A comparative study of daily followed by twice or once weekly regimens of ethambutol and rifampicin in retreatment of patients with pulmonary tuberculosis. The results at 1 year. A cooperative tuberculosis chemotherapy study in Poland. The present report concerns the results at 1 year of a co-operative controlled clinical study carried out in Poland of the retreatment of patients with active, chronic, polyresistant far-advance pulmonary tuberculosis with an oral regimen of daily followed by intermittent ethambutol and rifampicin. A comparison was made of once- and twice-weekly supervised intermittent regimens of rifampicin 1200 mg plus ethambutol 50 mg/kg body weight under out-patient conditions after an initial inpatient phase of rifampicin 600 mg and ethambutol 25 mg/kg daily for 12 weeks. Patients were allocated at random to the regimens. Of 247 patients admitted to the study, 201 (81 per cent) completed 1 year's treatment as prescribed by the protocol, 46 (19 per cent) patients terminated their treatment prematurely before 1 year. After the daily phase of 12 weeks' treatment, 82 per cent were negative on smear and 85 per cent on culture; in the continuation intermittent phase, 98 per cent of patients in the once-weekly (E1R1) regimen were negative on culture at 28 weeks and 98 per cent in the twice-weekly (E2R2) regimen. The corresponding proportions at 52 weeks were 97 per cent and 97 per cent. At 12 months, 96 per cent of 101 ER/E1R1 and 96 per cent of 100 ER/E2R2 patients who completed 1 years' treatment were culture-negative.


A trial to investigate reactions and responses to BCG vaccines of different strengths prepared from the Copenhagen 1331 strain. Seven hundred and ninety-three tuberculin-negative school-children were vaccinated with BCG vaccine prepared from either the 1077 substrain, at 0-3 mg/ml moist weight, or the 1331 substrain at 0-15 and 0-3 mg/ml moist weight. Local vaccination reactions and Mantoux tuberculin conversion were measured. There were no differences between the 1077 vaccine and the lower strength 1331 vaccine. The more potent 1331 product, however, produced marginally larger vaccination lesions and a slightly increased tuberculin allergy. The small increase in size of the vaccination lesions was considered acceptable and vaccine of this type would be satisfactory for use in the United Kingdom.


Propantheline bromide in massive upper gastrointestinal haemorrhage. The effectiveness of the anticholinergic, propantheline bromide, administered parenterally in patients with upper gastro-intestinal bleeding has been investigated in a double-blind study. The basic material consisted of 99 patients. No differences were found between the group receiving propantheline bromide and the group receiving placebo in regard to clinical factors such as duration of intensive care, total hospital stay and surgical frequency. However, 21 patients under 50 years of age showed a significantly lower blood transfusion requirement with the use of propantheline bromide.


Cardiac output determinations with ear piece densitometry. The results of cardiac output determinations by a dye dilution technique were compared using (a) a dichromatic earpiece which was calibrated as a flow-through cuvette, but also permitted automatic computing by virtue of a pressure capsule, and (b) an ordinary flow-through densitometer. Eleven subjects, some with cardio-pulmonary disease, were investigated. Cardiac outputs were systematically overestimated when automatically computed. The results obtained by manual calculation with the ear-piece corresponded more nearly with those derived from the flow-through cuvette, but still with a deviation from the identity line and with a residual standard deviation of 0.8 l/min. Double determinations had a residual standard deviation of 0.7 l/min. Despite its ease of handling, an earpiece densitometer seems to be too unreliable to be suitable for routine use.


Plasma erythropoietin activity before and after renal homotransplantation in humans. Plasma erythropoietin levels were determined by Keighley's method to study the changes in erythropoiesis before and after human renal homotransplantation. Results. Erythropoietin titres in pre-transplant patients were low, while they returned to normal after successful renal transplantation. In acute rejection they were significantly high. After its reversal normal levels of erythropoietin were obtained in accordance with a normalization of the graft functions. Reticulocyte counts paralleled with erythropoietin values. Conclusion. High levels of plasma erythropoietin contribute to the diagnosis of acute rejection. Normalization of the plasma erythropoietin levels after the acute rejection could be regarded as an indication for good function of the graft. The grafted kidneys seem to function in producing erythropoietin.


Regional differences in patterns of urinary tract infections. The identity of 693 pathogenic bacilli isolated from 2,175 urine specimens cultured during a two-year period in southeastern New Mexico is presented along with results of sensitivity testing by Kirby-Bauer technique.  The pattern of infections and sensitivity studies in hospitalized patients is compared with that of office patients and contrasted with results noted in other areas.


Urinary tract infections in black female children. It has been demonstrated in several studies that prepubertal black females have a lower incidence of urinary tract infection than do white females of the same age. Other racial differences in the natural history of urinary tract infection have been suggested, but thus far very few young black girls with urinary tract infection have been thoroughly studied. The records of 56 black female children with urinary tract infections were reviewed and the clinical, laboratory, and radiologic manifestations of their diseases documented. No attempt was made to compare data from blacks to that from whites since many studies composed primarily of white children are available in recent literature. This study is offered as baseline data on black female children to which future studies of black or white children may be compared.


Wallace method of ureteroileal anastomosis. The Wallace technique for ureteroileal anastomosis was used in 28 consecutive patients requiring urinary diversion. Details of the surgical technique are reported. The method is found to be appropriate for children and adults, for primary ureteroileal anastomosis, or for revision of previous ureteroileal anastomosis done by other techniques, and for patients with one or two ureters. Its continued use appears to be indicated.


Transplantation in the hemolytic-uremic syndrome. A case history of a fifty-seven-year-old white woman with hemolytic-uremic syndrome who was successfully transplanted with a cadaver homograft is reported. A review of the pertinent literature regarding the pathophysiology of the syndrome and the experience to date with transplantation is presented.


Reversal of hypercoagulable state by bilateral nephrectomy. The hypercoagulable state associated with select cases of glomerulonephritis is difficult to diagnose by standard laboratory techniques but is clinically manifested by recurrent shunt and fistula thrombosis which may be refractory to anticoagulant therapy. Bilateral nephrectomy reversed this hypercoagulable state. After renal allograft, however, the patient experienced hyperacute rejection, and transplant nephrectomy was required to cure the recurrent hypercoagulable state. The mechanism of this previously unreported phenomenon and its implications with regard to renal transplantation are discussed.


Cadaver donor nephrectomy.

Cadaver donor nephrectomy. Optimal preservation of renal and ureteral structure and function is attempted by maintenance of renal circulation during heart-beating cadaver nephrectomy. Modifications of Ackermann's en bloc procedure for removal of cadaver kidneys are suggested to adapt this procedure to the heart-beating cadaver situation.


Polycythemia following renal transplantation. Among 60 renal allograft recipients, 3 patients were found to be polycythemic  with hematocrits greater than 55 and were studied extensively with various hematologic and radiographic procedures. None of the patients showed evidence of erythropoietin-secreting malignancies, renal cysts, hydronephrosis, or hypoxemia. All had elevated erythropoietin levels, and 1 showed evidence of platelet trapping in his transplanted kidney, suggesting that the chronic polycythemia may be related to transplant rejection.


Experimental evaluation of bladder closure techniques. Two methods of bladder closure have been evaluated in dogs. A conventional two-layer closure including the mucosa and a single layer running horizontal mattress extramucosal closure have been compared. Observations including adequacy of healing, strength of scar, degree of inflammatory reaction, dna degree of bladder adhesions have been made. The extramucosal running horizontal mattress closure appears to approach the ideal bladder closure.


Acute renal failure in sickle cell trait. Acute renal failure and a syndrome characteristic of acute renal vein thrombosis developed in a patient with sickle trait and gram-negative bacteremia. It is suggested that intrarenal vaso-occlusion by sickled erythrocytes produced signs and symptoms typical of renal vein thrombosis and contributed to the severity of the acute renal failure.


Traveling bullets in genitourinary tract. A bullet lodged in the renal parenchyma, then migrated into the collecting system over a two-month period causing acute renal colic and necessitating removal by pyelotomy. A review of the literature discloses only 8 cases of projectiles migrating in the urinary tract, 5 involving metallic fragments and 3 involving bullets.


Prototype for an implantable micropump powdered by piezoelectric disk benders. A prototype for an implantable mul pump to be used in an artificial pancreas has been constructed, in which pressure is developed by a bellows formed from 2 apposed piezoelectric disk benders connected to the high impedance secondary winding of aminiature transformer. Active valving, properly phased, is achieved by a miniature solenoid valve connected in series with the transformer primary winding and a rectangular wave generator.


Continuous single pass perfusion of the isolated kidney. The use of continuous single pass perfusion to study the metabolism of isolated kidneys reveals that active metabolic processes continue in the hypothermically preserved kidney. These preliminary experiments described demonstrated a rapid uptake of substrates from the perfusion media in the first 24 hrs of storage, followed by a release of organic acids in the subsequent 24 to 72 hrs. Urea was found to be easily eliminated from the kidney. This technique may be useful for studying events related to loss of renal function by pinpointing specific residual biochemical activity and lesions that occur during prolonged preservations. An eventual correction or prevention of such lesions might be feasible in order to improve preservation techniques.


