Treatment of idiopathic thrombocytopenic purpura (ITP). In summary, idiopathic thrombocytopenic purpura (as defined here) should be treated initially with glucocorticoids unless there is life-threatening hemorrhage (such as intracranial bleeding), in which case emergency splenectomy is indicated, since it generally gives the most prompt improvement in platelet count of all modes of the disease and to better define the cause of the thrombocytopenia. A complete, sustained remission following treatment with steroids may occasionally be obtained. In most cases the steroid response is transient, and splenectomy is the most definitive measure with respect to a lifelong cure. Complete clinical cure is obtained in 70-80% of instances following splenectomy, with a very low operative risk. The remainder either fail to respond or experience relapse. In this group of patients steroids should again be tried; if a good response is obtained, steroids should be given every second or third day to lessen long-term side effects. If these measures fail, the use of immunosuppressive agents is justified. Both vinca alkaloids and cyclophosphamide are especially useful. Vinca alkaloids act more promptly, but cyclophosphamide may have a more lasting effect. Azathioprine may also be used; however, it appears to yield a lower remission rate. Nonsteroidal immunosuppressive agents should not be used as the primary modality of therapy. And, due to their carcinogenic and teratogenic potential, they should be avoided, if possible, especially in children and in women during their childbearing years.


Prophylaxis of infective endocarditis: a reevaluation. Established practice dictates that physicians and dentists give antimicrobial agents at the time of procedures associated with bacteremia in an effort to prevent IE in persons with underlying cardiovascular diseases. Although prospective controlled study has not been established efficacy, very few cases of IE have been reported in patients at risk who have been treated with regimens recommended by the American Heart Association. Furthermore, studies in rabbits in recent years have shown that IE can be prevented by antimicrobials. The results in rabbits have raised some theoretical questions regarding efficacy of currently recommended regimens for man and have led some investigators to propose revisions of the American Heart Association recommendations. We feel that direct translation of results from experimental IE in rabbits into recommendations for prophylaxis of IE in man is subject to question. It is unlikely that a prospective study comparing placebo with antimicrobials will be undertaken, but it is possible and reasonable to undertake studies to document the occurrence of IE in patients at risk who are given established antibiotic regimens. With such data, modifications of established regimens could be proposed and tested. Regimens that are found to be totally effective in a large number of patients at risk might be modified toward simpler programs--for example, modifying parenteral therapy to oral therapy or changing multiple doses of antibiotic to a single dose. If regimens fail, even once in several thousand patients at risk, the factors responsible might be determined and a clear rationale for modification achieved.


The role of ethanol in cardiac disease.

The role of ethanol in cardiac disease. The widespread use of ethyl alcohol suggests its potential importance in clinical medicine. There is no proven therapeutic effect in cardiac patients and its role as an etiologic factor in heart disease has been disputed over the years and attributed to coexistent malnutrition. The latter factor, however, has been dissociated from ethanol use in many patients with the cardiomyopathic form of heart failure. Major support for the role of ethanol as a toxic agent when used in large amounts for a prolonged period has been obtained in various species of animals, including the subhuman primate. Abnormalities include depression of ventricular function, and metabolic and morphologic changes that parallel the changes in humans with preclinical malfunction of the heart. While the mechanism of progression to heart failure or arrhythmias is not known, several factors may be associated. These include, particularly in males, the cumulative effects of ethanol alone or after intensified drinking episodes, simultaneous exposure to trace metals in excess, and occasional specific nutritional deficiency or superimposed infection. The low prevalence of clinical nutritional deficiency in patients with alcoholic cardiomyopathy and the infrequency of heart disease in patients with cirrhosis or neuropathy supports the view that the cardiac abnormality is commonly not dependent on malnutrition. Clinical data indicate that the cessation of alcohol intake may reverse the disease or interrupt its progression in many patients. However, the pathogenic process may continue unabated in some patients who become abstinent.


New concepts in the diagnosis of psychiatric disorders. The salient points in this paper include the following: (a) a description of categorical (typological) diagnosis, applicable to psychiatric as well as to medical illness; (b) description and discussion of the five steps necessary to validate clinically a categorical (typological) diagnosis; (c) a description of the currently primitive state of laboratory studies of functional disorders (e.g. schizophrenia, affective disorders, and other functional disorders); (d) a definition of various psychiatric illnesses and a description of the criteria necessary to qualify a symptom for describing them; and (e) the means and purposes of assessing diagnostic homogeneity or heterogeneity in psychiatric illnesses.


Diagnosis and treatment of fat embolism. Fat emboli syndrome is one of the major causes of early posttraumatic respiratory distress. Careful attention to the multiple factors associated with the early resuscitative period can minimize this lethal complication of multisystem injury. The use of high-dose steroids and appropriate ventilatory support will decrease the high mortality rate associated with this disease syndrome once it has developed.


[Penicillin amidase from E. coli. A comparative study of the stability of penicillin amidase immobilized by various means]. The properties of immobilized penicillinamidases prepared by different methods were studied. Immobilization of penicillinamidase was achieved by using the covalend binding ion exchange sorption, incorporation into gel and other procedures. The effect of the carrier type, purification level of the native enzyme and other factors on stability of the immobilized preparations was studied. In 4 cases significant stabilization of the enzyme in the immobilized state was observed, while in 3 cases destabilization was registered.


[Effect of prodigiozan on the phagocytic activity of the leukocytes in melioidosis intoxication]. In development of experimental melioidosis intoxication, the activity of the mechanisms controlling non-specific immunological reactions changed that was evident from changes both in the quantitative and qualitative indices of phagocytosis. The absorption function of the neutrophils was lowered during 2 days from the moment of administration of acetone killed bacterial mass of the melioidosis causative agent which was evident from decreased percentage and index of phagocytosis as compared to the control animals. The qualitative index of the digestive capacity of the neutrophils, i.e. the index of phagocytosis completeness was also low for 7 days of the experiment. The positive role of prodiglozan in activation of the host protective forces in cases with meliodosis intoxication was shown. Prodigizan administered 48 hours before injection of the bacterial mass of the melioidosis causative agent stimulated both the absorption and digestive capacities of the neutrophils.


[Effect of the peroral use of the antitumor antibiotic, carminomycin, on the immunological reactivity of the body of animals]. Carminomycin administered orally to mice for many times in doses of 2.5 and 1.25 mg/kg induced suppression of hemagglutinine production to sheep erythrocytes and formation of immunologically competent cells in the spleen of test animals. The content of DNA and RNA in the spleen of the test animals treated with carminomycin and sheep erythrocytes was somewhat lower than that in the control mice immunized but not treated with the antibiotic. Carminomycin prolongated the life time of the skin graft by 6.5 days as compared to that of the skin homotransplant in the control animals. The oral use of carminomycin in a dose of 2.5 mg/kg induced a statistically significant decrease in the absorption capacity of the cells of the reticuloendothelial system of the animals.


[Effect of bificol on the intestinal microflora of chronic colitis patients working in antiboitic prodiction]. Data on the use of bificol, a new Soviet preparation, and its effect on the intestine microflora of patients with chronic colitis occupied in production of penicillin are presented. It was shown that by the 28th day of the preparation use the level of the intestine bacteria in the patients' intestine reliably increased. The number of immobile strains decreased from 67.6 to 36.6 per cent. Bifidoflora normalized by the 14th day of the treatment. Some clinical inprovement, i.e. stool normalization, lessening of the stomach pain, increased appetite were observed by the 4th--5th day of the treatment with bificol. On the basis of the microbiological and clinical data it was shown that treatment of the patients with chronic colitis in antibiotic production should continue for at least 28 days and in individual cases for longer periods of time. It is recommended to use the preparation in 10 doses a day divided into 2 parts.


[Carbenicillin in the treatment of acute and chronic bacterial pneumonias]. A total of 50 patients suffering from acute and chronic bacterial pneumonia were treated with sodium carbenicillin. The bacteriological analysis of the sputum showed that Str. pneumoniae predominated in the monoculture or its association with other bacteria. Connection of the results of the bacteriological analysis with the clinical efficiency of the therapy was studied. When carbenicillin was administered intramuscularly in a dose of 1 gm, its therepeutic effect was maintained in the blood for 4 to 6 hours. A satisfactory clinical effect was registered in 41 out of 50 patients treated with carbenicillin in a daily dose 4--6 gm for 8--10 days. No toxic effect of carbenicillin on the parenchimatous organs and peripheral blood was noted.


Plasmid-mediated chloramphenicol resistance in Haemophilus influenzae. A clinical isolate of Haemophilus influenzae HC234 was found to be resistant to chloramphenicol and tetracycline. It was shown that both resistance markers are tranferable as one unit to other Haemophilus influenzae strains and also to Escherichia coli. Data are presented which indicate that conjugation is the most likely mechanism of resistance transfer. HC234 was shown to carry a single plasmid species with a molecular weight of 38 x 10(6).


In vivo effects of josamycin, erythromycin, and placebo therapy on nasal carriage of Staphylococcus aureus. Healthy nasal carriers of Staphylococcus aureus were randomly assigned to one of three treatment regimens: josamycin (1.5 g/day), erythromycin stearate (1.0 g/day), or placebo, each administered orally for 7 days. Quantitative nasal cultures were obtained from each subject at intervals before, during, and after treatment. All 25 placebo-treated subjects had positive nasal cultures for S. aureus at all culture intervals. Both josamycin and erythromycin were equally effective in reducing the carrier rates and in decreasing the total numbers of S. aureus isolated from subjects with positive cultures during treatment. No increase in in vitro antibiotic resistance was detected in isolates obtained after therapy. Both antibiotics were well tolerated, and toxicity was not encountered with either drug.


Antibiotic metabolites from a marine pseudomonad. An antibiotic-producing pseudomonad was isolated from a seawater sample from a La Jolla, Calif., tidepool. The pseudomonad produces two novel antibacterial compounds, 2-n-pentyl-4-quinolinol and 2-n-heptyl-4-quinolinol. It also synthesizes indole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and the known antibiotic p-hydroxybenzaldehyde. Each of these compounds was identified by analysis of spectral data, and the structures were confirmed by synthesis or comparison with authentic samples.


