Acute leukemia in polycythemia vera.

Acute leukemia in polycythemia vera. Virtually every aspect concerning the occurrence of acute leukemia in polycythemia vera is controversial. However, a list of those factors believed to have importance in leukemogenesis in this disease includes: maleness, ethnic origin, the presence of myeloid metaplasia and/or early WBC precursors in the peripheral blood at the time of presentation, the influence of prolonged survival, and a possible dose-response relationship with 32P treatment. Many of the features of PV suggest that it is a malignant disease per se, with other factors (such as clones of cells, or altered host response) combining to increase the leukemogenic potential of the agents used to control the disease. It does appear that the incidence of AL in PV treated with 32P and/or x-ray is many times higher than that for PV treated with phlebotomy alone. However, overall survival for 32P-treated patients appears to be longer than that for phlebotomy treatment. Further, for both 32P and phlebotomy treatments, patients with AL do not die an an earlier age than do patients not developing this complication. Since the transformation of PV into AL has been described in more than 20 patients treated with phlebotomy alone, and in more than 30 patients treated with chemotherapy and phlebotomy, the question concerning the occurrence of AL in PV no longer appears to revolve around whether this is a function of the leukemogenicity of 32P or the effect of prolongation of survival. The occurrence of AL in multiple myeloma, lymphomas, other malignancies, and in nonmalignant diseases following treatment with myelosuppressive agents, forces one to consider the leukemogenic potential of any agent capable of suppressing the panmyelopathy of this disease, as well as the inherent tendency to AL of the "untreated" disease. Hopefully, the next decade will give us a more complete understanding of the complex interrelationships between PV, its treatment, and AL.


An editorial anecdote.

An editorial anecdote. The quality and the influence of South African medical literature during the first half of this century owes a great deal to two outstanding medical editors: Drs William Darley-Hartley and C. L. Leipoldt who, in a curious fashion, were closely related in this field of medical endeavour although their origins were so very different.


[South African family doctor's contribution to public health during the period 1900-1950]. During the period 1900-1950 the general or family practitioners made significant contributions to the health care in South Africa. The historical details of these contributions were not always documented and are difficult to trace. The Department of Family Medicine is anxious to preserve this part of South African medical history and a research project to further this effort was carried out. All possible sources of information were used. Chairs of medical history should be established in our medical faculties.


Survey of the current status of the clinical uses of antilymphocyte serum. A limited degree of effectiveness of antilymphoid globulin in clinical kidney and bone marrow transplantation has been described. It may also be useful for the prolongation of temporary skin allografts for burn patients and may be valuable as an adjunct in the treatment of certain autoimmune diseases. The use of antilymphoid globulin with donor antigen to facilitate allograft enhancement has been reviewed. An instance of possible enhancement of a mismatched cadaveric renal allograft in a highly sensitized recipient given antilymphoid globulin and donor marrow is recorded. Use of antilymphoid globulin to facilitate enhancement with donor antigen is probably the next major application of antilymphoid globulin.


Graft survival of perfused vs nonperfused cadaver kidneys. No significant difference in the late survival rate of primary cadaver kidney transplants was demonstrated between perfused and nonperfused kidneys in the New England area. It is felt that the advantages of continuous perfusion to clinical renal transplantation continue to make it the preferred method of renal preservation.


Effect of coronal plane tilt on cat caloric nystagmus responses. The nystagmus slope responses to vestibular stimuli are strongly dependent on eye position, while the frequency responses shift predictably and are relatively independent of the eye position. Spurious directional differences may be introduced in nystagmus slope parameters by small tilts in the roll plane in comparison to the more predictable frequency responses.


Reliability of the enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of Trichinella spiralis infections in conventionally raised pigs. An enzyme innunoassay using horse radish peroxidase as teh marker enzyme for the detection of antibodies to Trichinella spiralis in pigs was described. In the enzyme-linked immunosorbent assay (ELISA) quantitation os specific antibodies is obtained by means of peroxidase labeled anti-species-immunoglobulin in antigen-coated tubes. The enzyme remaining in the tube after wasging provides a measure of the amount of specific antibodies in the serum. A crude saline extract of T. spiralis muscle larvae served as antigen. In experiments in which conventionally raised pigs intended for slaughter were infected with various numbers of T. spiralis larvae (25,000; 12,500; 5,000; 2,500; 1,500; 500; 150; 50) a positive correlation was found between initial dose of larvae administered and amount of antibodies detected by ELISA. Compared with immuno-fluorescence (IF) ELISA was more sensitive. IF yielded positive results in 11 out of 34 infected animals, whereas ELISA results were positive in 27 cases. In order to evaluate ELISA results under practical conditions extinction values os sera from both infected and non-infected conventional pigs were compared with the highest extinction value of a group of 74 negative conventional pig sera. Due to the relatively high background reaction of some of these negative sera the number of positive practical ELISA results decreased from 27 to 19 out of 34 animals. Furthermore, in 1 out of 10 non-infected animals a false positive practical ELISA result was obtained. Ways to improve the reliability of ELISA are discussed.


[Counts of aerobic bacteria using a droplet technique (author's transl)]. A new droplet method used in counts of aerobic bacteria was compared with the standard pour-plate method. The results obtained with the two methods were virtually identical (r finely chopped fillet steak = 0.95; r heated meats = 0.98). The advantage of the droplet method consists in the fact that it saves time (48 hours) and material (pipettes and Petri dishes).


[Polyarthritis in calves (author's transl)]. The development of polyarthritis was studied in thirty-six calves. Thirty patients were from two to eleven days of age; six animals were older than eleven days. Besides clinical studies, the synovial fluid was examined both biochemically and bacteriologically in addition, a blood culture was made. When the synovial fluids of twenty-six calves were studied bacteriologically, P. multocida was isolated in ten cases, P. haemolytica in two cases, E. coli in ten cases, streptococci in three cases and D. pneumoniae in one case; bacteriological examination of the synovial fluid was negative in ten cases. Blood cultures were positive in twenty animals (P. multocida in five cases, P. haemolytica in two cases, E. coli in eleven cases, S. subacidus in one case and D. pneumoniae in one case). Twenty-five calves were treated by intra-articular as well as intramuscular injection of kanamycin (sulphate); six animals were treated with similar injections of ampicillin. Treatment with ampicillin was initially instituted in five calves; after some time, however, kanamycine (sulphate) was substituted for this medication. Twenty-seven calves recovered completely.


[Residues of antimicrobial materials in the effluents of livestock farms (author's transl)]. Forty water samples were taken from streams of three different regions of Belgium, with intensive husbandry and examined for residual microbiological activity. In some samples, activity was detected against Staphylococcus aureus; none of them were active against E. coli and C. albicans. The substances in the few positive samples were not identified. With this low activity and the small proportion of positive samples (12 out of 41) any influence on the water biosphere due to the methods of farming, with their use of antimicrobials, can safety be neglected.


[The clinical value of histoautoradiographic studies during radiotherapy of cervix carcinoma]. Tissue samples from 35 patients with cervical carcinoma stage I up to stage III were incubated with H-3 -thymidine before and after a test dose of irradiation, as well as several times during treatment until application of the full irradiation dose and the percentage of labelled cells was determined autoradiographically. An important marked decrease in labelling index (subject to individual verification), was found during radiotherapy. The duration of observation was more than two years in the cases of 27 patients. Close correlation was found between the decrease in labelling index and the corresponding clinical course of the disease.


The distribution of enzyme variation in populations of Plasmodium falciparum in Africa. Isolates of Plasmodium falciparum collected from the east and west coasts of tropical Africa and also from several inland regions have been examined for electrophoretic forms of the enzymes GPI, LDH and 6PGD. Variation within and between isolates was found in the parasite forms of all three enzymes. While not disproving the existence of genetic divisions between P. falciparum populations in Africa the distribution of this variation provides no evidence for such a hypothesis.


Skin and heart allograft prolongation in tilorone-treated rats. Tilorone is a synthetic amino-alkoxyfluorenone with demonstrated antiviral and antitumor properties. This study gives evidence for immunosuppressive properties of the substance as well. Buffalo rats (AgB6) received skin grafts from rats of the Fischer (AgB1) strain. Control animals rejected in 9.9 +/- 1.1 days, compared to 13.7 +/- 2.3 days for recipients treated with Tilorone. Steroids when combined with Tilorone further prolonged skin allografts to 16.7 +/- 2.6 days. Heart allografts from Fischer (AgB1) and Brown-Norway (AgB3) to Lewis (AgB1) also were performed. In the Fischer to Lewis combination, allograft survival was prolonged from 14.7 +/- 1.0 to 31.0 +/- 3.8 days. In the Brown-Norway to Lewis combination, treated rats rejected in 10.2 +/- 1.4 days versus 6.6 +/- 1.1 days for controls. Increased levels of cytotoxic antibody specific to lymphocytes of the donor strain were noted in Tilorone-treated animals. The mechanism by which Tilorone prolongs allografts may well involve a combination of interferon production and specific suppression of thymus-derived lymphocytes.


Drainage of thoracic duct lymph in renal transplant patients. Lymphocyte depletion by drainage of lymph via a thoracic duct fistula was accomplished in 51 renal transplant recipients as an adjunct method for immunosuppression. The duration of lymph flow varied between 2 and 53 days and the total drained lymph volume between 1 and 168 liters. The graft survival of these patients was compared to that of a control group of patients undergoing transplantation during a similar period. The followup period was 2-6 years. In patients receiving transplants from living related donors, no beneficial effect of lymphocyte depletion was demonstrated, probably because of the satisfactory graft survival among the control patients (84% at 1 year). However, in recipients of cadaveric kidneys, a significantly higher 1-year graft survival was achieved in the lymph-drained patients. Drainage for more than 30 days and of more than 20 liters improved the results. Additional suppression by thymectomy and institution of antilymphocyte globulin suggested that the best treatment would be a combination of both these measures with lymph drainage continuing for more than 30 days. Infection around the thoracic duct cannula occurred in 5 patients, necessitating removal of the cannula in 2. Two patients developed septicemia. In one of them the infection originated from an infected incisional wound and in the other probably from reinfusion of contaminated lymph plasma. Two other patients developed malignant tumors 23 and 58 months after transplantation, respectively. It is felt that lymphocyte depletion by lymph drainage is an effective supplementary method of immunosuppression to enhance graft survival in recipients of cadaveric renal transplants.