Improved renal allograft survival using the mixed lymphocyte culture for selection of nonidentical living related donors. Our results concur with earlier published work, by other groups, showing that LRD-recipient pairs with low MLC stimulation usually have better and more prolonged graft success than do those with higher stimulation. Specific HL-A compatibilities or incompatibilities did not seem to affect these results, nor did the presence of an increased number of common loci, short of increasing the apparent chromosome compatibility. The presence of pre-transplant cytotoxic antibodies, in patients with a high MI, however, may unfavorably affect the LRD transplant. The overall results of our LRD transplant experience is shown in Figure 1, and superimposed upon Figure 2, is the current extrapolation of data showing MLC stimulation and haplotype success. Thus, it appears that graft survival may be improved and more closely approach the levels seen in a full-house, diplotype match, by using the MLC results in considering patients for transplantation. Not all patients with a high MLC, however, (see table) reject their grafts and it is impossible to predict pre-transplant who will develop specific allograft enhancement. Before the MI becomes a specific criteria for transplant selection, additional studies of patient stimulation in MLC should be done. Suppression of stimulation by donor cells in autologous serum, as compared to the response to unrelated controls, might provide pre-transplant clues to the presence of enhancing factors. Such studies could provide an index that would be more meaningful than the MI in AB sera alone. Since overall results from both our series and from the Transplant Registry continue to indicate better long term graft survival for LRD than for cadaver transplants, and since the evidence suggests that a successful transplant offers a patient a better quality of life, as well as decreased morbidity and mortality compared to concomitant time spent on hemodialysis, continued LRD transplants with high MI is warranted in some circumstances with the patient's understanding of the overall outcome and backgrouns. Until in vitro tests can be more predictive of individual rather than statistical graft success, the patient with an LRD and a high MI should be given a complete explanation of the probabilities for success or failure, and he and the donor allowed to make an informed decision. The following are guidelines that we proposed for the selection of LRD transplants: 1. Availability and willingness. 2. Medical and psycho-social clearance. 3. ABO compatibility. 4. Negative direct crossmatch. 5. HL-A diplotype or haplotype. 6. MI less than 10 if possible, with or without HL-A antibodies. 7. MI greater than 10 with no HL-A antibodies, if possible. 8. MI greater than 10, with HL-A antibodies, if both donor and recipient clearly understand the enhanced chance for failure.


The use of rapeseed meal as a protein supplement in poultry and pig diets. Rapeseed meal would be used in much larger amounts in poultry and pig diets if its use was related solely to cost and nutritive value. In certain circumstances there are undesirable effects that severely lmiit its use. Most of the rapeseed meal available at present in the UK is strongly goitrogenic when fed to poultry or pigs, but it is not certain if this is necessarily harmful, nor if this is related to other effects that occur in particular situations and are clearly undesirable. From current data, diets in which rapeseed meal can be included most satisfactorily are those for broilers, growing pullets and finishing pigs. Plant breeders are actively selecting types of rape that have low or zero thioglucoside content and it is hoped that these new varieties will cause none of the ill-effects described in this review.


Oral immunisation and its significance in the prophylactic control of enteritis in the preruminant calf. Oral immunisation using a feed-incorporated vaccine comprising heat inactivated Escherichia coli and Salmonellae antigens was examined in feeding trials with calves. The studies were conducted with batches of calves purchased at intervals throughout one year and reared in an environment created by continuous occupancy. Improved health was registered in terms of a significant reduction in the incidence and duration of diarrhoea (P less than 0.01) and in the need for treatment with medicament or antibiotics (P less than 0.01). Orally immunised calves showed a significantly better weight gain (1.44 kg, P less than 0.05) than the controls during the period 0 to 5 weeks. This gain was mainly obtained during the first three weeks when the antigen fed calves showed significantly improved faeces scores and a significantly better appetite for concentrates (P less than 0.05).


A new solid phase radioimmunoassay (CLB-RIA) for the detection of hepatitis-B antigen and antibody. A new competitive solid phase radioimmunoassay (CLB-RIA) has been developed for the detection of HBAg and HBAb in human serum and plasma. In the assay, sheep antibodies to HBAg, covalently linked to an insoluble carrier, highly purified 125-I labelled HBAg and the serum or plasma sample are incubated for 20 h at room temperature. After incubation, the bound and the free fraction of the tracer are separated by centrifugation. Both the presence of HBAg and HBAb, result in a decrease of the amount of bound tracer, when compared with a negative control serum. Differentiation between HBAg and HBAb requires the use of another type of radioimmunoassay. For this purpose a sandwich solid phase radioimmunoassay, for the detection of HBAb only, has been developed (CLB-AURIA). In this, assay-purified HBAg is covalently linked to an insoluble carrier. Using a mixture of both immunosorbents (insolubilized HBAg and HBAb), it is possible to detect and to  distinguish HBAg and HBAb in one single solid phase radioimmunoassay (CLB-MIRIA). The influence of three parameters on the CLB-RIA, the incubation time, the amount of tracer and the effect of Tween-20 has been studied. The sensitivity of the described solid phase CLB-RIA for the detection of HBAg is comparable to that of other radioimmunoassays reported in literature; its specificity is very high.


The effective oncotic pressure of dextran. Measurement of plasma volume before and after the acute infusion of commercial dextran revealed that all brands tested were hyperoncotic by a factor of approximately 2. By mixing 6% dextran with 0.9% saline in 1:1 proportion a 3% dextran solution was obtained which was nearly isoncotic in our dogs. The most likely explanation for the discrepancy is that the 6% solution contains a high proportion of molecules of lower molecular weight resulting in a greater oncotic pressure than predicted on the basis of the average molecular weight. In addition, this leads to a rapid loss of this solute from the blood. Clinicians and researchers should be aware of the possibility that the dextran preparation they are using is not truly isoncotic.


Erythroblastemia.

Erythroblastemia. The significance of erythroblastemia must be considered in the context of the clinical setting in which it is found. Interpretation should take into account the number and spectrum of maturity of the nucleated red cells; the presence or absence of reticulocytosis and other red cell abnormalities (for example, poikilocytosis); the presence or absence of anemia; the presence or absence of circulating immature granulocytes or bizarre platelets and the presence or absence of the spleen. Circulating nucleated red cells indicate intravascular hemopoiesis or disruption of marrow structure or the inability of the bone marrow's screen mechanism to prevent their passage into circulation. In the latter situations, it usually indicates an unfavorable prognosis.


An electron microscopic and cytochemical study of the cell coat of Trypanosoma cruzi in tissue cultures. Using the cytochemical method of Thiery, a polysaccharide surface coat was demonstrated with the electron microscope in the various developmental stages of Trypanosoma cruzi maintained in tissue cultures. The cell coat was observed on the whole surface membrane system of T. cruzi. A positive reaction, similar to that observed in the cell membrane, was also obtained in the membranes of some vacuoles in the cytoplasm of the parasites. No granules were found in the parasites. No granules were found in the parasite which could represent reserve polysaccharides. The possible role of the cell coat in such phenomena as adhesion, agglutination, phago- and pinocytosis and antigenicity is discussed.


Immunoprecipitation and class-specific immunofluorescence titration of human serum antibodies to Schistosoma mansoni antigens. Twenty sera of individuals with Schistosoma mansoni infections were examined by means of immunoelectrophoresis, Indirect Flourescent Antibody (IFA) technique and the Defined Antigen Substrate Spheres (DASS) system. Immunoprecipitins against S. mansoni antigen and against antigen of the intermediate host, Biomphalaria glabrata, were demonstrated. The presence of specific anti-S. mansoni IgA, IgM, IgG and IgE antibodies were demonstrated. The presence of specific anti-S. MANSONI IgA, IgM, IgG and IgE antibodies was identified with the IFA-technique on frozen sections of adult parasites. The DASS-system proved to be more sensitive than the IFA-technique.


[Phage typing and biotyping of salmonella typhi-murium (author's transl)]. 1998 strains of Salmonella typhi-murium from two different regions of West-Germany were investigated according to their biotype and phagetype. 132 strains were isolated from sewage, 320 strains from animals and the others from human beings. 60 different phagetypes were found. The phagetype 49 occurred most often (11,9% resp. 10,3%). A correlation between biotype and phagetype could not be observed. Nearly every phagetype could be divided into several biotypes. However, only few biotypes prevaled. These comprised the biotypes 1, 10 and 17. The examination of the splitting of trehalose was useful in the biochemical differentiation. Concerning strains of animal origin it was remarkable that most strains from cattle resp. calves belonged to the phagetype 49. Among 145 strains from pigeons 95,9% could be classified as phagetype 2. With exception of 3 strains all the other strains from pigeons did not possess the O-antigen 5. The majority of the strains belonged to the biotype 8. All these strains could not split maltose.


Membrane damage and incorporation of Escherichia coli components into Bdellovibrio bacteriovorus. Cytoplasmic membrane of E. coli is degraded within 20 min following infection with Bdellovibrio. 50% of cellular 42-K is lost during the first 10 min. The cytoplasmic membrane, 20 min after infection, centrifugated on a sucrose gradient produces a wide band containing the main enzyme activities (succinic dehydrogenase and lactic dehydrogenase) bound to the membrane. The incorporation into Bdellovibrio of labelled host cell constituents during intracellular growth has been studied at successive intervals during the development cycle in diluted nutrient broth (about 3 hrs). The cells were broken in a Sorvall-Ribi cell fractionator and the Bdellovibrios separated by centrifugation on sucrose gradient. Polysaccharides, proteins and lipids of Bdellovibrio derive from the utilization of components of the host cells and not from the utilization of the components present in the medium. The incorporation of precursors into polysaccharides and proteins shows the same exponential pattern.


Classification of coagulase-negative staphylococci of human origin. A total of 191 coagulase-negative staphylococci isolated from man were identified as Staphylococcus epidermidis on the basis of their biochemical properties. When classified according to the classification scheme suggested by BAIRD-PARKER (1972), 144 of the strains were found to belong to biotype 1, one strain was biotype 2, and four were biotype 3; the remaining 42 strains could not be classified within any of the 4 biotypes of this scheme. Using the classification scheme suggested by PELZER et al. (1973), 158 strains were found to belong to subgroup IIb, one was subgroup IIIb, four were subgroup IV, and 28 were subgroup V, with no strains remaining unclassified. The biochemical properties of the strains were not related to the site of isolation except that urease was produced by only 15 per cent of strains isolated from pus but by 81-92 per cent of strains isolated from a variety of other sources. The majority of the strains (64 per cent) were resistant to penicillin, while 72 per cent were sensitive to streptomycin.


Frequency distribution of S. typhi-murium phage types in various countries. The phage type and antibiogram of 5199 S. typhi murium strains from 13 countries and of 4949 strains from The Netherlands was determined. For a number of countries it could be established that types predominating in pigs or calves predominate also in humans in that country. However, the predominant phage types were not the same in the various countries. Type 505 predominated in The Netherlands and, to a lesser degree, also in Belgium and the German Federal Republic. Type 131 predominated in Poland and was also frequently found in the German Democratic Republic. In the German Democratic Republic, type 450 was the most frequently found type. Phage patterns not accepted as a type and occurring one country only, were found to predominate in Italy, Hungary, Israel and Sweden. The majority of antibiotic-resistant strains belonged to a limited number of phage types only.


