Results of 310 cases of rapid maxillary expansion selected for medical reasons. 1. Rapid Maxillary Expansion is a comparatively simple, conservative method of treating impaired nasal respiration. 2. It can be used from 4 years to 25 or 30 years of age, but the younger the patient the better the long term results. 3. The medical indications are a combination of poor nasal airway, septal deformity, recurrent ear or nasal infection, allergic rhinitis and asthma, and prior to septoplasty. 4. The dental indications are mainly unilateral or bilateral cross bite, class III (prognathoid) malocclusion, maxillary compression, and cleft palate. 5. The dental contra-indications are normal occlusion in the permanent dentition and to a lesser degree severe class II occlusion and micromandible. 6. In selected cases, it produces a change of over 80 percent from mouth to nose breathing. In this series of 310 consecutive cases 87 percent were greatly improved, 9 percent had a fair result and 4 percent a poor result. 7. It also gives considerable improvement in colds and respiratory infection, nasal allergy and many cases of asthma. The improvement in health and confidence and concentration in over 30 percent of cases is particularly pleasing. 8. The rationale of Rapid Maxillary Expansion can be explained by the maxillary moulding theory of production of septal and facial deformities.


Primary amyloidosis of the trachea.

Primary amyloidosis of the trachea. A case of primary amyloidosis of the trachea in a 40-year-old female is described. It appeared clinically as a tumour-like lesion in the trachea. The specificity of amyloid deposits was confirmed by a positive reaction to Congo red stained sections viewed under polarised light and Thioflavine--T stained section showing characteristic fluorescence. Excision of the lesion with a split thickness graft was the mode of treatment.


An alternate method for calculating an odds ratio. Methodological problems involved in the use of the standard Woolf-Haldane analysis of epidemiological retrospective studies are examined and an alternate method of analysis is proposed. This alternate method involves a population constructed to match the cases in numerical size and to match the controls in proportion of exposures. This method allows for finer subclassification of the data and provides a meaningful summary estimate of the relative risk. The proposed method is contrasted with the Woolf-Haldane method in the analysis of the relative risk of exposure to sick pet bird versus no pet bird for adult leukemia cases versus controls. Data is from the Tri-State Leukemia Survey. Mathematical considerations involved are contained in the appendices.


The impedance machine: a new bedside coagulation recording device. A new continuously recording bedside coagulation screening device is described. The instrument, called an empedance machine, functions by measuring the changing mechanical impedance exerted on a minutely vibrating probe by the progressing fibrin formation of the specimen to be analyzed. The impedance machine works with 0.04-0.4 ml both of whole blood or plasma. During the recordings, the clotting process can be observed in the specimens which are transilluminated. The rugged machine is extremely simple to handle. The two parts which come in contact with blood are disposable. Various examples (recordings) for clinical and experimental applicaton are given and discussed.


Termination of aquired and natural immunological tolerance with specific complexes. It was possible to terminate the induced unresponsive state to bovine serum albumin (BSA) and the natural unresponsive state to autologous thyroglobulin in rabbits (RTg) by immunization with complexes composed of heterologous cross-reacting antibody and the tolerated antigens. The unresponsive state was terminated in rabbits made unresponsive by neonatal injections of BSA and then 3 mo later injected with complexes composed of BSA and guinea pig antihuman serum albumin. This termination was manifested by the presence of anti-BSA plaque-forming cells. Similarly, the natural unresponsive state was terminated in adult rabbits injected with complexes between RTg and guinea pig antibovine thyroglobulin (BTg) in that thyroid lesions and circulating anti-RTg were produced. The results can be best explained by the presence of unresponsive T cells and competent B cells, where the guinea pig gamma globulin (antibody) activates T cells specific for the guinea pig gamma globulin portion of the complexes and thus permits stimulation of B cells competent to the exposed determinants of the tolerated (BSA or RTg) portion of the complexes. The detailed mechanism for the activation of B cells in tolerant animals is discussed.


The lipoprotein of the outer membrane of Escherichia coli: a B-lymphocyte mitogen. The lipoprotein of the outer membrane of Escherichia coli is a B-cell mitogen in mice.  Polyclonal activation of B lymphocytes was measured by an increase in thymidine uptake, by the development of plaque-forming cells against densely coupled trinitrophenylated sheep red cells, and by selectively increased rates of synthesis and secretion of leucine-labeled IgM. Murein-free and muropeptides-containing lipoprotein are effective in B-cell activation, while free murein is inactive.  Removal of ester-linked fatty acids from the amino-terminal end of the lipoprotein by alkaline hydrolysis abolishes the mitogenicity of the lipoprotein. B lymphocytes from high responder (C3H/Tif and BALB/c nu/nu) or from low responder (C3H/HeJ) mice to the mitogen lipopolysaccharide (LPS) both respond well to the lipoprotein.  Anti-immunoglobulin antibodies inhibit the mitogenic stimulation of B cells by lipoprotein.  A complex of structures including the Ig-receptor molecules, the LPS receptor, and the lipoprotein receptor appear involved in the regulation of mitogenic stimulation of B cells to proliferation and differentiation to IgM-secreting cells.


Studies on cell differentiation: inducing capacity of sulfhydryl-containing amino acids on post-nodal pieces of chick blastoderms. The inducing capacity of sulfhydryl (SH)-containing amino acids (cysteine and glutathione) on post-nodal pieces (PNPs) of stage 4 chick blastoderms was investigated. PNPs were treated for different lengths of time with chick Ringer's solution (control group) or chick Ringer's solution containing cysteine or glutathione, followed by culturing for 2-10 days on Spratt-Haas agar medium or on the chorioallantoic membrane of 8-day chick embryos. Control PNPs rarely showed differentiation, but those treated with the amino acids for six hours or longer developed structures such as neural tissue, notochord, somite mesoderm, and nephric tubules. The pulsatile tissue was only seen in the PNPs cultured for four days or longer. Two-four hours of treatment was too short to provoke induction in a statistically significant number of PNPs. The highest frequency of induction was noted in those pretreated with glutathione (8 mug/ml) for eight hours, followed by culturing for four days. The magnitude of the inducing capacity and toxicity of the amino acids were concentration dependent: a deleterious effect was observed at 14 mug/ml; the highest frequency of induction occurred at 8 mug/ml, but the frequency decreased as the concentration decreased; at 2 mug/ml all PNPs remained viable, but only a few (9-14%) showed differentiation. The inducing capacity of the amino acids was counteracted by equimolar concentrations of rho-chloromercuribenzoic acid or omega-chloroacetophenone. The effects of glutathione (8 mug/ml) differed from those of Hensen's node grafts in that the former caused sublethal cytolysis and inhibited H-3-uridine uptake in competent ectodermal cells during the first 18 hours of cultivation.


Restriction of DNA in Yersinia enterocolitica detected by recipient ability for a derepressed R factor from Escherichia coli. A derepressed R factor, RY2drd2, was transferred at a frequency of 5x10minus 3 between two strains of Yersinia enterocolitica mated on a membrane. Under the same conditions transfer of this R factor from Escherichia coli to Y. enterocolitica was observed at a frequency of only 7-7x10minus 6. This frequency was greatly increased when the recipient strain was heat-treated before mating. Heat exposure for optimum fertility was 50 to 52 degrees C for a period of 2 to 3 min. Mutants of Y. enterocolitica were isolated which were infected by RY2drd2 from E. coli or from Y. enterocolitica at the same frequency. These observations strongly suggest that a DNA restriction and modification system in Y. enterocolitica causes its low recipient ability for plasmids from other species.


R factors from Proteus mirabilis and P. vulgaris. Eighty-nine R factors were transmitted by conjugation to Escherichia coli K12 from isolates of Proteus hauseri (P. mirabilis  plus P vulgaris). More than half were non-selftranmissible. The remainder included plasmids assigned to the previously defined groups FII,A-C complex, J, N and P, as well as some not belonging to any knwon compatibility groups. R factors from strains isolated in India, Thailand and Japan carried plasmids whose inheritance was extremely unstable in E. coli K12. All belonged to a new compatibility group, V.


Construction and phenotypes of double sporulation deficient mutants in Streptomyces coelicolor A3(2). In whiA, B, G and H mutants of Streptomyces coelicolor A3(2), aerial hyphae develop but sporulation speta are not formed. Septa are produced by whiI mutants but are spaced abnormally far apart. Mutants in each locus have a distinctive aerial mycelium morphology, except for whiA and B mutants which are closely similar. Seven strains were made with pairwise combinations of whiA and B mutations with whiG, H and I mutations and with each other. The genotypes of these strains were confirmed by suitable crosses and their aerial mycelium morphology examined. An indirect procedure was used to determine the aerial mycelium morphology of whiGH, GI and HI double mutants. The double mutants always closely resembled one of the single mutant parent strains in morphology and a consistent scheme of epistasis was obtained--whiG being epistatic to whiH, A, B and I; whiH to whiA, B and I; and whiA or B to whiI. These results point to the absence of any complex interactions between gene products, which might have been revealed by the occurrence of novel phenotypes in double mutants or by inconsistencies in the epistasis scheme.


Polyene sensitivity during germination of conidia of Aspergillus fumigatus. A system for the rapid and relatively synchromous germination of conidia from a clinical isolate of Aspergillus fumigatus is described. The polyene-mediated release of K plus from germinating conidia has been determined. Ungerminated conidia were insensitive to amphotericin B methyl ester (AME) at concentrations greater than 50 mug/ml, but rapidly became sensitive to 1 to 2 mug AME/ml during the intitial stages of germination. These findings have been correlated with minimum inhibitory concentration values obtained in studies of conidial germination and hyphal outgrowth using a variety of growth tests.


Metoclopramide and pimozide in Parkinson's disease and levodopa-induced dyskinesias. Metoclopramide is an antiemetic drug which occasionally produced acute dystonic reactions. Although known to interfere with central dopamine mechanisms, it is frequently used in Parkinson's disease to prevent levodopa-induced nausea and vomiting. In this study metoclopramide did not increase Parkinsonism or reduce levodopa-induced involuntary movements in patients with Parkinson's disease. Pimozide, by contrast, increased Parkinsonism and reduced involuntary movements. The capacity of metoclopramide to produce acute dyskinesias while being apparently free of Parkinsonism effects is pharmacologically unique and differentiates this drug from the phenothiazines and butyrophenones.


