trifluoroisopropyl 2-cyanoacrylate (Flucrylate (TM), MBR4197), was tested for hemostatic efficacy in acute laparotomy experiments using a canine model of acute bleeding gastric ulcer. An improved delivery system suitable for endoscopic use was developed. Hemostatic efficacy of the adhesive was tested in both briskly bleeding ulcers and in oozing ulcers after partial treatment with a heater probe. In pilot studies at laparotomy, primary and adjunctive cyanoacrylate therapy of 81 bleeding ulcers were evaluated in seven unheparinized foxhounds. Hemostasis was produced in 11% of ulcers treated with cyanoacrylate alone and in 31% of ulcers treated with cyanoacylate as an adjunctive after partial heater-probe treatment; no sham-treated control ulcers stopped bleeding under the conditions of the experiment. To evaluate Flucrylate (TM) using out standard heparinized ulcer model, a randomized study was performed in six heparinized foxhounds at laparotomy. Ulcers were randomized to treatment with cyanoacrylate alone, adjuctive cyanoacrylate, heater probe alone or untreated control. Sham-treated control ulcers or ulcers treated with cyanoacrylate alone did not stop bleeding; 42% of ulcers treated with cyanoacrylate as an adjunctive stopped bleeding; all ulcers treated with a heater probe stopped bleeding. In this experimental model of acute bleeding gastric ulcer, trifluoroisopropyl 2-cyanoacrylate (Flucrylate(TM),MBR4197) did not stop severe bleeding and was unpredictable as an adjunctive treatment.


Detection of cellular immunity derangements in chronic gastritis by a skin window test.

An autologous "skin window test," used lately for the study of cellular immunity in cancer, was applied here successfully to 54 patients with upper-gastrointestinal ailments, 48 of whom had a coexistent fundic and/or antral chronic gastritis of varying severity. The diagnoses of gastritis were made by multiple fiber-gastroscopic biopsies. The ether-alcohol-fixed cryostat sections of fundic and antral biopsies were mounted on cover slides and placed on small cutaneous abrasions of the forearm of the same patients for 24--28 hr. The exudates on cover slides and on imprints of the abrasions were read blindly for the mononuclear cell response according to criteria set for this test by Black and Leis (10). A positive reaction was obtained in 8 of the 54 patients using autologous fundic mucosal biopsy. An autologous antral mucosal biopsy gave positive reaction in only 2 of the 26 of the patients in whom it was used. The positive yield of this autologous skin window test in chronic advanced fundic gastritis was somewhat higher than that obtained by other authors using lymphocytes blast transformation or macrophages migration inhibition test in vitro. It was much higher than the yield obtained by others who used skin tests in vivo, with homologous or heterologous gastric mucosal extracts as antigens. The autologous skin window is safe in regard to possible transmission of hepatitis. Its applicability for detection of cellular immunity derangement in chronic gastritis carries promise.


The effect of glucagon on the exocrine pancreas. A review.

Glucagon can depress normal animal and human pancreatic exocrine secretions and modify experimentally-induced pancreatitis in animals. It has yet to be demonstrated that glucagon has any efficacy in the treatment of the diseased pancreas in man. Glucagon might act on the exocrine pancreas by 1. reducing pancreatic blood flow, 2. decreasing gastric secretion, 3. lowering serum calcium levels by the release of calcitonin, 4. acting to inhibit the secretin mechanism, 5. causing a hyperglycemia and 6. degranulating pancreatic acinar cells. While a reduction in pancreatic blood flow, an inhibition of the secretin mechanism and a hyperglycemia seemed to have been ruled out as possible mechanisms of action, there is too little available data to effectively speculate on the mechanism(s) of action of glucagon on the exocrine pancreas.


The geographic hypothesis and lactose malabsorption. A weighing of the evidence.

Reviewed in this article is evidence bearing on the geographic hypothesis advanced eight years ago to explain the striking ethnic or racial differences in prevalence of primary adult lactose malabsorption that are found around the world. Most evidence is found to support the hypothesis and the likelihood that some human groups came to have low prevalences of such lactose malabsorption because of selective pressures over a long historical period that favored the adult lactose absorber under particular ecological conditions.


Leukocyte alkaline phosphatase.

In summary, LAP is an intriguing enzyme and its control is related to pituitary-adrenal function. A review of the changes in LAP activity which occur in some physiological conditions and in disease states has been presented. The function of LAP, however, is unknown. Table I summarizes those conditions in which the LAP is consistently altered enough so to help in the diagnosis of the disorder. Of prime importance is the differentiation of CML from a leukemoid reaction or agnogenic myeloid metaplasia with a leukocytosis. However, in no instance is the LAP value alone diagnostic of any disease. It remains a laboratory test to be utilized in conjunction with all other available clinical data.


Lactic acidosis and diffuse histiocytic lymphoma (DHL).

Four patients with advanced diffuse histiocytic lymphoma who developed lactic acidosis are described. All four patients demonstrated disturbed liver function tests. In two of the patients, the lactic acidosis was unresponsive to treatment. The third patient responded successfully to the early initiation of combination chemotherapy with achievement of a clinical remission and correction of the lactic acidosis. The fourth patient responded to the initiation of chemotherapy with abatement of his lactic acidosis, but expired probably as the result of a pulmonary embolus. It seems likely that extensive hepatic infiltration may be one of the factors contributing to lactic acidosis in patients with diffuse histiocytic lymphoma. The early initiation of antineoplastic therapy may be important in the management of patients with histiocytic lymphoma and lactic acidosis.


Methods for establishing a working immunoradiometric assay for serum ferritin.

The two-site immunoradiometric assay for measurement of serum ferritin requires purified human ferritin and an avid high-titer antihuman ferritin antibody. Some of the antibody is radioiodinated following purification by immunoadsorption. All methods for preparation of these materials for the assay are described in minute detail. Performance of the assay itself and calculation of results are also described, and attention is drawn to several potential pitfalls. Adherence to these detailed descriptions will help to eliminate difficulties experienced by centers wishing to establish their own working serum ferritin assay.


The "Hageman" connection: interrelationships of blood coagulation, fibrino(geno)lysis, kinin generation, and complement activation.

The activation pathways for the generation of enzymes involved in blood clotting, clot lysis, complement activation, and kinin generation are briefly reviewed. The interrelationship of the four systems is illustrated by the multiple functions of four key enzymes: Factor XIIa, kallikrein, plasmin, and C1 esterase. The pivotal role of Factor XIIa in establishing this connection is elucidated.


Inbreeding as measured by isonymy, pedigrees, and population size in Törbel, Switzerland.

