Tranexamic acid in the preoperative management of ruptured intracranial aneurysms. A randomized, controlled clinical trial was carried out to study the effect of tranexamic acid (AMCA, trans-AMCHA) in prevention of early rebleeding after proven rupture of an intracranial aneurysm. The series comprises 46 patients admitted to the hospital within three days after the first bleeding. Twenty-three were treated with tranexamic acid and 23 were controls. Nine patients in the control group and one in the group treated with tranexamic acid had confirmed rebleeding. The incidence of vasospasm, cerebral ischemia and hydrocephalus as well as mortality and morbidity is discussed.


Humorally mediated alterations in cardiac performance as a consequence of positive end-expiratory pressure. Two experimental designs were used to study the mechanism of the decreased cardiac output associated with the use of positive end-expiratory pressure (PEEP). In the first study of nine dogs the application of 15 cm H2O PEEP led to a decrease in cardiac output (CO) from 2.68 +/- 1.05 to 2.01 +/- 1.26 liters/min (+/- SD) (p less than 0.05) concomitant with an increase in transmural central venous pressure of 5.2 +/- 0.9 to 8.4 +/- 2.7 mm Hg (p less than 0.05) and a slight increase in transmural left atrial pressure of 6.8 +/- 3.3 to 7.3 +/- 3.6 mm Hg (p less than 0.1). These data are consistent with altered ventricular performance. In a second study nine pairs of dogs were cross-circulated. Application of 15 cm H2O PEEP to one member of the experimental pair led to a decrease in the CO of the other member from 2.71 +/- 0.98 to 2.21 +/- 0.81 liters/min (p less than 0.001). This decrease returned toward baseline with the removal of PEEP (p less than 0.02). Results indicate that one mechanism whereby PEEP reduces the cardiac output is through the action of a humoral agent.


Protective effect of propranolol in the treatment of ischemically damaged canine kidneys prior to transplantation. Warm ischemia is a potential problem during the harvesting of cadaveric kidneys for transplantation purposes. This ischemia can cause impaired renal function following transplantation. The purpose of our study was to determine whether the beta-adrenergic blocking agent propranolol was effective in improving renal function after ischemia. Dog kidneys were subjected to 30 minutes of warm ischemia followed by hypothermic pulsatile preservation for 24 hours. The kidneys then were autotransplanted with immediate contralateral nephrectomy. In this model only 50% of the untreated control group survived. Three different protocols using propranolol were tested. Administration of propranolol to dogs before the ischemic period, or installation of propranolol into the renal artery at the start of the ischemia, or addition of propranolol to the preservation perfusate lessened the severity of acute tubular necrosis and resulted in 100% long-term survival. Although the mechanism was not investigated, it has been suggested that propranolol is acting through its blockade of beta-mediated renin release and/or through its so-called membrane-stabilizing effect.


A modified fundoplication which preserves the ability to belch. This report describes a transabdominal antireflux procedure which combines some of the features of the operations described by Nisse, Belsey, and Hill. From 1972 through 1976, 61 patients underwent a conventional Nissen fundoplication and 54 patients were operated according to the method described in this report. None of the patients who had a Nissen operation was able to belch freely; 15% had a "gas-bloat syndrome". Return of the ability to belch often signified partial or complete brakdown of the plication, which occurred in 11% of the cases. By contrast, all but one of the patients who had modified plication were able to belch freely; there has been only one instance of recurrent reflux.


Portal hypertension following renal transplantation. Portal hypertension and variceal hemorrhage may be found in the renal transplant patient with chronic liver disease. The development of portal hypertension was found to occur after long-term graft survival without significant rejection. The development of positive cytomegalic virus and negative hepatitis-associated antigen appeared to be common. Splenomegaly and prominent venous collateral were the most frequent physical findings, while ascites and hepatomegaly were less frequent. Portasystemic decompression can be performed successfully, however, the mortality and morbidity appear to be higher for this group than for other cirrhotic patients with comparable hepatic reserve.


The use of arterial--central venous oxygen differences to calculate cardiac output and oxygen consumption in critically ill surgical patients. Simultaneous determinations of cardiac output (using the cardiogreen indicator dilution technique) and arterial--central venous oxygen differences [C(a-cv)O2] were obtained in 200 critically ill surgical patients. The average initial values +/- SD included arterial--central venous oxygen differences of 3.6 +/- 1.6 vol%, cardiac index of 3.4 "/- 1.2 liter/min/sq m, and oxygen consumption of 100 ml/min/sqm. As might be expected, low arterial--central venous oxygen differences, especially if less than 2.0 vol%, were associated with high cardiac indices, but the oxygen consumptions were much lower than normal and the mortality rates were increased. The cardiac indices calculated from the C(a-cv)O2 averaged 4.1 liter/min/sq m and correlated rather well with the measured cardiac indices, particularly if the patients with a C(a-cv)O2 of less than 2.0 vol% were excluded. Arterial pH values did not correlate well with the calculated oxygen consumption. Arterial oxygen contents of more than 16.2 vol% equivalent to a hemoglobin of 12.5 gm/dl or higher with an oxygen saturation of 95%, provided better arteriovenous oxygen differences, oxygen consumptions, and survival rates than those found with lower hemoglobin values. Arterial--central venous oxygen differences and calculated oxygen consumptions can be practical clinical and prognostic value.


Prognostic factors of peritoneal infections in transplant patients. Twenty-eight cases of peritoneal infections occurring in 686 transplant patients (4%) are reported. The mortality was 78.5% (22 of 28 patients) and accounted for 13.2% of all transplant deaths. Recipients of cadaver kidneys were more prone to develop intraperitoneal infection, whereas the age, the presence of diabetes, and the tissue typing had no influence on the likelihood to develop intraperitoneal infections. Sixteen patients developed intraperitoneal infection secondary to the transplantation or another operation, whereas the intraperitoneal infection was due to a disease process unrelated to previous surgery in 12 patients. Only 64% of the patients presented with abdominal symptoms, 24 presented with septic shock, and 11 with a wound infection without peritoneal signs. The uncharacteristic clinical findings resulted in a delay of 8.7 days between the onset of symptoms and the recognition of the peritoneal infection and made a preoperative diagnosis possible in only 22 patients. It became clear that patients with generalized peritonitis, concomitant distant infections, opportunistics organisms in the peritoneal cavity, and the infections caused by postoperative complications have a poorer prognosis than the remainder of the group. Early recognition of the problem, especially after operation, and vigorous treatment seem to be the keys for improved results in the treatment of this serious condition.


[Effect of SL 25 on radiogenic xerostomia in the radiotherapy of tumors in the region of neck and face (author's transl)]. The radiogenic xerostomia often poses problems to the radiotherapeutist because this symptom can become so severe that treatment has to be interrupted or in some cases even stopped. The therapeutic success can become uncertain because of such deviations from the irradiation scheme. Because of promising observations reported in literature, we have examined the stimulating effect on the salivation produced by the test preparation SL 25 from Kali-Chemie Pharma GmbH in Hannover. A double blindfold test was made. Only three out of fourteen patients (22%) in the active substance group declared to feel a relief of the xerostomia, whereas in the control group five out of twenty patients (25%) felt this relief.


Immunosuppressive activity of carrageenan for cell-mediated responses in the mouse. Unfractionated carrageenan was highly toxic to CBA mice. By using moderately nontoxic regimens, the immunosuppressive properties of carrageenan were examined in several assays. The growth of tumour allografts was only modestly enhanced at low dosages, but dramatic enhance ment of tumour growth and feeble prolongation of skip allograft survival occurred only at a very high dose. Mixed lymphocyte culture reactivity was significantly diminished at both high and low doses. Phytohaemagglutinin responsiveness was suppressed in the spleen but not in the mesenteric lymph node cells. Changes in the ability of normal syngeneic lymphoid cells to "home" to the lymphoid organs of treated mice were confined to the period immediately after carrageenan administration, an observation that was not temporally related to the suppressive action of carrageenan. It is concluded that, compared with its effect on antibody formation, carrageenan is a very poor inhibitor of cell-mediated responses. Possible reasons for this are discussed.


Absence of reaction of a xenogenic anti-H-2 serum with mouse embryonal carcinoma cells. A rabbit antiserum raised against papain-solubilized H-2 antigens has been used to investigate the eventual expression of H-2 antigens and related molecules on embryonal carcinoma cells and on other types of mouse cells. No material reacting with this serum could be detected on cells carrying the F9 antigen. It is concluded that no H-2 antigen or cross-reacting material is expressed on these cell types.


Kidney transplantation across positive B and T cell crossmatches. Cadaveric renal transplants were performed despite a positive conventional crossmatch (usually intermediate positive) resulting from donor-specific B cell lymphocytotoxins (both IgG and IgM) or IgM cold-reactive T cell lymphocytotoxins. Graft survival at 2 months was 72% in the 14 patients with B cell-specific antibodies and 71% in the 7 recipients with T cell antibodies. No correlation was observed between graft rejection and warm (mainly IgG) or cold (IgM) B cell-specific antibodies. These results indicate that not all positive crossmatches are a contraindication to transplantation. Attempts should be made to study the nature of the lymphocytotoxins before withholding the allograft from the recipient.


ABO-incompatible bone marrow transplantation: preparation by plasma exchange and in vivo antibody absorption. The threat of fatal hemolytic transfusion reaction has been a major deterrent to the use of ABO-incompatible bone marrow donors. An eighteen year old type O male with acute leukemia was prepared to receive type A HLA identical marrow using large volume plasma exchange prior to and following cyclophosphamide administration. Saline agglutinating anti-A antibody was initially present at a titer of 1:128. The initial antiglobulin titer of dithiothreitol (DTT) treated serum was 1:64. Initially the T 1/2 of 51Cr labeled type A red blood cells was less than five minutes. The first plasma exchange removed large quantities of anti-A antibody but 51Cr survival of type A red blood cells was unchanged. A second plasma exchange after an interval of three days, increased the T 1/2 of 51Cr labeled cells to 20 minutes. Saline agglutinating anti-A was not present at a titer of 1:8 and the antiglobulin titer of DTT treated serum was 1:4. Reaction to subsequent transfusion of type A red blood cells (5 units) was limited to a single febrile episode during the first unit. Survival of 51Cr labeled red blood cells increased to T 1/2 equal to 21 hours. These data indicate that plasma exchange and infusion of ABO incompatible red blood cells effectively reduce antibody concentration and prolong survival of ABO incompatible erythrocytes. It is suggested that the prolongation of 51Cr survival of ABO-incompatible red blood cells to a point that extravascular destruction is predominant be used to establish the safety of ABO-incompatible marrow infusion.