Cerebrospinal fluid formation in ventricles and spinal subarachnoid space of the rhesus monkey. The authors perfused rhesus monkeys from lateral ventricles to lumbar sac with an artificial cerebrospinal fluid (CSF) containing a Blue Dextran 2000 marker. Analysis of marker dilution at steady state showed ventricular CSF formation occurring at a rate of 28.3 plus or minus mu1/min. No significant CSF formation was found in the spinal subarachnoid space.


Vasodilator system for the face.

Vasodilator system for the face. The authors describe investigations in cats to delineate a vasodilator system to the face, which they undertook after a previous study showed that radiofrequency coagulation of the trigeminal ganglion produced a pronounced flush in the skin of the corresponding division. Results demonstrate a vasodilator system emerging from the brain stem with the facial nerve which, by way of the greater superficial petrosal nerve, reaches the trigeminal ganglion. There the fibers are distributed to each of the divisions of the fifth nerve; in addition, a moderate number of vasodilator fibers also appear to leave the brain stem directly with the trigeminal nerve. Vasodilator fibers also appear to leave the brain stem directly with the trigeminal nerve. Vasodilator effects were elicited by stereotaxic  stimulation of the facial and trigeminal nuclei in the brain stem. There is, therefore, a dual vasomotor control of the facial cutaneous vascular bed; the classical sympathetic vasoconstrictor system of the face is complemented by a vasodilator system capable of producing changes of equal but opposite amplitude in vessel caliber.


Vernix caseosa meningitis and laryngeal stridor in an infant with myelomeningocele. Case report. The authors present the case of an infant with laryngeal stridor, apneic spells, and an open lumbar myelomeningocele; granulomatous vernix caseosa meningitis was found at autopsy. The suggest that chemical meningitis which also involved the cranial nerves might be held partly responsible for the laryngeal stridor.


Method for measuring brain tissue pressure. Response to alteration in pCO-2 systemic blood pressure, and middle cerebral artery occlusion. The authors report a method for measuring total local brain tissue pressure (BTP) using a miniature catheter transducer stereotaxically introduced into the white matter of the cat's cerebrum. Quantitative rapid phasic pressure changes were satisfactorily demonstrated. Due to some drift of baseline of the transducers and inability to perform in vivo calibration, reliable long-term quantitative pressure measurements sometimes could not be studied. The BTP from each cerebral hemisphere and the cisternal pressure (CP) were monitored during alterations of pCO-2 and systemic blood pressure, and distilled H20 injection prior to and after right middle cerebral artery (MCA) ligation. The catheter transducers functioned well on chronic implantation for up to 6 weeks. Compared to the chronically implanted catheters, acutely implanted catheters responded identically except for drift. The response of intracranial pressure and CP to MCA occlusion, alterations in pCO2, and systemic blood pressure were similar. No BTP gradients appeared in response to MCA ligation, hypercapnia, hypertension, or progressive swelling of the resulting infarction.


Accumulation of gold in various organs of mice injected with gold thioglucose. The response of either male or female mice to the administration of gold thioglucose (GTG) was observed in food intake, in body and organ weights, and in gold accumulation in respective organs. Male mice were more sensitive to GTG toxicity than females. During 103 days after GTG administration, the adipose tissues of the females and males increased in weight 15 times and 2.5 times as high as those of control mice, respectively. The weights of heart, lung, and brain were not affected by GTG administration. In the respective organs, gold concentrations, which were determined by neutron activation analysis, were high in liver, kidney, spleen, adrenal, and adipose tissue (especially in female) within a shorter time after the GTG injection. In various organs of nonobese mice, the concentrations of GTG were significantly less than those in the typical obese mice. Even after more than 100 days after injection, gold was detected in the respective organs. In the control mice without any GTG administration, no gold could be detected.


Color essays.

Color essays. Webster's New Collegiate Dictionary defines "essay" first as "an effort to do something; attempt; trial." Only second it is defined as "a literary composition, analytical or interpretative, dealing with its subject from a more or less limited or personal standpoint." This article is an essay (second meaning) about a few essays (first meaning) that have been made to understand color. Genesis, Aristotle, Plato, Newton, Palmer, Young, Helmholtz, Maxwell and Frederic Ives are represented.


A comparative study of three etching solutions: effects on enamel surface and adhesive-enamel interface. The chemical treatment of enamel surfaces is an approach in obtaining increased bonding of dental materials to tooth srufaces. Three etching solutions commonly used at present are 50% H3PO4, 50% H3PO4 attenuated with 7% zinc oxide and 50% citric acid. The effects of these three conditioning solutions on normal and polished enamel surfaces and on the interfaces between untreated enamel and etched enamel surfaces were studied by scanning electron microscopy. The variable etching pattern observed with each of the acids made a comparative study difficult. This was further complicated by the dependence of the etching action on prism orientation on polished enamel surfaces. Additional factors that have to be considered are the presence of prismles enamel and perikymata. Surface profile recordings of polished and acid-etched polished enamel surfaces provided some quantitative measure of the etching action of the conditioning solutions. The 50% citric acid solution had the mildest etching action while 50% H3PO4 and 50% H3PO4 attentuated with 7% zinc oxide elicited comparable responses.


Polymethylmethacrylate as a denture base material in service. Assessments of the practical deficiencies of polymethylmethacrylate in service have been carried out by several workers. Some of these studies and one further one have been compared so as to seek any common factors, especially those concerned with the age of the appliance at failure. Times of vulnerability for different types of dentures have been demonstrated, and the scope for time-based studies in the laboratory and in service has been discussed.


Functional analysis of fixed bridges on abutment teeth with reduced periodontal support. The present study examines the function of fixed bridges on abutment teeth with reduced but non-inflamed periodontal tissues. Eighteen patients with advanced periodontal breakdown and indication for oral rehabilitation received periodontol treatment and their dentitions were restored with fixed bridgework. The analysis of function performed 2-5 years after insertion of the reconstructions was made by (1) evaluation of the patients' opinion on chewing ability and function of the masticatory system; (2) clinical examination of the border movements of the mandible, the status of the temporomandivular joints and the chewing muscles, and (3) measurements of the bite force indifferent areas of the dentition. The results of the study show that the functional capacity of the type of extensive bridgework discussed is good and that the patients--in spite of severe loss of periodontal tissue--achieve bite force values that are almost comparable to those in individuals with natural teeth. Comparison of the function of fixed bridges and that of removable dentures is also discussed.


Adaptation of silicate and Adaptic to the margins of cavities. A scanning electron microscope study. The effects of etching of the enamel, on the adaptation of silicate and Adaptic to the cavity walls was examined with the scanning electron microscope. Replica methods were utilized to ensure that no shrinkage of the filling materials was caused by the vacuum in the instrument. It was shown that following etching of the cavity margins, Adaptic adhered to the enamel with absent, or minimal, fissure formation on one side of the filling, and some on the opposite side. The adaptation of silicate to the margins of the cavities was not improved by etching.


Changes of cheek pressure during swallowing following expansion of the maxillary dental arch in repaired cleft palates. Cheek pressure during swallowing was measured on six operated complete cleft lip and palate cases (4-8 years of age) before and after expansion of buccal segments of maxillary arch. As control, seven non-cleft subjects with acceptable occlusion of the same age level were used. Before expansion, the pressures in the cleft cases were much higher than the controls. Immediately after expansion, increase in pressure was observed in cases which received rapid expansion. However, a few months after expansion, most cases showed a decrease in pressure. This is explained as being due to the adaptation of the perioral musculature to the expanded dental arch and/or the disappearance of hyperactivity of the perioral musculature during swallowing.


Chalmers J. Lyons memorial lecture: Metal implants and the mandibular staple bone plate. To briefly summarize our results, two of the five three-pin staples (40%) have survived and have functioned well for more than six years. Four of the five four-pin staples (80%) have survived five years or longer and are functioning well. Twenty-four of the 25 seven-pin staples (96%) are functioning well, some for a period of 4-1/2 years; a few in this group have been used a little less than a year. Our total percentage of survival with good function is 30 of 35, or 86%, which includes our pilot study of the three- and four-pin staples. A more significant statistic, however, might be those patients with staples who we feel have been free of any significant trouble; these are 27 of 35, or 77%. All of our patients have been subjected to peer review examination and grading by members of the oral surgery staff at Sinai Hospital. They were examined and graded according to three criteria. The first was clinical appearance which included firmness of the staple and clinical appearance of the gingiva (Fig 16). The second was radiographic evidence of bone loss along the transosteal pins and retentive pins (Fig 17). The third category was patient evaluation of improved function and stability of the lower denture (Fig 18). The peer review group used marks A, B, C, D, as excellent, good, fair, and failure. Four points were assigned to A, 3 points to B, 2 points to C, and 1 point to D, so that the grade averages for all three categories were as follows: clinical appearance, 3.6; radiographic appearance, 3.5; and patient evaluation, 3.9. The conclusion of the review group was that the mandibular staple was functioning well and that it was clinically useful. I have presented an overview of some of the characteristics of metallic implants that make them implantable devices, and some of the qualities of the host tissues that will allow placement of foreign material. We do not yet understand all of the factors that make alloplastic materials biocompatible or some of the reasons for rejection by the host. We need continued research in animal models to study new devices and new materials that might permit biologic attachments of the host to implant. We also need controlled clinical studies with peer review to establish reliability of those devices that are clinically useful. The mandibular staple has had an initial clinical trial that seems very promising and is worthy of continued clinical study and clinical application.


Split portal flow in heterotopic hepatic transplantation. Heterotopic hepatic transplantation was carried out in 31 pigs using three different methods of homograft revascularization. In one experimental group the host portal inflow was split between the homograft and native liver so that the graft was provided with intestinal-pancreatic effluent; the host liver with gastric-splenic venous blood. The liver grafts flourished in this environment. A small and variable degree of atrophy took place in the host liver. In the other two experimental groups in which the grafts were supplied with different kinds of systemic inflow only, atrophy invariably followed. Long-term homograft analysis was prevented by the intensity of immunologic rejection regardless of the location of the ectopic liver. The implications for clinical auxiliary liver transplantation are (1) heterotopic liver homografts must be supplied with a portal inflow from the host splanchnic bed, but (2) the total host splanchnic effluent is unnecessary. (3) The portal inflow must contain the pancreatic venous blood. (4) There is a criticial recipient--donor size relationship for successful portal revascularization in this type of auxiliary hepatic graft.