Studies on the energetic metabolism of Shigella flexneri times Escherichia coli hybrids devoid of penetration ability I. Glycolysis. The aerobic and anaerobic (in presence of KCN) glycolysis is studied of avirulent hybrids of Shigella flexneri according to the keratoconjunctivitis test of Sereny with genetic characteristics lac-+kcp-minus devoid of penetration ability. It is established that lac-+kcp-minus hybrids which have lost their ability to penetrate the cells due to replacement of KCP-gene of the chromosome of donor strain E. coli K-12 P4 times, are characterized with a steep decrease of their glycolitic activity in both aerobic and anaerobic conditions. The data shows that the loss of penetrate ability of the Shigella flexneri hybrids correlates with the decrease of their glycolitic ability.


[The morphology of a nocardia asteroides-bacteriophage (author's transl)]. The morphology of a new bacteriophage isolated from Nocardia asteroides has been investigated by negative staining. The percent results suggest a model which is valid for many phages. The head of the bacteriophage has the shape of an icosaeder with a diameter of about 420 AU. It probably contains a spherical core which is surrounded by a capsid of 15 AU thickness. A flexible non-contractible tail is connected by a collar to one of the head's edges. Its length is about 1400 AU and its diameter 60 AU. The tail shows a cross striation with a periodicity of 40 AU and a channel. At the distal side it passes over into a conical end structure. Conforming this morphological criteria the new bacteriophage belongs to the group B of Bradley.


Confirmation of the protective role of proteins from S. typhimurium in infection of mice with their natural pathogen. The protective role of proteins from S. typhi-murium in infection of mice with their natural pathogens was confirmed. Hyperimmunization with either toxic or detoxified proteins, from the same batch, induced the synthesis of strongly precipitating antiprotein antibodies, and the mice were protected against infections with 15-75 LD100 of S. typhimurium. Reinfection of the same animals with 300-500 LD100 of S. typhi-murium induced, in the vaccinated mice, the synthesis of only anti-protein antibodies precipitating in agar-gel.


[Cryptococcoma and amphotericin B. Therapy of cryptococcosis - animal experiments. 2nd Communication: Patho-histological results (author's transl)]. Since cryptococcosis is characterized by cryptococcoma formation, the antimycotic effect of amphothericin B was examined in view of such pathological-anatomical conditions. In white mice (NMRI), cryptococcoma formation was induced by intramuscular injection of Cryptococcus neoformans strain W71 into the hind leg (STAIB, 1962), using a suspension (0.2 ml) containing approximately 2.8 times 10-7 cells/ml. The mice were treated daily with 1 mg amphotericin B in 5% dimethyl sulfoxide by gastric intubation. Course of infection and effectivity of therapy were assessed by microbiological and patho-histological examination of the organs. In the present paper (2nd Communication) comparative patho-histological results in mice, treated with amphotericin B either immediately or from the 16th day p.i. or not at all, are reported. In the non-treated animals the course of infection we controlled by sacrificing 2 animals per day from the 2nd to the 25th day. Cryptococcoma found in the muscle, fat, and connective tissue in the hind leg of these animals were characterized by the two different patho-histological alterations: a) Masses of encapsulated cryptococci side by side were filling a paucireactive or non-reactive reticular structure with blood capillaries. b) Non-specific granulomatous tissue. The fungi were less abundantly found as non-encapsulated cells. On the 5th day after infection the first alterations due to dissemination were found in the lungs, then in other parenchymatous organs. Under immediate amphotericin B-therapy, no cryptococcoma was found at the place of infection; after a therapy of 30 days duration, C. neoformans could be detected in small conglomerates of non-encapsulated cells in muscle, fat and connective tissue. Histologically, a septic dissemination of the agent could not be found in this group. After a therapy of 25 days duration a shrinking of cryptococcoma was observed in animals treated from the 15th day after infection. Presumably this was caused by a loss of capsule and formation of non-specific granulomatous tissue. In the surroundings of blood vessels non-encapsulated cells were detectable. After therapy with amphotericin B, single cryptococci e.g. such disseminated into the lungs were increasingly showing morphological alterations which might be explained as forms of degeneration. The animal experiment in connection with microbiological and patho-histological follow-up studies is discussed with a view to the therapy of cryptococcosis in man. Because of the variable virulence of C. neoformans it has to be mentioned that this experiment was carried out with a strain of C. neoformans characterized by its capability to form cryptococcoma in mice.


[A device for safe handling of vacuum-dried microbes (author's transl)]. By analogous application of the way of packing which is common for the transportation of infectious material (glass tubes in protective covers) in the handling of vaccuum-dried microbes (ampoule within the ampoule) the risk encountered when opening such receptacles may be reduced to an almost complete absence. Technical details are explained by a schematic representation. The method is suitable for the preservation of freeze-dried vaccines. All processes involved in the practical performance of the method which is ready for routine application are considered in detailed instructions for use.


[A modified immunofluorescence test to demonstrate toxoplasma antibodies (author's transl)]. A modified test to demonstrate toxoplasma antibodies by immunofluorescence is described in detail. This test was used in more than 16 000 cases. The antibody content of a patient's serum is assessed from a single dilution of 1:4 by two criteria: 1. The number of toxoplasms in the assay is kept constant. The percentage of antibody loaded cells varies with the concentration of antibodies in the patient's serum. 2. The intensity of fluorescence is correlated to the antibody content of the serum and the latter can be determined by means of standard sera. The results of this method are expressed in degrees of brightness. We compared three different methods and found an identical behaviour of the FATOX III and the Sabin-Feldman test. Between the complement-fixation test and the FATOX III there is the same relation as between JFT and SFT. This is shown in tables presenting the results for 1621 sera. The method is described in detail.


Inactivation of bacteriophages T7 and phiX174 by radiomimetics. Inactivation of phages T7 and phiX174 induced by the radiomimetics N-nitroso-N-methylurea (NMU) and N-acetylethylenimine (AEI) has been studied. In semilogarithmic scale the kinetic curves of phage inactivation were steplike in character. This was connected with the occurrence of several processes in the system. A possible kinetic model has been proposed for the process of NMU-induced phage inactivation. The model is applicable to initial phage inactivation only. From the model a kinetic curve parameter, rho can be determined which characterizes the radiomimetic effect on different phages and determines the changes in the repair system after caffeine treatment. NMU exerted a post-inactivation effect on the phage T7. Also the NMU-induced phage T7 post-inactivation kinetic curves were of steplike character. They can be described as a sum of two exponential processes of different rate constant. The rate constant for the first stage of the post-inactivation process was close to the depurinization rate constant found in the literature.


Acetylsalicylic acid in a trial to diminish thromboembolic complications after elective hip surgery. Fifty-one patients were investigated concerning thromboembolic complications in the operated leg after elective surgery of the hip. Suspicion of clinical deep venous thrombosis (DVT) arose in 11 patients, i.e. 21 per cent. Thirty-five patients were investigated with phlebography. The incidence of DVT among those patients was 15 cases, i.e. 43 per cent. It is concluded that acetylsalicylic acid, a drug which inhibits the platelet release reaction and thereby blocks the platelet aggregation, given orally in a dose of 2 gram per day from the first postoperative day, is not effective in diminishing the incidence of postoperative deep venous thrombosis.


The contribution of endocervical smears to cervical cancer detection. Data from a Colposcopy Clinic have been presented in which endocervical and cervical smears were evaluated in singly and in combination for accuracy and effectiveness. In patients with marked dysplasia, carcinoma in situ and early invasive cancer, false negative results rarely occurred using either cervical or endocervical smears; more false negatives were encountered in the minimal to moderate dysplasia group of lesions. Endocervical smears were found to be unreliable in determining the distribution of cervical neoplasia when correlated with endocervical curettage specimens. These smears contributed little as supplemental screening procedures for early cervical neoplasia since less procedures for early cervical neoplasia since less than three per cent of lesions would have been missed had only a cervical scrape smear been performed. It should be pointed out, however, that this was a young population in which cervical  eversion with exposure of endocervical tissue and the neoplastic lesions was the rule. The accuracy of endocervical aspiration and endocervical swab techniques was similar although there was a much higher proportion of unsatisfactory specimens with the dry cotton swab technique.


The TICAS-RTCIP real time cell identification processor. A preliminary model of a real time processing system, the TICAS-RTCIP (for Taxonomic Intra-Cellular Analytic System--Real Time Cell Identification Processor) has been disigned and is being tested under operational conditions, proving the substantial advantages of employing a network of microprocessors operating in parallel. The system is designed only to demonstrate the feasibility, while more extensive development and biologic testing will be required to assess general applicability to automated uterine cytology.


Hand reconstruction.

Hand reconstruction. To conclude, one must apologize for having introduced so many subjects and left so many loose ends. Hand reconstruction poses a multitude of problems which are presently in an evolutionary phase. In discussing the notion of hand surgery specialization one draws upon orthopaedic, plastic and microsurgical techniques. But is it not precisely this adaption of diverse techniques to one organ which constitutes a speciality? Rapid progress in hand surgery was achieved the moment surgeons confined the major part of their activities to the treatment of this organ. But let us repeat that progress implies collaboration and not isolation. Advances highlighted in this review resulted mostly from collaboration between the laboratory and the operating theatre. It is worthwhile creating hand centres not only for the benefit of patients but also for research and for training surgeons. These centres must become places of collaboration between numerous clinical and preclinical specialities: namely orthopaedics, traumatology, plastic surgery, rheumatology, neurology, physiotherapy, and applicance makers, as well as biologists and anatomists, all applied to the reconstruction of the hand.


