Follow-up methods to trace women treated for pulmonary tuberculosis, 1930-1954.

A retrospective cohort study, designed to examine the relationship between multiple chest fluoroscopies and subsequent breast cancer risk, was conducted in which 93.6% of 1764 former sanatorium patients were successfully located. The methodology used to trace former female patients who were treated for pulmonary tuberculosis between 1930 and 1954 (20-45 years before the study began) is presented. Extensive use of city directories and telephone resulted in locating the majority of study subjects. Outpatient medical records and state vital statistics departments were also of value. Searching for death certificates of parents was helpful as the informant named on the certificate was often the woman being traced or her husband. The Postal Service was of limited use. No difference in the proportion of breast cancer cases was found between the more easily traced patients and the last 9.7% of patients who were difficult to locate. Fewer of the last patients located had died, however, than those located without intense effort. Patients lost to follow-up were younger at the time of sanatorium admission, had a higher proportion of Protestants and non-white women, had shorter lengths of hospitalization and had less severe tuberculosis requiring less aggressive treatment than patients located.


Passive immunization against hepatitis B: a review of recent studies and comment on current aspects of control.

Several independent studies suggest that both hepatitis B immune globulin (HBIG) made from plasma pools containing high titers of anti-HBs and standard immunoglobulin (IG) containing some anti-HBs may be effective for pre- and post-exposure prophylaxis of hepatitis B. Based on a synthesis of current data, it seems reasonable to recommend HBIG for the post-exposure prophylaxis of individuals sustaining accidental needle stick or mucosal exposure to blood known to contain hepatitis B surface antigen (HBsAg). If HBIG is unavailable there is also reason to expect that administration of standard IG which contains some anti-HBs may confer benefit. Although available data regarding prophylaxis of infants born to mothers with HBsAg positive hepatitis at time of delivery are insufficient to warrant firm recommendations on globulin administration, a temporary set of guidelines supporting use of either HBIG or standard IG containing some anti-HBs seems warranted in view of the serious implications for induction of the HBsAg chronic carrier state in infancy. Because appropriate environmental control measures may significantly reduce the transmission of hepatitis B in certain endemic settings such as hemodialysis units or homes for the mentally retarded, IG prophylaxis in these surroundings cannot be routinely recommended. Since current data show no evidence for superiority of HBIG over standard IG in these settings, and because there is some evidence that use of lower anti-HBs titer globulins may provide for acquisition of passive-active immunity, it seems reasonable to suggest that if IG is to be used for pre-exposure prophylaxis, the material to be used should be standard IG containing some anti-HBs.


Hematopoietic engraftment following transplantation of bone marrow cells carrying a Philadelphia (Ph')-like chromosome.

A phenotypically normal donor for bone marrow transplantation was found to have a previously unreported karyotype, 46, XY, t(18q+;22q-), resulting in a Ph'-like chromosome. Identification of the Ph'-like chromosome in cultures of skin fibroblasts, phytohemaglutinin-stimulated peripheral blood cells, and bone marrow cells from the marrow donor, but not in cell cultures from siblings or parents, indicated that it represented an acquired somatic mutation. Demonstration of the Ph'-like chromosome in the marrow graft recipient's blood and bone marrow cells after transplantation provided a unique and definitive marker of engraftment. Hematopoiesis appeared normal in both the donor and recipient after transplantation. This study indicates that a mutation creating a Ph'-like chromosome in hematopoietic cells need not produce hematologic abnormality. Presence of this translocation did not appear to interfere with normal hematopoietic or lymphoid differentiation and replication in the transplant setting.


Autoimmune hemolytic anemia associated with ulcerative colitis.

Three patients are reported in whom autoimmune hemolytic anemia developed during the course of ulcerative colitis. A review of the literature yielded 11 additional cases, and the clinical, immunologic, and therapeutic characteristics are summarized. The results of steroid therapy and splenectomy are similar to those for idiopathic autoimmune hemolytic anemia. The cause and effect relationship between these two diseases is not clear, but colectomy appears to produce remission in hemolysis when the latter is refractory to both steroids and splenectomy.


Acute myelogenous leukemia subsequent to therapy for a different neoplasm: clinical features and response to therapy.

The clinical characteristics of 10 patients with acute myelogenous leukemia (AML) which developed subsequently to treatment for another neoplasm are described. This disease appears to differ from "spontaneous" AML in being associated with lesser degrees of leukemic infiltration of the marrow and more frequent chromosomal aberrations. Only one of the nine patients who received chemotherapy attained remission status, and the mean and median survivals from the initiation of chemotherapy were 2.7 months and one month respectively. Nine of the 10 patients died as a result of infection. The refractoriness of this form of AML to chemotherapy was borne out by a review of the literature, which revealed only two remissions in 32 treated patients. The implications for the management of this disease are discussed.


Drug therapy reviews: management of hypothyroidism.

The therapeutic management of hypothyroidism caused by deficient thyroid hormone production is discussed. The therapeutic use of the following thyroid agents is reviewed: levothyroxine sodium, Thyroid USP, thyroglobulin, liotrix, and liothyronine sodium. Myxedema coma, neonatal hypothyroidism, primary hypothyroidism, and secondary and tertiary hypothyroidism are specific hypothyroid states for which drug therapy is discussed. Levothyroxine sodium is the preferred agent because of consistent potency, restoration of normal, constant serum levels of thyroxine (T4) and triiodothyronine (T3) and ease of interpretation of thyroid hormone levels. Other agents, because they contain T3, result in postabsorptive elevated T3 serum concentrations that may cause thyrotoxic symptoms and reduction of T4 levels. This, in turn, may give rise to misleading estimates of thyroid dosage. Patients with the sick euthyroid or low T3 syndromes are not candidates for thyroid hormone therapy.


Regulatory aspects of investigational new drugs.

Federal regulations governing the introduction of new drugs in the United States are reviewed. The discussion includes the legislative background, what constitutes a "new drug," drug development, investigational new drugs, new drug applications, pharmacist involvement in clinical trials, the approval process and postmarketing surveillance.


Breast cancer: potentially predisposing and protecting factors. Role of pregnancy, lactation, and endocrine status.

Risk factors of breast cancer have been correlated with the availability of estradiol and estrone. Mechanisms protecting from breast cancer are thought to be due to the mitotic rest of mammary epithelium (low deoxyribonucleic acid synthesis), as encountered during pregnancy and lactation, and to the actions of estriol and progesterone in opposing the "carcinogenic" estradiol and estrone.


Scleral ring as template for corneoscleral graft.

A 19-year-old woman sustained a corneal laceration in her right eye. After bacterial keratitis was treated by antibiotics and a conjunctival flap, she developed a corneoscleral ectasia. We used a 15-mm diameter scleral ring as a template for corneoscleral graft. We obtained uniform donor and host buttons by suturing the ring alternately to donor and host eyes. One year postoperatively, the patient had a retrograft fibrous membrane with corneal edema, a visual acuity of R.E.: 6/60 (20/200), and intraocular pressure of 16 mm Hg.


Endocarditis associated with disseminated group B streptococcal infection.

Endocarditis due to group B streptococci occurred in two men associated with meningitis in one and septic arthritis in the other. Therapy with penicillin failed in the first patient necessitating aortic valve replacement. Clindamycin therapy was not curative in the second and the patient responded to a four-week course of vancomycin therapy.


Islet cells as a component of pancreatic ductal neoplasms. I. Experimental study: ductular cells, including islet cell precursors, as primary progenitor cells of tumors.

