Digestive enzymes of the mucosa of the small intestine and trypsin and chymotrypsin proteolytic activity of the intestinal contents of germ-free, monocontaminated and conventional rabbits.

The activity of the membrane-bound enzymes of the microvillous zone of the entreocytes (maltase, sucrase, trehalase, lactase, cellobiase, alkaline phosphatase and leucylaminopeptidase) was studied in mucosal smears from the proximal jejunum, ileum, caecum and sigmoid flexure in a group of control (C) (8) and germ-free (GF) (7) rabbits. The trypsin and chymotrypsin activity of the contents of the ileum, caecum and sigmoid flexure was studied in 6 C, 5 GF and 5 monocontaminated (MC) rabbits. In summing up it can be stated that the individual membrane-bound enzymes have a different gradient in the various intestinal segments of C and GF rabbits and that they differ reciprocally in character. The maximum statistically significant differences between GF and C rabbits were found in the ileum; in the jejunum they were somewhat smaller and in the caecum smaller still (in this localization the difference was C versus GF). Striking differences in the proportion of the individual disaccharidases were found inthe jejunum and ileum of C rabbits compared with GF rabbits, in which, in both these segments of small intestine the relationship maltase greater than sucrase greater than trehalase greater than lactase was preserved. The proteolytic activity of the intestinal contents likewise had a different gradient character in C, MC and GF rabbits. The maximum activities (especially trypsin) were found in MC animals. The microbial flora is one of the factors regulating the enzymatic activities of the microvillous zone of the enterocytes and it also significantly influences the proteolytic activity of the intestinal contents. This influence is particularly marked in the distal part of the alimentary tube.


Specificity of gastric proteinases.

The aim of our study was to isolate the gastricsin fraction in the purest possible form and to verify some of its properties for further study of the specificity of synthetic substrates. The next step in our research will be a similar analysis of pepsin.


Effect of probucol in hyperlipidemic patients during two years of administration.

Probucol, a new cholesterol-lowering agent, was administered to ambulatory outpatients representing several classes of hyperlipoproteinemia (HL) for two years without dietary restriction. In 32 patients with Type II HL and 12 with Type IIB HL, statistically significant reduction in mean serum cholesterol levels occurred within two weeks and persisted throughout two years of therapy at constant dosage (500 mg. twice daily). In smaller numbers of patients with Type IV HL (five patients) and Type V HL, (one patient) similar trends in mean serum cholesterol were observed but failed to achieve statistical significance. Mean triglyceride levels were generally lower during probucol therapy but varied widely between individuals. The drug was well tolerated, with no toxicity and few side effects (mild diarrhea, gas, bloating, and anal pruritus). Probucol should be a valuable addition to the therapeutic armamentarium for hypercholesterolemia.


Submaximal exercise testing after acute myocardial infarction: myocardial scintigraphic and electrocardiographic observations.

The relation between global and regional left ventricular function and electrocardiographic signs of ischemia at rest and during submaximal supine exercise was studied in 27 patients 2 to 3 weeks after acute myocardial infarction. Dynamic myocardial scintigraphy was performed at rest and during submaximal exercise utilizing an in vivo method of labeling red blood cells with technetium-99m pertechnetate. Gated radionuclide blood pool scintigrams were obtained in a modified left anterior oblique, and in some patients also in the right anterior oblique projection, to measure left ventricular ejection fraction and segmental wall motion. Electrocardiographic monitoring of heart rate and rhythm was provided during the exercise. The submaximal exercise test was terminated when the patient's heart rate reached 125 beats/min or if angina, malignant ventricular ectopy or electrocardiographic evidence of myocardial ischemia developed before this rate was reached. The data demonstrate that patients with a recent anterior myocardial infarct, in contrast to patients with a recent inferior or nontransmural infarct, manifest a significant reduction in left ventricular ejection fraction with submaximal exercise. Of the eight patients with an anterior infarct, seven had segmental wall motion abnormalities at rest. Four of these eight manifested more severe abnormalities with submaximal exercise; three had abnormalities at rest that did not change with exercise. Four of the eight had a positive electrocardiographic response during exercise (two were taking digoxin). Of these four, only two had more marked wall motion abnormalities with effort. Of the 13 patients with an inferior infarct, 11 had apparently normal wall motion in the modified left anterior oblique projection at rest, including 2 who manifested segmental wall motion abnormalities with submaximal exercise; the 2 remaining patients had wall motion abnormalities at rest that, on exercise, became more marked in one and were unchanged in one. Four of the 13 had a positive electrocardiographic response with exercise (one was taking digoxin); only one of these had a detectably more severe wall motion abnormality with exercise. Of the six patients with a nontransmural infarct, four had no identifiable wall motion abnormalities at rest; in one of these, an abnormality developed with exercise. The remaining two patients had wall motion abnormalities at rest; in one, a positive electrocardiographic ischemic response developed with exercise. Patients with an anterior infarct appear to have a different functional ventricular response to submaximal exercise at the time of hospital discharge than patients with an inferior or nontransmural infarct. To identify ischemic responses with submaximal exercise in these patients one should ideally use both electrocardiographic monitoring and dynamic myocardial scintigraphy.


The biological suppression of malaria: an ecological and nutritional interrelationship of a host and two parasites.

The interrelationship of malaria and severe ascariasis was studied in Anjouan children with a previously described syndrome of enlarged parotids, localized forehead edema, heavy infestation with Ascaris lumbricoides, and unusual freedom from malaria. After treatment of 37 such children with the ascaricide piperazine, 35 had resolution of parotid enlargement and forehead edema, but 19 developed attacks of malaria. Children treated with placebo had neither resolution of clinical findings nor attacks of malaria. We propose that suppression of the malaria in these children is a nutritional consequence of severe ascariasis and may represent an ecological balance for optimum co-survival of the host and the two parasites.


Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled, double-blind clinical trial.

In a double-blind, randomized study the efficacy of lactulose was compared with neomycin-sorbitol in 45 episodes of acute nitrogenous portal-systemic encephalopathy (PSE) induced by dietary protein, azotemia, or gastrointestinal hemorrhage. All patients had underlying cirrhosis, and at the time of randomization had encephalopathy of at least grade 2 severity and arterial ammonia concentrations greater than 150 microgram/100 ml. Two thirds of the patients in each group returned to normal mental status and more than 80% in each group showed at least one grade improvement in mental state. In addition, there was equivalent improvement in asterixis, in the performance of the Number Connection Test, in the electroencephalographic pattern, and in arterial ammonia concentration. The principal difference between the two groups was a greater reduction in stool pH after lactulose therapy than after neomycin-sorbitol therapy. One patient randomized to neomycin-sorbitol had to be withdrawn from the study because of persistent vomiting related to the administration of the medication. Otherwise there were no complications attributable to therapy in either group. These data suggest that neomycin-sorbitol and lactulose are equally effective in the treatment of acute nitrogenous portal-systemic encephalopathy.


Acute pancreatitis following renal allotransplantation. A lethal complication.

Since first described by Starzl in 1964 (1), acute pancreatitis following renal homotransplantation has been the subject of sporadic reports and reviews (2-5). The generally reported incidence has been around 2%, with a mortality rate of 50-60%. A recent experience with such a patient caused us to retrospectively analyze our own series of renal transplant recipients. In an eight-year period, there were six patients who had documented pancreatitis out of a total 120 renal homograft recipients, an incidence of 5%. The mortality was distressingly high; five out of the six succumbed directly to this complication, a rate of 83%. The purpose of this paper is to review these six patients in detail, with special attention to the protean etiologies and manifestations of this lethal complication.


Granulocytic colonies on macrophage-coated membranes.

A macrophage cell coating covering a cellulose acetate disk was an effective microenvironment for the production of peroxidase-positive hematopoietic colonies. These developed after intraperitoneal injection of marrow cells with a linear cell relationship of dose to colonies formed. One colony formed for every 2,000 nucleated marrow cells injected. Observation of colony formation daily showed a steady increase in number and size until seven days after cell inoculation. X-irradiation (400 rads) eliminated intrinsic colony formation in BALB/c mice. Irradiation of the donor of the ip marrow cells resulted in a d0 of 95 rads. Treatment of the marrow donor with cytosine arabinoside had a suppressive effect on colony formation as did treatment of the host animal after receipt of the ip marrow. These results indicate that the precursor of the granulocytic colonies seen in the macrophage layers are more similar to committed granulocytic precursors than to the pluripotential stem cell.


Glutathione reductase deficiency in a kindred with hereditary spherocytosis.

A kindred with hereditary spherocytosis was found to have erythrocyte glutathione reductase deficiency. The glutathione reductase was evaluated enzymatically and immunologically. The enzyme activity could not be restored either by flavin adenine dinucleotide (FAD) in vitro, or by oral administration of FAD. Kinetic and electrophoretic studies, heat stability tests, and pH curves revealed no evidence of a varient enzyme. The results of electroimmunodiffusion and neutralization tests using an antiserum indicated that the deficiency is caused by a diminished production of enzyme protein. Hereditary spherocytosis and glutathione reductase deficiency traits segregated independently. The amount of reduced glutathione in the erythrocyte was normal, and the deficiency state without hereditary spherocytosis was asymptomatic. All deficient members in this kindred were heterozygous and the residual enzyme activity in the heterozygote might be sufficient to maintain the reduced glutathione level to prevent oxidative stress.


Evaluation of a commercial multitest system for identification of yeasts.

A new commercial yeast identification system, the Randolph Multitest Mycology Plate, was evaluated. This system is based on the assimilation of carbohydrates, growth on birdseed agar, resistance to cycloheximide, hydrolysis of urea, and reduction of nitrate. The 184 clinical isolates used in the evaluation included 20 species of the genera Candida, Cryptococcus, Saccharomyces, Torulopsis, Trichosporon, Rhodotorula, and Geotrichum. Agreement with the standard Wickerham carbohydrate assimilation and other conventional biochemical results was found in 84 percent of the tests, and 91 percent of the yeasts were correctly identified with the aid of microscopy, cultural characteristics, and germ-tube formation. Identification of the tested strains was achieved within 96 hours.


Microwave fixation versus formalin fixation of surgical and autopsy tissue.