Törbel provides an interesting test case for the study of the relationship between inbreeding measured by pedigrees and inbreeding measured by isonymy. At the start of this investigation, we were aware that isonymy could introduce biases into the calculation of the inbreeding coefficient in either direction. However, it was expected that in Switzerland, inbreeding from isonymy would be an overestimate due to patrilocal residence and polyphyletic names. One way of dealing with this problem [13] was not to be concerned with the absolute value of inbreeding but only in the difference between estimates. Any bias introduced in the estimate itself disappears in such comparisons, so that a trend of inbreeding can be ascertained correctly. However, it was considered equally important to subject several populations to both a complete pedigree analysis and an isonymic analysis to determine the relationship between estimates of inbreeding. Despite the fact that several authors (Swedlund [18], for example) warned users of isonymy to exercise caution, the careless application of isonymy still persists. In the present study, estimates of inbreeding from isonymy were brought into line with other methods based on pedigree analysis and population size. However, it was possible to do this only in Törbel where pedigree depth was extensive and relatively complete. Similar corrections are possible only when the distribution of mono- and polyphyletic names is known and when migration data are reliable. If the trouble is taken to make these corrections, the same time and effort might as well be spent in pedigree analysis (when fairly complete ascertainment is possible) to achieve the same end result.


Current drug therapy: cardiac glycosides.

The following aspects of the cardiac glycosides are reviewed: chemistry; pharmacology; absorption, distribution, metabolism and excretion; uses; toxicity; cautions; drug interactions and laboratory test interferences; and dosage.


Antiplatelet drugs in arterial thrombosis: a review.

The thrombotic process, basic mechanisms of action of antiplatelet drugs, and clinical trials with platelet inhibitors are reviewed. The role of prostaglandins in platelet reactions and the mechanisms of aspirin's, dipyridamole's and sulfinpyrazone's inhibition of platelet function are discussed. Clinical studies of the use of these three drugs, alone or in combination with each other or with anticoagulants, for the treatment of thrombotic disorders associated with valvular heart disease, prosthetic heart valves, cerebral vascular disease (e.g., transient ischemic attacks), coronary artery diseases (including myocardial infarction), peripheral vascular disease, renal disease and renal allograft rejection are reviewed and evaluated. Clinical evidence suggests that antiplatelet drugs are useful in preventing thromboembolism associated with coronary and cerebral vascular disorders. In peripheral vascular and renal diseases and in renal allografts, their benefits have not been proved. Further controlled clinical studies of the preventive use of these drugs for arterial thrombosis are needed.


Nosocomial respiratory tract infection and colonization with Acinetobacter calcoaceticus. Epidemiologic characteristics.

Nosocomial respiratory tract infection with Acinetobacter calcoaceticus occurs frequently in many hospitals. An outbreak of respiratory tract infections in an intensive care unit provided an opportunity to study clinical and epidemiologic characteristics of such infections. Retrospective studies demonstrated that A. calcoaceticus in sputum was significantly associated with endotracheal intubation (p = 0.03) and continuous positive pressure ventilation (p less than 0.02). After control measures had interrupted the outbreak, a prospective microbiologic investigation demonstrated that one third of the hospital personnel had transient hand colonization with multiple strains of A. calcoaceticus. Pharyngeal, vaginal and rectal carriage was rare. A pulmonary therapist with chronic dermatitis had persistent hand colonization with the epidemic strain, and he contaminated respiratory therapy equipment. Cross contamination of respiratory therapy equipment occurred while in use, but no other inanimate reservoir was demonstrated. Although previous studies have implied that the inanimate hospital environment has unique reservoirs of A. calcoaceticus, these reservoirs were not implicated in this outbreak. Human skin must be considered an important reservoir of A. calcoaceticus.


Genital mycoplasma infections.

Three different species of mycoplasmas--M. hominis, M. fermentans, and Ureaplasma urealyticum--have been found to infect human genitalia. In the man, mycoplasmas appear to play a role in the etiology of nonspecific urethritis and prostatis. Mycoplasmas repeatedly have been cultured from the tubes of patients with acute salpingitis and a significant antibody response to the organisms during recovery has been reported. Obstetric infections and puerperal sepsis occasionally seem to be caused by mycoplasmas. These organisms also appear to induce spontaneous abortion as well as cause infertility in a small proportion of couples.


Pituitary tumors and pregnancy.

This paper contains a review of the natural history of pituitary tumors in nonpregnant and pregnant patients. Data were drawn from previously published reports and from responses to a questionnaire and were analyzed by life-table techniques. Follow-up of 62 nonpregnant patients with untreated pituitary tumors with and without visual field changes revealed a median time to treatment of 15 1/2 years and similar, relatively constant hazard functions. In 91 pregnancies occurring in 73 women with previously untreated pituitary tumors, ovulation had occurred spontaneously in 9 per cent, headache occurred in 23 per cent, and visual disturbances in 25 per cent with 61 per cent remaining asymptomatic. In those patients who developed symptoms, median time to headache was 10 weeks and to visual disturbance, 14 weeks. The hazard functions were relatively constant and similar. The relative risk of developing symptoms is independent of whether or not the first or second pregnancy occurred in the presence of the pituitary tumor. Of the pregnant patients with previously untreated pituitary tumors, 30 per cent required surgery or radiation therapy. Median time to treatment was 19 weeks. None of the 69 pregnant women without pituitary therapy had permanent sequelae. Only four patients who underwent surgery or received radiation treatment developed permanent symptoms and none was serious. In 78 pregnancies occurring in 73 women with previously treated pituitary tumors, headache occurred in 4 per cent and visual disturbances in 5 per cent. Only one patient required therapy. Treatment during pregnancy results in significantly increased prematurity rates but unchanged abortion and perinatal mortality rates. Small pituitary tumors do not constitute a contraindication to either induction of ovulation or pregnancy.


Endogenous intraocular Nocardia asteroides in Hodgkin's disease.

A 60-year-old man receiving antituberculous and corticosteroid therapy for a granulomatous disease of uncertain etiology was found to have a chorioretinal mass in his right eye. Fluorescein angiography showed blockage of fluorescence by the mass and late leakage. Autopsy findings were compatible with Hodgkin's disease with disseminated nocardiosis caused by Nocardia asteroides. Organisms typical of Nocardia were found in the choroid and subretinal space. The patient's history, ophthalmic examination, and fluorescein angiographic findings suggested a type of chorioretinal involvement.


Histocompatibility (HLA) antigens and keratoplasty.

In 84 cases of keratoplasty, all patients had densely vascularized corneas and a history of prior exposure to HLA antigens by pregnancy, blood transfusion, or previous transplantation. Donors were selected on the basis of a negative crossmatch to avoid donor antigens to which the recipient was preimmunized. The overall rate of graft failure from rejection was 15%. A retrospective analysis of donor-recipient HLA matching in 103 high-risk cases showed no consistent correlation between the number of antigens shared and graft outcome. These findings indicated negative cross-match to be important in donor selection for keratoplasty in high-risk cases.


Midpalatal suture opening during functional posterior cross-bite correction.

