[Results of studying a live mumps vaccine from strain L-3 manufactured by the Moscow Research Institute of Viral Preparations. The reactogenic and antigenic properties of the vaccine]. The reactogenic and antigenic properties of live mumps vaccine from the L-3 strain were studied in 1507 children of 1 to 12 years of age. A single injection was given, one immunizing dose containing 10(4)HAdU50 of mumps virus. The live mumps vaccine from the L-3 strain irrespective of the lot of preparation, kind (live or lyophilized), method of application (jet-injector or needle/syringe), age of the vaccinees and the amount of virus in the immunizing dose received by a vaccinee, was demonstrated to be practically areactogenic and markedly antigenic. Serological examinations by neutralization tests of 346 paired serum specimens established variation in seroconversion between individual lots to be within 62.5--82.3% (average 69.9%) of cases. Comparative studies on the postvaccination and postinfection immunitiy in mumps showed the level of antibody in the vaccinees to vary within 4.2--5.1 log2 in different years, and in convalescents within 5.1--5.9 log2 in the same years. The results indicate a sufficiently high and intensive immunity for 5 years (the observation period).


[Gastric secretory function in peptic ulcer in youth and the effect on it of diet therapy]. In 110 patients with peptic ulcer aged from 16 to 25 years and in 15 healthy youths the secretary function of the stomach was studied by using fractional tubage with 300 ml of a 7% dry cabbage water as a stimulator. The secretory function was assessed according to the titrated acidity, pepsin and gastricsin data. Investigations were conducted repeatedly, viz. On admission to the clinic, following treatment with No 1 diets with an elevated protein and fats content (120--130 g) and also 8--10 months after discharge from the inpatient department. The dietotherapy (carried on for 42--45 days) did not produce any substantial normalization of the secretory gastric function, and this despite the improvement in the general condition of the patients and scarring of the ulcerous defect. A well marked tendency toward normal secretion of hydrochloric acid and proteolytic enzymes was seen to take place late after institutional dietetic treatment (in 8--10 months), provided the patients kept strictly to the prescribed dietary regimen. The normalization of the hourly HCl yield and the fall of the pepsin and gastricsin activity with the disease in the phase of remission (in 8--10 month time) concerned the first phase of secretion exclusively.


[Study of the properties of a tissue smallpox vaccine manufactured by the Moscow Research Institute of Viral Preparations]. The tissue culture vaccine against smallpox has some important advantages over the dermal preparation: it is free from bacterial contamination, contains no serum proteins, and suitable for intradermal inoculation with jet injections. The virus for the tissue culture smallpox vaccine is grown in Japanese quail embryo cultures controlled for the absence of contaminating viruses. In trials of the tissue culture smallpox vaccine in 800 revaccinated volunteers no untoward reactions or complications were observed. The antigenic activity of the tissue culture smallpox vaccine was superior to that of dermal vaccine used in the same dose: the geometric mean neutralizing antibody titre after vaccination with the tissue and dermal preparations was 1 : 256 and 1 : 158, respectively, and the antibody rise was 4.5- and 2.5-fold.


[Evaluation of the actiom of lipoic acid in ischemia and hypertension]. A total of 203 patients, 48 -- with ischemic and 155 -- with hypertensive disease in the 11A and 11B stages, were examined. The effect of lipoic acid (LA) was assessed on the ground of the dynamics in the clinical picture of the patients, some vitamins allowance figures and the activity of a number of enzymes in leucocytes, erythrocytes and in the blood serum. The LA was administered in the form of tablets, in a dose of 75 mg per day, for 10 dyas. As controls served 90 patients with ischemic and hypertensive diseases. Investigations showed the LA to have but a little influence on the clinical picture of the disease, raising somewhat the beta-lipoproteids level in patients with hypertensive and ischemic disease, irrespective of their age, and increasing the level of free fatty acids in patients over 50, forcing it down in those below 50. An age-specific effect of the LA on the blood proteinic spectrum was disclosed, viz. in patients below 55 it increased the proportion of albumins and reduced that of gamma-globulins, whereas in those aged above 55 reverse picture was in evidence. In the young LA had the tendency of bringing down the coagulating activity of the blood; whereas disaggregation of thrombocytes changed not depending upon the age, but on the form of the affection, decreasing in patients with hypertensive disease and remaining unchanged in those with ischemic heart disease. The LA helped normalize the thiamine metabolism in the organism and that of the thiamine-diphosphate containing enzymes with concurrently disturbed utilization of riboflavin in the examined patients.


[Study of the biological value of rice groats proteins]. The content of essential amino acids in the total rice protein and its fractions was determined; the degree to which the in vitro protein and starch are liable to be charged by enzymes was studied and also the biological value of the total protein and its fractions underwent appraisal by using the Tetrahymena pyriformis W. as a test organism. As to the amino acids content the protein fractions differ from one another, with lysine level in albumin amounting to 4.07, globulin--2.46, prolamine--0.88 and gluteline--3.15 per cent. Because of a low prolamine content of 1.9 per cent, the biological value of rice is greater than that of other cereals. Following heat treatment the lysine and methionine levels go down by 7 and 6 per cent, respectively, while the degree of the proteins and starch hydrolysis---increases. The hydrolysis of starch forming part of the milled rice results in a greater accessibility of proteins to the action of proteolytic enzymes. The relative nutritional value correlates with the lysine content.


[Antigens of adeno-associated viruses in children dying from acute respiratory disease]. Infection with adeno-associated viruses (AAV) early in life and extensive dissemination of these viruses in infants were discovered by detection of AAV antigen by the fluorescent antibody procedure in autopsy materials from infants dying of acute respiratory viral diseases. AAV antigens were found in cells from various organs of infants aged 2,5, 7, 9 days and older. In each individual case AAV of the same serological type was found in different organs. In 4-months-old twins AAV antigens of the same serotypes, 1 and 4, were found in the trachea, lungs, liver, kidney, brains. Out of 21 infants dying of adenovirus infection, 20 had AAV antigens the distribution of which in cells of various organs was analogous to that of the adenovirus antigen, with a few exceptions. Three infants had no adenovirus infection and no AAV antigne. In the other 6 infants no adenovirus antigen but AAV antigens were found. In the latter cases herpes virus infection is not excluded. Possible modes of transmission of AAV infection are discussed.


[Splitting and rejoining simian adenovirus type 7 DNA by using Eco RI restriction endonuclease and DNA-ligase]. Optimal conditions for ligation of simian adenovirus type 7 (SA-7) DNA fragments formed under the effect of treatment of the intact molecule with Eco RI endonuclease were established. It was shown that up to 30% of the original material may be ligated and transferred into a structure with molecular weight 23 X 10(6) daltons which corresponded to the molecular weight of the intact SA-7 DNA. The data of the existence of one recognition site for Eco RI in SA-7 DNA were confirmed. The biological activity of the ligated material was demonstrated on lambda-III phage DNA.


[Nosology of bullous disorders on the basis of recent advances in dermatological research (author's transl)]. A reappraisal is attempted of the various forms of immunopathologically-mediated bullous disorders: pemphigus and bullous pemphigoid groups; herpes gestationis; and dermatitis herpetiformis. Particular regard is paid to recent developments in the field of immunopathology of the skin. The elaboration of delicate immunological parameters at the same time illustrates the usefulness of laboratory research and the application of these results to clinical dermatology.


[Various technical diagnosis problems in the early diagnosis of parathyroid dysfunctions]. During the last years the functional diagnostics of the parathyroid glands has been considerably enlarged. Nevertheless, the results concerning an early recognition of conditions of hypofunction and hyperfunction are up to now unsatisfying. Despite of the increasing diagnostic importance of the direct determination of the parathormone which is at first available only in special institutions in these cases methodical problems play a less important part than the still not infrequent appearing misunderstanding of the adequate basic disease. The without doubt great variability of the clinical phenomenology of the parathyreogenic dysfunctions is particularly to be established in their initial stages. The demonstrated processes of investigation apart from the description of complexes of diagnostic problems summarize the experiences of many years of a treatment of outpatients directed to the forms of disturbances of the parathyroid glands.


[New viewpoints on the therapy and prevention of renal osteopathy]. Dihydrotachysterol which was developed already 50 years ago is above all used in the substitution therapy of hypoparathyroidism. Its parathyreomimetic effectivity has led to an enlargement of the spectrum of indication during the last years; it allows the prophylactic use of dihydrotachysterol in chronic nephropathy in order to prevent by this means the risk of reactive hyperparathyroidism as well as its sequelae. On the basis of own experimental results the pathophysiologic prerequisites of this new form of treatment are discussed.


[Hepatic coma--causes, recognition, treatment]. The name of the disease coma hepaticum is a collective notion for etiologically, pathologo-anatomically and biochemically different kinds of a failure of the function of the liver. A demarcation of different forms of the liver coma is necessary above all for prognostic and therapeutic reasons: hepatic disintegration coma, coma in hepatic failure, mixed coma, false hepatic coma, ferment block coma. Despite certain progress the therapeutic possibilities in hepatic coma cannot satisfy in recent years. Also the use of different, partly very expensive methods of the so-called liver substitute (exchange function and plasmapheresis, heterologous and homologous extracorporal liver perfusion, parasymbiotic crossed circulation, haemoperfusion with encapsulated activated charcoal, liver transplantation) up to now did not lead to a decisive improvement of the nearly infaust prognosis of the hepatic disintegration coma. Therefore preventing measures and careful control of endangered patients deserve particular attention.