The ductular complex of the Syrian hamster pancreas represents a system of conduit which encompasses intercalated (intralobular), periinsular, and intrainsular ductules. The intercalated (intralobular) ductules comprise centroacinar and intercalated cells. A meshwork of small ductules (invisible by usual histologic procedures) surrounds islets (periinsular ductules) and extends in the form of often ramified tiny channels within the islet (intrainsular ductules). Although the function of the latter ductules is obscure, their cells seem to make up one of the undifferentiated cellular units of the pancreas, and as such are also the progenitors of beta-cells of the islets (islet cell precursor = IP). Systematic histologic examination of the pancreas in this species treated with pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine indicated that ductular cells, especially those of periinsular and intrainsular origin, are the most responsive to this carcinogen. The neoplastic process was initiated with hyperplasia of intercalated (intralobular) ductular and interlobular ductal cells associated with newly formed islets (nesidioblastosis). This process was followed by excess formation of mature but especially of immature islet cells and their precursors (IP) in the islet periphery, as well as with the appearance, distention, and multiplication of periinsular and particularly of intrainsular ductules. The hyperplasia, metaplasia, and malignant alteration of these periinsular and intrainsular ductules (including IP) and, to a lesser degree, of intercalated ductules indicated their histogenetic relationship and their potency for reproducing embryonic tissue on carcinogenic stimulus. The similarity of some induced lesions to diabetes has been emphasized.


Implementing the developmental assessment component of the EPSDT program.

This paper discusses the role of developmental assessment within the EPSDT program, describes efforts to develop guides for implementing this component of the program, and summarizes the "developmental review" proposed by the American Association of Psychiatric Services for Children.


Mental health work in children's health centers: learnings from five years' experience.

A five-year-old program of an EPSDT-kind is examined with respect to 1) its potential for prevention of disabling conditions, and 2) the kinds of problems encountered and solutions attempted. Two glaring needs appear--for stronger support systems, and for more relevant training in outreach work.


Developmental assessment in EPSDT: the American Orthopsychiatric Association.

This study, initially aimed at preparation of a guide for state and local administrators and service providers responsible for EPSDT developmental assessment and treatment, concludes that EPSDT, as currently constituted, cannot adequately meet the urgent developmental needs of the poor children it is meant to serve. Professional and administrative limitations of the program are outlined, and pilot studies to seek sound solutions are suggested.


Effect of fatty acids on isolated ovine pancreatic islets.

A procedure was developed for the isolation of intact islets of Langerhans from sheep pancreas. The pancreas was disrupted by syringe injection of Hanks solution followed by collagenase incubation and islet separation by sedimentation. The islets were incubated in varying concentrations of glucose and butyrate. The rate of insulin release was approximately linear while the glucose and butyrate concentrations were increased. In additional studies at 2.5 and 5.0 mM levels of substrate concentration, the stimulation of insulin had the following pattern: octanoate greater than hexanoate greater than butyrate, whereas beta-hydroxybutyrate, lactate, acetate, and propionate had only slight stimulatory effects that were not statistically significant. Decanoate did not alter insulin release from isolated islets. These data confirm earlier in vivo reports that fatty acids stimulate pancreatic hormone release in sheep and that the stimulus is related to chain length of the fatty acid through C-8 but that C-10 has no effect. A hypothesis was suggested to explain these results based on chain length, solubility, and plasma membrane alterations.


Ionic basis of electrical activity in cardiac tissues.

Cardiac electrical events are described in terms of membrane physiology. The concept that cardiac membranes possess specific ionic channels controlled by gates bearing electrical charges is discussed. When open, these channels permit ions to cross the membrane, giving rise to passive inward (depolarizing) and outward (repolarizing) currents. Two different inward and four or five different outward currents appear to be responsible for the development of cardiac electrical activity; both inward currents appear to be controlled by activation and inactivation variables, whereas outward currents are essentially controlled by activation variables and/or inward-going rectifiers. The potential range in which the different currents activate and inactivate (or are limited by inward-going rectification), and the kinetics of activation and inactivation processes explain the development of electrical activity in normal cardiac tissues and in partially depolarized fibers. In addition to passive ionic currents, electrogenic active transport participates in the development of electrical phenomena. The conductance of the membrane for potassium ions and the electrical coupling between cardiac cells depend on the intracellular concentration of calcium ions.


Adrenal contribution to coronary regulation in the newborn.

Evidence for adrenergic regulation of the coronary vessels was sought in 27 newborn lambs. Sympathetic activity was altered by temporarily lowering cephalic perfusion pressure (CPP) from 90 to 20 mmHg while aortic pressure was held constant. Heart rate (HR) and left ventricular dP/dt max increased markedly, while end-diastolic pressure and stroke volume fell. These changes were accompanied by an increase in coronary blood flow (CBF), myocardial O2 consumption (MVO2), and reduced coronary resistance (CF) (P less than 0.005). After beta blockade, which prevented an augmentation of metabolic demand, the same maneuver resulted in coronary vasoconstriction, reflected by reduced CBF and increased CR (P less than 0.02). This response was eliminated by alpha blockade with phentolamine (2 mg/kg). In 13 lambs subjected to bilateral adrenalectomy or sham operation, lowering CPP elicited similar positive chronotropic and inotropic changes, increases of MVO2 and CBF, and reduced CR. Following beta blockade, lowering CPP in the sham group caused coronary constriction. However, no changes in CBF or CR were elicited in the adrenalectomized lambs. These observations indicate that integrity of the adrenal glands is required for adrenergic control of the coronary vessels in the newborn. Chronotropic and inotropic regulation is mediated by direct neural action and is not dependent on adrenal function.


Antibody to Escherichia coli enterotoxin in meat-packing workers.

Meat-packing plant employees exposed to raw animal products had serological evidence of higher infection rates with heat-labile toxin producing enterotoxigenic Escherichia coli (LT-EEC). In those employees with multiple sera available for study over a ten-year period, a drop in mean anti-LT-EEC titer was observed, suggesting altered ecology of or exposure to the organism during this time. Prospective studies need to be done to determine if meat-packing workers actually experience a greater incidence of LT-EEC-induced diarrheal disease.


Schneiderian papillomas: a clinicopathologic study of 30 cases.

Schneiderian papillomas are tumors involving the nasal cavity and paranasal sinuses that tend to recur. A long-term clinical follow-up of 30 patients revealed histologically confirmed recurrences in 20 of the 30 patients (67%) and probable recurrences in two additional patients (combined recurrence percentage 73%). Recurrences were most frequent within 1-2 years following primary thrapy and were generally more frequent in patients with more extensive disease and involvement of paranasal sinuses. Histologic features were not helpful in predicting recurrence. One patient in the study (1/30 = 3%) developed a carcinoma at the site of a histologically confirmed benign Schneiderian papilloma after four recurrences over a period of 9 years. No patients died from the tumor. Twenty patients were alive and free of disease at last follow-up; four patients died of unrelated causes and without evidence of disease; four patients are alive with evidence of disease; and two patients died with disease but of unrelated causes. These tumors often pursue a relentless local course requiring multiple surgical excisions but are rarely responsible for death of the patient and seldon undergo a malignant "transformation" (less than 5%).


Bile acid composition in patients with and without symptoms of postoperative refulx gastritis.

Reflux of bile into the stomach is common after surgery for duodenal ulcer disease; however, only a minority of patients may develop significant gastritis and pain. Gastric aspirates from two groups of patients after operation for duodenal ulcer were quantitatively and qualitatively analyzed. Group A patients were asymptomatic and the bile composition was normal. Group B patients were symptomatic and had a significant increase in the secondary bile acid, deoxycholic acid. The concentration of bile acid was similar in the two groups. This alteration in bile acid composition, with an increase in deoxycholic acid, may be an important factor in determining which patients with bile reflux develop gastritis.


The effect of metronidazole on the incidence of postoperative wound infection in elective colon surgery.

A prospective randomized clinical trial assessing the relative effectiveness of erythromycin-neomycin and metronidazole-neomycin as a preoperative bowel preparation was carried out. Bacteriologic studies of feces and colon content revealed no significant difference in the reduction of aerobic bacteria between the two groups. There was, however, a significantly greater reduction in anaerobic bacteria in the feces and colon contents of patients receiving metronidazole. Wound infection rate was 25% in the erythromycin group, and organisms recovered from the wound in all cases were fecal in nature. Two wound infections occurred in the metronidazole group (5%) and in both cases the organisms recovered were staphylococci of presumed skin origin. These studies suggest that anaerobic bacteria are the major contributors to wound infection after colon surgery and that their specific reduction is associated with a lower incidence of wound infection.