The purpose of this study was to determine whether opening of the midpalatal suture occurs during treatment of posterior cross-bites by means of a Porter or W appliance. In eight of the ten cases treated there was radiographic evidence of midpalatal suture opening. Posterior cross-bite correction with a Porter of W appliance may occur either by a combination of midpalatal suture opening and buccal tipping of posterior teeth or by buccal tipping alone.


Pituitary siderosis. A histologic, immunocytologic, and ultrastructural study.

Pituitaries of 6 patients with various iron overload states have been studied by morphologic techniques, including immunostaining and electron microscopy. The immunoperoxidase technique combined with the prussian blue reaction revealed iron deposition in all five adenohypophysial cell types, indicating the iron uptake per se does not entirely block hormone storage. Iron distribution was uneven; more iron was demonstrated in PAS-positive cells than in orangeophils, and a preferential localization was disclosed in the gonadotrophs. In 2 cases of hemochromatosis, reduction of pituitary gonadotrophs was implicated in the genesis of hypogonadism. By electron microscopy, iron particles were noted in the cytoplasm of various adenohypophysiocytes, partly incorporated into lysosomes. Some adenohypophysiocytes with iron accumulation showed degranulation by light and electron microscopy and decreased hormone storage by the immunoperoxidase technique. Although these changes may be causally related to iron deposition, more work is required to prove that iron has a direct toxic effect on adenohypophysial cells.


Bladder surface mucin. Its antibacterial effect against various bacterial species.

We previously reported the results of quantitative and histochemical studies implicating the surface mucin of the bladder mucosa as an important antibacterial defense mechanism, which functions by preventing bacteria from adhering to the bladder wall. We call the mucin "anti-adherence factor" and we feel this is a previously undocumented role for mucin as a type of host antibacterial defense. These experiments were conduced with Escherichia coli. In an effort to determine whether the anti-adherence ability of the vesical mucin was a generalized phenomenon, we repeated these studies using unrelated bacterial species, including E coli, Klebsiella pneumoniae, and Staphylococcus aureus. The ability of the vesical mucosa to resist bacterial adherence to its surface was found to be independent of the bacterial species that was investigated.


Natural killer cells. In vitro and in vivo.

A nonadherent, nonphagocytic mouse cell found in lymphoid organelles, but lacking characteristic surface markers of mature lymphocytes, is capable of lysing a wide spectrum of tumor cells but shows little cytolytic activity toward normal cells. This cytotoxic cell, termed a "natural killer" (NK) cell, shows a marked capacity to lyse lymphomas (syngeneic, allogeneic, or even xenogeneic) to the effector cell source. Its activity is inhibited by a variety of pharmacologic agents, eg, cytochalasins, cAMP-"active" drugs, and colchicine, over the same dose range at which these drugs inhibit other cytotoxic cells. We have no evidence that NK cell "specificities" are clonally distributed. Two sets of evidence are presented which suggest that the same NK cell population is responsible for lysing a variety of tumor target cells. Preliminary evidence suggests that modulation of NK cell levels in vivo is correlated with resistance to challenge with a syngeneic tumor, inferring that NK cells may play a salient role in host defenses against neoplasia.


Composite epithelial and endothelial basal laminas in human lungs. A structural basis for their separation and apposition in reaction to injury.

A new method for electron microscopic identification of endothelial basal lamina has been developed by treating fresh human lung tissues with 5 M guanidine HCl, pH 7.2, at 20 C for 24 hours. The guanidine treatment causes significant differential swelling and substantial decrease in electron density of the endothelial basal lamina and makes the latter readily distinguishable from the epithelial basal lamina. In the thin part of alveolar septums, the unit basal lamina shared by the epithelium on one side and the endothelium on the other is found to be composed of discrete epithelial and endothelial layers in close apposition. There is no structural modification at the site of apposition. The epithelial and endothelial basal laminas in alveolar septums seem to be two independent scaffold systems with distinct structural identities despite frequent close physical contact. The findings provide a structural basis for considering separation and apposition of epithelial and endothelial basal laminas in lung reaction to injury and in the pathogenesis of alveolocapillary block.


Macrophage fusion factor elicited from BGG-sensitized lymphocytes.

Lymphocytes obtained from rabbit lymph nodes sensitized to bovine gamma globulin produce in vitro the lymphokine macrophage fusion factor (MFF) which mediates the fusion of approximately 100% of normal alveolar and oil-induced peritoneal macrophages. Giant cells (GC) of Langhans and foreign body type form large syncytia containing as many as several hundred nuclei per cell. Nuclei of GC appear more spherical and larger than those of the normal mononucleated macrophages, and they possess several prominent nucleoli. Giant cells of peritoneal macrophage origin show enhanced intracytoplasmic vacuolization. Normal macrophages cultured as a monolayer in MFF-rich supernatants form cell clusters which progressively fuse during the 24-hour incubation period. A signoid dose-response curve was obtained for cell fusion with MFF-rich supernatants possessing high titers, ie, the latter supernatants undiluted partially inhibited macrophage fusion. MIF-like activity was detected in MFF-rich supernatants as well as a factor(s) which inhibited 3H-thymidine uptake by giant cells.


The pathogenesis of respiratory syncytial virus infection in cotton rats.

The cotton rat is susceptible to respiratory synctial virus infection in both the upper and lower portions of the respiratory tract. Virus replicates to high titer in the nose and lungs and to relatively low titer in the trachea. Immunofluorescence studies demonstrated viral antigen in the nasal epithelium and the bronchial and bronchiolar epithelium but not in the trachea or the alveolar cells of the lungs. Histopathologic changes included a desquamative, exudative rhinitis of moderate severity and a mild proliferative bronchiolitis. Serum neutralizing antibody developed in all animals by the ninth day after infection, reaching extremely high titer in several instances. Unlike the previously described response of experimentally infected infant ferrets, cotton rats are uniformly susceptible to pulmonary infection throughout life, thereby offering a model for long-term pulmonary studies heretofore not available.


Smoking and life expectancy among U.S. veterans.

Life expectancies were estimated for selected groups of smokers, ex-smokers, and nonsmokers based on the results of a 16-year mortality follow-up of 198,820 U.S. veterans. Life expectancy varied inversely with number of cigarettes smoked per day. The most pronounced differences were between nonsmokers and heavy cigarette smokers (40+ per day). These differences in life expectancy were greatest at the younger ages--nearly 9 years at ages 35 and 40. Life expectancies for cigarette smokers varied directly with age began smoking. For all ages, differences in life expectancy between nonsmokers and ex-cigarette smokers who stopped for other than doctor's orders were less than those between nonsmokers and current cigarette smokers. Results in the present study clearly confirmed Hammond's earlier findings.


A statistical analysis of two chemotherapy trials in lepromatous leprosy. II. Interactions among patient variables.