Malignant glial neoplasms: definition of a humoral host response to tumor-associated antigen(s). There is increasing evidence that human tumors possess tumor-associated neo-antigens. The host mounts an immunological response to these antigens, as evidenced by the detection of circulating humoral antibodies in a variety of human neoplasia.An indirect immunofluorescent antibody technique was employed to detect antibodies to tumor-associated antigens in the sera of patients with malignant gliomas. Viable single cell suspensions were used to demonstrate antibodies to surface contents of tumor cells and cell preparations were snap-frozen at -160° C to demonstrate antibodies to cytoplasmic components of tumor cells. After incubation with serum, the preparations were treated with polyvalent sheep antihuman globulin conjugated to isomer-1-fluorescein isothiocyanate, washed, and examined with a Leitz incident fluorescent microscope.Of the 17 sera from histologically proven malignant glial neoplasm patients, 2 (11%) were positive for an autologous surface antibody reaction. Five (23%) of 21 were positive for an autologus cytoplasmic antibody, however, 10 (47%) of 21 of the sera gave a positive reaction for cross-reacting cytoplasmic antibodies when tested with a battery of tumor cells obtained from different patients with malignant glial tumors.No reaction was observed with normal brain tissue. Absorption studies indicated the presence of a tumor-associated antigen.This study demonstrated that certain patients with malignant gliomas possess circulating antibodies to cytoplasmic components of their own tumor cells. The fact that a number of sera cross-reacted with tumor cells obtained from different patients suggests that antigenic cross-reactivity exists between malignant glioma cells from different patients. It is suggested that with further refinement, immunofluorescent detection of antibodies could evolve as a useful diagnostic adjunct in malignant glioma.


Grey-scale ultrasound in the imaging of urinary tract disease. Grey-scale ultrasound defines smaller renal lesions that had previously been appreciated and is able to define associated lesions of the liver such as metastases and cysts. The appropriate technique to delineate the normal anatomy of the kidney is described. Ultrasound plays a central role in the identification and characterization of renal mass lesions thus leading to appropriate further work up. In renal transplant evaluation ultrasound is useful as a complementary modality to other imaging studies permitting the recognition of pelvic fluid collections, rejection, and hydronephrosis. Specific findings are present in renal abscess, perirenal abscess, and in several of the renal cystic diseases. Adrenal lesions can be identified and clarified. In the lower urinary tract, ultrasound can identify bladder and prostatic tumors.Ultrasound provides a rapid, safe and non-invasive modality which is complementary to other imaging techniques in the diagnosis of urinary tract disease.


[Immunofluorescent-histologic localization of a placenta-antigen with antibodies from pregnancy blood (author's transl)]. Placenta-specific antibodies were isolated by the incubation of washed placental tissue with pregancy serum and then desorption with citric acid pH3. The antigen responsible for the formation of the antibody could be localized via the immunofluorescence technique together with application of the placenta antibody in the syncytiotrophoblast layer. The antibodies are not complement-fixing and belong to the IgG class.


[Cultural and serologic examination for saccharomycetic infection in pregnant women (author's transl)]. Cultures from retrolingual, vaginal, and anal smears were used to determine the presence of saccharomycetic infection in 177 pregnant women. The retrolingual smear was saccharomyces-positive in 29.1% of the cases; the vaginal smear, in 18.1%; the anal smear, in 7.3%. The fungus differentiation revealed the pathogen Candida albicans 85 times and the pathogen Candida krusei, 1 time. The Candida HA Test and the Candida JF Test (Roche) were carried out in 160 of the patients. A relationship could be determined between the clinical findings and the serologic results. The danger to the newborn when the mother has a saccharomycetic infection as well as the fundamentals for therapy were discussed.


[Does medicine limit enlightenment?].

[Does medicine limit enlightenment?]. In the first, historical part the most important programs of "Medical Enlightenment", are pointed out, beginning with Leibniz, followed by the public health movement of the 18th century, up to the time of Immanuel Kant. Based on this historical background several concepts of a "Medical Culture" are analysed in detail, for instance the "Theorie einer Medizinal-Ordnung" by Johann Benjamin Ehrhard (1800), the "Medicinische Reform" by Rudolf Virchow (1848) and the programs of the "Gesellschaft Deutscher Naturforscher und Arzte" (about 1850-1890), the latter bearing both scientific and political character. Following the historical part, the question is raised whether "Enlightenment" is limited by medicine and whether medicine is able to provide a program for individual health education resulting in a more cultivated style of private life, and lastly how this might be realized.


[The occurrence of cross-reactive antigens in myocardial tissue and in streptococcus pyogenes. IV. Cytotoxic effect of lymphocytes sensitized in vivo to group A streptococci on primary cultures of heart muscle cells (author's transl)]. The cytotoxic effect of rat lymphocytes in vivo sensitized to group A streptococci, rat heart tissue or streptococcal M proteins was investigated in primary cultures of beating rat heart cells. Cytotoxicity was found in 75 to 82% of heart cell cultures in contact with lymphocytes sensitized to streptococcal whole cells or lysates and in 100% of those exposed to lymphocytes sensitized to rat heart tissue. Lymphocytes sensitized to M protein exert a cytopathic effect only in 8 and 12% cultures, respectively, and to a much more limited extent. Controls were affected in 6%. The cytotoxicity test seems to be useful to examine the presence of cross-reactive antigens within streptococcal vaccines.


Simultaneous presence of HBsAg and anti-HBs in the serum of different subtypes (serological and immunofluorescent studies). Serological and immunofluorescent studies were performed in 3 patients with the simultaneous presence of HBsAg and anti-HBs in the serum. Our investigations revealed the following results: HBsAg and anti-HBs in the serum were of different subtypes. HBsAg in the serum and in the liver had the same subtype. HBsAg in the liver did not react with the circulating anti-HBs in the patient's own serum. HBsAg-anti-HBs immune complexes could not be detected in the serum or in the liver tissue. These phenomena can most readily be explained by at least 2 contacts with hepatitis-B-viruses of different subtypes, one leading to immune tolerance and the other to an immune response. In a follow-up study there was no evidence for a short-term change in HBsAg subtype. Unexplained remains the cause why one contact with HBV did lead to immune tolerance and a second to an immune response.


An immunoperoxidase method for the identification of B lymphocytes by light microscopy. Peroxidase-conjugated anti-human immunoglobulin was used to determine the percentage of B lymphocytes in the mononuclear cell fraction of peripheral blood of 100 healthy persons (blood donors). Peroxidase activity was revealed by incubation with the usual mixture of 3'3 diaminobenzidine and hydrogen peroxide. Cells which were peroxidase-positive after incubation with benzidine solution alone were considered to be monocytes. The number of T lymphocytes was estimated by the formation of E rosettes. 19.6% mononuclear cells could be shown to be B cells, 4.1% were monocytes and 57.0% T cells. The use of peroxidase-conjugated anti-human immunoglobulin gives rise to the same percentage of B cells as the use of fluorescein-conjugated anti-human immunoglobulin. The advantage of the method described here is that B lymphocytes can be counted by conventional light microscopy.


The pathogenesis of tropical splenomegaly syndrome--the role of immune complexes. For the last few years it has been known that high molecular weight circulating immune complexes containing IgM, other immunoglobulins and complement are usually present in TSS. Similar material to be found in the Kupffer cells of affected patients, and on the surfaces of their red cells. The recent demonstration that the immune complexes contain malarial antibody activity strengthens the belief that they also contain malarial antigen and are due to the basic immunological abnormality. As indicated in this review, further studies are required fully to confirm their role in the production of the splenomegaly, the auto-immune phenomena and the haemolysis of TSS. The balance of evidence favours a genetic rather than a purely environmental basis for development of the syndrome. Treatment is simple, inexpensive and relatively free of risk. It is feasible even in rural communities pending the advent of successful malaria eradication, the ultimate means of prevention and cure.


Gel diffusion--a simple and sensitive technique for the assay of proteinase inhibitors and its use for the determination of the ratio of proteinases in mixtures. In casein-containing agarose gels, pepsin and chymosin form radial diffusion zones; the diameters of these zones show rectilinear correlations with the logarithm of the enzyme concentration at constant time. The sensitivity for both enzymes is below 1 microgram. Addition of the inhibitor pepstatin A to these enzymes causes a reduction of the diameters of the diffusion zones, with large differences for both the enzymes. With this procedure, the pepsin/chymosin ratio in rennet preparations was assayed with an accuracy of +/- 5%. Identification of the inhibitors allows the determination of amounts in the namomole range. This method is a simple technique for the evaluation of proteinases and their inhibitors in screening systems.


[Various aspects of surgical technics in renal-pole resection]. The authors give a survey concerning history and operation techniques, indications and use of the renal pole resection. They report on the method developed by them, by means of which the effect of haemostasis is increased, the loss of parenchyma is decreased and the patients may earlier be mobilized. Their experiences are based on the observation of 29 patients operated by means of the method described.


[Experiences with nephrolith in the treatment of patients with kidney calculi]. In patients with urolithiasis "Nephrolith" has a favourable influence on many parameters which are responsible for the development of renal calculi. I could never observe a complete dissolution of the urinary calculi.


[Marginal nephrectomy for the removal of coral calculi]. Efforts aimed at surgical solutions conserving the organs obtained importance also in renal surgery in recent years. This fact meant a milestone in the life of patients suffering from coral calculi, since it has been recommended to perform nephrectomy only in rare cases, and in the majority of cases young mothers were concerned. On the basis of the operation material comprising 12 cases--out of which some cases are described--the points of view of the marginal nephrectomy are discussed in detail. Among the modified techniques on the one hand the hairpin-shaped suture, on the other in the case of the local disease of the calyx system the marginal nephrectomy combined with wedge-shaped resection are explained, for the reduction of the danger of a recidivation of calculi an essential importance is ascribed to the last mentioned method.


[Effect of ionizing energy on the bladder dilated by dura, with special reference to the implantation technic. Animal experimental study]. On 60 female rabbits we examined the influence of the postoperative irradiation on the urinary bladder dilated by liophilized human dura after resection of the wall. Compared with former examinations as to the implantation technique the submucous deposition of the dura and fixation with single-button U-sutures (chromic catgut 000) has proved as superior. Vascular trophic disturbances on the margins of the resection could not be proved. When 4,500 R, 6,000 R and 7,500 R were irradiated the regeneration process through the dura serving as "live" rail retarded considerably. Problems in connection with the suture technique and the total focal dosage are discussed taking into consideration literature.


[3 new urinary ducts in the animal experiment. Preliminary report]. It is reported on the temporary results of three new conduits from muscle, siliconised dura and stalked skin in six dogs and six rabbits. The adhesions of the muscle conduit due to contact of the interior walls were unavoidable. The slight stress during operation in the conduit of the dura as well as the tangentially broader ueterostomia cutanea for avoiding a stenosis in the conduit of the skin seem to contribute to the solution of the suprapubic passing of the urine.