[Comparison of the cyanogen bromide peptides of vitreous body collagen and type II collagen (author's transl)].

Pepsin-soluble collagen was isolated from bovine vitreous humor. This collagen showed only one alpha-chain in disc electrophoresis, migrating in the alpha1-chain position and between the alpha- and beta-components some colored bands were visible. The disc electrophoretic patterns of the cyanogen bromide peptides of pepsin-soluble vitreous body collagen and pepsin-soluble type II collagen revealed no identity.


[Synthetic, absorbable suture in eye-muscle surgery (author's transl)].

A synthetic, absorbable suture (Vicryl), was investigated for its usability in eye-muscle surgery. In experimental investigations on animals and strabismus surgery in humans, properties of the suture were compared with those of plain catgut. Histological investigations after modified strabismus surgery on rabbits clearly showed a smaller degree of tissue reaction around the hydrolytically dissolvable synthetic suture than around plain catgut. After implantation of Vicryl or catgut into the anterior chamber of rabbit eyes, within the first eight days both cause infective reactions which were somewhat stronger with Vicryl, which caused more scarring over the iris, than with catgut. One-hundred and eighty strabismus operations on man showed that the synthetic suture handles better and rips less markedly than plain catgut, whereas duration and amount of postoperative irritations are similar. Overreactions and granuloma were rare.


Atenolol 4% eye drops and glaucoma. A double-blind short-term clinical trial of a new beta1-adrenergic blocking agent.

We studied the effect of a single dose of atenolol 4% eye drops on 21 patients with primary open-angle glaucoma during a double-blind clinical trial. We monitored intraocular pressure (IOP), blood pressure, and pulse rate. At three and six h after medication, the average reduction of IOP was 7.3 and 4.1 mm Hg, respectively, compared to the baseline readings without medication. The reduction of IOP at four h after medication was 6.3 mm Hg compared to the pretreatment value. This corresponds to an average change from the pretreatment value of 22%. Blood pressure and pulse rate did not change significantly. We observed no subjective or objective ocular side effects. The duration of the effect of a single dose of atenolol 4% eye drops is approximately six h. Atenolol 4% eye drops may become a useful agent in the medical treatment of glaucoma if a long-term effect and no ocular side effects (especially a local anesthetic effect) can be proven.


Then and now. Anaesthesia thirty years ago (1947) Volume 2.

The year 1947 was a year of consolidation for the specialty of anaesthesia in Britain. The medical profession in the United Kingdom was poised between the old order of the voluntary hospitals and the new order of the National Health Service. Anaesthetists had gained a new status as a result of their wartime service and the occasional anaesthetist was about to be replaced by the full time specialist consulants. Volume 2 of Anaesthesia reflects this change. It reviews the past, both political and scientific and looks forward to the future with anticipation tinged with some apprehension.


[Investigations on knowledge of the pancreas before Vesal, with special regard to the anatomical technique in the 16th and 17th century (author's transl)].

In the centuries before Vesal is the pancreas described. The name "pancreas" is created by Galenos (1565). This organ has after Galenos (1565) a function of cushion. The supposition that the pancreas is a gland is created by Berengario da Carpi (1521). The technique of the anatomical section is the basis on knowledge of VESAL. He has created many instruments.


Current trends in the management of esophageal atresia and tracheoesophageal fistula.

The present trends in care have been reviewed. There is an inclination for the use of the patient's esophagus when at all possible rather than resort to interposition. Following the evolution of treatment for the primary tracheoesophageal anomalies, current efforts are being directed toward treatment of associated anomalies and long-term problems associated with the lesions. The result has been an overall improved survival rate and decrease in morbidity.


Does skin have antimicrobial properties? An in-vitro experiment and literature review.

Skin grafts placed over burn wounds were first reported to reduce bacterial growth levels about 20 years ago. Recently, three separate groups of investigators have studied effects of skin in vitro in order to better understand the mechanism of this in vivo phenomenon. Although significant bacterial inhibition was not found, the interaction of host tissue factors with the skin which is possible in vivo was not included in these experiments. Hence, the question of in vitro activity of skin was still not resolved. In this experiment human and pig skin, fresh and preserved, intact and homogenated, were all tested separately with and without active serum against four representative bacteria and one fungus, individually and in mixed cultures. No growth inhibition was observed under any circumstances on daily review for up to three-week periods. In light of conflicting reports related to antibacterial effects of skin grafts used clinically, it now seems important to definitively clarify whether skin really possesses antibacterial properties in vivo.


[Burns in children. Experience of 53 cases (author's transl)].

A series of 53 children admitted during a 20-month period to the Hospital for burns due to hot liquids is reported 88.6% were under three. 34 children were seen during spring and fall months. Most patients were recently burnt and in the majority of cases (27) burned surface was under 20%. l.v. fluids were used in 17 cases and management protocol included: Closed local care after the 3rd or 4th day with nitrofurazone cream and antibiotics only in selected cases. Mortality was 5.5% (three cases) due to acute renal failure at the 3rd, 5th and 10th days. 24.5% had a local infection in the first two weeks, gram negative bacteria being present in 75% of these cases. 33.2% (18 cases) required grafting. This was more frequently needed in boiling oil burns. In seven cases, grafting was necessary before the 30th day (average 23.2 days), and in the remaining patients after this time (average 42.1 days). Authors advise a strict prevention of acute rend failure and early grafting.


[Antimicrobial factors in milk and colostrum: their importance for the newborn infant (author's transl)].

The antimicrobial activity of various proteins and other substances in milk and colostrum is discussed. These factors include antibodies, complement, lactoferrin and transferrin, lactoperoxidase and lysozyme. The possible importance of these factors in protecting the newborn infant against infectious diseases is discussed.


[Complications on two cases of peritoneal dialysis (authors transl)].

Two newborns with abdominal perforation during peritoneal dialysis are presented. The first probably before dialysis and the second iatrogenic. Both needed surgical intervention. Incidence in children in comparation with adults is discussed. Severe clinic complications of both patients that needed complete parenteral nutrition, mechanic ventilation and treatment of Candida sepsis are comented. Both survived without sequels in spite of severe complications.


[Group B streptococci: serotyping data and susceptibility to antibiotics (author's transl)].

A study of the prevalence of group B streptococci in women (covering 6,000 samples) shows the vaginal presence to be comprised between 6.34 and 16.8%. The highest rate is found in a Centre for venereal diseases. The use of selective media results in a 50 to 75% increase in the number of germ-carries. The distribution found after serotyping of 1,469 strains has been studied. Over half of the strains isolated from the vagina and from infants belong to serotype II and III, one third of the strains causing serious infections are of type III; however, there is a wide dispersion of the serotypes found in neonatal infections. The test for pigmentation on Columbia medium offers an excellent approach for the diagnosis of group B streptococci. MIC testing of 7 antibiotics for 782 strains of various serotypes demonstrates high susceptibility to the beta-lactam antibiotics and makes it possible to detect rare strains with features of polyresistance to chloramphenicol and some macrolide antibiotics.


The effect of digoxin on the contractility of transplanted heart.

The effects of digoxin on the contractility of orthotopically transplanted heart was studied in dogs. Intravenously administered digoxin produced a fall in the rate and output of the transplanted heart without any change in stroke volume, whereas the output of the intact heart was slightly improved due to a small increase of stroke volume. This difference was thought to be due to the action of digitalis which is mediated via the nervous pathways, which are interrupted in the transplanted heart.


Inhibition of human neutrophil chemotaxis by corticosteroids.