Preparing cell suspensions from cervical smears with pepsine and ultrasonic treatment. Since flow-through fluorometry seemed to be a workable method for prescreening cytological material, it became important to have available a reliable method of preparing suspensions of single cells with naked nuclei. An experiment was performed with cervical smears and tissue cultures exposed to varying degrees of pepsination and ultrasonication. The results were disappointing as it appeared impossible to digest cytoplasm completely without damaging the nucleus. Ultrasonic treatment appeared to have an effect only in combination with pepsin; sonication therefore is not a useful technique for dispersion of cell clusters. Moreover, a proposal found in the literature to apply sonication to effect selective damage to leukocyte nuclei was assessed but found to be unsuccessful. Pepsin treatment and ultrasonic treatment appeared conclusively to be unreliable methods for preparing suspensions of single and naked nuclei.


Injury patterns in traffic accidents and suggested preventive measures. A short survey is given of the main patterns of injuries sustained in traffic accidents. The following injuries are accounted for: ruptures of the parasagittal bridging veins and gliding contusions of the brain, axis fractures, and aortic and pelvic injuries.


Influence of neonatal thymectomy on blood pressure and hypertensive vascular disease in rats with renal hypertension. The effect of neonatal thymectomy on the degree and prognosis of hypertension and on the vascular lesions in rats with renal hypertension was studied. There were no differences between thymectomized and sham operated hypertensive rats. The degree of hypertension, the frequency of spontaneous death and heart infarcts were the same in both groups. The occurrence and degree of perivascular cell infiltrations, deposits of perivascular connective tissue and fibrinoid degenerations of the media were found to be the same in both the thymectomized and the sham operated hypertensive animals. The results do not support the assumption that delayed type immune reactions are important in the pathogenesis of hypertensive vascular disease in renal hypertensive rats.


An ultrastructural study of pancreatic islet cell destruction by n-nitrosomethylurea. An ultrastructural study of the early effects of intraperitoneal injection of 50 mg/kg body weight of N-nitrosomethylurea on the pancreatic islet tissue in Chinese hamsters was performed. Thirty minutes after injection there was slight dilatation of the endoplasmic reticulum and mitochondrial swelling in a few peripheral alpha2-cells near to capillaries and also in some beta-cells. After 1 hour these changes were more pronounced. After 3 hours, distinct nuclear pyknosis was seen in endocrine islet cells of all types together with beta-cells granular irregularities, disruption of granular cores and autophagy of alpha2-cell granules. During the following hours, marked derangement of intracellular structures, ending in obvious cellular destruction, was observed. The results indicate that N-nitrosomethylurea has a direct cytotoxic effect on the beta-, alpha2- and alpha1-cells of the islet tissue. The similarity between the ultrastructure of the pancreatic islets after injection of N-nitrosomethylurea and streptozotocin is discussed.


Quantitative studies of the renal corpuscles iii: the influence of post mortem delay before taking renal tissue samples and of the duration of tissue fixation. Comparative quantitative studies of glomeruli in biopsies of the guenon monkey kidney were made to give a numerical measure of the effect of varying periods of fixation of the biopsy tissue in Carnoy's fluid (1-2-24 hrs.), and of the effect of progressive post mortem delay before renal tissue samples were taken (2-4-6-12 hrs.). Additional aims were to determine possible quantitative differences between subcapsular, intermediate and juxtamedullary glomeruli, and to determine whether the glomerular area should be determined with reference to the inner aspect of Bowman's capsule (total area) or to tangents laid at the top of the capillary loops (corrected total area). The quantitative methods used were total and differential counts of glomerular nuclei by light microscopy and point counting for determination of glomerular and mesangial areas. Statistical evaluation was made by a two-way analysis of variance. The differential counts of nuclei were not affected by duration of fixation, nor by post mortem delay up to 12 hrs. before tissue samples were taken. The mesangial area expressed as a percentage of total area was significantly lower two hours post mortem, while total nuclear concentration was significantly lower at time 0 and two hours post mortem than at four, six and 12 hours post mortem. Total nuclear concentration increased as duration of fixation was increased, probably a reflection of tissue shrinking. Differences in nuclear concentration were also noted at different levels of the renal cortex. These differences were only apparent when the glomerular area was determined with reference to the inner aspect of Bowman's capsule, and disappeared when the corrected total area was used. It is concluded that duration of tissue fixation and post mortem delay before tissue samples were taken both affect method sensitivity, as reflected by some, not all, of the parameters measured. The numerical differences in the parameters were not large, however, and it will be the specific study which will determine whether variable fixation times and post mortem delay in obtaining tissue samples is acceptable. As most renal biopsies contain both subcapsular and juxtamedullary glomeruli there is probably no advantage in using the corrected glomerular area instead of the total glomerular area limited by Bowman's capsule.


The heat production of pancreatic beta-cells stimulated by glucose. A recently developed batch microcalorimeter was used for studying heat production in beta-cell-rich pancreatic islets isolated from obese-hyperglycemic mice. In the absence of glucose, the rate of heat production was 50 nW/islet increasing to 90 nW/islet when the islets were exposed to 20 mM glucose. The data obtained are consistent with an increase in the caloric value of oxygen with glucose concentration, as might be expected when the beta-cells utilize proportionally more carbohydrate as a source of energy.


Control of the neurotoxicity of 6-hydroxydopamine by intraneuronal noradrenaline in rat iris. In vitro studies with the neurotoxic compounds 6-hydroxydopamine (6-OH-DA) and 6-aminodopamine (6-A-DA) showed that noradrenaline (NA) markedly inhibited the autooxidation of 6-OH-DA, but not of 6-A-DA. In vivo studies of the adrenergic nerves in rat iris showed that the neurotoxic potency of 6-OH-DA, but not 6-A-DA, was increased after NA depletion by alpha-methyl-p-tyrosine methylester (H44/68). Neurotoxicity was evaluated by measuring the associated decrease in 3-H-NA uptake. Intraocular injection of NA counteracted the degenerative action of 6-OH-DA in both untreated and H44/68 pretreated rats. Intraocular NA did not interfere with the neurotoxicity of 6-A-DA. Additionally, octopamine did not affect the rate of autooxidation nor the neurotoxic potency of 6-OH-DA or 6-A-DA. Control experiments with 3-H-6-OH-DA showed that the intraneuronal NA levels did not significantly affect the intraneuronal accumulation of 6-OH-DA. The parallelism between the in vitro results on autooxidation and in vivo data on neurotoxicity makes it appear that the neurotoxic potency of 6-OH-DA and 6-A-DA is closely associated with their rates of autooxidation. The control of the degenerative action of 6-OH-DA by intraneuronal NA may be mediated via reaction of NA with radicals formed from oxygen during autooxidation of 6-OH-DA.


Observation of click-evoked compound VIII nerve responses before, during, and over seven months after kanamycin treatment in the guinea pig. Compound VIII nerve action potential responses to clicks and filtered-clicks were recorded regularly over a period of 7 months following Kanamycin treatment (8 days, 400 mg/kg), in 3 awake guinea pigs each with an implanted electrode on the round window (left ear). From the end of the treatment the responses to the click became dissociated in various degrees within three major phases: (1) a rapid phase (8 to 10 days) where the responses were dramatically altered, (2) a recovery phase which lasted about 2 months, (3) a slow phase over the subsequent 5 months where the responses to the click decreased slowly but gradually while the N 1 component, as well as the responses to the 8 000 Hz filtered-click (which became recruiting at the end of the treatment), disappeared progressively. Responses to the low frequency filtered-clicks were less affected. Cochlear cytograms showed almost complete degeneration of the inner and outer hair cells of the first turn only.


The effect of social class on psychiatric psychological evaluations in patients with pulmonary tuberculosis. The present study is a methodological examination in which the social and psychic background factors of 100 tuberculous patients, aged 20 to 45 years, were explored using psychiatric interview and psychological tests (MMPI, Rorschach, and Wartegg). The purpose of the study was to analyse the effect of social background factors on the psychiatric and psychological examination. With the help of correlation coefficients and three-factor factor analysis, the variable indicating the social class of the subject could be proved to correlate significantly to the projective test variables (Rorschach, Wartegg). No such correlation between the social group variable and those obtained in the psychiatric interview or the MMPI test could be demonstrated. On the basis of the projective tests, subjects in the lower social classes were considered more disturbed. It can be supposed that the background factors characteristic of lower social classes would contribute to the unfamiliar test situation, causing reactions disturbing the test performance. This suggests that the mentioned tests should be used with caution in the evaluation of personality disturbances.


A double-blind comparison of fluphenazine decanoate and flupenthixol decanoate in the treatment of acute schizophrenia. A double-blind comparison of fluphenazine decanoate and flupenthixol decanoate in 40 consecutive admissions showed no difference in anti-psychotic effect or extrapyramidal side effects after 56 days. However, the trial identified a different effect of the drugs on mood. Flupenthixol decanoate had an elating effect that was most marked during the week following injection. Fluphenazine decanoate tended to lower mood. The results would suggest that in acute schizophrenia, fluphenazine decanoate would be the more appropriate drug in elated or acutely disturbed patients, but that in patients with a lowered mood or a history of depression, flupenthixol decanoate would be the more appropriate drug. It was emphasised that these mood changes were observed in patients with acute schizophrenia and that extrapolation from these results to maintenance therapy of chronic relapsing schizophrenia should only be made with caution. The results suggest that 40 mg of flupenthixol decanoate is approximately equal to 25 mg of fluphenazine decanoate. Analyses of covariance showed a significant positive correlation between the incidence of extrapyramidal side effects and duration of illness.


The influence of food on side effects and absorption of lithium. In a cross-over study, 24 mmol of lithium sulphate was given as a single dose in slow release tablets to 30 healthy volunteers fasting and after a standardised meal. Comparisons were also made with lithium citrate in slow release tablets and placebo. Postprandial administration of lithium gave practically no side effects, while lithium on an empty stomach gave diarrhoea in about 20% of the subjects. The absorption was measured by determination of the amount of lithium excreted in the urine in a group of ten subjects. Lithium was completely absorbed when given after food, but when given on an empty stomach the absorption was lower in some subjects, apparently due to rapid gastrointestinal passage in connection with diarrhoea. Lithium should therefore preferably be administered after meals.