Utilization of agricultural wastes of Aspergillus awamori for the production of glucoamylase. The principal industrial use of glucoamylase is in the production of crystalline D-glucose. Aspergillus awamori was used. Variations in the specific type of carbohydrate source affected the yield of enzyme markedly. Of all the substrates tried, maltose supported satisfactory enzyme yields. Sucrose, lactose, fructose, and galactose gave abundant growth which seemed to be necessary but no sufficient condition for maximum yields. The specificity of the carbohydrate structure for gluco-amylase production was tried. The synthesis of enzyme was significantly stimulated when two-third of the starch in the medium was replaced by maltose. The adaptation seemed to be specific to maltose structure, since the substitution of maltose by structurally related compounds, a.o. lactose, in the medium did not give a comparable glucoamylase yield. Maltose or compounds composed of maltose gave maximum yields of enzyme. These results seemed to favour the theory that glucoamylase production is adaptive. Agricultural wastes produced locally in large quantities from plants manufacturing starch and other products were discussed. Rice bran, followed by glucose syrup, corn bran, wheat bran, and can sugar molasses supported good yields of glucoamylase.


[The problem of gallstone dissolution (author's transl)]. Stones in the gallbladder and the bile ducts can be dissolved by oral medication. The stones present in the bile ducts can also be dislodged and caused to disappear by local irrigation. For cholesterol stones the most effective treatment at present is application of Chenodeoxycholic Acid. However, surgery must be considered in the first instance. In case of bile duct stones it is suggested that prophylactic and conservative treatment should be attempted.


Streptococcus group B typing: comparison of counter-immunoelectrophoresis with the precipitin method. The method of counter-immunoelectrophoresis (CIE) was tested for its applicability to group B streptococcus typing. The results obtained were compared with the typing by the ring precipitin test. Identical antigens and identical hyperimmune typing serum batches had been used in both methods. A large majority of 75 freshly isolated strains were typed identically by both methods. Five strains with a weak antigenic outfit were untypable by the ring precipitin test but were typed by CIE owing to a higher sensitivity of CIE method. Two strains were typable by the precipitin test but not by CIE; an explanation for this phenomenon is lacking. The CIE method in group B typing is specific, rapid, highly sensitive and relatively simple. It requires strict maintenance of standard conditions. The method is economical with respect to manipulation and material, requires small amounts of diagnostic antisera. Potent antisera may be used diluted. Moreover, sera for CIE typing need not be absorbed to remove group B antibodies. CIE method is practicable for group B streptococcus typing, especially in laboratories carrying out routine large scale type identification.


[Heat-stable Escherichia coli-enterotoxin: reduced action after administration of phenylbutazone in infant mice (author's transl)]. Heat-stable Escherichia coli enterotoxin was assayed by the method of DEAN determining gut weight to body weight ratios in infant mice. The enterotoxic responses were significantly lower than in saline treated controls when Phenylbutazone at 20 mcg/mouse was administered subcutaneously 30 minutes prior to intragastric toxin challenge. The trials were performed with lyophilized culture filtrates of E. coli O 149:K91 (B) K88 ab (L), and three other enterotoxigenic strains one of which was isolated from an outbreak of swine oedema disease, the other two strains originated from the stools of diseased children.


[Experiences with the API 20A system in routine species identification of anaerobes (author's transl)]. The API 20A System was tested in three modifications: a) The microtubes were inoculated with the API anaerobe basal medium, filled up completely with sterile mineral oil and incubated aerobically. b) The test strips were inoculated with the basal medium and incubated in an anaerobic chamber. c) The strips were inoculated with a modified Viande-Levure medium containing Tween 80, vitamin K3 and hemin. The microtubes were covered with sterile mineral oil and incubated in an anaerobic chamber. Each procedure was compared with the conventional method (PRAS) of the Virginia Polytechnic Institute. The overall agreement between the three modifications of the API System and the conventional method was 83.2, 91.7, and 98.5% related to the number of tests performed. The advantage of the modified medium was also demonstrated by measuring the growth rate of some anaerobes in thioglycolate broth, API basal medium and VL-medium, modified as mentioned above, nephelometrically. So the micromethod is more accurate and reliable when inoculated with an improved medium.


[Usability of three alcohols for a standard disinfection method to be employed for the evaluation of procedures for the hygienic disinfection of hands (author's transl)]. Following a former suggestion (4) always to evaluate, the efficacy of procedures for Hygienic disinfection of hands in comparison with the results of a certain standard disinfection method, Ethanol, iso- and n-Propanol were tested in various concentrations and for various times of action on their usability in such a standard method. The disinfecting power was dependent upon (i) the alcohol (Ethanol less than iso-Propanol less than n-Propanol), (ii) the concentration (Ethanol: 60 less than 70 less than 80% ml/ml, iso-Propanol: 50 less than 60 less than 70, n-Propanol: 40 less than 50 less than 60 = 70) and (iii) the time of action (0,5 less than 1 less than 2 min). n-Propanol proved to be the fastest acting disinfectant. However, as standard disinfection method iso-Propanol (60% ml/ml) being used for 1 min has been proposed. Furthermore, the following results that have been obtained also in former investigations (8) could be confirmed: (i) there is no systematic difference between the release of test-bacteria from the fingertips of right and left hands of test-persons (ii). The efficacy of procedures for Hygienic disinfection of hands is besides other factors influenced by the testpersons. This factor may be eliminated by using the same testpersons for both, the disinfection procedure under investigation and the standard method. The results of both may, then, be related to each other and the efficacy of the former may be evaluated in comparison to the latter.


[Experience gained with ozone/activated-charcoal treatment of swimming-pools filled with sea water (author's transl)]. An ozone/activated charcoal stage in the water treatment also lends itself extremely well to improving the quality of sea water in swimming pools. This improvement is typically reflected in the low content of organic substances and nitrogen compounds (ammonia, urea) and, as a result, in the high redox potentials in the swimming-pool water which are even likely to bring about a rapid inactivation of the viri. A small percentage of the bromide in the sea water is oxidised to free bromide which passes through the activated charcoal filter, counteracts the growth of germs, keeps the filtrate largely free from germs and contributes to the disinfection of the swimming pool.


[Testmethod for the evaluation of procedures for the hygienic disinfection of hands. Part 1: Discription of testmethod (author's transl)]. A detailed test design for the evaluation of procedures for the hygienic disinfection of hands is described together with suitable methods for statistical analysis of the results. In principle the release of testbacteria from the finger-tips of artificially contaminated hands is measured before and after disinfection. A procedure under test is accepted if it is not less effective than a standard-disinfection procedure. As such the disinfection with iso-propanol 60% (ml/ml) applied through 1 min was agreed upon. This standard procedure is to be performed the same day with the same day with the same testpersons and under identical environmental conditions prior to the procedure under test.


[Synthesis and properties of carrier-fixed enzymes. VII. Linking of glucoamylase to dialdehyde cellulose, carboxymethylcellulose hydrazide and carboxymethylcellulose azide]. Glucoamylase (alpha-1,4-glucan glucohydrolase, EC 3.2.1.3) has been covalently linked to dialdehyde cellulose resulting in an immobilized enzyme containing 0.98% protein and an activity of 4.5 mg of the native enzyme per g of matrix, i.e. 46% relative activity. The complex lost its activity in continuous and batch hydrolysis of starch at 55 degrees C down to a limit of 18% of its original value. In contrast, the activity of the complex did not change when working at a temperature of 25 degrees C. Glucoamylase-carboxymethylcellulose complexes synthesized via carboxymethylcellulose hydrazide and azide, in contrast to MAEDA und SUZUKI [1], showed only an activity of 1 mg of the native enzyme per g of matrix. We did not succeed in coupling periodate-oxidized glucoamylase to carboxymethylcellulose hydrazide because the enzyme used lost nearly all of its activity already during periodate oxidation.


Urinary gonadotrophins and luteinizing hormone-releasing hormone (LH-RH) like immunoreactivity during three normal reproductive cycles. Highly specific and sensitive radioimmunological methods were applied to determine the levels of LH-RH like immunoreactivity in urine previously extracted by spherosil and methanol, and to assay the gonadotrophins, after extraction with acetone. The endogenous urinary LH-RH like immunoreactivity material was identified by chromatography on Sephadex G25, as having physicochemical properties similar to those of the hormone found in unextracted urine after iv injection of synthetic LH-RH, but different from those of the synthetic decapeptide. The LH-RH like immunoreactivity and the gonadotrophins were assayed in daily collected urine during the reproductive cycle of 3 normal women. A midcycle peak of both FSH and LH was found in each subject. No increases of LH-RH like immunoreactivity were found before or concomittant with the gonadotrophins surge. But peaks of urinary LH-RH like immunoreactivity were observed during the luteal phase, without subsequent increase of gonadotrophin secretion.


Exfoliative cytopathologic studies in organ transplantation. V. The diagnosis of rejection in the immediate postoperative period. This study shows that the cytologic profile of rejecting and non-rejecting patients in the immediate post-transplantation period can be distinguished. The presence of activated lymphocytes is the most important single feature of rejection, but may not be present in all cases of rejection. For this reason the use of a cytologic profile including a dirty background, red blood cells, lymphocytes, tubular cells, and nuclear changes in epithelial cells is recommended.


Fundamental study of automatic cytoscreening for uterine cancer. V. Data analysis for imporvement of CYBEST. The particles selected by CYBEST as "abnormal cells" at the stage of coarse scanning were examined by direct microscopy to determine whether they were actural cells or not. Approximately 20 to 30 per cent of these were cell clusters and/or clumped leukocytes and red cell or specks of dust. Such incidents interfered considerably with a precise cytologic assessment. To eliminate this problem by means of a software algorithm, experiments were carried out setting thresholds for cell feature values. When the values obtained by machine measurement exceeded the theshold values the particles concerned were automatically disregarded, as interfering indidents, at the state of the coarse scanning. The approach was found to have substantial value in the operation of CYBEST as a pescreening device.