A refinement of the immunofluorescent complement fixation test for trypanosoma infections. The sandwich immunofluorescent complement fixation test proved to be as sensitive as the indirect fluorescent antibody test when anti-C1q was used to detect the binding of complement to antigen-antibody complex of four species of trypanosomes in experimentally infected domestic animals.


The Plasmodium berghei-infection in isogenic F1 (C57Bl x DBA)-mice. I. The course of the infection and immunization experiments. The malarial infection caused by Plasmodium berghei (strain K 173) was observed in the isogenic mouse strains C3H, C57Bl, DBA, and the F1 (C57Bl x DBA)-hybrids. In addition immunization experiments were carried out by intermittent suppression of the parasite multiplication through maintaining the infected animals on a milk diet for various length of time. The F1-hybrids were the most resistant mice and immunization was most effective in these animals, too. But if the course of the infection was not influenced experimentally all animals succumbed to the infection. If the mice were inoculated with very small parasite numbers a bimodal mortality pattern was usually observed with a pronounced peak of eary mortality. The changes in body weight, temperature, and hematocrit during the infection are shown.


[Demonstration of antigenicity in adult dipetalonema vitae by the indirect immunofluorescence test using serum from filariasis patients (author's transl)]. The localization of the antigen-antibody reactions on methacrylate embedded sections of an adult male and female of the nematode Dipetalonema vitae by the indirect immunofluorescence test was found to be as follows: female D. vitae: in the egg-shell and circumference of sections of the microfilariae as well as amorphous structures in the vesica seminalis and vas deferens. In both sexes: partially in the somatic muscle cells according to their glycogen content, the interstitial spaces between the muscle cells and the connecting pseudocoelomic cavity. Reference to the possible application of this technique in the immunofluorescence diagnosis of filariasis is made.


A controlled trial of daily and intermittent rifampicin plus ethambutol in the retreatment of patients with pulmonary tuberculosis: results up to 30 months. In a controlled clinical trial in Hong Kong, 575 Chinese adults with smear-positive isoniazid-resistant pulmonary tuberculosis, who had previously been treated with first-line chemotherapy, were allocated at random to regimens of rifampicin plus ethambutol daily (ER7), twice-weekly (ER2), once-weekly (ER1), or daily for 2 months and then once-weekly (ER7ER1), or to a standard retreatment regimen of daily ethionamide plus pyrazinamide plus cycloserine (EtZC). The ER7 patients were allocated to 12 or 18 months of chemotherapy, and the remainder to 18 months. As assessed at 18 months, a favourable response was achieved in 87 per cent of 91 ER7 patients, 79 per cent of 84 ER2, 81 per cent of 53 ER1, 87 per cent of 62 ER7ER1, and in 88 per cent of 68 EtZC patients (93 per cent of 59 EtZC patients if those with ethionamide-resistant strains pretreatment are excluded). As assessed at 18 and 30 months the ER7 regime was as effective as the control EtZC regimen, and 18 months of chemotherapy on the ER7 regimen conferred no benefit over 12 months. No patient on either regimen relapsed after 18 months. Adverse reactions were uncommon on the daily rifampicin regimen but relatively common on the intermittent and control regimens. The commonest reaction to the intermittent regimens was the 'flu' syndrome, which was associated with the presence of circulating rifampicin-dependent antibodies (P less than 0-001).


[Use of "catgut ligatures" in treatment of trophic ulcers of the lower limbs]. Ligatures with fine-cut catgut were employed by the author for treatment of ulcers in 73 patients. Ulcer healing was obtained in 72 patients, while in one case the ulcer was reduced in size. No ulcer recurrence within the terms from 2 months to 6 years was noted.


[Hemangiomas of the skin in children].

[Hemangiomas of the skin in children]. In the article the indications to and results of surgical treatment of 2420 children with skin hemangiomas are discussed. An operative excision of hemangiomas was used in 1139 cases, electrocoagulation--in 1648, sclerosing therapy--in 21, combined treatment--in 4. In 5 children hemangiomas were removed with subsequent free skin graft plasty. Late results were followed up in 795 (32.8%) children within the terms from 4 months to 10 years, following the excision--in 348 cases and after electrocoagulation--in 447.


Salmonella infection in poultry.

Salmonella infection in poultry. Poutry may require a wide range of salmonella serotypes from various sources including feedingstuffs, breeding flocks, rodents, wild birds and other vectors. Clinical disease is uncommon, but all infections are of importance as potential sources of food poisoning in man.


[Type differentiation of V. fetus and V. bubulus by using fluorescent antisera]. Obtained were type-specific fluorescent vibrionic antisera for the laboratory identification of Vibrio fetus strains. They produced positive fluorescence only with the homologous strains, and did not react with the heterologous strains. This showed that the sera were strongly specific. Their use is suggested for the differentiation typing of the Vibrio strains.


[The transketolase activity in erythrocytes as a criterion for thiamine balance in the body]. In deficiency of thiamin the transketolase activity was decreased in patients and in experimental animals. The data obtained showed the high sensitivity of transketolase from erythrocytes to hypovitaminosis B1. At the same time, in diseases, especially accompained by hypoxia (and also by avitaminosis B1), the transketolase activity was shown to be increased. The effect was observed in relation to an increase in amount of young erythrocytes, which contained more transketolase. In these cases it was reasonable to estimate not only the transketolase activity but also other characteristics of thiamin metabolism (content of the vitamin in food, urine and blood).


[Nucleotide composition of RNA, synthesized by polynucleotide phosphorylase, in toluene-treated cells of Escherichia coli]. On incubation of cells of E. coli B and MRE 600 (logariphmic phase of growth), treated with toluene in presence of a mixture 14C-nucleoside-5'-diphosphates, Mg2+ or Mn2+ and tris HCl buffer pH 8.0, intracellular synthesis of heteropolyribonucleotide was observed. The synthesis was catalyzed by polynucleotide phosphorylase (PNPase, E. C. 2.7.7.8). An increase in GDP concentration in the medium distinctly decreased the incorporation of other NDP into the polymer (poly-AGUC). If the ratio of ADP, UDP, CDP, GDP in the medium was 1:1:1:0.2, the composition of nitrogenous bases in the heteropolymer produced reflected completely the NDP concentrations in the incubation mixture. Addition of different amino acids (1-lysine, 1-histidine, glycine, 1-phenylalanine) and their mixtures stimulated poly-AGUC synthesis markedly and caused an appreciable alteration in the nucleotide composition of the poly-AGUC synthesized. This phenomenon resembled the effect of amino acids on the activity of partially purified PNPase and on RNA synthesis, catalized by the enzyme in vitro. These data suggest that in bacterial cell, i. e. in vivo, PNPase synthesizes specific RNA polyribonucleotide sequences, participating in protein synthesis or in its regulation.


[Disorders in sugar utilization by peripheral tissues in lung cancer]. In 140 patients with lung cancer the rate of sugar utilization by antebrachial tissues was determined by the method of arteriovenous difference, in 20 of them the pancreatic functional activity was investigated, using the double sugar stress. In most patients (70%) an impaired peripheral tissue metabolism was observed, that was manifested in a marked reduction of the arterio-venous difference in sugar in some patients and its release by tissues into blood in others. In the latter a reduced activity of the pancreatic insular apparatus was noted.


[Penetration of 35S-lipoate into cells of animals subjected to overloading with the lipoate]. Penetration of 35S-lipoate into nucleated and nucleus-free erythrocytes, isolated cells (enterocytes) and accumulating tissue preparations from intestinal mucosa was studied in presence or in absence of other vitamins. Effect on this process of overloading the penetration of 35S-lipoate into rat and pigeon erythrocytes was found to be increased; under these conditions the enterocytes bind less 35S-lipoate than in control animals. Water-soluble vitamins (nicotinate, riboflavine, thiamin and, especially, panthotenate) decreased the rate of 35S-lipoate penetration into the cells. The mixture of the vitamins caused less distinct inhibitory effect, than the panthotenate only.


[Impairments of lipid metabolism in liver, kidney and heart tissues of mice infected with Proteus vulgaris]. Intraperitoneal administration of Proteus vulgaris living culture of various age (12 hrs and one day) caused impairments in lipid metabolism in mice liver, kidney and heart tissues. The one day-old culture was more toxic. The impairment in lipid metabolism was manifested as distinct increase in cholesterol content in liver tissue and kidney and a decrease in phospholipid content in liver, kidney and heart tissues. These changes were accompanied by an increase in content of sialic acids in liver tissue.


[Comparative characteristics of PBV-1 and PBV-3 viruses isolated from Penicillium breve-compactum]. PBV-1 and PBV-3 viruses isolated from mycelium of Penicillium brevi-compactum show similar morphology and practically the same size of virus particles. Both viruses have been shown to lyse very effectively E. coli C, K12, W3350, CR63. Reproduction of the viruses in E. coli CK cells is limited due to the phenomenon of modification by the host, and negative colonies formed by each on E. coli CK sheet differ in morphology. PBV-1 virus is highly infectious for E. coli B, while the capacity of PBV-3 to multiply in these cells is very low. The limited reproduction appears to be explained by modification of PBV-3 DNA in the E. coli B system. PBV-1 and PBV-3 viruses have been shown to differ serologically, although serological cross reactions indicate their antigenic relationship. The two viruses under study differ in the constituency and molecular weight of the main structural proteins: 36,000: 28,000: 26,500 and 17,000 daltons for PBV-1 and 39,000; 36,000; 32,500; 31,000 and 18,000 daltons for PBV-2.


[Determination of antibody specificity to a new influenza B virus variant by means of the immunoadsorption test]. Immunoadsorption test was used for determination of the strainspecificity of antibody to a new antigenic variant of influenza B virus (B/Hong Kong/5/72 and B/Yamagata/1/73) in human sera collected in April, 1973--March, 1974. The new strains were shown to be circulating in Moscow City only late in February and in March 1974. The experimental data show the immunoadsorption test to give more definite ideas not only on the qualitative differences between strains but also on the specificity of the immunologic response.


Scleroma of the nose and pharynx.