Resistance plasmid transfer by Serratia marcescens in urine. Resistance plasmids were transferred in urine from a multi-drug-resistant Serratia marcescens to Escherichia coli. Transfer of resistance to kanamycin, tetracycline, chloramphenicol, streptomycin, ampicillin, and carbenicillin occurred readily after 4 h of incubation at room temperature (25 degrees C). The urinary catheter collection bag is postulated as a potential site for extraintestinal resistance plasmid transfer in the Enterobacteriaceae, especially for pathogens such as Serratia, which do not frequently colonize the intestinal tract.


Comparison of the actions of 5-fluorouracil and ftorafur in Escherichia coli. The actions of 5-fluorouracil (FU) and Ftorafur (NCS 148958) were compared in Escherichia coli B3 to determine if Ftorafur can act in ways other than through the production of FU. Very high concentrations of Ftorafur relative to FU were necessary to achieve a comparable inhibition of cell growth. Inhibition by both agents could be reversed by uracil. An FU-resistant strain and an Ftorafur-resistant strain were isolated and found to be cross-resistant to Ftorafur and FU, respectively.


Mobilization of morganocin 174 plasmid and kinetics of morganocin production in Proteus and Escherichia coli hosts. Morganocin 174 is coded by a plasmid, Mor174. The plasmid is not self-transmissible but may be mobilized by resistance factor R772. Morganocin synthesis in all Proteus and Providencia strains carrying Mor174 was characterized by a longer lag period after induction and higher titers than in Escherichia coli B(Mor174). The low titers obtained in E. coli B(Mor174) are due to a heatstable inhibitor produced by this strain. Synthesis of morganocin is not constitutive and may be induced by ultraviolet irradiation or mitomycin C. Morganocin production is not influenced by the growth medium of the organism.


Characterization of an R-plasmid associated with ampicillin resistance in Shigella dysenteriae type 1 isolated from epidemics. Ampicillin-resistant strains of Shigella dysenteriae type 1 isolated in epidemics in Mexico, Central America, and Bangla Desh were examined for the presence of plasmid deoxyribonucleic acid (DNA) by gel electrophoresis. All strains contained a heterogeneous population of plasmids. Transfer experiments to Escherichia coli K-12 indicated that the ampicillin resistance determinant (Ap(r)) was located on a 5.5-megadalton (Mdal) plasmid identical in all Shiga strains examined, as judged by DNA hybridization and by its molecular properties. This 5.5-Mdal plasmid contained the ampicillin transposon (TnA) sequences. There was not a high degree of homology between the Shiga Ap(r) plasmid DNA and DNA obtained from Ap(r)Salmonella typhi strains isolated from typhoid epidemics in Mexico, previous to the dysentery outbreaks. Although low, the degree of reassociation observed indicated that probably part of the TnA sequence was present in S. typhi DNA. The DNA hybridization experiments showed, in addition, that there was a high degree of homology among Ap(r) plasmids isolated from different enterobacteria, and this identity was confirmed by restriction endonuclease activity. These results together with their similarities in molecular and replicative properties indicate that the Ap(r) plasmids, as was suggested for the Sm(r) Su(r) plasmids, possibly evolved once and then epidemiologically spread in the Enterobacteriaceae.


Action of the N-trifluoroacetyl analogue of D-chloramphenicol. The N-trifluoroacetyl analogue of chloramphenicol was found to inhibit the growth of Escherichia coli less than chloramphenicol, rather than more as previously reported by others. It also inhibits protein synthesis by E. coli and rat liver mitochondria less.


Influence of antioxidants on the bioactivity of amphotericin B. Four antioxidants, propyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, and d-alpha-tocopherol acid succinate were found to stabilize amphotericin B and to prolong its antifungal activity against Candida albicans. Although each of the antioxidants was effective in this respect, propyl gallate and butylated hydroxyanisole were better than butylated hydroxytoluene and d-alpha-tocopherol acid succinate. None of the antioxidants alone adversely affected normal cell growth. It is suggested that amphotericin B instability is due, at least in part, to lability of the carbon-carbon double bonds of the polyene moiety toward autoxidation. By protecting the drug molecule with an antioxidant, it is possible to significantly lower the quantity of AB necessary to obtain particular antifungal effects.


Growth inhibition of Escherichia coli W by D-norvalyl-D-alanine: an analogue of D-alanine in position 4 of the peptide subunit of peptidoglycan. Position 4 analogues of d-alanine in the peptide subunit of uridine 5'-diphosphate-N-acetylmuramyl-Ala(1)-dGlu(2)- Lys(3)-dAla(4)-dAla(5) have a significant inhibitory effect on penicillin-sensitive peptidoglycan synthesis in Gaffkya homari (C. V. Carpenter, S. Goyer, and F. C. Neuhaus, 1976). The specificity profile of this in vitro system has been used as a basis for designing analogues with potential antibacterial activity. To circumvent the specificity determinants exerted by d-alanine:d-alanine ligase (adenosine 5'-diphosphate), attention was directed to dd-dipeptides of the type d-alanyl-analogue-d-alanine as a method for incorporating analogues into position 4 of the peptide subunit in vivo. Of the three dipeptides, dAbu-dAla, dNva-dAla, and dVal-dAla, only dNva-dAla (5 x 10(-4) M) inhibited the growth of Escherichia coli W in the presence of 5 x 10(-6) M d-cycloserine. This concentration of d-cycloserine did not inhibit growth, but it potentiated the bactericidal activity of the dipeptide. The lack of antibacterial activity observed with dAbu-dAla and dVal-dAla was correlated with the poor ability of these dipeptides to be taken up via the dipeptide transport system of this organism. Prevention of lysis induced by dNva-dAla plus d-cycloserine by certain dipeptides and not by others supported this correlation. It is proposed that the d-norvalyl residue of the dipeptide is incorporated in vivo into position 4 of the peptide subunit of peptidoglycan, and that this subunit is not an effective substrate in the reaction(s) catalyzed by the penicillin-susceptible enzyme(s) of cross-linked peptidoglycan synthesis.


Cefazaflur, a new parenteral cephalosporin: in vitro studies. Cefazaflur was tested in vitro against 262 strains of bacteria. Inhibitory and bactericidal concentrations were determined with two inoculum sizes of bacterial cells in Mueller-Hinton broth and nutrient broth. Agar dilution studies also were performed. When tested in agar, 5.0 mug or less of cefazaflur per ml inhibited almost all strains of Staphylococcus aureus, Escherichia coli, Klebsiella, and Proteus mirabilis. The drug was less active against Enterobacter and indole-positive Proteus, and 7.5 mug of antibiotic per ml inhibited approximately two-thirds to one-fourth of the strains. A concentration of 50 mug of cefazaflur per ml was required for inhibition of the enterococci. There was negligible activity against Pseudomonas. The drug demonstrated less activity in broth than in agar, and a major inoculum effect was seen with some strains. For example, with a lower inoculum, 2.5 mug of cefazaflur per ml killed all strains of E. coli, whereas with the higher inoculum, 7.5 mug of cefazaflur per ml, inhibited 64% and killed only 8% of strains. The activity of the drug for some strains was greater in Mueller-Hinton broth; for others, it was greater in nutrient broth. There were considerable differences in the results of the broth and agar studies for some species when the same medium was employed. Because of differences in activity found with different media, inocula, and method of testing, an evaluation of the eventual usefulness of cefazaflur must await the results of in vivo studies.


Therapy of antimicrobial-resistant typhoid fever. Antimicrobial-resistant typhoid fever in Saigon was studied by examining in vitro antimicrobial susceptibilities of Salmonella typhi strains and conducting a randomized clinical trial of ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ). Isolates of S. typhi were obtained from blood or stool cultures of 90 patients. Of 87 isolates tested for antimicrobial susceptibility, 65 (75%) were resistant (R) to chloramphenicol, streptomycin, sulfonamide, and tetracycline, and 22 (25%) were susceptible (S). The drug resistance was transferable to Escherichia coli and was found in 11 different Vi-phage types. All isolates were susceptible to ampicillin and to TMP-SMZ. Agar dilution studies of TMP and SMZ showed synergistic inhibition of growth in all 18 S isolates and in 12 of 48 R isolates tested. The clinical trial of ampicillin and TMP-SMZ showed that both drugs were equally effective. Treatment failure with both drugs was more frequent in patients with S isolates than in patients with R isolates. Therefore, in an area where antimicrobial-resistant typhoid fever exists, patients with R isolates should receive either ampicillin or TMP-SMZ, but patients with S isolates should be treated with chloramphenicol.


Side effects of minocycline: a double-blind study. We studied the incidence and type of side effects of minocycline in a double-blind study. A total of 45 volunteers (18 men and 27 women) were given minocycline, and 44 volunteers (23 men and 21 women) were given placebo. The men in both the minocycline and placebo groups were significantly (P < 0.0001) larger than the women in the comparable groups. Minocycline dosage was 100 mg every 12 h for 5 days, and placebo was administered in an identical manner. Minocycline serum concentrations were determined in 12 volunteers at 1, 2, 4, and 6 h after the morning doses on days 1, 3, and 5 of the study. Side effects were recorded by volunteers in diaries and also through daily interviews and were evaluated by examination and electronystagmography. Peak minocycline serum concentrations were seen by day 3 and correlated with the peak onset of side effects. These concentrations were significantly higher in women than in men. Vestibular side effects occurred in 70.4% of the women on minocycline and significantly (P < 0.0001) exceeded the rate of the women on placebo (9.5%). Only loss of balance was significantly (P < 0.05) increased in the men taking minocycline as contrasted with men on placebo. Electronystagmography generally revealed no abnormalities. Side effects were usually not severe: four volunteers in the minocycline group and two in the placebo group discontinued their capsules because of side effects. It is concluded that women experience an unacceptably high incidence of side effects from minocycline, and this may be related to their higher serum concentrations, which in turn may relate to their smaller size.


Bullous pemphigoid responding to sulfapyridine and the sulfones. Since 1968, a total of 84 patients with bullous pemphigoid have been seen at the Mayo Clinic. Of these, 41 were given a trial of sulfapyridine or dapsone, and six showed a significant response. In five patients, the condition was controlled completely. All responsive patients showed indirect and direct immunofluorescent tests indistinguishable from typical bullous pemphigoid. The patients, however, were somewhat younger (mean 54 years) than others having pemphigoid; and in two patients, biopsy specimens showed a reversal of the usual eosinophilic predominance over neutrophils. Three of the six patients were also diabetic.