Prolonged survival of alymphatic skin allografts in the rat. A humoral component. Immunological mechanisms of increased graft survival in "immunologically privileged" sites were defined by comparing host responses against orthotopic and alymphatic skin allografts in rats. The conventional skin grafts reject by day 8; grafts placed on alymphatic skin pedicles heal in normally, but begin by day 16 to 18 to contract inexorably until only a scar remains by day 35 to 40. Lymphocyte-mediated cytotoxicity rose significantly in spleen and draining lymph nodes 8 to 10 days after orthotopic grafting, but was absent as long as 35 days after skin transplantation to alymphatic pedicles. No significant activity in antibody-dependent lymphocyte-mediated cytotoxicity was noted in either recipient group, while complement-dependent cytotoxicity was slightly elevated 8 to 10 days postoperatively in both groups. Passive transfer of serum from recipients of alymphatic skin grafts, taken 8 and 12 days after grafting, prolonged survival of test cardiac allografts significantly, although neither control serum from recipients of orthotopic skin allografts, or serum taken 28 days after alymphatic skin grafting increased test heart survival. We conclude that prolonged survival of skin grafts on alymphatic sites may be based, at least partially, on the development of host humoral factors.


Clinical significance of the 1-hour biopsy in renal transplantation. Biopsy specimens were obtained from 43 transplanted kidneys at the time of excision from the donor but prior to revascularization, and 1 hr after revascularization. Two independent laboratories evaluated specimens by immunofluorescent techniques for the presence of IgM, IgA, IgG, C'3, and fibrin. Results from the two laboratories examined for reproducibility and immunological specificity, and correlated with clinical course. Results show that immunoglobulin deposition seen in the 1-hr renal biopsy specimens is of little significance, because: (1) immunoglobulin deposition was difficult to quantitate reliably, (2) the presence of immunoglobulins did not correlate with clinical course, and (3) the majority of immunoglobulin deposition detected was not immunologically specific, since it was most often either present prior to vascularization or disappeared with vascularization.


A study of three protocols of blood transfusion before renal transplantaion in the dog. Three protocols of blood transfusion were evaluated in a canine model for (1) the strength and breadth of leukocytotoxin induction, (2) the induction of cell-mediated immunity against the blood donors, (3) haemagglutinin production, and (4) any effect on kidney graft survival. At the end of the transfusion schedule, each dog received a kindey graft and was given azathioprine and prednisolone postoperatively. All dogs were unrelated and blood donors were not used as kidney donors. All three transfusion protocols, comprising i.v. injections of blood twice weekly or every 2 weeks from one or three donors, induced unacceptably strong and broad leukocytotoxins. All transplants performed across a positive crossmatch failed to function. However, where a negative crossmatch was available, the trend of results was that the transfused dogs had better graft survival than nontransfused animals similarly treated with azathioprine and prednisolone. Only one dog produced haemagglutinins. Several animals had positive cell-mediated immunity against the blood donors, but the response was not strong and was frequently not sustained.


[Genetic nature of neoplastic transformation]. The necessity is substantiated to discriminate between the two notions: the oncogenic potency of cell genome and the conditions which either favour or prevent its realization. Both epigenetic alterations and mutations may cause neoplastic transformation of the cell but the expression of the tumor phenotype, composed of normal structural and functional elements, occurs exclusively at the epigenetic level. An impaired selectivity of nucleus-to-cytoplasm transport of mRNAs presumably is involved in this process.


[Method of preparing suspended cells for scanning electron microscopy]. To preserve the lifetime morphology of the surface of suspended cells, these must be fixed in suspensions. The subsequent stages of cell preparation for scanning electron microscopy (dehydratation, critical point drying, coating) are considerably facilitated if fixed cells are preliminary attached to some substrate surface. An effective substrate should provide a firm rather than selective attachment of the overwhelming majority of fixed cells; the substrate should be also available for a wide application. The trial of different types of substrates showed a sufficient effectivity of plates made of commercial aluminium foil. In tests with murine embryonal and transformed fibroblasts as well as with human blood leukocytes, in average 90 per cent of cells fixed with glutaraldehyde in suspensions got attached to foil substrate surfaces; the fixed cells both settled from suspension and attached were seen distributed evenly on the substrate surface. The use of aluminium foil substrates made it possible to study the surface topography of some types of suspended cells.


[Additional limitations of the Shrikhande method and their verification]. Shrikhande's method was checked on linear-variety common wheat Lutescens 62. Two causes for a distortion of the ratio of genotypic and paratypic components of the variance were established: parameter b of Smith's law is not constant for a given field and depends on the method of parcelling: Smith's law is not confirmed at all. A two-stage test of Shrikhande's method correctness is suggested for checking its limitations in practice. The analysis of variance for any given parcelling is done at the first stage. Significant ratios of between-cluster mean squares and within-cluster mean squares indicate that Smith's law is confirmed. The second stage consists in the analysis of variance of lg V(X) linear regression by lg X or in the graphical analysis of the function lg V(X) = = f (lg X).


[Variability in chromosomes number during plant ontogenesis]. The experiments on chromosome variability of cells in the ontogenesis of higher plants are reviewed. The polyploidization of somatic cells during the ontogenesis is shown to be the natural phenomenon for most plant tissues and it is correlated with the intensification of cellular metabolism. The functional and chromosome variability of somatic cells is supposed to depend mostly on the hormonal regulation. The possible role of the phytochrome system in this process is discussed.


[Cytochemistry and ultrastructure of frog pancreatic exo- and endocrine epithelium under normal conditions]. The pancreatic epithelium of intact frog has been studied using morphometry, cytochemistry and electron microscopy. A low level of DNA synthesis was shown to be characteristic of pancreatic epithelium of frogs caught in winter. The B/A cell volume ratio is 3.68 +/- 0.16 and 2.55 +/- 0.36 in small and median pancreatic islets, resp. A-, B-, D-cells are found in pancreatic islets, and intermediate acinar A and acinar B cells in intact frog pancreas.


A controlled trial of anterior spinal fusion and débridement in the surgical management of tuberculosis of the spine in patients on standard chemotherapy: a study in two centres in South Africa. Seventh Report of the Medical Research Council Working Party on tuberculosis of the spine. In 2 centres in South Africa 159 patients with a diagnosis of tuberculosis of the thoracic and/or lumbar spine were allocated at random to operation by radical resection of the spinal lesion and insertion of autologous bone grafts (Rad. series) or by débridement of the spinal focus (Deb. series). All the patients were treated with isoniazid plus PAS daily for 18 months and daily streptomycin for the first 3 months. They have been followed up to 36 months. The main analysis of this report concerns 55 Rad. and 52 Deb. patients. The clinical and radiographic condition of the 2 series on admission was similar. Central nervous system involvement was common; 27% of the patients were paraplegic and 12% paraparetic. The mean period of initial stay in hospital was 179 days for the Rad. and 133 days for the Deb. patients and of strict recumbency 97 and 37 days, respectively. Seven per cent of the Rad. and 12% of the Deb. patients had a sinus and/or clinically evident abscess initially, all of which resolved by 18 months. Of 23 Rad. and 8 Deb. patients with a radiographyically evident mediastinal abscess initially, but never a sinus or clinically evident abscess, the shadow had disappeared by 12 months in 91% and 88%, respectively. It was still present in only 1 patient (Rad.) at 36 months. Radiographically complete bony fusion of the affected vertebral bodies had occurred in 11% of 46 Rad. and 13% of 45 Deb. patients by 6 months, in 39% and 22% by 12 months, in 59% and 33% by 18 months (P = 0.05) and 74% and 69% by 36 months. The mean vertebral loss on admission was 1.0 vertebra in the Rad. and 1.1 in the Deb. series. At 36 months there was a mean loss of a further 0.2 of a vertebra in each series. The mean angulation of the spine at the start of treatment was 33 degrees for the Rad. and 35 degrees for the Deb. series and the mean increase at 3 years was 15 degrees and 8 degrees (P = 0.06), respectively. At 18 months, 64% of the Rad. and 69% of the Deb. patients had a favourable response to treatment and at 3 years 81% and 88%, respectively, non-significant differences. Patients with central nervous system (CNS) involvement on admission stayed in hospital initially for an average of 204 days compared with 129 days for those with no CNS involvement, the period of strict recumbency being 84 days compared with 60 days. The prognosis was also less favourable, 14% compared with 2%, respectively, died (P = 0.03) and 32% compared with 3%, respectively, had an unfavourable response at 36 months (P = 0.0003). At 6 months the paralysis had resolved in 6 (21%) of the 29 paraplegic patients compared with 7 (54%) of the 13 paraparetic patients (P = 0.07). The corresponding proportions at 21 months were 72% and 69%. At 18 months, 28% of the paraplegics responded favourably compared with 62% of the paraparetics (P = 0.08) but at 36 months the proportions were similar, namely 65% and 67%. Specimens from spinal lesions were obtained at operation in 149 patients...


Ultrasonic modification of experimental bruising in the guinea-pig pinna. Both pinnae of anaesthetized male guinea-pigs were contused in a reproducible manner and one immediately treated with 0.75 MHz ultrasound at an average therapeutic intensity of 0.61 W cm-2 for a period of 2 min. The lividity and rate of resorption of the rusultant bruises were measured by a photometric method. The results fell into two distinct classes. In the majority of cases, the bruises formed on the insonated pinnae were significantly less intense and were resorbed at the same rate as their corresponding controls. In the remaining cases, ultrasonic irradiation resulted in an increased initial lividity and a significantly greater rate of resorption.