Microwave irradiation of surgical and autopsy tissue penetrates, fixes, and hardens the tissue almost immediately (the fluid media used in the microwave consisted of saline, ten percent phosphate buffered formalin, and distilled water). Tissue sections from a representative sample of organs were tested. Comparable sections were simultaneously fixed in a phosphate buffered ten percent formalin bath in a vaccum oven as a control. Hematoxylin and eosin were used to stain the sections. Results equal to and superior to the control method were obtained. Saline microwave fixation was superior to formalin microwave fixation. Tissues placed in Zenker's solution and fixed in standard microwave oven (for approximately one minute) yielded results at least equal to conventional Zenker fixation (approximately two hours). No tissue hardening resulted from Zenker microwave fixation. A unique time versus temperature graph (microwave heating curve) reduces individual variation with this technique.


Alternative procedures for identification of anaerobic bacteria.

Recognizing the need for practical inexpensive procedures which allow identification of anaerobes commonly encountered in clinical laboratories, a number of investigators have in recent years proposed various alternatives to the expensive, time-consuming techniques presently recommended by reference anaerobe laboratories. Some of these techniques are potentially good alternatives. In this paper we review some of the more promising approaches and present a detailed description of two commercial microbiochemical systems for characterization of anaerobes. When used in conjunction with other available tests, the microsystems are useful and convenient methods for identification of anaerobic bacteria at a reasonable cost.


Endothelial cell loss during penetrating keratoplasty.

We studied the central donor endothelium of 27 clear, penetrating corneal transplants with the specular microscope before and after keratoplasty. We examined the donor corneas first, in vitro, while they were immersed in McCarey-Kaufman preservation medium before transplantation. This preoperative examination proved valuable for screening donor corneas, several of which were not used on the basis of the specular microscopic appearance alone. We examined the donor endothelium again within one week after keratoplasty and calculated the number of endothelial cells per square millimeter from photographs. The reproducibility of the counting method was acceptable. Comparison of the examinations before and after transplantation on each patient showed that, on the average, 23% of the donor endothelial cells were lost during keratoplasty. The 12 phakic transplants lost significantly more endothelial cells than did the 15 aphakic grafts (37% vs 12%). A possible explanation for the increased cell loss in phakic keratoplasties is the shallow anterior chamber present during the initial placement of the graft. Phakic grafts that were larger or had shorter time intervals between donor death and enucleation lost fewer cells. Aphakic transplants had larger postoperative corneal thicknesses than did phakic transplants.


Cellular immunity in Mooren's ulcer.

Seven patients with the clinical diagnosis of Mooren's ulcer underwent macrophage migration inhibition factor testing for evidence of cellular immunity to corneal antigen. Six of seven patients demonstrated positive macrophage migration inhibition in response to corneal antigen, thus suggesting that cell-mediated immunity may play a role in the cause of Mooren's ulcer. One of these patients had a negative macrophage migration inhibition factor when the disease was inactive, but developed a positive response in association with a homograft rejection episode.


Ocular cryptococcosis.

We studied ocular cryptococcosis in a 59-year-old man who had received extensive chemotherapy for abdominal malignant lymphoma. Mucinous lesions containing abundant cryptococci, but no inflammatory cells, formed in the posterior choroid of the eye. Electron microscopy revealed that mucin, a filamentous substance, coated the encapsulated organisms. Except for a few degenerating ones in histiocytes, most cryptococci appeared in the extracellular space.


Dermatologic reaction in Stevens-Johnson syndrome after ophthalmic anesthesia with proparacaine hydrochloride.

A 53-year-old woman, treated in the acute phase of Stevens-Johnson syndrome, received one drop of proparacaine hydrochloride 0.5% in each eye for topical anesthesia. One hour later she developed new bullae of the hands and feet.


Mackay-Marg tonometry over therapeutic soft contact lenses.

We evaluated the accuracy of Mackay-Marg electronic applanation tonometry over Bausch and Lomb Plano-T therapeutic soft contact lenses on eye bank, postoperative keratoplasty, and normal eyes. Intraocular pressure (IOP) measurements were compared in the same eye without and with the lens in place. The mean difference of IOP readings through the lens was not statistically different from that without the lens over an IOP range of 10 through 50 mm Hg. We constructed confidence intervals to predict the accuracy of future observations. Results revealed that with 95% confidence, the range of difference between IOP readings without and with the lens in place was from -4.7 to +3.6 mm Hg in eye bank eyes, from -4.3 to +7.4 mm Hg in postoperative penetrating keratoplasty patients, and from -3.5 to +7.4 mm Hg in postoperative lamellar keratoplasty patients, from -3.3 to +2.7 mm Hg in normal eyes. We concluded that IOP can be measured with the Mackay-Marg tonometer through a therapeutic soft contact lens over a corneal graft. Although the readings are not as accurate as without the lens, they are probably adequate as a guide to the necessity of treating increased IOP in postoperative keratoplasty patients.


Clinical implications of aqueous humor studies in uveitis.

We studied the serologic findings in serum and aqueous humor samples from 693 cases of uveitis. Specimens were tested for the presence of humoral antibodies against tuberculosis, toxoplasmosis, antistreptolysin-O, herpes simplex and herpes zoster viruses, mumps virus, and adenovirus. Serologic analyses rarely indicated tuberculous or streptococcal infections, but frequently showed toxoplasmosis and viral diseases.


Prevention of vitreous loss in aphakic keratoplasty.

Controlled aspiration of aqueous before excising the recipient cornea resulted in maintenance of an intact vitreous face during aphakic penetrating corneal transplants in eight of 11 eyes. Vitreous corneal contact or subsequent graft opacification has not occurred in the study group during the observation period.


Clinical trial comparing timolol ophthalmic solution to pilocarpine in open-angle glaucoma.

A ten-week, double-masked, randomized, clinical trial compared timolol ophthalmic solution and pilocarpine in the therapy of open-angle glaucoma. Timolol decreased the intraocular pressure at least as much as pilocarpine and did not induce miosis, accommodative spasm, or other annoying side effects. The pulse was slowed by timolol, but blood pressure was unaffected. Significant decreases in intraocular pressure were still present after ten weeks of maintenance therapy with the same concentration of drug.


A simple technique for removal of recurring granular dystrophy in corneal grafts.

A 63-year-old man and his 24-year-old son developed recurrences of granular dystrophy in their three corneal grafts within three years after surgery. We regrafted one of the son's corneas. Histologic examination of the corneal button removed during surgery showed an avascular connective tissue layer with the histochemical characteristics of granular dystrophy interposed between the epithelium and Bowman's layer. In the remaining two corneal grafts, we fixed the globe with corneal forceps and removed the opaque dystrophic layer by separating it from the cornea with a spatula. Postoperatively, all three corneal grafts were once more transparent.


Intraocular pressure and corneal thickness after penetrating keratoplasty.

We correlated the intraocular pressure readings and measurements of corneal thickness in 71 patients who had had penetrating keratoplasties and found that in the acute post keratoplasty period, increased intraocular pressure caused corneal thinning rather than thickening.


Modifying the pattern of prescribing multiple pairs of glasses.

The New York City Medicaid program uses computerized monitoring techniques as part of its effort to control the quality and utilization of services. The system can identify certain aberrant patterns of practice. For optometric services, one such practice by some providers is the prescribing of separate distance and near eyeglasses in lieu of bifocals. Sending a notification letter to these providers succeeded in modifying the practice. Computerized monitoring and association roles for professionals are discussed.


How environment affects visual development: a selected review.

This selected review covers 60 papers on animal and human studies in which the development of vision, particularly the neural pathways, has been investigated in terms of environmental stimuli or their absence. Most of these studies are summarized in a single table. Emphasis is given to the early treatment of vision deficits.


Calcium fluxes and contractility in isolated guinea pig atrium: effect of A23187.

The Ca2+ ionophore A23187 (10(-6) to 3 X 10(-5) M) increased the force of contraction is isolated guinea pig atria. In individual twitches, peak tension, maximum rate of tension development, time to peak tension, and total twitch duration were all increased by A23187. Tripelennamine, indomethacin, and atropine did not significantly alter the inotropic effect of A23187. Serotonin produced changes in individual twitches that differed qualitatively and quantitatively from those of A23187. Therefore, the inotropic action of A23187 is probably not mediated by release of endogenous histamine, prostaglandins, acetylcholine, or serotonin. 45Ca influx and efflux were increased by A23187. The enhanced 45Ca efflux exceeded that which would be predicted if the ionophore acted only to increase the passive Ca2+ permeability of the myocardial cell membrane. These results suggest that A23187 facilitates the entry of extracellular Ca2+ into the myocardial cell and the release of intracellular Ca2+ stores into the myoplasm. The resultant increase in intracellular Ca2+ activity could account for the positive inotropic action of A23187.


Questions and replies: renal mechanisms for urinary concentrating and diluting processes.

Mechanisms for urinary concentration or dilution depend on counterflow processes, both tubular and vascular, within the renal medulla. Recently, there have emerged differing hypotheses about the renal tubular processes responsible for maintaining a hypertonic medullary interstitium. In this Editorial Review, R.W. Berliner frames three questions germane to this issue, and J.P. Kokko and D.J. Marsh provide their responses to these queries. The major issues addressed are: 1) What are the major unresolved question(s) concerning the mechanism by which concentrated urine is formed? 2) Current evidence suggests that the urea concentration in thin ascending limbs is slightly lower in the lumen than in interstitial fluid. Is the transepithelial concentration gradient between thin ascending limb and renal medullary interstitium sufficient to permit an entirely passive mechanism for diluting tubular fluid in the thin ascending limb? 3) A simple three-compartment model for the renal medullary concentrating process would include the tubular lumen, peritubular capillary, and the interstitium. Is it possible to generate a model that, by juxtaposing medullary structures, might explain renal medullary counterflow processes more adequately than the simple three-compartment model?


Redistribution of blood flow in acute hypometabolic behavior.

Cardiac output, renal and hepatic blood flows, arterial lactate concentration, and minute volume were measured before, during, and after 40 min of rest induced either by the practice known as "transcendental meditation" (TM) or by an ordinary eyes-closed rest-relaxation period. Two groups of normal young adults were studied: one group consisted of regular practitioners of TM and the other of similar individuals studied prior to learning this technique. Marked declines of renal blood flow were noted in both groups. Decline of hepatic blood flow, increased cardiac output, decreased arterial lactate, and minute volume were also recorded in the TM-induced rest period. These changes imply a considerable increase of nonrenal, nonhepatic blood flow during TM (44%) and, to a lesser extent, during rest (12%). Increased cerebral and/or skin blood flow is hypothesized to account for part of the redistributed blood flow in the practitioner.