Fundamental study of automatic cytoscreening for uterine cancer. IV. Sample requirements for CYBEST and simulation test of cell dispersion. The preparation of samples with good cell dispersion and without cell overlapping is a particularly important problem, whether for image processing systems or for flow systems. Simulation tests were carried out to estimate a cell density with good cell dispersion and a minimum number of overlapping cells. A little less than 50 cells per mm2 was disclosed to show a condition of sufficient cell dispersion. By microscopical observation and counting of the malignant cells using ten cases of uterine cervical carcinoma, it was found that in most instances over 50 malignant cells were contained in 20,000 to 40,000 cells on the smears. When the cell density is approximately 50 per mm2, the scanning area of the CYBEST of 40 X 20 mm may contain up to 40,000 cells. The probability that such a number of cells contains malignant cells is extremely high, in fact, nearly 100 per cent. By field tests, it was experimentally confirmed that these cell densities are very adequate for the function of the CYBEST.


The effect of gastric distension on the secretion of acid and pepsin by patients with duodenal ulcer. Twentyfour patients with active duodenal ulceration were subjected to gastric distension with a balloon, in an attempt to assess the "neural tone" affecting the parietal and chief cells of the stomach. Distension stimulated gastric secretion in a manner similar to, but weaker than, pentagastrin. No evidence was found that distension provides a specific "neural" stimulus to the gastric secretion of acid or pepsin in man.


Proteinlosing gastropathy with gastric hypersecretion of acid (H+) and pepsin and hypergastrinemia. A case report. A case with proteinlosing gastropathy with gastric hypersecretion of H+ and pepsin as well as hypergastrinemia is presented. Zollinger-Ellison syndrome was excluded by reduction in acid secretion and serum gastrin during the observation period as well as by the effect on gastric secretion and serum gastrin after injections of secretin and glucagon.


Studies on intra-pulmonary gas distribution in the extremely obese. Influence of anaesthesia and artificial ventilation with and without positive end-expiratory pressure. Intrapulmonary gas distribution was studied in 10 extremely obese patients: (1) during spontaneous breathing awake; (2) during anaesthesia with controlled ventilation and zero end-expiratory pressure (ZEEP), and (3) as under (2) but with a positive end-expiratory pressure of approximately 15 cmH2O (PEEP). Gas distribution was assessed quantitatively by means of a multiple-breath nitrogen wash-out technique and subsequent fractional analysis, which permitted the calculation of nitrogen wash-out delay (NWOD). Gas distribution was also analyzed by means of a single-breath nitrogen wash-out in order to determine the slope of the "alveolar plateau." Gas distribution was within normal limits during spontaneous breathing, judged from multiple-breath as well as single-breath wash-out. With anaesthesia and ZEEP, NWOD was higher, indicating less efficient gas mixing, and the slope of the "alveolar plateau" was twice as steep as during spontaneous breathing. With PEEP, distribution of inspired gas improved (lowered NWOD and flatter slope). Theoretical considerations and clinical experiments led to the conclusion that uneven distribution in the anaesthetized obese is caused both by regional differences in the pulmonary time constants (as in obstructive lung disease) and by airway closure.


Evaluation of impedance cardiography druing anesthesia in extremely obese patients. In three anesthetized markedly obese patients, non-invasive stroke volumes (the transthoracic electrical impedance method) were compared to simultaneously obtained invasively measured stroke volumes (dye-dilution method). Close correlations were obtained (r = 0.90--0.98) between the two methods, although constant lower impedance stroke volumes were found in these patients when the values usually employed for the electrical resistivity of the blood (zeta) were used for calculation of the impedance stroke volume. No statistically significant difference (P greater than 0.10) between the two methods was found when a zeta of 175 ohm X cm was used for the calculations, or when the percentage changes in stroke volumes were analyzed. The impedance method is safe and reliable; it also permits non-invasive measurements of stroke volume during anesthesia in markedly obese patients.


Comparison of the analgesic effects of intravenous nalbuphine and pentazocine in patients with postoperative pain. One hundred patients, who were in pain during the immediate postoperative period after upper abdominal operations, were included in this double-blind, between-patient, two-dose study. During N2O-O2-halothane-relaxant anaesthesia no analgesics were given. The patients received 0.07 mg/kg or 0.14 mg/kg of nalbuphine or 0.3 mg/kg or 0.6 mg/kg of pentazocine by intravenous injection. Pain and side effects were assessed for 4 h after administration of the test drug, or until the pain returned to the pre-injection level, when a conventional analgesic was given. The onset of pain relief was similar and the peak effect occurred about half an hour after the injection after both drugs. On a milligram basis, nalbuphine seemed to be about three times as potent as pentazocine. The duration of action seemed to be slightly longer after nalbuphine, but 2 1/2 hrs. after the injection the pain had returned to preinjection level in 2/3 of the patients, even after the higher doses of both drugs. Except for sleepiness, there were few side effects and they were similar after both drugs. No psychotomimetic effects were observed.


Hydrostatic pulmonary edema in the cat. Effects on pulmonary blood and water volumes and on lung compliance. The effect on lung compliance of changes in intra- and extravascular volumes has been studied. Such changes were induced by inflation and deflation of a balloon placed in the left atrium in open-chest cats. Blood constituents were labeled with isotopes, and tissue water content was found from the wet/dry labeled with isotopes, and tissue water content was found from the wet/dry weight ratio. When left atrial pressure (PLA) was elevated to a value not exceeding 32 mmHg (4.256 kPa), there was only a minute increase in tissue water volume, and we observed a reversible reduction in lung compliance related to the rise in lung blood volume. At higher PLA, a rapid rise occurred in extravascular fluid volume, with evidence of alveolar flooding. Earlier experiemtns have shown that, in isolated perfused lung, a situation of slow, steady increase in interstitial fluid can be created. This does not seem to be the case with lungs in situ: once the lymphatic drainage is unable to cope with transvascular fluid flow, an unstable situation is created. This rapidly leads to alveolar flooding and a fall in compliance in addition to that caused by a rise in blood volume. From our fluid and pressure determinations, we calculated a filtration coefficient (Kf) of 0.45 ml/100 g wet lung X cmH2O X h. This is within the range reported for sheep lungs. Observation of dynamic lung compliance cannot be used for detection of interstitial fluid accumulation. It appears, however, that in contrast to isolated lungs, this phase of edema-formation rapidly leads to alveolar flooding.


Bromocriptine versus placebo in levodopa treated patients with Parkinson's disease. Twenty patients with idiopathic parkinsonism who had been on optimal levodopa therapy for at least 3 months prior to the investigation and where effect of the treatment was decreasing or side effects were increasing, were treated with bromocriptine in a double-blind crossover trial during a 12 + 12 weeks period. Reduction in disability scores was found significant. Hyperkinesia was more frequent in the bromocriptine period than in the placebo period, but reduction of dose in six patients for this reason was not followed by deterioration. Both hyperkinesia and other side effects disappeared after dose reduction. Doses were 2.5 mg-40 mg. Bromocriptine seems a valuable supplement to previous therapy in these patients.


Bromocriptine in the treatment of advanced Parkinsonism. The dopaminergic agonist bromocriptine in doses of 2.5-40 mg was compared with placebo in a double-blind cross-over study (12 + 12 weeks) in 11 Parkinson patients in whom bothering dyskinesia occurring after prolonged levodopa treatment limited in the levodopa dose to a level, where Parkinson symptoms still were present to an unsatisfactory degree. On the basis of changes in rating scales and the patients' preference, bromocriptine was significantly superior to placebo. Dyskinesia, occurring during bromocriptine treatment in 9 of 11 patients, disappeared within the period of study in 6 patients after dose reduction without changes in Parkinson disability scores to placebo level. Bromocriptine seem to be of value in cases where the balance between minimal dyskinesia and Parkinson symptoms is impossible to obtain with levodopa treatment alone.


[Association of Alzheimer's disease and Creutzfeldt-Jakob's disease (author's transl)]. Serial EEG studies and full neuropathological investigations (optic and electronic microscopy of biopsy and necropsy material) were carried out on two patients: 1. A 68-year-old man: development in two and a half months of Creutzfeldt-Jakob's disease signalled by early clinical and EEG changes and confirmed by associated spongiosis of the triad characteristic of Alzheimer's disease, which was unexpected in this case. 2. A 43-year-old man: first phase of four years of progressive deterioration, followed by an encephalopathic syndrome with myoclonus developing in twelve months. The serial EEG studies showed discontinuous periodic paroxystic activity from the start of the second phase of the disease, although the first biopsy still showed nothing but the signs of Alzheimer's disease. A fortnight later, a second biopsy revealed ultrastructural microspongiosis. Examination of necropsy material confirmed the extensive association of the characteristic images of the two processes. On the basis of these two case studies and some similar cases published in the literature, the authors discuss the possible etiological links between these two diseases and stress the importance of the EEG and cerebral biopsy for the purposes of differential diagnosis. (Acta neurol. belg., 1977, 77, 202-212).


Brain-associated cell surface antigens on neuroepithelial cells in a transplantable mouse teratoma. Mouse neonatal brain cell fractions enriched for surface membranes were used as immunogens to produce a heterologous immune serum. Following absorption to remove non-neural anti-mouse activity, this serum demonstrated by microcomplement fixation an anti-brain activity that was completely removed by absorption with neonatal mouse brain or with solid tumors of the mouse transplantable teratoma OTT-6050. Indirect immunofluorescence applied to living monolayer cultures of differentiating teratoma embryoid bodies showed the absorbed serum's reaction with neural cell surfaces only. In material studied with frozen sections, the absorbed serum recognized antigenic sites in all examined areas of both neonatal and adult mouse brain, and only within neuroepithelial cell populations of solid transplants of the teratoma.


The blood-brain barrier to horseradish peroxidase under normal and experimental conditions. This review paper deals with the transport of the protein tracer horseradish peroxidase across cerebral vessels under normal and various experimental conditions. Electronmicroscopical investigations have revealed that, under normal conditions, a minor vesicular transfer of intravenously injected peroxidase occurs across the endothelium in segments of arterioles, capillaries and venules, especially in arterioles with a diameter about 15-30 mu. This normally occurring vesicular transport is susceptible to various experimental conditions. Thus the transfer of tracer increases when a hypertonic solution is injected into the internal carotid artery presumably due to vesicular transport. Extensive acute hypertension of short duration also increases the vesicular transfer of peroxidase from blood to brain. Identical observations are obtained when the hypertension is evoked by intravenous injection of phentolamine and by electrically induced seizures. During the postischemic period, one hour after release of the occlusion of an internal carotid artery in the Mongolian gerbil the vesicular transport of peroxidase is increased across the endothelium of cerebral vessels. The explanation may be release of serotonin from blood platelets during the occlusion. The serotonin could then increase the blood pressure locally in the brain resulting in an enhanced permeability. Serotonin, after perfusion through the cerebral ventricular system, is also able to increase the normally occurring vesicular transfer. The most likely mechanism behind this phenomenon seems at the moment to be local hypertension evoked by serotonin-induced vasoconstriction of arterioles. Finally, the enhanced vesicular transport across cerebral endothelium caused by porto-caval anastomosis is mentioned and the possible role of disturbances in the metabolism of amines as responsible for the extravasation is discussed.