Congenital chloride diarrhoea. Clinical analysis of 21 Finnish patients. Clinical findings in 21 Finnish children with congenital chloride diarrhoea are reported. Inheritance of this disease by the autosomal recessive mode is established. All children were born 1-8 weeks prematurely. Hydramnios was present in every case and no meconium was observed; intrauterine onset of diarrhoea is thus apparent. In most cases the diarrhoea or passing of large volumes of "urine" was noted on the first day of life and the abdomen was usually large and distended. The neonatla weight loss was abnormally large, and was associated with hypochloraemia and hyponatraemia. Some infants survived the neonatal period without adequate therapy. They presented later with failure to thrive and usually had hypochloraemia, hypokalaemia, and metabolic alkalosis associated with hyperaldosteronism. However, these features may be absent and the diagnosis is based on a history of hydramnios and diarrhoea, and a faecal Cl- concentration which always exceeds 90 mmol/l when fluid and electrolyte deficits have been corrected. Lower faecal Cl- concentrations were seen only in chronic hypochloraemia, which is also associated with achloriduria. Adequate treatment consists of full continuous replacement of the faecal losses of water, NaCl, and KCl. This should be given intravenously in the early neonatal period; later a solution can be taken orally with meals. The dose has to be adjusted to maintain normal serum electrolyte concentrations, normal blood pH, and some chloriduria. This therapy prevents the renal lesions and the retarded growth and psychomotor development which were seen in the children who were diagnosed late and in those who received inadequate replacement therapy. The watery diarrhoea persists and increases slightly with age, though patients learn to live with their disease and to make an adequate social adjustment.


Persistent ductus arteriosus complicating the respiratory distress syndrome. Persistent ductus arteriosus (PDA) complicated the clinical course in 45 (15%) of 299 babies with the respiratory distress syndrome (RDS) presenting over a 3-year period. The incidence of PDA complicating RDS rose with decreasing birthweight and was highest in babies with severe RDS as judged by the use of assisted ventilation. In babies with a birthweight of less than 1500 g, PDA occurred as a complication of RDS in 25% of cases. In babies who recieved intermittent positive pressure ventilation (IPPV) for management of RDS, the incidence of PDA was 35%. Overall mortality for babies with RDS was 17%; when PDA occurred as a complication mortality was 31%. In survivors, spontaneous closure of the PDA occurred in all except one infant. The development of signs of PDA in 19 babies either necessitated a renewal of IPPV or prevented "weaning" from IPPV or from continuous positive airways pressure. 9 (47%) of these babies died, 8 of them after the first week of life. The frequency of PDA complicating RDS and the relatively high mortality in this conservatively-treated group of babies is emphasized. The incidence reported here is likely to increase with the increased survival of very low birthweight infants with severe RDS. The high incidence of late deaths in babies who develop signs of PDA associated with an inability to wean from assisted ventilation suggests that early surgical ligation of the PDA in these babies should be considered. The results of a conservative approach to management of these infants are presented.


Heavy meromyosin binding microfilaments in epidermal cells during wound healing. Studies have been conducted which demonstrate that heavy meromyosin binds to cortically positioned microfilaments in migrating epidermal cells during early stages of wound healing. This finding demonstrates the presence of actin within these nonmuscle cells and may suggest a role for this contractile protein during epidermal cell migration.


Neonatal and infantile hypoglycemia due to insulin excess: new aspects of diagnosis and surgical management. Persistent hypoglycemia in the neonate and young infant usually results from inappropriate, excessive secretion of insulin, or a deficiency of one of the hepatic gluco-regulatory enzymes. Hypoglycemia due to hyperinsulinism, whether associated with nesidioblastosis, islet cell hyperplasia, adenoma or normal islets, may have devastating consequences in this age group and demands recognition and effective treatment. Medical management consisting primarily of frequent feeding, the intravenous infusion of glucose and the administration of glucagon, glucocorticoids, epinephrine, and diazoxide is often ineffective and may be punctuated by repeated episodes of hypoglycemia, convulsions, and central nervous system damage. Although subtotal-total pancreatectomy is effective in restoring blood sugar to normal, almost half of the reported patients are mentally retarded. This may be due in part to unwarranted delays in performing pancreatectomy. Experience with 6 patients undergoing subtotal--total pancreatectomy for intractable hypoglycemia supports the contention that this procedure is effective. A euglycemic state was restored in all 6 patients and there was no evidence of residual central nervous system damage. The spleen should be preserved in view of its importance in maintaining normal immunodefense mechanisms.


The omentum: an account of its use in the reconstruction of the chest wall. Ten patients with lesions of the chest wall amenable to surgical therapy were reconstructed by a transposition flap of the greater omentum. Eight of these patients had been previously treated for cancer of the female breast by mastectomy and irradiation or by irradiation alone (in one instance). Of these 8, 6 had progressive ulceration of the chest wall consistent with radiation necrosis and three had residual carcinoma within the ulcer. One patient had melanoma of the chest wall still persistent after surgical resection and irradiation. Another had epidermoid carcinoma, whereas two sought breast reconstruction after successful mastectomy for cancer. In five patients the omentum was transposed directly on the pleura and lung or chest wall. In three patients prolene mesh was interposed to stabilize the chest wall. In two patients the defect attendant upon a Halsted mastectomy was ameliorated by a one-stage reconstruction using transposed omentum to cover a silastic gel prosthesis and to support an overlying skin graft. In three patients there were mild transient symptoms of gastric outlet obstruction postoperatively. In one patient delayed healing occurred because of partial separation of the omentum from the underlying irradiated pleura and in another there was partial loss of skin graft and omentum due to hematoma. A closed wound was achieved in all cases without infection.


Selectivity in the management of hepatic trauma. Retrospective review of 178 consecutive patients who sustained hepatic injuries confirms that selective application of hepatic artery ligation is an efficient means of definitive hemostasis. Only two of 20 immediate deaths resulted from hepatic parenchymal hemorrhage. Over-all mortality (20%) was not significantly increased where hepatic artery ligation was used. Sepsis was the most frequent complication after severe hepatic trauma.


Hypertonic mannitol in the therapy of the acute respiratory distress syndrome. Increased pulmonary artery pressure, an increase in pulmonary vascular resistance and an increase in physiologic dead space are consistent findings in patients with post-traumatic respiratory distress. Since mannitol has been shown to decrease renal vascular resistance following trauma, the effect of a bolus injection of 100 ml of 25% solution of this drug on pulmonary hemodynamics and physiologic dead space was investigated in 11 patients who had suffered multiple trauma. Five minutes after the injection, pulmonary vascular resistance fell (p less than .01), cardiac index increased (p less than .001) and physiologic dead space decreased (p less than .05). In contrast, the administration of 40 mg of furosemide produced no significant change in any of these parameters. Mannitol rapidly equilibrates in the extracellular space and exerts an osmotic effect across cell membranes. We postulate that the beneficial response to mannitol on the pulmonary vascular resistance and the improved perfusion of ventilated regions of the lung is due to a reduction in cell swelling and is not explainable by its diuretic effect. Improvement in the distribution of perfusion of pulmonary blood flow by mannitol may be a useful aid in the treatment of the post-traumatic form of the respiratory distress syndrome.


Incidence and significance of intra-operative bacterial cultures during abdominal aortic aneurysmectomy. Eighty patients undergoing abdominal aortic aneurysmectomy were studied to identify sources of potential graft sepsis. All but one patient received perioperative antibiotics. Samples obtained from aneurysm contents in 78 and bowel bag fluid in 45 were cultured for organisms. Twelve of 78 (15%) aneurysm cultures and five of 45 (11%) intestinal bag cultures yielded bacterial growth. Sixteen patients had positive cultures from either source and one from both, an overall incidence of 20%. Forty-four patients had asymptomatic aneurysms, 23 had symptomatic aneurysms, and 13 had ruptured aneurysms. A significantly greater frequency of bacterial growth occurred from ruptured than from non-ruptured aneurysms (p less than 0.05). Two patients (2.5%) developed graft sepsis. Comparing survivors followed a minimum of 6 months in the positive and negative culture groups, the late graft sepsis rate was 10% and 2% respectively. Two heretofore not widely recognized sources for late graft sepsis were identified: aneurysmal contents and intestinal bag fluid. Reasons for difference between potential graft sepsis incidence of 20% and actual incidence of 2.5% may include antibiotic therapy, host resistance, or other unidentified variables. Routine culture of aneurysm and intestinal bag contents is recommended. Upon identifying bacterial growth from such sources, organism-specific antibiotics are required.


Intraoperative antibiotic wound lavage: an attempt to eliminate postoperative infection in arterial and clean general surgical procedures. Intraoperative antibiotic wound lavage has been used in all arterial reconstructive procedures for the past 7 years and reduced the incidence of early and late postoperative infections from 1.5% in 400 operations prior to 1969 to 0.23% (one post-hospital) in 434 patients operated since that date. In 226 consecutive clean major general surgical procedures since June 1971 there has been no early or late wound infections following intraoperative antibiotic wound lavage in contrast to an infection rate of 1.5% in 185 operations prior to that date. A double blind study of 200 patients undergoing operations for varicose veins was carried out as follows: The wounds of alternate patients were irrigated either with normal saline or with antibiotic solution. There were no gross (grade II) postoperative wound infections. Minor skin changes were noted in 93 of 632 incisions in the saline group and only 49 of 608 incisions irrigated with antibiotic solution (P less than 0.001). In clean operations without antibiotic wound lavage there was a 0.73% rate of in-hospital wound infections in 685 patients in contrast to a zero rate in 760 patients wherein intraoperative wound lavage was carried out throughout the operative procedure.


Perforated duodenal ulcer managed by proximal gastric vagotomy and suture plication. Twenty-one patients with acute perforated duodenal ulcer were managed by proximal gastric vagotomy without drainage and simple closure of the perforation reinforced with an omental patch. There was no operative mortality. No recurrent duodenal ulcers have developed. All patients have achieved a good to excellent clinical result from their operation. Dumping, diarrhea, and reflux gastritis have not developed. Follow-up studies extend to three and one-half years. Proximal gastric vagotomy with simple closure is safe, effective management for the patient with an acute perforated duodenal ulcer. This operation is a satisfactory compromise between simple closure alone which does not protect against recurrent ulcer and definitive ulcer operations which may subject patients who would not have further ulcer symptoms to the unnecessary risk of increased mortality, morbidity, and postgastrectomy disorders.