Mortality and morbidity in pretransplant bilateral nephrectomy: analysis of 305 cases. The surgical riks were analyzed in 305 patients with end stage renal failure who underwent bilateral nephrectomy through midabdominal approach in preparation for kidney transplantation. The over-all mortality rate was 3.6 per cent. Age was the most significant risk factor in the mortality. Patients less than fifty years of age had an operative mortality rate of 3.1 per cent while those more than fifty years had an operative mortality of 11.1 per cent. Other pertinent risk factors were preoperative complications of renal failure and additional surgical procedures at the time of bilateral nephrectomy. The leading causes of death were those of cardiovascular complications and infection. The morbidity rate was 58.7 per cent being major in 18 per cent and minor in 40.7 per cent. Bilateral nephrectomy is recommended selectively in patients with (1) chronic pyelonephritis with urinary tract infection, (2) major vesicoureteral reflux, (3) immunologically active glomerulonephritis, (4) severe hypertension uncontrollable by adequate dialysis, and (5) extremely large or infected polycystic kidneys.


Kidney stones and renal transplantation. Only 10 cases of renal calculi in transplanted kidneys are reported in the literature. Etiology is not uniform in all the cases. Some of these cases were managed conservatively. We herein report a case in which the etiology of the stone may be urinary tract infection. This patient was managed conservatively.


Staghorn calculus due to migration of foreign body: unusual complication of ileal conduit. An unusual late complication of ileal conduit diversion is described. To our knowledge this is the first case reported in which a foreign body apparently migrated from an ileal conduit to the renal pelvis and served as a nidus for stone formation.


Visceral larva migrans and alveolar hydatid disease. Dangers real or imagined. For both visceral larva migrans and alveolar hydatid diseases, it is the feces of companion animals that are the primary source of human infection. Clearly, whatever is done to reduce this form of environmental contamination and the prevalence of the parasites' infective stages will help to protect the health of the human population in the United States and Canada, particularly the children. Very important are appropriate anthelmintic treatment programs, especially for T. canis, and proper control of close associations between pets and people. Probably the known incidence of visceral larva migrans in humans and the range of its known pathogenicity will increase as better diagnostic methods become available. In addition, other animal helminths, for instance Toxocara cati and Toxascaris leonina, may become more substantially documented as causes of human visceral larva migrans. Until more is known of the geographical distribution and prevalence of Echinococcus multilocularis among animals in North America, it will be difficult to assess accurately the future significance of alveolar hydatid disease in the continent's human population. Another important advance would be the development of anthelmintics that are effective for somatic second stage larvae of T. canis, and others effective for adult or larval Echinococcus species. Meanwhile it is a most important responsibility of the veterinary profession to educate its clients thoroughly concerning these dangerous helminths.


Leprosy in a chimpanzee. Morphology of the skin lesions and characterization of the organism. Microscopic features of lepromatoid lesions in a chimpanzee inoculated with bovine leukemia virus consisted of diffuse dermal infiltrations of foamy histiocytes, except for a subepidermal "clear zone" devoid of infiltrating cells. Acid-fast organisms were in histiocytes, dermal nerves and a branch of the left radial nerve. The organisms were more intensely acid-fast with the Fite-Faraco than with the Ziehl-Neelsen stain. The organisms did not oxidize 3,4-dihydroxyphenylalanine (dopa) to indole but their acid-fast staining quality was removed by pretreatment with pyridine. Human leprosy patients, inoculated simultaneously with chimpanzee and human lepromin, reacted similarly to both lepromins. Organisms, when inoculated into mouse footpads, multipllied in 6 months to a quantity that was compatible with their identification as Mycobacterium leprae.


Scanning electron microscopy of the small intestine of a normal unsuckled calf and a calf with enteric colibacillosis. Sections of the small intestine were taken under general anaesthesia from a normal calf and from a calf with enteric colibacillosis and examined by scanning electron and light microscopy. In the normal calf villi were long and oval throughout the intestine and in the challenged calf there was villous stunting and fusion in the distal small intestine.


The effect of Gn-RH on the pregnancy rate of artificially inseminated cows. One hundred and nine pure bred Holstein Friesians were injected intramuscularly with 0.125 mg of a synthetic Gn-RH analogue at the time of the first service to study the effect of Gn-RH on the fertility of inseminated cows. Sixty-four cows or 58.7 per cent were diagnosed as pregnant after one insemination compared to 54 animals or 49.5 per cent in the untreated control group. Total pregnancy rate of 81.65 per cent was 8.3 per cent higher than in the controls, while the services per conception rate improved from 1.49 to 1.39. Gn-RH administration at the time of oestrus could improve herd fertility through its including effect on follicular rupture and regulatory influence on ovarian function.


[Distribution and characteristics of the R factors in E. coli isolated from poultry]. It has been demonstrated that Escherichia coli organisms isolated from birds in the district of Haskovo are up to 65 per cent resistant to drugs. It has been experimentally shown that the genetic determinants of resistance to chemotherapeutics are transferred via conjugation. The possibility of transferring R-factors from Escherichia coli to Salmonella typhimurium points to one of the routes for the occurrence of drug resistance in Salmonella bacteria.


[Effect of low temperatures on the count and virulence of salmonellae in slaughtered poultry]. Studied was the effect of shock freezing at -34 degrees C and the storing of slaughtered birds at -18 degrees C up to six months on the survival and the change in the virulence of Salmonella typhimurium, S. meleagridis, and S. gallinarum-pullorum. It was established that the number of the tested Salmonella species decreased steadily, however, no complete devitalizing was attained. The Salmonella count was most intensely reduced in the first fifteen days of storing. Most resistant to the effect of low temperature were S. typhimurium organisms, and least resistant was S. meleagridis. It was found that the virulence of the tested Salmonella strains gradually dropped, the amount of disappearing organisms correlating with the drop of their virulence.


[Milk protein digestion in the stomach at an early age]. In the mucosa and gastric contents of young rats proteolytic activity was investigated. The pepsinogen content in the mucosa and proteolytic activity of the gastric contents does not change over a period from the 1st till the 11th day and then abruptly increase. A change-over from milk to mixed nourishment in the period from 12 to 20 days of life is attended by a growing pepsinogen content and a drastically reduced prorennin content in the gastric mucosa. The change-over from mixed to a definitely fixed nutrition after 20 days of life is accompanied by an intensive discharge into the gastric content of HCl and pepsin.


Neurological syndromes produced by some toxic metals encountered industrially or environmentally. Toxic metals encountered industrially or environmentally may produce the following syndromes: 1) Peripheral neuropathy: which is mainly sensory in arsenic and entirely motor with inorganic lead, organophosphorus compounds and tallium produce a mixed form of peripheral neuropathy. 2) Encephalopathy: usually with lead poisoning where ataxia and hemiplegia or optic atrophy may occur. 3) Optic neuritis: transient or permanent impairment of vision in arsenic poisoning and blurring of vision followed by field fedects with thallium poisoning. 4) Cerebellar disturbances: in the form of ataxia in organic mercury. 5) Parkinsonism: extrapyramidal signs occurs in manganese poisoning shown as mask face and rigidity of muscles. 6) Mental changes: as acute psychosis in organic lead and erethism in organic mercury.


[Treatment of acute kidney failure].

[Treatment of acute kidney failure]. By the rapid development of the chronic haemodialysis and the transplantation of kidneys the treatment of the acute renal failure is not so often dealt with in literature, though the haemodialysis since its clinical use in 1944 for 15 years exclusively has been used for the treatment of acute renal failure. Alarming reports on the increase of the mortality up to 80% were the cause to deal with treatment and developmental tendencies in form of a survey. The conclusions were that during the last 6 years in the GDR annually about 300 cases of acute renal failure are constantly treated. The total mortality rate is without any essential variations on an average about 44.9%. In comparison to international statistics these figures are remarkably good. According to the  basic etiological cause of the acute renal failure the mortality rate varies between 60% in surgical diseases and about 30% in intoxications with uraemia. Apart from these analyses the author enters indication, causes and prognosis in form of a summary.


[Possibilities and limits of kidney transplantation]. Chronic haemodialysis and renal transplantation are mutually supplementing methods for the treatment of patients with terminal renal lesion. The two methods have proved their worth in clinical practice. The expectance of life of patients with chronic renal insufficiency could essentially be improved during the last years. In last consequence the successes of the transplantation of kidneys depend on the solution of immunobiological problems, which are not yet cleared up nowadays. 1. In the determination of genotypical determinants possibly not all are known or recognizable. 2. The at present clinically usable examination methods do not yet allow to recognize rejections so early that by an aimed immunosuppressive treatment irreversible damages on the graft may be prevented. After a transplantation of kidneys of relatives a long survival time of transplanted patients is better than after a transplantation of kidneys taken from dead bodies. The rejection is still the main factor of the failure of the graft, the sepsis is the most frequent cause of death. It is neccessary, to develop less toxical remedies for the adaptation of the graft. Nevertheless, thousands of optimally transplanted patients prove the usefulness of the allogenic transplantation of the kidney.


Sudden cardiac death.

Sudden cardiac death. Over the past decade, there has been a significant decrease in the hospital mortality of patients with coronary artery disease. However, sudden cardiac death, which accounts for the majority of deaths from coronary artery disease, hasbeen little affected. This report reviews the pathology, electrophysiology, demographics and clinical presentation of sudden cardiac death. Emergency care and possible preventative measures are examined.


[Current problems in the pathophysiology of the adrenal glands and its clinical importance]. In recent years new knowledge on the pathophysiolgy of the parathyroid gland has led to a series of not unimportant consequences for the endocrinological clinic. To this belongs the glandular translocation which under certain circumstances is regarded as favourable and the principal practicability so which is without any question. In certain, above all urologically conditioned clinical pictures with consecutive stimulation of the parathyroid secretion an inhibition effect on the parathyroid glands which can be evoked by drugs is discussed. Here the problem is a possibly significant preventive measure. The question of the maintained or disturbed euparathyroidism must be interesting in such cases, in which alone from the result of the conventional calcium-metabolic diagnostics an obligatory evidence remains questionable. Difficulties are above all in such cases, where the transitions of a functional adaption mechanism to an autonomized process with own laws may be present or it must be feared that the overloaded glandular function comes to an end. On the basis of own findings the authors adopt a definite attitude to these problems.