Experimental and clinical data on Cyclabil. The effects of a 2-phase preparation on the parameters of cycle function were studied in 14 normally menstruating women. The preparation, Cyclabil, is administered in a series of 11 tablets with 2.0 mg oestradiol valerate and 10 tablets with 2.0 mg oestradiol valerate in combination with 0.5 mg D,L-norgestrel. The cervical function, the spinnbarkeit of the cervical mucus and its crystallisability and, by means of RIA, FSH, LH, 17beta-oestradiol and the progesterone serum levels were determined continuously in a control cycle before the treatment, in the first and third treatment cycles and in a subsequent control cycle. The results show that no impairment of the normal cycle function were found during cyclical administration of the 2-phase preparation in 13 women. Two pregnancies occurred during the therapy. The process of ovulation was inhibited in one subject during the medication. 20 other women with pronounced premenopausal deficiency symptoms and cycle irregularities were treated with the 2-phase preparation for 6 months. Apart from the good cycle regulation, the deficiency symptoms were eliminated completely in 19 women and almost completely in 1 woman. Checks of the FSH, LH, 17beta-oestradiol and oestrone serum levels conducted at random during a medication cycle showed only a slight influence on the gonadotropin level. During the medication, E2 can be demonstrated in comparison to E1 at a ratio of 1:10.


Carbohydrate metabolism and hormonal replacement therapy: problems and clinical results. Substitution treatment with a biphasic hormone combination (Cyclacur) was administered to twenty women in menopause. Nine of these had undergone hysterectomy and/or ovarectomy. The experimental cycle consisted of a daily dose of 2 mg estradiol valerianate as estrogen for 11 days, the identical dose of estrogen plus 0.5 mg dl-norgestrel as gestagen for 10 days, and a 7-day medication-free period. An initial placebo cycle was administered, followed by 7 experimental cycles and one final placebo cycle. Laboratory tests were carried out regularly. There were no significant changes during the investigation in serum lipids, blood sugar values, or serum enzyme tests used as parameters of hepatic function. Of the hematological parameters a moderate rise in hematocrit was observed. There was no change in serum protein-bound iodine.


The immunological paradox of pregnancy.

The immunological paradox of pregnancy. During a normal pregnancy the fetus can be regarded as a transplant inside the uterus. The reason why this transplant is not rejected is still unclear. In this work various models for this immunological paradox and recent results within the field of pregnancy immunology are discussed. From an immunological point of view the development of a normal pregnancy is almost impossible. During all stages the embryo can be regarded as a transplant (4), but instead of the expected rejection an intimate parasitic graft - host relationship is established. The sperm has already been shown to be the carrier of transplantation antigens and thus theoretically capable of initiating an immune response. The fertilized egg also carries transplantation antigens on its surface after the first division. Foreign transplantation antigens release in the receiver a cell mediated immune reaction, which normally causes a rejection within some weeks.


The relationship between age-dependent immunological competence of host and tumor growth in the hamster-bovine adenovirus type 3 system. The relationship of aging to carcinogenesis was immunologically examined in the hamster-bovine adenovirus type 3 system. The age of animals at the time of virus inoculation influenced the tumor growth and latency period, but not the tumor incidence. The immunological competence of hamsters to sheep red blood cells became matured around 4 weeks after birth and was not affected by the infection of bovine adenovirus type 3 (BAV-3). The strength of transplant immunity was dependent on the age of animals at the time of immunization. The growth of progressive type of tumors induced by inoculation with BAV-3 into younger animals was inhibited by the repeated inoculation of excess dose of BAV-3, administration of BCG and transfer of sensitized lymphocytes during the tumor latency. The growth of non-progressive type of tumors induced by inoculation with BAV-3 into adult hamsters was accelerated by administration of antithymocyte serum or thymectomy. The tolerance to tumor specific transplantation antigens did not play a critical role in the present system. The blocking activity to sensitized lymphocytes was demonstrated in the sera taken from hamsters developing a progressive type of tumor even in the early period of carcinogenesis.


Quantitative determination of free amino acids by gas-liquid chromatography with special reference to yeasts. A gas-liquid chromatographic method for quantitative determination of free amino acids in yeasts is described. The amino acids are extracted with boiling water and separated from interfering substances on a cation-exchange resin. They are analyzed as their n-propyl N-acetyl esters. The best separation of the derivatives was achieved when using glass columns containing a mixture of three polar phases.


Application of gas chromatography to diagnosis of microorganisms and infectious diseases. Gas chromatography (GC) can be used to characterize microorganisms chemically. Microbial whole cells and cell extracts can be analysed by GC after being thermally or chemically degraded, i.e. pyrolysed or hydrolysed. Microbial metabolic products can be detected by GC analysis of culture media or the atmosphere above such media, i.e. headspace analysis. Pyrolysis products can be analysed direct, while hydrolysis products and non-volatile metabolites must be derivatized before being chromatographed. Differences in the chromatographic patterns can be used to differentiate between microorganisms. Detection of metabolic products in body fluids by means of GC constitutes a potential technique for the rapid diagnosis of infectious diseases.


Diagnosis of anaerobic infections by gas-liquid chromatography. Anaerobic bacteriology of clinical specimens is an expensive and time-consuming operation. In the present investigation it was shown that fatty acids produced by anaerobic bacteria may serve as bacterial markers in clinical material. Ten specimens of pus were analyzed by gas liquid chromatography and the results were compared with the bacteriological findings. Good correlations were found for the recovery of Bacteroides fragilis and the presence of isobutyric, butyric and succinic acids. It is concluded that direct gas-liquid chromatography of clinical specimens provides a rapid presumptive test for the presence of B. fragilis in anaerobic infections.


Effect of local irradiation on the acute rejection process in transplanted kidneys. The graft in 178 renal transplant patients was irradiated in an effort to halt acute rejection phenomena. Of the patients, 61 per cent received their transplant from either a sibling, parent or child and 38 per cent received cadaveric kidneys. Of the irradiated kidneys 61 per cent were functioning at 6 months, 58 per cent at 12 months and 49 per cent at 18 months. The rational for irradiation of transplanted kidneys with acute rejection is discussed.


Effect of clofibrate and calcium in type II A hyperlipoproteinaemia. In type II A hyperlipoproteinaemia, treatment with cholestyramine (12 g), calcium clofibrate (2 g) and a combination of calcium clofibrate and calcium carbonate (2 + 2 g) reduced the cholesterol concentration. The combination of calcium and clofibrate was at least as effective as cholestyramine. Calcium clofibrate decreased very low density and low density lipoprotein cholesterol, triglycerides and phospholipids, whereas no changes were found in high density lipoproteins. Cholestyramine decreased low density lipoprotein lipids.


Chemical basis for pharmacological and therapeutic actions of penicillamine. The pharmacological and therapeutic action of penicillamine are very largely explained by its ability to chelate metal ions and take part in oxidation-reduction reactions, sulfhydryl-disulfide interchange, and nucleophilic addition. Effects of penicillamine on particular enzymes are explained by its chemical properties. Possible interactions with amino acids, tissue proteins, food constituents, and intermediates in the metabolism and biosynthesis of sulfur containing amino acids are discussed.


[Reconstruction of the postcranial skeleton of an infant of Neanderthal man from Kiik-Koba (the Soviet Union) (author's transl)]. The first study concerning the postnatal skeleton of Neanderthal man gives us information about the development of the skeleton of Neanderthal man in the earliest stage of postnatal ontogenetic development. The very good state of preservation of the postcranial skeleton of the infant of Neanderthal man from Kiik-Koba in the Crimea made it possible to carry out for the first time a graphic reconstruction of the entire skeleton in norma frontalis and norma lateralis, in natural size. In this way we have obtained the necessary information for evaluation of body height, for the establishment of body proportions of an infant of Neanderthal man, and for a comparison of these proportions with those of a recent infant of a European that is on the same stage of ontogenetic development.


[To the foundation year of the leading German breast milk bank in Erfurt (author's transl)]. The character of the breast milk bank after the model introduced by Dr. med. M.-E. Kayser is dealt with and an attempt is made by using old records to determine approximately exactly the date the Erfurt breast milk bank was established, as this date is still being disputed in the bibliography.


Managing soft tissue injuries.

Managing soft tissue injuries. The management of soft tissue injuries of the face is best approached in an organized manner. The goal is early functional and cosmetic rehabilitation. The steps to be undertaken should be: initial evaluation, planning, repair and follow-up. Thorough cleansing with minimal debridement, use of fine suture material and early suture removal are some of the important principles.


Effects of intravenous verapamil on hemodynamics in patients with heart disease. The hemodynamic effects of intravenous verapamil (10 mg.) were evaluated in 13 patients with coronary artery disease and in seven patients with rheumatic valvular disease during cardiac catheterization. The peak effects were apparent at 3 to 5 minutes after injection and lasted about 10 minutes. The mean arterial pressure fell from 97.8 +/- 3.4 to 85.9 +/- 2.7 mm. Hg (-12%; p less than 0.01) accompanied by a significant decrease (-21%, p less than 0.001) in systemic vascular resistance (from 1435 +/- 80 to 1131 +/- 82 dynes-sex.-cm.-5) with an increase in left ventricular end-diastolic pressure (from 11.0 +/- 0.9 to 15.0 +/- 1.0 mm. Hg; +36%, p less than 0.01) and a reduction in LV dp/dt max (from 1343 +/- 152 to 1007 +/- 102 mm. Hg/sex.; -25%, p less than 0.05). The changes in heart rate (from 75.7 +/- 3.0 to 80.2 +/- 2.8 beats/min.), cardiac index (from 3.17 +/- 0.15 to 3.61 +/- 0.17 L./min./M.2), left ventricular minute work (from 3.63 +/- 0.28 to 3.31 +/- 0.23 Kg.-m./min./M.2) and mean pulmonary artery pressures (from 15.7 +/- 1.0 to 18.1 +/- 0.8 mm. Hg) were not statistically significant. The intrinsic negative inotropic action of verapamil is, therefore, minimized by its effect on afterload so that cardiac index is not reduced by the drug in patients with cardiac disease.