A direct inhibitory effect of hydrocortisone on granulocyte chemotaxis has been demonstrated with an increasing inhibition between concentrations of 5 microgram to 12.5 microgram per ml. Washing the granulocytes after incubation with hydrocortisone did not reverse the inhibitory effect on chemotaxis indicating a direct cellular effect. Bacteriocidal capacity of the hydrocortisone treated cells was not reduced. These studies indicate corticosteroids, alter motility of granulocytes irreversibly possibly by incorporation into the cell membrane.


[Biological properties of L-asparaginase preparations from E. coli in cell cultures].

Non-specific cytotoxicity and specific antitumor activity of 5 preparations of L-asparaginase from E. coli were studied. Two cell line, i.e. the asparagine-dependent (Berkitt lymphoma cells) and asparagin-independent (human ovary cancer cells) were used as the test-system. Incorporation of 3H-thimidine into DNA was the criterion of the preparation effect on the cells. Preparation I with the specific activity of 60-90 IU per 1 mg of protein obtained at the first stages of purification had high non-specific cytotoxicity. Preparation II obtained after further purification of preparation I, as well as preparation II without any stabilizer with the specific activity of 200 IU/mg were not inferior to the "Bayer" preparation by their biological properties. Addition of L-asparaginase to the preparation as a stabilizer of excessive glycine (preparation IV) increased its non-specific cytotoxicity and interfered with the study of its properties in the cell systems. Mannitol (preparation V) had no effect on the biological activity of L-asparaginase preparation.


[Physiological characteristics of Salmonella typhimurium treated with penicillin].

Growing bacteria of the two strains of Salmonella typhimurium differing in the sensitivity levels to UV-light formed multinuclear non-septal filaments in the penicillin-containing nutrient medium. The maximum number of the lifefull filaments was formed by the 4th hour of incubation in the beaf-peptone broth at a temperature of 37 degrees C in the presence of 5 gamma/ml of penicillin. The strains exposed to penicillin were less sensitive to UV-light. Exclusion of penicillin from the nutrient medium resulted in a new division of the filamentous cells and reduction of the initial UV-light sensitivity level. It was concluded that the low UV-light sensitivity level of the filaments induced by penicillin was associated with their multinuclear state.


Apparent bisexual behavior of yeast strains obtained from hybridization of industrial yeasts of the genus Saccharomyces with auxotrophic diploids.

During a genetic study of some hybrids of brewer's and distiller's yeast strains with impaired sporulation characteristics and genetically marked auxotrophic aa and alpha alpha diploids, strains which showed positive mating reactions with both a and alpha haploid tester strains were observed. These strains proved to be homothallic and sporulated freely. The original hybrids, which appeared to be tetraploid, usually yielded sporulating single-spore clones on dissection of asci formed from them, with few or no mating strains among them. Dissection of asci from these clones yielded some single-spore clones which showed mating reactions with one or the other or both haploid tester strains, and further selection produced strains which on sporulation and dissection yielded single-spore clones which were apparently bisexual and sporulated freely. These strains proved to be homothallic, yielding single-spore clones which were all of the a mating type, and in which the mating reaction and, possibly, the action of the genes for homothallism were impaired, so that sporulating, non-mating diploids and haploids of both mating types were present in cultures originally obtained as single-spore clones.


Characterization of some fish and shrimp spoiling bacteria.

The classification of some important groups of bacteria involved in fish and shrimp spoilage was studied. Trimethylamine is produced by Pseudomonas putrefaciens, a "non-defined" group resembling Ps. putrefaciens, Photobacterium spp. and some Moraxella-like bacteria. Hypoxanthine is produced by the same groups of bacteria except the last named and also by the "typical shrimp spoilers" (presumptive Alteromonas). Strong off-odours are produced on fresh fish by Ps. putrefaciens, dextrose-oxidative Pseudomonas spp. (Groups I and II according to Shewan, Hobbs and Hodgkiss, 1960), the above mentioned "non-defined" group and by only some of the "typical shrimp spoilers", whereas Moraxella-like bacteria and Photobacterium spp. failed to produce strong odours. Strong off-odours are produced on boiled shrimp by the "typical shrimp spoilers" (presumptive Altermonas). Ps. putrefaciens, the dextrose-oxidative Pseudomonas spp. and the "non-defined" group; Moraxella-like bacteria produced less offensive odours or none, nor did Photobacterium.


Comparison of miniaturized multitest systems with conventional methodology for identification of Enterobacteriaceae from foods.

Four miniaturized multiple test systems were compared with tube methodology used to identify Enterobacteriaceae encountered in foods. Identification aids supplied with each system were used to assign names to isolates at the species level. For the 129 strains tested, the Minitek system demonstrated a 96.9 percent agreement with reactions in tubed media. The Inolex, Analytab, and PathoTec test systems exhibited 94.3, 93.8, and 92.7 percent agreement, respectively. Analytab identified 96.1 percent of the isolates to the species level, whereas the Minitek, PathoTec, and Inolex systems were able to identify 78.3, 32.6, and 27.1 percent, respectively. The results indicate that the Analytab and Minitek systems are acceptable substitutes for the tube methodology routinely employed in identifying enterics from foods. Although the PathoTec system might be used to screen isolates for their identity, neither the presently available PathoTec nor the Inolex systems should be substituted for current methodology when definitive identification of foodborne organisms is required.


Application of the fluorescent-antibody technique to the study of a methanogenic bacterium in lake sediments.

Fluorescent antibody (FA) was prepared for a methanogenic bacterium isolated from Wintergreen Lake pelagic sediment. The isolate resembles Methanobacterium formicicum. The FA did not cross-react with 9 other methanogens, including M. formicicum strains, or 24 heterotrophs, 18 of which had been isolated from Wintergreen Lake sediment. FA-reacting methanogens were detected in heat-fixed smears of several different lake sediments and anaerobic sewage sludge. Pretreatment of all samples with either rhodamine-conjugated geletin or bovine serum albumin adequately controlled nonspecific absorption of the FA. Autofluorescent particles were observed in the sediment samples but, with experience, they could easily be distinguished from FA-reacting bacteria. FA direct counts of the specific methanogen in Wintergreen Lake sediments were made on four different sampling dates and compared with five-tube most-probable-number estimates of the total methanogenic population that was present in the same samples. The FA counts ranged from 3.1 X 10(6) to 1.4 X 10(7)/g of dry sediment. The highest most-probable-number estimates were at least an order ofmagnitude lower.


Comparison of Andersen eight-stage and two-stage viable air samplers.

The two-stage, disposable Andersen air sampler gave lower values for aerial concentration of bacterial colony-forming particles than did the eight-stage Andersen viable air sampler in either a swine house or a classroom.


Multichannel electrochemical microbial detection unit.

A compact multichannel unit for electrochemical detection of microorganisms that automatically displays detection time length is described. This unit was successfully tested with various members of the Enterobacteriaceae group.


Enhancing nitrite inhibition of Clostridium botulinum with isoascorbate in perishable canned cured meat.

Addition of sodium isoascorbate to the formulation for perishable canned comminuted cured meat markedly enhanced the efficacy of nitrite against Clostridium botulinum. This effect was reproducible through a series of three tests. In one test it was found that the initial addition of 50 microgram of sodium nitrite per g plus isoascorbate was as effective as 156 microgram of sodium nitrite per g alone.


Breaks induced in the deoxyribonucleic acid of aerosolized Escherichia coli by ozonized cyclohexene.

The inactivation of aerosolized Escherichia coli by ozone, cyclohexene, and ozonized cyclohexene was studied. The parameters for damage were loss of reproduction and introduction of breaks in the deoxyribonucleic acid (DNA). Aerosolization of E. coli in clean air at 80 percent relative humidity or in air containing either ozone or cyclohexene hardly affected survival; however, some breaks per DNA molecule were induced, as shown by sucrose gradient sedimentation of the DNA. Aerosolization of E. coli in air containing ozonized cyclohexene at 80 percent relative humidity decreased the survival by a factor of 10(3) or more after 1 h of exposure and induced many breaks in the DNA.


Tail formation in man. Some historical notes on a case report.