Scleroma of the nose and pharynx. Scleroma of the respiratory tract was first recognized just over a century ago. The disease is endemic in a number of North African, Central American and Latin American countries. However, it has been only rarely seen in the United States. The progression of scleroma takes place through three stages. The first stage of rhinitis has an early catarrhal phase which progresses to one of atrophic rhinitis. The second stage is seen as a proliferative granulomatous growth which obliterates the nasal fossae. The third cicatricial stage is usually accompanied by pronounced scarring and retraction of the tissues involved. Because of the increased ease of international travel by both sea and air, more cases can be expected to occur in the United States. This paper is presented to alert physicians to suspect scleroma in any case of granulomatous disease of the respiratory tract.


The founding of a Medical Service Bureau in King County, Washington -- 1933. The events leading to the establishment of the King County Medical Service Corporation, now King County Medical-Blue Shield, were varied and complex. Under pressure, the King County Medical Society redefined its code of ethics, expanded its view of acceptable practice and gave birth to a major provider of prepaid health care services.


[Comparison of short and protracted streptokinase therapy in acute myocardial infarction]. In numerous controlled studies the effectivity of the streptokinase therapy of the acute myocardial infarction is proved by a significant decrease of the early lethality. The main difference of the therapeutic methods lies in the duration of the application of streptokinase. Of the number of patients of an intensive therapy ward for internal diseases comparisons of the results of therapy of one year with short-term lysis (3 hours) are contrasted with one year with protracted lysis therapy (24-72 hours). The findings demonstrated plead for the fact that by means of the short-time lysis may also be achieved good, perhaps even better results. Issuing from the therapeutic mechanisms of the lysis therapy in the sense of a prevention of the formation of thrombi in disturbed microcirculation by the achieved hyperplasminaemia the short-term lysis is to be regarded as optimum introduction of an anticoagulant long-term therapy.


[72. Evaluation of the cardiac performance by means of radiocardiographic studies]. In 2 series of investigations could be established that there exist relations between the radiocardiographically determined stroke volume and minute volume in rest and the maximum receptivity of oxygen and that the effect of a digitalisation is to be judged according to the increase of stroke and minute volume in rest and under load. The values obtained by the use of 113m indium allow an evidence concerning the functional capacity of the heart. A clear reduction of the stroke volume correlates with a diminution of the maximum oxygen pulse established during an ergometric examination and the maximum receptivity of oxygen.


[Possibilities of differentiation of antinuclear antibodies]. Antinuclear antibodies can give diagnostic informations according to their titre values, the belonging to different classes of immune globulins and on the basis of different patterns of immunofluorescence connection. The determination of granulocyte-specific antibodies which frequently appear in progressive chronic polyarthritis further contributes to the differential-diagnostic classification of diseases of the connective tissue. An antibody against extractable nuclear antigen is specific for the so-called mixed connective tissue disease, an antimitochondrial antibody for the pseudo-LE-syndrome. Moreover, the own examinations resulted in a particularly high and frequent ability of complement fixation of the antinuclear factors in systematic lupus erythematosus and sclerodermy. In contrast to this in the progressive chronic polyarthritis the complement fixation was clearly more insignificant.


[Radioimmunologic diagnosis and pathobiochemistry of the renin-angiotension-aldosterone system. Report of the workshop conference of the German Society for clinical chemistry on January 31 and February 1, 1975 in Bonn (author's transl)]. Studies on the individual components of the renin-angiotensin-aldosterone system are of crucial importance for the investigation of hypertension. The purpose of the workship conference was to give occasion for discussion amongst German speaking research groups on the determination of the individual components of this system, and for the consideration of new results and their pathophysiological significance, as well as possibilities for the evaluation of radioimmunological data with the aid of electronic data processing. The following report is a summary of the contributions to the discussion by those taking part in the workshop conference.


[Treatment of lumbar intervertebral disc lesions by intradiscal instillation of pressurereducing substances (author's transl)]. Direct intradiscal instillation is a possibility to treat lumbar disc lesions. Different substances can be instillated. They are different as far as the effectivity and the side effects are concerned. Therapyresistent nerve root irritations caused by lumbar disc protrusions which generally require operative treatment, are the main indication for instillating pressureducing substances. The technic of the medial transdural injection is described. During the last 2 years 137 patients were treated with lumbar intradiscal instillation with Trasylol. This is a report of our experiences and the first results.


[Radiologic differentiation between pathologic osteoporosis and bone atrophy due to age (author's transl)]. Loss of architecture within the femoral neck due to ageing follows a distinct pattern. This may serve as an index of physiologic ageing of bone. In pathologic osteoporosis (e.g. Cushing's disease, thyreotoxicosis and idiopathic osteoporosis) this systematic reduction of trabecular structure cannot be seen in the femoral neck although the vertebral bodies show all the signs of severe osteoporosis. Radiographic comparison between the proximal end of femur and the spine may, therefore, serve as a useful means of differentiation between pathologic and age-osteoporosis.


[Infected endoprosthesis of the hip - an actuel problem (author's transl)]. Out of 49 infected total hip replacements which were treated at the Orthopedic Hospital of the University of Heidelberg, 39 were taken out and not replaced by a new one. The advantage of such doing was an almost total cure of the infection and a relief of pain. The functional result is the same found in head-neck-resections. The patient's opinion about this method is surprisingly good. It is worth to be considered as an alternative to a replacement of a new prosthesis.


[The frequency of sex chromatine occurring in cell nuclei of internal organs determined by the smear method (author's transl)]. The frequency of sex chromatine occurring in cell nuclei of twelve organs from 25 male and female corpses was determined using the smear method. It was found to be about 60% in the case of female, and about 6% in the case of male corpses.


[Use of a new culture procedure in the diagnosis of vaginal mycoses--a contribution on the improvement of diagnosis]. On the basis of our good experiences with the application of the spoon culture procedure in the quantitative bacteriological urine diagnostics, we tested the applicability of the plastic spoon in the diagnostics of vaginal mycoses. Our investigations show that the spoon culture procedure means an optimization and rationalization in mycological diagnostics due to omission of several stages of work and of the risks of transport, and due to improvement of diagnostic reliability and acceleration of the transmission of findings.


[The need for early therapy in gynecologic patients with postoperative indvelling catheters]. Different conceptions on value or method of chemoprophylaxis or early therapy in case of postoperative carriers of indwelling catheters caused us to compare the effectivity of Nifurantin and Sulfaclomid. Patients were randomised in three groups (target therapy as per antibiogram, "blind" begin with Nifurantin or Sulfaclomid). A simple blind test was made. Evaluation of results was made on the basis of the antibiograms. No essential microbiological differences were found to exist between trans-urethral and suprapubic catheters. Due to the frequency distribution and the resistance situation, we recommend a "blind" early therapy with Nifurantin and simultaneous urine culture, the result of which may lead to a target change in therapy. Microbiological after-checks are just as essential as the correct use of optimal catheters.


[Blastomycoid flora of the urogenital tract in nonpregnant and pregnant patients]. Vaginal and vulva smears and urine obtained by catheters from 232 pregnant and 251 non-pregnant women were examined for the growth of yeasts. These fungi could be grown from the vulvo-vaginal smears from 26,7% of the pregnant women. Yeasts were found in 6,4% of the urine samples. In the case of non-pregnant women, fungi were found in 19,9% of the vulvo-vaginal smears, whereas 3,2% of the urine samples contained yeasts. The growth of yeasts was encouraged by the addition of various urine dilutions using to a nutrient solution containing Candida albicans of Torulopsis glabrata the urine obtained via catheters from both pregnant and non-pregnant women. There was no difference in the intensity of the effect between the two urine charges. Due to the relatively rare occurrence of yeasts in the urine from pregnant and non-pregnant women it suspected that the increased frequency of vaginal mycoses during pregnancy is not caused by a general disposition, but that locally effective factors are responsible.


[Birth injury and colposcopic status of the cervix uteri following labor]. A colposcopic examination is made of uterine cervix 3 to 4 months after delivery to 629 women divided into 4 groups: with Caesarian section and vaginal delivery without cervical rupture after inspection, with suture and without suture after cervical rupture. Higher incidence and severe colposcopic changes in the uterine cervix were found in unsutured cervical ruptures after delivery. Suturing of the cervical ruptures after delivery reduces these changes by 25 per cent. For this reason the author recommends cervical inspection and suturing of the existing cervical ruptures after every delivery.


[New serological investigations into O-antigenic relations between Escherichia coli, Salmonella, Arizona and Citrobacter (author's transl)]. During a systemic investigation into O-antigenic relations within the family Enterobacteriaceae, with special emphasis on serological relationships between O-antigens (or O-groups) of E. coli and various O-groupps of Salmonella, Arizona, and Citrobacter, our tests confirmed some findings previously descried by other authors, some were not confirmed, and other antigenic relationships were discovered which have not yet been published. Individually tested were O-Antigens of 142 serologically defined E. coli types by using O-factorsera of Salmonella, Arizona, and Citrobacter for the slide agglutination. The slide agglutination was applied in preference to the tube-agglutination, not only because the former has been generally adopted but it also shows broader reactions...


[Chemical and serological characterization of Salmonella lipopolysaccharides from different phases of growth (author's transl)]. Chemical and serological investigations were carried out on lipopolysaccharides of 4 Salmonella S-forms and of 1 SR-mutant, extracted from bacteria at different ages of culture (early exponential to stationary growth phase). The results show that the fatty acid composition of Lipid A (lauric-, myristic-, palmitic-, and beta-hydroxy-myristic acids) does not undergo any significant change during the growth of the cultures. However, there are differences in the molar ratios of the fatty acids from strain to strain. In all phases of growth Lipid A is substituted by basaloligosaccharide, to the same extent, as can be seen from the constant ratios of beta-hydroxy-myristic acid: heptose. Serological experiments (haemagglutination inhibition tests, absorption of antibodies by LPS-coated erythrocytes) showed that in no case the basaloligosaccharide is completely substituted by O-specific chains and that basaloligosaccharide exhibits free R-antigen structures which are mainly of chemotypes Ra, Rb and Rc, for the SR-mutant only of types Ra and Rb. There is no demonstrable dependence upon the phases of growth. In the O-specific polysaccharide chains the sugars of the main chain and the side bound dideoxy sugars (abequose and tyvelose) show a constant 1:1 molar ratio in all phases. In the case of S. typhimurium, antigen factors 1, 4 and 12(2), the biosynthesis of which is controlled by modifying oaf genes and/or by a lysogenic phage, are of a somewhat weaker expression in the exponential phase than in the latter phases of growth. In the SR-mutant, lipopolysaccarides with (low) serological O1 and O12(2) activity are only extractable by the phenol/water method, but not by the PCP method. In three out of four S-forms, changes occur in the length of the O-specific polysaccharide chains, whereas the number of repeating units of the fourth strain remains almost unchanged. The lipopolysaccharides of the SR-mutant contain in all phases of growth about one repeating unit. In all strains the covering of the cell surface by lipopolysaccharide molecules changes during the course of growth, as can be seen by comparing the relative cell surface and the content of Lipid A fatty acids of the bacteria. Lipid A synthesis in the 4 S-forms is reduced in the exponential phase and/or in the phase of delayed growth acceleration. The extent of biosynthesis of the carbohydrate moiety of lipopolysaccharides is independent of that of Lipoid A. In the SR-mutant, Lipoid A and Polysaccharide are formed in increased amounts in the exponential growth phase.