["Functional relaxation" as a method in anthropologic medicine]. "Funktionelle Entspannung" (F.E.)--functional relaxation--according to M. Fuchs resumes Weizsäcker's "Gestaltkreis". Its medium is the body (comprising body, soul and mind) and its "rhythm", which penetrates and supports the individual human sphere. Somebody who is in agreement with his own body is also in agreement with the world around him; somebody who sets up tensions between the world and himself loses his personal rhythm. This becomes obvious in the "body-language" in the form of false tensions. In the F. E. these are not approached in a verbal way or by way of set exercises, but in each case individually--beginning at the spine and the joints and then continuing with the inner cavities and spaces. Approach and method of the F. E. are exemplified (e. g. hypertonie, asthma bronchiale, where other psychotherapeutic methods--psychoanalysis, autogenes training etc.--did not help).


[Local Sanarelli-Shwartzmann-phenomen after hemipelvectomy (author's transl)]. We report a case of haemorrhagic necrosis after hemipelvectomy, which shows nearly all characteritic criterions of local Sanarelli-Shwartzman-phenomenon.


[Exceptional suicide of a physician (author's transl)]. A 57 years old psychiatrist committed suicide through insufflation of powder from a chemical fire extinguisher his respiratory and gastrointestinal tract. Death was due not to mechanically induced asphyxia but to asystolia. The latter disturbance is explained as a vagal reaction to trauma because of the characteristic position of the corpse at the scene and because the victim did not exhibit any signs of gas or foreign body embolism. A further point of interest in the context of trauma mechanism, is the absence of significant disruptions in spite of the high pressure (10-12 atu) developed by the extinguisher. No conclusive interpretation can be given about the psychological mechanisms behind this suicidal act. On the other side the modality of the procedure used by the victim became manifest already a few months before the critical act.


[Exhumation for suspected poisoning--reticulum cell sarcoma (author's transl)]. A 57-year-old woman showed somnolence, extreme stiffness of the neck and atypical CSF findings which led to her death within a few days. During legacy controversy the possibility of poisoning was considered. The post mortem, pathological and toxological examinations of the exhumed corpse permitted the diagnosis of reticulum cell sarcoma 16 months after death. Such a diagnosis 16 months after death has, to our knowledge, not previously been reported.


[New knowledge in the treatment of post-traumatic strictures in the posterior urethra]. At present on principle 3 methods are taken into consideration for the treatment of the posttraumatic strictures of the urethra: 1. the skin filling methods, 2. the methods used by us personally, based on bursting the stricture and using the abundantly mobilised distally flapped distal stump of the urethra and 3. the urethrotomy under vision with sharp cut. Whether one method may claim exclusiveness, we shall know probably already in the next years.


Antibiotic NRC-501, a new antibiotic produced by Streptomyces species. A new antibiotic, NRC-501, was isolated and purified from the fermentation broth of Streptomyces species NRC-501. Physical, chemical, and biological characteristics of the antibiotic NRC-501 were revealed.


A simple method for preparing specimens of Claviceps purpurea for scanning electron microscopy. The method is a modification of freeze-drying and includes also a simultaneous coating during rotation. It utilizes a common vacuum coating apparatus with a modified miniature electric motor. The cells of C. purpurea in the resulting specimen retain their original shape.


[Bone transplantation in the treatment of haematogenous and posttraumatic osteomyelitis (author's transl)]. The author presents 602 patients--436 with haematogenous osteomyelitis and 166 with posttraumatic suppurative osteitis. The clinical material is analysed according to the following criteria: age, localization, morphology, kind of infection, operative methods. The author recommends bone replacement ot the donor area with allogenous cancellous bone. No complications were observed in 285 operations of this kind. The osteoplastic treatment of haematogenous osteomyelitis provides healing 86% and of posttraumatic suppurative osteitis--in 79% of the cases. Thanks to reoperations, this percentage increases to 97% for the haematogenous osteomyelitis and to 98% for posttraumatic purulent osteitis respectively.


[Soft tissue plastics in treatment of chronic osteomyelitis (author's transl)]. Soft tissue plastics are indispensable in the surgical treatment oft chronic osteomyelitis (56 cases in 10 years). Myoplastics (27 operations) are simple, successful, but only suitable with stabile bones. The treatment of osteomyelitis in the distal parts of the extremities often requires additional skin flaps (25 operations), rarely free skin grafts.


[Lymphocyte transformation test with streptococcal antigens in newborn infants and their mothers]. Following streptococcal mitogens and antigens were tested in the lymphocyte transformation test with human cord blood and maternal blood: streptococcal M1- and M19-proteins, mucopeptide, erythrogenic toxins and additional phytohemagglutinin. There are no significant differences in the blastogenic response with the different mitogens and antigens in maternal and cord blood. The cord blood lymphocytes show the same degree of blastogenic reaction to the mitogens and antigens as the maternal lymphocytes, that may reflect the state of readiness for cellular immunological defence. The spontaneous incorporation of 3H-labelled thymidine into cord blood lymphoblasts is significant higher than in lymphoblasts of maternal blood.--The results of specific and unspecific stimulation by means of steptococcal antigens are discussed.


[Clinical studies on the effect of pregnancy and labor on the pharmacokinetics of ampicillin]. After giving 5 g Ampicillin intravenously to a total of 33 women (gravidae during the VIII. month pregnancy, women in labor and health controll persons) the serum levels of the mothers were analysed according to the pharmacokinetic parameter half-life of elimination.--Our results show that only the delivery cause significant differences of the kinetic of ampicillin.--Our results are discussed with the data given by literature.


Insulin secretion reactivation of pancreatic islets from starved rats in vitro. Starvation of Wistar rats induced a shift of glucose threshold for insulin secretion of isolated islets above 5 mM, which can be restored by pretreatment of the tissue with glucose, mannose, glyceraldehyde, an theophylline, but not with acetylcholine or lactate. The improved insulin secretion is not connected with an enhanced glucose utilization.


A simple method for cloning and replica plating of mammalian cells using multicellular spheroids. V 79/4 Chinese hamster cells or HeLa cells grow in Eagle's MEM supplemented with 25 microgram/ml dextran sulphate to form clonal multicellular spheroids. These cell clones, consisting of 5-10(2) cells, are easy to separate, to transfer from one culture vessel into another and grow as normal monolayer colonies on Dederon cloth circles after subculture in Eagle's MEM without dextran sulphate. A simple replica technique is described by which 500 clones can be transfered onto at least 3 replica cloth circles, 10 cm in diameter, with a replica plating efficiency of approximately 100%.


Antihypertensive therapy in patients above age 60. Third interim report of the European Working Party on High blood pressure in Elderly (EWPHE). Three hundred forty nine hypertensive patients above the age of 60 have entered the double-blind multicentre trial of the European Working Party on High blood pressure in the Elderly (EWPHE). After stratification and randomisation half were treated with one or two capsules containing 25 mg hydrochlorothiazide and 50 mg triamterene and if blood pressure control was insufficient methyldopa was added up to 2 g daily; the other half received matching placebo. No significant differences between the groups were present prior to randomisation. A significant blood pressure difference of 25/10 mm Hg was obtained between the groups and maintained during two years of follow-up. No major disturbances in serum potassium or serum sodium were noted with the present drug combination. However, during the initial phase an increase in serum creatinine and serum uric acid was noted in the actively treated group, which was maintained for two years. Also glucose tolerance was impaired after 2 years in the actively treated group. A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances. But this benefit must be proven by observed statistical differences in terminating events between the groups. Therefore the patients are being followed for a longer period of time and more patients are admitted into the trial.


Gastrointestinal hormones.

Gastrointestinal hormones. The chemistry, localisation, release and effects of gastrointestinal hormones and some related peptides are surveyed. Their main presumed physiologic actions are: gastric acid and pepsin secretion are stimulated by gastrin and to a less degree by secretin. Acid secretion is inhibited by bulbo-enterogastrone and GIP. Biliary water and electrolytes are augmented by gastrin, CCK-PZ, secretin and VIP and inhibited by Substance P. Pancreatic bicarbonate and enzyme secretions are stimulated by secretin and CCK-PZ, especially in combination. Lower oesophageal and antral motility and tonus are elevated following gastrin and motilin; the gallbladder and small intestine empty following CCK. Gastrin regulates gastrointestinal, and CCK pancreatic, tissue growth. Somatostatin inhibits all gut hormones. All peptides are vasoactive within the splanchnic area, each one in a specific manner.


Detection of immunoglobulin-bearing lymphocytes in humans with special reference to patients with contact dermatitis. Factors likely to influence the detection of immunoglobulin-bearing lymphocytes by immunofluorescence (IF) have been studied. Several of the examined anti-immunoglobulin reagents reacted to other Ig-classes but the relevant as demonstrated by hemagglutination test. When the indirect IF-method was used most anti-Ig reagents reacted with a significantly larger population of lymphocytes. Neither cytophilic Ig, nor plasma membrane dynamics did seem to exert any critical effect on classification of human lymphocytes. With selected sera lymphocytes of 24 patients with contact dermatitis were studied. No difference in number of Ig-bearing cells (direct and indirect technique respectively) between the patients and normals was found. In most individuals there was a good correlation between EA-rosette-forming cells and number of Ig-bearing lymphocytes including IgD-bearing using the indirect technique. This indicates the detection of a Fc-positive rather than a Ig-bearing cell population.


Male prolactin secreting pituitary adenomas in humans studied by peroxidase-labelled antibody method. In order to identity the source of excess secretion of prolactin in male patients, the pituitary tumors of 11 males with hyperprolactinaemia were studied by peroxidase-labelled antibody method using antibodies against human prolactin. Using light microscope, prolactin was demonstrated in most tumour cells in all cases. Ultrastructurally, prolactin was localized mainly on the secretory granules. Immunohistochemically positive cells were thought to correlate with first type of tumour cells which were the major component observed by regular electron microscopic study without immunohistochemical staining. These findings indicated the secretion of excess amount of prolactin by the tumour cells and were considered to be responsible for the category of Male Prolactin Secreting Pituitary Adenoma. The mechanism by which these male hyperprolactinaemic patients are endocrinologically non-functioning is also discussed.