Does piracetam counteract the ECT-induced memory dysfunctions in depressed patients? A double-blind, intra-individual cross-over comparison of the effect of piracetam on retrograde memory impairement as measured by the KS memory test battery was performed in connection with second and third Bi-ECT in 18 patients diagnosed as suffering from depression. The seizure duration and the post-ECT EGG patterns were examined visually and the post-ECT confusion time was measured. Piracetam was given orally in the dose of 4.8 g/day for 3 days. No significant effects were obtained on memory scores, electrical stimulus duration, EEG pattern or post-ECT confusion time. The findings may indicate that the protective effect of piracetam shown in animal electroconvuslive stimulation (ECS) is due to a counteraction of the disturbing effect of hypoxia on memory functions. It is concluded that more information is needed as regards the pharmacokinetics and the mode of action of the drug.


EEG in unilateral and bilateral electroconvulsive therapy. The investigation concerned 100 patients with endogenous depression treated with ECT, 52 unilaterally on the non-dominant hemisphere, and 48 bilaterally. A double-blind investigation of the therapeutic effect and the effect on memory and on EEG was carried out. With unilateral treatment, mainly diffuse and same-sided EEG changes appeared, while with bilateral treatment mainly diffuse and left-sided changes occurred. Bilateral treatment led to significantly more EEG changes than did unilateral treatment. For both groups there was a tendency to greater changes after the last than after the sixth treatment. At termination of treatment, a significantly better therapeutic effect was found in cases where EEG changes appeared, especially severe EEG changes. This applied to the total material but not to the groups of unilaterals and bilaterals taken separately. In the entire material after the first six treatments, the greatest representation of patients with unchanged and impaired memory was found in cases with deteriorated EEG compared to cases with no EEG deterioration. After the entire series of ECT, this correlation no longer was present. After separation of the patients into unilaterals and bilaterals it was not present at any of the stages. In the bilateral group ECT treatment gave more frequent and stronger EEG changes, among the older than among the younger patients. For the unilateral group, there was no comparable difference. The number of weak seizures was significantly greater among the unilaterals than among the bilaterals. The therapeutic effect was not correlated to the number of weak seizures, but the number of weak seizures was positively correlated to the number of treatments applied.


Anxiety and EEG alpha activity in neurotic patients. The literature is reviewed on EEG alpha activity in different psychological states, i.e., morbid anxiety, attention and mental relaxation. In the present study, 20 male neurotic inpatients suffering from chronic moderate anxiety were assessed with respect to anxiety level and EEG alpha activity (frequency and per cent time) and fast activity. No significant EEG asymmetry was found. The average alpha per cent time was very low, most of the patients being low-alpha subjects. Anxiety and alpha index were significantly correlated. The patients were then treated with either 80 mg per day of temazepam or placebo for 2 weeks (double-blind). Significant effects were detected in the anxiety state, the drug group showing more improvement, but not in the EEG profile. The measures were expressed at this stage as change scores from the pre-treatment values and correlations between them were computed. The only correlation of significance was a negative correlation between anxiety level and alpha index found after 1 week in the drug group.


Peroral and parenteral administration of long-acting neuroleptics: a double-blind study of penfluridol compared to flupenthixol decanoate in the treatment of schizophrenia. Fifty-six out of 60 schizophrenic patients completed a double-blind study of two long-acting neuroleptics, penfluridol (peroral) and flupenthixol decanoate (parenteral). Half of the patients were on maintenance therapy of flupenthixol prior to the study, the other half on penfluridol. The actual double-blind study (12 weeks) was commenced after a preliminary period of 4 weeks, the patients in the two main groups being randomly divided into two further groups, one continuing the medication unchanged, the other changing to the alternative drug. It was found possible to make a sudden switch from penfluridol to flupenthixol decanoate and vice versa without any significant change in the condition of the patient. The same dosage (in 70% of the patients from 40 to 80 mg) of penfluridol was used per week as was employed for flupenthixol decanoate per fortnight. Changes in the intensity of the symptoms (total Brief Psychiatric Rating Scale (BPRS) score) were moe pronounced in the preliminary period (during unchanged treatment) than on changed medication in the blind period. Both drugs induced approximately the same degree of akathisia, Parkinsonism and autonomic side effects. The practical consequences of equipotent therapeutical effect of a peroral and parenteral long-acting neuroleptic are briefly discussed.


The effect of hydrochlorothiazide and amiloride administered together on muscle electrolytes in normal subjects. Hydrochlorothiazide, 150 mg daily, and amiloride, 15 mg daily, have been administered together to 10 normal subjects during one week. Muscle biopsies were performed before and after the period of administration of the diuretics and the material was analysed for water and electrolytes. The body weight decreased by 1.9 kg. The serum sodium, chloride and potassium concentrations decreased significantly and standard bicarbonate and blood pH increased. In muscle tissue, extracellular water, chloride and sodium contents and intracellular sodium concentration decreased but the muscle potassium content, the intracellular potassium concentration and the muscle magnesium content were unchanged. A comparison with the results of an earlier study, in which hydrochlorothiazide was given without amiloride, showed that the intracellular potassium depletion and the increase in intracellular sodium concentration, observed with the benzothiazide diuretic, could be fully prevented by simultaneous administration of amiloride. The degree of hypokalemia and alkalosis was also smaller with hydrochlorothiazide + amiloride than with hydrochlorothiazide alone.


Metabolic correlates of ethanol, acetaldehyde, acetate and methanol in humans and animals. Following the administration of alcoholic beverages, ethanol exerts a number of direct and indirect effects on the body and in turn, ethanol is itself metabolized. Liver and brain are twomajor organs which are immediately concerned with the effects of ethanol. Ethanol acts as CNS depressant and as a source of energy. Since the metabolism of ethain the liver proceeds at a constant rate until completion,acetate is produced regardless of energy requirements of the body. Thus, ethanol plays the role of an aberrant nutrient. Although ethanol has no effect on oxygen consumption in the liver, it severely suppresses the productionof carbon dioxide in the Krebs cycle resulting in the corresponding suppressionof respiratory quotient. This indicates that ethanol diverts the utilizationof oxygen for the oxidationof reducing, equivalents which accumulate as a consequence of increased formation of NADH. This is reflected in the shift from the oxidative to reductive components of a number of oxido-reductive couples, e.g.: pyruvate-lactate, oxaloacetate-malate and acetoacetate-beta-hydroxybutyrate. These actions of ethanol are exarcerbated by the fact that the metabolism of ethanol is also associated with the diversion of the availability of a number of enzymes and coenzymes from the metabolism of endogenous substrates towards the metabolism of metabolites of ethanol, thus resulting in the competitive inhibitionof a number of enzyme catalyzed reactions, e.g., inhibition of methanol metabolism during long-term consumption resulting in the acumulation of methanol in body fluids; shift in the peripheral metabolism of biogenic amines from oxidative to reductive pathways; and formation of aberrant neurotransmitters (in vitro); inhibition of the oxidation of fatty acids in the liver...


Effects of ethanol on protein synthesis. Cardiac: Cardiac protein synthesis is influenced by the state of nutrition with reduction of cardiac size in starvation. Ethanol per se may not affect this synthesis directly, but the metabolite of ethanol, acetaldehyde, profoundly decreases normal protein synthesis in the heart in vitro. The interference with the synthetic process may play a role in the ultimate cardiomyopathies of malnutrition and alcoholism. Hepatic: In vivo albumin synthesis is sensitive to environment, oncotic pressure, normal balance, nutrition, as well as toxins and state of health. Thus, to study the acute effects of alcohol alone, it was necessary to employ the isolated perfused liver. Fasting reduced albumin synthesis 50%, with loss of RNA and a disaggregation of the endoplasmic membrane bound polysome. Tryptophan, arginine and ornithine added to the perfusate at a final concentration of 10 mM reversed these findings. Alcohol likewise reduced albumin synthesis; disaggregates the bound polysome without a marked loss of RNA. Ornithine, arginine and tryptophan are able to reverse this loss in albumin synthesizing capacity. The combination of fasting and alcohol, while not lowering albumin synthesis below that seen with either stress alone, prevents the recovery from either stress.


Some endocrine aspects of alcoholism.

Some endocrine aspects of alcoholism. This review has focused on the more recent studies of ethanol-endocrine relationships. The data were evaluated from a fairly unbiased point of view and an attempt was made to point out some of the deficiencies in knowledge of the effects of ethanol on the endocrine system and the underlying mechanisms. The adrenal, for example, has been given the greatest attention in alcohol research, and yet the occurrence of atrophy or hypoplasia, despite alcohol's role as a stressor which can increase cortisol secretion, remains unexplained. In addition, our studies of the alcoholic subject have been conducted exclusively on the "skid-row" individual and may not be descriptive of the middle-class alcoholic subject who has not undergone similar nutritional and environmental stresses. While it is far from obvious that alcoholism is primarily an endocrine disease, the effects of ethanol on hormone metabolism are numerous and deserve further attention.


Marihuana vs. alcohol: a pharmacologic comparison. A review of the pharmacology, behavior, toxicity and therapeutic actions of alcohol and marihuana shows many similarities between the two drugs and few striking differences. Both drugs have fundamental non-specific actions on the neural membrane in common with the sedative-hypnotic-anesthetic group of drugs. They differ mainly in the quantitative aspects of their action owing to variation in 1) the ratio of stimulant to depressant effects, 2) their distribution in the body because of the greater lipid solubility of delta-9-tetrahydrocannabinol (delta-9THC), 3) the route of intake and 4) in their metabolic transformation. Despite marked contrasts in potency, toxicity and therapeutic potential as a result of these differences it is proposed that the proper pharmacologic classification of both drugs is in the sedative group based on their activity at non-toxic levels rather than regarding marihuana as a primary hallucinogen as presently done in many texts.


Induction of physical dependence upon alcohol in nonhuman primates. Following the description of the alcohol withdrawal syndrome in man, efforts have been made to use the nonhuman primate as an animal model for studying the development of physical dependence upon alcohol. There is now general agreement regarding the qualitative description of the withdrawal reaction in the rhesus monkey, and various approaches, including intravenous infusion, intragastric intubation, and nonvolitional oral intake of ethanol have been successful in producing withdrawal in these animals. There still remain the major problems of developing objective procedures for quantitatively assessing the severity of the withdrawal syndrome and establishing the dose dependent and time dependent relationships between ethanol intake and the development of physical dependence. Until these basic issues are empirically resolved, little progress can be expected in our understanding of the critical determinants of the addictive process.