A technique to narrow the lumen of a Waterston anastomosis. A technique is described for narrowing the Waterston anastomosis by placing a horizontal mattress suture buttressed with felt pledgets through the aortic wall at the cephalad side of the anastomosis. This maneuver produces a slight but safe narrowing of the anastomotic lumen.


Lung preservation techniques.

Lung preservation techniques. Some of the barriers to successful lung transplantation include the lack of acceptable methods for ischemic protection and the  absence of reliable systems for preservation. The lung response to 60 minutes of warm ischemia basically consists of alveolar-capillary edema and disruption, mitochondria swelling, interstitial hemorrhage, significantly depressed pulmonary function, elevation of pulmonary vascular resistance, and considerable drop in levels of glucose, phospholipids, and adenosine triphosphate. The tolerance to warm ischemia increases to several hours with the use of different systems of ventilatory assistance with or without positive end-expiratory pressure. Several methods of preservation have been attempted: hypothermia, hyperbaria, and hypothermic pulsatile or nonpulsatile perfusion. Hypothermic pulsatile perfusion appears to offer longer periods of protection than the other methods. Longer periods of ischemia and extended preservation may be made possible by advances in the use of drug protection during warm ischemia and the utilization of intracellular colloid or noncolloid solutions for hypothermic storage or hypothermic pulsatile perfusion.


Sequential hospitalwide outbreaks of resistant Serratia and Klebsiella infections. Late in 1973 at the Nashville Veterans Administration Hospital, an intrusion of Serratia marcescens infections that were resistant to gentamicin sulfate and other antimicrobial agents occurred. This abated somewhat, only to be superseded by another wave of multiply-resistant infections due to Klebsiella pneumoniae beginning in the spring of 1974. Approximately 400 patients had substantial infections with these organisms during the 2 1/4 year period, imposing considerable morbidity and mortality. Due to the serious and lasting impact that these events imposed on patient care in our hospital, we sought explanations for the sequential infectious outbreaks. Both may have arisen because of the same persisting pressures favoring prevalence of multidrug-resistant bacteria. Indirect evidence including the sequential order of the outbreaks, similarity of antibiotograms, transferable multiple drug resistance from Serratia to Klebsiella, and possession of approximately equal molecular weight plasmids supported the notion that the two outbreaks were causally related.


Somatostatin. Its possible role in carbohydrate homeostasis and the treatment of diabetes mellitus. Somatostatin, a peptide inhibitor of growth hormone release originally isolated from the hypothalamus, is also present in D cells of pancreatic islets. Its ability to inhibit the secretion of insulin and glucagon suggests that it may be a local regulator of pancreatic A- and B-cell function. Studies using synthetic somatostatin have provided evidence that glucagon is a physiologically important hormone that exacerbates the consequences of insulin deficiency in human diabetes mellitus. The ability of somatostatin to diminish both fasting and post-prandial hyperglycemia and to forestall the development of ketoacidosis after withdrawal of insulin in insulin-dependent diabetics suggests a potential therapeutic use of this agent in diabetes. Presently, however, its short half-life and diverse actions preclude such use and have prompted the search for more specific and longer-acting analogs.


Psychiatric disorder in children with speech and language retardation. A critical review. This article critically reviews the literature concerning psychiatric disorder in children with speech and language retardation. The data indicate that speech- and language-disordered children are at risk for psychiatric disorder, that there is some correlation between the presence of psychiatric disorder and the type of speech and language disturbance, and that there is a likely correlation between certain types of speech and language problems and the type of psychiatric difficulty. Firm conclusions in this area are hampered by many methodological difficulties. Finally, a review of the nature of the association between psychiatric disorder and speech and language retardation reveals that except in rare instances psychiatric disorder does not cause speech and language retardation, and that in most cases psychiatric disorder is indirectly caused by speech and language retardation.


Children of psychotic mothers. Performance of 3-year-old children on tests of attention. Children of mentally ill mothers (N = 21), believed to be at risk for the subsequent development of psychopathology (high-risk group) were compared with children of well mothers (N = 21)(low-risk group) on the Embedded Figures Test (EFT) and the Peabody Picture Vocabulary Test (PPVT). Results indicated that children in the high-risk group perform less well than low-risk children on the EFT (particularly on the more difficult stimuli), but do not differ from low-risk children on the PPVT. These results are interpreted as showing greater impairment of attention among children of mentally ill mothers than among children of well mothers.


Mycobacterium bovis infection in baboons (Papio papio). Two tuberculin-positive baboons in a primate colony were found to have grossly visible tuberculous lesions in the liver, spleen, lung, and  mediastinal lymph nodes on necropsy. Results of histopathologic examination of the tissues showed granulomas with Langhans giant cells. An acid-fast organism was isolated from tissues of each baboon; the isolates were identified as Mycobacterium bovis by being negative for niacin production and nitrate reduction and by their susceptibility to thiophen-2-carbosylic acid hydrazide and to 5% glycerol.


Pneumoperitoneum complicating mechanical ventilator therapy. Subdiaphragmatic air arouses the clinical suspicion of a perforated intra-abdominal viscus. In patients with respiratory failure requiring mechanical ventilation, the retroperitoneal dissection of air from the mediastinum may give rise to radiologic evidence of subdiaphragmatic emphysema. The present report describes four patients with this syndrome. In three of them, a perforated gastric or duodenal ulcer was initially suspected. None of these three patients underwent surgery. Autopsy examinations in two patients revealed extraperitoneal subdiaphragmatic emphysema with secondary rupture into the free peritoneal cavity. The third patient had an uneventful recovery and was discharged from the hospital. In a fourth patient, signs of peritonitis prompted an exploratory laparotomy. No perforation of an intraperitoneal viscus was identified. Upper gastrointestinal contrast roentgenography and peritoneal lavage may help determine the etiology of subdiaphragmatic air in patients undergoing therapy with a mechanical ventilator.


[Dissolution of polyhedra of the nuclear polyhedrosis virus of the leatherjacket Tipula paludosa MEIG. Ultrastructural study of the virion (author's transl)]. The inclusion bodies of the nuclear polyhedrosis virus of T. paludosa MEIG. were purified by sucrose density gradients, their morphology described using scanning electron microscopy, and the conditions for their solubilization investigated. These inclusions known to be unusually resistant to dissolution, were successfully dissolved in conditions maintaining the integrety of the virus particles by using a 0.125 M sodium thioglycolate + 0.125 M sodium bicarbonate solution, pH 10.5. The virions extracted from the inclusions were purified by sucrose density gradients and their fine structure studied in electron microscopy. In PTA-stained preparations the virion is rod-shaped measuring 230--240 nm in length and 100 to 110 nm in diameter. It consists of an inner nucleocapsid surrounded by a loose envelope. Partially degraded virions reveal small subunits arranged in a regular helix (pitch of approximately 40 A) at the surface fo the capsid. These subunits likely represent the virus capsomers. A flexuous ropelike structure protruding at one end of the capsid is sometimes observed in partially degraded virions stained with uranyl acetate. In thin sections of infected hemocytes, the virions occluded on polyhedra or free in the nucleoplasm exhibit the same morphology although their diameter does not exceed 80--85 nm. The muclear polyhedrosis virus of T. paludosa meets all the criteria for incorporation into the Family Baculoviridae.


[Study of the myoid cells of the thymus by the immunofluorescent method]. Muscular proteins were found in the cytoplasm of myoid cells of the thymus in all investigated species (chicken, mouse, rat, guinea pig, rabbit, cattle, human) by the method of immunofluorescence using the human serum containing antibodies to antigens of muscular fibres of striated muscles and fluorescent antibodies to human immunoglobulins. Under study were the characteristic features of the content and localization of the myoid antigen in the sarcolytes of the thymus of animals and man. The obtained data show a permanent presence of muscular antigens in the internal medium of the thymus and speak in favour of their possible participation, in addition to other heteroorganic antigens of the thymus, in the formation of natural immunological tolerance to the proper antigens of the organism in the process of differentiation of thymocytes.


[Use of methods of spectral-correlation analysis for studying the temporal and spatial organization of tissues]. Tissues within the organism represent multidimensional systems organized in time and space and having statistical dispersion in each parameter. Changes in its state may have a character of a monotonous trend and be periodical (the matter of chronobiology). The methods for detection of latent periodicities, developed in chronobiology, are applied for estimation of not only temporary but also spacial characteristics of the object. One of such methods is the calculation of the power spectrum of the autocorrelative function. Examples of its application are given.


[In vitro action of mepartricin in combination with chlortetracycline]. The microbiological activity of a mepartricin + chlortetracycline hydrochloride association was evaluated on the principal agents causing cervico-vaginal infections. Beside confirming the antimycotic and antiprotozoal efficacy of mepartricin, is was possible to demonstrate an absence of antagonism with chlortetracycline. On the other hand, in some cases this antibiotic could potentiate the antitrichomonas effect of mepartricin.


[Interaction of cholera vibrios and escherichiae with the intestinal epithelium (histologic and electron microscopic study)]. Histological and electron-microscopic investigations were carried out of ligated small intestinal loops of 147 rabbits within 24 hours after challenge with cholera vibrios El Tor, different enterotoxigenic E. coli, choleragen and E. coli enterotoxins. These ogranisms attached themselves to enterocytes and multiplied on the surface of the unaltered intestinal epithelium. Thereafter, a greatly pronounced secretion of enterocytes, rather than inflammation, developed, like after the exposure to sterile enterotoxins of E. coli and choleragen, the lumen of isolated rabbit gut loops was overfilled with great amount of fluid discharged. At later period dystrophic alterations in enterocytes also appeared. They were partly associated with excessive secretion, but the severest of them (including even necrotic foci) were caused by the compression of the isolated gut loops epithelium with fluid. The first and obligatory stage of pathogenesis of cholera and cholera-like escherichioses was apparently the attachment of the causative agent to enterocytes and its multiplication on the intestinal epithelium surface, followed by hypersecretion induced by enterotoxin effect.