Gonadotrophin regulation in the lactating rat. Post-partum lactation in the rat is associated with follicular quiescence and an attenuation of gonadotrophin secretion. The present study demonstrates that the lactating rat responds to exogenous LH-releasing hormone (LH-RH) in a manner similar to dioestrous rats. Oestrogen priming increases the LH and FSH response to LH-RH to a smaller degree in ovariectomized, lactating, than in non-lactating, ovariectomized rats. Pituitary LH levels throughout lactation did not seem to be related LH-RH-induced LH release. A diminished post-castration rise in both LH and FSH, and a diminished positive feedback response to oestrogen administration were also observed and may indicate a disruption of gonadotrophin regulation at both the hypothalamic and the pituitary level.


Intravenous lidocaine as a suppressant of persistent cough caused by bronchoscopy. The effect of intravenous lidocaine in the treatment of persistent cough occurring after diagnostic bronchoscopies performed under general anaesthesia was investigated in a controlled clinical trial. The study comprised 28 adults patients, all of whom had regained consciousness after anaesthesia. Fifteen patients were treated with lidocaine (1.05 mg/kg body weight) and 13 patients with placebo (saline). In each patient the intravenously injected dose was repeated once after 5 min. In 11 of the 15 patients (73%) who received lidocaine coughing ceased, while it continued in all 13 patients in the placebo group. The difference is highly significant (P less than 0.001). None of the patients developed side effects such as hypotension, arrhythmias, central nervous system symptoms or respiratory depression after injection of lidocaine. It is therefore concluded that intravenous lidocaine in man is a safe and useful cough-suppressant.


Serum diazepam and serum creatine kinase after intra-muscular injection of diazepam in two different vehicles. Serum diazepam concentration and serum creatine kinase activity (serum CK) were measured in 35 patients (who were divided into three groups (A, B, and C)), over a period of 24 hours after administration of diazepam. An increase in serum CK was regarded as an indication of local muscle injury. In group A, diazepam in a polyethyleneoxydricinolate vehicle was injected intramuscularly; in group B, diazepam in a propyleneglycol-ether alcohol vehicle was injected intramuscularly; and in group C, diazepam was administered orally, combined with intramuscular administration of the vehicle used in group B. The investigation was double-blind and randomized. Serum diazepam absorption expressed as the area under the concentration curve was identical in groups A and C and significantly higher than in group B. Serum CK rose in all groups. The differences among the groups were not significant. There were considerable individual variations in all three groups, and almost half the patients showed no increase in serum CK at all. No negative correlation was found between serum diazepam and serum CK. Thus no effect of muscle injury--if present--on absorption rate could be demonstrated.


Two early Danish respirators designed for prolonged artificial ventilation. Two Danish respirators are described. The first one was made by August Krogh in 1931 and was based on the principles of the Drinker tank respirator. The original feature was a motor driven by water from an ordinary water tap. It was never widely used, most likely due to practical problems connected with nursing care, etc. The polio epidemic in Copenhagen in 1952 initiated the era of the IPPV-methods and gave rise to the construction of a great number of new respirators. Among the first of these was the Claus Bang respirator. Although it contained many modern features, it proved technically unreliable and was only used for 3-5 years.


Electron-microscopic and cytophotometric studies on the abdominal pre- and paravertebral ganglia of the cat. Electron-microscopic and cytophotometric studies of the cat abdominal pre- and paravertrebral ganglia have revealed that in the prevertebral ganglion there are neurons of two distinct types. The paravertebral ganglion was found to consist of a structurally homogenous neuronal population.


Histocytology of the avian (Gallus domesticus) carotid body. The histotopography of the silvery-white glistening carotid body and the branchial derivates in the cranial thoracic inlets as well as the histocytology of the particular organ were revealed by various microtechniques. Three types of randomly distributed epithelioid cells, many capillaries, and small and large sinuses are observable. Myelinated fibres are sparsely distributed. 25 clinically healthy white leghorn males were used for this investigation.


The influence of fetal circulation on liver cell ultrastructure. This study shows that autolytic changes in liver tissue from mini-pig fetuses are less extensive if, after removal of the uterus, the fetal circulation is left anatomically intact until excision and fixation. It must be concluded that, if it is not possible to remove and fix fetal material immediately, the fetus should be kept in the intact amniotic cavity with an intact umbilical cord.


Resection and reconstruction for bone tumours. For the surgical treatment of tumours in long bones a technique in which the resected bone segment is autoclaved and replaced is described. The results in three patients who had undergone this operation 7 to 11 years previously, one for chondrosarcoma and two for giant cell tumour, are reported. In all three cases sound union has been achieved. The advantages of boiled autografts are the immediate availability and the excellent fit of the graft. In order to avoid the problem of slow union of the autoclaved bone segment rigid fixation with long-term stability, preferably with a Küntscher nail and the use of supplementary fresh autogenous bone, is necessary. Two patients with traumatic bone loss from the femoral shaft treated in a similar way are reported from the literature.


V-Y plasty as treatment of finger tip amputations. V-Y plasty was performed in 28 patients who suffered from a transverse amputation of the finger tip. Bilateral V-Y plasty was carried out in 16 cases and single volar V-Y plasty in 12 cases. The average follow-up period was 32 months. Six patients had postoperative complications, requiring reoperation in four patients. The follow-up results were satisfactory. The results showed that V-Y plasty is indicated in transverse amputations through the distal one-third to one-half of the nailbed, but only in patients to whom the length of the finger is of importance.


Asymptomatic diabetes in childhood and adolescence. A review. An account is given of the present conception of asymptomatic (chemical) diabetes in the pediatric age group, which also has been named MODY (maturity-onset type of diabetes of young people). Long-term studies show that about 10% will eventually decompensate to overt diabetes. In contrast to classical juvenile-onset type of diabetes the inheritance of MODY seems to be autosomal dominant in many cases. Some authors have suggested that insulin resistance exists in non-obese patients with asymptomatic diabetes, but this view is not supported by observations of the author. Obese patients should reduce their body fat, but other therapeutic approaches are difficult to evaluate because of the normal fluctuation of the disease. There is no general agreement in the literature concerning the value of insulin treatment. The author supports the view that insulin treatment should be started in the late stages of chemical diabetes just before symptomatic disease emerges. In the long run this approach may ameliorate the condition due to the preservation of some beta-cell function for long periods. An unsettled question is whether early insulin treatment in asymptomatic diabetes will delay diabetic vascular complications.


Phylogeny of insulin. Some evolutionary aspects of insulin production with particular regard to the biosynthesis of insulin in Myxine glutinosa. Preceding phylogenetic studies on the occurrence of insulin have shown--e.g. by bioassays and immunocytochemical procedures--that insulin producing B-cells are present in all vertebrates and even in several invertebrates, both protostomian and deuterostomian. The most original B-cells are obviously endocrine cells of open type, situated in the mucosa of the alimentary tract. Moreover, the results of these studies show that insulin is not only a polypeptide hormone of considerable age but also that the insulin molecule seems to have been kept surprisingly stable during evolution. Best known of all non-mammalian insulins is that from the hagfish, Myxine glutinosa. It is probably the most original insulin of all in the vertebrate series. Both the amino-acid sequence and the three-dimensional structure of the dimer of hagfish insulin differ only little from those of pig insulin. The biosynthesis occurs via proinsulin and is also in most respects similar to mammalian insulin biosynthesis. There are, however, some differences. Although it readily crystallizes as tetragonal bipyramids, hagfish insulin does not form hexamers. In a test system, with isolated rat fat cells, its binding affinity is 23% and its potency 5% of that of pig insulin, a discrepancy indicating a "partial antagonism" on the receptors. Although the conversion of proinsulin to insulin seems to occur in the secretion granules, they contain no crystalline cores. Since a strictly tryptic-like enzyme was found to destroy hagfish insulin rapidly, the enzyme converting proinsulin to insulin must--in addition to a carboxy-peptidase-B-like activity--have a different specificity in Myxine.


C-peptide in juvenile diabetes.

C-peptide in juvenile diabetes. C-peptide can be used as a measure of endogenous insulin secretion in insulin treated diabetics with insulin antibodies. At the onset of juvenile diabetes insulin production is thought to be absent or minimal, but we have found rather high levels of C-peptide, even in ketoacidotic patients. The ketoacidosis does not mean an irreversible beta cell failure. In the postinitial remission period with stable metabolism many patients have normal or almost normal C-peptide levels and their beta cells have the capacity to respond to natural stimulation with an increased insulin secretion. For some unknown reason the metabolism becomes more labile coinciding with decreasing C-peptide values. However, even several years beyond the postinitial remission period many juvenile diabetics have some persistent beta cell function, and it has been shown that even trace remnants of beta cell function are of importance for stabilization of the metabolism. There is no reason to believe that the beta cell failure should be predetermined e.g. by genetic factors. However, little is known how to influence the progression and stop the increasing beta cell failure. Some of our results suggest that an early detection and an intensive treatment of diabetes before severe metabolic disturbances and pronounced insulin deficiency have appeared, may increase the possibility of preserving some beta cell function.


Transplantation of islets of Langerhans in diabetic rats. In the present work, homogeneous isolated pancreatic islet-cells were transplanted to diabetic rats with the aim of verifying if the transplanted tissue could survive and reduce the plasma glucose concentration on the alloxan-induced diabetic receptors. For the isolation of the pancreatic islets, pancreas was incubated in collagenase solution for about 13 +/- 3 minutes, followed by centrifugation in Ficoll gradients. The islets, 3 000 to 5 000, were transplanted to alloxan diabetic recipients, in a territory, preferentially with portal-hepatic drainage (mesentery and spleen). Sixty per cent of the recipients exhibited a fall of the plasma glucose concentration, up to 70%, while in the control animals, the diabetes persisted. The islets were found in the recipients mesentery up to 10 days after transplantation, and all of them showed heavily granulated (aldehyde fuchsin positive) beta cells. After this time, islets were not found. These results indicate that islets can survive and attenuate diabetes in alloxan-treated rats, and that, probably, the number of islets transplanted as well as the receiving areas play an important role.