Interrelationships among six patient characteristics recorded upon entry into the trial were analyzed for 67 patients with lepromatous and near-lepromatous leprosy admitted into two chemotherapy trials. Sex was found to be significantly associated with age and with the histopathologic classification; disproportionately large numbers of older patients and of patients classified as borderline-lepromatous (BL) were males. Classifications of the disease process by clinical and histopathologic criteria were closely associated, but many patients classified BL on histopathological grounds were classified fully lepromatous by the clinical criteria. Measurements of the number of Mycobacterium leprae in the patients made by three methods were also significantly correlated. No significant correlations were found between either classification of the disease process on the one hand, and any of the measurements of the numbers of organisms on the other.


Electron microscopy of peroxidase and acid phosphatase in leprous and uninfected armadillo macrophages: a macrophage subpopulation contains peroxisomes and lacks bacilli.

Lepromatous tissue from armadillos inoculated 24--36 months earlier with Mycobacterium leprae was obtained for electron microscopic studies. Cytochemically stained lepromas revealed a subpopulation of macrophages containing peroxisomes. These peroxidase reactive macrophages were not infected with bacilli. Acid phosphatase was present in macrophages and many of these were infected with bacilli and contained vacuoles and lipid globules. Within the membrane-bound vacuoles, acid phosphatase surrounded bacilli. However, the reaction product ended abruptly at a 15--40 millimicron thick zone of low electron density surrounding intact bacilli. Acid phosphatase was more intensely reactive and localized less precisely in heavily infected and vacuolated macrophages than in lightly and non-infected cells. The effectiveness of this bacillary barrier and the numerous infected macrophages with substantial acid phosphatase argue against the ability of acid phosphatase to protect host cells from leprosy bacilli. Evidence suggests a protective action of peroxidase or the rapid turnover of macrophages within lepromas. Granular and membranous debris were commonly seen within vacuoles of infected macrophages. A portion of the debris was ultrastructurally similar to bacillary matrix and was nonreactive for peroxidase and acid phosphatase. Following homogenization and centrifugation, similar materials banded with bacilli above 60% sucrose. Another portion of the debris was ultrastructurally similar to host lysosomal matrix and was reactive for acid phosphatase. Results support the concept of dual host and parasitic origins of the debris found in phagolysosomes of infected macrophages. Transparent, oval Epon defects remained eccentric to the majority of intact bacilli in centrifuged fractions. Apparently, an intrinsic property of leprosy produced these Epon defects.


Response of Plasmodium falciparum in Sudan to oral chloroquine.

The chloroquine sensitivity of Plasmodium falciparum was studied in two areas of Sudan. In the Gezira, 99.2% of the patients tested responded completely to the drug. Two patients (0.4%) and one patient (0.2%) showed, respectively, RI and RII responses. However, in those showing RI response reinfection could not be excluded. In an area of southern Sudan patients could only be followed-up for 7 days; nevertheless, this was sufficient to exclude the presence of RII and RIII responses there. This study also showed that malaria is a common cause of fever in Sudan, as over 90% of fever cases tested in the Gezira were positive for malaria and P. falciparum was the predominant species in these cases.


Species prevalence of malaria in northern and southern Sudan, and control by mass chemoprophylaxis.

A survey in northern and southern Sudan showed that Plasmodium falciparum is the predominant species in malaria cases, occurring in 91% and 87%, respectively of the positive cases in these two regions. P. ovale was extremely rare in southern Sudan and was absent in the north. The survey, which was carried out during the transmission season in  northern Sudan, showed that malaria is common, occurring in 62% of those tested in some villages. A trial of mass chemoprophylaxis resulted in a marked decline in prevalence after 1 year, demonstrating the importance of chloroquine and establishing that malarial parasites in Sudan are highly sensitive to the drug.


Levamisole in ascariasis. A multicenter controlled evaluation.

An analysis is presented of 10 clinical studies from various countries where levamisole 50--150 mg was compared to pyrantel, piperazine, and placebo in a total of 1,734 patients, mostly children (levamisole: 830, controls: 904), suffering from ascariasis either as a single infection or usually mixed with other nematode infections. Degree of infection and efficacy of treatment were determined by quantitative coproparasitological methods. Levamisole produced higher cure rates (91%) and egg reduction rates (98%) than pyrantel, piperazine, or placebo. The efficacy of levamisole was unrelated to the patients' sex and age, the severity of infection, the presence of another worm infection, the type of associated worm infections, or the egg-counting technique. The overall incidence of reported adverse reactions was lower after levamisole than after piperazine, pyrantel or placebo; abdominal pain and headache, the most frequent complaints after levamisole, were related to the initial severity of ascariasis. Follow-up examinations 6 months after treatment suggested that levamisole might delay reinfection.


Bacteriuria in urinary schistosomiasis in Egypt a prevalence survey.

An epidemiologic survey to assess the prevalence of bacteriuria in urinary schistosomiasis was carried out in a region endemic for urinary schistosomiasis in Egypt. Twenty of 390 (5.1%) school boys aged 5--16 years were bacteriuric. This prevalence rate is more than 10 times greater than that found in comparable surveys in areas non-endemic for urinary schistosomiasis. In this endemic population bacteriuria was found in 6.5% of active egg excreters and 2.3% of non-egg excreters.


Antibody response to a polysaccharide antigen present in the schistosome gut. I. Sensitivity and specificity.

By using paraffin sections of adult schistosomes fixed in Rossman's fixative, specific human IgM and IgG antibodies to a polysaccharide present in the epithelial cells of the schistosome were measured by using indirect immunofluorescent techniques. Of the 49 patients, mostly infected with S. mansoni but a few infected with S. haematobium or S. japonicum, all had antibody present at a 1:8 dilution of serum. Specific IgM antibody was more sensitive than IgG, yielding 100% and 86% positivity respectively. The false positive rate was 3% in a panel of sera obtained from patients most of whom were infected with other parasites. Antibodies were detected by the 3rd week in experimentally infected animals. Unisexual infections also induced antibody production. As a diagnostic test, the measurement of antibody to the polysaccharide is an easily performed reliable test with high sensitivity and specificity.


Antibody response to a polysaccharide antigen present in the schistosome gut. II. Modulation of antibody response.

Specific IgM and IgG antibody to a polysaccharide present in the epithelial cells of the gut of adult schistosomes was measured in four groups of infected patients: I) patients with documented acute schistosomiasis; II) Americans exposed to schistosomiasis within the preceding 0--4 years; III) chronically and heavily infected patients, mostly from Puerto Rico, without hepatomegaly or hepatosplenomegaly; and IV) heavily infected Brazilian children with hepatic or hepatosplenic schistosomiasis. Specific IgM and IgG titers were both highest in the acute Group I patients and lowest in the chronically infected Groups III and IV. Total IgG and IgM levels  were compared to specific antibody titers. Immunoglobulin levels tended to follow specific antibody titers except in the chronically infected Groups III and IV in which total IgG rose to high levels. The decrease in specific antigen titers over the course of time occurred despite continued antigenic stimulation and suggests a modulation of the humoral response. The mechanism remains obscure.