Field evaluation of primaquine in the control of Plasmodium vivax.

Two regimens of primaquine in combination with amodiaquine have been compared with amodiaquine alone in known cases of Plasmodium vivax in an endemic area of El Salvador, C.A. A 5-day regimen of primaquine, with dosages based on an adult dose of 15 mg per day, produced a substantial reduction in the numbers of patients experiencing renewed parasite activity and in the number of parasitemias experienced by the group during 9 mo of posttreatment observation, when compared with patients treated only with amodiaquine. A single dose regimen, based on an adult dose of 45 mg, similarly reduced the number of patients with renewed parasite activity and the number of parasitemias in the group. Those patients who experienced malaria attacks subsequent to treatment with either primaquine regimen experienced fewer such attacks than did those receiving amodiaquine alone. It is concluded that such primaquine regimens, which are more practicable for field use than the full 14-days curative regimen, are of value to both the patient and the community through the reduction of parasite episodes and the reduction of the source of mosquito infection for continuation of transmission.


Biochemical characterization of some species of Trypansoma (Schizotrypanum) from bats (Microchiroptera).

Trypanosoma (Schizotryanum) species isolated from bats (Microchirotera) in Europe and Latin America were examined by determining the buoyant densities of their nuclear and kinetoplastic deoxyribonucleic acid (DNA) and the electrophoretic patterns of six isoenzymes. By these criteria they were separated into three distinct groups -- two from Europe (T. dionisii and T. vespertilionis) and one from America. T. dionisii was also separable by its morphology in vitro. Geographical location and DNA buoyant densities suggested that the American stocks were more closely related to T. cruzi than to the European species, though they differed from it marginally in kinetoplastic DNA density and in being noninfective to mice. Similar stocks studied by other workers have been shown to differ from T. cruzi also in reduced infectivity to, and lack of natural association with, Triatominae, and in antigenic composition. It is therefore proposed that trypanosomes of the subgenus Schizotryanum occuring naturally in Microchiroptera and differing from T. cruzi sensu stricto as outlined above should be treated as a distinct subspecies, T. cruzi marinkellei ssp. nov. T. cruzi sensu stricto thus becomes the nominate subspecies T. cruzi cruze Chagas 1909.


Serological diagnosis of bancroftian and malayan filariasis.

A study was undertaken to define the sensitivity and specificity of serological tests in bancroftian and malayan filariasis and correlate the findings with clinical disease. Sera were collected from subjects on three different islands in the Philippines: one endemic for bancroftian filariasis, another endemic for malayan filariasis and the third without endemic filariasis. Antibodies were measured, using rugia malayi as the source of antigen. Antibodies against adult worms measured by indirect immunofluorescence were found at a titer of 1:8 or greater in all patients with bancroftian or malayan filariasis but not in the control subjects. There was no relationship of antibody titer to clinical status. Antibodies against microfilariae were measured by indirect immunofluorescence and microfilarial agglutination. A high correlation was observed between the two methods. These antibodies were found in only one quarter, approximately, of patients with filariasis. Microfilarial antibodies were found more commonly in those patients with chronic lymphatic obstruction. It is concluded that measurement of antibodies to adult worms is a useful indicator of infection while microfilarial antibodies are correlated with disease.


Animal salmonellosis in peninsular Malaysia. II. Annual and zoological distribution of Salmonella serotypes over the 10-year period 1966-1975.

A total of 860 Salmonella isolations were made in Peninsular Malaysia from 15 animal species (domestic and wild), eggs, molluscs, flies, and animal feed. The isolations were distributed among 31 serotypes in eight groups. The most common serotype isolated was Salmonella pullorum, followed by S. choleraesuis and S. infantis. S. typhimurium had the widest zoological distribution. The importance of controlling animal salmonellosis is emphasized.


Safety of colostomy closure.

A retrospective study of colostomy closures was prompted by recent reports detailing frequent postoperative complications. In a series of 125 intraperitoneal colostomy closures there was a low incidence of complications. There were no anastomotic breakdowns, fistulas, or deaths. We conclude that closure of a well healed colostomy is a safe operation, the success of which is determined by the careful technic with which it is performed.


Ultrastructural localization of anaplasmal antigens (Pawhuska isolate) with ferritin-conjugated antibody.

Antibodies from a cow with an experimentally induced infection of the Pawhuska isolate of bovine anaplasmosis were conjugated with ferritin and used to label antigenic sites in preparations of parasitized erythrocytes. Intact erythrocytes did not label on the extracellular surface. Ferritin-conjugated antibody did not pass through the intact erythrocyte to label the parasite, probably due to the large molecular size of the antibody. Damage to erythrocytic plasmalemma and inclusion body in the hemolyzed erythrocytes and complement-fixation antigen allowed labeling of anaplasmal inclusion structures. The positively labeled structures were outer surface of the pellicle, chromatin of the initial body, and inclusion appendage. Unlabeled structures included inner organismic membrane of the initial body, inclusion membrane, fibrillar protoplasmic network of the initial body, and small electron-dense bodies derived from the initial body.


Mycobacteria isolated from nasal secretions of tuberculin test reactor cattle.

Nasal secretions of 103 Holstein cows from a tuberculosis-infected herd in Argentina were bacteriologically cultured for mycobacteria. Mycobacterium bovis was isolated in 8.7% of the cultures. This method was useful for the detection of active tuberculosis with open lesions. Other mycobacteria, most of which grew rapidly on culture media, were isolated in 32% of the cultures and were of little importance as sensitizing agents to mammalian tuberculin in experimental studies in guinea pigs.


Phage typing of mycobacteria using paper discs.

The suitability of phage-impregnated paper discs for the phage typing of mycobacteria was studied. The relevance of the routine test dilution, the volume of the phage used, the mode of incubation, and the effect of prolonged storage of phage-impregnated paper discs were considered. By using paper discs, each impregnated with one of 5 different mycobacteriophages (BG1, BK1, G37, CRI-3 and LG) that lyse Mycobacterium smegmatis 607B, it was determined that 100 x the routine test dilution in a volume of at least 20 microliter was required for phage lysis. Soaked and dried paper discs produced larger areas of lysis than those with 20-microliter volumes. Soaked discs were found to be stable even after storage for 8 weeks at 4 degrees C.


Central hypoventilation syndrome: experience with bilateral phrenic nerve pacing in 3 neonates.

Successful long-term phrenic nerve pacing has been reported in adults with acquired central hypoventilation syndrome. This report summarizes our experience with phrenic nerve pacing in 3 infants with congenital central hypoventilation syndrome. The electrodes were implanted in the lower thoracic portion of each phrenic nerve. In all patients. bilateral simultaneous pacing was required to maintain an adequate arterial PO2, tidal volume, and minute ventilation during quiet sleep. Case 1 died of problems primarily related to the severe cor pulmonale that had been present before pacemaker insertion; at autopsy, the pacemaker system was intact and there were no significant phrenic nerve abnormalities. Case 2 later developed failure of awake ventilatory control and died because of extensive phrenic nerve damage incurred by 19 days of continuous pacing. Case 3 has received quiet sleep pacemaker support since September 1977 and has been able to maintain normal quiet sleep ventilation in this manner. Phrenic nerve pacing can be successful in infants as long as continuous pacing is not required. Bilateral simultaneous pacing appears to be an appropriate alternative to home-based intermittent positive-pressure breathing for long-term management of children with central hypoventilation syndrome.


Pathogenesis of respiratory syncytial virus infection in ferret and fetal human tracheas in organ culture.

The pathogenesis of human respiratory syncytial virus infection was studied in ferret and fetal human tracheas in organ culture. Although the patterns of virus growth were similar in these species, the sites and morphologic consequences of virus replication differed markedly. In human trachea, synthesis of respiratory syncytial virus occurred in a population of ciliated epithelial cells, whereas other cells in the epithelial layer were spared. Virus replication was associated with cell injury characterized by ballooning degeneration and syncytium formation. In ferret trachea, virus growth occurred in fibroblasts of the lamina propria and serosa. Ciliated epithelial cells did not contain viral antigen and remained histologically normal. These observations are relevant to understanding the pathogenesis of human disease and the evaluation of animal models of respiratory syncytial virus bronchiolitis.


Pumonary aspergillosis during hospital renovation.

During a 4-week period, Aspergillus fumigatus caused disease in 2 patients and colonized a third patient in a renal transplant ward. Our investigation indicated that increased exposure of these patients to spores probably occurred during renovation of the ward one floor above it. Cases were significantly clustered (P = 0.014) during the period when work overhead caused dust to filter down through pores in the acoustical tiles of the false ceiling of the renal transplant ward. Swab cultures demonstrated A. fumigatus in the dust, and air samples showed heavy contamination with A. fumigatus and other fungi at and below a renovation site, but not on 2 distant wards. We concluded that dust can be an important source of aspergilli and that release of dust and spores during activities such as renovation may increase the risk of nosocomial Aspergillus infection in exposed, immunosuppressed patients.


Stainless steel wire for closure of abdominal operative wounds.

In this prospective study, the abdominal wounds of 500 consecutive patients were closed with buried retention monofilament stainless steel wire. The strength of the suture material, the rapidity of the closure, the very low 0.4% dehiscence rate and the almost total lack of wound complications seems to override the relatively minor inconvenience of handling the wire. These results seem to justify the rountine use of this method of wound closure in abdominal surgery, especially in the elderly and high-risk patients.


An appraisal of tests for native DNA antibodies in connective tissue diseases. Clinical usefulness of Crithidia luciliae assay.