Genetic determinants of alcohol addiction. Animal and human studies indicate strain, species, and racial differences in biological responses to alcohol. Presumably, these are at least partly determined by genetic factors. However, until recently there has been little evidence suggesting that the condition called alcoholism is influenced by genetic factors. Although alcoholism is strongly familial (about one quarter of male relatives of alcoholics are themselves alcoholic), the condition is also associated with vocational and ethnic differences and at present there is no consistent evidence linking alcoholism to specific biochemical abnormalities. In recent years, however, an increasing body of evidence has suggested that genetic factors may play a role. These studies generally have been of two types: (1) twin and adoption studies, and (2) genetic marker studies. Two twin studies have been conducted. One indicated that monozygotic twins are more concordant for alcohol problems than are dizygotic twins. The other produced equivocal findings. Genetic marker studies have had inconsistent results. Of two adoption studies conducted, one found evidence for a hereditary factor and the other did not. It is hypothesized that severe forms of alcoholism may be heritable while milder forms have nongenetic origins. The virtues and limitations of the various studies are discussed.


Pathways of ethanol metabolism in perfused rat liver. The primary pathway of hepatic ethanol metabolism involves alcohol dehydrogenase. Hydrogen generated from ethanol metabolism enters the mitochondrial space most likely as malate over a substrate shuttle mechanism, and is subsequently oxidized by the mitochondrial respiratory chain. The rate-limiting step in this overall multicompartmental process is the rate of reduced cofactor (NADH) reoxidation by the respiratory chain. Since the electron flux in the respiratory chain is controlled by the ADP supply, alcohol dehydrogenase-dependent ethanol metabolism can be activated by perturbations which circumvent the rate-limiting step, such as artificial electron acceptors, gluconeogenic precursors, and uncoupling agents. Moreover, an ATP utilizing process is responsible for the stimulation of ethanol metabilism observed following chronic pretreatment with ethanol. In perfused rat liver catalase also participates in ethanol metabolism to a lesser extent than alcohol dehydrogenase. Quantitative assessments indicate that the predominant ethanol oxidase at low ethanol concentrations (less than 20 mM) is a alcohol dehydrogenase; however, at higher ethanol concentrations, a significant portion of total ethanol metabolism (up to 50%) is mediated by catalase-hydrogen peroxide complex. This pathway is limited by the rate of generation of hydrogen peroxide in the hepatocyte, and can be stimulated with substrates for intraperoxisomal hydrogen peroxide generation such as glycolate, urate and D-amino acids. Considerable evidence implicates catalase-hydrogen peroxide complex in the mechanism of NADPH-dependent microsomal ethanol oxidation.


Drug-induced dyskinesia in monkeys.

Drug-induced dyskinesia in monkeys. Easily definable dyskinetic syndromes have been produced by injection of L-DOPA, apomorphine, trivastal, carbachol, sodium azide, tetrahydrocannabinol, phenothiazines, and amphetamines into one or more sites. Three species of monkeys have been used: rhesus, green, and squirrel. The descriptive information available on each of these dyskinetic syndromes indicates a striking degree of similarity among the effects of these various drugs and combinations of drugs. The behavior patterns produced can be roughly divided into three areas: (1) increased movement (hyperkinesia) and vigilance, determined at least in part by the area in which the animal is confined; (2) a wide range of adventitious movements of extremities, as well as face and tongue; and (3) "stereotypic" behavior, sometimes destructive, such as grooming, biting, and drinking. None of the above studies or models has been employed in monkeys free-ranging in open areas with other animals. It might be expected that the effects of the drugs would be somewhat already by the social setting of the animal. It now seems adequately confirmed that the production of dyskinesia in monkeys is biochemically related to dopaminergic systems in the neostriatum. The evidence at present also points to a form of denervation hypersensitivity as the basis for the production of these syndromes in patients with dyskinesias on L-DOPA therapy (Chase, Holden, and Brody, 1972), although it is clear that in relatively high doses these drugs regularly produce dyskinesias in primates having no anatomical or biochemical pathology in the nervous system. These drug-induced dyskinesias in monkeys, especially those produced by L-DOPA in combination with other drugs or with anatomical and biochemical stereotaxically placed lesions, appear to be developed to a degree to be useful in the further evaluation of the mechanisms of dyskinesias in humans as well as providing methods of testing the effectiveness of various forms of therapy.


Dopaminergic agonist effects on Parkinsonian clinical features and brain monamine metabolism. The effect of a new dopaminergic agonist, piribedil, was studied in 16 patients with Parkinson's disease and compared with placebo and L-DOPA. Piribedil appeared to have a moderate therapeutic effect that was significantly less than that of L-DOPA. Tremor appeared to be the main clinical feature to benefit. Nausea, vomiting, and somnolence were most frequent during the buildup of treatment and confusion and hallucinations during long-term treatment. Piribedil caused a significant decrease in probenecid-induced accumulation of HVA in the CSF, suggesting reduced turnover of endogenous dopamine in the brain. There was a significant relationship between dopamine receptor activation by piribedil and improvement of parkinsonian disability.


The use of an interactive computer terminal in the assessment of cognitive function in elderly psychiatric patients. The use of a teaching machine is the assessment of mental function has been described by Gredye and his colleagues. This report concerns its use in testing 56 elderly patients suffering from functional psychiatric disorders of dementia. After a diagnostic interview patients were tested on the teaching machine as well as on the Mill Hill, Progressive Matrices, Paired Associate Learning Test and Digit Copying Test. After a fixed period all tests were repeated and clincal progress rated. Results showed a significant correlation (P less than 0.01) between teaching-machine scores and those on the standard psychological tests. The correlation between the machine scores on the two occasions was high (r equals 0.58) but this was complicated by practice effects and by low 'ceiling' of the test. It is concluded that the test provided a relatively reliable and valid measure of cognitive function but that its value would be increased by providing a parallel form and by extending its level of difficulty.


Calibration standards for counting asbestos. A laboratory proficiency testing program has been initiated by NIOSH to permit standardization of asbestos counting procedures by various state agencies. This has required preparation of multiple membrane filter samples containing "identical and predictable" concentrations of asbestos fibers, with consistent particulate backgrounds. A technique to filter liquid (toluene) suspensions was developed to provide chrysotile asbestos standards ranging from 200 to 1,500 fibers/mm-2 of filter area, with an aluminum oxide particulate background. Details of the necessary techniques are described. To evaluate variations inherent in preparing these "identical" samples and to estimate variations between different counters, extensive replicate fiber counting was performed. Count data from several counters at a single facility show that this liquid suspension filtration technique provides reproducible asbestos standards as measured by optical microscopy with a coefficient of variation of plus or minus 20% with the maximum individual variations of plus or minus 50%.


Technological feasibility of the 2 fibers/cc asbestos standard in asbestos textile facilities. The technical feasibility of developing dust control practice which would bring the asbestos industry into compliance with the OSHA I fibers/cc standard, scheduled to become effective July 1, 1976, has been questioned since its promulgation. This paper presents the results of industrial hygiene surveys, including the results of 243 asbestos air samples, conducted at two asbestos textile production facilities which have achieved the 2 fibers/cc standard. Both facilities use nonconventional production techniques. Conclusions drawn from the investigations express the need for: (1) a study of new products; (2) a tool to motivate consumers to switch to the new products when appropriate; and (3) legislation which will protect all domestic producers of asbestos textiles from certain producers who do not have to absorb the added expense of meeting the OSHA standard.


Background documentation of evaluation of occupational exposure to airborne asbestos. This review presents background information and literature documentation to supplement the "Recommended Procedures for Sampling and Counting Asbestos Fibers: Procedures for the Evaluation of Occupational Exposure to Airborne Asbestos" prepared by the joint ACGIH-AIHA Aerosol Hazards Evaluation Committee. It reviews the nature of the inhalation hazard associated with asbesots fibers, the sampling and analytic methods which have been used, and a rationale for the selection of the membrane filter sampling-optical phase microscope identification and assay methodology which is recommended.


A simple method for anzlyzing multifactorial data. A simple method of isolating significant factors from multifactorial data has been outlined. The factors must be at two levels, but any number of factors can be handled. Variable group sizes and empty groups do not invalidate the method.


Effect of microorganisms isolated from the upper gut of malnourished children on intestinal sugar absorption in vivo. The effect of microorganisms isolated from the upper gastrointestinal tract of malnourished children on intestinal sugar absorption was studied in rats in vivo. Pure cultures of organisms were grown overnight in a nutrient broth and the resultant supernatant fluid which contained microorganisms in similar numbers to those found in the patients was used as the basic solution for jejunal perfusions which were done in anesthetized adult Wistar rats. The substrate used was arbutin (p-hydroxphenyl-beta-glucoside), a recognized marker of intestinal active sugar transport. Of the gram-positive cocci studied, only the saprophyte, Staphylococcus saprophyticus, did not adversely affect the intestinal absorption of arbutin. The only gram-positive rod studied, a lactobacillus, also significantly inhibited arbutin absorption. Of the Enterobacteriaciae studied, Salmonella paratyphi B, a Shigella and Proteus sp. did not affect arbutin absorption. All the species of Escherichia coli studied, including a nonpathogenic variety, inhibited absorption. Klebsiella sp. and Pseudomonas sp. were also effective. Of the Candida sp., C. albicans and C. parapsilosis were inhibitory while C. tropicalis was not. These results suggest that microorganisms not generally considered enteropathogenic may adversely affect intestinal function when present in the lumen of the gut in excessive numbers and contribute to the production of diarrhea in children with malnutrition.