Molecular changes in lymph node tissue after skin heterografts. Changes in the rat lymph node RNA base composition and in ribosomal aggregation induced by heterologous skin graft have been characterized by the base composition analysis of the phenol extractable RNA, by the density gradient centrifugation of the ribosomal particles and by amino acid incorporation in the newly synthetized protein. Following skin grafts, the changes in base composition of total RNA in lymph . nodes were mainly due to the synthesis of ribosomal type RNA. Ribosomes were assembled as single units or as polyribosomes. The present findings also show an increase in amino acid incorporation by polyribosomes after the first graft reaction.


Prophylactic treatment with miconazole in patients highly predisposed to fungal infection. A placebo-controlled double-blind study. In a placebo-controlled double-blind study the prophylactic value of oral systemic treatment with the antimycotic agent miconazole was assessed in 30 highly predisposed patients receiving intensive cytostatic chemotherapy because of haematological malignancies. Patients colonized with Candida before treatment were not freed from this micro-organism by miconazole treatment. However, only 3 out of 6 initially non-colonized miconazole-treated patients became colonized during the study, against 10 out of 10 placebo-treated patients (p = 0.036). Seven out of 15 patients in the placebo group developed clinical mycosis, against only two out of 15 in the miconazole group. The miconazole-treated patients remained clinically free of mycosis for 252 out of 264 treatment days, while the placebo-treated patients remained free of mycosis for only 263 out or 338 treatment days (p = 0.0001). The results indicate that systemic miconazole treatment protects highly predisposed patients from colonization with Candida and prevents or postpones clinically established candidosis.


Multidisciplinary treatment for central nervous system tumours with nitrosourea compounds. The authors report the results of a controlled clinical trial in patients with primitive and metastatic CNS tumours treated with combined therapy: surgery, radiotherapy, and chemotherapy (BCNU or CCNU). A total of 102 patients were treated, 50 with BCNU, and 52 with CCNU. The overall response (R. + P.R.) was 68% for the BCNU group, and 65% for the CCNU group. No significant differences were found between the two types of treatment, either in terms of response or in terms of quality and length of survival.


[Immunfluorescence of human brain tumours (author's transl)]. Sera of 38 patients with various intracranial tumours were examined by indirect immunofluorescence for antibodies against their own tumours. The frequency of antibodies found in this investigation corresponds to the frequency of antibodies against tumours of other organs. Antibodies were found in 9 out of 14 glioblastomas, in 3 out of 10 slower growing gliomas, and in 2 sarcomas. Antibodies could not be demonstrated in metastases, meningiomas, or Lindau tumours. Localization of antigens by immunofluorescnece suggests that they are surface antigens. Antibodies are found in sera collected two days after surgery as well as in sera obtained two weeks after surgery. The method used did not demonstrate any complement dependency. Possibilities for diagnostic use are discussed.


Animal models: importance in research on hemorrhage and thrombosis. Despite some sentiments against animal research, animal models continue to be important in studying hemorrhage and thrombosis. Examples of genetic models are dogs and pigs with von Willebrand's disease. The homozygous von Willebrand pig appears to be resistant to arteriosclerosis, presumably due to impairment of the platelet aggregating function. Among acquired models, pigs are gaining in favor, perhaps because their clotting and platelet characteristics resemble those in humans. Species vary markedly in their normal plasma levels of platelet aggregating factor/von Willebrand factor (PAF/vWF). One promising approach to the study of thrombosis is using platelet anti-aggregating drugs to inhibit PAF/vWF dependent platelet thrombus formation; a drug-induced von Willebrand state seems feasible.


Platelets, endothelium, and smooth muscle cells in atherosclerosis. A factor derived from platelets stimulates the proliferation of smooth muscle cells in culture, and is likely important in stimulating smooth muscle proliferative lesions of atherogenesis in vivo. The platelet factor is produced during platelet aggregation when serum is made from whole blood. In vitro, smooth muscle cells are potent aggregating agents for platelets, while endothelial cells can inhibit this aggregating effect. Better understanding of the interactions of platelets, smooth muscle cells, and endothelium would facilitate developing effective means of intervening in or preventing the smooth muscle proliferative lesions of atherosclerosis.


Vessel injury and atherosclerosis.

Vessel injury and atherosclerosis. Repeated endothelial injury causes lipid-rich lesion in animals on a normal diet. In severely thrombocytopenic animals these lesions do not form or are markedly inhibited. The occurrence of lipid in some experimental designs is related to continued or repeated deposition of thrombus. Lipid deposition occurs in areas where endothelium is repeatedly removed and regrows. Repeated deposition of thrombus may bring about changes in the metabolism of the neo-intima which favor lipid deposition.


Venous thrombosis: mechanisms and treatment. The role of Virchow's triad in the etiology and treatment of venous thrombosis, the natural history of  postoperative thrombosis, and methods for monitoring venous embolism are described. In patients with hip joint replacements the effects of several drugs or drug combinations or placebos on wound hematoma and the effects of age, obesity, and activity and several drug combinations on venous embolism are reported.


Cardiac thromboembolism: evidence for role of platelets and value of platelet suppressant therapy. Thromboembolism remains a frequent and serious problem in cardiac patients. Methods to identify the thrombosis prone patient and the identification of safe and effective forms of treatment would be of great value. The accumulating evidence which indicates that abnormalities in platelet tests are often present in cardiac patients and may help identify those at greatest risk of thrombosis is encouraging. It suggests that patients with cardiac disease are desirable groups for investigation. It also indicates that the platelet survival test may be useful as a reference against which new and more practical tests can be compared, as well as a means to identify useful platelet suppressant drugs or to monitor the effects of these drugs.


Rationale for antiplatelet agents in diabetic vascular disease. Studies summarized in this paper indicate that some diabetics have increased sensitivity to platelet aggregating agents. The problem is in the platelet release reaction and may reflect increased synthesis of prostaglandins or their precursors. An interaction of plasma factor such as von Willebrand factor with platelets may also be involved. Based on these and other considerations, a prospective study on the use of aspirin and dipyridamole on diabetic lower extremity vascular disease is underway as a Veterans Administration Cooperative Study.


Diabetic angiopathy--its lessons in vascular physiology. Progress in our understanding diabetic angiopathy has been slow, but we are now learning a number of lessons of interest to the cardiologist. Diabetic angiopathy is a collective term for conditions specific to the diabetic state and related to its duration more than to patient age. The angiopathy produces calcification of the media of larger arteries, but its major effects are in the microcirculation. Intense interest in one feature, skeletal muscle capillary basement membrane thickening, has dominated the last decade. Capillary basement membrane thickening, while characteristic of diabetes, is associated with little direct impairment of the microcirculatin. It appears to play no role in the pathogenesis of diabetes itself. The pathology of diabetic retinopathy and diabetic nephropathy suggests that arteriolar changes may be the major mediator of diabetic angiopathy. This concept is supported by the interactions between hypertension and diabetes in the eye and kidney. The course of diabetes of youthful onset differs from that of maturity onset. The relative frequency of diabetic angiopathy is higher, and of atherosclerotic complications is lower. This has made it difficult to demonstrate the potential value of preventive measures. Benefit to one type of problem may become hidden by worsening of the other. If the diabetic benefits from what is learned about how ischemic heart disease risk can be reduced, he will require even more effective management to prevent or control diabetic angiopathy.


Value of coronary bypass surgery. Controversies in cardiology: Part I. The value of coronary bypass surgery has been studied carefully during the last decade. Four methods, none perfect, have been used to compare the results of such surgery with the results of medical therapy. New data are likely to be merely supportive rather than the outcome of a definitive study with a new and a acceptable experimental design. It is therefore time to analyze the available data in light of the treacherousness of the disease and to determine if a clear trend is evident. There appears to be sufficient evidence to state that properly performed coronary bypass surgery will increase coronary blood flow and relieve angina pectoris in 90 percent of patients; total relief of angina can be expected in 60 percent and partial relief in 30 percent. Compared with modern medical therapy, properly performed coronary bypass surgery appears to prolong the life of patients who have obstruction of the left main coronary artery or triple or double vessel disease. There is not adequate evidence to state that the procedure will prolong the life of patients with single vessel obstruction. However, patients with single vessel obstruction and unacceptable angina pectoris should be considered for bypass surgery (especially patients with obstruction of the left anterior descending coronary artery). In practice, at Emory University Hospital, Atlanta, bypass surgery is recommended for young people with few symptoms if compelling obstructing lesions are present and in older patients only if their symptoms require it. Medical therapy is given before and after bypass surgery. When bypass surgery is performed in an excellent fashion (operative risk 1 percent) a great deal of "controversy" about this problem vanishes.


Carotid sinus hypersensitivity and syncope. Hyperactivity of the carotid sinus reflex is common in older men. However, an unequivocal diagnosis of carotid sinus syncope is difficult to establish because the symptoms are nonspecific, and both hyperactivity of the carotid sinus reflex and syncope are common. Twenty-one men were evaluated for episodes of lightheadedness or syncope, or both, associated with a hypersensitive carotid sinus reflex. Seventeen patients had the cardioinhibitory type, two the vasodepressor type and two both the cardioinhibitory and vasodepressor types. Patients with the cardioinhibitory type benefited from the insertion of a permanent pacemaker if they had multiple episodes of syncope. A history of syncope associated with some event capable of stimulating the carotid sinus was also helpful in selecting patients for pacemaker treatment. The combination of the cardioinhibitory and vasodepressor types may be missed unless carotid sinus stimulation is repeated after the administration of atropine. The results of electrophysiologic studies in 17 patients with the cardioinhibitory type suggest that intrinsic sinus nodal dysfunction is not the major cause for asystole after carotid sinus stimulation.


Reduced quinidine clearance in elderly persons. The influence of age on quinidine pharmacokinetics was assessed in 22 healthy male and female volunteers; 14 of the subjects were young (aged 23 to 34 years) and 8 elderly (aged 60 to 69 years). All subjects received 180 to 300 mg of quinidine base by constant rate intravenous infusion over 10 to 15 minutes. The concentration of total and unbound quinidine in multiple serum samples and in urine collected within 48 hours after the administration of quinidine qas determined with spectrophotofluorometric assay. Mean kinetic values for total quinidine in the young subjects were: elimination half-life (t 1/2 beta), 7.3 hours; total volume of distribution (Vd), 2.39 liters/kg; total clearance, 4.04 ml/min per kg; renal clearance 1.43 ml/min per kg; and percent unbound, 24.6 In the elderly subjects, the values for Vd (2.18 liters/kg) and percent unbound (28.2) did not differ significantly from these values in the young subjects. However, in the elderly subjects t 1/2 beta was significantly longer (9.7 hours, P less than 0.05) and total quinidine clearance significantly less (2.64 ml/min per kg, P less than 0.005) than in the young subjects. Renal clearance of quinidine in the elderly was also significantly less (0.99 ml/min per kg, P less than 0.05) than in the young and was associated with lower rates of creatinine clearance in the elderly (r = 0.66). Reduced clearance of quinidine and prolongation of its elimination half-life could predispose to toxicity in the elderly unless the dose were appropriately adjusted.