Antibody to native DNA was measured by five techniques: the Crithidia luciliae immunofluorescence (CL-IF) test; filter radioimmunoassays using either untreated human KB DNA, endonuclease-treated KB DNA, or a synthetic polynucleotide (poly dAT); and the Farr immunoprecipitation assay using KB DNA. The specificity and sensitivity of the CL-IF assay was similar to that of the filter radioimmunoassay procedures using KB DNA. The CL-IF test showed an increased frequency of positive tests in patients with active disease and severe renal involvement. In patients with severe renal involvement, high titers of serum nDNA antibodies were measured by this procedure. A unique advantage of the CL-IF test was its ability to identify complement-fixing nDNA antibody. The presence of such antibody was correlated with high antibody titer and the presence of severe renal disease. The CL-IF assay is a simple and useful procedure for measurement of anti-nDNA.


Use, costs, and quality of medical services: impact of the New Mexico peer review system. A 1971-1975 study.

To assess the effect of areawide peer review (such as that conducted by Professional Standards Review Organizations [PSROs]) on use, cost and quality of medical services, we evaluated 4 years of data on the efforts of the New Mexico Experimental Medical Care Review Organization in reviewing medical services for the Medicaid population. Utilization review had no demonstrable impact on hospital use; hospital days per 100 eligible persons rose 5.0% and 43.4% for persons enrolled all 4 years in Aid to Families with Dependent Children (AFDC) and Aid to the Permanently and Totally Disabled, respectively. Peer review produced no net dollar savings; over 4 years, the amount paid for all services per AFDC-eligible person rose 85%. Peer review improved the quality of ambulatory care through large reductions (75%) in medically unnecessary injections. If these findings are replicated elsewhere, they suggest that the goal of the PSRO program to control costs by curtailing utilization may be difficult to achieve, the quality of care goal may be pursued successfully, and the PSRO mission should be focused more on the latter.


A Marxist view of medical care.

Marxist studies of medical care emphasize political power and economic dominance in capitalist society. Although historically the Marxist paradigm went into eclipse during the early twentieth century, the field has developed rapidly during recent years. The health system mirrors the society's class structure through control over health institutions, stratification of health workers, and limited occupational mobility into health professions. Monopoly capital is manifest in the growth of medical centers, financial penetration by large corporations, and the "medical-industrial complex." Health policy recommendations reflect different interest groups' political and economic goals. The state's intervention in health care generally protects the capitalist economic system and the private sector. Medical ideology helps maintain class structure and patterns of domination. Comparative international research analyzes the effects of imperialism, changes under socialism, and contradictions of health reform in capitalist societies. Historical materialist epidemiology focuses on economic cycles, social stress, illness-generating conditions of work, and sexism. Health praxis, the disciplined uniting of study and action, involves advocacy of "nonreformist reforms" and concrete types of political struggle.


Trephination of donor corneal buttons: a scanning electron microscopic study.

Corneal buttons were cut from cat and human donor eyes by anterior trephination (with or without scissor completion) and from excised corneoscleral rims by posterior trephination (with or without a press). Scanning electron microscopy was used to evaluate the slope and quality of the cut edge, the diameter of the section of Descemet's membrane that was actually cut, and the loss of endothelial cells around the cut edge. With anterior trephination, the diameter of the section of Descemet's membrane that is cut was found to be less than that of the trephine because the cut edge slopes inward. Posterior trephination with or without a press consistently produced circular buttons with accurately cut outward-sloping edges. This resulted in a diameter of Descemet's membrane which was greater than in the anteriorly trephinated buttons. There also was less damage to peripheral Descemet's membrane and endothelium with the posterior method, especially when compared to scissor cut buttons. A 360 degree peripheral ring of Descemet's membrnae (0.05 to 0.28 mm in width) was denuded of endothelial cells with all techniques.


Cataract extraction without a conjunctival flap.

Wound healing in 350 cases of senile cataract extraction done with a corneal incision without a conjunctival flap and closed with 3 deep 6-0 chromic gut sutures is examined. There were no cases of epithelial downgrowth and a low incidence of conjunctival blebs. There was one case of endothalmitis and 4 of iris prolapse. Sutures fell out between the 9th and 16th days and the large knots did not cause excessive irritation while in place. There was an 18% incidence of wound leak manifested by shallow or flat anterior chamber. All of these anterior chambers reformed spontaneously soon after the sutures fell out, indicating the wound leak was probably along the sutures tract. One patient with wound leak developed mild glaucoma postoperatively. Wound healing after cataract surgery is discussed. Epithelial downgrowth and conjunctival blebs are related more to tight silk sutures than absence of conjunctival flap. The early loss of the gut sutures does not decrease wound strength since the sutures have already lost their tensile strength. The epithelium which grows into the cataract wound postoperatively when a flap is not used activates stromal fibrocytes and covers any delayed iris prolapse.


Fate of endothelium in a corneal graft.

An 81-year-old white man with bullous keratopathy received a corneal graft from a 13-month-old donor. The postoperative course has been uneventful. The endothelium of the donor cornea was studied on specular microscopy both before grafting and up to 9 months after surgery. There has been no change in the morphologic characteristics of the corneal endothelium nor has there been any decrease in cell density. The donor endothelium seems to persist for at least 9 months unchanged. This case provides a good illustration since it is not too often that a cornea from a 13-month-old donor is used for grafting in an 81-year-old individual. This experience also gives an indication of the value of specular microscopy as a very useful method to monitor the changes in the endothelium of a corneal graft.


Ultrastructure of the cell wall of Candida albicans blastospores: study of its constitutive layers by the use of a cytochemical technique revealing polysaccharides.

Cytochemical detection of polysaccharides, using the Thiéry method (PATAg) for the ultrastructural localization of periodic acid-engendered carbohydrate macromolecules, suggests eight constitutive layers in the cell wall of the blastospore of C. albicans. Each layer has been assigned a probable chemical composition according to its reactivity at the ultrastructural level. These results are discussed with respect to previous work in the field and to our present knowledge of fungal physiology.


Early visual rehabilitation after keratoplasty: a double running suture technique.

A series of keratoplasties was performed using 2 running nylon sutures of unequal size, 23 micrometer (10-0) and 16 micrometer. Visual acuities were assessed within 6 months of surgery and following removal of the 10-0 suture at 2 months. Thirty percent of aphakic and 80% of phakic had acuities of 20/70 or better.


[Immunology of human warts (author's transl)].

Specific immune reactions in man subsequent to infection by wart virus have been the subject of various studies. Most concern humoral immunity and show an antibody distribution which rises with age comparable to the viral exanthems of childhood with a maximum at 20 years and show decline thereafter. The acquisition of antibody is prolonged and sometimes irregular and its role in wart healing is questionable. The most recent work on cellular immunity has demonstrated profound abnormalities in cases of profuse verrucosis and in epidermodysplasia verruciformis, increased incidence of warts in immunodeficient states and the existence of specific reactions to viral antigen both in vitro and in vivo. Such results indicate and predominant role for cellular immunity in the evolution of this viral infection and suggest the possibility of specific immunotherapy. Very recent studies of biochemical identification of purified virus particles of various clinical types of wart show viral heterogeneity. This fact implies the need to reexamine these immune reactions in the light of the existence of crossed serological reactivity and specific wart treatment.


[Adult Letterer-Siwe's disease. Review of literature (author's transl)].

Letterer-Siwe syndrome is usually encountered in children. It very rarely occurs in adults. 23 cases are found in the literature and analyzed: clinical signs are the same as in infantile observations. Prognosis in some cases is surprisingly very good when only the skin is involved.


Antineoplastic-drug effect evaluated with a new X-ray stereophotographic measurement of the tumour volume.

A method for determination and follow up of the size of inoperable intraabdominal tumours has been devised. At laparotomy, tantalum balls are deposited into the capsule of the tumour. An X-ray stereophotogrammetric method determines their position, which define a polyhedron whose volume can be computer calculated. The value of the method was proved in four patients with inoperable ovarian carcinoma, which provides a simple way for the continuous follow up of the effect of antineoplastic therapy in advanced malignant tumours.


Effect of anaesthesia and surgery on the number of and mitogen-induced transformation of T- and B-lymphocytes.

Lymphocyte responses are affected by anaesthesia and surgery. 52 patients were studied to ascertain the affect on lymphocytic responses of thiopentone +N2O +O2, combined, diethyl ether +N2O +O2, and local anaesthesia in connection with surgery. The variables followed were: the leucocyte and differential count, the T- and B-lymphocyte count, and lymphocyte transformation by phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and purified protein derivative of tuberculin (PPD) in cultures using separated lymphocytes and whole blood. Thiopentone +N2O +O2 anaesthesia together with uterine curettage caused a decrease in the total lymphocyte and T-lymphocyte counts. The Con A response of separated lymphocytes decreased, but the response to other mitogens increased. Combined anaesthesia with thiopentone +N2O +O2 + analgesic + muscle relaxant together with surgery decreased the total lymphocyte and T-lymphocyte counts. The separated lymphocytic and whole blood cultures revealed throughout a decrease in the mitogen and PPD responses. Diethyl ether +N2O +O2 and local anaesthesia, both together with surgery, produced no statistically significant changes in the total lymphocyte or in the T- and B-lymphocyte counts. The mitogen and PPD responses in these groups showed throughout a fall in lymphocyte transformation. Neither patient's age, sex, nor the duration of the anaesthesia or operation affected the magnitude of the changes. The increase in the leucocyte count and in the percentage of neutrophils and the decrease in the percentage of eosinophils and lymphocytes and in the mitogen- and PPD-induced lymphocytic responses increased with the severity of the operative trauma. A new finding was the correlation observed between the changes in the leucocyte and differential counts and the decrease of lymphocytic responses in whole blood culture. The findings in this study indicate that operative trauma determine the decrease in lymphocytic responses associated with anaesthesia and surgery.


Double-blind study of carbenoxolone in gastric ulcer and erosions.

The effect of carbenoxolone on the healing of gastric ulcer and erosions was compared with that of placebo. The series consisted of 20 patients with chronic gastric ulcers and 20 patients with superficial erosions of the stomach. The diagnosis as well as the follow-up of the lesions were based on gastroscopic examinations. The ulcers were measured gastroscopically. A double-blind method was used. Besides carbenoxolone 50 mg or placebo three times daily, all the patients received antacids in fixed dosage for six weeks. Subjective symptoms and cardiovascular side-effects were recorded. Maximal acid output and serum gastrin levels were measured before and after the treatment. No difference was seen between carbenoxolone and placebo groups with regard to the healing rate of the ulcers of disappearance of the erosions. The subjective symptoms subsided significantly faster in the treatment groups than in the control groups. No cardiovascular side-effects were evident during the treatment with carbenoxolone. One patient needed potassium supplements. Carbenoxolone had no effect on the pentagastrin-stimulated gastric acid secretion nor on the serum gastrin values.