Richter's syndrome. A terminal complication of chronic lymphocytic leukemia with distinct clinicopathologic features. Long, John C., AND Aisenberg, Alan C.: Richter's syndrome. A terminal complication of chronic lymphocytic leukemia with distinct clinicopathologic features. Am J Clin Pathol 63: 786-795, 1975. Two patients with chronic lymphocytic leukemia of 8 and 9 years duration had a terminal illness characterized by weight loss, persistent fever, lymphadenopathy, and dysglobulinemia. In both cases autopsy revealed a pleomorphic histiocytic lymphoma which contained multinucleate tumor cells and was associated with persistent chronic lymphocytic leukemia. These two cases are examples of Richter's syndrome, a clinically distinct complication of chronic lymphocytic leukemia that may be confused pathologically with Hodgkin's disease. Review of the medical literature suggests that this syndrome has frequently gone unrecognized. (Key words: Richter's syndrome; Chronic lymphocytic leukemia.)


Erosive gastritis as a manifestation of secondary syphilis. In a case of secondary syphilis with gastric involvement, the clinical history and roentgenographic and gastroscopic examiniations initially suggested an infiltrative malignant neoplasm. However, macroscopic and histologic examination of the partial gastrectomy specimen demonstrated an erosive, inflammatory lesion. Subsequently, numerous Treponema pallida were demonstrated in formalin-fixed eroded gastric mucosa by silver impregnation and fluorescent antibody technics. Although the true incidence of syphilitic gastritis is unknown, it may occur commonly during the secondary stage of syphilis and should be considered in the differential diagnosis of diffuse erosive gastritides and infiltrative lesions of the stomach.


Toxoplasmosis. Historical review, direct diagnostic microscopy, and report of a case. A case of congenital toxoplasmosis diagnosed by the detection of Toxoplasma gondii organisms in the ventricular fluid of a living patient, confirmed by mouse inoculation, is reported. The subject of toxoplasmosis is reviewed historically, especially in regard to cases diagnosed by direct microscopic examination of cerebrospinal or ventricular fluids. Although several such cases have been reported in the world medical literature, an extensive survey failed to reveal such a case previously reported in the United States.


Recovery of Cryptococcus neoformans from sputum using new technics for the isolation of fungi from sputum. Three sputum-digesting agents, N-acetyl-l-cytseine, dithiothreitol, and pancreatin-trypsin, were shown to be equally effective in allowing for the isolation of Cryptococcus neoformans from sputum samples in quantitative comparisons.  By quantitative plating on bird-seed medium it was also shown the centrifugation after digestion concentrated C. neoformans into a platable sediment and, further, that the organisms, when present in concentrations as low as 10 yeasts per ml. of sputum, could be isolated with much higher frequencies than when no digestion-centrifugation procedure was used.


The accuracy of calcium analysis in the United States. The accuracy of the methods commonly used for calcium analysis in clinical laboratories in the United States was studied with the aid of the National Bureau of Standards (NBS). Samples from six large serum pools that had been analyzed by 4,258 clinical laboratories were sent to NBS. At NBS the calcium contents of the samples were determined using isotope dilution and mass spectrometry (ID-MS). The findings show that the bias of the routine methods varies from levels that are insignificant to levels that would have an impact on patient care. The accuracy of the automated methods is comparable to the accuracy of the best manual methods. The accuracy of the proposed calcium reference method is comparable to the accuracy of a number of the methods in current routine use. There is evidence of a widespread lack of standardization at the extremes of the clinical range; this effect is not shown by the results obtained by automated methods. The study underlines the value of developing technology, such as ID-MS, that is capable of providing definitive values. The definitive values can then be used to assess the bias of routine methods on a nationwide scale, using existing programs.


Treatment of laryngotracheobronchitis (croup). Use of intermittent positive-pressure breathing and racemic epinephrine. Use of racemic epinephrine hydrochloride (Vaponefrin), delivered by intermittent positive-pressure breathing, in the treatment of laryngotracheobronchitis (croup) produced acute beneficial results in a controlled study. However, symptoms often recurred within two hours, suggesting that this form of treatment should not be used in the emergency room and the patient then sent home. This treatment had no effect on arterial oxygen gas pressure. The changes in clinical status 24 to 36 hours after admission into the study were similar for the patients in the treatment and control groups, suggesting that the natural history of the disease was not drastically altered by this form of treatment.


Flouride. Ten-year prospective study of deciduous and permanent dentition. A ten-year longitudinal prospective study compared the effect of fluoride on dentition of 1,500 children from infancy through age 10 years. In Kalamazoo, Mich, and Oneida, NY, parallel groups were given a fluoride-vitamin supplement from infancy and from age 4 and compared with fluoridated water and control groups. Incidence of new caries activity in both deciduous and permanent teeth was measured by mean number of new decayed and filled teeth, as well as percentage of children with no caries throughout the periods studied. Prevalence of caries was also studied in six-year molars. The results indicate a consistent (and, for selected groups, a statistically significant) diminution in caries activity for both deciduous and permanent teeth for groups ranked from greatest retardation of caries to least: infant fluoride group, water fluoride group, age 4 fluoride group, and controls.


Stimulation of human pepsin output by tropical hydrochloric acid. Pepsin secretion is stimulated by the back-diffusion of acid across the mucosa of the vagally denervated canine pouch.  If back-diffusion is enhanced by damage, pepsin secretion increases.  The current study investigates whether this mechanism exists in man.  The stomach of normal human volunteers were irrigated for 1 hour with either buffer of 0.01 N HCl, 1 hour with 0.2 N HCl, and a final hour with buffer or 0.01 N HCl.  During the middle hour both the concentration and output of pepsin increased three- or fourfold.  From these studies it appears that the human gastric mucosa contains a mechanism similar to the dog's which results in the stimulation of pepsin secretion when exposed to acid.  This mechanism could be of etiologic significance in gastric ulcer disease, which has been shown to be associated with increased gastric-mucosal permeability.


Hemorrhagic pancreatitis with duodenopancreatic fistula in a renal homograft patient. A 39-year old man who developed hemorrhagic pancreatitis seven months after his second renal homograft survived. Azathioprine was stopped but prednisone was continued. A pseudocyst spontaneously vanished and an upper gastrointestinal series showed a duodenopancreatic fistula. His homograft maintained good function.


The "fetoscope"--a new clinical tool for prenatal genetic diagnosis. Our experience in 65 patients using a "fetoscope" and local anesthesia prior to saline abortion is described. Visualization of the intrauterine contents improved with experience, was optimum at 16 to 18 weeks' gestation, and was superior to the quality of photographic records. Four fetal skin biopsies and 6 amnion biopsies were done. Six blood samples were taken from the fetal surface of the placenta. The limitations of this instrument are described. No significant complications have occurred. Current and probable future indications for fetoscopy are reviewed. Until both the safety of the procedure is proved and problems of visualization due to limitation of visual field are solved, extreme caution is urged in the employment of this instrument in genetic high-risk pregnancy.


Preinduction priming with oral prostaglandin E2. A double-blind study was undertaken to determine the effectiveness of prostaglandin E2 as a means for improving the prelabor pelvic conditions preparatory to induction of labor at term in 30 patients with unfavorable Bishop scores of less than 6. An interval of priming was followed after 8 to 12 hours by induction with oxytocin infusion. No meaningful differences were found in index cases as compared with controls to verify that PGE2 has any priming or enhancing effect under the conditions of the investigation.


Clinical applications of complement measurements in rheumatic diseases. There is now convincing evidence that the complement system is involved in the pathogenesis of at least some of the manifestations of human rheumatic diseases.  Complement measurements in serum and/or pathologic fluids from patients with these disorders not only reflect this involvement but also may provide important clues regarding the activity and extent of the disease processes.  Future studies should provide additional information concerning the usefulness of such measurements for predicting the outcome of specific therapeutic regimens, and perhaps also be the basis for the evolution of new and more rational forms of therapy.


The demands and limits of care--ethical reflections on the moral dilemma of neonatal intensive care. Decisions regarding the care of deformed and retarded infants pose difficult ethical and moral dilemmas for both physicians and parents.  Ethical inquiry regarding such questions must be concerned with how we see and understand the dilemma for conceptualization of the problem often shapes the decisions that are made.  The fundamental issue that provides the background for the kind and amount of care defective newborns should receive is the obligation parents have to care for their children.  New medical technology has so extended the limits of care that the extent of parental (and societal) obligation is unclear.  In dealing with the problem of defective newborns, the action of both physicians and parents is determined in part by concern to act in a manner congruent with assumed roles and identity.  With no moral consensus regarding the care of defective newborns, the doctor is put in a precarious position.  What is revealed is how dependent medicine is on its underlying moral community to give it moral direction in instances of ambiguity and uncertainty.


Uterine contractility and regional blood flow responses to oxytocin and prostaglandin E2 in pregnant rhesus monkeys. The effects of oxytocin and prostaglandin E2 (PGE2) infusions on regional blood flow (measured by radioactive microspheres) and myometrial contractility were studied in 18 pregnant rhesus monkeys near term. We observed no significant differences between PGE2 and oxytocin in cardiac output, hemodynamics, or uterine activity. Their effects on the regional distribution of systemic blood flow were similar although the gastrointestinal tract received an increased percentage of cardiac output after PGE2. A relative placental ischemia, together with a myometrial hyperemia, was observed during labor. Uterine contraction produced a large reduction (average 73 per cent) in placental blood flow whereas myometrial blood flow was maintained or sometimes increased. A significant negative correlation was observed between intra-amniotic pressure and placental blood flow. During uterine relaxation, placental flow partially recovered whereas myometrial flow nearly doubled the prelabor values. We conclude that (1) in the dose ranges studied, oxytocin and PGE2 produce similar effects on myometrial contractility and uteroplacental blood flow, and (2) the vascular beds of the placenta and myometrium respond differently to labor of moderate intensity.