In a newborn boy, a tumor was removed from the coccygeal area. The growth was identical in all respects to the caudal formations in human described in the literature. A few medical-historical aspects are discussed.


Renal allograft fracture: clinicopathological study of 21 cases.

Experience with renal allograft fracture occurring in 21 of 246 transplants performed over a 29-month period is reviewed. Clinical manifestations included pain and tenderness at the graft site, fever, and falling hematocrit. The fracture occurred without exception in the course of an acute rejection episode. Diagnosis was made from two days to seven weeks following transplantation; in 13 patients (62%) diagnosis was made within two weeks of surgery. Severe damage to the kidney necessitated nephrectomy in all but two transplants. Of those not removed at initial exploration only one regained function to permit a dialysis-free existance for several months. Histologic examination of the fractured kidneys revealed the pathogenesis to be acute rejection in 13 (62%), accelerated acute rejection in four (19%), and a combination of these processes in four (19%). Conclusions from this study are that fractures of renal allografts: (1) are more frequent than commonly realized; (2) are primarily due to the swelling of acute rejection; (3) are often characterized by sudden onset of pain in the region of the graft accompanied by fever and falling hematocrit; (4) should be treated by prompt surgical intervention to control hemorrhage, to perform nephrectomy if indicated, and to evacuate the hematoma in order to reduce the possibility of secondary infection.


Hypothermic lung preservation functions, six or more years later.

The functions of each lung were measured 41 and 79 months following hypothermic twenty-four four lung preservation and autotransplantation in six and four dogs respectively. Functional results were compared with long-term autotransplanted canine lungs. Compliance, total lung capacity, functional reserve capacity and ventilation of preserved lungs were similar to autotransplanted lungs, and only slightly decreased as compared with normal animals. There was no statistically significant difference between the pulmonary diffusion capacity and oxygen uptake of the preserved and autotransplanted lungs group and autotransplants alone. However, in both groups, diffusion capacity and oxygen uptake were decreased as compared with intact animals. Pulmonary hypertension was found on occlusion of the contralateral lung's artery: it was due to increased pulmonary vascular resistance. No gross narrowing of the pulmonary artery or venous anastomosis was found that could explain the increased resistance. Diffuse emphysema of various degrees was observed in all animals. This study seems to indicate that hypothermic preservation of the lung does not affect significantly the long-term functional ability of the organ, and probably will have practical value in future clinical lung transplantation.


[An epidemic of bacillary dysentery caused by Shigella dysenteriae, type 1, in Mogadiscio].

An epidemic of bacillary dysentery broke out at Mogadiscio in the first months of 1976 produced by Shigella dysenteriae type 1 supplanting all other familiers of Shigella before present in the zone. The date are relative to 675 cases with 27 deceased. The hydrological origin of epidemy was not probable.


Successful renal vein reconstruction with bovine arterial heterografts.

Extensive damage to a short right renal vein complicated transplant surgery in two patients. The use of a segment of modified bovine arterial heterograft permitted successful transplantation in both cases. These results are in contrast to the reported inability of bovine arterial heterografts to remain patent elsewhere in the systemic venous system.


Division and repair of the sphincteric mechanism at the gastric outlet in emergency operations for bleeding peptic ulcer. A new technique for use in combination with suture ligation of the bleeding point and highly selective vagotomy.

In three of 26 patients who were treated by highly selective vagotomy (HSV) plus suture of the bleeding point for massive hemorrhage from peptic ulceration, access to the ulcer could not be obtained by means of a duodenotomy or gastrotomy which spared the pylorus. Instead, a wide gastroduodenotomy was performed, the artery in the base of the ulcer underrun and HSV performed. The gastroduodenotomy incision was closed longitudinally, rather than as a pyloroplasty. In this way, the integrity of the antral mill and of the pyloric sphincter was restored. The patients were followed up for six months, one year and three years respectively, and were found to be in good health, without clinical or radiological evidence of gastric retention or of recurrent ulceration. Thus the sphincteric mechanism at the exit of the stomach can, like the anal sphincter, be divided and subsequently repaired with good restoration of function.


[Control of fertility outcome in artificially inseminated gilts and old sows. 2: Addition of oxytocin to boar semen. Its effect on length of insemination, pregnancy rate and litter size].

Toleration-oriented insemination was applied to 1,373 oestrous sows that had undergone bio-engineering treatment, with two insemination portions having been used for each oestrous. Five International Units of oxytocin were added immediately before insemination proper to the semen applied to 315 gilts and 377 old sows. The control group included 296 gilts and 385 old sows inseminated in parallel. Semen intake, on average, was complete between four and eight minutes with the majority of gilts and between four and seven minutes with most of the old sows, but no evidence was obtained as to any action of the oxytoxin upon intake intensity. The treated gilts were superior to the controls by 6.3 per cent in pregnancy rate and by 56 born piglets to each 100 first inseminations. Superiority, consequently, was significant. In both gilts and old sows added oxytocin prolonged insemination by more than five minutes and gave clearly better fertility results.


[Detection of Salmonella in surface waters].

After a detailed description of some of the methods used for the research of Salmonella in superficial waters, the AA. examine some problems relative to the collection of the samples and to the culture of these bacteria. Results obtained in the Po river and its affluents are also briefly presented; the high incidence of samples positive for Salmonella is stressed and some aspects of an epidemiological nature are considered.


Rat ciliary process in chronic serum sickness: light, immunofluorescence, and electron microscopy.

The ciliary processes of 26 male Wistar rats that survived a prolonged period of immunization with bovine serum albumin (BSA) and a similar number of age- and sex-matched controls were studied by immunofluorescence and electron microscopy. The findings in the ciliary process were compared with those of the renal glomeruli. Granular subepithelial deposits of rat IgG, C3, and BSA were demonstrated by direct immunofluorescence in the ciliary process and renal glomeruli of 38% and 85% of experimental animals, respectively. Electron microscopy of the positive immunofluorescent cases disclosed electron-dense single masses and clusters in the basement membrane regions below the epithelial layers. Experimental chronic serum sickness appears to offer an excellent approach toward understanding the pathogenesis of uveal involvement in human serum sickness and in the "collagen-vascular" diseases.


Intrasellar paraganglioma associated with hypopituitarism.

A 37-year-old with a history of postpubertal arrest of sexual development and delayed growth was found to have an enlarged sella turcica. The clinical and biochemical features were consistent with hypopituitarism. A tumor was removed transsphenoidally that, through light microscopy, histochemistry, and electron microscopy, proved to be a paraganglioma. We report the possible origin of intrasellar paraganglioma, as well as the pathogenesis of hypopituitarism.


[From the observation of natural phenomena to experimentation in biology].

Observation and experimentation as are discussed as means for the acquisition of knowledge concerning natural phenomena. The concept of disease is described in the light of its origins and down to modern times. The development of experimentation in biology is illustrated and emphasis is placed on its importance for the acquisition of knowledge concerning disease in man.


[Erythema nodosum in childhood. Nosographical classification and case studies].

A survey of the relevant literature, with particular attention to clinical and immunological studies propounding pathogenetic theories, is followed by the presentation of 32 cases of erythema nodosum observed in infants examined at the Turin Paediatrics Clinic and Regina Margherita Hospital. The clinical laboratory data showed that streptococcal infection was hardly less significant than T. B. as the cause of this condition.


Species differences in activating and inactivating enzymes related to the control of mutagenic metabolites.