A comparative study of carticaine and prilocaine in epidural anaesthesia.

Carticaine and prilocaine (without adrenaline) in epidural anaesthesia were compared in a double blind study. Carticaine and prilocaine were used in 2 % concentration without adrenaline. The latency time was not significantly different, but carticaine was a shorter acting local anaesthetic. The motor block in both series was similar. Carticaine is a good and reliable analgesic in short operations but in operations longer than one and a half hours catheter technique, adrenaline addition or local anaesthetics of longer duration ought to be used.


The macrophage electrophoretic mobility (MEM) test--an investigation of its value as a routine laboratory test in the detection of malignant disease.

A previous study of the MOD-MEM test showed promising results. We have attempted to repeat the study using a blind coded series of 210 blood samples from normal subjects and patients with either benign or malignant disease. Using standard criteria the false negative rate for cancer patients averaged 43% and the false positive rate for non-cancer patients averaged 34%. The results indicate that the test at the present time, under routine laboratory conditions, is not reliably reproducible and does not have the ability to effectively discriminate between benign and malignant disease. It is suggested that blind coded studies be used more frequently in assessment of tests with cancer detection potential.


The efficacy of oral theophylline and the combination of theophylline + hydroxyzine in chronic bronchial asthma.

The efficacy of 265 mg theophylline (150 mg of the theophylline being slow-release) and the combination of 265 mg theophylline + 7.5 mg hydroxyzine hydrochloride were compared in a double-blind cross-over placebo-controlled study in 12 patients with chronic reversible bronchial asthma. The patients took their drugs at 7.00 a.m., 1.00 p.m. and 7.00 p.m. During the trial the patients measured their peak expiratory flow (PEF) every day at 7.00 a.m., 10.00 a.m. and 9.30 p.m. The frequency and severity of symptoms and side-effects as well as the auxiliary use of isoprenaline inhalations were also recorded. The trial involved three three-day periods. Both oral theophylline and the combination of theophylline + hydroxyzine caused significant improvements in PEF in all measurement times. The PEF-level was higher when the combination was used than with plain theophylline, though the difference was not significant. Only the combination of theophylline + hydroxyzine had a significant effect on the symptoms, and the use of additional isoprenaline inhalations was also reduced during the combination period. Side-effects were minimal. Circadian variation of bronchial obstruction was seen in all these patients.


[Relationship between dose of injected serum albumin and appearance of cells synthesizing immunoglobulins or antibodies].

Mice were given increasing doses of sheep serum albumin emulsified with Freund's complete adjuvant in hind footpads. The kinetics of development of cells which synthesize antibody or immunoglobulins without antibody function was studied in the draining lymph nodes. Results show the relationship between the two cell populations: as the number of antibody synthesizing cells increased, the number of immunoglobulin synthesizing cell increased, and conversely. Between 0.050 and 2.5 mg of antigen, the number of cells of each population increased with the dose injected whereas with 5 and 10 mg, this number is smaller than that obtained with smaller doses and decreased with an increasing dose.


Treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm with tranexamic acid: a double-blind clinical trial.

A double-blind clinical trial of tranexamic acid was carried out on 39 patients with fresh subarachnoid hemorrhage from a ruptured aneurysm. Twenty patients received tranexamic acid, 6 gm daily for 14 to 21 days, while 19 patients received conventional therapy of bedrest and dexamethasone when cerebral edema developed, plus isotonic saline. Rebleeding and mortality were reduced by one-fourth and one-fifth, respectively (p less than 0.001). No side-effects were observed. Tranexamic acid is valuable in the treatment of subarachnoid hemorrhage caused by ruptured intracranial aneurysms.


The isolation of thirteen cloned hybrid cell lines secreting mouse strain A derived antibodies with specificity for group A streptococcal carbohydrate.

Thirteen hybrid cell lines originating from the fusion of a BALB/c myeloma with strain A spleen cells were isolated each of which secreted an antibody with specificity for the carbohydrate of group A streptococci. The cell lines were stable over many in vivo passages in (BALB/c X A/J)F1 mice and secreted large amounts of antibodies into the serum and ascitic fluid of their hosts. Seven of the hybrid cell antibodies belonged to the IgM class, five were typed as IgG2a and one as an IgA immunoglobulin.


Transplantation immunology 1957-1975.

Knowledge of the transplantation immunity has increased rapidly in the past twenty years. The rejection of allograft is now known to involve the interaction of several subsets of lymphocytes, as well as humoral immunity. Efforts to suppress immunity to the allograft are effective but suppress other kinds of immunity also, thus rendering the recipient susceptible to opportunistic infections. Two approaches to modification of the immune response by impairing the ability of cells sensitized specifically against allograft antigen to kill such cells are described. These agents can and have been used therapeutically in humans for other reasons and have been shown in the laboratory to actually markedly prolong the life of renal allograft, without impairing the immune response to other antigens.


[Sensitivity of beta-hemolytic streptococci to antibiotics].

Susceptibility of 64 beta-hemolytic streptococcal strains isolated from the patients with sore throat was studied by the method of serial dilutions in fluid nutrient medium (Konikov broth). Heterogenecity with respect to the sensitivity was investigated in 34 strains among separate populations of the microbes (10 to 15 in every strain). The MIC of benzylpenicillin, oxacillin and erythromycin ranged within 0.007--0.24 U/ml, 0.02--0.36 gamma/ml and 0.005--0.1 gamma/ml respectively. The MIC of benzylpenicillin with respect to separate populations most sensitive to it was 0.007--0.015 U/ml, while that with respect to the lease sensitive populations ranged from 0.015 to 0.24 U/ml. The respective values for oxacillin were 0.02--0.12 and 0.18--0.36 gamma/ml and those for erythromycin were 0.005--0.025 and 0.05--0.1 gamma/ml. Therefore, the beta-hemolytic streptococci isolated from the patients with sore throat were characterized by a rather high sensitivity to the antibiotics which was important precondition for their efficiency in treatment of the patients with the above disease.


[Kanamycin films for ulcerative lesions of the cornea].

The kanamycin films were used once for the treatment of 28 patients with the cornea ulcers. The positive effect was registered in 20 patients. Eight patients were treated with the films and the antibiotic acqueous solution. The best results were observed in the patients with affection of the surface layers of the cornea. The positive therapeutic results were registered in 20 patients after operations in connection with cataracta and glaucoma when treated with the films containing kanamycin and dexametazon.


[Effect of terrilytin on antifungal antibiotic activity].

The antifungal activity of terrilitine, an enzymatic preparation of microbial origin and its effect on the activity of antifungal polyenic antibiotics and griseofulvine were studied in vitro. It was found with the method of serial dilutions in Sabourand's liquid medium that terrilitine was active against C. albicans and certain dermatophytes. In combination with amphotericin B, amphoglucamine, mycoheptine, levorin, nystatin or griseofulvin it increased the activity of these antibiotics 2-16 times.


[Treatment of dysentery in children with a combination of monomycin and Eleutherococcus].

An acute dysentery process was studied in 100 children at the age of 1 to 14 years treated with monomycin; 54 patients (the 1st group) were treated with monomycin in combination with eleuterococcus and 46 patients (the 2nd group) were treated with monomycin alone. The dysentery process in the both groups was close. However, the increase in the levels of gamma-globulin, antidysentery antibodies and the phases of changes in the index of phagocytosis completeness during the disease were more pronounced in the patients of the 2nd group than those in the children of the 1st group. Recovery of the patients of the 1st group was registered earlier. It was concluded that eleuterococcus as an adaptagen provided recovery of the patients at lower efforts of the protection mechanisms. Wide use of eleuterococcus in combination with monomycin for the treatment of children with dysentery is recommended.


[Clinical and laboratory comparisons of tetracycline penetration through the blood-cerebrospinal fluid barrier in central nervous system diseases].

The data on tetracycline penetration from the blood into the serebrospinal fluid of patients with different diseases of the central nervous system are presented. Clinico-laboratory comparisons showed that the antibiotic penetration did not depend on the character and severity of the main disease of the brain (tumor, trauma, abscess). No dependence on the surgical intervention was either found. The index of tetracycline penetration from the blood into the liquor did not depend on the drug administration route, i.e. intramuscularly or orally. The presence of the post-operative meningitis increased permeability of the brain membranes for tetracycline.


Cofactor role of iodide in peroxidase antimicrobial action against Escherichia coli.

The mechanism of antimicrobial activity of the peroxidase-hydrogen peroxide (H(2)O(2))-iodide (I(-)) system was investigated. Inhibition of respiration and loss of viability of Escherichia coli were used as measures of antimicrobial activity. Because the bacteria destroyed H(2)O(2), peroxidase antimicrobial action depended on the competition for H(2)O(2) between the bacteria and the peroxidase. Utilization of H(2)O(2) by the peroxidase was favored by (i) increasing either the peroxidase or the I(-) concentration, so as to increase the rate of oxidation of I(-), (ii) lowering the temperature to lower the rate of destruction of H(2)O(2) by the bacteria, and (iii) adding H(2)O(2) in small increments so as to avoid a large excess of H(2)O(2) relative to I(-). When utilization of H(2)O(2) by the peroxidase system was favored, the peroxidase system and iodine (I(2)) were equivalent. That is, antimicrobial action per mole of H(2)O(2) equaled that per mole of I(2). Also, identical antimicrobial action was obtained either by incubating the bacteria directly with the peroxidase system or by preincubating the peroxidase system so as to form I(2) and then adding the bacteria. On the other hand, peroxidase antimicrobial action could be obtained at low I(-) concentrations. These I(-) concentrations were lower than the concentration of I(2) that was required for antimicrobial action. It is proposed that peroxidase-catalyzed oxidation of I(-) yields I(2), which reacts with bacterial components to yield the oxidized components and I(-). The I(-) that is released can be reoxidized and participate again in the oxidation of bacterial components. In this way, I(-) acts as a cofactor in the peroxidase-catalyzed oxidation of bacterial components.