[Salmonella typhimurium masked as an Enterobacter species (author's transl)]. A bacterial strain at first sight appearing to be an Enterobacter species causing enteritis could be identified as Salmonella typhimurium showing only a low formation of H2S. This small degree of H2S formation could not be demonstrated on commercial media ready for use. The high antibiotics resistance of the strain in question points to the possibility of its having undergone several antibiotics passages without recognition. Thus, serological verification is recommended in the case of so-called Enterobacter species appearing as agents of enteritis.


Reactivity of lipopolysaccharides from various salmonella SR and R chemotypes Ra-Re mutants with concanavalin A. Lipopolysaccharides from different R mutants of Salmonella minnesota and Salmonella typhimurium belonging to chemotypes Ra to Re, as well as from three SR mutants of Salmonella typhimurium were selected for a study of their precipitability with Concanavalin A. Predictions as to the outcome of the reaction could be made since both the chemical structure of the Salmonella R lipopolysaccharides and structural requirements for a positive reaction with Concanavalin A are well established. Precipitation studies in the immuno-electrophoretic assay and in the microcapillary test were carried out with alkali-treated lipopolysaccharides as untreated lipopolysaccharide is too highly aggregated to allow a sufficient migration in agarose layers. Lipopolysaccharides of all mutants--except the SR mutants--were obtained by the phenol/chloroform/petroleum ether method in order to avoid contaminations by glucans or glycogen which are known to occur in phenol/water extracted lipopolysaccharides and which would lead to erroneous results. Additional precipitation studies were carried out with two other lectins of different polysaccharide specificity: Wheat Germ Agglutinin and Soybean Agglutinin. As expected, lipopolysaccharides of chemotypes Ra, Rb1, and RcP- mutants reacted strongly with Concanavalin A, whereas no reaction was demonstrable with lipopolysaccharides of chemotypes Rb2, Rb3, Rd and Re mutants. The lipopolysaccharide of an RcP+ mutant unexpectedly failed to precipitate unless it was dephosphorylated with HF. This artificially prepared RcP-lipopolysaccharide showed a strong reaction, thus demonstrating that negative charges in the direct neighborhood of reactive sugar units as in RcP+ LPS may prevent precipitation with Concanavalin A. No reactivity demonstrable by precipitation could be obtained using either Wheat Germ Agglutinin or Soybean Agglutinin with alkali-treated lipopolysaccharide even of those chemotypes which had the supposedly reactive sugar in a terminal position, such as N-acetyl-D-glucosamine in Ra mutants (Wheat Germ Agglutinin) or D-galactose in Rb2 or Rb3 mutants (Soybean Agglutinin).


Receptors for T2, T4 and T6 phages in Sh. dysenteriae 7 and other serotypes of Sh. dysenteriae. The sensitivity of four strains of Sh. dysenteriae and of nine strains representing other serotypes of Sh. dynsenteriae to phages T2, T4 and T6 was examined. Different extracts, prepared from sensitive strains were tested for their capacity of phage inactivation. We found that the receptor substance for phage T2 is localized differently in various strains: In Sh. dysenteriae 7, it was found in bacterial extracts obtained by water/phenol at 68 degrees C and in extracts obtained by trichloracetic acid; in Sh. dysenteriae 2 and Sh. dysenteriae 6, it was found in extracts obtained by heating in water at 65 degrees C. None of the tested extracts of strains Sh. dysenteriae 1, Sh. dysenteriae 4 and Sh. dysenteriae 9, sensitive to phage T2 and T6 and T6, revealed receptro activity for these phages. Most of the extracts, which showed receptor activity for phage T2, appeared to be weak or completely inactive for phage T6. Several strains appeared to be sensitive to phage T4 and the receptor active substance was found in the bacterial extracts obtained by water/phenol at 68 degrees C. The sensitivity of Sh. dysenteriae smooth strains to "rough specific" T4 phage is discussed.


[Indirect flourescent antibody test in toxoplasmosis. Advantage of the use of fluorescent anti-IgG conjugate (author's transl)]. The indirect fluorescent antibody (IFA) test effected with anti-human conjugate gives appreciably equivalent results to those obtained with the dye (SABIN-FELDMAN) test, but weak serum dilutions may raise non specific reactions, due to the presence of substances possessing the IgM antibody properties. Those substances are not present in the serum of children during the first months of their life. The application of an anti-IgG conjugate allows to prevent those unspecific reactions. The application of the modified IFA test for detecting the toxoplasmic infection during pregnancy and the use of the REMINGTON test for the early diagnosis of the congenital toxoplasmosis are discussed.


[Results of a quantitative study of the interaction of pathogenic enterobacteria with a cell monolayer]. A study was made of the cytopathic effect and dynamics of intracellular reproduction of S. typhimurium and shigellae in the monolayer of HeLa cells, macrophages (monocytes) of the peritoneal exudate of rabbits and rats and microphages (granulocytes) of the pleural exudate of rabbits. The presence of bactericidal mechanism in the host cell to the invaded infectious agent is postulated. An important role of the cell component of defence in insensibility in shigellosis is supposed.


[Reactivity and immunogenicity of the Sonne dysentery detergent monovaccine]. The authors elaborated a method of isolation under industrial conditions of Shigella sonnei surface antigens by the treatment of the culture with a detergent (sodium laurylsulfate). The antigens obtained possessed a much lesser toxicity in comparison with the tryptic ones. A method of preparation of a detergent Sonne monovaccine with an increased antigen content (1.3 mg/ml) was described. Experimental series of the preparation were tested on 38 volunteers. A lower reactogenicity of the detergent vaccine (in comparison with the tryptic) and its marked immunological efficacy was demonstrated.


[Detection of autoimmune changes in white mice as a method of studying the biological properties of Shigella sonnei]. An attempt was made of using for the purpose of studying the virulence of Sh. sonnei of the method of determination of autoimmune plaque-forming cells in infected albino mice. By the mentioned method a total of 231 strains of Sh. sonnei of various biochemical types were examined. The virulence of 103 strains was checked in paralled by the keratoconjunctival test. It was shown that the method of determination of the autoimmune plaque-forming cells in the blood of infected mice could be used as a test for the virulence of Sh. sonnei, which was more sensitive than the keratoconjunctival test. Among the cultures studied 14.7% proved to be avirulent, 51.5%-of low virulence, 21.2%-moderately virulent, and 12.6%-highly virulent. Strains of the II biotype proved to be the most virulent, and strains of the III biotype-the least. The virulence of the cultures isolated from the patients with acute dysentery was more than double that of the cultures isolated from persons who came in contact with the patients.


[Study of the role of colicins in the formation of microbial association in experiments in chick embryos]. Experiments were conducted on chick embryos; conditions of formation of bacterial cenosis of Shigella sonnei and E. coli were reproduced. The role of colicinogenia in the formation of bacterial cenosis was demonstrated. An accumulation of colicines in high titres (1: 5120- 1:2560) in the chick embryonic cavity was noted in combined or separate cultivation of colicinogenic shigellae and E. coli. An intergenera transmission of the col-factor was traced in experiments on chick embryos. The data obtained served as foundation for recommendation of the accessible and economic model (chick embryos) for the in vivo study of colicinogenia of the enteric bacteria representatives.


[Serologic interrelations of choleragen and the neurotoxins of enterobacteria]. Antibodies reacting with the endotoxins of enterobacteria or antibodies to homologous endotoxin were eliminated from the sera to cholerigen, cholerigen-toxoid by precipitin abosrption. Sera to neurotoxin of enterobacteria were exhausted in the same way. The exhausted sera continued to form precipitation lines with heterologous toxic complexes. The presence of affiliated antigens in the composition of cholerigen and of shigellae, salmonellae and escherichia neurotoxins was also shown by the method of immune electrophoresis.


[Detection, quantitative calculation and identification of bacteria of the Proteus genus in objects of the environment]. The author suggests a complex of nutrient media which aid in detection, quantitative recording and identification of bacteria belonging to Proteus genus and also of the species included into this genus, as well as of the biochemically similar bacteria. The complex of the media constitutes a complete cycle of study: the first stage-fluid enrichment medium, the second stage-isolation and preliminary identification on a hard differential medium with a narrow directed action, and the third stage-determination of the reference of the isolated culture by 9 signs in three integrated media.


[Cultivation of F. tularensis in developing chick embryos]. In cultivation of the causative agent of tularemia in the organism of chick embryos (8-10 days of incubation) it was found that the virulent strains multiplied intensively in the yolk sacs causing the death of the embryos on the 3rd-4th day after the infection; as to the virulent strains-they were only preserved in the embryos. The period of death of the embryos and the accumulation of bacteria depended on the strain virulence. No differences in the anatomical structure of the cells belonging to the virulent and avirulent strains could be found.


[Comparative study of the antigens of Streptococcus group A. Rport I. Comparative characteristics of the immunologic activity of partially purified M-protien and the cytoplasmic protective antigen]. Experiments were conducted on mice. A study was made of the protective properties of the cytoplasmic fraction of streptococcus, group A, Type 1 and of an antigen isolated from it by sedimentation with ammonium sulfate, in comparison with M-protein partially purified by the method of Lancefield and Perlman. Cytoplasmic antigen was not inferior by immunogenicity in comparison with M-protein. In difference from the latter, it was thermolabile and sensitive to the action of hydrochloric acid. The protective antigen was revealed in the cytoplasm not only of the virulent, but also of avirulent strains of streptococcus devoid of M-protein.