[Experimental study of bacteremia and its role in the pathogenesis of dysentery]. In experiments on white mice pathophysiological, bacteriological, histological and immunofluorescent methods of investigation were used; it was shown that Sonne dysentery bacteria were capable during a short period of time to penetrate into the blood from the lumen of the stomach and the small intestine and moreover to deposit in the cells of the mucosa of the said organs. Into the large intestine the pathogen penetrates from the above situated departments of the intestine, which was most often observed in impairment of the evacuatory function of the stomach; moreover, the possibility of elimination of Sonne Shigella, as well as products of their desintegration, by the large intestine wall was shown. Bacteriemia is a short-term phenomenon and could be identified at early periods following infection, which may account for the fact of rare identification of Shigella in the blood of patients with dysentery.


[Methodologic basis for studying the morphology of infectious processes]. The present survey emphasizes the need for further study of pathological anatomy of infectious diseases. Particular attention should be given to the dynamics of development and causes of morphological alterations. Such investigations aimed at shedding a new light on the pathogenesis of infectious diseases, should elucidate biological properties of the causative agent and special features of reactive processes occuring in the diseased organism. They must be multi-disciplinary in character and include the efforts of physicians, microbiologists and other experts. Some investigations are critically surveyed, some methodological problems are discussed.


[Role of increased vascular permeability in the formation of dimorphic amyloid in mouse myocardium]. Electron-microscopic investigation carried out following the intravenous administration of ferritin revealed an increase in permeability of the myocardium capillary wall in mice in experimental casein amyloidosis. Additionally, a complex electron-microscopic, immunohistochemical and histological investigation of the development of amyloidosis in the myocardium of mice was conducted. It was established that deposits of typical amyloid in the myocardium of mice consisted of two ultrastructural components--granular material and fibrils. It was shown that formation of amyloid with characteristic tinctorial properties was preceded by depositions of specific antigen fibrils of granular ultrastructure.


[Non-skeletal forms of fluorosis].

[Non-skeletal forms of fluorosis]. Concepts of nonskeletal forms of fluorosis are set forth in the light of the author's own investigations and reports in the available literature. Descriptions of pathology of the central nervous system, skeletal musculature, stomach, liver, kidney, cardiovascular system, retina, and the skin are presented. The evidences obtained indicate that disturbances in soft tissues in chronic intoxication with fluorine develop early, usually long before the onset of typical changes in teeth and skeletal bones; these changes characterize the preskeletal phase of fluorosis.


Johann Baptist Schmidt. A pioneer in the history of aphasia. Wernicke is usually credited with the first significant description of comprehension disorders in aphasia. Before Wernicke, however, others had reported patients with impaired comprehension. This communication deals with one of those pioneer papers, that written by Schmidt, an obstetrician, in 1871. It concerns a 25-year-old woman who developed sudden language difficulty ten days after delivery. She had trouble understanding oral or written language. Through careful examination, Schmidt showed that she was neither deaf nor psychotic. He concludes his paper with a prediction of the area of the brain he suspected to be involved. Schmidt's paper represents an early, noteworthy effort to clarify the relations between brain and behavior.


Spinal cord injury. The role of vascular damage in the pathogenesis of central hemorrhagic necrosis. We postulated that damage to the endothelial lining of the spinal cord vasculature is a major factor in the pathogenesis of the characteristic lesion of the spinal cord (progressive, central, hemorrhage necrosis) that occurs after acute trauma. Endothelial damage may occur as a result of primary injury to the vessels or after arterial spasm. This damageresults in deposition of platelets and formation of thrombi on the exposed subendothelial tissues and embolization of such thrombi to smaller vessels of the spinal cord parenchyma.


The conjunctival sickling sign, hemoglobin S, and irreversibly sickled erythrocytes. Sixty-five patients with hemoglobins AS, SC, and SS were investigated in a masked fashion. We observed a statistically significant positive correlation between the severity of conjunctival sickling signs and the counts of irreversibly sickled cells in each hemoglobinopathy group. We also observed a statistically significant positive correlation between the severity of the conjunctival vasculopathy and the percentage of sickle hemoglobin in the total group of patients with hemoglobins AS, SC, and SS.


Staphylococcal blepharitis.

Staphylococcal blepharitis. A detailed discussion of various aspects of staphylococcal blepharitis is presented. These include epidemiology, pathogenesis and immunity, microbiologic characteristics, clinical signs, associated systemic diseases, differential diagnosis, and treatment.


Adjustable rectus muscle recession surgery. A follow-up study. Fifty-six patients underwent an adjustable rectus muscle recession procedure. This procedure permits the surgeon to enhance or diminish the amount of muscle recession on the evening after surgery or the first postoperative day if cover-testing indicates an inappropriate amount of undercorrection or overcorrection. The adjustable rectus muscle recession technique seems to be a practical and effective means to change the strabismic deviation postoperatively. The procedure requires patient cooperation and is most suitable for patients age 15 years and older. The procedure has been effective in altering the angle of deviation, and this alteration has been stable during the follow-up period in most cases. In this initial series, the reoperation rate was low, postoperative alignment was excellent, and complications were minimal.


Regeneration of nasal skeletal structures after subperiosteal and subperichondrial resection. The degree of regeneration of nasal structures after surgical resection was evaluated in six mongrel dogs that underwent selective resection of the nasal bones and upper lateral cartilages. Preservation of the periosteal and periochondrial flaps was accomplished during the resection. In several cases, different tissues were interposed between the flaps before their closure. The dogs were killed at two-and eight-month intervals after the original resections. No evidence of new cartilage regeneration was found on microscopic evaluation in the region of the resected upper lateral cartilages. Minimal new bone foci were noted at the edge of the resected nasal bones in three of the cases. The findings failed to support any significant degree of nasal structure regeneration after resection.


The vessels of the rabbit trachea and ischemia caused by cuff pressure. By intraarterial injection of silicone rubber we visualized the main feeding vessels of the rabbit trachea. They originate from the right subclavian artery and supply bilateral longitudinal tracheo-esophageal arteries. These lie in the groove between the trachea and the esophagus, giving off numerous segmental branches to both of these organs. In the trachea these pass submucosally between the tracheal cartilages, feeding a rich capillary network within the mucosa. The membranous part of the trachea is extremely well supplied with vessels, originating in arteries running longitudinally in the space between the trachea and the esophagus. The mucosa contains many sinusoidal ectasias, forming an almost cavernous arrangement in the tracheal wall. It is probable that these vessels are of great importance for the conditioning of inhaled air. Experimental studies on intubated animals have shown that a large-volume tracheal tube cuff, inflated to a pressure of 50 mm Hg, decreases or completely hinders capillary silicone rubber perfusion of the tracheal mucosa.


Recurrent basal cell carcinoma of the facial region -- a clinico-pathological challenge. The observation that the majority of patients with basal cell carcinomas of the face presenting for surgical treatment did previously have radiotherapy or have undergone inadequate excision due to cosmetic considerations of the surgeon, induced us to review our own case material. According to this reassessment, a concept of radical removal was developed which took particular account to the direction of growth of basal cell carcinoma into the depth. Of considerable importance seems to be the unequivocal marking of the excised material prior to its histological work up and the additional removal of sub-focal specimens for separate histological examination.


[Today's status of facial cleft surgery (author's transl)]. Cleft lips, jaws and palates numerically represent the major part of facial clefts. These abnormalities are evolutionary and they are characterized by a continually recurring anatomic pattern. The necessity of reconditioning form and function implies the application of surgical therapy. Regarding the one-sided closure or suturing of cleft lips, priority is nowadays given to the angular-type incisions, whereas the linear-type incision is still reserved for the double-sided cheiloschisis. In the following, there will be indicated the approved techniques and methods of suturing the cleft palate and a new method will be discussed related to the reciprocal Z-type plastic operation. In the case of speech-improving operations, excellent results can be achieved by implanting autologous costal cartilages into the posterior wall of the pharynx. Apart from a brief mutioning of transverse and diagonal facial clefts, the provision of nasal clefts with composite grafts is finally recommented.


Current prospects for renal transplantation in veterinary practice. In dogs, the surgical techniques and other technical considerations for the transplantation of most tissues and organs in the body are well established. The last remaining obstacle to uniformly safe and successful organ transplantation is the immune response to foreign tissue antigen and our present inability to completely suppress this response in a specific and safe manner. Immunosuppressive techniques currently available are largely non-specific and unfortunately cause many potentially fatal side effects. As a result graft recipients must be constantly monitored so that enough immunosuppressive treatment is given to prevent rejection but not so much that the recipient develops life threatening complications. The enormous cost and the services necessary to provide this attention in view of the relatively poor survival rates of tissue and organ grafts in dogs will continue to prevent organ transplantation becoming a reality in veterinary practice. Hopefully future advances in tissue-typing and the induction of specific immunological adaption in dogs by ensuring consistently safe and successful transplantation will ead to minimal postoperative attention.


[Basic techniques of plastic surgical repair in defects of the skull and face (author's transl)]. Ommitting historical datas, ancient theories and old-fashioned surgical techniques, the author gives a summary of current plastic surgery in the head and neck. After a review of aesthetic charateristics of the face, basic principles of surgical skin closure and different forms of local and distant flaps are discussed. Emphasis in placed on tissue transplanation. The biological problems in transplanatation of skin, subcutaneous and supporting tissues, using autografts, allografts and xenografts are mentioned in addition to several methods of concervation. The clinical importance of various autogenous supports used for transplantation to the skull and face is stressed. Concerning foreign implants, the author discusses the problem of the so-called foreign-body sarcoma and the foreign-body reaction to synthetic and metallic implants. Indications for using synthetic implants are mentioned. Microsurgical techniques seem to be important for further development of facial plastic surgery.


[Special methods of reconstructive surgery in the facial region (author's transl)]. Extensive knowledge in reconstructive surgery of the face and head area is the basis for successful functional reconstructive surgery after injuries and tumor resection. Particularly in the tumor therapy reconstructive surgery is an essential curative element, because lacking this knowledge radical tumor surgery will not always be possible. The purpose of this paper is to summarize and discuss the proved and fundamental methods out of the immense number of reconstructive surgical methods published. For six regions of the face and head (forehead, nose, orbit, cheek, lip and auricle) the most important and basic operative procedures are reviewed. In some cases of surgical techniques the historical development was investigated, because the origin of these methods was not always clearly enough known or reported.