Schistosoma mansoni infection in intact and B cell deficient mice: the effect of pretreatment with BCG in these experimental models.

The course of infection with Schistosoma mansoni was determined in B cell deficient mice by means of a schistosomule lung recovery assay 6 days after infection or by determination of the adult worm burden 7 weeks after infection. The intensity of infection was not significantly different from that in age- and sex-matched intact controls. B cell deficiency was demonstrated by absence of surface immunoglobulin-bearing cells in the spleen and by absence of B cell areas in the lymphoid follicles of the spleen and mesenteric lymph nodes. In addition, B cell deficient mice infected for 7 weeks with S. Mansoni were unable to form anti-schistosome antibodies detectable by the Cercarienhüllenreaktion. A normal granulomatous response, however, was observed around schistosome eggs. Pretreatment with BCG suppressed infection with S. mansoni comparably in intact and B cell deficient mice. A marked depletion of eosinophils occurred in the schistosome egg granuloma of all BCG treated mice.


The organization of tissues of the eye by different collagen types.

Bovine cornea, sclera, iris, ciliary body, choroid, zonular fibers, lens capsule, lens nucleus, vitreous body, and retina were investigated for collagen content and type. Cornea, sclera, iris, ciliary body, choroid, lens capsule, and vitreous body contain hydroxyproline, whereas in zonular fibers, lens nucleus, and retina no hydroxyproline was detectable. Preparative isolation of collagen was achieved by digestion of the different eye tissues with pepsin. The pepsin-solubilized collagen was separated by differential salt precipitation into different collagen types. The polyacrylamide gel electrophoresis of the pepsin-solubilized collagens revealed type I collagen in cornea, sclera, iris, ciliary body, and choroid. As well as type I collagen, type III collagen was isolated from cornea, sclera, and uveal tissues. The identification of types I and III collagen was supported by the CNBr-derived peptides of these collagens. Lens capsule collagen consisted mainly of type IV collagen. Zonular fibers contained no hydroxyproline but when examined by polyacrylamide gel electrophoresis, a band migrating in the alpha-position of collagen was observed. Polyacrylamide gel electrophoresis of both the pepsin-solubilized component and the CNBr-derived peptides of vitreous body protein showed no relation to any of the four common collagen types.


Identification and prevalence of culturable mesophilic microfungi in house dust from 100 Danish homes. Comparison between airborne and dust-bound fungi.

In order to encircle possible allergen sources, fungi from house dust were cultivated and identified. Dust from vacuum cleaners was inoculated on Petri dishes containing V-8 agar with addition of penicillin and streptomycin to eliminate the bacterial flora. The number of genera identified were for the most part consistent with the genera trapped from the air. However, presumably owing to their dispersal biology it was demonstrated that members of Mucorales were much more frequently represented in the samples obtained by this method compared with gravimetric and volumetric measurements. The method is recommended as a simple way to demonstrate and identify the mould contents in house dust and as a tool for the identification of some of the real allergenic sources in house dust.


An analysis of the role of IgE in intolerance to aspirin and tartrazine.

Total serum IgE and eosinophil count were determined for 30 patients with intolerance to aspirin. Total IgE levels in the aspirin intolerant patients were similar to those expected in a non-atopic population. In contrast, total eosinophil count (TEC) tended to be elevated in the aspirin intolerant group. Elevated TEC was observed both in bronchospastic (57%) and in urticarial (25%) aspirin intolerance. Specific anti-aspiryl and anti-tartrazyl antibodies of the IgE class were assayed by the galactosidase immunosorbent test (GIST). IgE anti-aspiryl antibodies were possibly detected in one patient, but did not correlate with clinical intolerance to aspirin. It is unlikely that the clinical symptoms and the eosinophilia of intolerance to aspirin and tartrazine are mediated by antibodies of the IgE class.


The immediate care of potential donors for cadaveric organ transplantation.

The selection and management of potential donors for kidney and liver transplantation has been discussed and the procedures necessary for successful transplantation are outlined.


Claude Bernard (1813-1878).

The life and works of Claude Bernard (1813-1878) have been discussed with special reference to the importance of his researches in relation to modern anaesthesia and in commemoration of the centenary of his death.


Efficiency of manual ventilation using the original EMO system.

The efficiency of the Oxford Inflating Bellows for intermittent positive pressure ventilation using a partially closed Heidbrink expiratory valve has been assessed by measuring the arterial carbon dioxide tension (PaCO2) after various intervals of IPPV on eight patients. It was found that satisfactory alveolar ventilation was achieved if a degree of hyperventilation was employed.


[Orthotopic liver transplantation in man from the anaesthesiological point of view (author's transl)].

We report our experience of anaesthesia for orthotopic liver transplantation in seven patients. Pre-, intra- and postoperative management requires highly cooperative team-work. Advantages of neuroleptanalgesia are pointed out for this operative procedure. Intraoperative problems such as mass transfusion, clotting disturbances, changes in haemodynamic parameters, metabolic acidosis, hypovolaemia, hypoglycaemia and hypothermia are discussed and adequate therapeutic measures proposed. The value of an extensive perioperative monitoring is demonstrated. Controlled ventilation has been performed during the immediate postoperative period in all patients.


[The effect of domperidone and metoclopramide on antral motility (author's transl)].

The effect of domperidone and metoclopramide on antral motility was studied by measuring the intraluminal pressure in the antrum of 10 normal persons and of 8 patients suffering from duodenal ulcer. Both drugs stimulated the rhythmic activity of the antrum. The antiemetic effect and the therapeutic effect of domperidone on complaints by gastrointestinal retention was the result of the influence on gastrointestinal motility, which is similar to that of metoclopramide.


[Anaesthetic problems during resection of the carina (author's transl)].

Benigne tracheo-bronchial constriction is an infrequent indications for resection of the bifurcation of the trachea. In former times resection and reconstruction of the bifurcation have been performed using extracorporal oxygenation. Nowadays, the method of separate ventilation of both lungs is used more frequently. Pathophysiological variations should be taken into consideration, which may occur during interruption of the ventilation of one side of lung caused by operating procedures. Rapidly developing atelectasis of the non-ventilated but perfused lung endangers the patient, as a result of an increased intrapulmonary right-to-left-shunt. Hypoxaemia can be prevented by temporary occlusion of the pulmonary artery of the nonventilated lung. This procedure is to be recommended in view of the fact that there is no prompt constriction of the vessels. Investigations with dogs show that a slightly developing accommodation of the perfusion can be disturbed by variations of cardiac output or mean pressure of ventilation.


[Increasing incidence of Serratia marcescens bacteraemia in intensive care patients (author's transl)].