Surgical closure of patent ductus arteriosus in the premature infant with respiratory distress. During the period from February, 1971 to February, 1973, 30 premature infants underwent surgical ligation of patent ductus arteriosus. The gestational ages ranged from 25 to 36 wk (mean 30), and the birth weights ranged from 760 to 2010 g (mean 1274). The patients were divided into two groups on the basis of the indications for assisted ventilation. Group I consisted of 21 patients with severe hylanine membrane disease who required assisted ventilation during the first 2 days of life and could not be weaned off the respiratory by 10 days of age. Group II was composed of nine infants who required intermittent positive-pressure breathing after a mean age of 8 days because of repeated apneic spells secondary to uncontrollable heart failure. All infants in Group II survived the operation and left the hospital well. Fourteen of the 21 patients in Group I survived; the seven deaths were all due to underlying severe pulmonary disease (bronchopulmonary dysplasia). The value of PDA ligation in premature infants with uncontrollable heart failure is demonstrated in this study; this procedure also appears to be beneficial in neonates with severe respiratory distress syndrome.


The effects of antiepileptic drugs on estrogen-induced electrographic spike-wave discharge. In locally anesthetized, paralyzed cats with bilateral conjugated estrogen (CE)-induced foci in sensory motor cortex, electrographic activity was characterized by 2 to 3 Hz spike and slow wave discharge. Commonly used anti-petit mal drugs (esthosuximide, trimethadione, acetazolamide and diazepam) all reduced CE-induced spike wave activity while diphenylhydantoin converted such activity into 9 to 12 Hz polyspike bursts separated by periods of interictal silence. Correlation appears to exist, therefore, between the ability of the drug to reduce CE-induced spike wave activity and its clinical utility in petit mal epilepsy. In addition to the above compounds, five drugs of less proven utility were evaluated. Of these, two benzodiazepine derivatives (clonazepam and clorazepate) were found to exert a potent and prolonged depressant action on CE-induced activity. The relation of CE to clinical petit mal epilepsy and the potential usefulness of CE as a laboratory model for the evaluation of anti-petit mal drugs are discussed.


The influence of aortic baroreceptors on venous tone in the perfused hind limb of the dog. 1. The aortic arch and both carotid sinuses were vascularly isolated and perfused. A hind limb was vascularly isolated and blood was pumped at constant flows into the femoral artery and the central end of a superficial metatarsal vein. 2. Large increases in aortic arch pressure resulted in decreases in arterial blood pressure, heart rate and femoral arterial perfusion pressure. The average response of the vein was a decrease of 11% in the pressure gradient between the perfused vein and the femoral vein. Similar responses were obtained when carotid sinus pressure was increased. 3. Crushing or cooling the lumbar sympathetic trunk caused responsed similar to those induced by increasing baroreceptor perfusion pressure. Stimulation at 1 HZ resulted in venous responses four times as great as the average reflex response, whereas frequencies of 2-5 Hz were required to produce changes in arterial resistance as great as those induced reflexly. 4. These experiments indicate, that although the large superficial veins of the dog's hind limb participate in the baroreceptor reflexes, the activities in the nerves supplying arterioles and veins must have been different.


Alterations in secretory patterns following antrectomy in rats with Pavlov pouches. 1. In conscious rats provided with Pavlov pouches, with the antrum retained or resected,the gastric secretory response to various stimuli has been studied. Each acid secretory response was related to that obtained with maximal doses of methacholine and histamine in combination, presumed to reflect the maximal secretory capacity of the mucosa. 2. Three weeks after the operation, the maximal acid secretory capacity was 60 percent lower in the antrectomized than in the intact Pavlov pouch rats; the difference was still larger at 6 weeks and 3-5 months, owing to a gradual increase in the rats with the antrum retained. 3. Antrectomy reduced interdigestive secretion of acid to the same degree as the concomitant reduction in maximal secretory capacity. 4. Acid secretion in response to a maximal infusion of pentagastrin was reduced by about 50 percent at 3 and about 65 percent at 6 weeks after antrectomy. No significant difference was, however, noted between the antrectomized and intact rats when the responses were related to the maximal secretory capacity. The dose response curve to pentagastrin revealed a redcued responsiveness to submaximal doses of this agent following antrectomy. 5. The maximal acid secretory response to histamine was reduced after antrectomy, although the sensitivity to submaximal infusions of histamine appeared to be increased. 6. The mean secretroy output to 2-deoxy-D-glucose was reduced by about 65 percent and that to food by about 85 percent following antrectomy. 7. After antrectomy a background infusion of pentagastrin enhanced the secretory responses to 2-deoxy-D-glucose and to food but did not restore the responses to the levels in the intact rats. The feeding responses as related to the maximal secretory capacity were, however, similar in the two groups on infusing pentagastrin in the antrectomized rats. 8. Interdigestive secretion of pepsin was reduced by about 60 percent after antrectomy, while the peak response to 2-deoxy-Dglucose was about twice the interdigestive level in both groups. Pepsin secretion in response to food showed an increased secretion above the interdigestive level of longer duration in the antrectomized than in the intact Pavlov pouch rats. 9. The irreversibily reduced responsiveness of the gastric mucosa after antrectomy is discussed in relation to known morphological and biochemical changes.


Electrical characteristics of pancreatic islet cells. 1. The electrical properties of mouse pancreatic islet cells have been explored in vitro using a single intracellular micro-electrode for both voltage recording and current injection. 2. The frequency of spontaneous electrical activity induced in islet cells by concentrations of D-glucose greater than 2-8 mM was enhanced by depolarizing, and reduced by hyperpolarizing, current injection.  Post-stimulus inhibition and facilitation were also observed. 3. Intracellular current injection evoked a spike potential in Krebs solution containing a low D-glucose concentration (2-8mM), and in glucose-free, but not Ca-free solution.  Evoked spikes were observed in approximately 10% of the cell population impaled. 4. The relationship between the rate of rise of an evoked spike and membrane potential displacement by intracellular current injection a sigmoid curve suggesting the presence of an inactivation process in spike potential genesis. 5. High [K]o, 30-50mM, induced electrical activity rarely, and then only transiently, thereafter blocking it; conditioning hyperpolarizing current tended to restore spike activity. 6. D-600, 5 times 10-minus 5M, blocked the electrical activity induced by D-glucose, tolbutamide or current injection; these inhibitory effects were reversed by a threefold increase in [Ca]o to 7-68 mM. 7. From these results it is concluded that the electrical activity induced in islet cells by Dglucose, tolbutamide and current injection is due mainlu to Ca-2+ influx and is dependent on the level of the membrane potential


Pancreatic islet cells: electrogenic and electrodiffusional control of membrane potential. 1. Responses of the membrane electrical characteristics of mouse pancreatic islet cells to ionic environmental changes have been used to assess the role of [Na]0 and [K]0 in the control of membrane potential, i.e. by electrodiffusion or via an electrogenic sodium pump. Islet cell electrical properties were measured in vitro with intracellular glass micro-electrodes. 2. Substitution of LiCl for extracellular NaCl did not change the islet cell membrane potential significantly in low (2.8 mM) glucose solutions, but readmission of NaCl caused a transient hyperpolarization (membrane potential maximum: -70 mV) in high glucose; when choline chloride was substituted for NaCl no hyperpolarization was observed on NaCl re-admission. 3. Superfusion with K-free solution gave no marked change in membrane potential during 30 min incubation in either low (2-8 mM) or high (28 mM) glucose concentrations but longer periods of exposure to K-free solutions caused progressive depolarization. 4. Readmission of K+ induced a transient hyperpolarization of up to 30 mV magnitude and 10 min duration in the presence of high (28 mM) but not low glucose (2-8 mM) concentrations. At the level of maximum hyperpolarization the membrane potential reached -60 mV, the electrical activity induced by the high glucose concentration being concurrently completely blocked. Replacement of [Cl]0 by isethionate accentuated these effects. 5. Ouabain, 10(-3) M, or a decrease in temperature from 37 to 7 degrees C depolarized the islet cells and blocked the transient hyperpolarization induced by readmission of K+. 6. Diphenylhydantoin, 1-5 times 10(-4) M, caused a significant hyperpolarization of the islet cells in low glucose (2-8 mM) and inhibited the electrical activity induced by high glucose (28 mM) or tolbutamide (0-7 mM). 7. It is concluded from these results that both an electrogenic and ionic component contribute to the membrane potential of the mouse pancreatic islet cell although electrodiffusional control normally predominates; acceleration of the Na-K exchange pump by diphenylhydantoin inhibits glucose-induced electrical activity. These findings are discussed in relation to the permeability characteristics of the islet cell membrane and the mechanism of insulin release.


Pancreatic islet cells: effects of monosaccharides, glycolytic intermediates and metabolic inhibitors on membrane potential and electrical activity. 1. The effects of monosaccharides, glycolytic intermediates, metabolic inhibitors and anxia, have been studied on the membrane electrical activity of mouse pancreatic islet cells in vitro using a single intracellular micro-electrode for both voltage recording and current injection. 2. In addition to D-glucose (28mM), D-mannose (16-6mM), and L-leucin (10mM), the substances D-glyceraldehyde (11mM), and acetoacetate (20 mM), induced action potentials in islet cells but other glucos analogues and metabolic intermediates including L-glucose dod not. 3. Mannoheptulose 20 mM), but not D-galactose or 2-deoxy-D-glucose, antagonized the electrical activity induced in islet cells by D-glucose, 28mM.  Prior treatment of the cells with mannoheptulose caused them to hyperpolarize and completely prevented the appearance of electrical activity on subsequent exposure to D-glucose. 4. Electrical activity induced by D0glucose 28mM, was progressively inhibited by phloridzin, 10mM, if the cells were exposed to D-glucose and inhibitor simultaneously, and abolished on pretreatment with inhibitor for 30-60 min.  Phloridzin also caused depolarization of the islet cells which was independent of extracellular glucose. 5. Anoxia completely blocked the electrical activity induced by glucose but not that evoked by D-glyceraldehyde, L-leucine, tolbutamide or glibenclamide. 6. Iodoacetic acid, 5 mM, rapidly blocked glucose-induced electrical activity whilst that elicited by tolbutamide was relatively resistant to inhibition. 7. The nature and possible location of the glucoreceptor in pancreatic islet cells is discussed in relation to the origin and functional significance of glucose-induced electrical activity and insulin secretion.