Prevention of Salmonella typhimurium infection inpoultry by pretreatment of chickens and poults with intestinal extracts. Day-old chickens or turkey poults when pretreated with an oral dose of intestinal fluid froma healthy adult bird, were considerably more resistant to the subsequent establishment of Salmonella typhimurium in their intestinal tract than were non-treated chickens or turkey poults. Caecal fluid was more effective as a pretreatment than were washings taken from other parts of the gastro-intestinal tract of a healthy adult bird. This increased resistance of pretreated chickens or poults is thought to result from the rapid establishment of a conventional indigenous microflora which inhabits establishment and growth by the invading enteric pathogen.


Amyloidosis of the isletes of Langerhans in relation to diabetes mellitus and aging. The authors, after presenting a review of research work on amyloidosis of the islets of Langerhans,, provide the information obtained from their study of a random sample of 200 autopsies. Special attention was paid to the correlation between amyloidosis of the islets of Langerhans, diabetes mellitus and aging. The analysis of the sample would show there is a close relationship between the general process of aging and insular amyloid deposits; diabetes mellitus would then occur, increasing the amount of the above-mentioned deposits only in patients of a more advanced aged.


[Aesthetic surgery of the nose (author's transl)]. The world-wide acceptance of rhinoplastic corrections has let to the development of multiple surgical techniques in an attempt to improve the ultimate result. After short mentioning of the preoperative measurements the article contains a description of the current concepts of performing osteotomies, tip corrections and the treatment of saddle nose deformities. Surcical methods dealing with secondary deformities including free grafts are discussed. The second chapter is devoted to cosmetic corrections of the face including lid surgery and the so called face lift operation. The value of such procedures is weighed against dermabrasion and chemical face peel in the attempt to improve the appearance. In the thierd chapter the author mentions the newest development in facial nerve surgery in regard to free muscle transfer and nerve cross over operations.


Lymphocytes eluted from synovial tissue of juvenile rheumatoid arthritis patients. Synovial tissues from 11 patients with juvenile rheumatoid arthritis were investigated. The elution of lymphocytes was performed according to a procedure previously described for synovial tissue of adult rheumatoid arthritis patients (1). The T lymphocytes were pre dominant (mean: 71%) in all cell suspensions studied, whereas the average proportion of B lymphocytes was 4%. In addition, Fc-receptor-bearing lymphocytes were demonstrable (mean: 8%). Transformation of the lymphocytes was induced by the unspecific mitrogens phytohemagglutinin, pokeweed mitogen, and concanavallin A, whereas antigens such as ppd and candida albicans antigen were usually ineffective.


Antibody levels to enteric bacteria in juvenile rheumatoid arthritis. In order to determine the immunologic status and possible susceptibility to bacterial infection in children with juvenile rheumatoid arthritis (JRA), titer of hemagglutingating antibodies to E coli 055, E coli 086, common antigen, and Shigella polyvalent antigen were measured. Immunoglobulin G was the predominant antibody. IgA antibodies were found in higher titer in children with JRA. No significant differences were found between children with JRA do not have any deficit in antibody production to specific bacterial antigens, and any increased appearance of infection in these children is more probably due to deficiencies in cellular factors.


Immunohistochemical localization of prostaglandin E in rheumatoid synovial tissues. Synovial tissues removed at synovectomy from patients with active rheumatoid arthritis (RA) or osteoarthritis (OA) were examined for prostaglandin E (PGE) by immunohistochemical techniques using rabbit antisera specific for PGE. Marked increments of PGE were noted in RA synovia in comparison to OA, with staining concentrated in synovial lining cells, interstitial inflammatory cells, and endothelial cells of blood vessels. A correlation was noted between the degree of synovial lymphocytic infiltrate and the intensity of PGE staining. These studies provide initial cellular localization of PGE in such tissues.


An immunofluorescent method using Crithidia luciliae to detect antibodies to double-stranded DNA. The immunochemical specificity of the immunofluorescent Crithidia luciliae method for detection of antibodies to double-stranded DNA (dsDNA) was confirmed by demonstrating abolition of staining by DNase digestion and by absorption with dsDNA. This method was less sensitive than a Millipore filter method for detecting antibodies to DNA. It was positive only in subjects with systemic lupus erythematosus or drug-induced antinuclear factors. This technique appears suitable for study of the immunochemical characteristics fo antibodies to dsDNA.


Increased spontaneous activity of antibody-forming cells in the peripheral blood of patients with active SLE. Thirty-seven patients with criteria for systemic lupus erythematosus (SLE) and 18 normal controls were studied for their spontaneous background IgM antibody plaque-forming clell number to specific chemical haptens. Active SLE patients had significantly more plaque-forming cells in their peripheral blood to a total of five chemical determinants than did patients with inactive disease or controls. This increased number of plaque forming-cells correlated with depressed serum C3 levels by Spearman rank-order analysis. The finding of elevated numberof spontaneous IgM plaque-forming cells to defined chemical haptens supports the concept that active SLE demonstrates a generalized increase in B-cell activity toward a variety of antigens.


Renal localization of antiglobulins in glomerulonephritis and after renal transplantation. Localization of fluorescein-conjugated heat-aggregated IgG (FA IgG) was demonstrated by immunofluorescence in renal glomeruli of 16 of 69 patients with glomerulonephritis. FA IgG bound more frequently in kidney biopsies from patients with diffuse glomerulonephritis and depressed renal function, and localized selectively in glomeruli that contained heavy deposits of IgM, C3, and C4. The factors that caused FA IgG to bind were specifically reactive with the Fc piece of the IgG molecule and were resistant to 56 degrees C heat for 30 minutes. Localization of FA IgG in the kidney did not correlate with the presence of soluble immune complexes or detectable antiglobulin antibodies in the sera. Binding of FA IgG was also seen in glomeruli and arteries of 18 of 21 kidney allografts studied at the time of impending rejection. But the factors responsible for binding FA IgG in the allografts were heat labile and thus could have been C1q. Although the role of these "antiglobulins" in the immunobiology of glomerulonephritis remains unknown, the fact that they occurred mainly in patients with relatively severe glomerular injury suggests that they could play some part in promoting renal glomerular injury.


Macrophage migration inhibitory factor in rheumatoid pericarditis. The pericardial effusion in a case of rheumatoid pericarditis was studied to determine whether immune complexes and mediators of cellular immunity, represented by migration inhibitory factor (MIF), were present. MIF-like activity was detected in the pericardial fluid, but only traces of immune complexes were revealed by ultracentrifugation. The MIF-like activity was partially characterized by column fractionation and sugar inhibition tests. The role of lymphokines in the pathogenesis of this case of rheumatoid pericarditis is strongly suggested.


Pathology of skeletal muscle in mixed connective tissue disease. To characterize the pathology of muscle involvement in mixed connective tissue disease (MCTD), skeletal muscle biopsies from 13 patients with MCTD were examined by routine light microscopy, histochemistry, and direct immunofluorescence. The histologic and histochemical changes observed corresponded closely to changes seen in idiopathic polymyositis and the myopathy associated with systemic lupus erythematosus. Eight of 13 cases examined by direct immunofluorescence demonstrated immunoglobulin deposition either within normal appearing vessels, within normal fibers, around or on the sarcoplasmic membrane, or within the perimysial connective tissue. The histologic findings support Sharp's observation of the high incidence of focal inflammatory lesions in skeletal muscle biopsies of patients with MCTD. Immunoglobulin deposition in these muscle biopsies suggests an immunologic basis for the muscular symptomatology in MCTD.


[Effects of a new cardioselective beta-adrenergic blocker (atenolol) on airway resistance in chronic obstructive disease (author's transl)]. The effect of 4-(2-hydroxy-3-isopropylamino-propoxy)-phenyl acetamide (atenolol, ICI 66 082) (100 mg) on airway resistance (Rt), thoracic gas volume (IGV), pulse rate and blood pressure was tested as a double blind study in 20 patients with chronic obstructive airway disease in comparison to propranolol (80 mg) and placebo. The effect on pulse rate was equipotent, but when using propranolol the mean increase of Rt was larger and increased Rt-values (greater than or equal 1.5 cm H2O/l/sec) were observed more frequently than after atenolol application. These differences were significant for 1 h after application. The augmentation of IGV was significantly larger after propranolol than after atenolol. We conclude that atenolol, in comparison to propranolol, has a relative but no specific cardioselectivity.


[Influence of oxprenolol on the affect level in an exam situation. A follow-up study under double-blind conditions (author's transl)]. In a double-blind study on student nurses the curves of three affectivity components and the pulse rate under exam conditions were observed. One group had received 1-(o-allyloxy-phenoxy)-3-isopropylamino-propan-2-ol hydrochloride (oxprenolol, Trasicor and the other group a placebo. In the examination stress the affectivity component "aggression" was particularly obvious. With placebo the states and actions of aggression were more extreme than in the oxprenolol group. It appeared that the severe affectivity inclinations resulted in a reduction of examination performance. Under oxprenolol, in accordance with recently published results, there was no decrease in performance under exam conditions. Quite the opposite: as it seems to curb extreme affectivity inclinations the decreases in performance connected with them are often prevented.


[Tardive dyskinesia. Synthetic-critical review and case contribution]. The clinical features, etiology and treatment of tardive dyskinesia, a neurological syndrome observed during or after withdrawal of long term neuroleptic therapy, are discussed in reference to the literature records and to the contributions drawn out from 16 new cases.


Heparin-induced release of lipase activity in the human forearm: an immunological study. Low doses of heparin were injected into the brachial artery of three volunteers. The lipase activities in the deep vein of the same forearm, draining mainly muscle tissue, and in the artery were monitored over a 10-min period. Lipase activity, rapidly released by heparin in the deep vein, was immunologically similar to lipoprotein lipase (E.C. 3.1.1.3), i.e. (1) it did not react with antiserum against human post-heparin plasma hepatic lipase and (2) it was inhibited by an antiserum against bovine milk lipoprotein lipase, which cross reacts with human post-heparin plasma lipoprotein lipase. The evidence that human muscle contains lipoprotein lipase is discussed.


Praecordial ST segment elevation. New technique for continuous recording and analysis. The measurement of praecordial ST segment elevation after myocardial infarction is of value in assessing the natural history of ischaemic injury and the effectiveness of intervention. Hand analysis is, however, time consuming and inaccurate. A technique for continuous recording from 35 praecordial leads and subsequent computer analysis is presented, together with illustrative case studies. Changes in body posture and in heart rate are of importance in subsequent data interpretation.