[Construction of new types of chemical vaccines for the prevention of intestinal infections, and their qualitative assessment. IV. Physical properties and immunological characteristics of the experimental series of chemical vaccines presented for comparative study]. The authors present the results of study of physico-chemical properties of the chemical sorbed monovaccines from the antigens of the causative agents of typhoid fever, paratyphoid A and B and Sonne and Flexner dysentery obtained by various methods; the results of investigation of their reactogenic properties and immunological activity of limited groups of volunteers also given. The vaccines from the antigens obtained by sparing methods were less reactogenic than the rest experimental and control vaccines obtained from the tryptic antigens. The majority of the experimental vaccines caused a significant increase of the specific antibody titres in the sera of the vaccinated persons: typhoid vaccines--of the O-, VI- and H-antibodies, paratyphoid B vaccines--of the O- and H-antibodies; the control vaccines from the tryptic antigens failed to induce the H-antibody synteisis in the vaccinated persons. Experimental dysentery monovaccines induced a greater increase in the antibody titres than the control vaccines.


[Condition of microflora of the nasopharynx in immunization with live influenza vaccine for oral administration]. The authors present data concerning the state of the microflora of the nasopharynx in the immunization of adults and schoolchildren with the living influenza vaccine for oral administration. During the vaccinal process there occurred qualitative changes in the microbial pattern of the nasopharynx and a reduction in the level of the salivary lysozyme. The most pronounced changes were seen after the first vaccination, when the seeding efficiency of the pathogenic staphylococcus the E. coli and the Pr. mirabilis increased considerably. At the same time the incidence of isolation of the pathogenic staphylococcus, neisseria, and hemolytic streptococcus was decreased. The mentioned changes in the microbial flora directly depended on the dynamics of the survival of the vaccine influenza virus.


[Nomenclature of the S. coli (E. coli) No. 2624/36 and 5396/38 strains]. The author confirmed the fact that S. coli (E. coli) No. 2624/36 and 5396/38 strains were referred to the serological type O37 : H1,5(Salmonella) : Vi of the Citrobacter genus. Strains of this serological type of Citrobacter failed to ferment cellobiose, starch, contained no decarboxylase of glutamic acid, and did not utilize sodium malonate; they fermented glycerine.


[Characteristics of bacteriophages used in the detection of disturbances in the synthesis of the O-antigen polysaccharide of Shigella flexneri]. A study was made of the sensitivity spectra of various strains of Sh. flexneri and R-mutants of various chemotypes to bacteriophages used for lysotyping of shigellae and to some bacteriophages specific of the R-mutants of salmonellae and E. coli. As a result of study there was selected and characterized a collection of bacteriophages specific of the S-strains and R-mutants of shigellae of different chemotypes, which could be used in genetic and immunochemical investigations.


[Morphological manifestation of the action of the complement-antibody system on the surface structures of S. typhimurium]. An electron-microscopic study of the negatively-stained S. typhimurium cells from the culture subjected to the action of a specific hyperimmune antiserum in the presence of a complement (the "complement-antibody" system) pointed to increase in the population of morphological signs of cell destruction--an increase in the number of small bacterial fragments. Many cells which retained the configuration of bacterial cells also had signs of specific affection. The determining sign of specificity of the process was the presence on the surface of the great majority of the mentioned morphological types of accumulations of bacterial fragments of the stain in the form of dark stains surrounded by a lighter ring. The stains were as a rule round with the diameter of the dark zone of about 80 A. The light framing of about 30 A in width consisted of 12 subunits. A conclusion was drawn that further experimental analysis was necessary for detalization of this process and reproduction of a complete picture of bacteriolysis.


[Functional asymmetry of the human cerebral hemispheres]. On the basis of a critical analysis of Soviet and foreign literature, as well as on some results of long-term personal observations, the authors discuss some modern concepts (clinico-diagnostical, neurosurgical, rehabilitative, neurophysiological) of functional asymmetry in the human hemishperes. The authors underline a necessity for a detailed multidisciplinary study of this problem, having  in view its importance for the theory and practice of medicine.


[Catecholamines in the pathochemical structure of depressive conditions (according to material from a biological study)]. By a combination of biochemical and pharmacodynamical analyses the author conducted a differentiated study of the role of separate neurohormones (adrenalin, noradrenalin, dopamine, serotonine) and their interconnection with other regulating systems (corticosteroids, nucleic acids) in the neurochemical structure of experimental models in depressive behaviour (reserpine depressions, depressions due to inhibitors of dopamine-beta-oxydase). In the aspect of the author's concept concerning reciprocity of relationships between the central and peripheral catecholamine mechanisms on the basis of the obtained experimental data, their comparison with the previous clinico-biochemical investigations and literary data is considered to be the pathochemical basis of depression. This is considered to be a multicomponent structure of pathologically fixed changes of the central noradrenergic activity, relationships in the catecholaminergic system (hypothalamus--medullau substance of the adrenal glands) and processes of reswitching catecholamine influences on the state of other neurochemical regulatory systems.


[Rupture of the duodenum due to blunt injury]. Injuries of the duodenum, although rare, have increased in frequency of occurence during the past ten years. Careful attention must be given to them, especially if the injury was brought about by a blunt blow of the abdominal, and lower thoracic regions. X-rays are the most important means used in diagnosing such cases. Injuries of the duodenum often occur along with injuries of other related structures, especially in polytraumatized patients. Early diagnosis, and surgical treatment are conditio sine qua non for successful results. During the operation itself, a compete inspection of the entire duodenum, both intra and extraperitoneal parts, careful placement of sutures about the perforation and an exact drainage are of utmost importance in the prevention of postoperative complications. In cases in which the duodenal wall has lost its vitality for accepting suture, a gastrojejunal, duodenojejunal anastomisi, or gastrostomia are performed, the content of the duodenum is aspirated, the duodenum is decompressed and adequate drainage of the peritoneal cavity is established. In cases of accompanying injury of the pancreas, or choledochus, a drainage of the extrahepatic bile duct is recommended. The authors discuss one case with a ruptured duodenum, resulting from blunt trauma, in which all of the above mentioned procedures were used; they insist that any suspicion of a duodenum's rupture indicates an immediate laparotomy.


The significance of local malignant lesions of the neck diagnosed accidentally during parathyroid exploration. Three cases are presented in which strictly localized, malignant lesions in reticuloendothelial or mesenchymal tissue of the neck with varying degrees of differentiation were diagnosed accidentally during parathyroid exploration. No signs of metastatic dissemination or primary tumour with other localization were found. In all three cases, the identified changes were removed and a careful follow-up has not hitherto indicated that further treatment in these cases were necessary.


Morphological studies of the duct-ligated canine pancreatic allograft in the early period after transplantation. Eighteen previously pancreatectomized dogs were transplanted with duct-ligated pancreatic allografts. Fourteen grafts were preserved for 24 hours with either continuous hypothermic perfusion or simple hypothermic storage. Four grafts were immediately transplanted. Azathioprine was given as sole immunosuppressive treatment. Three dogs died from early post-operative bleeding. The remaining 15 animals had an adequate endocrine function. After four to eight days the gross appearance was registered and the histopathological changes of the graft were studied with light and electron microscopy. The grafts were enlarged and of a firm consistency. Light microscopically the inter-lobular septa and the interstitial tissue showed an inflammatory reaction with oedema and fibroblastic proliferation. Collagen deposition was found after five days. In spite of an inflammatory reaction of the grafts, islets of normal appearance were recognized both light and electron microscopically which corresponded to an adequate endocrine function. In the 24-hour preserved glands fibrosis seemed to appear earlier and a smaller number of islets were recognized than in the immediately transplanted glands.


Oestrone, oestradiol and testosterone in normal and hypogonadal men following LH-RH or HCG stimulation. oestrone, oestradiol-17beta and testosterone in serum were measured during a LH-RH infusion test and a Leydig cell function test with HCG in healthy men and in patients with primary or secondary hypogonadism. Following infusion of LH-RH increases of LH (+112%), oestradiol (+62%) and testosterone (+51%) were observed in normal men, while oestrone remained unchanged. Of the patients only those with Klinefelter's syndrome showed a significant increase in testosterone and oestradiol after LH-RH infusion. During the Leydig cell function test oestradiol and testosterone exhibited a largely parallel pattern under normal and pathological conditions as well as in subjects with experimental hypogonadism. Augmentations of plasma oestrone were usually smaller than those for oestradiol.


Changes in pituitary and ovarian hormones following injection of ultra low dose LH-RH in normal and amenorrhoeic women. The results of the ultra low doses of synthetic LH-RH, 1.56, 3.125 and 6.25 mug, are presented in 8 normal women during the first week of the menstrual cycle and 14 patients with secondary amenorrhoea. Seven of these patients had "stress" amenorrhoea, and 7 had preceeding oligomenorrhoea. There was no significant difference between the mean basal gonadotrophin levels in the normal volunteers and those patients with secondary amenorrhoea. There was no significant difference in basal gonadotrophin levels or the response to LH-RH, between the two groups of amenorrhoea, stress and previous oligomenorrhoea. Basal FSH and oestradiol levels do not appear to influence the response to LH-RH. However, those patients with secondary amenorrhoea and a low basal LH (5 patients) had a significantly higher response to LH-RH at 1.56 and 3.125 mug than the amenorrhoeic patients with normal basal LH levels. Two patients with stress amenorrhoea and weight loss had an exaggerated response to LH-RH. The significance of this is discussed.


Cellular sensitization in kuru, Jakob-Creutzfeldt disease and multiple sclerosis: with a note on the biohazards of slow infection work. Following intramuscular injection of Kuru and Jakob-Creutzfeldt brain material into chimpanzees, circulating lymphocytes became sensitized to scrapie mouse brain (and spleen) to a greater degree than to normal tissue. This sensitization subsided after about a month, to be followed some 90 days later by a secondary peak attributed to establishment of changes in the nervous system. Special sensitization to scrapie material occurs in Kuru and Jakob-Creutzfeldt disease, but is not specific to them. The immunological evidence suggests that parenchymatous destruction may precede astroglial hypertrophy in these diseases. An early peak occurred in animals inoculated with multiple sclerosis brain and normal brain, but neither showed a delayed second peak. Thus there was no evidence of establishment of infection, even though all four animals were in intimate contact for over 200 days, and no evidence of the injection of MS material itself having established an infection. Biohazards in Kuru, Jakob-Creutzfeldt and MS work appear to be very low. The significance of the increased sensitilization to scrapie material in Kuru and Jakob-Creutzfeldt disease, especially in relation to normal ageing (where it also increases), is discussed.