Spermatogenesis in mature and regressed testes of the vole (Microtus agrestis). Eight stages of spermatogenesis, each with a characteristic frequency and germ cell association could be recognized in the vole. There was no difference between laboratory bred and field animals in the frequency of the stages. Counts of the different types of germ cell showed that there was considerable cell loss during spermatogonial mitotic and spermatocytic meiotic divisions. Only 60% of germ cells became spermatozoa in sexually mature animals, and 19% in the regressing testes of voles exposed to short photoperiods. Animals with regressed testes probably have lowered circulating levels of gonadotrophins and testicular hormones, so that the greater germ loss suggests the importance of these hormones in the regulation of germ cell wastage. From the cell counts in mature animals, a scheme of cell divisions has been suggested by which spermatogonia produce progressively more highly differentiated germ cells while continuing to perpetuate stem cells.


Control of time of ovulation in heifers treated with progesterone and gonadotrophin-releasing hormone. The time of ovulation was determined in twenty-nine heifers by laparoscopy following treatment with progesterone. In addition, twenty-five of the animals received 100 mug Gn-RH 30 hr after the end of the progesterone treatment. Only eight of the heifers treated with Gn-RH ovulated. This contrasted with results obtained following examination of ovaries after slaughter in similar animals treated in identical fashion. Heifers which were treated with progesterone for 12 days and then slaughtered had not begun to ovulate 65 hr after the end of treatment, but five of eleven animals had ovulated 4 hr later. When Gn-RH was given, ovulation had started 60 hr after the end of progesterpme treatment, 60% of heifers had ovulated at 65 hr and 90% at 69 hr. Treatment with Gn-RH can synchronize and hasten the time of ovulation in heifers given progesterone. Possible reasons for the discrepancy between the results obtained following laparoscopy and slaughter are discussed.


An interactive computer program for studying fetal electroencephalograms. Fetal electroencephalogram (FEEG), recorded during labor, produces very large volumes of data for visual interpretation. An established terminology, developed for the interpretation of neonatal electroencephalogram, has been found to be useful for visual pattern recognition of FEEG. A program, which identifies FEEG patterns within ten second epochs and provides direct comparison between visual and programmed analysis, has been developed using an interactive computer system. This program provides 85-90 percent consistency with visual interpretation.


Male sterilization in El Salvador: A preliminary report. The expectation that male sterilization would not be an acceptable method of fertility control to the Latin American male has not been upheld in the initial phases of male sterilization programs in Colombia, Costa Rica, Guatemala, and El Salvador. On the contrary, in all of these programs and also at the Asociación Demográfica Salvadoreña, a free-standing, non-profit family planning clinic in San Salvador, the initial success has been impressive, with 180 men accepting sterilization during the first two years (February, 1972 to February, 1974). All sterilizations were performed by excising a 10-15 mm segment of each vas and ligating each vas end. Procedures were performed on an outpatient basis using a local anesthetic. Follow-up examinations were conducted at one week and three months after the procedure. Although complications were reported by 24.0% of the subjects at the one-week follow-up, the complications were minor: most were scrotal infections not requiring antibiotic therapy. Rates of complications were low for subjects returning for a three-month examination and semen test. Only one subject had a positive semen test.


A quality filtering system for medical literature. An algorithmic method for selecting quality journal articles is presented. The procedures are based on formalizations of existing evaluation mechanisms in scientific publication. The method was actually applied to the journal literature of the pharmacology of cardiac arrhythmias for the period 1967 to 1970. A comparison with the selected bibliographies of four recent publications showed that the method approximated some of the selections made by conventional subjective judgment.


Urinary and faecal Escherichia coli O-sero-groups in symptomatic urinary-tract infection and asymptomatic bacteriuria. The degree of correspondence between urinary and faecal Escherichia coli O-groups has been assessed in non-pregnant women with symptomatic urinary-tract infection or asymptomatic bacteriuria. In 20 of 26 patients with symptomatic urinary tract infection E. coli of the same O-groups as that of the urinary infecting strain was also present in the patient's faecal flora of only five of 25 patients with asymptomatic bacteriuria. This finding indicates that the majority of episodes of symptomatic urinary tract infection in non-pregnant women are not preceded by a significant period of asymptomatic bacteriuria. E. coli O6 showed correspondence between urinary and faecal isolates more frequently than did other O-groups, but it had a relatively low prevalence in the faecal flora of patients with urinary-tract infection caused by E. coli of other O-groups. This finding lends support to previous suggestions that E. coli O6 may be especially pathogenic for the urinary tract.


Immunological studies on leprosy: separation and evaluation of the antigens of Mycobacterium leprae. Chromatographically separated antigens of Mycobacterium leprae were tested for their ability to elicit skin reactions in guinea-pigs sensitised with homologous and heterologous mycobacteria. Of the three antigen-positive fractions obtained, one showed specific activity and the other two cross-reactivity, as indicated by studies of hypersensitivity and passive cutaneous anaphylaxis. The fraction exhibiting specificity contained only one antigen, which was protein in nature, whereas the other two fractions contained more than one antigen and possessed both protein and polysaccharide constituents. Because the single-antigen-containing fraction showed both positive skin and PCA reactivity, the suggestion is made that this fraction may contain either an antigen with two determinants or may contain two antigens that are not easily distinguishable by immunodiffusion methods.


Assessment of a new selective medium for the isolation of Salmonellae. Shanson's medium, a MacConkey-type agar containing added inhibitors, was compared with deoxycholate-citrate agar for the examination of faeces. The isolation rate of samonellae on the two media was similar, but Shanson's medium was the more selective; this meant that the amount of work required to produce a result was reduced.


Reversible permeability changes in the membrane of a yeast cell sugar compartment. Sorbose uptake by Saccharomyces cerevisiae was increased 40 to 60% by glucose and other metabolizable sugars. Neither growth nor binding accounted for the increased uptake. However, accessibility of a restrictive intracellular compartment was increased as shown by counterflow and efflux measurements. Efflux from the compartment was more than doubled by glucose. This effect was reversed by washing and was prevented by iodoacetic acid and other inhibitors, but not by cycloheximide. No evidence was found for a facilitated transport system in the compartment membrane such as exists in the external cell membrane.  It was concluded that sorbose crosses the compartment membrane by simple diffusion and that a reaction requiring the metabolism of sugars increases the permeability of the membrane. Arabinose and fucose entered and were lost from the compartment like sorbose, whereas dimethylsulfoxide was unaffected by the compartment. All three of these later compounds were bound by the cells when glucose was available in uptake suspensions. Binding was prevented by iodoacetic acid, but not by cycloheximide.


Single atom image contrast: conventional dark-field and bright-field electron microscopy. Single atom inage intensities are calculated for bright-field and various dark-field modes, including the ideal beam stop, a wire beam stop, tilted illumination and a displaced aperture. Comparisons of scattering amplitudes and elastic scattering cross-sections are made with different object potentials and scattering formulations. The image contrast for one mercury atom (Z equals 80) on a column of carbon atoms (Z equals 6) as the substrate is also discussed for both the bright-field and the various dark-field situations.


V. Effect of enzymes and temperature on the serological activity of the antigen of Fasciola gigantica. The partially purified extract of Fasciola gigantica was incubated with enzyme pepsin and samples were taken at different time intervals from 0-24 hours, and tested intradermally for diagnosing bilharziasis. The enzymatic degradation of the protein molecule results in the progressive decrease and eventually the complete disappearance of serological activity. This showed that the protein portion of the antigen was deemed necessary for its activity in intradermal tests for diagnosing schistosomiasis. Amylase, even at a concentration of 5 per cent, did not influence the activity of the partially purified extract of Fasciola gigantica. This showed that the carbohydrate portion of the antigen has no effect on serological activity. The partially purified extract of Fasciola gigantica was subjected to heating at 37 degrees C, 50 degrees C, and 60 degrees C for periods of two, six and 24 hours, and tested intradermally for diagnosing schistosomiasis. Heating decreased the reactivity of the supernatant liquid of the protein solution but did not completely inactivate the serologically active component which is fairly stable at 50 degrees C. Temperatures higher than 50 degrees C started to affect the serological activity of the protein solution. The higher the temperature, the shorter is the time required for the inactivation of the protein. This shows that the serologically active component is protein and not polysaccharide which resists much higher temperatures.


Chloroquine resistant malaria in West Malaysia. Chloroquine resistance is a well established entity in South East Asia, and presents a problem of increasing importance. Strains of P. falciparum resistant to chloroquine have also been found to be resistant to amodiaquine and a combination of pyrimethamine and sulphadoxine. Knowledge of the drug sensitivity of the strains of malaria parasite in a given locality is important so that the right choice of drugs can be made in treatment of the disease. The treatment of chloroquine resistant malaria in West Malaysia is a subject of another paper but suffice it to say that increased doses of chloroquine have still been found to be effective in treating many cases of falciparum malaria from areas of chloroquine resistance.


Phospholipase activity in bacteriophage-infected Escherichia. II. Activation of phospholipase by T4 ghost infection. The release of free fatty acids from the phospholipids of Escherichia coli is initiated immediately after the attachment of T4 ghosts. A similar accumulation of free fatty acids is observed if the cells are infected with T4 phage in the presence of chloramphenicol or puromycin. An early accumulation of free fatty acids, however, is not observed in T4 infections in which chloramphenicol or puromycin are not present, nor does it occur if the E. coli are infected with T4 phage before ghost infection, suggesting that phage products can prevent the phospholipid deacylation. If E. coli is infected with T4 ghosts before T4 phage infection, the accumulation of free fatty acids is not suppressed. When phospholipase-deficient E, coli are infected with T4 ghosts the appearance of free fatty acids is not observed, suggesting that T4 ghost attachment can activate the phospholipase of wild-type E. coli. Although the formation of free fatty acid apparently is a consequence of activation of the detergent-resistant phospholipase of the outer membrane, it is not observed in mutants deficient in the detergent-sensitive phospholipase.