Comparison of dobutamine and dopamine in treatment of severe heart failure. The haemodynamic effects of dobutamine, a new synthetic catecholamine, were studied in 12 patients with severe congestive heart failure and compared with those of dopamine in 10 clinically similar patients. Dobutamine produced a distinct increase in cardiac index, while lowering left ventricular end-diastolic pressure and leaving mean aortic pressure unchanged. Dopamine also significantly improved cardiac index, but at the expense of a greater increase in heart rate than occurred with dobutamine. Dopamine was ineffective in lowering left ventricular end-diastolic pressure, but increased mean aortic pressure. We conclude that dobutamine is an effective, positive inotropic agent in patients with severe congestive heart failure. Because it has comparatively little effect on heart rate and aortic pressure, both major determinants of myocardial oxygen consumption, it may be of special value in patients with the low output syndrome associated with coronary heart disease.


Comparison of lidoflazine and quindine in prophylactic treatment of arrhythmias. The efficacy of quinidine versus lidoflazine therapy was compared in the maintenance of sinus rhythm after electrical cardioversion for atrial flutter or fibrillation in a group of 35 patients. Both quinidine and lidoflazine were relatively ineffective in maintaining sinus rhythm after cardioversion. Lidoflazine was also used to prevent supraventricular and ventricular tachycardias in a miscellaneous group of patients; one of these with paroxysmal supraventricular tachycardia developed runs of venttricular tachycardia soon after starting lidoflazine. The trial was stopped after 4 patients died while receiving lidoflazine, on the suspicion that their deaths may have been related to drug-induced arrhythmias. The arrhythmogenic potential of lidoflazine when used in patients with supraventricular arrhythmias constrasts with reports of its apparent safety in large numbers of patients with angina pectoris.


Efficacy and tolerance of Flunixin (SCH 14714) in the treatment of postoperative pain, with observations on the methodology of postoperative pain studies. A new anti-inflammatory, antipyretic and analgesic drug 2(2'-methyl-3'-trifluoromethylanilino)-nicotinic acid (Flunixin, Sch 14714) was compared with aspirin and a placebo in a double-blind study of pain after four different types of operation. Sch 14714 proved to be superior to the two other drugs after herniorraphy and venous surgery of the leg. The frequency of adverse effects after this drug was, at most. 1.2% which did not differ from the side-effect rates of aspirin or placebo. The second and third days after operation yielded a very high rate of optimal pain relief scores resulting in poor discrimination. Thus cross-over studies seem to be superfluous in the study of pain-relieving drugs in the period following surgery. The patients' rather low demand of analgesic drugs indicated that more stringent enrollment criteria should be adhered to. It was also shown that radical venous surgery constituted a good model for pain studies.


Anaesthetic management of thoracotomy in the presence of chronic carbon dioxide retention. A patient suffering from chronic carbon dioxide retention with persistent pneumothorax, following spontaneous rupture of an emphysematous bulla, underwent thoracotomy. The surgical and anaesthetic management are reported.


Effect of X-irradiation on host-cell infiltration and growth of a murine fibrosarcoma. Whole body X-irradiation (400 rad) of C57BL mice, either before or after i.m. implantation of the syngeneic fibrosarcoma, FS6, influenced both the growth of the tumours and their cellular composition, particularly their macrophage content. Pre-irradiation resulted in slower initial growth of tumours, and a concomitant lack of host-cell infiltration, but when tumours began to grow at a rate parallel to controls infiltration by host cells was demonstrable. Similarly, irradiation of the tumour-bearing host resulted in a temporary cessation of growth, and a decrease in the macrophage content, which did not return to control levels for 2-3 weeks after irradiation. The significance of these results is discussed in relation to the possibility that infiltrating host cells, particularly macrophages, may stimulate the growth of this tumour.


Ultrastructure of cell surface abnormalities in neoplastic histiocytes. In an ultrastructural study by transmission and scanning electron microscopy of two cases of malignant histiocytosis and a case of leukaemic reticulum-cell sarcoma, unusual blisters, blebs and worm-like processes were detected on the cell surfaces. The blisters (containing clear fluid) appear to develop by a single-membrane-bound vacuole approaching the cell membrane, and acquiring another membrane on discharging from the cell. The blebs (containing cytoplasm) appear to correspond to the already described phenomenon of zeiosis. The term "vermipodia" is given to the worm-like processes. The underlying factors responsible for these phenomena is not clear, but the exocytosis of the clear blisters resembled that of leukaemic blasts exposed to the action of vinca alkaloids. As two of the cases were being treated with vincristine, it may be that a drug action is implicated. However, it is also possible that these changes may be the morphological expression of some of the changes in the cell surface membrane that occur in malignant transformation.


Colorectal cancer and beer drinking.

Colorectal cancer and beer drinking. Evidence is presented of a significant statistical association between beer drinking and colorectal cancer, particularly rectal cancer. This finding is based on correlations between consumption and cancer mortality and between changes in consumption and changes in cancer mortality for 47 states in the United States of America. Also various secular trends, an urban-rural gradient, socioeconomic gradients and sex ratios in the United States are shown to be generally consistent with a relationship between beer consumption and colorectal cancer, particularly rectal cancer. The limitations on drawing sound aetiological inferences from such data are acknowledged. In particular, several other variables are shown to be associated with both beer drinking and colorectal cancer. Also, a discussion of previous epidemiological studies is given, and it appears there is only a limited amount of direct evidence in humans to support the statistical demographic relationships.


Indoramin--an alpha adrenoreceptor antagonist for airway obstruction. Indoramin, an alpha adrenoreceptor antagonist, was given in tablet form, in addition to regular salbutamol by aerosol, to 30 patients with airway obstruction. Indoramin produced a small increase in peak flow rate, no change in forced expiratory volume in one second and no improvement in symptoms. Troublesome unwanted effects occurred in six patients.


Asthmatic pulmonary eosinophilia: a review of 65 cases. In a series of 65 patients with asthma with pulmonary eosinophilia 54 were adequately investigated for allergic aspergillosis and this was present in 32 (59%). Asthma with pulmonary eosinophilia was found to carry a relatively poor prognosis in terms of permanent symptoms, impairment of pulmonary function and residual radiographic abnormality. The prognosis was least favourable when allergic aspergillosis was associated with long-standing asthma. On the other hand there was a group of patients with asthma with pulmonary eosinophilia who had relatively little permanent disability. These were mainly women with asthma of recent onset, and in these evidence of allergy to Aspergillus fumigatus was less apparent. Those patients who received long-term daily corticosteroid therapy were less likely to develop further radiographic opacities than those given intermittent corticosteroid therapy. To prevent recurrent pulmonary infiltrates it is probably necessary to give prednisolone in a daily dosage of at least 10 mg for an indefinite period.


Urinary LDH isoenzyme 5 excretion in experimental pyelonephritis. Studies to determine the effect of kidney parenchymal infection upon urinary lactic dehydrogenase (ULDH) isoenzyme composition were performed in 12 female Sprague-Dawley rats on Day 0 and on Days 2, 5, and 10, after experimental inducement of Escherichia coli pyelonephritis. An additional group of 12 animals was subjected to similar experimental manipulations and served as sham controls. Repeated 12-h urine collections revealed lower urine osmolalities and significantly higher levels of ULDH 5 excretion in the experimental than in the sham operated animals (P less than 0-05). These differences persisted for the length of the experiment (10 days). Leucocyte excretion rates were also higher in the experimental than in the sham group, and a high correlation with ULDH 5 activity was demonstrated (r = 0-815). No other evidence that the two variables may be causally related was found.


Immunofluorescent patterns in the skin in Besnier's prurigo. The eczema asthma syndrome. The immunofluorescent patterns in the skin of eighteen patients with Besnier's prurigo were studied at different stages of eczematous lesions. The presence, distribution pattern, and numbers of immunoglobulin and complement-positive lymphocytes in twenty-nine biopsies are reported. In all cases IgE-positive lymphocytes were present in both clinically uninvolved and involved skin. IgG, IgM and IgE-positive lymphocytes showed a characteristic distribution pattern in the dermis. In the acute stages IgM deposition was prominent in the basement membrane zone and it is suggested that damage to the basement membrane results in diffusion of immunoglobulin and complement into the epidermis. These features were not present in a control group of normal skin and of other dermatoses.


Erysipelas and necrotizing fasciitis.

Erysipelas and necrotizing fasciitis. The clinical course of necrotizing fasciitis in 8 patients is compared with observations on 22 other patients with erysipelas. In necrotizing fasciitis the early erythematous areas turn into a dusky blue colour with later vesiculation and formation of bullae. An important finding is a non-pitting oedema extending outside the erythematous patches. The disease often progresses and involves further skin areas proximal to the initial ones. Gangrene tends to follow in multiple sites after the 1st week of illness. Group A streptococci in conjunction with widespread thrombosis and vascular necrosis of the involved skin are two major factors in the pathogenesis of the gangrene. Early debridement and excision of necrotic tissue in combination with large doses of penicillin and cloxacillin are confirmed as mandatory to remove toxaemia and inhibit further necrosis of the skin. In 3 of the 8 patients with necrotizing fasciitis the syndrome of disseminated intravascular coagulation complicated the course of the disease. A promising therapeutic result was seen in 2 further patients exhibiting alarming signs and symptoms of early necrotizing fasciitis; the combination of heparin, given intravenously in therapeutic doses guided by activated partial thromboplastin time studies, and of systemic antibiotics alleviated the symptoms, which vanished within 10 days of the start of treatment.


High-resolution nuclear magnetic resonance determination of transfer RNA tertiary base pairs in solution. 1. Species containing a small variable loop. Eight class I tRNA species have been purified to homogeneity and their proton nuclear magnetic resonance (NMR) spectra in the low-field region (-11 to -15 ppm) have been studied at 360 MHz. The low-field spectra contain only one low-field resonance from each base pair (the ring NH hydrogen bond) and hence directly monitor the number of long-lived secondary and tertiary base pairs in solution. The tRNA species were chosen on the basis of their sequence homology with yeast phenylalanine tRNA in the regions which form tertiary base pairs in the crystal structure of this tRNA. All of the spectra show 26 or 27 low-field resonances approximately 7 of which are derived from tertiary base pairs. These results are contrary to previous claims that the NMR spectra indicate the presence of resonances from secondary base pairs only, as well as more recent claims of only 1-3 tertiary resonances, but are in good agreement with the number of tertiary base pairs expected in solution based on the crystal structure. The tertiary base pair resonances are stable up to at least 46 degrees C. Removal of magnesium ions causes structural changes in the tRNA but does not result in the loss of any secondary or tertiary base pairs.