The injury-vasospasm hypothesis of ischemic heart disease, revisited. The injury-vasospasm hypothesis of IHD was discussed in relation to coronary artery autoregulation and the anoxic-feedback mechanism. Observations in the recent literature, not usually attributed to spasm, were examined in light of this phenomenon. This includes reperfusion models of experimental AMI, the association of AMI with myocarditis, and findings in AMI and SCD as necrotic microlesions, prodromata, and epicardial arterial plaque rupture and hemorrhage. The disparity between the severity of coronary disease and the occurrence of the various types of IHD suggest that atherosclerosis itself does not precipitate attacks of chest pain. It was emphasized that plaque rupture due to spasm might help induce CAT. With exercise, the possible importance of the autoregulatory system was explored in the prevention and induction of AMI and SCD, and the improvement of AP. The role of spasm in IHD should be defined.


Immunocytochemical localization of a gastric imhibitory polypeptide-like material within A-cells of the endocrine pancreas. In rat pancreatic islets, the glucagon-producing A-cells also contain a GIP-like material as revealed by the peroxidase-antiperoxidase immunocytochemical technique. Control studies showed that this dual staining was not due to the cross-reactivity of anti-GIP with glucagon. It is concluded either that the A-cells synthesize a GIP-like peptide or that it is taken up from the circulation.


Correlative fluorescence-immunocytochemical technique for the localization of monoamines and neurophysin (NP). A correlative fluorescence-immunocytochemical technique for the localization of monoamines and neurophysin on sections of freeze-dried tissues is described. An extensive network of monoamine-containing perikarya and terminals was found throughout the hypothalamus and median eminence. Immunocytochemical localization of antisera for neurophysin was found in the supraoptic and paraventricular nuclei of the hypothalamus and in both the zona interna and zona externa of the median eminence. This correlative demonstration of both catecholamines and neuropeptides within the same tissue provides a new approach to the study of neurotransmitters and neurohormones and their role in the regulation of the peripheral endocrine system.


Correlation of cutaneous hypersensitivity with lymphocytic response to Candida albicans. The relationship between delayed cutaneous hypersensitivity to Candida albicans and in-vitro lymphocytic proliferative response using a highly sensitive micro-technic was studied in 26 healthy adult subjects and six children with chronic mucocutaneous candidiasis. The maximum in-vitro lymphocytic proliferative response in adult subjects with cutaneous hypersensitivity, 18.94 +/- 4.16 (SE), was significantly greater than that in those without cutaneous reactions, 2.49 +/- 0.45 (SE) (P less than 0.005). A close correlation was found between cutaneous hypersensitivity (mean diameter of induration at 48 hours) and in-vitro lymphocytic proliferative response (r = 0.73, P less than 0.001). A cutaneous reaction of 5 mm or more of induration after injection of 0.1 ml of 1:100 Candida albicans extract corresponded to an in-vitro lymphocytic proliferative index of 5 or more (P less than 0.005), which supports the previously empiric use of 5 mm of induration as an indicator of intact cellular immunity in clinical practice. In the children with chronic mucocutaneous candidiasis, no consistent relationship between cutaneous hypersensitivity and lymphocytic proliferative response was found. Administration of Levamisole resulted in increased lymphocytic proliferation in vitro, and the development of cutaneous hypersensitivity, suggesting potentiation of cellular immune function.


Viral and immunological bases of beta cell failure in insulin-dependent diabetes. Pathologists have confirmed the specific nature of the insulitis lesion in diabetes requiring insulin. Data from genetic studies implicate both genetic and environmental influences as important in the appearance of overt disease. Certain HLA histocompatibility antigens are associated with insulin-dependent diabetes and have been interpreted as markers for closely linked immune response genes, a situation that may lead to beta cell susceptibility to viral injury or to uncontrolled beta cell autoaggression following beta cell damage. There is much circumstantial evidence that viruses may precipitate the disease (coxsackie) or may precede the disease onset by a long interval (mumps, rubella). However, susceptibility to virus, if it exists in human insulin-requiring diabetes, would appear on clinical grounds to be localized to the pancreas. Autoimmune phenomena are common in insulin-requiring diabetes, and there is both human and animal evidence that suggest that cell-mediated immunity may have a central pathogenic role. The recent explosion of new findings should lead to a clearer understanding of the nature of the disease, and this knowledge will hopefully lend itself to the prevention or arrest of the disease through immunological intervention, vaccination programs, or other means yet to be discovered.


Nature and nurture in the expression of diabetes mellitus and its vascular manifestations. The prevailing concept of etiologic heterogeneity for the diabetes mellitus syndrome is one of multiple genetic factors interacting with a variety of environmental influences. Variation in expression of the disorder, particularly the need for insulin, does not correlate with known etiologic distinctions. There is much evidence for genetic heterogeneity, as well as phenotypic variation when etiology can be presumed to be identical. The vascular manifestations of diabetes include microangiopathy unique to diabetes and larger vessel disease that differs from that of normal aging only by its prematurity. There is as much evidence for heterogeneity of the vascular expression as there is for glucose intolerance. Approximately 25% of persons with insulin-dependent diabetes may never develop the microvascular disease. The pathogenesis of vascular disease in diabetes may involve a number of abnormalities of plasma, circulating cells, and vascular tissue. Were absolute control of glycemia possible, some of the contributing factors involved in vasculopathy would possibly be alleviated. In the absence of automated physiologic insulin replacement the potential deleterious effect of our current methods of treatment might be reduced by specific inhibition of excess catecholamine, growth hormone and/or glucagon responses.


Radionuclide diagnosis of bleeding Meckel's diverticulum in children. The preoperative diagnosis of rectal bleeding due to Meckel's diverticulum in children has major difficulties when only standard clinical and radiographic technics are utilized. During the past three years we have done 70 studies with Tc99m pertechnetate for this suspected diagnosis using scintillation camera imaging and computer analysis. Five positive cases were identified and all verified at surgery. No false positives were noted. We believe this to be a safe and available procedure that should be considered a primary diagnostic modality in the investigation of young children with suspected bleeding Meckel's diverticulum.


Hepatitis B in ward and clinical laboratory employees of a general hospital. After a sharp increase in viral hepatitis cases, mostly type B, among the 2000 employees of a general hospital during three years, we conducted an investigation which consisted of obtaining data on employee cases and surveying many current employees. Of the 38 cases, 22 occurred in non-physician, ward employees. Of 189 current ward employees, 8% had antibody to hepatitis B surface antigen (anti-HBS) and 1% had hepatitis B surface antigen (HBSAg). Hepatitis B virus (HBV) seropositivity was highest for employees who worked closely with hemodialysis and renal transplant patients and for those who claimed that their ward was understaffed. Nine of the 38 cases occurred in clinical lab workers. Of 70 current lab employees, 17% were positive for anti-HBS and none for HBSAg. HBV seropositivity was highest for those working in the chemistry section (highest there among those performing blood-gas determinations and those working with the multi-channel autoanalyzers) and those who routinely got blood on their skin and clothes at work. All seropositive employees worked routinely with blood. These data support the hypotheses that many hospital employees contract hepatitis B from exposure to HBSAg-positive patients and many clinical laboratory employees contract it from exposure to HBV-contaminated blood.


Comparison of bovine lung and porcine intestinal heparin for arterial thrombosis in man. The clinical effectiveness of bovine lung heparin and porcine intestinal heparin for reducing arterial thrombosis was compared in a study of 64 surgical patients (mean age, 63.8 years). Immediately prior to operation, the radial artery was cannulated. The catheters were flushed continuously at a flow rate of 3 ml/hr with 0.9% sodium chloride solution without heparin or with two units per milliliter of either beef lung or pork intestinal mucosa heparin. After 24 hours, arteriography was performed, and vessel diameter and the amount of thrombus present were recorded. The addition of heparin to the flush solution significantly reduced the accumulation of thrombotic material on the surface of intra-arterial cannulae, thus lowering the incidence of clinically detectable arterial occlusion. No significant difference was found in the anticoagulant effectiveness of beef lung-derived heparin as compared with heparin obtained from pork intestinal mucosa.


Joint Commission on Accreditation of Hospitals' 1977 standards for pharmaceutical services. New standards for pharmaceutical services in hospitals, recently approved by the Board of Commissioners of the Joint Commision of Accreditation of Hospitals (JCAH), are presented and compared with the previous standards. The efforts of the American Society of Hospital Pharmacists in working with JCAH to upgrade the pharmacy standards are reviewed. The new standards reflect progressive hospital pharmacy practice and focus of the hospital pharmacist's patient-care activities.


Joint Commission on Accreditation of Hospitals--twenty-five years of promoting improved health care services. A brief history of the Joint Commission  on Accreditation of Hospitals (JCAH), as well as its structure, purpose and activities, is presented. The procedure for developing JCAH standards for health care facilities is discussed. Also presented are the survey and accreditation processes. It is concluded that as long as the United States values its tradition of voluntarism and believes in positive motivation, the JCAH will be an effective influence on improved health care services.


Drug therapy reviews: tricyclic antidepressant and monoamine oxidase inhibitor combination therapy. Combinations of monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are discussed with regard to general toxicity, drug interactions, animal studies, clinical reports, efficacy of combination therapy and usage conditions. Although MAOI-TCA combinations are usually considered contraindicated, informed opinion has shifted to cautious recommendation for the combination. Only refractory patients in whom less hazardous treatment has failed should be considered for combination therapy. The preferred dosage regimen is administration of the MAOI t.i.d. during the day and the entire TCA dose at bedtime. Patients should be informed of the immediate need for medical advice should side effects occur. It is concluded that the simultaneous administration of these agents is potentially efficacious and safe is carefully monitored and controlled.