The incidence of serratia marcescens in an intensive care unit was investigated in course of several years. After a trial of Cephalosporin-Gentamycin prophylaxis, infection and death due to serratia rose dramatically. The significance of decreased resistance to infection, hygiene regimes as well as mode of administration of antibiotics is related to selection of this rare microorganism causing septicemia.


Bacterial contamination of telephones in an intensive care unit.

Pathogenic and potentially pathogenic bacteria were found on telephones of an intensive care unit. Direct contamination by microorganisms from throats, hands, and noses of the staff members is real although airborne contamination would also play a role. The awareness of environmental risk in intensive care units is underlined.


The Stocks suction bullet.

The Stocks suction bullet is a device allowing maintenance of positive pressure ventilation, continuous distending pressure and high inspired oxygen concentrations during tracheal toilet in intubated patients. The effectiveness of this device was studied using an experimental apparatus and a dummy lung to represent neonates being treated with either C.P.A.P. or I.P.P.V. and P.E.E.P. By using appropriate combinations of suction catheter type and size, bullet lumen size, ventilator settings and suction pressure limit, it was possible to maintain during suctioning ventilation peak pressures between 50% and 100% of presuction levels and continuous distending pressures (P.E.E.P. or C.P.A.P.) at or in excess of 80% of presuction levels.


Whither allergy or wither allergy.

The specialty of allergy appears to be at a scientific and economic crossroad. With a significant number of scientific papers questioning the value of immunotherapy, the movement of the country towards prepaid care and the necessity for demonstrating cost/benefit ratio for all therapeutic procedures, the specialty of allergy can present an enigma.


Steroid-dependent asthma treated with inhaled beclomethasone dipropionate in children.

The efficacy of beclomethasone diproprionate aerosal (BDA) was studied in 27 steroid-dependent asthmatic children. In the double-blind portion of the study BDA was found to be superior to placebo. The benefits of BDA therapy were sustained through the two-year, open-label portion of the study. Adverse effects were few and minor. Transfer from oral corticosteroid therapy to BDA was carried out uneventfully and was not associated with untoward effects.


Pulmonary clearance of Serratia marcescens in calves.

The pulmonary clearance rate of Serratia marcescens was determined in 17 calves exposed to an aerosol from a modified Hendersen apparatus. The mean bovine pulmonary clearance was 50.2 +/- 4.1% at postaerosolization hour (PAH) 1, 72.5 +/- 7.0% at 2 hours, 88.6 +/- 5.2% at 4 hours, 97.3 +/- 2.8% at 8 hours, and 99.9% at PAH 24 and 48. Regional pulmonary mean percent retention (MPR) of S marcescens in 10 calves was determined in dorsal or ventral and in cranial or caudal regions. Dorsal MPR was less than ventral MPR for PAH 1, 2, and 4, whereas cranial MPR was greater than caudal MPR for PAH 1, 2, 4, and 8. Difference in regional airway oxygen tensions was suggested as the most probable reason for differing regional MPR values.


[Evaluation of hydric compartments in 83 normal subjects (author's transl)].

A study of plasmatic volume, extra-cellular liquids and total body water was performed on 83 healthy subjects. This study was realised by dilution of three isotopic tracers. The results are expressed as a function of lean body mass determined by anthropometric method (skin folds). The results obtained for three water compartments studied are given and compared with valours found in literature.


Comparison of effects of dietary T-2 toxin on growth, immunogenic organs, antibody formation, and pathologic changes in turkeys and chickens.

The effect of T-2 toxin (trichothecene mycotoxin) consumption on Broad-Breasted White turkey poults and White Leghorn chicks was studied. Groups of ten 8-day-old poults were fed rations containing T-2 at 10 ppm, 2ppm, or 0 ppm (controls) for a period of 4 weeks; a 4th group (inanition control) was fed control rations equal to the amount consumed by the group fed rations containing T-2 at 10 ppm during the previous 24 hours. A similar experimental design was used to study the effect of the toxin on 1-day-old chicks. The thymus glands of the poults given the feed containing 10 ppm were markedly decreased in size compared with thymus glands from poults in the control group, 0.182 vs 0.331 (percentage of body weight). There was no significant (P less than or equal to 0.05) decrease in thymus gland size in poults given 2 ppm or in the inanition controls. Dietary treatment did not appear to affect the size of the bursa or spleen of the poults. Histopathologic examination of thymus glands from poults given 10 ppm of T-2 revealed a depletion of cortical lymphocytes. Chicks appeared less sensitive to T-2 toxin than did the poults. There was no effect by any dietary treatment on the size of the thymus gland, bursa, or spleen of chicks. Reductions were noticed in feed efficiency and weight gain. There was no effect of T-2 toxin on agglutinating antibody formation to Pasteurella multocida bacterin.


Immunologic studies in Holstein-Friesian cattle: an immunocompetence profile.

An immunocompetence profile has been developed for Holstein-Friesian cattle. In vitro and in vivo immunoassays were used to determine (1) the percentage of peripheral blood lymphocyte (PBL) subpopulations bearing surface-membrane receptors for sheep erythrocytes, complement, or surface immunoglobulin; (2) the PBL blastogenic response to leukoagglutinin, concanavalin A, or pokeweed mitogen, (3) the serum immunoglobulin concentrations of IgG, IgM, and IgA, (4) the humoral antibody response to keyhole limpet hemocyanin, and (5) the in vitro blastogenic response and in vivo delayed hypersensitivity skin reaction to purified protein derivative in cattle immunized with BCG.


Comparison of full- and partial-thickness autogenous skin transplantation in dogs: a pilot study.

Thin partial-thickness (0.063 cm), medium (0.127 cm) partial-thickness, and full-thickness skin autografts were transplanted to surgically created granulating foreleg wounds of dogs. Thin partial-thickness grafts had an 89% survival, medium partial-thickness grafts had 47% survival, and full-thickness grafts had a 58% survival. Of the successful grafts, only the thin partial-thickness grafts did not grow adequate hair after transplantation.


Cefazolin.

After 5 years of use, cefazolin can be considered similar to cephalothin as a therapeutic agent and in its potential for adverse reactions. When cefazolin and cephalothin are compared by appropriately designed clinical trials, neither cefazolin's slightly greater in-vitro susceptibility to staphylococcal beta-lactamase inactivation, nor its slightly greater microbiologic activity for some enterobacteraciae has been shown to result in any readily apparent therapeutic differences. The important differences between cefazolin and cephalothin--and this is also probably true with respect to cephapirin and cephradine--are not in therapeutic effectiveness, microbiologic activity, or toxicity but rather in pharmacokinetics and cost-effectiveness.


Standards for practice: effectiveness and acceptance.