Microsomal monooxygenases catalyze the biosynthesis of epoxides from olefinic and aromatic compounds whilst microsomal epoxide hydratase and cytoplasmic glutathione S-transferases are responsible for their further biotransformation. Although catalytically very efficient the cytoplasmic glutathione S-transferases play, due to their subcellular localization, a minor role in the inactivation of epoxides derived from large lipophilic compounds and were, therefore, not included in this study. It was shown with such a lipophilic compound, benzo(a)pyrene, as a model substance and with liver enzyme mediated bacterial mutagenesis as biological endpoint that species and strain differences in epoxide hydratase and monooxygenases are reflected in very dramatic differences in mutagenicity of benzo(a)pyrene which varied from extremely potent to a degree which could easily be overlooked. In order to investigate whether the differences in enzyme activities were causally linked to the observed differences in mutagenicity, the enzyme activities were modulated by inhibition and induction. These manipulations were always accompanied by the corresponding changes in mutagenicity. It is concluded that species such as mice which possess high monooxygenase activity but very low epoxide hydratase activity are much more susceptible than man to those toxic effects which are mediated by metabolically formed epoxides which are substrates of epoxide hydratase. In this regard, it is especially noteworthy that mice possess a much lower hepatic epoxide hydratase activity than man.


[Principles of the structural organization of the cetacean neocortex].

The investigations performed demonstrate that morphologically cetacean neocortex is organized on the same principles as that of other mammals, as it has six layer structure, layer IV including. The results of investigations done for many years gave the possibility to establish quantitative characteristics of neocortex in different zoological cetacean genera, such as volume of neocortex, total number of its nervous cells (for dolphin the data were obtained for the first time), and clarify the problem fully enough. It became clear that morphologically dolphins belong to different genera. Three quantitative gradations of morphological enrichment of the dolphin neocortex are demonstrated. The only genus of Tursiops (bottle-nosed) can be compared with man, as to on what neuromorphological criteria it is behind, equal and surpasses the man. Representatives of the two other genera investigated, according to all neuromorphological indices studied, are far behind the man.


[Morphofunctional changes in the insular apparatus of the pancreas following hypophysectomy and administration of somatotropic hormone].

Mature white male rats were used to study effects of hypophysectomy and STH on sugar content after fasting and after reiterated glucose loading. Morphological and morphometrical investigation of the pancreatic endocrine tissue were made. Zinc content and distribution in the pancreas, as well as aldehydefuchsinophil granulation in B-cells of the islets of Langergans were studied. Hypophysectomy was stated to increase functional activity of the pancreatic insular apparatus. Injection of STH for 9 days resulted in the stimulation of the cells in the insular apparatus. Prolonged injection of STH (for 20 days) produced exhaustion of the pancreatic insular apparatus.


Group B streptococcal meningitis associated with a CSF fistula.

An elderly man had group B streptococcal meningitis. The infection may have seeded the meninges through a rhinocerebral fistula. Despite the frequency of nasopharyngeal colonization with this organism, reports of adult meningitis secondary to group B Streptococcus are rare; to our knowledge, no previous cases specifically associated with rhinocerebral fistula have been described. Reasons for the discrepancy between the frequency of nasopharyngeal colonization and the rarity of meningitis are suggested.


Clinical syndromes of myasthenia in infancy and childhood. A review.

Ten clinical syndromes of defective neuromuscular transmission in infancy and childhood are reviewed. Autoimmune, genetic, infectious, and pharmacologic mechanisms have been implicated. These disorders manifest themselves in a variety of ways including severe respiratory insufficiency. Prompt diagnosis and treatment may be lifesaving.


Bacterial corneal ulcers in cosmetic soft contact lens wearers.

Soft contact lenses provide a safe alternative to spectacles for more than 1 million patients. However, the hazard of bacterial corneal ulcers exists. This report describes five cosmetic soft contact lens wearers who developed bacterial corneal ulcers. In three cases, the resulting visual acuity was 6/120 or less. Possible sources of contamination are discussed, but in no case was it determined.


Penetrating keratoplasty and cataract extraction: combined vs nonsimultaneous surgery.

In the presence of corneal opacification associated with a cataract, the surgeon is left with two alternatives: a penetrating keratoplasty followed months later by extraction of the cataract or a combined procedure. The results of 16 nonsimultaneous procedures and 22 combined operations were compared with each other. The visual prognosis and incidence of complications were similar in the combined and nonsimultaneous procedures.


Percent distribution of T- and B-cells in tonsils of children, juveniles and adults.

The percent distribution of T- and B-lymphocytes in tonsilar tissue of 122 patients from 2--68 years and both sexes was investigated. T-cells were determined by the E-rosetting technique and B-cells by immunofluorescence. We found 50.3% B-cells and 30.6% T-cells in tonsilar tissue. There was a significant decrease of IgM-receptor carrying cells with increasing age and with a converse behavior of the sum of IgA-, IgD-, IgE-receptor B-cells. In tonsils with acute inflammation and with hyperplasia IgM cells were also increased significantly when compared to cell counts in chronic tonsillitis. The results are discussed and compared to data from the literature.


The influence of different fixatives and osmolality on the ultrastructure of the cochlear neuroepithelium.

To investigate which fixative is most suitable for the preservation of cochlear hair cells three main groups of fixatives were used: 1. 3% glutar aldehyde in various buffers (osmolality altered). 2. Glutar aldehyde/paraform aldehyde combination (ad modum Karnovsky). 3. Osmic acid solutions (OsO4) in veronal acetate buffer according to Rhodin (1954). The 2% osmic acid fixative (350--370mosm/kg) resulted in an excellent ultrastructural preservation; an acceptable result was obtained with a 3% glutar aldehyde fixative in 0.1 M sodium phosphate buffer, 600--700 mosm/kg and the Karnovsky's fixative.


An electron microscopic study of the mode of donor cell death in unmodified rejection of pig liver allografts.

The only type of cell death found in pig liver allografts 1 week after technically successful operation was apoptosis. Its extent paralleled the degree of mononuclear cell infiltration of the liver parenchyma, and mononuclear cells were found applied to the surfaces of hepatocytes showing early stages of the process. The results suggest that cellular immune attack induces apoptosis of donor cells, and that the action is a direct one. However, implication of other factors such as vascular damage in the induction of apoptosis in the grafts could not be excluded.


The response of foetal sheep to the somatic and flagellar antigens of Salmonella typhimurium.

Following the injection of polymeric flagellin (POL), foetal sheep older than 70 days gestation produced haemagglutinating antibody and synthesized IgM. The maximum titre of antibody in the blood increased with the age at which the foetus was injected. All foetuses synthesized 2-mercapto-ethanol-sensitive antibodies, while older foetuses (approximately 120 days gestation) also produced 2-mercaptoethanol-resistant antibodies and synthesized IgG1. During the primary immune response, there was a poor correlation between the antibody titre and the amount of immunoglobulin synthesized. The majority of IgM synthesized and almost all IgG1 had no demonstrable specificity for POL. During the secondary response to POL, the majority of IgG1 synthesized was specific and in one case appeared to be monoclona. There was no detectable primary antibody response in foetal sheep to the somatic antigens of Salmonella typhimurium, although all foetuses synthesized IgM. Only one of six foetuses receiving a second injection of antigen produced antibody. There was an increase in the numbers of blood lymphocytes following the injection of both POL and S. typhimurium, but only POL induced a rapid increase in the numbers of neutrophils in the blood and produced histological changes in the draining lymph nodes and spleen.


Immunofluorescence studies on formalin-fixed and paraffin-embedded material.

In an attempt to apply immunomorphologic techniques to formalin-fixed material, various tissues were studied by indirect immunofluorescence. To minimize nonspecific background staining, formalin-fixed paraffin sections were treated with pronase prior to incubation with the antisera. This technique was published by Huang in 1975 to study hepatitis B core and surface antigen in formalin-fixed liver-tissue. Our examination demonstrate that this technique might enable the morphologist to identify immunoglobulins in formalin-fixed tissues and so to get new criteria for their diagnosis.


[Diagnosis of anthrax and para-anthrax with reference to immunofluorescence technic].

504 diagnostic samples were subjected to a fluorescence serology and culturah test for black quarter and malignant oedema. In 459 cases (91.1%) the results of both testing methods wede identical. 26 first results were made by culture (14 X malignant oedema, 12 X black quarter). 19 results (14 malignant oedema, 5 X black quarter) were obtained by immuno-fluorescence only. Culture was shown to be not significantly better than fluorescence, especially in determining black quarter. In the diagnosis of black quarter and malignant oedema the combination of immunofluorescence with culture can be considered as the optimal testing method available at the present time, in that by this method there would be no need for an additional diagnostic test on the animal.