High-dose methotrexate with folinic acid rescue. A brief review of the pharmacology of methotrexate is presented, and the rationale for the administration of high-dose methotrexate and the necessity of a folinic acid rescue to prevent methotrexate toxicity are discussed. Critical factors concenrning the use of this therapy, as well as unusual toxicities associated with the use of high-dose methotrexate, are presented. Several drug-and patient-related variables which may affect the toxicity of this dual drug administration are discussed to better enable pharmacists to monitor patients receiving this form of therapy. High-dose methotrexate with folinic acid rescue has improved the therapeutic index of methotrexate. The optimal dosage and duration of the two agents are yet to be determined.


Intramuscular injections and bioavailability. Bioavailability of drugs following intramuscular injection is reviewed, with particular emphasis on diazepam, chlordiazepoxide, phenytoin, digoxin and lidocaine. Clinical experience with these drugs has shown that i.m. absorption may be slow, erratic or incomplete. Factors which play a role in the bioavailability of i.m. medications include the water solubility of the drug, dispersion of the injected solution and blood flow at the muscle site. For many drugs, intravenous injection is the parenteral route of choice, and oral administration may be more efficacious than i.m. injection.


Cadaver renal transplantation in children with cystinosis. Five children with end-stage renal disease resulting from cystinosis received seven cadaver renal allografts. Four recipients have functioning grafts eight to 55 months after receiving the transplant and one recipient lost two grafts at 17 and 26 months after the transplant. There was no florid recurrence of the Fanconi syndrome although proximal renal tubular dysfunction developed in two patients, in one in association with chronic rejection and in one without apparent etiology. Free cystine content of white blood cells, cultured skin fibroblasts and allograft tissue was significantly increased. Cystine crystals were observed in the mesangium of two grafts and in the interstitial tissue of all grafts; however, no cystine crystals were found in the tubules. The location of the cystine crystals, as well as the fact that the highest free level of cystine of allograft tissue was observed in the graft undergoing chronic rejection. led to the hypothesis that recipient cells infiltrating the graft were the source of cystine deposition. The data indicate that successful cadaveric transplantation does not correct the primary metabolic defect in cystinosis, thereby explaining the persistence of the extrarenal clinical manifestations, such as photophobia and hypothyroidism, after renal transplantation in cystinosis.


One hundred years of cytogenetic studies in health and disease. Cytologic observations have greatly contributed to our understanding of the modes of transmission, expression, and action of genetic determinants in tissues and organisms. While the elucidation of chromosome migration and distribution during gametogenesis (i.e., the segregation and independent assortment of chromosomes in the germ cells) provided a physical basis and a mechanism for the implementation of Mendelian principles, cytogenetics did not illuminate our practical knowledge of human biology until it was applied to eukaryotic somatic cells with ease, speed, and accuracy. As a result of these achievements of the late 1950s, the study of the chromosome complement is now routinely available. Karyotypic analysis established that genetic imbalances such as trisomies and deletions account for one-fifth or more of all spontaneous abortions and for one-fifth of all serious but viable birth defects, most of them with impaired mental development. Most chromosome errors are the result of a gametal or zygotic mishap and can be detected by fetal cell sampling through amniocentesis. In recent years more refined techniques (chromosome banding methods) have further increased the level of resolution at which anomalies can be detected. These techniques, along with the development of methods to hybridize somatic cells, have greatly assisted in the assignment of particular genes to particular chromosomes.


Recurrence of macular corneal dystrophy after lamellar keratoplasty. A 20-year-old man required bilateral lamellar keratoplasties for macular corneal dystrophy. Histochemical proof of macular corneal dystrophy was demonstrated in both of the excised lamellar corneal buttons. Eleven years later, the patient underwent a penetrating kiratoplasty in his left eye. Light microscopic, histochemical, and electron microscopic study of the excised button disclosed characteristic features of macular corneal dystrophy in the donor cornea. Recurrence of macular corneal dystrophy in a corneal graft appeared to be the result of replacement of the donor keratocytes by genetically defective host cells.


Corneal sensation in Adie's syndrome.

Corneal sensation in Adie's syndrome. Using the Cochet-Bonnet esthesiometer, we evaluated the corneal sensation of 11 patients with unilateral Adie's tonic pupil. We eliminated six other patients with bilateral Adie's pupil or disease that lowered corneal sensation. An observed unfamiliar with each patient's condition tested 12 clock hour positions in the midperiphery in both eyes of all patients. We studied 30 normal subjects (60 eyes) in a similar fashion. Of those 11 patients with unilateral Adie's syndrome, ten had a regional decrease in corneal sensation. The 30 normal subjects examined did not exhibit any significant decrease in corneal sensation in any areas. Our study supports the concept that the lesion of Adie's tonic pupil is in the ciliary ganglion or short location where the innervation of the iris sphincter and corneal sensation are found together.


Ineffectiveness of indomethacin in the treatment of chronic cystoid macular edema. A controlled, double-masked study in which patients with cystoid macular edema of more than four months' duration were treated with indomethacin failed to demonstrate a significant visual improvement when compared to patients who were treated with placebo.


Macular lesions in Alport's disease.

Macular lesions in Alport's disease. In three male patients with Alport's disease, two of them successfully treated by kidney transplantation, ophthalmoscopy revealed bilaterally densely packed whitish-yellow lesions around, and to some extent in, the macular area. These spots, superficially located in the retina, have not been previosly desribed in Alport's disease.


Conjuctivitis and keratoconjunctivitis associated with primary immunodeficiency diseases. Nineteen patients with a variety of well-defined primary immunodeficiency diseases were examined for ocular abnormalities. Eight patients with low levels, or absence, of all the major serum immunoglobulins had conjunctivitis or keratoconjunctivitis associated with bacterial infection. The remaining 11 patients, who had at least one immunoglobulin class present in normal concentration in the serum, showed no inflammatory ocular lesion. Absence of only IgA, the major tear immunoglobulin, did not predispose the eye to these lesions.


Ultrastructural appearance and morphogenesis of renal glomerular hematoxylin bodies. The fine morphology of hematoxylin bodies--structures which, by light microscopy, are considered to be pathognomonic for systemic lupus erythematosus--is described in renal glomeruli. These bodies are highly pleomorphic and are predominantly of cellular origin. The nuclear components, which are responsible for the characteristic tinctorial properties, appear as aggregates of clumped chromatin and/or irregular masses of finely granular, moderately dense, lobulated material, generally enveloped by membranes. The cytoplasmic components consist of a multitude of vesicles, vacuoles, degenerating granules, and glycogen. Hematoxylin bodies are usually contained within the bounderies of mesangial cells. A transition from circulating leukocytes to typical hematoxylin bodies could be demonstrated. It is suggested that the changes in leukocytes which culminate in hematoxylin bodies are intiated by the action of antinuclear antibodies and also possibly by the ingestion of immune complexes. This proposed appearance and morphogenesis of hematoxylin bodies is in general agreement with a few previously published investigations on these structures and also with the in vitro counterpart, the lupus erythematosus (LE) cell.


Structural changes within the media of coronary arteries related to intimal thickening. From observations on 454 coronary arteries from subjects ranging in age from prematurely newborn to 90 years, six structural patterns of medial smooth muscle are interpreted as representing, or related to, the proliferation and/or migration of medial smooth muscle into intima. By measuring the extent of inner medial circumference occupied by four of the six patterns, it was possible to calculate a numerical value designated the medial proliferatice and / or migratory activity (MP-MA) of each artery. During the first three decades, nonatherosclerotic diffuse intimal thickening was the characteristic intimal process, and during this phase of the arterial maturation span, the MP-MA of the arteries was significantly related to the degree of intimal thickening. Following a peak MP-MA level by the end of the third decade, there was a progressive decrease in the MP-MA level as the incidence and severity of atherosclerotic intimal thickening increased. At advanced stages of atherosclerotic intimal thickening, which were associated with thinning of adjacent media, intimal-medial structural patterns indicating a relationship between medial smooth muscle proliferative activity and the expanding atherosclerotic plaque were also apparent. The observations support the concept that the movement of medial smooth muscle into intima is a critical step preceding and during the evolution of the atherosclerotic plaque.


Glomerular mesangial and endothelial cell swelling following temporary renal ischemia and its role in the no-reflow phenomenon. The purpose of these experiments was to define changes in glomeruli of rats kidneys which could account for a marked reduction of blood flow immediately following temporary ischemia. After the renal artery had been clamped for 60 minutes, mesangial and endothelial cellular swelling was sufficiently severe to compress and trap intracapillary erythrocytes, obstruct capillary lumens, and prevent reflow of an isotonic carbon suspension. Perfusion of saline solution before the renal arteries were clamped washed blood from the kidney, and the resulting cellular swelling alone was not sufficient to block capillary lumens. Erythrocyte trapping did not occur after 15 minutes of ischemia. Swelling of glomerular and tubular epithelial cells produced some extrinsic capillary compression that could contribute to erythrocyte trapping, but this appeared to be of minor importance in producing the no-reflow phenomenon.


Ultrastructural basis of the vasculopathy in and around brain tuberculomas. Possible significance of altered basement membrane. The fine structure of small blood vessels in and around ten brain tuberculomas was examined. In the peripheral reactive zone of the tuberculomas, examination of 1-mu-thick survey sections established the chronic inflammatory process and the vasculitis characterized by infiltration of the vasomurium (vessel wall) by large and small mononuclear cells. This reaction was typical of chronic epithelioid cell granuloma. Electron microscopic examination of the reactive zone confirmed the vascular proliferation and vasculitis, the venule being the most frequently involved type of blood vessel. It showed the infiltrating cells to lie amidst osmiophilic, concentrically proliferated basement membrane laminae, which formed the greater part of the thickened vessel wall, generally surrounding the endothelial cells directly, the pericytes having disappeared. This appearance, together with the results of Gomori's reticulin stain on paraffin sections, suggested that the altered basement membrane material was reticulin. The possibility is discussed that the altered basement membrane material could be antigenic and that it might be responsible for perpetuating the necrotic vascular and perivascular reaction in tuberculous meningitis and tuberculomas. The above change in the basement membrane was not encountered in the blood vessels of the surrounding edematous brain. The endothelial cells and tight junctions were relatively well-preserved. Intact arterioles could be recognized even in severely edematous brain tissue. At both sites the fine structure of the blood vessels was typical of that expected in the central nervous system. Fenestrated vessels were not seen. The perivascular astrocytic end-feet were destroyed in the reactive zone and either distended or ruptured in the overtly edematous brain tissue also. In the central caseous part of the tuberculoma, there were few blood vessels, and they were in a state of advanced necrosis, but ghost outlines of proliferated basement membrane could be seen.