Carefully designed and highly specific standards for medical practice can improve the pattern of practice when applied by interested and committed physicians or by other similarly motivated health care providers. However, this is not popular with the physician, and the improved pattern of practice is dependent on continued feedback. The standards must be designed with a specific population and setting in mind; therefore it is unlikely that an effective operational plan can be devised and implemented that will achieve improved practice patterns in the immediate future. Meanwhile, more general standards might be used to identify a smaller number of cases, which can then be reviewed by other physicians, using professionally accepted but subjective practice criteria.


Guidelines of the Food and Drug Administration for study of new drugs in human subjects.

The Food and Drug Administration recently has published general guidelines for the clinical evaluation of drugs used in adults and in infants and children. Specific guidelines for a number of drug classes, including anti-infective drugs, are also available. Marketing approval of a new drug requires that its benefits be judged to exceed its risks, that it be accurately and truthfully labeled, and that it be manufactured properly. Foreign studies are commonly accepted in support of new drugs, but approval requires at least one domestic trial unless the disease does not occur in the United States (for examply, tropical diseases).


Federal regulation: philosophy and practice.

The philosophy of drug regulation as expressed by Congress has progressively embraced concepts of misbranding and adulteration, safety, efficacy, and, most recently, control of the investigational process. The intent of Congress has been implemented by a series of regulations intended to protect the public health and to assure that available drugs are safe and effective. This has resulted in more centralized, standardized, uniform government control, with a slowdown in the development and approval of new drugs, an increase in the cost of developing and marketing new drugs, and costly control procedures. It is time to ask whether the benefit of more centralized government control is being exceeded by its cost.


Process of developing a new antimicrobial drug.

The network for development of a new antimicrobial drug, from discovery of the compound to submission of the New Drug Application, is reviewed. The key problems encountered during this process, as elucidated through a survey of 62 American pharmaceutical companies, include difficulties in discovering new and significant antimicrobial drugs, the unpredictability of in-vitro and animal studies, lack of specific criteria for the bacteriologic response to therapy, difficulties in setting up well-controlled clinical studies, and difficulty with the timely enrollment of suitable patients with precise microbiologic diagnosis before treatment.


The need for controlled clinical studies in antimicrobial therapy.

In recent years in-vitro and in-vivo studies have greatly advanced our understanding of the action of antimicrobial agents and have opened new potential avenues for treatment of infectious diseases. Unfortunately, little interest or financial support has been available to test these observations in rigid, controlled clinical studies. New regimens have thus been used without proof of increased efficacy of reduced toxicity over old regimens. Carefully controlled clinical trials are particularly needed to evaluate the efficacy, toxicity, and cost of newly developed regimens in the therapy of chronic bacterial and fungal infections.


Reversible severe congestive cardiomyopathy in three cases of hypophosphatemia.

Three patients presented with severe congestive cardiomyopathy of unknown cause. All three had a profound depression of serum phosphorus levels resulting from the chronic ingestion of large quantities of a phosphorus-binding antacid. Results of physical examination and echocardiograms were consistent with cardiomegaly and severe myocardial dysfunction, and chest films showed enlargement of the cardiac silhouette with interstitial pulmonary edema. Serum phosphorus was restored to normal levels, and within 2 to 5 weeks the results of physical examination and echocardiogram of each patient returned to normal. We conclude that these patients had reversible hypophosphatemic cardiomyopathy and show the importance of inorganic phosphorus in myocardial metabolism and function. Serum phosphorus measurements should be a part of the routine evaluation of patients with congestive cardiomyopathy because, at least in some patients, hypophosphatemia appears to be a reversible cause of this disorder.


UCLA Conference. Pancreas transplantation for diabetes mellitus.

Despite the best efforts of physicians and diabetic patients in the use of insulin for control of juvenile-onset (insulin-deficient) diabetes, vascular complications occur in most patients. The many advantages of the whole fetal pancreas as a donor organ make transplantation of the pancreas a promising improvement in therapy. A rat model has been developed for future application to human beings. After transplantation of one fetal rat pancreas into a diabetic recipient, maturation and growth of the transplant is adequate for complete reversal of the diabetic state of the recipient. Because of the atrophy of exocrine elements after transplantation of the fetal organ, many of the technical problems inherent in adult pancreas transplants are avoided. The small size of the fetal pancreas permits cryopreservation and permanent storage without apparent loss of function. Cryopreservation provides time for typing, matching, and preparation of the recipient to receive the donor organ and thus may alleviate rejection problems.


Osteomalacia: current concepts.

Recently acquired knowledge about vitamin D metabolism has improved our understanding in different varieties of osteomalacia. Many new causes of osteomalacia continue to be found. Radiologic and biochemical changes are not always characteristic and may occasionally be misleading. Bone biopsy after a double tetracycline label is helpful in differentiating osteomalacia from high bone turnover conditions and is recommended in most patients with a generalized rarefying skeletal disorder. Even if the underlying disease state cannot be corrected, effective therapy is available in most varieties of osteomalacia. The newer metabolites of vitamin D should soon be generally available to the medical profession. Their use will make treatment of osteomalacia more individualized and specific.


William B. Castle and intrinsic factor.

Fifty years ago, William B. Castle described the properties of intrinsic factor. By so doing, he advanced the first acceptable theory of the pathogenesis and pathophysiology of pernicious anemia. Enveloping Castle's discovery were prevalent ideas in the medical community of the time, such as the importance of nutritional factors in the pathogenesis of disease, and the intriguing possibility that many disorders could be ameliorated or even cured by administration of a "missing" substance. When viewed in a contemporary perspective, Castle's observations of a half century ago are remarkable examples of ingenuity and single-minded dedication to uncovering the pathogenetic mechanism of a previously fatal disorder.


[Ubiquity of plasmids belonging to incompatibility group B (author's transl)].

An Algerian strain of Salmonella typhi (56/75), resistant to tetracyclines and minocycline has been studied in our laboratory. Conjugation, transduction and spontaneous loss experiments suggest that these resistance characters are mediated by one R plasmid, referred to as pPA4. This "Tb" plasmid is incompatible with plasmids from groups incB (Grindley), com10 (Scavizzi) and inc0 (Datta). These results suggest that incompatibility group B is world-wide distributed.


[Occurrence of R plasmids belonging to incompatibility group incC in Aeromonas hydrophila strains isolated from sewage water (author's transl)].

The susceptibility to antimicrobial agents of 321 strains of Aeromonas hydrophila was studied: 319 strains were found to be resistant to one or several antibiotics. Transfer of resistance markers was obtained from 24 strains. Five plasmids from these strains were classified into incompatibility group incC. Epidemiological consequences of R plasmid diffusion in water bacteria are discussed.


Induction of oocytic maturation and differentiation: mode of progesterone action.