A spectrum of cutaneous angiogenesis.

A spectrum of cutaneous angiogenesis was observed ranging from normal epidermis to hyperproliferative-but-benign psoriatic epidermis to wildly proliferating neoplastic epidermis. This spectrum of vascular response appears to parallel the metabolic and mitotic activity of the tissues studied.


Vasomotor reactions in the islets affecting the blood glucose levels.

1. The spiral nerve fiber and the nerve ganglion are demonstrated adjacent to the small pancreatic duct, artery and vein of the mouse in vivo. 2. Epinephrine and ephedrine, which are sympathomimetic amines, cause vasoconstriction of the afferent and efferent vessels of the islets of Langerhans and cause the interruption of circulation in the intrainsular capillary plexuses, which results in increased blood glucose levels. 3. Methacholine chloride, a parasympathomimetic drug, causes vasodilatation of the afferent and efferent vessels of the islets along with slower but continuous blood flow in the intrainsular capillary plexus, thus causes decreased blood glucose levels. 4. These changes in microcirculation of the islets of Langerhans in mice prove that one of the mechanisms of glucose homeostasis is mediated through autonomic nervous system by alteration of the vascular supply of the islets, which may be classified as neurovascular homeostatic regulator.


Influence of defined gene blocks on the competitive ability of yeast genotypes.

Competition experiments were carried out under varying exogenic and endogenic conditions. The genotypes were marked by combinations of two esterase loci, each with two alleles. When genotypes of the line W7 were used, there was no demonstrable influence of the gene blocks marked by the Est-1 locus on the competitive ability at temperatures of 21 and 29 C. However, genotypes carrying the fast allele of the Est-2 locus were favored. At 38 C, the outcome of the competition was reversed. The defined gene blocks showed different effects when interacting with different genetic backgrounds (line M7). Genotypes marked by the slow allele of the Est-2 locus were now favored (21 and 29 C), and even the gene blocks marked by the alleles of the Est-1 locus influenced the genotypes' competitive abilities. Again, the results were partly reversed at 38 C. The results are discussed with regard to the importance of enzyme variants for the genotypic selection value.


Bioautography: a general method for the visualization of isozymes.

A new method has been developed for visualization of isozymes which are difficult or impossible to detect with standard histochemical or autoradiographic methods. The principle of this method, bioautography, is the use of a microbial reagent to locate an enzyme after gel electrophoresis. When bioautography was compared to other staining procedures, the bioautographic method yielded identical results to those observed by the histochemical method for lactate dehydrogenase (LDH) or by the autoradiographic method for the adenine phosphoribosyltransferase (APRT). Using the bioautographic method, stains for enzymes which could not be visualized by any other procedure have been developed: argininosuccinate lyase and branched-chain aminotransferase. By employing appropriately genetically marked bacterial strains, it should be possible to develop new isozyme stains for a large number of unstudied isozymes.


Incorporation of methionine-derived methyl groups into sirohaem by Escherichia coli.

Sirohaem is a new type of haem that has been detected as a prosthetic group of several bacterial and plant enzymes that catalyse the six-electron reductions of sulphite to sulphide or of nitrite to NH(3). When a methionine-requiring mutant of Escherichia coli K12 was grown on a minimal medium supplemented with d-glucose and l-[Me-(3)H]methionine, 2.4 methyl groups per spectrophotometrically detectable haem group were incorporated into the sirohaem prosthetic group of the NADPH-sulphite reductase isolated from the organism. When the same strain of cells was grown on minimal medium supplemented with d-[U-(14)C]glucose and l-[Me-(3)H]methionine, the sirohaem isolated was found to contain a ratio of glucose-derived carbon/methionine-derived methyl of 19.8. This ratio is in excellent agreement with the value of 20 predicted by the iron-dimethyl-urotetrahydroporphyrin structure for sirohaem proposed by Murphy, Siegel, Kamin & Rosenthal [(1973) J. Biol. Chem.248, 2801-2814]. It can be concluded that sirohaem is indeed methylated, with the methyl groups derived from methionine (rather than by modification of existing side chains, as in protohaem). The structure proposed by Murphy et al. (1973) is therefore probably correct in its essential features. A possible relationship between the pathway for biosynthesis of sirohaem and that for synthesis of vitamin B(12) is discussed.


The first step in the activation of chicken pepsinogen is similar to that of prochymosin.

Chicken pepsinogen was incubated at pH2.5 with pepstatin. The zymogen activated itself by a sequential mechanism and an intact peptide derived from residues 1-26 in the protein was released in the first step. This peptide was found to inhibit the milk-clotting activities of pig and chicken pepsins and calf chymosin but to different extents.


Toxic and immunodepressive effects of L-asparaginase from E. coli and from Erwinia carotovora following chronic administration in rats.

The effects of the administration of L-asparaginase from E. coli and Erwinia carotovora were studied in rats treated for 90 days with 800 or 3200 IU/kg body weight. The studies included overall toxicity on the liver, pancreas, and enteric mucosa as evaluated by both opitcal and electron microscopic examination, biochemical findings, behaviour of IgM-hemolysin producing cells, and antias-paraginase antibody production. The toxic effect and the immunodepressive activity appeared rather early, tending later to decrease. No sex correlation or clear cut dose correlation were observed. However, slight differences in toxicity between the two types of L-ASN-ase were present.


[Experimental studies in animals on the influence of fluocortin butylester on the course of generalized infections (author's transl)].

The influence of butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit), a new corticosteroidal compound with a marked dissociation between local antiinflammatory and systemic action, upon resistance against infections was studied in experimental bacterial and fungal infections in mice. The results of the experiments showed, that fluocortin butylester, even after repeated s.c. or oral administration of dosages up to 100 mg/kg did not depress the resistance of the animals against microbial infections. The relevance of the animal models was checked by parallel experiments with fluocortolone, hydrocortisone, prednisolone and cyclophosphamide.


[Clinical trial of fluocortin butylester in a double-blind contralateral comparison versus fluocortolone and hydrocortisone acetate (author's transl)].

Butyl 6alpha-fluoro-11beta-hydroxy-3,20-dioxo-16alpha-methyl-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) is a recently developed corticosteroid, its distinguishing properties being that it is non-embryotoxic and has practially no systemic effects. In the course of 6 multicentre studies fluocortin butylester was tested in the forms of cream, ointment and fatty ointment in a comparison with corresponding formulations containing fluocortolone (Ultralan) caproate or pivalate, or hydrocortisone acetate. The total study population comprised 1705 patients with various dermal disorders. The results of these double-blind contralateral studies permit the conclusion that the efficacy of the Vaspit preparations ranges between those of fluocortolone and hydrocortisone acetate. Considering the risks involved with local corticosteroid therapy in children the development of a local corticosteroid with the properties of fluocortin butylester must be acknowledged as an advance.


Preliminary clinical evaluation of a new topical corticosteroid, halopredone acetate, as compared to fluocinonide.

17,21-Bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon), a new corticosteroid for topical use, was compared with fluocinonide in a double blind sequential study. The tests were made on a total of 16 patients affected with psoriasis and exudative dermatitis. In each patient, the symmetrically distributed skin lesions were separately treated with either halopredone acetate or the reference compound. The two active substances were in the same concentration (0.05%) in the same carrier (cream), and both reduced the subjective and objective symptoms of these skin conditions. No statistically significant differences were observed between the two medicated areas. Haloperidone acetate, the excipients of the cream and the reference compound were all excellently tolerated.


Effect of systemic lupus erythematosus antibodies against DNA on RNA synthesis.

The majority of tested systemic lupus erythematosus (SLE) sera inhibited RNA synthesis in vitro on the stage of RNA chain elongation. Two sera were also active in inhibiting the binding of the enzyme to the template. No correlation has been found between the sera activity in filter radioimmunoassay, their specificity to double- or single-stranded DNA, and the degree of RNA synthesis inhibition.