Study of the suppression of lactation and the influence on blood clotting with bromocriptine (CB 154) (Parlodel): a double blind comparison with diethylstilboestrol. Inhibition of lactation was studied in 38 puerperal women in a double blind trial to assess the effect of bromocriptine in comparison with diethylstilboestrol (DS). Simultaneously the influence of both compounds on blood clotting was studied, along with a control group of 20 women not receiving any medication. Bromocriptine was given in a daily dose of 5 mg for 14 days and DS in a daily dose of 20 mg for 7 days followed by a placebo for a further 7 days. The first doses were not later than 8 hours after delivery. Both compounds showed an inhibitory effect on the onset of lactation and mammary congestion. This inhibitory effect on both parameters was significantly in favour of bromocriptine during the last days of the treatment due to rebound in the DS group. The bromocriptine doses used (5 mg daily for 2 weeks) caused no objective side effects and no subjective restraint. Treatment with bromocriptine caused no untoward effect on the blood clotting, while in the DS group a slower return to normal antithrombin III could be observed. Also in this group one case of thrombophlebitis occurred. Bromocriptine can be administered to puerperal women for the suppression of lactation.


Extramembranous pregnancy with amniorrhoea. A case of extramembranous pregnancy is reported. From about the 10th week of pregnancy there was an intermittent loss of liquor amnii, which from about the 25th week, became continuous. The infant was born alive in the 31st week, but died 15 days later because of the respiratory distress syndrome. The placenta was circumvallate with short, thick membranes unable to cover more than a small part of the infant. The course of the pregnancy and the prognosis of the infant are discussed on the base of previous publications. Because of the poor prognosis for the infant it is suggested that interruption of the pregnancy should be considered in early cases of amniorrhoea.


The periurethral aerobic bacterial flora in healthy boys and girls. The present study was undertaken to provide information about the presence of bacterial flora in the periurethral region of healthy children and its variation with age and sex. It was intended as a basis for subsequent studies in individuals prone to urinary tract infection. Quantitative methods were used for bacteria sampling and culture. The study included 394 girls and 305 boys from birth to 16 years. During the first few weeks of life a massive aerobic bacterial flora (E. coli, enterococci, staphylococci) was established in the periurethral region of both sexes. The colonization with E. coli and enterococci began to diminish already during the first year of life and became very scanty after the age of 5 years. In newborns E. coli colonization was dense in boys and scanty in girls. Later E. coli was the dominating gram-negative species in girls of all age groups. In boys E. coli dominated during the first half year of life, later Proteus was as common as E. coli; staphylococci did not change very much. Urine samples from healthy school-children contained very few gram-negative bacteria; even when collected without preceding cleansing. The results suggest that there might be a local defence mechanism maturing during the first year of life, eventually protecting the exposed area from colonization with gram-negatives and enterococci.


The periurethral aerobic flora in girls highly susceptible to urinary infections. After the age of 5 years, normal children have but few aerobic gram-negative rods periurethrally. This study examines whether there is an abnormal periurethral colonization in urinary tract infection-prone girls during infection-free intervals, indicating a defective local defence. In 13 girls with a history of recurrent infection, daily bacterial samples were obtained from the periurethral area and from urine. Sampling continued until an infection eventually occurred. Seven girls contracted a urinary tract infection within 3-30 days. All were heavy colonized with gram-negative rods, often several species, before infection appeared. Serotyping of E. coli confirmed that it was the colonizing strain which later invaded the bladder. The findings suggest a local defect in the antibacterial defence of infection-prone individuals and gives strong evidence for ascending infection. Six girls remained uninfected during an observation period of 9-123 days. They all had a normal periurethral flora. A reasonable hypothesis would be that the same factor counteracted colonization and infection. Since abnormal periurethral colonization was not a constant phenomenon the postulated defect may vary. This might explain the fact that urinary tract infections often appear in quick succession, often followed by long infection-free intervals.


Glucose tolerance and serum lipids in man after long-term lithium administration. Intravenous glucose tolerance and serum lactate concentration during the tolerance test were determined in the same 12 patients after 6 months of placebo and after 6 months of lithium treatment. At the end of these periods values of glucose, lactate, serum free fatty acids, and serum triglycerides were measured in fasting patients. Long-term lithium treatment had no influence on these parameters.


Comparison of unilateral dominant and non-dominant ECT on verbal and non-verbal memory. An intraindividual, double-blind cross-over comparison of the effects of dominant (D) and non-dominant (ND) temporo-parietal unilateral electroconvulsive therapy (ECT) was performed in connection with the second and third treatment, the type of electrode placement being allocated at random. Four memory tests were used. The 30 Word-Pair Test is an audio-visual verbal recall test, the 30 Figure Test is a mainly visual recognition test with easily verbalized items. The 30 Geometrical Figure Test and the 30 Face Test are nonverbal recognition tests of visual complex and unfamiliar material. Compared with dominant ECT, non-dominant ECT has a more negative influence in the complex non-verbal visual tests, whereas dominant ECT has a more negative effect on verbal memory. In the non-verbal tests, as compared with the verbal ones, the encoding (or learning) is relatively more influenced and the retention (or storage) relatively less. An impairment either of complex apperceptive function or of memory may be responsible for the relatively lower performance in non-verbal tests after non-dominant ECT.


Three-dimensional reconstruction of the human heart by video technique. Three-dimensional reconstruction of different plastic phantoms, organic material and beating human heart was achieved by utilizing a standard roentgen-television system. In continuous stabilized fluoroscopy the television images of the object obtained from different projections were digitized in real time and computerized for reconstruction. Despite a cone beam being used, the spatial resolution seems to be quite adequate for evaluation of gross anatomic structures like the cardiac walls without enhancement by contrast medium.


[The Dualism drive in Freudian theory].

[The Dualism drive in Freudian theory]. The author discusses Freudian dualistic conception of drives and contends that it can be reduced to a monistic one, on the basis of modern conceptions of Biology, and after scanning the original writings of Freud on the subject of drive and instinct. The word Trieb (drive) is used by Freud as compared with Instinkt (instinct); in 1915 the concept is defined through its attributes: thrust, source, objet and goal; being object and goal contingent for the drive and fixed for instincts. The first dualism is love vs. hunger; the drives are either sexual or autoconservative. But Biology demonstrates today that all life movements are autoconservative. The second dualism, love vs. hate, and the third one, Eros vs. Thantos, interpreted through Biology, show that there is always a prevailing therm, the first one. In this view, instinct should be but one successful drive, "frozen" through time because of its very success, and transmitted through philogenetic channels, in order to be enlivened in each ontogenetic process.


Photographic subtraction. I. Theory of the subtraction image. The purpose of subtraction of angiographic images is to demonstrate the vessels free of superimposed, disturbing image noise. With the aid of physical film parameters the theoretic basis for an optimum subtraction technique is presented.


Angiography in disease of the peripancreatic lymph nodes. Angiography was performed in 8 patients with peripancreatic lymph node disease. The findings were similar to those caused by pancreatitis and pancreatic carcinoma. The angiographic characteristics of the disease, respectively, are discussed.


A double-blind placebo-controlled cross-over study with lidoflazine (Clinium) in post-infarction patients. The effects of lidoflazine on exercise tolerance have been tested during a double-blind cross-over trial in 14 male post-infarction patients with a median age of 47 years (range 24-85). Each treatment phase lasted three months. Lidoflazine dosage was one 60 mg tablet t.i.d. At rest, significant decreases in diastolic blood pressure (DBP) and heart rate (HR) were noted during lidoflazine treatment. Bicycle ergometric tests revealed a significant increase in maximum work load and a significant decrease in the product HRXsystolic BP at a 100 W work load during lidoflazine. No similar changes were recorded during placebo periods. Five patients were able to resume their professional activities whilst on lidofalzine, against only two on placebo.


Evaluation of a computer-based system for detecting ventricular arrhythmias. A digital system for real-time arrhythmia monitoring in the coronary care unit has been designed. The system is based on an algorithm for discrimination between normal complexes and ventricular ectopic beats (VBs). A beat is classified as normal if the absolute difference from a running average of the patient's normal QRS is below an adaptive threshold. To prevent artifacts and beats of non-ventricular origin from being falsely interpreted as VBs, each abnormal beat is correlated with a typical VB waveform, incorporated into the program. A VB is recognized only when the correlation coefficient exceeds 0.8. In a performance study, ECGs from 15 patients were recorded on magnetic tape and replayed to the computer. Independent evaluation by two physicians showed a total of 1 306 VBs, 94% correctly classified by the computer. In the group labelled "suspected VBs" the detection rate was lower (average 69%). Out of the whole number of complexes (53 260), 0.45% were falsely interpreted as VBs by the computer. Artifacts giving rise to false VBs are included in this figure. The causes of false positive and false negative VBs were thoroughly investigated and on the basis of these results, possible improvements in the system are discussed.


Beta1-blocker (practolol) and exercise in patients with chronic obstructive lung disease. Ventilatory and circulatory data from 20 patients suffering from chronic obstructive lung disease have been obtained before, during and after exercise at 600 kpm/min for 5 min on a bicycle ergometer. The patients had been given intravenously practolol, 15 mg, or saline alternatively, using a double-blind cross-over technique. A slight postexercise reduction of FEV1 (8%) was noted after practolol medication as compared to placebo, with an accompanying decrease in PaCO2; PaO2 did not differ substantially. No wheezing or inappropriate dyspnea attributable to the medication was noted in any of the patients. The well known beta1-blocking effects on the circulation were confirmed, with maintained Q and reduced HR, together with a lowered systemic BP during and after exercise. There was a significant positive relationship between the postexercise reduction of FEV1 and the concomitant fall in HR. It is concluded that practolol in doses with near maximal circulatory effects had a slight, but clinically insignificant effect on the ventilatory parameters.