Oxidation of Escherichia coli sulfhydryl components by the peroxidase-hydrogen peroxide-iodide antimicrobial system.

The chemical modification of bacterial components was studied following incubation of Escherichia coli with the peroxidase-hydrogen peroxide (H(2)O(2))-iodide (I(-)) antimicrobial system or with iodine (I(2)). The oxidation of cell sulfhydryls and the iodination of cell components were measured. Both the peroxidase system and I(2) oxidized sulfhydryls. When the I(-) concentration in the peroxidase system was greater than 100 muM, the peroxidase system and I(2) were equivalent. That is, sulfhydryl oxidation or killing per mole of H(2)O(2) equaled that per mole of I(2). These results were consistent with peroxidase-catalyzed oxidation of I(-) to yield 1 mol of I(2) per mol of H(2)O(2). Sulfhydryls were oxidized to yield sulfenic acids and free I(-). With I(-) concentrations in the range of 10 to 100 muM, the amount of sulfhydryls oxidized by the peroxidase system could exceed the amount of I(-). Because the oxidation of sulfhydryls to sulfenic acids did not consume I(-), one I(-) ion could participate in the oxidation of many sulfhydryls. With I(-) concentrations lower than 10 muM, complete oxidation of sulfhydryls was not obtained. Incorporation of I(-) into iodinated derivatives of bacterial components partly depleted the system of I(-) and limited the formation of I(2). These results indicated that antimicrobial activity was due to peroxidase-catalyzed oxidation of I(-) to I(2), followed by I(2) oxidation of cell components. There was a direct relationship between sulfhydryl oxidation and antimicrobial action. Although iodination of bacterial components accompanied sulfhydryl oxidation, the amount of I(-) incorporation was not directly related to antimicrobial action. Also, incorporation of I(-) interfered with antimicrobial action at low I(-) concentrations.


Microbial degradation of cephalothin by cephalothin-susceptible Escherichia coli.

Cephalothin (CET)-susceptible Escherichia coli, which can degrade CET after prolonged incubation in broth containing a concentration of the drug greater than the minimum inhibitory concentration, was found in a clinical specimen. The substrate specificity of the partially purified enzyme to cephalosporin analogs strongly indicated the occurrence of CET-specific degradation. Nuclear magnetic resonance analysis of the degradation reaction demonstrated the appearance of two new signals attributed to deacetyl CET. This suggests the possibility of the presence of acylesterase.


Susceptibility of Canadida albicans to miconazole.

A total of 439 clinical isolates of Candida albicans were tested for susceptibility to miconazole by the agar dilution technique. When tests were read at 48 and 24 h, 56 and 84%, respectively, of the strains were completely inhibited by 4.0 mug of miconazole per ml, the estimated upper limit of probable clinical susceptibility.


Comparison of netilmicin with gentamicin in the therapy of experimental Escherichia coli meningitis.

Netilmicin (SCH 20569), a new broad-spectrum aminoglycoside derived from sisomicin, was compared with gentamicin in the therapy of experimental Escherichia coli meningitis in rabbits. Meningitis was produced in 48 animals by the intracisternal inoculation of 10(5)E. coli colony-forming units. The minimum bactericidal concentration was 2 mug/ml against the test strain for both gentamicin and netilmicin. The two aminoglycosides demonstrated comparable penetration into the cerebrospinal fluid (CSF). The mean percent penetration [(CSF concentration/serum concentration) x 100%] was 22.5 +/- 6.0 and 20.6 +/- 7.2 for netilmicin and gentamicin, respectively (P = 0.18). However, netilmicin achieved bactericidal activity in the CSF at lower levels than did gentamicin. When mean CSF concentrations ranged from 4 to 8 mug/ml, mean CSF bacterial titers decreased 2.98 logs in rabbits treated with netilmicin but only 0.16 log in rabbits treated with gentamicin. A 2-log decrease in CSF bacterial counts was produced by a mean CSF concentration of 1.4 mug of netilmicin per ml as compared to 14.1 mug of gentamicin per ml. Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer an advantage over gentamicin in the therapy of gram-negative bacillary meningitis.


Comparative susceptibility of four kinds of pathogenic fungi to amphotericin B and amphotericin B methyl ester.

The activity of amphotericin B methyl ester was compared with that of amphotericin B, using Candida albicans (34 isolates), Torulopsis glabrata (12 isolates), Filobasidiella neoformans (stat. conid. Cryptococcus neoformans) (14 isolates), and Coccidioides immitis (37 isolates) and tube dilution in a totally synthetic, completely defined medium (SAAMF) with inocula of 10(4) colony-forming units per ml. Minimal inhibitory concentrations were read after 24 h at 34 degrees C for C. albicans and T. glabrata, and after 48 h at 34 degrees C for C. immitis and F. neoformans. Minimal lethal concentrations were determined by subculture of 10% of the volume of the cultures without evident growth onto Sabouraud glucose agar medium. Overall, amphotericin B methyl ester was slightly less active than amphotericin B, with the differences attaining statistical significance for: (i) inhibition of C. albicans and T. glabrata and (ii) killing of T. glabrata.


Dissociation between ion permeability and the lethal action of polyene antibiotics on Candida albicans.

Kinetic data on potassium release from and killing of Candida albicans by the four polyene antibiotics amphotericin B, amphotericin B methyl ester hydrochloride, nystatin, and nystatin methyl ester hydrochloride are presented. The nystatins were relatively more effective than the amphotericins in causing potassium release rather than killing. These data suggest that the aqueous channels or pores formed by the polyene antibiotics are not central to the lethal action of the drugs.


Comparison of cephalothin and cefamandole prophylaxis during insertion of prosthetic heart valves.

Cefamandole nafate (CM) and cephalothin sodium (CP) were administered as prophylaxis in a randomized, prospective study to 30 consecutive patients undergoing prosthetic cardiac valve insertion. A single dose of 20 mg/kg was given intramuscularly during anesthesia induction, and serial plasma antibiotic concentrations, atrial muscle and cardiac valve tissue antibiotic levels, plasma bactericidal activity against pathogenic staphylococci, and infectious complications were determined and compared for the two drugs. Both antibiotics produced high plasma levels (>20 mug/ml 30 min after injection) which fell less than 25% during the period of cardiopulmonary bypass. However, CM levels were significantly higher at most time periods (P<0.05) than CP levels. CP levels were undetectable in atrial muscle from 14 of 15 patients and in valves from 10 of 15 patients. In contrast, CM bioactivity was found in all tissues. Differences in tissue antibiotic concentration could not be accounted for by differences in plasma concentrations or by CP tissue binding and were assumed to be caused by differences in penetration. Plasma bactericidal activity against staphylococci was equal for the two drugs (median titer, 1:16). No infections were seen in either group. CM appeared to be an effective and perhaps preferable prophylactic antibiotic for use during cardiac surgery.


Effect of an interferon inducer, 9-methylstreptimidone, on Candida albicans infection in mice.

The protective effect of an interferon inducer with a low molecular weight, 9-methylstreptimidone (9-MS), against Candida albicans infection in mice was investigated. The antibiotic was effective only when given prophylactically. When administered in such a manner, the growth of C. albicans in the kidneys and brain was inhibited at the initial stage of infection. The growth of C. albicans was not inhibited by the antibiotic in vitro, and no antifungal effect was obtained in a preparation containing induced interferon. These results suggest that the antifungal action of 9-methylstreptimidone in mice might be manifested not by direct antifungal activity but rather by a host-mediated activity that excludes interferon-inducing capability.


Therapeutic failures with miconazole.

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 mug or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 mug/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis.


Comparison of the toxicities of patulin and patulin adducts formed with cysteine.

The toxicities of patulin and of the patulin adducts formed with cysteine were compared using the mutation-sensitive strain Escherichia coli W3110 thy polA1 and its polA1+ revertant. The acute toxicities of patulin and of the adduct mixture were also compared using NMRI mice. The adduct mixture was shown by thin-layer chromatography to consist of one ninhydrin-positive, one ninhydrin- and MBTH (3-methyl-2-benzothiazolinone hydrazone)-positive, three MBTH-positive, and two ninhydrin- and MBTH-negative components. The results showed that patulin was over 100 times more toxic to E. coli than the adduct complex. Neither patulin nor the adduct mixture was found to induce the repair effect in E. coli. In the mouse feeding tests, the oral 50% lethal dose for patulin was 29 mg/kg, while that of the adduct mixture was greater than 2,370 mg/kg.


Antagonism among the normal anaerobic bacteria of the mouse gastrointestinal tract determined by immunofluorescence.

Strictly anaerobic Bacteroides sp., Eubacterium sp., and Fusobacterium sp. were isolated from the cecum of a conventional mouse. An immunofluorescent method utilizing rabbit antisera specific for each of these three strains was developed to determine their population levels in the gastrointestinal tracts of gnotobiotic mice. Population levels of these anaerobes in groups of gnotobiotic mice colonized with either Bacteroides, Eubacterium, or Fusobacterium were compared with those of gnotobiotes colonized with all three strains. Bacteroides population levels in gnotobiotes colonized with all three strains were 100-fold less than the Bacteroides population level in gnotobiotes colonized with only the Bacteroides strain. Eubacterium or Fusobacterium population levels were not reduced by the presence of the other anaerobic strains. Thus, strictly anaerobic Eubacterium sp. and Fusobacterium sp. that colonized gnotobiotic mice caused a reduction in the in vivo population levels of a strictly anaerobic Bacteroides sp.


Reversal of the silver inhibition of microorganisms by agar.

Increasing use of silver in the treatment of water has necessitated an examination of microbiological methods for the measurement of silver inactivation of microorganisms. Three common agar media were tested for their ability to neutralize the bacteriostatic effects of silver. Results suggested that growth media differed in their neutralizing capacity; that is, the non-inhibitory media tryptone glucose agar and Trypticase soy agar showed more neutralizing capacity than eosin methylene blue agar. Furthermore, the neutralizing effect appeared to be a function of the soluble component of the media and not of the agar itself.


Method for the detection of injured Vibrio parahaemolyticus in seafoods.