Synthesis of viral and rRNA in bacteriophage R17 infection of a stringent strain of Escherichia coli. A previous paper (1973) indicated that infection with bacteriophage R17 permits the synthesis of RNA and spermidine in Escherichia coli (CP78 in the absence of the exogenous essential amino acid, arginine. We have now isolated RNA formed under such conditions and analyzed the newly synthesized species by agarose-acrylamide electrophoresis. It has been shown that infection of the stringent cells in the absence of exogenous arginine resulted in a marked incorporation of uracil into rRNA, as well as into R17 RNA. It was shown that, although the organism was nonauxotrophic for uracil, addition of [-14C]uracil resulted in the rapid formation of TUP, the specific radioactivity of which approached that of the exogenous uracil. This indicated that the incorporation of exogenous uracil into rRNA in R17 infection of the stringent strain reflected a true stimulated synthesis of this nucleic acid. Infection of the essentially isogenic relaxed strain, CP79, under the same conditions inhibited the RNA synthesis to a much less extent than the inhibition caused during the normal infection. These observations provide another example of the close correlation between synthesis of spermidine and of host RNA, even in cells infected by an RNA bacteriophage.


Chloramphenicol stimulation of lysogeny by lambda regulatory mutants. Inhibition of protein synthesis in Escherichia coli by amino acid starvation or chloramphenicol addition increases the frequency of lysogeny by lambda phage two- to fourfold. Lambda cIII mutants, which normally lysogenize at very low frequencies, lysogenize at very high frequencies in the presence of chloramphenicol.


The absence of vesicoureteral reflux in the neonate with myelodysplasia. Urologic evaluation of 21 newborns with myelomeningoceles revealed a rarity of infection and an absence of vesicoureteral reflux on cystourethrography. An hypothesis has been advanced to explain the absence of reflux and the high incidence of reflux reported in older children with myelomeningoceles. The absence of reflux in these neonates indicates that reflux in children with myelomenigoceles is not caused by a primary congenital ureterovesical junction abnormality but rather is secondary to infection and/or progressive bladder dysfunction.


Vesicoureteral reflux in babies with myelomeningocele. Reflux was present at birth in 24 per cent of 100 babies with meningomyelocele, indicating a marked tendency toward spontaneous improvement in infancy. Reflux starts in some children after birth but the number is too small to draw definite conclusions on the cause of this onset. Of the children with myelomeningocele 16 per cent had asymptomatic infection of the urine on 1 occasion only and 33 per cent had recurrent infections. There was a greater incidence of upper tract anomalies in patients with a high level spinal lesion.


Spiral advancement skin flap for stomal revision. The spiral advancement skin flap procedure for stomal revision is a simple technique when the size of the skin defect must be reduced. The technique is described herein.


Semen cultures in the diagnosis of bacterial prostatitis. The bacterial flora of semen from normal men has been studied. Positive cultures were obtained in 45 per cent of these individuals but only in smally colony counts of non-pathogenic bacteria. The seminal flora of patients with bacterial prostatitis was then studied. Excellent correlations have been noted between cultures of prostatic secretions and semen. Semen cultures will almost invariably be diagnostic in patients with bacterial prostatis. This technique has definite usefulness in selected patients in whom it is otherwise difficult to establish a diagnosis of bacterial prostatis.


Emphysematous pyelonephritis: report of 3 cases treated by nephrectomy. Three cases of emphysematous pyelonephritis are presented. All 3 patients were diabetics, they all had Escherichia coli and there was evidence of ureteral obstruction in 1 case only. All 3 patients underwent nephrectomy and survived. Initial evaluation should be performed to rule out ureteral obstruction. Treatment should consist of a brief trial of high dose antibiotic therapy with serious consideration of nephrectomy in the face of persistent symptoms or gas. Incision and drainage are reserved for poor surgical risk patients. All patients should remain on antibacterial therapy and have frequent followup examinations.


Cine-fluoroscopic studies of ureteral function in the human renal transplant. During a 14-month period 73 satisfactory fluoroscopic studies were done on 59 kidney transplant recipients. Ureteral peristalsis was seen in 90 per cent of these studies and there was no difference between patients receiving living related donor kidneys and those receiving cadaveric kidneys. When ureteral activity was studied during rejection episodes only 54 per cent of the studies showed activity. An effort was made to relate aperistaltic ureteral activity to renal function, warm ischemia time, urinary tract infection, number of rejection episodes and tissue matching but no positive correlation could be made except the concurrent clinical diagnosis of rejection.


The surgical approach to Peyronie's disease. Seven patients with Peyronie's disease were treated by surgical exposure of the fibrous plaque and dermo-jet injection of steroids into the plaque under direct vision. Relief of pain was obtained in 2 of 3 patients and curvature was only moderately improved i 2 of 7 patients. One of 4 patients who were unable to perform coitus because of the curvature noted improvement after the injections. The low rate of response in this small series of patients would suggest that there is no additional benefit in the use of the dermo-jet over percutaneous injection of the plaques. The latter procedure can be performed more easily on a repeated basis over a longer period. Two patients whose plaques were excised and repalced by a dermal inlay graft have had a good response to treatment and it would appear that this technique is useful for the patient who has failed to respond to conservative measures and who is significantly disabled by the disease.


A modification of the Young procedure for radical perineal prostatectomy. A modification of the Young procedure for total perineal prostatectomy is described herein. The modification consists of an anterior and posterior paraurethral mattress suture that approximates the distal urethra and the bladder neck without constricting or interfering with the function of the sphincter muscle. None of the 55 patients with early prostatic carcinoma who have undergone this procedure has had incontinence.


Nephrocalcinosis in infancy and childhood. The diangosis, clinical manifestations and management of 11 children with nephrocalcinosis encountered in a 20-year period are presented. Renal tubular acidosis, primary hyperoxaluria, primary hyperparathyroidism, exogenous hyperadrenocorticism and idiopathic hypercalcemia of infancy were the principal causes of nephrocalcinosis in this series. In the presence of normal or near-normal renal function, a 55 per cent or better cure rate can be expected. Children with significantly diminished renal function have a poor prognosis and should be considered for renal transplantation.


Hamartoma and renal transplant implications. A 19-year-old woman with tuberous sclerosis, bilateral renal hamartomas and polycystic kidneys required separate nephrectomies for severe hemorrhages 6 months apart. The case is presented, the diagnoses of the disease in relation to a negative family history are considered and the importance of early diagnosis in a potential transplant recipient and the use of leukocyte-free transufusions are discussed.


A rabies epidemic in recently captured skunks. An epidemic of rabies occurred within a colony of captive skunks (Mephitis mephitis). One of the animals has been infected with the virus in the wild and developed clinical illness near 7 weeks after capture. She transmitted the virus to three of her five offspring and one other adult. The disease spread to additional skunks when orphaned infants were adopted by lactating females. Although the animals were in close contact with each other, the epidemic spread slowly. Furious rabies generally did not occur and frequently rabid skunks were found dead without any clinical signs of the disease having been observed.


Ibuprofen or aspirin in rheumatoid arthritis therapy. Ibuprofen is a nonsteroidal drug with analgesic, antipyretic, and anti-inflammatory properties that was recently introduced for use in antiarthritis therapy in the United States. In a year-long double-blind multiclinic trial in 885 patients with rheumatoid arthritis, ibuprofen was at least as satisfactory as aspirin, considering both efficacy and tolerance. In the majority of patients, daily doses ranged from 800 to 1,600 mg of ibuprofen and 3 to 6 gm of aspirin. The drugs did not differ greatly in providing relief from arthritis symptoms, but ibuprofen was definitely better tolerated, especially in regard to gastrointestinal complaints. Seven percent of the ibuprofen group dropped out of the study because of adverse reactions, as compared with 16% of the aspirin group; 17% of the ibuprofen group and 31% of the aspirin group had gastrointestinal symptoms.


[Differential diagnosis of acute myocardial infarct and ECG interpretation with the aid of long-distance computer inquiry]. Data are presented on the differential diagnosis of some forms of the ischaemic heart disease, myocardial infarction including, performed with the help of a long--distance enquiry of the "Nairi-K" computer. This is one of the adjunct methods of early and timely diagnosis of myocardial infarction that permits to differentiate it from angina pectoris, postinfarction cardiosclerosis, acute abdominal pathology, pleuropneumonia, and to determine the localization of the necrosis. The exactness of the diagnosis ranges from 93 to 95%. An information system was developed that permits a more objective assessment of the nature of the ECG changes.


[Covering of fistulae after operations of glaucoma (author's transl)]. It is recommended to use a certain method to cover cystic oozing cushions after filtering operations of glaucoma. To this effect a lamellar scleral flap is formed which is laid over the previously exposed scleral fissure. An impediment of the filtration of aqueous humour is avoided by means of suitable fixation of Tenon's capsule.


[Correction of Blepharochalasis (author's transl)]. Blepharochalasis implies the symptom or general term (Kettesy) applied to the slackening and thinning out of the upper lid. From a clinical point of view and in a wide sense this includes Cutix laxa senilis or senile epiblepharon. The following surgical procedures restore the lost contract between the skin and the lid elevator. 1. Upper plapebral furrow formation sutures (Kettesy). 2. Blepharochalasis surgery according to the method of Imre. This is a "mild ptosis operation" which is indicated in advanced slackening and dehiszenz of the Fascia tarso orbitalis. 3. The "controlled skin resection" which permits a testing of the function before the skin resection, prevents the excision of muscle fibres as well as too large and irregular skin stripes and provides for a minimum haemorrhage. For this purpose the skin fold near to the upper tarsal margin is lifted up and marked with running sutures along the line of expected upper palpebral furrow. After resection of the lifted lid skin the scarcely bleeding wound is closed with running sutures.


Self-mutilation in mice associated with otitis media. Mutilation of the external ear and adjacent tissues was an enzootic problem in outbred Mcr:(ICR) breeder mice in a commercial colony. Necropsy examination of affected and randomly selected, nonaffected adult breeder mice revealed a probable association of the cutaneous lesions with suppurative otitis media. Several microorganisms, including Mycoplasma pulmonis and Pasteurella pneumotropica, were isolated from the tympanic bullae.