Efficacy of lidocaine in preventing primary ventricular fibrillation within 1 hour after a 300 mg intramuscular injection. A double-blind, randomized study of 300 hospitalized patients with acute myocardial infarction. The effectiveness of intramuscular lidocaine in preventing in-hospital primary ventricular fibrillation within 1 hour after injection of the drug in patients with acute myocardial infarction was assessed in a double-blind randomized study performed in 300 such patients admitted within 6 hours of myocardial infarction. Six of 147 patients treated with 300 mg of intamuscular lidocaine had ventricular fibrillation compared with 4 of 153 control subjects. The lidocaine blood level of the patients who experienced ventricular fibrillation was 1.4 +/- 0.7 microgram/ml (mean +/- standard deviation) at the time of fibrillation, a value not significantly different from that of treated patients who did not experience fibrillation. Lidocaine blood levels in the latter were 1.9 +/- 1.1, 2.1 +/- 1.1, 2.1 +/- 1.1 and 1.7 +/- 0.7 microgram/ml, respectively, 7, 15, 30 and 60 minutes after injection. In this study intramuscular lidocaine was ineffective in preventing ventricular fibrillation, possibly because the given dose, 300 mg, prevented attainment of adequqte blood levels of the drug.


Natural history of myocardial infarction in the coronary drug project: long-term prognostic importance of serum lipid levels. Coronary Drug Project Research Group. The relation between baseline fasting serum lipid levels (serum cholesterol and triglycerides) and 5 year rates for four end points--mortality from all causes, mortality from coronary heart disease, sudden death due to coronary heart disease and incidence of nonfatal myocardial infarction plus coronary death--was studied in 2,789 men. These were patients in the Coronary Drug Project placebo group who were 30 to 64 years old on entry and had recovered from one or more previous documented myocardial infarctions. Serum cholesterol was significantly related to all four end points, in both univariate and multivariate regression analyses (with control of 38 or 39 other factors in the latter). This significant relation of cholesterol to these end points was shown at low, medium and high levels of serum triglycerides. In contrast, baseline fasting serum triglyceride levels were not positively related to any of these end points. In these postmyocardial infarction patients, findings indicative of cardiovascular status at  baseline evaluation, particularly the state of the myocardium, were more powerful prognosticators than serum cholesterol. These findings underscore the importance of efforts to prevent the first coronary episode. They also indicate the possibility after recovery from acute myocardial infarction of improving long-term prognosis through reduction of serum cholesterol.


Aseptic necrosis after renal transplantation in children. Aseptic necrosis developed in 11 (6%) of 171 recipients of renal allografts who underwent transplant operations at Childrens Hospital of Los Angeles between February 1967 and August 1977. Pain was the predominant presenting symptom and preceded roentgenographic evidence of aseptic necrosis by as long as seven months. Initial symptoms occurred two months to four years posttransplant. Limited weight bearing and reduction in the dosage of prednisone failed to prevent the progressive destruction of five femoral heads in three patients. Hip replacement led to an amelioration of the symptoms and a resumption of normal activity in each patient. Two patients with involvement of multiple osseous structures have persistent knee and elbow joint pain and effusions, and one of them has required prosthetic replacement of the proximal humerus. No therapy was required for patients with aseptic necrosis of single bones of the hand and foot. There was no statistically significant difference in the total steroid dose received during the first posttransplant year between patients in whom aseptic necrosis developed, and those in whom it did not develop.


Complications of corticosteroid therapy. The complications of corticosteroid therapy in children are protean. Perhaps the most important of these are adrenal insufficiency after withdrawal of steroids, immunosuppression, and growth failure. The physician who is caring for a child receiving corticosteroids must be aware of these common complications as well as the many less frequent side effects, such as cataracts, pseudotumor cerebri, pancreatitis, and steroid myopathy, to name a few. In all children, the risk of using corticosteroids should be weighed carefully before therapy with these agents is begun.


Mortality and morbidity associated with pressure- and volume-limited infant ventilators. The effect of pressure-limited (PL) and volume-limited (VL) ventilation on mortality and morbidity in infants with severe hyaline membrane disease (HMD) was examined in a prospective controlled study. Criteria for mechanical ventilation were PaO2 value of 50 mm Hg or less or a Paco2 value of 70 mm Hg or greater, while the infant was receiving nasal continuous positive airway pressure (CPAP) at oxygen concentrations (FIO2) of 0.8 or greater and CPAP of 8 cm H2O or greater; HMD associated with severe perinatal asphyxia requiring mechanical ventilation in the delivery room. Consecutive patients were alternately assigned to receive either PL or VL ventilation. Twenty infants were ventilated with PL machines using low peak inspiratory pressures (mean maximum inspiratory pressure of 28 cm H2O) and prolonged inspiratory times. Twenty other infants were ventilated with VL machines, using essentially unlimited peak inspiratory pressures (mean maximum inspiratory pressure of 62 mm H2O) and prolonged expiratory times. There were no significant differences in survival, incidence of pneumothorax or pulmonary interstitial emphysema, or noteworthy bronchopulmonary dysplasia.


New dimensions in the laboratory diagnosis of pancreatic disease. The laboratory diagnosis of pancreatic disease has been made more precise by certain modifications in older methods and by the introduction of a variety of new technical procedures. The principal human isoamylases may now be distinguished and their activities in serum and urine measured. A test has been devised which helps indicate the presence of acute pancreatitis by showing relatively increased excretion of amylase in the urine as compared with creatinine. The ratio of amylase to creatinine in the urine appears to be a good index of relative hyperamylasuria. A screening test for pancreatic-type hyperamylasuria has been formulated that allows increased urinary excretion of this isoamylase to be identified. These additions and developments have sharpened the interpretation of hyperamylasemia and hyperamylasuria and have added new dimensions to the laboratory diagnosis of pancreatic disease.


A controlled trial of 6-methylprednisolone in acute alcoholic hepatitis. With a note on published results in encephalopathic patients. In a prospective double-blind study, 27 patients with alcoholic hepatitis were randomized for 6-methylprednisolone (12 patients) or placebo treatment (15 patients). The mortality was 50% among steroid treated patients and 47% in the control group (P less than .05). The role of liver biopsy feasibility at selection is emphasized since the mortality in this group was 10% as opposed to 71% when the procedure was contraindicated (P less than .01). Complications in the steroid-treated subjects were similar quantitatively and qualitatively to those observed in the control series.


The diagnostic significance of the immunoglobulin A to M and A to total ratios in the pancreatoduodenal fluid of patients with benign and malignant pancreatic diseases. Immunoglobulins A, M and G in the pancreato-duodenal fluid (PDF) of 35 pancreatic disease-free individuals and 48 patients with chronic pancreatitis (25), hypersecretory disorders (10), renal transplanted (4) and with pancreatic cancer (9), were determined by a single radial immunodiffusion method. Although a trend of immunoglobulin hypersecretion in benign diseases and hyposecretion in malignancies was present, individual levels of Ig-A and Ig-M differed statistically only between cancer and other groups. Calculating the ratios of Ig-A to Ig-M (A/M) and Ig-A to total immunoglobulin contents (A/T) in the PDF of patients with chronic pancreatitis or cancer, however, a significantly higher or lower ratio, respectively, was found compared to control group. Differences in A/M ratios could not be detected between patients with benign diseases, but were constantly present when these patients were compared to pancreatic cancer. The underlying mechanism(s) of the disturbed immunosecretory system in pancreatic diseases remains speculative. Nevertheless, immunoglobulin measurements in the PDF of patients with pancreatic diseases offer a simple diagnostic aid in clinical differentiation of pancreatic pathology.


Epidemiology of common-source outbreaks of shigellosis in the United States, 1961-1975. In 1961-1975, there were 72 foodborne and 38 waterborne outbreaks of shigellosis reported in the United States. Foodborne outbreaks were most often caused by salads with contamination attributed to poor hygiene of a food handler. Waterborne outbreaks most often involved semipublic water systems, and were usually the result of inadequate chlorination of water contaminated by human feces. In 110 common-source outbreaks, 16,541 persons were ill. The attack rate for both food- and waterborne shigellosis was 47%, and the case-fatality ratio was 0.1% in foodborne outbreaks and 0.2% in waterborne outbreaks.


Efficacy of trimazosin and prazosin therapy on cardiac and exercise performance in outpatients with chronic congestive heart failure. The effect of trimazosin versus placebo therapy in 16 patients and of prazosin versus placebo therapy in six patients on treadmill exercise performance was evaluated in two double-blind, randomized studies in patients with chronic left ventricular failure despite therapy with digitalis and diuretics. The administration of trimazosin and prazosin was effective in lowering resting systolic and diastolic blood pressures and resting heart rate times systolic blood pressure, and the administration of trimazosin was effective in decreasing exercise diastolic blood pressure. Trimazosin and prazosin therapy was also effective in diminishing clinical symptoms, in lessening roentgenographic evidence of pulmonary venous congestion and in improving exercise duration until marked dyspnea. Based on these data, we conclude that the vasodilators, trimazosin and prazosin, are effective in treating chronic left ventricular failure.


Multiple peripheral pulmonary carcinoids and tumorlets of carcinoid type, with restrictive and obstructive lung disease. Multiple peripheral carcinoid tumors were found on lung biopsy in a 53 year old woman with an eight year history of pulmonary nodules. The biopsy specimen showed nodules varying from 1 to 7 mm in greatest diameter. The larger lesions were typical bronchial carcinoids whereas the smaller ones resembled pulmonary "tumorlets." Electron microscopy showed neurosecretory granules typical of carcinoids. The common multicentric origin of carcinoids and tumorlets from Kulchitsky cells is discussed. Pulmonary function testing revealed mild obstructive and restrictive defects, both attributed to the carcinoid tumors. The history, pathology and physiology of this unusual case are presented in detail, with a review of the literature. Obstructive airways disease, presumably due to the extensive bronchiolar involvement, has not previously been reported in this entity.