Physiopathological effects of rapeseed oil: a review. Rapeseed oil has a growth retarding effect in animals. Some investigators claim that the high content of erucic acid in rapeseed oil alone causes this effect, while others consider the low ratio saturated/monounsaturated fatty acids in rapeseed oil to be a contributory factor. Normally erucic acid is not found or occurs in traces in body fat, but when the diet contains rapeseed oil erucic acid is found in depot fat, organ fat and milk fat. Erucic acid is metabolized in vivo to oleic acid. The effects of rapeseed oil on reproduction and adrenals, testes, ovaries, liver, spleen, kidneys, blood, heart and skeletal muscles have been investigated. Fatty infiltration in the heart muscle cells has been observed in the species investigated. In long-term experiments in rats erucic acid produces fibrosis of the myocardium. Erucic acid lowers the respiratory capacity of the heart mitochondria. The reduction of respiratory capacity is roughly proportional to the content of erucic acid in the diet, and diminishes on continued administration of erucic acid. The lifespan of rats is the same on corn oil, soybean oil, coconut oil, whale oil and rapeseed oil diet. Rats fed a diet with erucic acid or other docosenoic acids showed a lowered tolerance to cold stress (+4 degrees C). In Sweden erucic acid constituted 3-4% of the average intake of calories up to 1970 compared with about 0.4% at present.


The anginal syndrome without evidence of coronary artery disease. It is apparent that a variety of factors may be responsible for myocardial ischemia, and even infarction, in the absence of occlusive major vessel coronary disease. In particular, it must be emphasized than angina-like chest pain may well have its origin in myocardial ischemia, even in younger patients with unusual patterns of chest pain but without predisposition to premature CAD. Increasing awareness of disorders such as coronary arterial spasm, functional impairment of subendocardial blood flow and the possible role of variant patterns of anatomic distribution of the coronary arterial tree, will provide a better understanding of their significance as determining or contributing factors in patients with the anginal syndrome.


Acute bacterial diseases.

Acute bacterial diseases. The manner by which bacteria cause diarrhea has been clarified as a result of the understanding of mechanisms involved in fluid secretion. It is conceivable that many of the undiagnosed mass of diarrheal cases are in fact caused by E. coli or other organisms capable of eleborating an enterotoxin or of invading the epitehlial surfaces of the gastrointestinal tract. Confirmation of this concept would permit a better estimation of the importance of "viruses" in causing diarrhea. Proper treatment for bacterial diarrhea requires fluid replacement. Antibiotic therapy and antidiarrheal drugs need to be used with caution since they may worsen the diarrheal process or may complicate recovery.


Senile and postmenopausal osteoporosis.

Senile and postmenopausal osteoporosis. Obviously, the relentless decrease in bone mass that accompanies aging will continue the long sought "elixir of youth" is discovered. Individuals, because of race, sex, environmental, dietary, genetic or activity differences, will be more or less predisposed to symptomatic osteoporosis with increasing age. The careful and knowledgeable physician should, however, make every attempt to rule out potentially remediable, subtle forms of demineralizing disorders, such as apathetic or T3-thyrotoxicosis, hyperparathyroidism, malabsorption and osteomalacia or multiple myeloma. Not only do these diseases result in an accelerated loss of bone mass and an increased incidence of skeletal fractures but they mimic postmenopausal or senile osteoporosis radiologically. Once the metabolic or malignant disorders of bone metabolism have been effectively considered and ruled out, the senescent or postmenopausal osteoporotic patient should be treated judiciously with short-term estrogen therapy, a diet sufficient in vitamin D and calcium content and continued attempts to insure adequate skeletal mobilization. The addition of sodium fluoride and/or calcitonin to this regimen should not be attempted without extreme caution until the potentially harmful systemic effects of prolonged therapeutic trials have been appropriately assessed.


The enterohepatic circulation of bile acids in man. It is clear that a truly spectacular increase in our understanding of the biliary circulation has occurred during the past 5 years. A steady-state situation has now become dynamic. In a sense, we have clarified the anatomy and physiology of the biliary circulation, and the challenge now is to describe its biochemistry. Specifically, we remain totally ignorant of the mechanism of cell transport of bile acids, the regulation of their synthesis and the action of bile acids in bile formation. When we understand the biliary circulation, we can then clarify its diseases. That, in turn, should lead to the development of a new specialty of biliary therapy.


Clinical research by the family phtsician. After the safety and the tolerable dosage range of a new drug have been determined, it must be evaluated for efficacy and safety in patients having the condition for which the new drug is intended. The nature of certain drugs or diseases of of the patient population desired may suggest a family physician as the best director of a clinical trial. There are important obligations for physicians participating in such programs, as well as deep professional satisfactions.


The detection of carriers of classic hemophilia. H. P. Smith Memorial Lecture. The authors summarize their experience with detection of the carrier state in classic hemophilia. Their test depends upon the observation that the plasma of patients with classic hemophilia, deficient in functional antihemophilic factor, contains normal amounts of precipitating antigenic material. By inference, the plasma of carriers should be relatively deficient in functional antihemophilic factor, but should contain normal amounts of antihemophilic factor-like antigenic material. Data obtained from 81 obligate carriers suggest that at least 90% of these women can be identified as carriers in the laboratory by demonstrating that there is an excess of antihemophilic factor-like antigenic material in plasma relative to functional antihemophilic factor. Further, at least two-thirds of mothers of individuals with isolated cases of hemophilia are carriers, suggesting that mutation is a relatively rare cause of hemophilia. Only about one-third of daughters of carriers who had no sons can be identified as carriers, a result due to the systematic exclusion of those daughters who had already had a hemophilic son.


The histiocytic nature of dermatofibrosarcoma protuberans. Tissue culture and electron microscopic study. Specimens from four cases of dermatofibrosarcoma protuberans when explanted in vitro exhibited a typical ameboid outgrowth, confirming the histiocytic nature of these tumors. The cultures displayed the same evolution from macrophages to fibroblast-like cells observed previously in cultures of other types of histiocytomas. Electron microscopic study of the cultures confirmed the light microscopic findings and suggested that the fibroblast-like cells were histiocytes with some secondarily acquired fibroblastic features. The possibility that neoplastic histiocytes may transform into true fibroblasts was deemed unlikely, but could not be excluded.


Histologic identification of malignant lymphoma cutis. Sections of 47 skin biopsies diagnosed during 1960-1970 as suggestive of or diagnostic of malignant lymphoma were retrospectively analyzed. Thirteen with monomorphous cutaneous infiltrates of reticulum cells or poorly differentiated lymphocytes were encountered; all were from patients who had extracutaneous manifestations of reticulum-cell sarcoma, poorly differentiated lymphosarcoma, or leukemia at the time of biopsy or within a year after biopsy. Diagnosis of well-differentiated lymphosarcoma or leukemia cutis is more tenuous, since mature lymphocytic infiltrates were encountered in patients with or without evidence of extracutaneous lymphoma. These are designated "unclassified" lymphocytic infiltrates of skin, requiring careful clinical exclusion of these types of malignant lymphoma. Other purported histopathologic discriminants of malignant lymphoma and pseudolymphoma, the latter term utilized to designate banal disorders characterized by a polymorphous infiltrate with or without atypical reticulum cells, are of little value for their distinction. These diagnostic criteria for malignant lymphoma cutis should clarify much of the pathologic and clinical uncertainty attendant upon the so-called "lymphoreticular" infiltrates of the skin.


Comparison of the efficacies of closed trephine needle biopsy, aspirated paraffin-embedded clot section, and smear preparation in the diagnosis of bone-marrow involvement by lymphoma. Bone marrow aspirates totaling 1,024 and trephine biopsies totaling 386 were obtained from 234 patients with various diagnoses of lymphoma. The study analyzed the morphologic patterns of bone-marrow involvement by each entity and compared the sensitivity of aspiration versus biopsy for detecting lymphomatous involvement of bone marrow. Lymphoma may appear in one of three forms: nodular, diffuse (packed bone marrow), and diffusely infiltrative. Trephine biopsy was superior to aspiration in most instances, especially for the nodular form. In some cases, however, examination of paraffin-embedded clot sections and smears was diagnostic of lymphoma whereas the biopsy section appeared negative.


Unusual morphologic abnormalities of megaloblasts in pernicious anemia and folate deficiency. Three types of morphologic abnormalities of megaloblasts in the bone marrows of eight patients with severe untreated pernicious anemia and two patients with folate deficiency are described. A fourth type of abnormality, probably indicating disturbances in hemoglobin synthesis, was also observed in megaloblasts from patients with these conditons. In addition to the phenomenon of erythrophagocytosis in these disorders, the degenerating megaloblasts and those showing disturbances of hemoglobinization may constitute additional cytologic evidence for intramedullary destruction of erythroid precursors contributing to ineffective erythropoiesis in these disorders.


A simple, highly sensitive colorimetric method for the determination of zinc in serum. A simple, reliable, highly sensitive method for the determination of zinc in biological fluids is described. Interfering trace metals are removed as insoluble iodides or hydroxides prior to complex formation of zinc with dithizone in a Tris-buffered trichloroacetate centrifugate. Absorbance of the chelate is read at 555 nm. The sensitivity of the new method is comparable to that of atomic absorption spectrophotometry, and the results of zinc determinations of 23 sera by the two procedures agree to within acceptable limits of experimental error.


Computer-assisted differential diagnosis of laboratory abnormalities and follow-up testing. Evaluation of the accuracy of a computer program. An evaluation is made of a computer program which generates a differential diagnostic list given a set of input data obtained from an admission chemistry screening profile. The program is tested by supplying input data on patients for whom diseases are known. The laboratory data from 367 patients are examined. Accurate computer diagnosis is obtained in many disease categories. The original computer program is modified to suggest the follow-up tests indicated based on the diagnoses it makes. By using this program and some additional clinical input from the physician, the clinical pathologist can select the most appropriate computer diagnosis and begin the follow-up testing. Accelerated diagnosis and patient care should result.


Bubbles in samples for blood gas determinations. A potential source of error. The presence of small gas bubbles in devices used to collect blood gas samples is considered. A gas bubble whose relative volume is 0.5 to 1% or more that of the liquid in the collection device is a potential source of significant error. Relationships describing the possible magnitude of this error are derived and substantiated.