The sensitivity of Vibrio parahaemolyticus cells to refrigeration and frozen storage and the development of a method for detecting injured and uninjured V. parahaemolyticus cells were studied. Cell suspensions in different kinds of seafood homogenates were either regrigerated (4 degrees C) or frozen (-20 degrees C), stored, and examined for cell survival during storage. V. parahaemolyticus cells were sensitive to both storage temperatures. Many cells died, and many survivors were sublethally injured. In general, refrigeration storage appeared to be more injurious than frozen storage. The initial recovery of the sublethally injured cells was highest in a nutritionally rich, nonselective liquid medium such as Trypticase soy broth, whereas maximum cell multiplication was observed in Trypticase soy broth containing 3% NaCl. The sublethally injured V. parahaemolyticus cells demonstrated sensitivity to the selective enrichment medium, glucose salt teepol broth. From these findings, a new method (designated as the "repair-detection" method) was developed for the isolation and enumeration of V. parahaemolyticus. Comparative studies between the recommended and the repair-detection methods showed that injured V. parahaemolyticus cells were present in commercial seafoods and that the repair-detection method was definitely more effective for the detection of total numbers of V. parahaemolyticus cells.


Detection of mutagens produced by fungi with the Salmonella typhimurium assay.

Forty-one fungal isolates (one isolate per species) representing common plant pathogens and food crop contaminants were grown on sterile, polished rice and assayed for mutagenic activity in the Salmonella typhimurium-microsome system. Initially, single doses of aqueous and chloroform extracts of the moldy rice were assayed against the TA100 tester strain by incorporating extracts into the growth medium and by applying small quantities on disks placed on the agar surface. Suspected activity was examined further by analysis of several doses in the plate incorporation assay. Extracts of two aflatoxin-producing isolates (Aspergillus flavus and A. parasiticus) showed pronounced mutagenic activity, as did extracts of five other isolates (A. heterothallicus, A. nidulans, A. terricola, Alternaria tenuis, and Fusarium moniliforme) which did not contain detectable aflatoxins. Seven additional isolates (Botrytis cineria, Ceratocystis fimbriata, Cladosporium herbarum, Fusarium solani f. sp. pisi, Penicillium oxalicum, Thermomyces lanuginosus, and Verticilium albo-atrum) revealed activity which was possibly mutagenic; i.e., mutagenic responses were not observed in both the disk and incorporation assays, and clear dose-related activity was not observed in the incorporation assay. Extracts of the remaining fungi were not mutagenic in the bacterial assay.


Survival of a Salmonella typhimurium experimental contaminant during cooking of beef roasts.

Twenty-one raw boneless beef roasts were experimentally injected with 2 X 10(7) cells of a nalidixic acid-resistant strain of Salmonella typhimurium per roast. Contaminated roasts were cooked to center internal temperatures of 137.0 to 147.5 degrees F (58.3 to 64.1 degrees C) in a gas-fired pilot plant food-processing oven. Viable experimental contaminants were recovered from two core samples of the 21 roasts (one cooked to 137.0 degrees F [58.3 degrees C] and one cooked to 141.5 degrees F [ca 60.8 degrees C]). All of 17 cooking net samples taken from the contaminant injection side of roasts were salmonella positive, whereas 7 of 9 net samples from the side opposite injection were positive and all of 11 net samples from the bottom of roasts were positive. The implications of these results are discussed in relation to salmonella contamination of precooked beef roasts.


Restriction endonuclease analysis to distinguish two closely related nuclear polyhedrosis viruses: Autographa californica MNPV and Trichoplusia ni MNPV.

Restriction endonuclease fragment patterns of the deoxyribonucleic acid genomes of Autographa californica nuclear polyhedrosis virus (multiply embedded type) and Trichoplusia ni nuclear polyhedrosis virus (multiply embedded type) demonstrate that the two viruses are distinct but closely related variants.


Use of [14C]lysine to detect microbial contamination in liquid foods.

A radiometric method for microbiological control in food industries is suggested. This method, based on the labeling of cells by [14C]lysine, was tested by using nine species of yeast and two species of bacteria.


Familial primary cutaneous amyloidosis. Clinical, genetic, and immunofluorescent studies.

Familial primary cutaneous amyloidosis, a rare, autosomal dominant genodermatosis, affected 16 of 46 family members of German descent. Previous case reports involved families of Russian, Spanish, or Chinese descent. The finding of IgG, IgM, C3 in the amyloid deposits confirms recent reports of immunofluorescent dermal amyloid deposits.


Coexistence of bullous pemphigoid and systemic lupus erythematosus.

A vesiculobullous eruption with clinical and histological features of bullous pemphigoid developed in a 28-year-old woman with proven systemic lupus erythematosus (SLE). Serum of this patient contained elevated titers of antinuclear antibodies but basement membrane antibodies could not be detected at first, though they did appear in blister fluid. Normal monkey skin explants cultured on this patient's sera gave positive direct immunofluorescence (IF) at the basement membrane zone (BMZ) for IgG deposits. The use of tissue culture methods may be helpful because of the capacity of this test system to reveal the presence of the antibodies to the BMZ despite the presence of the antinuclear antibodies that appear to interfere with their demonstration in standard indirect IF tests.


Complement-fixing pemphigus antibodies.

The serum of a patient with a typical case of pemphigus vulgaria contained complement-fixing intercellular autoantibodies (pemphigus antibodies). Complement-fixing pemphigus antibodies were demonstrated only during the untreated active stage of the disease and titrated lower than corresponding IgG autoantibodies, which paralleled well with the disease activity. Pemphigus lesional skin, which contained in-vivo-bound IgG, showed the capability of further binding C3 in vitro from normal human serum. It was suggested from these findings that the complement system may play an active role in pemphigus acantholysis through complement-fixing pemphigus antibodies.


Immunopathology of epidermolysis bullosa acquisita. Association with mixed cryoglobulinemia.

We describe a case of epidermolysis bullosa acquisita with immunoglobulin and complement demonstrated at the dermal-epidermal junction. Essential mixed cryoglobulinemia was also present in the patient, reemphasizing the association of epidermolysis bullosa acquisita with other diseases.


Escherichia coli bacteremia in patients with malignant diseases.

Of 142 episodes of Escherichia coli bacteremia that were reviewed, appropriate antibiotics were administered during 98 episodes diagnosed premortem and 74 episodes (71%) responded. The highest cure rates were observed when the portals of entry were the urinary tract and soft tissues. Administration of adrenal corticosteroids did not affect the outcome of these patients. The patients' neutrophil counts at the onset and during infection were important factors in predicting survival. Septic shock occurred in 13% of all episodes, and only 11% of these patients responded. Of those patients who died, 63% died within the first 24 hours. Aminoglycosides, cephalosporins, and semisynthetic penicillins used alone or in combination offered optimal coverage.


Hyperkalemia after renal transplantation. Occurrence in a patient with insulin-dependent diabetes.

An insulin-dependent diabetic patient received a renal transplant from a living related donor without evidence of rejection. In the posttransplant period, his serum potassium concentration (3.7 to 6.7 mEq/liter) fluctuated widely with the serum glucose concentration (165 to 470 mg/dl) during the day. Serum glucose and potassium concentrations were directly correlated (r = .734, P less than .001). Other factors controlling the serum potassium concentration were examined. Plasma and urinary aldosterone levels were normal, plasma renin activity and aldosterone levels rose during upright activity, and urinary potassium excretion increased with the administration of exogenous mineralocorticoid. Thus, mineralocorticoid secretion and responsiveness were intact. These observations indicate that hyperkalemia in a diabetic patient can occur in the absence of a defect in potassium excretion and are consistent with the interpretation that insulinopenia, as evidenced by hyperglycemia, can result in hyperkalemia due to diminshed translocation of both potassium and glucose from the extracellular to the intracellular compartment.


Relationship of renal transplantation to hypertension in end-stage renal failure.

The relationship of renal transplantation to new onset or persistence of previously established hypertension was analyzed in 164 transplant recipients in whom the renal allograft functioned for six months or longer. Of the 164, thirty-seven (23%) had normal blood pressure and 127 (77%) were hypertensive prior to transplantation. Following transplantation 83 patients (51%) were normotensive; high blood pressure was found in 81 (49%). Posttransplant hypertension could not be correlated with the recipient's original renal disease, age, sex, renal donor source, donor age, or maintenance dose of prednisone. More normotensive paients had undergone prior binephrectomy when compared with the hypertensive group (P less than .05). Mean serum creatinine levels was higher (2.0 mg/dl) in hypertensives than in normotensives (1.54 mg/dl) (P greater than .05). Selective renal veins' renin measurements in patients with severe hypertension were not helpful in predicting the beneficial effects of either bilateral nephrectomy or surgical correction of transplant renal artery stenosis.


[Description of a method for measuring sera with a high level fo IgE: test through the inactivation of anti-IgE covered phages].

The Fab fragment of an anti-IgE serum was conjugated with the  bacteriophage T4 through the use of glutaraldehyde. The conjugated phage was inactivated by human sera which contained IgE. The degree of inactivation allowed to make a distinction between the sera of normal individuals and that of those in whom it is known that high levels of Ig E exist, as in patients with allergic diseases. The method is quite sensitive, economical and does not require costly equipment. Besides, the conjugated phage is preserved for prolonged periods of time.


[Adrenal function in topic corticotherapy].

It has been shown that corticosteroids for dermatological use produce an inhibition of the adrenal function, and it is considered that in our milieu these products are used without any precise indication. In this study, 29 ambulatory children from 3 to 15 years of age were selected, who were suffering from dermatoses with different degrees of extension, on whom urinary 17-ketosteroids, 17-ketogenicsteroids and serum cortisol were measured before and after non-occlusive treatment of two weeks, using 0.01 percent fluorocorticoids and controls after 24 hours and 8 days. A significant drop of the 17-keratogenicsteroids was found in patients studied at the end of the treatment, with immediate recovery. Additionally it was observed, in patients who had over 30 percent of skin area involved, that there was a decrease in serum cortisol, which persisted even 24 hours after discontinuing treatment, with normal levels in a measurement taken eight days later. It is therefore concluded that glucocorticoids applied topically are capable of inhibiting adrenal function.


Electron microscopy of germinating ascospores of Saccharomyces cerevisiae.

The wall of mature ascospores of Saccharomyces cerevisiae showed in sections under the electron microscope a dark outer layer and a lighter inner layer. The latter was composed of a greyish inner part and a light outer part. During germination, the spore grew out at one side and the dark outer layer was broken. Of the light inner layer, the inner greyish part became the wall of the vegetative cell, but the extended part of the cell had a new wall.