Immunohistochemical demonstration of hepatitis B core and surface antigens in paraffin sections. An immunohistochemical staining to demonstrate the hepatitis B core and surface antigens (HBc&sAg) on formalin-fixed, paraffin-embedded liver tissue was investigated. The staining is believed to be valid for the reasons that: (1) HBc&s AG-positive and control tissues were properly selected. (2) The immunospecificities of the antisera to HBc Ag or HBs Ag were verified by immunoelectron microscopy and by conducting the neutralization controls in the staining procedure. (3) The staining results were identical with those shown on unfixed frozen sections from the same cases. The immunoreactive sites of HBc&s Ag are shown to be preserved in the formalin-fixed, paraffin-embedded tissue, and they can be demonstrated by either direct or indirect immunofluorescent and immunoperoxidase methods. The pronase digestion of the tissue sections quenches the nonspecific background staining and thus facilitates the microscopic examination. The indirect immunofluorescent method is more sensitive than the direct. The localization of HBs Ag in liver cells shown by immunohistochemical method is identical with that demonstrated by orcein histochemical stain. The described method demonstrating the HBc Ag in paraffin tissue may offer an additional means in making a specific etiologic diagnosis of hepatitis B viral disease.


Pharmacological and ultrastructural maturation of serotonergic synapses during ontogeny. Studies were made on the course of maturation of serotonergic synapses during ontogeny in rat brain. Mature synaptosomes containing the same five types of synatic vesicles as in the adult, including small dense core vesicles, could be isolated in low proportion from the brain of 1-day-old rats. Although the buoyant density of these synaptosomes varied more than in the adult, the 5-hydroxytryptamine (5-HT) synaptosomes at the two age groups had similar sedimentation characteristics. Ouabain and imipramine, which block active transport of 5-HT, and reserpine, which blocks its granular storage, resulted respectively in a similar slight inhibition of uptake and accumulation of (-14C)5-HT in synaptosomes of 19-day foetuses. Transport and storage of (-14C)5-HT in the brain stem matured simultaneously with endogenous 5-HT content. In subcellular fractionation of the brain 5-HT content, the percentage of 5-HT in the supernatant was significantly lower in neonatal than in adult rats. After treatments with monoamine oxidase inhibitors (MAOIs) and reserpine plus MAOI, respectively, the maximum brain content and subcellular distribution of 5-HT were similar in 1-day-old and adult rats; the result suggests the existence of some other binding mechanism besides the Mg++-ATP-dependent granular storage. Imipramine and N,N-dimethyltryptamine, which cause stimulation of 5-HT receptors, decreased the turnover of brain 5-HT by 40% in adults but had no effect in neonatal rats. Immobilization increased the turnover of brain 5-HT by 35% in adults but had no effect in neonatal rats, whereas fasting increased it by 20% in adults and by 150% in neonatal rats. At 3 weeks of age the responses to imipramine, immobilization and fasting resembled those seen in adults. These responses occurred later than the appearance of the endogenous content, transport and storage of 5-HT and may require maturation of synaptic junctions, the latest neuronal structures to develop.


Copayments for ambulatory care: penny-wise and pound-foolish. The California "copayment experiment" imposed a charge of $1 on certain Medicaid beneficiaries for the first two visits to a doctor and 50 cents for the first two drug prescriptions each month, effective January 1, 1972. Data on utilization rates were gathered for six months before this date and for 12 months after it. While other administrative requirements, like prior authorization of certain services, doubtless also played a part, it was found that, following the start of copayment, utilization of ambulatory doctor's office visits and other services associated with them showed a decline, relative to that of the non-copayment cohort. After a brief lag, however, hospitalization rates in the copay cohort rose to levels higher than those of the non-copayment cohort-more than offsetting the savings to the state from the reduction of ambulatory service use rates. Due presumably to the neglect of early medical care because of the inhibiting effect of the copayments, these higher use rates of costly hospitalizations suggest that financial deterrents on access to ambulatory service by poor people are penny-wise and pound-foolish, not to mention their effects on health and well-being.


Emphasizing "level of care" over "length of stay" in hospital utilization review. Utilization review has heretofore emphasized "length of stay" as the criterion for deciding when the patient is ready to leave the hospital. We suggest that "level of care" (the type, number, and/or intensity of a combination of physician, skilled nursing, and ancillary services) received by the patient should replace length of stay as the major "decision" criterion for deciding on continued hospitalization: "appropriate hospital placement" means the patient is currently receiving a level of care available only in the hospital. Length of stay should be the criterion for signaling intervals when patients are (re) reviewed to determine the currently needed level of care. Explicit criteria for determining when a patient is receiving a hospital level of care should be developed. Explicit criteria will increase objectivity, provide guidance to utilization review coordinators, and assist the hospital in defending its utilization review decisions to an intermediary or Professional Standards Review Organization (PSRO). Level of care will be reflected in a patient's "service profile," a listing of all the services being received by the patient on any given day of hospitalization. The services profile varies throughout hospitalization; hospitalization is appropriate when a patient's current services profile constitutes a level of care available only in the hospital.


Optometric prescribing patterns: a quality comparison of Medicaid and non-Medicaid practitioners. This study analyzes five variables related to quality and utilization of optometric prescribing of eyeglasses. The practices of optometrists participating in the New York City Medicaid Program were compared with those not participating. The variables chosen for this study can be analyzed by computer and seem to have wide applicability for monitoring of optometry services. Significant differences were found in four of the five variables under review. Overall, non-Medicaid patients appear to be receiving higher quality optometric care and less unnecessary care. Many of these differences, however, depend on the setting of the practice-whether solo, group, or corporate. Of additional note, wide variations occurred in the patterns of practice for non-Medicaid, as well as Medicaid, optometrists.


Medicine's great schism: prevention vs. cure: an historical interpretation. All societies, primitive and advanced, demand therapeutic services, but a society must develop sophisticated prerequisites before it can support preventive services. This discordance in the origins of curative medicine and public health does not explain why a schism between them still persists. This gap should be closed since medicine has cured most curable diseases and the residue of chronic conditions is best handled by preventing them or detecting them before they become medical crises. Reasons for persistence of the schism include; early concentration of public health on environmental sanitation to the exclusion of medicine; identification of public health was governmental bureaucracy; linking care of the poor with tight-fisted welfarism; existence of two separate educational systems, the view of doctors, who are activists by nature, toward the excitement of cure; the custom of paying only for active therapy; and the orientation of the Hippocratic ethic toward individuals.


Cost-sharing and prior authorization effects on Medicaid services in California: part I. The beneficiaries' reactions. In January 1972, California initiated a cost-sharing "experiment" as a means of containing rising costs of the Medicaid program. Beneficiaries who had some personal assets were required to pay a token amount for each doctor visit or prescription. This was expected to deter unnecessary services without affecting really needed care. An interview survey was made of beneficiaries continuously in copayment status throughout the 18 months of the experiment. Most beneficiaries had poor knowledge of the program, and tended to confuse copayment with the concurrent constraint of prior authorization for certain classes of service. The beneficiaries reported that the copayment was almost always collected, and most thought it had not affected their health care, but a significant 17 per cent throught it had reduced the care available to them, and these 17 per cent were for the most part in households with high medical need.


Kinetics of tumor growth and of cell proliferation in U.R.D.T. cancers: therapeutic implications. After a brief survey of the factors of clinical tumor radioresistance the available data on the growth rate and on the kinetics of cell proliferation of U.R.D.T. tumors are reviewed.  The growth fraction and the cell turnover rate appear to be similar in U.R.D.T. tumors and in other squamous cell carcinomas.  These two parameters are correlated with clinical tumor radiosensitivity and chemosensitivity.  The possible value of tailoring fractionation and drug administration to the biological characteristics of the tumor is discussed.


Acalculous parotid sialadenopathy.

Acalculous parotid sialadenopathy. Acalculous inflammation of the parotid gland has been regarded by some as a specific disorder that can be staged as to the severity of the disease process.  A review of the literature, however, indicates a divergence of opinion.  It is the purpose of this study to test this hypothesis by a retrospective double-blind analysis of clinical, sialographic and histopathologic findings.  Forty-two patients who were seen by the Department of Otolaryngology, Washington University School of Medicine from 1961 to 1970 were evaluated by two separate teams.  There were 20 sialograms and 30 pathologic specimens, and all were re-examined.  Eleven patients had both sialographic studies and histopathologic examination.  The clinical presentations and sialographic findings were reviewed.  These findings were then compared to each other.  Our results indicate that we could not evaluate the severity of the clinical disease by sialography or histopathology.  There was no consistent method of staging the sialographic and pathologic findings.  In addition, there was no correlation between these two parameters.  They reflect neither the patient's clinical syndrome pattern nor the extent of disease.  It appears that the parotid gland responds variable to inflammation.  These observations are exemplified by case histories.


Regional skin flaps in partial laryngectomy. The use of regional neck flaps for rehabilitation has permitted an extension of operations on the glottis.  The resection may include both vocal cords, both ventricular bands, one arytenoid and slight subglottic extension in a one- or two-stage technique.  The resultant voice is low pitched, soft and has limited range.  The cure rate was 85 percent.


Steroids and steroid metabolism in plant tissue cultures. The steroids which have been isolated from plant callus and suspension cultures are reviewed. In addition, the research involving the use of plant tissue cultures to investigate steroid biosynthesis and metabolism is summarized.


Behçet's disease. Report of 41 cases and a review of the literature. Several important conclusions may be derived on the basis of our experience with Behcet's disease (B.D.) and a review of the literature, namely: 1. B.D. is a systemic disease characterized by exacerbations and remissions of unpredictable duration, which affects mainly males between the ages of 20 to 30 years. Although its incidence is higher in the eastern hemisphere cases presented in all parts of the world. 2. The common histopathological lesion of all clinical manifestations appears to be a vasculitis. The etiology of B.D. is unknown. A viral etiology has been proposed but not confirmed. The presence of autoantibodies and lymphocyte sensitization to mucosal antigen has been observed but the precise significance of these findings in relation to the pathogenesis of the disease is presently undetermined. 3. The clinical manigestations present in most of the patients and considered diagnostic for B.D. are oral and genital ulcers, uveitis and skin lesions (especially erythema nodosum-like lesions or non-specific skin reactivity to needle pricks). The presence of three of the above manifestations are obligatory for the diagnosis. The other common clinical manifestations occurring in B.D. are: arthritis (44%); thrombophlebitis (24%), and various neurological syndromes (18%). Less frequent complications of the disease include: arterial thrombosis and aneurysm of both the systemic and pulmonary circulation, colitis, epididymitis and orchitis. 4. The serious chronic sequelae of this disease consist of blindness in up to 33% of patients with uveitis, vena caval obstruction and paralysis of limbs. Mortality, usually caused by meningoencephalitis, is rare. 5. The patients may present to different medical specialities, e.g., dermatology, gynecology, ophthalmology, neurology and internal medicine. To facilitate the correct diagnosis the essential criteria should be actively sought as they are not always the cause for medical consultation. 6. The diagnosis of B.D. is based only on clinical grounds as there are no pathognomonic laboratory or histopathological features. 7. Evaluation of treatment in B.D. is difficult, because of the naturally unpredictable course of the disease. Many drugs have been tried in the treatment of B.D. including antibiotics, anti-inflammatory drugs and corticosteroids, all with equivocal effects. Recently several additional treatment schedules have been suggested. Immunosuppressive drugs have been shown to have some beneficial effect, especially on uveitis. Fresh blood or plasma transfusions may prolong remissions. 8. The finding of decreased plasma fibrinolytic activity in patients with active B.D. represents the first observation of a possible disturbance in the blood coagulation mechanism and suggests that the use of fibrinolytic agents may be rewarding.