Vasopressin analog DDAVP in the treatment of diabetes insipidus. A synthetic vasopressin analog, 1-desamino-8D-arginine vasopressin (DDAVP also known as desmopressin), was found to be highly effective in the treatment of seven children and one adult with vasopressin-sensitive diabetes insipidus. The average duration of action of DDAVP was 10 to 11 hours, and with proper adjustment of dose, the subjects were able to control their symptoms satisfactorily with one or two inhalations daily. The youngest child in whom adequate control was achieved was 2 years of age. All subjects found the use of intranasal DDAVP superior to other forms of therapy, and none experienced any known side-effects after six months of treatment. All subjects in this study are currently using 2.5 mug to 10 mug of DDAVP once or twice daily.


Streptococcal pharyngitis. Evaluation of a new diagnostic kit for clinic and office use. One hundred sixty-eight children with upper respiratory infections were screened for beta-hemolytic streptococcal pharyngitis. A recently developed throat culture kit was processed in comparison with the conventional blood agar plate using a duplicate swab technique. Kits and plates were examined independently. Three individuals with no previous bacteriologic experience were allowed to interpret results of the culture kit after receiving instructions for approximately 15 minutes on three consecutive days. The interpretations of two of these individuals approached 95% accuracy, and those of the third individual surpassed this rate. The kit appears to be at least equal to the conventional blood agar plate in supporting the growth of beta-hemolytic streptococci. Moreover, its selective nature allows the nontechnical office staff to interpret results of the cultures promptly and accurately with a minimum of instruction.


Erythromycin therapy for streptococcal pharyngitis. Streptococcal eradication rates of 86% were demonstrated in 97 patients seen on day 14 and in 73 patients seen on both days 14 and 28 after a ten-day course of erythromycin estolate therapy given at a dosage of 20 mg/kg/day, administered in two equal doses. The efficacy of this regimen compares favorably with other results in which this and other erythromycin preparations have been employed at higher doses, usually in the range of 30 to 50 mg/kg/day. Our reported effectiveness at a lower than usual dose of erythromycin is probably explained by the following factors: the known susceptibility of group A streptococci to low concentrations of erythromycin, the uniform absorption of the estolate formulation of erythromycin, and adequate compliance in adhering to the treatment regimen by the majority of our patients. This dosage schedule of erythromycin is simple to administer; and a reduction by half of the total dose usually recommended provides an economical advantage for patients.


Anaphylactic shock following banana ingestion. A 15 1/2-year-old girl experienced anaphylactic shock, asthma, angioedema, and urticaria after eating a banana. Reagin-mediated hypersensitivity was demonstrated by direct skin tests, passive transfer tests, and the radioallergosorbent test.


A controlled study of the effects of single doses of hydrocortisone on the resolution of acute attacks of asthma. To evaluate the effects of corticosteroids on the resolution of acute attacks of asthma, 38 young, acutely ill, asthmatic subjects were given a single intravenous injection of either 0.25, 0.50 or 1.0 g of hydrocortisone hemisuccinate or a placebo (sterile saline solution) in a random, double blind manner. Each was then treated with isoproterenol, at hourly intervals, for a minimum of six hours, and the serial changes in plethysmography, spirometry, lung volumes, subjective complaints and physical findings that occurred as the patients improved were observed. No statistical differences were found in any of the physiologic or clinical variables between those patients given any dose of steroids and their matched controls. From this it has been concluded that hydrocortisone, in the doses and route of administration employed, does not produce any immediate benefits in the treatment of acute asthma.


Recurrence of membranoproliferative glomerulonephritis following kidney transplantation. Serum complement component studies. Sixteen patients with membranoproliferative glomerulonephritis who required kidney transplantation because of renal failure were evaluated for evidence of recurrence of the original disease by serologic and morphologic studies. Of the 12 patients with transplant tissue available for study, seven showed membranoproliferative glomerulonephritis by light morphology. Four of these seven also had hypocomplementemia, and this hypocomplementemia was characterized by decreased serum CH50, C3 beta1A or C3-C9 but norma serum C1, C4 and C2 by hemolytic assay. Immunofluorescent microscopy demonstrated more intense glomerular deposition of C3 and properdin in the hypocomplementemic patients. Ultrastructural studies demonstrated intramembranous deposits typical of dense deposit disease in one patient who also had marked hypocomplementemia. One patient who had two transplant biopsies and persistent hypocomplementemia showed progression from predominantly mesangial glomerular changes to both capillary wall and mesangial abnormalities. This study has shown a high rate of recurrence of membranoproliferative glomerulonephritis in the transplanted kidneys. A high death rate was noted in persistently hypocomplementemic patients. The serum C profile in hypcomplementemic patients who received translants was similar to that seen before transplantation, but the signficance of this finding remains unknown.


Rotor's syndrome. A distinct inheritable pathophysiologic entity. Urinary total, isomer I and isomer III coproporphyrin excretion was determined in 11 patients with Rotor's syndrome, 23 phenotypically normal family members, 16 patients with the Dubin-Johnson syndrome and 20 normal control subjects. Control subjects excreted 24.8 +/- 1.3 per cent (mean SEM) of urinary coproporphyrin as isomer I. Patients with the Dubin-Johnson syndrome excreted 88.9 +/- 1.3 per cent as urinary coproporphyrin I, and patients with Rotor's syndrome excreted 64.8 +/- 2.5 per cent as urinary coproporphyrin I, significantly different from the control subjects and the patients with the Dubin-Johnson syndrome (p less than 0.001). Eight phenotypically normal parents and children of patients with Rotor's syndrome excreted 42.9 +/- 5.4 per cent as urinary coproporphyrin I, intermediate between results in patients with Rotor's syndrome and control subjects (p less than 0.001). Total urinary coproporphyrin excretion was markedly increased in patients with Rotor's syndrome (332 +/- 86 mug/g creatinine) as compared to that in control subjects (p less than 0.001) or obligate heterozygotes (p less than 0.025). With respect to urinary coproporphyrin excretion, Rotor's syndrome and Dubin-Johnson syndrome are both inherited as autosomal recessive traits and are separate pathophysiologic entities. Study of  rare but distinct inheritable disorders, such as these, provide insight into the functional dissociation of hepatic transport mechanisms.


Pathophysiologic studies in human rabies. Six patients with proved rabies were studied with a combination of clinical, physiologic and pathologic technics. Three were given a type of intensive care but died with evidence of respiratory failure. Although circulatory failure did not develop in any of the six patients, three had supraventricular arrhythmias: interstitial myocarditis was found in one of these and rabies virus was isolated from the myocardium of another. Inspiratory muscle spasm was the dominant clinical feature in all cases. This occurred as part of the hydrophobic response and followed stimulation of the upper respiratory tract and skin. Hydrophobia may represent an exaggerated respiratory tract irritant reflex with associated arousal. Later in the course of the disease, various patterns of periodic and ataxic breathing were observed. Widespread brain stem encephalitis was discovered at autopsy, with particular involvement of the neighborhood of the nucleus ambiguous in two of three patients examined. In one patient cerebral metabolism was grossly abnormal, with greatly reduced cerebral oxygen consumption suggesting irreversible brain damage. Respiratory and circulatory disturbances may well be immediate causes of death in patients with rabies, but the present studies reemphasize the severity of the encephalitis which remains the ultimate barrier to survival. In the developing countries in which rabies is still a major problem and in which the cost precludes intensive care, the clinical management of rabies can aim only to reduce suffering by heavy sedation.


Miconazole in coccidiodomycosis. II. Therapeutic and pharmacologic studies in man. Fourteen patients with chronic coccidioidomycosis, many of whom had complicating concurrent diseases and/or had failed to respond to amphotericin therapy, were treated with intravenous miconazole, a synthetic imidazole drug previously shown to be effective in experimental murine coccidioidomycosis. Up to 3.6 g/day was given for up to three months. 7inimal inhibitory concentrations of mycelial and endospore phases of all clinical isolates of C. immitis were less than 2.0 mug/ml. Peak concentrations in the blood of up to 7.5 mug/ml (by assay against C. immitis in vitro) were achieved. Doses above 9 mg/kg or 350 mg/m2 were more efficacious in producing blood levels over 1 mug/ml. Serum protein binding, determined by several methods, was approximately 90 per cent. The disappearance of bioactive drug from blood after infusion has a rapid initial phase (t1/2 approximately 30 minutes) and a final plateau (t1/2 approximately 20 hours). Eight patients had objective evidence of response, three had slight or equivocal responses, two could not be evaluated, and one was a treatment failure. Side effects were generally uncommon, minor and transient except for phlebitis. Infusion into central venous catheters appears to circumvent this problem. Miconazole is a potentially useful drug in the treatment of coccidioidomycosis.


Familial Sjögren's syndrome with associated primary salivary gland lymphoma. Primary salivary gland lymphoma has been rarely documented in patients with or without Sjögren's syndrome. The association of disseminated lymphoreticular neoplasms with Sjögren's syndrome has been recognized, and the malignancy is usually widespread at the time of diagnosis. Familial occurrence of Sjögren's syndrome is likewise infrequently observed. In the present report we describe a patient with Sjögren's syndrome in whom a primary parotid gland lymphoma subsequently developed. In addition to the propositus, two of four siblings had definite evidence of Sjögren's syndrome and a third had several abnormal studies commonly associated with the disease. This observation suggests that genetic influence alone or in conjunction with other factors may facilitate the development of Sjögren's syndrome.


Cushing's syndrome in a patient with an empty sella turcica and a microadenoma of the adenohypophysis. A patient with Cushing's syndrome and an empty sella turcica is presented. A pituitary microadenoma was removed by the transsphenoidal approach. The Cushing's syndrome was alleviated, and the function of the other pituitary trophic hormones has remained normal eight months after surgery. It is emphasized that an empty sella turcica does not rule out a pituitary tumor. The therapeutic implications are discussed.


Unusual manifestation of tuberculosis: TE fistula. Fistulas between the tracheobronchial tree and the esophagus (TE fistula) caused by tuberculosis are rare; usually they are associated with readily apparent pulmonary and/or mediastinal infection, and require surgical management. The patient we describe presented with a TE fistula as the only manifestation of active tuberculosis. This case represents the first report of successful nonsurgical treatment of tuberculous TE fistulas.