The acute effects of ritodrine infusion on maternal metabolism: measurements of levels of glucose, insulin, glucagon, triglycerides, cholesterol, placental lactogen and chorionic gonadotropin. Twenty-nine women in premature labor were randomly assigned to a ritodrine (N = 14) or placebo (N = 15) treatment group. Thirteen serial blood samples were drawn during the first 12 hours of therapy by intravenous drug infusion and they were analyzed for a variety of metabolic substances. There was a significant increase in the blood glucose level in the ritodrine group after one hour and this persisted for the 12 hours of intravenous drug treatment. Plasma insulin levels similarly did not increase in the placebo but significantly rose in the ritodrine group by 30 minutes, peaked at 2 1/2 hours, and remained elevated throughout the infusion. There were no significant differences between levels of plasma glucagon, cholesterol triglyceride, human placental lactogen, or human chorionic gonadotropin in the two treatment groups. Ritodrine caused significant maternal and fetal tachycardia. Its use in women with carbohydrate abnormalities should be monitored carefully. The increased glucose levels may lead to an increased fetal weight.


A comparison of two indirect methods for localizing the site of urinary infection: beta glucuronidase levels and the presence of antibody-coated bacteria. A comparison of two of the indirect methods used for localization of the site of urinary tract infection was made for 218 obstetric patients. There was no correlation between urinary beta glucuronidase activity and the presence of a positive fluorescent antibody test. The ranges of beta glucuronidase activity were so variable that this test could not differentiate between the presence of renal, bladder, or absence of infection.


Failure of serial chest radiographs to predict recovery from respiratory distress syndrome. Chest radiographs of 29 patients with the clinical and radiographic diagnosis of RDS during the 5 days of the illness were graded according to a modification of the classification of Bomsel. There was no significant difference between the radiographs of surviving neonates and those who died of RDS. Mean L/S ratios were also collected from 26 of the 29 patients. Those who survived had significantly more mean L/S ratios greater than 2.5 than did the nonsurvivors (p less than 0.01). This difference did not correlate with the staging of the chest radiographs. The mean L/S ratio is a better predictor of survival than chest radiographs during the first 5 days of RDS.


Plastic procedures in cancer of the lower genital tract. Plastic procedures were performed on 12 patients with cancer in situ of the vulva or vagina or after pelvic exenteration. All patients are alive and well on follow-up from four to 47 months with no evidence of recurrence. Plastic procedures are very important in treatment of cancer of the lower genital tract. The split-thickness graft used in this study is optimal in terms of treatment appearance, and restoration of sexual function.


Maternal smoking, birth weight, infant death, and the self-selection problem. Several aspects of the relationship between maternal smoking and birth weights of infants are discussed. No satisfactory explanation for Yerushalmy's results has been given other than that low birth weight appears to relate more to the smoker than to the smoking. Recent studies by Silverman support this position. The possibility that nicotine may induce a physiologic response that serves to alleviate bioenergetic deficiency in some individuals should not be overlooked. In this view, both smoking and low birth weight are symptoms of deficient maternal bioenergetic systems.


Herpes gestationis: clinical features of immunologically proved cases. Clinical features of eight immunopathologically proved cases of herpes gestationis (HG) are presented. They are compared with those of anearlier, clinically defined series. The important, features of the disease are identical in the two groups, particularly the worsening with subsequent pregnancies, absence of intervening HG-free pregnancies, and the exacerbation with delivery and estrogens. The immunopathologic investigations are a reliable, diagnostic aid in differentiating HG from other dermatoses of pregnancy with which it may, at times, be confused.


Male transsexualism--a review of genital surgical reconstruction. Transsexualism is a poorly understood, uncommon, and controversial entity of recent interest to the lay public and medical profession. Important features of the condition are discussed, surgical procedures for genital conversion in male transsexuals are compared, and our experience at the University of Virginia where 53 patients have been treated surgically is presented. All patients have made satisfactory postoperative psychosocial adjustment despite a surgical complication rate approaching 50 per cent. It is concluded that alternative (better) surgical procedures for male transsexuals should be explored.


The effect of varying prolactin levels on pituitary luteinizing hormone and follicle-stimulating hormone response to gonadotropin-releasing hormone. Seventy-one women with menstrual irregularities were investigated by measurement of basal plasma estradiol, prolactin, and gonadotropin levels. They were each given an intravenous injection of 100 microgram of gonadotropin-releasing hormone (GnRH), and both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured for two hours. The women were divided into three groups on the basis of the prolactin levels: "normal," "mild elevation," and "severe elevation." For each prolactin group there was no difference in age or estradiol or basal LH and FSH levels. The pituitary response to the GnRH injection was also similar for the three groups. These data suggest that elevated prolactin levels do not interfere with pituitary gonadotropin cell function.


Computer-assisted eye examination. VI. Identification and correction of errors in the Refractor III system for subjective examination. A computer-assisted subjective eye examination was administered to 80 patients. They were also examined in the conventional manual way. The results of the computer-assisted examination were compared with those obtained by conventional subjective methods to identify errors of hardware, software, and optometric flow charting and other problems. An 87.5% satisfactory prescription level was found for the distance prescription. The 12.5% unsatisfactory results are accounted for by several kinds of error. The percentage of unsatisfactory refractive results was greater for near than for distance measures because of special flow-chart and software problems, which were subsequently corrected. With implementation of the changes initiated as a result of this investigation, satisfactory refractive results approaching 95% can be expected.


Clinical comparison of direct versus indirect bonding with different bracket types and adhesives. A longitudinal clinical trial was made in forty-two children to compare some commonly used techniques for orthodontic bracket bonding. A particular study design (Figs. 1 and 5) allowed blind quadrantwise comparisons in the same patient of six different variables, including direct versus indirect bonding, adhesives of the filled diacrylate resin type with small versus large filler particles, and metal brackets with mesh-backed versus perforated bases. The same person bonded all brackets within one week and performed the orthodontic treatment by a friction-free edgewise light-wire technique. Efforts were made to minimize gingival irritation by using eccentrically placed brackets on small bases, by careful trimming of excess adhesives flash around the bases, and by directing much emphasis on oral hygiene measures. The plaque situation around the brackets and along the gingival margins and the gingival condition were assessed according to the criteria of the plaque and gingival index systems by a dental hygienist at each monthly visit during a test period of 6 months. The study demonstrated that both direct and indirect bonding with the different adhesives and bracket types could give clinically satisfactory results. Still, there were statistically significant differences in plaque retention, gingival inflammation, and bond strength. The bonding adhesive with small filler particles was more hygienic than and about as strong as two adhesives with larger, coarser filler particles. The mesh-backed brackets retained less plaque and gave stronger bonds than the brackets with perforated pads. Advantages of direct bonding over the indirect procedure were that (1) the bracket bases were fitted closer to the tooth surface (which improved bond strength), (2) it was easier to work clean and to remove excess adhesive flash around the bracket bases (to help prevent gingival inflammation and decalcification and facilitate debonding), and (3) the bonding adhesive constantly filled out the entire contact surface of the brackets (thus avoiding artificial undercuts and deficiency areas which are prone to promote decalcification). A number of other clinical observations were also discussed.


Enamel surface characteristics on removal of bonded orthodontic brackets. Thirty-six premolars which were scheduled for routine extraction were bracketed with either N or G system adhesives. After one week the brackets were removed and the residual adhesive removed by low-speed green stone, a hand scaler, or an ultrasonic scaler. Half the teeth were given a final pumice, and then all were extracted. The SEM was used to evaluate the enamel surface, and quantitative assessments were made for the area covered with retained adhesive and for damage to the surface. All three removal techniques left appreciable amounts of retained adhesive 20 to 60 per cent coverage for G and 55 to 75 per cent for N adhesive. All detectable adhesive was removed by final pumicing. The detectably roughened area was over 50 per cent for the green stone treatment for both materials and appeared to introduce unnecessary roughness. The hand scaler and the particular ultrasonic scaler used in this study did not severely roughen the enamel for either material and appeared to be effective for initial adhesive removal. All three techniques introduced occasional gouges 10 to 20 micrometer in depth which could not be removed. All other roughness was generally smoothed by final pumicing. Thus, pumicing is a necessary final step with all removal procedures studied.


Substances which aggregate neutrophils. Mechanism of action. Several agents which influence calcium fluxes in neutrophils were tested for their influence on human neutrophil aggregation. Formyl-methionyl-leucyl-phenylalanine, a synthetic chemotactic tripeptide, aggregated the cells. Cytochalasin B and high levels of extracellular calcium or phosphate enhanced this effect; 10(-6) M to 10(-5) M lanthanum inhibited it. In addition, the calcium ionophore A23187 aggregated the cells. Aggregation induced by the chemotactic factor and A23187 required extracellular calcium. These results correlate with the known or postulated ability of chemotactic factors, A23187, calcium, phosphate, lanthanum, and cytochalasin B to enhance or inhibit the influx and intracellular accumulation of the calcium ion. Transmembrane fluxes or intracellular levels of calcium may modulate PMN aggregation. Aggregation induced by the chemotactic tripeptide and A23187 also required extracellular magnesium. Since calcium and magnesium cannot substitute for each other in the aggregation response to the chemotactic factor or A23187, each bivalent cation must play a separate role in PMN aggregation. The role of magnesium is unknown. Since magnesium, unlike calcium, is known to be necessary for PMN adherence to glass, it may play a permissive role in PMN aggregation. Thus, magnesium may foster the formation of cell-cell adhesions. In addition to inhibiting chemotactic factor-induced aggregation at concentrations of 10(-6) M to 10(-5) M, lanthanum, at concentrations of 10(-4) M to 10(-3) M, aggregated the cells. Lanthanum-induced aggregation did not require extracellular calcium or magnesium. This aggregation may result from the formation of intercellular adhesions by the lanthanum ion directly.