[Phagocytosis of cell wall defective bacteria by human macrophages (author's transl)]. Statistically significant better phagocytosis of spheroplasts was found by comparing the rate of phagocytosis of normal and Penicillin-G induced cell wall defective bacterial (spheroplasts) by human macrophages in isotonic media using a Proteus mirabilis strain as test organism. This provides additional information concerning the minor role of cell wall defective bacteria as persisters in chronic infections.


Bacteriophages of Nocardia asteroides.

Bacteriophages of Nocardia asteroides. 101 Nocardia strains from different species and different sources were examined with respect to their lysogeny. 18 phages from 17 Nocardia asteroides strains could be isolated, purified, and propagated. All phages were released spontaneously. Induction experiments with mitomycin C and UV-rays brought no practicale advantages. Using 14 of the 18 phages, 38 of the 101 Nocardia strains tested could be grouped into 18 phage patterns. Nearly all of the typable strains belonged to the species Nocardia asteroides.


Proteolytic activity of Mycoplasma salivarium and Mycoplasma orale 1. Proteolytic activity was found in whole cells and cultural supernatants of Mycoplasma salivarium (PG20 and B isolates) and Mycoplasma orale 1 (CH 19299 and B isolates). Additionally, the activity was examined in cell membrane soluble fractions of PG20 and CH 19299, and detected in them. The level of the activity appeared higher in M. salivarium than M. orale 1. And some differences were found between these mycoplasmas in the affinity for substrates as a result of examination of the activity in cultural supernatants using horse serum, casein and bovine albumin as substrates. That is, PG20 had a higher affinity for horse serum proteins than casein, while CH 19299 the latter than the former, although the lowest affinity for bovine albumin was common to these two strains.


Structural aspects of the milk clotting process. Comparative features with the blood clotting process. The enzyme chymosin and its substrate, a casein fraction called k-casein, are involved in the milk clotting process. Recent data concerning the structure (peptide and sugar moieties) of various k-caseins and their role in casein micelles formation and stabilization are presented. The molecular events occurring during the primary phase of chymosin action on k-casein are discussed. Finally some structural features concerning more particularly the caseinoglycopeptides and the fibrinopeptides as well as the action of chymosin and thrombin involved in the milk and blood clotting processes are compared. Three examples of sequences of portions of k-caseins and fibrinogen presenting homology are presented.


Induction and mutagenesis of prophage lambda in Escherichia coli K12 by metabolites of aflatoxin B1. Like most carcinogens, aflatoxin B1 must be activated by mammalian microsomal enzymes to give rise to coupounds active on bacteria. These compounds act as inducers of E. coli K12 (lambda) at a high efficiency, whereas unmodified aflatoxin B1 has no effect. Moreover, metabolites of aflatoxin B1 have a mutagenic action on phage lambda, as shown by the appearance of clear plaque mutants. We propose the hypothesis that the same derivative is responsible for carcinogenesis of liver cells by aflatoxin B1. Therefore, our system provides a simple way of measuring in vitro, in the same assay, the mutagenic and inducing activities of compounds to which the cells are permeable, thereby detecting potentially carcinogenic agents.


An evaluation of the micronuclei test using triethylenemelamine, trimethylphosphate, hycanthone and niridazole. To determine the feasibility of the micronuclei procedure for cytogenetic studies, a comparatively weak chromosome breaking agent, trimethylphosphate (TMP) and the potent alkylating agent, triethylenemelamine (TEM) were evaluated. The procedure followed was that of Matter and Schmid with the following modifications: (a) direct flushing of bone marrow with 0.2 ml calf fetal serum. (b) air drying slides for a period of only I h, and (c) the use of pH 6.0 phosphate buffer to dilute both Wright and Giemsa stains. With this technique a dose response curve was generated for both TMP and TEM, using mice as the experimental animal. With TMP, a doubling over background was found when a concentration of 0.5 g/kg per day for five days was administered. To establish a statistically significant doubling dose over the control, a minimum of five animals must be used with 2000 polychromatic cells being analyzed per animal. Of the two antischistosomal agents tested, hycanthone yielded an increase of 20-fold in the number of micronuclei over control at 40 mg/kg administered i.p. for five days, while with niridazole no increase in micronuclei at several concentrations tested both by single and multiple injection was found. The results obtained with these compounds compare favorably with what has been reported for the standard in vivo metaphase analysis.


Mutagenicity testing with Salmonella typhimurium strains. I. Unusual phenotypes of the tester strains. Some of the Salmonella typhimurium strains in mutagenesis testing are atypical. Unlike the wild S. typhimurium these do not produce H-2-S, are not agglutinated by S. typhimurium typing sera and on fermentation of carbohydrates they do not produce gas. Thus these tester strains cannot readily be identified as S. typhimurium by standard laboratory procedures. This may cause a problem in the differentiation of tester strains from bacterial contaminants. The possibility exits that these phenotypic traits may affect the response of the strains to mutagens.


Protein synthesis and the recovery of both survival and cytoplasmic "petite" mutation in ultraviolet-treated yeast cells. I. Nuclear-directed protein synthesis. The contribution of nuclear-directed protein synthesis in the repair of lethal and mitochondrial genetic damage after UV-irradiation of exponential and stationary phage haploid yeast cells was examined. This was carried out using cycloheximide (CH), a specific inhibitor of nuclear protein synthesis. It appears that nuclear protein synthesis is required for the increase in survival seen after the liquid holding of cells at both stages, as well as for the "petite" recovery seen after the liquid holding of exponential phase cells. The characteristic negative liquid holding effect observed for the UV induction of "petites" in stationary phase cells (increase of the frequency of "petites" during storage) remained following all the treatments which inhibited nuclear protein synthesis. However, the application of photoreactivating light following dark holding with cycloheximide indicates that some steps of the repair of both nuclear and mitochondrial damage are performed in the absence of a synthesis of proteins.


Protein synthesis and the recovery of both survival and cytoplasmic "petite" mutation in ultraviolet-treated yeast cells. II. Mitochondrial protein synthesis. The contribution of mitochondrial proteins in the repair of UV-induced lethal and cytoplasmic genetic damages was studied in dark liquid held exponential and stationary phase yeast cells. This was performed by using the specific inhibitors, erythromycin (ER) anc chloramphenicol (CAP). It was shown that mitochondrial proteins are involved in the recovery of stationary phase cells. Mitochondrial proteins are partly implicated in the mechanisms leading to the restoration of the (see article) genotype in UV-irradiated dark liquid held exponential phase cells. Here again, in stationary phase cells, mitochondrial enzymes do not seem to participate in the negative liquid holding (NLH) process for the (see article) induction, as shown by inhibiting mitochondrial protein synthesis or both mitochondrial and nuclear protein synthesis. When cells are grown in glycerol, the response after dark liquid holding of UV-treated cells in the different growth stages are similar to that found for glucose-grown cells. In other words, the fate of cytoplasmic genetic damage, in particular, is not correlated with the repressed or derepressed state of the mitochondria.


Host-mediated assay with yeast and rats using probenecid (Benemid) to block the renal tubular excretion of cyclophosphamide metabolites. The genetic activity of cyclophosphamide (Cy) was tested in the host-mediated assay (injection of yeasts into the peritoneal cavity of rats) modified by the use of probenecid (Pro) (Benemid) to block the renal tubular excretion of the genetically active metabolites. The genetic test system used was the induction of mitotic gene conversion in two unliked loci of a diploid strain of Saccharomyces cerevisiae. By this method the genetic effect of By was doubled in comparison with the case of administering Cy alone. Compared with the animals which received only Pro, increases of conversion frequencies of 20 times in the ade2 locus and of 15 times in the trp5 locus were found.


Testing the mutagenic potency of chemical substances in a linear host-mediated assay. I. Experimental microbiological basis. By the use of the mutagenic substance hydrazine sulphate it is shown that the currently used single determination method for determining point mutations in host-mediated assays with calculation of mutation frequencies can lead to erroneous results. The microbiological basis for a linear-method is presented in which the population growth of the auxotrophic and substance-induced mutants used int he test can be described mathematically during their logarithmic growth phase with regression lines.


Umbra limi: a model for the study of chromosome aberrations in fishes. Due to the lack of information available on the effect of various clastogenic agents on the chromosomes of fishes, an in vivo cytogenetics model system was developed. The central mudminnow, Umbra limi, was chosen fro this study because of its ideal karyotype consisting of 22 large meta- and submetacentric chromosomes. Various organs of the fish were investigated to determine their suitability for chromosome preparations. The tissues of the intestines, stomach, kidneys, and gills were found to be the most suitable for clastogenic studies. Phase contrast observations were made on the chromosomes of control mudminnows and mudminnows exposed to 325 R of X-radiation. The control rate of spontaneous chromosome aberrations was found to be low (about 0.03%). In contrast, fish exposed to 325 R of X-rays had aberrations in approximately 30% of the metaphases per fish examined. An apparent increase in clumping and a decrease in the mitotic index were also noted. It was concluded that the chromosomes of Umbra limi displayed typical responses to low level radiation exposure and that this fish would be an ideal cytogenetics model for this study of induced chromosome aberrations in fishes.