In situ study of the glycolytic pathway in Saccharomyces cerevisiae.

1. The problem of the influence of protein concentration on the kinetic parameters of enzymes has been approached studying the glycolytic enzymes from Saccharomyces cerevisiae in permeabilized cells (in situ). 2. The values of Km and Vmax for the different enzymes were essentially the same in dilute solutions of protein and in concentrated ones (in situ) except in the case of enolase where some differences were observed. 3. Functioning of the whole glycolytic pathway was compared in situ and in vitro measuring the rate of the fermentation of glucose. The rate of fermentation in situ was two fold higher than in vitro and the lag before active fermentation was also much shorter. 4. An unidentified phosphorylated compound, possibly polyphosphate, accumulates during the fermentation of glucose under in situ conditions.


[Cadaverine is an intermediate in the biosynthesis of arthrobactin and ferrioxamine E (author's transl)].

Cadaverin was more readily incorporated than lysine into arthrobactin from Arthrobacter pascens and into ferrioxamin E from Streptomyces glaucescens. From a racemic mixture only the L-isomer of lysine is incorporated. The L-lysine decarboxylase activity was measured in vivo and in vitro. The enzyme from Arthrobacter pascens is not inducable by lysine and completely repressed by 5.10(-6) M Fe3+. In Klebsiella pneumoniae, the producer of aerobactin, only a very low activity of L-lysine decarboxylase was detected.


Diagnosis in schizophrenia and manic-depressive illness: a reassessment of the specificity of 'schizophrenic' symptoms in the light of current research.

Present clinical and research methods of differential diagnosis of schizophrenia and affective psychoses rely very heavily on presenting symptoms and signs, especially in acute psychosis. We have reviewed studies bearing on this issue, including studies of the phenomenology of psychotic illness, outcome, family history, response to treatment with lithium carbonate, and cross-national and historical diagnostic comparisons. We conclude that most so-called schizophrenic symptoms, taken alone and in cross section, have remarkably little, if any, demonstrated validity in determining diagnosis, prognosis, or treatment response in psychosis. In the United States, particularly, overreliance on such symptoms alone results in overdiagnosis of schizophrenia and underdiagnosis of affective illnesses, particularly mania. This compromises both clinical treatment and research.


Implications of sex differences in the prevalences of antisocial personality, alcoholism, and criminality for familial transmission.

We describe three multifactorial models of disease transmission in which the prevalences of a disease differ in men and women. These models demonstrate explicitly how such sex differences may be caused by genetic factors, home environment, sociocultural, or other nonfamilial factors. Independent sets of family data about antisocial personality and alcoholism in the United States and criminality in Danish twins are analyzed according to these quantitative models. Relevant clinical and adoption data about these disorders are reviewed. The sex differences observed in the development of antisocial personality and of crime appear to be due to familial factors whereas the differences between male and female alcoholics are due to nonfamilial factors. The models and results are discussed in terms of their general implications for testing hypotheses about gender-related differences.


[Diagnosis, therapy, and prognosis of primary reticulum cell sarcoma of the cervix uteri (author's transl)].

Until now 12 cases of primary reticulum cell sarcoma of the cervix uteri have been described in the literature. Two more cases are reported. Diagnosis is only possible after exclusion of a systemic disease. Principle rules for therapy cannot be given by these few cases. However it seems that combined surgical and radiological treatment provides the best chances for longer surviving. Experiences in chemotherapeutical treatment of reticulum cell sarcoma of the cervix uteri are not yet published. Four of the 14 patients mentioned in this study died from relapse. The prognosis of this type of cervical tumor seems to be rather good.


The neuro-endocrine complex in the gastro-entero-pancreatic endocrine system.

The pancreatic islet is one of the well-studied endocrine tissues in regard to innervation. This neuro-insular complex has been known since the 1920's. The direct contact of the nervous element to the gastro-enteric endocrine cells has recently been reported in the proventricular mucosa of the finch. Here, the majority of the endocrine cells lie in the lamina propria and form a neuro-endocrine complex with unmyelinated nerve fibers. A similar neuro-endocrine complex was also reported in the rat stomach and in the duodenum of the human fetus. The occurrence of the neuro-endocrine complexes in the gastro-entero-pancreatic endocrine system might provide supportive data to the neuro-ectodermal theory on the origin of the endocrine cells proposed by Professors A. G. E. PEARSE and T. FUJITA.


Physiology of paraneurons.

An attempt is made in this review to elucidate the functional characteristics of paraneurons. The secretory functions of neuron, neurosecretory cell and paraneuron consist of three main phases: secretion, transmission and reversion. Secretion can be divided into a steady state and an activated state. A paraneuron behaves characteristically in the active phase of secretion and in the phase of transmission. There are three main events in the activated phase of secretion ("stimulus-extrusion coupling") in paraneurons, reception of stimulus, conduction of excitation, and extrusion of secretory substances. These three events seem to correspond to the functional characteristics in the three different regions of the paraneuron membrane. A stimulus-induced change in conformation in the input region of paraneurons may result in the inward movement of Na+ and Ca++. The inward movement of Na+ sometimes coincides with a graded depolarization which may occasionally generate all-or-nothing, short-duration action potential possibly in the intermediate region. A rise in [Ca++]i, whether it coincides with Na-dependent depolarization or not, may initiate extrusion of granules. If eccytosis is the mode of extrusion of secretory granules of paraneurons, the cell membranes at the output region should be rearranged by fusion with the membranes of granules. Ionic permeability of the output region might decrease during eccytosis if ionic permeability of the granule membrane is lower than that of other regions. Somatostatin in most cases and insulin in a special case may act locally on the adjacent target cells, and such a mode of transmission may come into the category of paracrine secretion.


Electron microscopical and immunohistochemical study on parafollicular cell complex with reference to parafollicular cell as a paraneuron.

In mammalian species, parafollicular cells were usually disseminated among the follicles of the thyroid gland; but they occasionally formed fairly large clusters around the parathyroid IV and thymus IV. These cell clusters were called parafollicular cell complexes and were regarded as the remnant of the embryonic ultimobranchial body. The parafollicular cell complex contained follicular cells in addition to parafollicular cells. Colloid-containing follicles also occurred. In order to assess the developmental and functional relationship between follicular cells and parafollicular cells, the parafollicular cell complex in the dog was investigated by means of immunohistochemical method and electron microscopy. Follicular cells in the parafollicular cell complex showed various ultrastructures representing every developmental stage. The cells forming solid clusters without follicles were indistinguishable from the precursor cells of the parafollicular cells. Parafollicular cells occasionally formed narrow colloid-containing follicles. The results of the immunoperoxidase study indicated that the follicular cells in the parafollicular cell complex elaborated 19s thyroglobulin and stored it as colloid droplets in the follicular lumen. The antigenicity of the colloid droplets in the parafollicular cell comples was much stronger than that of the thyroid follicles. Based on these results, the origin of the parafollicular cells was discussed with special reference to the paraneuron concept of FUJITA (1976). The theory that both follicular and parafollicular cells were of endodermal origin seemed valid.


Monoamine-containing paraneurons in the sympathetic ganglia of mammals.

1. A combined method for glyoxylic acid induced catecholamine fluorescence and electron microscopy was introduced in this study of the small intensely fluorescent (SIF) or granule-containing (GC) cells of the sympathetic ganglia. 2. Adrenergic interneurons were demonstrated in the sympathetic ganglia of the rat and the rhesus monkey. 3. Existence of adrenergic paraneurons (neuro-endocrine cells) in the sympathetic ganglia of several mammalian species was suggesed by the following observations: a) catecholamines are contained in the granular vesicles of SIF cells; b) SIF cells are innervated by preganglionic cholinergic nerves and are often in close relation with fenestrated capillaries; c) SIF cells develop from the neuroblast which originated from the neural crest, and ; d) substantial surface areas of GC cells are covered by basal lamina alone. Figures indicating exocytosis of granular vesicles were often seen here. 4. There are remarkable species differences in quantity and quality of SIF cells and great discrepancies among the physiological, biochemical and the morphological observations on SIF cells.


Ultrastructure and function of the granule-containing cells in the anuran sympathetic ganglia.

In the sympathetic ganglia of various anuran species clusters of small granule-containing cells (GC cells) appeared more often in the 5th to 7th paravertebral granglia rather than in the 9th and 10th ganglia of the sympathetic chain. The GC cells were classified into four types according to the granular vesicle morphology. Types I, II and III cells probably acted as endocrine cells which secrete catecholamines into blood capillaries or extracellular spaces. Type IV cells, however, resembled sympathetic ganglion cells. They seemed to be a special type of postganglionic adrenergic neuron rather than a type of interneuron. All these four cell types received cholinergic innervations. Ganglion cells in the anuran sympathetic ganglia formed no synapses with the adrenergic elements or the GC cells. Hence, it was unlikely that s-IPSP was mediated by catecholamines released from GC cells. Serial section studies revealed that both B- and C-neurons received only cholinergic innervation. A mechanism of s-IPSP production was discussed in correlation with the morphological findings.


Innervation of the chief cells of the carotid body: an ultrastructural review.

Recent serial ultrathin section studies have shown that a single kind of nerve fiber innervates chief cells of the carotid body through various types of endings. These nerve endings have been described in previous papers as being vesicle-rich, mitochondria-rich or small and large calyciform; these endings occurred in en passant and bouton forms. The intracranial section experiments of the glossopharyngeal nerve seem to support the view that the nerve fiber innervating chief cells is sensory, the soma of which is located in the inferior (petrosal) ganglion, although conflicting data still exist. Two types of synapses have been found at the sites of apposition between nerve fibers and chief cells: one, named efferent or type 1 synapse, in which chief cells are postsynaptic; the other, named afferent or type 2 synapse, in which chief cells are presynaptic. The serial ultrathin section study has shown that a single nerve fiber forms both types, with the latter type predominating. The possibility is strongly suggested that most of efferent synapses on the chief cells are formed by sensory fibers which form numerous afferent synapses, but not by proper efferent fibers. The similarity between chief cells and SIF cells in the autonomic ganglia is suggested in terms of synaptic relations with neuronal elements.