Myocardial changes in malignant hyperthermia. Although consideral information is available concerning the structural and biochemical changes in the skeletal muscles of patients with malignant hyperthermia, little is known of the cardiac changes in this disease. However, ventricular fibrillation and cardiac arrest are frequent in these patients. In 3 patients with malignant hyperthermia, contraction bands and foci of myofiberlysis were found in the heart at necropsy. Ultrastructurally, areas of myofiber overstretching adjacent to contraction bands and foci of extensive myofiberlysis were associated with disruptions of the sarcolemma. Similar ultrastructural findings have been reported in the skeletal muscles of these patients and are thought responsible for the hyperkalemia which is a constant feature of malignant hyperthermia. Our findings suggest that the ventricular arrhythmias, frequent in this disease, are the result of direct damage to cardiac muscle rather then secondary to elevated plasma levels of potassium.


Ethanol--its nephrotoxic effect in the rat. The nephrotoxic effect of ethanol feeding on renal structure and function was evaluated in rats and compared to that in dextrose-fed isocaloric control animals. Alcohol-fed animals had larger kidneys than their controls. Despite this increase in renal mass, the alcohol-fed animals had a 50% reduction in creatinine clearance and a 67% reduction in osmolar clearance compared to their controls. When specific renal constituents were compared, the alcohol-fed animals were found to have twice the renal protein and a 50% increase in renal lipid. Despite these marked structural and functional differences, the light microscopic appearance of the kidneys of the two groups did not appear significantly different. In contrast, the electron microscopic differences were substantial. The renal epithelial cells, particularly of the distal tubules and Henle's loops, were found to show varying degrees of cellular injury and were observed to be sloughing into the lumens. These electron microscopic observations are similar to those obtained in tubular necrosis due to a variety of nephrotoxic agents. We propose, therefore, that chronic alcohol feeding of rats produces significant renal dysfunction and abnormalities of structure such that ethanol should be considered a true nephrotoxin.


Ultrastructure of the degradation of erythrocytes by thyroid epithelial cells in vivo. The ultrastructure of the degradation of red blood cells (RBCs) in vivo by rat thyroid epithelial cells was studied. Two morphologically distinct degradative pathways appeared evident. The granular pathway was characterized by a finely mottled appearance of RBC phagosomes, first observed about the RBC periphery and later extending to the entire RBC matrix. Such phagosomes became gradually smaller, less electron dense, and indistinguishable from cellular lysosomes. The hemolytic degrative pathway was characterized by a progessive, usually homogenous decrease in the density of the RBC matrix except at the periphery of the RBC, where a thin, dense layer persisted for some time. Such phagosomes often appeared swollen relative to freshly ingested RBCs and resembled RBC ghosts. In later stages, they became irregular, smaller, and gradually indistinguishable from cellular lysosomes. Both degradative pathways were associated with ferritin-like particles. The earliest visualization of ferritin was in the cytoplasm, but in later stages it was also found to be concentrated within lysosomes and phagolysosomes.


Sheep lactate entry-rate measurements: error due to sampling jugular blood. Carotid arterial and jugular venous blood samples were taken simultaneously during primed continuous infusions of L-[U-14C]lactate in four sheep. The mean rate (n = 4) of total net formation of lactate (0.394 +/- 0.047 mg C/min per kg) calculated from the results obtained by analyzing the jugular blood samples for lactate concentration and specific radioactivity was significantly higher (0.01 greater than P greater than 0.005) than the mean rate (n = 4) calculated from the results of analysis of the arterial samples (0.302 +/- 0.036 mg C/min per kg). The error in the estimation of the rate of total net formation of lactate due to jugular sampling resulted from the negative arteriovenous difference found for lactate across the tissues of the head. These results illustrate the general need for examination of the suitability of venous sampling in experiments that make use of the continuous infusion isotope-dilution method.


Evidence for a histamine H2 receptor that inhibits pepsin secretion in the dog. H+ and pepsin output were studied in four gastric fistula dogs with histamine and in five dogs with 4-methylhistamine (4(Me)H), an H2 histamine receptor agonist with little H1 effect. Each amine was given in 45-min incremental step doses to constitute full dose-response curves. Pepsin output was biphasic with both drugs. Peak pepsin output occurred at low doses (less than or equal to 5 microgram/kg-h) and progressive inhibition of output was seen at higher doses, but H+ output was stimulated at all doses. The H2 receptor antagonist, cimetidine, competitively inhibited H+ stimulation. The pepsin response to histamine or 4(Me)H was converted to a positive logsigmoid response when cimetidine was given at the same time. In the presence of cimetidine (1 mg/kg-h), the outputs of H+ and pepsin were positively correlated in the full histamine dose range. These data show that histamine effects on pepsin secretin are a mixture of stimulation and inhibition and that the receptor responsible for pepsin stimulation is of a high affinity, low Km, H2 type, whereas inhibition at high doses of histamine is probably mediated by a low affinity, high Km receptor, also H2 type.


Physiological parameters of indicator dilution curves. A model incorporating the effects of recirculation time lag, cardiac output, clearance, volume of distribution, and the variance of the distribution of recirculation times is applied to the analysis of indicator dilution curves. Experiments on dogs with use of radioactively labeled diethylenetriaminepentaacetic acid were done to evaluate the model. This five-parameter model can be fitted to data obtained during the period from less than 1 min to 3 h after a single injection of indicator. Estimates of cardiac output and clearance are in satisfactory agreement with estimates obtained by alternative techniques. Estimates of the time lag and volume of distribution are of physiologically plausible magnitude. The variance of the distribution of recirculation times is a new parameter, of which the possible usefulness to physiologists is discussed.


Comparison of metabolic alterations in hypothalamic and high fat diet-induced obesity. The heterogeneous nature of the experimental obesities induced by ventromedial hypothalamic (VMH) lesion and high fat diet (HFD) have been demonstrated by comparing VMH-lesioned and sham-operated rats fed a HFD or low fat diet (LFD). VMH rats had increased fat mass serum insulin and serum triglycerides but lower serum glucagon and smaller salivary glands than sham-operated animals. The body weight of HFD obese rats was intermediate between VMH and sham-operated animals on the LDF. Liver and fat pad weights showed effects of lesions and diet. Diet did not affect plasma glucagon or insulin. Pair-feeding VMH rats with sham-operated rats prevented weight gain but did not prevent the increase in insulin and fall in glucagon. Studies of insulin secretion from isolated perifused islets showed that basal and both phases of stimulated secretion were significantly increased in VMH groups. The changes in plasma insulin, plasma glucagon, and salivary gland weight in VMH groups are interpreted as showing decreased activity of the sympathetic nervous system following VMH lesions.


Prostaglandins and the kidney.

Prostaglandins and the kidney. This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cyclo-oxygenase in the kidney to PGF2, PGF2alpha, PGD2, and, possibly, to PGI2 and thromboxane A2. Production of PGE2 and PGF2alpha is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2alpha and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis.


Autoregulation of nephron filtration rate in the dog assessed by indicator-dilution technique. Micropuncture studies were conducted in anesthetized dogs to evaluate single nephron glomerular filtrate rate (SNGFR) and SNGFR autoregulation when assessed by means of an indicator-dilution technique (SNGFRID), which does not require interruption of distal volume delivery. In 18 dogs, control renal arterial pressure was 124 +/- 11 mmHg (SD), renal blood flow (RBF) was 185 +/- 58 ml/min, and whole kidney GRF was 37 +/- 7 ml/min. SNGFRID averaged 57 +/- 15 nl/min and was significantly lower than SNGFR determined on the basis of total collections (SNGFRTC) from proximal tubules (75 +/- 17 nl/min). However, SNGFRID was not significantly different from the overall average SNGFR of 62 +/- 12 nl/min estimated from whole kidney GFR and the total number of glomeruli (613,000 +/- 74,000). In 10 animals, renal arterial pressure was reduced to an average of 94 +/- 8 mmHg; whole kidney autoregulation was highly efficient and average RBF and GRF remained within 1 and 3% of their control values. Likewise, SNGFRID was not significantly altered at 52 +/- 17 and 52 +/- 16 nl/min. In contrast, SNGFRTC decreased significantly from 72 +/- 17 to 51 +/- 13 nl/min. These results indicate that the indicator-dilution technique provides a reliable assessment of SNGFR and allows the manifestation of single nephron autoregulatory behavior. They provide further support for the hypothesis that maintenance of distal volume delivery may be a necessary aspect of the autoregulation phenomenon.


Heterogeneity of intracortical peritubular plasma flow in the rat kidney. The 86 Rb-accumulation technique was adapted to the study of intracortical peritubule plasma flow patterns in the rat kidney. A rapid intravenous bolus of 86Rb (50 micronCi) was given to anesthetized nondiuretic rats. One kidney pedicle was tied at 6 s, the other at 12 s. In group I (1o rats) [3H]PAH clearance was measured prior to the 86Rb bolus. In group II (six rats) 86Rb and [3H]PAH (100 micronCi) were given together. The kidneys were snap-frozen, then sliced at -6 degrees C. There were no differences in renal plasma flow (RPF) as measured by either tracer in either group, no differences in the intracortical distribution of [3H]PAH and 86Rb, and no changes in the 86Rb distribution between 6 and 12 s. Tissue plasma flow (TPF) as measured by 86Rb in ml/min per g was 3.88 +/- 0.22 (SE) (142% of RPF/g kidney wt) for cortex 1 (outermost), 3.90 +/- 0.21 for cortex 2, 3.26 +/- 0.14 for cortex 3 (P less than 0.025), 2.17 for cortex 4 (P less than 0.001), 1.34 for cortex-medulla junction (P less than 0.001), and 0.88 +/- 0.07 for outer stripe (P less than 0.001). Peritubular capillary plasma flow, derived as TPF minus GRF/g in each slice, fell progressively from cortex 1 to outer stripe. This is thought to represent lower perfusion rate of "medullary rays."