The mutagenicity of saccharin.

The mutagenicity of saccharin. Seventeen different reports are available dealing with the mutagenic effects of saccharin. Many of these are short abstracts, carrying incomplete information. Mainly tested as its sodium salt, saccharin has been found to be weakly mutagenic in Salmonella at very high doses, in Drosophila at moderate doses, and in mice at moderate to high doses. The compound is a weak chromosome breaker in onion root tips and in Chinese hamster cells. For most of these, and for other test systems as well, a number of doubtful or negative results have also been reported. Altogether the evidence for chromosome-breaking properties is stronger than for the induction of point mutations. The overall picture is too conflicting and equivocal to classify saccharin as a proven mutagen. It is suggested that the observed contradictions might be related to the occurrence of varying amounts of impurities.


Factors affecting experimental infection with Cryptococcus neoformans in mice with special reference to an endotoxic substance of C. neoformans. A close correlation was observed between body weight and length of the survival time of mice inoculated intravenously (i.v.) with Cryptococcus neoformans (p less than 0.001). An endotoxic substance of C. neoformans (Cr-ET) increased the susceptibility of mice to i.v. infection of C. neoformans only when more than 50 mug of Cr-ET was injected i.v. 24 hours before infection. Intraperitoneal (i.p.) administration of dimethyl sulfoxide which is found to enhance bacterial infection did not enhance death rate of mice infected i.p. with C. neoformans.


[Antibiosis shown by a strain of Byssochlamys nivea Westling, 1909. III. Chromatographic characteristics and isolation of the active fraction]. Early papers revealed that culture filtrate of Byssochlamys nivea has antibiotic properties. Active filtrate of B. nivea is extracted with ethyl acetate. Paper chromatography is carried out on Whatman no. 1; thin-layer chromatography is carried out on Kieselgel; visualization with bioautographic technique reveals a single spot. Ethyl acetate extract is passed through silicic acid-celite column. Each isolated fraction is tested for antibiotic activity. Only one supports this activity; a crystallized matter, melting point 109-110 degrees C, thermostable, is obtained.


Isolation of histone genes from unfractionated sea urchin DNA by subculture cloning in E. coli. Histone genes have been cloned selectively in Escherichia coli directly from unfractionated sea urchin DNA using labelled mRNA probe. The cloning method used is potentially applicable for isolating any genetic sequence for which a probe is available. The several eukaryotic gene fragments introduced into bacteria by this method collectively contain all or nearly all of the DNA sequences represented in histone mRNA.


Relation between the amount of smooth muscle of venous tissue and the degree of supersensitivity to isoprenaline caused by inhibition of catechol-O-methyl transferase. The relation between the smooth muscle cell mass of dog saphenous vein strips and the degree of supersensitivity to isoprenaline caused by U-0521 (3,4-dihydroxy-2-methyl propiophenone), an inhibitor of the catechol-O-methyl transferase (COMT), was studied. For the quantitative determination of smooth muscle mass, the thickness of the muscle layer as determined by light microscopy and the maximal shortening induced by supramaximal concentration of phenylephrine were used. After the strips had been contracted by 3x10-6M phenylephrine, a concentration which was able to produce an about 90% maximal contraction, dose-response curves to the relaxant effect of isoprenaline were determined in the absence and in the presence of U-0521 (10-4M). It was observed that U-0521 caused marked supersensitivity to the relaxant effect of isoprenaline (varying between 3 and 81 times), as well as an increase of the  maximal relaxation caused by this amine (varying between 7 and 120%). The correlation between these data and the smooth muscle cell mass shows that there was a direct proportionality between these parameters. Oxytetracycline (10-4M), an inhibitor of binding of catecholamines to collagen, did not produce any enhancement of the effects of isoprenaline. It is concluded that COMT is related to smooth muscle cells in this tissue.


Measurement of plasma and hypothalamic luteinizing hormon-releasing hormone in pregnant mare serum-induced ovulating immature rats. A radioimmunoassay for luteinizing hormone-releasing hormone (LH-RH) is described which is capable of detecting LH-RH in plasma and brain tissues. Fluctuations in plasma and hypothalamic LH-RH as well as plasma LH were measured in immature female rats in which ovulation was induced by a single injection of pregnant mare serum (PMS). High plasma levels of LH-RH were found 47-49 h after the initial injection of PMS, coincident with high plasma LH concentrations. However plasma LH-RH levels were considerably lower at 55-57 h post-PMS, when plasma LH levels were elevated. Hypothalamic LH-RH content could not be correlated with either plasma LH-RH or LH levels.


Prostaglandin E2-induced release of luteinizing hormone-releasing factor (LRF). Prostaglandin E2 (PGE2) injected into the third ventricle (3rd V) of conscious ovariectomized rats bearing a permanent jugular cannula increased the percentage of plasma samples showing detectable immunoassayable LRF levels at 1, 3 and 5 min after injection. This percentage was small at 2 and 4 min. When plasma LRF and LH titers were measured in animals injected intraventicularly with PGE2 and decapitated 5 min later, both LRF and LH were significantly higher than control values of diluent-injected animals. These results indicate that PGE2 is acting on the hypothalamus to induce release of LRF sufficient in mangitude to be detected by measuring this neurohormone directly in peripheral plasma.


Modification of brain and CSF LH-RH following deafferentation. The effect of hypothalamic deafferentation upon levels of LH-RH in brain, cerebrospinal fluid, and plasma was studied in adult male rats. Deafferentation produced a significant increase in the LH-RH concentration of third ventricular CSF (from 140.6 to 343.9 pg/microl), while there was no change in median eminence or hypothalamic content. LH-RH in the pineal gland and the posterior pituitary was also elevated by hypothalamic isolation.


HMOs, competition, and government.

HMOs, competition, and government. This article considers the role of three sets of forces affecting the development of health maintenance organizations (HMOs) during the early 1970s: legal restrictions, market conditions, and the federal government's policy stance. Our review of the evidence suggests that the rapid increase in the number of HMOs during this period was primarily due to favorable market conditions in certain areas of the country combined with a highly encouraging federal policy toward HMOs. Legal restrictions do not appear to have been as serious a barrier to HMO development as was earlier believed. In 1973-74, major new legislation was enacted at both the federal and state levels, ostensibly to encourage HMO development. Our review of this legislation suggests that, while it removes many of the old legal requirements which apparently were not serious barriers to HMO development, the new legislation imposes a host of new conditions and requirements on HMO participation in the health care marketplace. Ironically, some of these new features may impede the operation of the very market forces which encouraged the earlier HMO growth.


The effects of prepayment on access to medical care: the PACC experience. The data reported herein are taken from a larger study in which a prepaid medical foundation was compared with a non-prepaid free-for-service system on a number of factors pertaining to how health care is perceived by both Medicaid recipients and physicians. The data to be presented are confined to the issue of the impact of prepayment on Medicaid recipients' perceptions of their access to health care. Two sets of questions are explored. The first set bears directly on the issue of gaining access to care. The second set addresses the issue of the acceptability of the services received. Few differences were observed between the systems in either accessibility or acceptability. Thus, the fears of some critics of the HMO concept with respect to prepayment creating incentives for the denial of services are not supported by the data. It is concluded that the organizational features of medical practice which affect access are actually quite similar in the two systems.


[Some elective procedures for cranioplasty]. The literature methods for cranioplasty in the repair of losses of bone substance are described. Autologous bone grafts from the iliac ala or the ribs are used at the Turin University Reconstructive Plastic Surgery Department. A method using solid silicone is also employed and will be discussed in greater detail in a subsequent paper. Three illustrative cases are presented.


[Aspects of humoral immunity in ulcerous colitis]. Various immunological indices, hitherto considered in isolation, were evaluated in a single group of 20 cases of ulcerous colitis. Immunofluorescence showed anticolon Ab in 3 cases (15%), whereas this features was absent in a control group. Antistomach, antithyroid and non-organ-specific Ab's (ANA, AMA, SMA) were equally incident in both groups. One caso is examined separately on account of its simultaneous presentation of human and rat antistomach and antithyroid and antismooth muscle Ab's. Reuma test, Waaler Roose reaction, L.E. phenomenon and test, and direct and indirect Coombs test results were negative in nearly all cases. Slight quantitative changes in serum proteins revealed by electrophoresis and immunodiffusion were indicative of inflammation with an immunitary tendency. The data are not sufficient to support the attribution of an autoimmunitary aetiology to ulcerous colitis, though simultaneous evaluation of reaction indices serves to strengthen this view.


[S-Adenosylmethionine: plasma levels in hepatic cirrhosis and preliminary results of its clinical use in hepatology. Double-blind study]. Since S-adenosylmethionine (SAMe) plasma levels are highly reduced in cirrhotic patients, this, showing that a more or less overt deficiency of SAMe-dependent biological transmethylations does exist in the hepatocyte pathology, mostley affecting the albuminopoyesis. Treatment with 15 mg SAMe i.v. or i.m. administered four times a day for 30 days' period, induced in 15 patients with hepatic cirrhosis a statistically significant improvement of the afore mentioned livel cell function, albuminopoyesis: a significant improvement was also observed in the other biohumoral parameters considered to test hepatic function. Administration of equimolecular (with respect to SAMe) doses of L-methionine and ATP to a group of 15 cirrhotic patients under clinical conditions similar to those of the group previously studied, induced none of the modifications observed in the latter. This proved that the therapeutic effects are due only to S-adenosylmethionine.


[Relations between protidopoiesis and biological transmethylations: action of S-adenosylmethionine on protein crasis in chronic hepatopathies]. After a diffuse introductory discussion on S-adenosylmethionine methyltransferase activity, the results of an experimental trial carried out on 70 hospitalized patients with chronic hepatitis either persistent or aggressive, and with hepatic cirrhosis at various degrees, are reported. A first group of patients was treated with SAMe (S-adenosylmethionine) intravenously administered for 20 days at two daily doses of 15 mg. The second group was instead-receiving, still by i.v. route, 20 mg of fructose-1-6-diphosphage sodium salt, as a drug for comparison given twice a day at the doses of 2.5 over a 20 days' period. The protidemia picture and in particular the albuminic fraction, generally altered in all the cases under study, have been rapidly and significantly restored only in the group of patients treated with SAMe this indicating the efficacy of this molecule on the liver function.