Changes in LH-releasing hormone content of the hypothalamus and electron microscopy of the anterior pituitary after prostaglandin E2 injection in rats. The purpose of this study is to present evidence that prostaglandin (PG) E2 stimulates a release of luteinizing hormone-releasing hormone (LH-RH) from the hypothalmus. In experiment 1, 72 hours after estrogen and progesterone treatment, a solution of 700 mug of PGE2 was injected into the jugular vein. Blood samples for plasma LH and the hypothalamus for LH-RH assay were collected before and 5, 10, and 30 minutes after PGE2 injection and subjected to radioimmunoassay. The total LH-RH content of the hypothalamus decreased from 20.4 to 15.3 ng. at 5 minutes after PGE2 and had returned to the pretreatment level by 30 minutes after PGE2 administration. On the other hand, plasma LH levels increased at 5 minutes, reached a peak at 10 minutes, followed by a decline at 30 minutes after PGE2 injection. In Experiment 2, 10 and 30 minutes after a single injection of PGE2 or synthetic LH-RH, the anterior pituitary were excised for an electromicroscopic study. Ten minute after PGE2, an enlarged Golgi apparatus, well-developed rough endoplasmic reticulum, and decreased secretory granules were observed in pituitary gonadotropins as compared with the control group. These changes were more conspicuous in the pituitaries obtained 30 minutes after PGE2. In Experiment 3, plasma LH levels were determined serially before and 10, 30, 60, and 90 minutes after a single injection of PGE2, LH-RH, or saline. There is a striking resemblance between the PGE2- and LH-RH-treated groups. Plasma LH levels in both these groups reached a peak at 10 minutes and started to decline 30 minutes after PGE2 or LH-RH administration. Our findings would indicate that PGE2 stimulates LH-RH secretion from the hypothalamus.


Bacterial growth inhibition by amniotic fluid. III. Demonstration of the variability of bacterial growth inhibition by amniotic fluid with a new plate-count technique. The ability of 50 human amniotic fluid samples to inhibit the growth of Escherichia coli was measured with a new semimicro plate-count technique. A range from bacterial growth-sustaining fluid to bactericidal fluid was observed. When the inhibitory capacities of the fluid samples were correlated with gestational age, a progressive increase was obtained with maximum inhibitory capacity at 36 to 40 weeks. All fluid samples obtained before 20 weeks' gestation were capable of supporting bacterial growth. Fluid samples of 36 to 40 weeks' gestation were all bactericidal or bacteriostatic. More variability in inhibitory capacity was seen after 40 weeks, with an over-all loss of inhibition observed.


Bacterial growth inhibition by amniotic fluid. IV. Studies on the nature of bacterial inhibition with the use of plate-count determinations. Bacterial growth inhibition in amniotic fluid is associated with a compound or class of compounds which resembles antibacterial cationic peptides. The inhibitor studied in amniotic fluid is sensitive to treatment with monobasic and dibasic potassium phosphate, and the inhibitory activity of amniotic fluid is lost following adsorption onto bentomite. The inhibitory component in amniotic fluid interacts with bacterial cells by adsorption or is internalized by viable cells only. The inhibitory quality of amniotic fluid is not destroyed by heating to 100 degrees C. for 15 minutes, and this heat-stable inhibitory activity is associated with the compound or compounds which are phosphate sensitive. A possible mode of antibacterial action which is consistent with the data presented is discussed.


The influence of advancing gestation on group B streptococcal colonization in pregnant women. An investigation to determine the throat and vaginal colonization rates of group B streptococci among second- and third-trimester pregnant women was performed. Group B streptococci were recovered from 25.4 per cent of third-trimester and 14.8 per cent of second-trimester parturient (p = less than 0.025). Serotype distribution of isolates was similar among these two study groups. No significant differences in colonization rates were noted on the basis of age, race, parity, or complications of pregnancy.However, postpartum fever occurred in 22 per cent of colonized and only 4 per cent of noncolonized second-trimester parturients. The reason for this significant increase in group B streptococcal colonization rates with advancing gestation remains speculative.


Principles in the management of oculomycosis. XXXI Edward Jackson memorial lecture. Effective antifungal therapy must be long-term, nondamaging, penetrating to the eye, and highly active against each patient's fungus. Results of antifungal sensitivity testing of 61 collected ocular fungal pathogens and observations in 25 cases treated with one of the nonpolyene antifungal drugs indicated that infection was rapidly controlled and eradicated with restoration of visual acuity, determined by the degree of disorganization present at the time of commencement of rational specific antifungal therapy. Pimaricin has the widest spectrum, a medium level of activity, and rather poor penetration but is recommended as an antifungal prophylactic and as first-line-therapy for ocular fungal disease while awaiting identification and sensitivity testing of the fungus. Flucytosine combined with amphotericin B, or possibly with clotrimazole or miconazole, is recommended for Candida infections. Clotrimazole is the drug of choice for Aspergillus species although miconazole and econazole are more effective with some isolates. Miconazole and econazole are recommended for miscellaneous filamentous fungi although clotrimazole or thiabendazole are superior in some cases. Each of these drugs may be useful in patients infected with Fusarium who do not respond to primaricin. In these cases, drug use should be guided by the results of antifungal sensitivity testing. In addition to medical antifungal therapy some eyes may require excisional keratoplasty with the lens removal and evacuation of the posterior chamber and anterior vitreous cavity.


Intermediate-term corneal storage for penetrating keratoplasty. Fifty-seven penetrating keratoplasties were performed using human donor corneal material stored in modified Tissue Culture Medium 199 (TC-199). Fifty-six grafts were clear on the first postoperative day and remained clear for at least three weeks. During the follow-up period (average, 3.7 months), only four additional graft failures occurred. The reduced incidence of early graft edema is attributed to prolonged viability of corneal endothelium maintained in modified TC-199 medium prior to keratoplasty.


Topical tetracycline and rifampicin therapy of endemic trachoma in Tunisia. A controlled chemotherapy trial of trachoma was carried out in a Tunisian oasis among schoolchildren with active disease. We compared 1% tetracycline ointment (79 patients) or 1% rifampicin ointment (76 patients) with 5% boric acid ointment (79 patients). Medications were administered twice daily, six days a week, for ten weeks. Slit-lamp examinations by three ophthalmologists were made independently before treatment as well as five, 19, and 39 weeks after treatment. Bacteriologic cultures were taken during treatment as were smears to detect trachoma agent at each clinical examination. Five weeks after treatment, the intensity of conjunctival disease in the tetracycline and rifampicin groups was reduced significantly when compared with boric acid, but at 19 weeks this suppression was found only in the tetracycline group. Ocular bacterial pathogens were eliminated almost entirely in the two antibiotic groups during treatment. The initial prevalence of trachoma (29to 31%) was significantly reduced in the two antibiotic-treated groups at five weeks and 19 weeks after treatment. The prevalence of trachoma was equally low (7%) in all three groups following retreatment with tetracycline. Although both antibiotics were effective, rifampicin offered no advantage over tetracycline in this trial. Recurrent disease in this school-based treatment study probably was due to reinfection from younger siblings at home. While systematic, community-wide, antibiotic treatment programs are not always possible in countries where trachoma is endemic, limited antibiotic therapy programs should be continued in these areas to reduce the intensity and prevalence of trachoma, even though the disease cannot be eradicated.


The development and resolution of glomerular basement membrane changes associated with subepithelial immune deposits. The morphogenesis of glomerular basement membrane changes associated with subepithelial immune deposits was studied in kidney biopsies from patients with gold-induced membranous glomerulonephoritis. Serial biopsies showed focal accumulations of additional basement membrane material around the deposits, suggesting that the deposited material stimulated the epithelium to increased synthesis. Moreover, the deposits were gradually displaced towards the inner (endothelia) side of the basement membrane during the course of the disease, suggesting that this layer undergoes a slow continuous turnover, with removal at its endothelial aspect. The two processes--increased epithelial synthesis and turnover--are suggested to constitute the basis of a natural healing process resulting in elimination of the deposits and structural restoration of the basement membrane. The epithelial slit membranes were dislocated externally by the deposits or the excessive basement membrane material, indicating that their barrier function is preserved even in this pathologic condition.


Immunologic enhancement of rat renal allografts. III. Immunopathologic lesions and rejection in long-surviving passively enhanced grafts. Immunologic enhancement of renal allografts from (Lewis times Brown Norway) F1 to Lewis rats was achieved by administering a single dose of antidonor serum at the time of transplantation. A series of grafts functioning for 1 to 4 months after transplantation were examined by light and immunofluorescence microscopy to evaluate the long-term protective effects of the enhancing serum and to determine if previously unobserved lesions appeared in long survivors. Despite the absence of detectable circulating cytotoxic alloantibody, long-term allografts showed necrotizing glomerular and arterial lesions which resembled those seen in acutely rejecting grafts and were compatible with humoral rejection. Thus, in this model, there is a late decline in the ability of passive enhancement to inhibit humoral rejection. Long-term grafts also developed tubular lesions with deposition of immunoglobulin and complement on the tubular basement membranes (TBM). Anti-TBM antibodies were demonstrated in recipients' sera and found to be organ specific but not major histocompatibility antigen or species specific. This tubular lesion is therefore a unique form of allograft injury in which the immune response is directed against tissue antigen(s) which are distinct from the major histocompatibility antigens that induce rejection.


Violence at home: A review of the literature. Studies on family violence have analyzed the phenomenon from psychological, social, and cultural perspectives. A review of the literature shows that the available evidence is not contradictory, leading to the conclusion that a comprehensive theory of violence at home must take into account factors at these several levels, placing individual functioning within the social group and within the culture norms by which the group operates. A theory of violence at home, and suggestions for further research, are offered.


New studies of post-Pleistocene human skeletal remains from the Rift Valley, Kenya. Prehistoric human crania from Bromhead's Site, Willey's Kopje, Makalia Burial Site, Nakuru, and other localities in the Eastern Rift Valley of Kenya are reassessed using measurements and a multivariate statistical approach. Materials available for comparison include series of Bushman and Hottentot crania. South and East African Negroes, and Egyptians. Up to 34 cranial measurements taken on these series are utilized to construct three multiple discriminant frameworks, each of which can assign modern individuals to a correct group with considerable accuracy. When the prehistoric crania are classified with the help of these discriminants, results indicate that several of the skulls are best grouped with modern Negroes. This is especially clear in the case of individuals from Bromhead's Site, Willey's Kopje, and Nakuru, and the evidence hardly suggests post-Pleistocene domination of the Rift and surrounding territory by "Mediterranean" Caucasoids, as has been claimed. Recent linguistic and archaeological findings are also reviewed, and these seem to support application of the term Nilotic Negro to the early Rift populations.