Full-grown amphibian oocytes, arrested in prophase I or meiosis, respond in vitro to progesterone and certain other steroids. They undergo an apparently normal sequence of nuclear maturation and cytoplasmic differentiation, which are necessary precedents for fertilization and embryogenesis. Individual oocytes or populations of these cells thus provide a model system for investigations concerning the nature and mechanism of hormone-cellular interactions. In this system, previous studies have shown that certain aspects of hormonal (progesterone, DOCA) induction of morphologic and biochemical differentiation in the nucleus can be induced in part, as a result of the formation of secondary cytoplasmic factors, some of which do not require the presence of the nucleus for their formation. In addition to initiating nuclear events, progesterone or DOCA alters the functional activity of the plasma membrane and establishes the conditions necessary for fertilization and activation. Uptake of radioactive vitellogenin, a yolk protein precursor, was inhibited by progesterone and DOCA. Maximum inhibition was dependent on induction of nuclear breakdown, the dose of steroid used, and was correlated with morphologic alterations at the oocytic surface. Estrone neither stimulated nor inhibited vitellogenin incorporation and had no effect on nuclear breakdown. Oocytic capacity to exhibit activation responses (vitelline membrane elevation) was dependent on oocytic exposure to progesterone or DOCA and development subsequent to the initiation of nuclear breakdown. Onset of the activation response after steroid treatment varied with the type of activation stimulus utilized (pricking or divalent ionophore A-23187). The results suggest that hormones cause ionic alterations in oocytes and that ions are directly involved in the activation response. To study steroid interaction with the cell surface, a method was developed for culturing oocytes that permits localized application of steroids to portions of the oocytic or follicular surface. The results obtained suggest that oocytes exposed to steroid over part of their surface do not respond, with regard to nuclear breakdown, in the same manner as do oocytes exposed over their entire surface to similar concentrations of steroid. Studies of isotopic distribution within the oocyte after local application of steroid indicate that hormone does not readily diffuse through the oocyte. Evidence for the role of cytoplasmic factors in the mediation of nuclear and cytoplasmic events is discussed.


[Presence of plasmids belonging to group incP and conferring chloramphenicol resistance in "Escherichia coli" strains of avian origin (author's transl)].

Plasmids pCG76, pCG83, pCG110 and pCG111 were transferred from multiresistant Escherichia coli strains of avian intestinal origin to E. coli K12. They were found to be compatible with reference plasmids of several incompatibility groups, except RP4. This incompatibility with RP4 is a proof that they belong to group incP. Other plasmids of this group were found in E. coli strains isolated from the feces of hens in two different breeding flocks. The incidence and the importance of this plasmid group in the intestinal bacteria of animals are presently investigated.


[Correlation between beta-glucuronidase activity and serotype in the genus "Salmonella" (author's transl)].

Out of 4,114 cultures of Salmonella belonging to various serotypes, 1,241 (30,1%) hydrolyze p-nitrophenyl-beta-D-glucuronide, the chromogenic substrate of beta-glucuronidase. Serotypes are found to be homogenous with respect to beta-glucuronidase activity. The qualitative test, as simple as the ONPG test, may be of diagnostic value to assign a strain to a serotype in case of a monophasic or not motile variant of a normally diphasic serotype. Phage conversion does not influence beta-glucuronidase activity.


[Chlamydosporulation in "Candida albicans": influence of sowing density and glucose, nitrogen, biotin and mineral salts concentration in rice-cream decoction (author's transl)].

Chlamydospore production by Candida albicans was investigated in rice cream decoction inoculated with a blastospore suspension. Effects of glucose, KH2PO4, (NH4)2SO4 and biotin addition were estimated using a "chlamydospore index" i.e. the mean-number of mature chlamydospores produced from a single blastospore development. If no other component was added, it appeared that better sporulation was obtained with both glucose concentration and inoculum size optimum (0.5 g/l and 7.8 X 10(3) blastospores/ml respectively). In glucose-KH2PO4 enriched medium, chlamydosporulation was the best with 0.5 g/l glucose and 0.5 g/l KH2PO4. The addition of biotin reduced the chlamydospore index at the concentrations tested (0.6 to 20 microgram/l). When glucose and (NH4)2SO4 were added together, it seemed that one of the C or N component had to be in low concentration for a good sporulation. The action of salts was also investigated; and finally a synthetic medium is proposed. The improvement of this medium is now in progress.


Acute laryngeal obstruction in children. A fifty-year review.

When dealing with acute laryngeal obstruction, the first important consideration is the differential diagnosis of the cause. The author considers the following six types: acute laryngotracheobronchitis, acute epiglottitis, diphtheria, supraglottic allergic edema (angioedema), subglottic allergic edema (spasmodic croup) and foreign body in the larynx or trachea. He traces the development of the treatments that have in 50 years lowered the mortality rate from 70% to practically zero. High humidity, best supplied by an ultrasonic nebulizer, antibiotics, and corticosteroids in very high dose have been the prime effective measures. There still is controversy about the choice between tracheostomy and nasotracheal intubation if medical therapy is delayed or ineffective. The primary physician must know when and where to send these children in order to prevent the fatalities so frequent in previous years.


Surgical treatment of acute blunt laryngeal injuries.

The best management of acute laryngeal fractures is an approach which promotes healing by primary intention and does not require the use of a lumen keeper or core mold. This presenentation outlines the theoretical considerations and practical steps which make it possible to achieve these goals. The basic emphasis is on proper diagnosis, good surgical exposure and proper wound management. Also included are some ideas about the special anatomical and physiological characteristics of the larynx which make it difficult to obtain primary healing. The material presented is a synthesis of pertinent basic laryngologic research, wound healing theory and clinical experience.


Urinary excretion of lysozyme and N-acetyl-beta-D-glucosaminidase in the diagnosis of renal allograft rejection.

The urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) has been claimed to be of high diagnostic value in indicating acute renal graft rejection. Similar claims have been made for the significance of urinary lysozyme excretion. Serial measurements of urinary lysozyme and NAG have been made in 35 patients after renal transplantation, and during 52 suspected rejection episodes. A close correlation has been found between these two parameters although they did not consistently change in parallel. The use of both assays may give a better indication of impending rejection than either assay alone.


Extrahypophyseal effects of somatostatin.

The tetradecapeptide somatostatin is widely distributed in the body in endocrine-like calls and in nervous tissues. When produced in endocrine cells, it seems to inhibit the secretion of hormones at the site of production, for example, it inhibits the secretion of growth hormone in the pituitary gland, insulin and glucagon in the pancreas, and the local hormones in the gastrointestinal tract. Its role in the nervous system is not clear, but it may act as an inhibitory transmitter substance or modulator. As for its mode of action, the data suggest that interference with the levels of cyclic nucleotides, within the cells as well as with Ca++ fluxes may be important. The clinical uses of somatostatin have been explored, especially in diseases characterized by hypersecretion of hormones known to be inhibited by somatostatin. But the wide distribution and multipotent inhibitory action calls for attention. Analogues to somatostatin with specific actions have already been produced and await clinical evaluation.