High-resolution nuclear magnetic resonance determination of transfer RNA tertiary base pairs in solution. 2. Species containing a large variable loop. The number of base pairs in the solution structure of several class III D3VN tRNA species from E. coli has been determined by analyzing the number of low-field (-15 to -11 ppm) proton resonances in their nuclear magnetic resonance spectra at 360 MHz. Contrary to previous reports indicating the absence of tertiary resonances, all the spectra exhibit the expected number of secondary base pair resonances plus approximately ten extra resonances derived from tertiary base pairs in the three-dimensional folding of these molecules. The possible origins of some of these tertiary resonances are discussed; none of the spectra exhibits the characteristic resonance of the 8-14 tertiary base pair seen in class I D4V5 tRNA spectra.


Modification-deficient transfer ribonucleic acids from relaxed control Escherichia coli: structures of the major undermodified phenylalanine and leucine transfer RNAs produced during leucine starvation. The structures of the major, chromatographically unique phenylalanine and leucine tRNAs produced during leucine starvation of a relaxed control (rel-) mutant of E. coli have been determined. The results demonstrate that the unique species are modification-deficient forms of the major, normally occurring isoacceptor species. The unique tRNAphe differs from the fully modified species at nucleotide positions 16, 37, 39, 47, and 55 from the 5' terminus. The unique species contains uridine (U) in place of dihydrouridine-16 (D16), isopentenyladenosine in place of 2-thiomethyl-N6-(delta2-isopentenyl)adenosine-37, a mixture of U and pseudouridine (psi) in position 39, a mixture of U and 3-(3-carboxypropyl)uridine at position 47, and a mixture of U and psi at position 55. The chromatographically normal isoacceptor from amino acid starved cells is deficient in D16 and psi55, indicating that that species is a mixture of mature and undermodified tRNAs. The unique tRNALeu isoacceptor consists of two subspecies which are undermodified forms of the major, normally occurring isoacceptor, tRNALeuI. Both unique subspecies lack the D and psi residues which occur at positions 16 and 39 from the 5' terminus; one subspecies also lacks D17. Compared with the tRNALeusI from wild-type strains of E. coli B and K12, both tRNALeuI from nonstarved cells and the unique, rel-tRNALeu are deficient in the modified guanosine which normally occurs adjacent to the anticodon and the pseudouridine in the GTpsiC sequence of the psi loop. Both the unique tRNAPhe and the unique tRNALeu lack dihydrouridine residues which occur in the 5' half of the D loop and pseudouridines which occur in the 3' half of the anticodon loop and adjoining stem. Taken together, these findings suggest that the same enzymes are responsible for the formation of these particular modified bases in both tRNAs. The results further suggest that several, perhaps most, of the tRNAs from cells cultured under conditions in which RNA and protein synthesis are uncoupled will be similarly deficient in dihydrouridine and pseudouridine and other minor nucleosides which occur less frequently. Because both modification-deficient rel-tRNAs have dihydrouridine at position 20 and pseudouridine in the psi loop (and at position 41 in the unique tRNALeu), the results support the view that there was multiple D-and psi-forming enzymes in E. coli, some of which may turn over rapidly or are selectively inactivated when protein synthesis is blocked. The results are discussed with a view toward understanding the structural basis for the altered biological activity of the unique tRNAPhe species and the order of events in the posttranscriptional modification of newly synthesized tRNA.


Interaction between the erythromycin and chloramphenicol binding sites on the Escherichica coli ribosome. The effects of chloramphenical on the binding kinetics of a fluorescein isothiocyanate derivative of 9(S)-erythromycylamine with 70S and 50S ribosomes have been studied by direct fluorimetric measurements. While chloramphenicol had little effect on the second-order 70S binding rate of the erythromycin analogue, it substantially reduced the dissociation rate of the fluorescent antibiotic-70S ribosome complex. This could be explained by simultaneous binding of both antibiotics to the 70S ribosome. The kinetic results suggest that chloramphenicol-saturated 70S particles bind the erythromycin analogue four times stronger and this was confirmed by direct binding studies. In additon, chloramphenicol causes a twofold increase in the intrinsic fluorescence of the 70S-bound analogue. This increase in fluorescence was used to study the kinetics of chloramphenicol binding to 70S  ribosomes containing the fluorescent derivative. The fluorescence change followed first-order kinetics, suggesting that chloramphenicol induces a conformational change in the 70S particle. This could explain both its effect on erythromycin binding and on the fluorescence of bound analogue. Less detailed results with the 50S particle indicate a qualitively similar picture of erythromycin-chloramphenicol interactions.


Heterogeneity of the kinetoplast DNA molecules of Trypanosoma cruzi. Kinetoplast DNA (kDNA) of the culture form of Trypanosoma cruzi is cleaved by restriction endonucleases (HpaII, HindII, EcoRI, and HaeIII). The analysis of the cleavage patterns proves that the minicircles (free circulargenome units) are heterogeneous in base sequences. The same results are obtained with the complex kDNA network which is composed of the association of minicircles and linear molecules. Kinetic studies of the renaturation of kDNA previously cleaved by HpaII into fragments of the genome unit size show at least two populations of molecules. About 75% of these molecules correspond to the fast renaturing population having the molecular complexity of the minicircles. The molecules of the slow renaturing population have a much higher molecular complexity than the minicircles and do not seem to be related to the majority of the long linear molecules.


The translocation of Ca2+ across phospholipid bilayers induced by a synthetic neutral Ca2+ -ionophore. The effect of a neutral synthetic Ca2+ -ligand, which induces selective Ca2+ transport in electrodialysis experiments in bulk membranes, on the Ca2+ permeability of phospholipid bilayers has been investigated. The ligand is able to promote the transport of Ca2+ across synthetic phospholipid bilayers and can therefore be classified as a Ca2+ -ionophore. Its activity is enhanced by the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). The efficiency of the neutral carrier-mediated Ca2+ transport is rather low as compared with that of the charged Ca2+ -ionophore X537A. The Ca2+ selectivity of the nuetral ionophore is decreased by its incorporation in the low dielectric ambient of the phospholipid bilayer.


Conversion of bacteriophage G4 single-stranded viral DNA to double-stranded replicative form in dna mutants of Escherichia coli. Host functions involved in synthesis of parental replicative form of bacteriophage G4 were investigated using various replication mutants of Escheria coli. In dna+ bacteria, conversion of single-stranded viral DNA to replicative form DNA was insensitive to 200 microng/ml of rifampicin or 25 microng/ml of chloramphenicol. At high temperature, synthesis of parental replicative form was unaffected in mutants thermosensitive for dnaA, dnaB, dnaC(D), dnaE or dnaH. In dnaG or dnaZ mutants, however, parental replicative from DNA synthesis was clearly thermosensitive at 43 degrees C. Although the host rep product was essential for viral multiplication, the conversion of single stranded to replicative form was independent of the rep function.


[Comparative study of bacterial agmatinase inhibition by derivatives of putrescine and aliphatic monoamines]. Aliphatic monoamines and some putrescine derivatives (10(-3) M) are found to inhibit agmatinase from Proteus vulgaris. Constants and the type of inhibition are determined. Investigation of the temperature effect on the inhibition has revealed an exotermic character of this process. Some thermodinamic parameters of agmatinase-anylamine binding reaction are calculated. 1-Guanidobutane is obtained by means of 1-amidobutane guanidilation, and it is found to be more efficient inhibitor than monoamines.


[Isotherms of globular protein hydration under dynamic conditions]. The hydration isotherms of alpha-chymotrypsin, lysozyme, pork insulin, pork pepsin and serum albumin were obtained by means of dynamic method. The values of BET-monolayers for processes of water sorption leads to (h) and desorption comes from (h) do not depend on the static or dynamic way of achieving of hydration equilibrium in spite of difference in the shape of isotherms. The values of comes from h for proteins with known tertiary structure (alpha-chymotrypsin, lysozyme and insulin) coinside with the number of exposed polar amino acid side chains. The lowering of leads to h values in comparison with comes from h is correlated with inability of omega-amido groups of Asn and Gln residues and of ion pair-forming residues to take part in the formation of sorptive BET-monolayer. These rules for the interpretation of hydration isotherms were used to evaluate the numbers of exposed and buried polar side chains in proteins with unknown tertiary structure--pepsin and serum albumin.


[Catabolyte inhibition of lactate transport in Escherichia coli]. E. coli cells growing on the medium containing glucose and lactate do not utilize lactate. One reason of preferential utilization of glucose is catabolite inhibition of lactate transport. It is necessary for glucose to penetrate into the cell to inhibit lactate transport. Besides glucose the inhibition of the lactate transport is also caused by fructose and by non-metabolized analogue of glucose--alpha-methylglucoside.


[Study of the laws of cardiac biopotential distribution]. Current knowledge on biophysical and physical nature of electrocardiograms does not permit to apply analytical information-extraction techniques. This paper proposes to replace the investigation of ECG's, comprising some variations of instantaneous values, by the investigation of their distributive laws (i. e. by the investigation of the rate of occurrence of instantaneous biopotential values). The essence of the technique is the introduction into the computer's memory of some biopotentials, heart-generatet during an arbitrary chosen time-interval. By programming of into the memory introduced digit mass histograms were constructed. The experience has shown that the type-printed histograms after processing of introduced into the computer's memory hearts biopotenials, differ one from another depending on the functional state of the myocardium.


Human models for cancer active immunotherapy. In this editorial,  the author considers the human models for research on cancer immunotherapy. He distinguishes between trials which have given a direct demonstration of the action of immunotherapy, in which the effect of this treatment has been compared to therapeutic abstention, and those which have shown an indirect proof of its action and in which immunotherapy is compared to chemotherapy of which the effect is known, or in which the combination of chemotherapy and immunotherapy is compared with the same chemotherapy applied alone. The author concludes with methodological and ethical considerations about clinical trials applied to active immunotherapy.