Clinical study of the relationship between dose and response to halopredone acetate in dermatoses.

A comparative clinical investigation with three different concentrations of 17,21-bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon), a new topical corticosteroid, has been made to assess the optimum concentration of active substance to be incorporated into cream on the basis of the therapeutic effects achieved in dermatologic patients. The remarkable therapeutical effectiveness of the new steroid, however, has made it impossible to ascertain statistically significant differences between preparations containing either 0.01%, 0.025% or 0.05% of active substance, and to gain thereby a clear answer concerning the relationship between dose and response. Numerous haematochemical controls were made during the trials. In particular, we determined the plasma cortisol levels in patients suffering from large lesions requiring prolonged occlusive medication. No significant alterations of the basal values were observed. As already observed in animals, halopredone, acetate is devoid in humans also of the wellknown effects on the hypophysial-adrenal axis due to transcutaneous absorption of steroids.


Clinical investigation of halopredone acetate, a new topical steroid, in dermatology. Controlled study.

17,21-Bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon) cream, a new synthetic corticosteroid for topical use, has been evaluated against betamethasone valerate by means of double-blind sequential study, where the patients, mainly affected with psoriasis, presented symmetrically located lesions which were treated with either the new drug or the reference cream so that each patient could serve as his own control. Activity and tolerability of the two preparations were equivalent. This equivalence is particularly significant when bearing in mind that the concentration of the active principle (0.01%) contained in the halopredone acetate cream is one of the lowest employed so far and 10 times lower than that of the reference steroid (betamethasone valerate 0.1%). A second open trial, made in 30 patients suffering from psoriasis, confirmed the positive anti-inflammatory properties which the new substance had already displayed during the previous pharmacological tests.


[Open study of befuraline (DIV 154) in 64 depressive patients (author's transl)].

The therapeutic efficacy of the new compound N-benzo[B]-furan-2-ylcarbonyl-N'-benzylpiperazine hydrochloride (befuraline) was evaluated in 64 patients presenting various depressive syndromes. Improvement was found in 33 cases (= 52%) under a daily dose of 150 mg befuraline; 31 of these patients improved within the first 8 days of treatment. Patients with endogenous depression responded favourably to the befuraline therapy, 23 (= 70%) of these (33) patients showing full recovery. Improvement was more frequently observed in patients with mild depression than in severe cases. It seems noteworthy that under befuraline treatment there was also a marked improvement in 21 cases in whom previous long-term therapy with other psychotropic drugs had remained ineffective. Side effects consisted mainly of reversible psycho-organic troubles; extrapyramidal disorders were not observed.


Effect of zimelidine (H 102/09) in depressive patients.

Z-1-(4-Bromophenyl)-1-(3-pyridyl)-3-dimethylaminopropene dihydrochloride hydrate (zimelidine; H 102/09), a newly developed bicyclic substance, was tested in a pilot study for its clinical effect in 10 female patients with a depressive syndrome. Zimelidine inhibits the 5-hydroxytryptamine (5-HT) reuptake more potently than does chlorimipramine. The action on the norepinephrine reuptake is weaker compared with imipramine, also the cardiotoxic and anticholinergic effects are lower. Zimelidine was administered for 20 days in a daily dose of 150 mg. A significant (p less than 0.05) improvement from the beginning of the treatment to the 15th day was demonstrated in Hamilton rating scale and a self-rating scale (von Zerssen). Nevertheless, the zimelidine treatment had to be discontinued between the 15th and 18th days in 3 patients, because of agitation symptoms. The antidepressant action in some patients justifies the performance of controlled studies.


Clinical electrophysiological effects of atenolol--a new cardioselective beta-blocking agent.

Atenolol, a cardioselective beta-blocking agent, at dose levels of 0.03, 0.06, and 0.12 mg/kg intravenously, produced prolongation of atrioventricular nodal conduction in 22 patients with suspected coronary artery disease. In a dose of 0.12 mg/kg body weight atenolol produced significant prolongation of sinus cycle length, sinus node recovery time, atrioventricular node conduction, and the effective and functional refractory periods of the atrium and the atrioventricular node. No significant effects were observed on the His Purkinje system or the effective refractory periods of the ventricle. In these actions atenolol closely resembles propranolol. However, because in contrast to propranolol it increases atrial refractoriness, it may have advantages in the treatment of atrial arrhythmias.


Haemodynamic effects of atenolol in patients with coronary artery disease.

The haemodynamic effects of atenolol, a new cardioselective beta-blocking agent, have been studied at rest in 8 patients with coronary artery disease. The drug was administered intravenously in cumulative doses of 0.03, 0.06, and 0.12 mg/kg body weight. A significant decrease in heart rate was associated with a fall in cardiac output. However, this cardiac output fall was not entiely rate dependent, since stroke volume fell significantly both during spontaneous sinus rhythm and when heart rate was maintained constant by atrial pacing. A dose related and significant reduction occurred in left ventricular dP/dt max without significant change in left ventricular filling pressure or mean aortic pressure. Total peripheral resistance at rest rose after atenolol. The haemodynamic findings more closely resemble those which follow intravenous propranolol than those after intravenous practolol in a similar group of patients. These actions of atenolol suggest that it may be a useful agent in the treatment of patients with angina pectoris.


Analgesic effect of ethyl alcohol.

The analgesic properties of ethyl alcohol administered i.v. were investigated, using elevation of the pain threshold for applied somatic stimuli as an index. Alcohol proved markedly superior to saline in this respect and produced an effect equivalent to that of i.v. morphine.


Effects of adrenaline and the concentration of solution on extradural block with etidocaine.

Forty patients allocated to four groups received extradural injections of etidocaine for the performance of lower abdominal surgery. Twenty millilitre of the 1% or 1.5% solutions with or without adrenaline (1:200 000) was given in a double-blind manner. The addition of adrenaline to etidocaine did not significantly prolong the duration of analgesia, but it produced significant more motor block. Etidocaine 1.5% caused significantly longer durations of analgesia and more motor block than the 1% solution. The spread of sensory analgesia was similar with all four solutions of local anaesthetic agent.


Effect of mianserin hydrochloride on peripheral uptake mechanisms for noradrenaline and 5-hydroxytryptamine in man.

1. Mianserin seems to have little effect on peripheral noradrenaline (NA) re-uptake mechanisms as shown by its lack of effects on the tyramine dose and NA dose/pressor response. 2. Mianserin has no effect on the hypotensive action of bethanidine. 3. Mianserin in vivo has a significant action on platlet transport (Vmax) of 5-hydroxytryptamine (5-HT), which changes toward normal values in depressive patients on the drug. This action is not observed in vitro. 4. It is possible that a metabolite of mianserin is responsible for this effect, and that this may be of therapeutic importance.


Cardiovascular responses to mianserin hydrochloride: a comparison with tricyclic antidepressant drugs.

1. The cardiovascular responses of mianserin hydrochloride and tricyclic antidepressant drugs were investigated using non-invasive methods of cardiac investigation. A study of the interaction of mianserin and antihypertensive drug therapy is reported. 2. In six normal volunteers, mianserin hydrochloride 20 mg was shown to prolong the corrected Q-T interval at 150 min (P less than 0.001). It did not affect heart rate, systolic time intervals or the peak normalized derivative of the apexcardiogram. Amitriptyline 50 mg increased the corrected pre-ejection period interval (PEPI) and the PEP/left ventricular ejection time (LVET) ratio of the systolic time intervals at 150 min (P less than 0.001). Q-T interval was shortened at 90 minutes. 3. In a double-blind patient study, clomipramine increased heart rate, P-R interval, QRS and corrected Q-T interval in one patient at 2 weeks. Mianserin prolonged corrected Q-T interval at 1 week but this returned to the pretreatment time by 2 weeks in two patients. 4. In an open study, mianserin 20 mg three times daily did not antagonize the hypotensive action of propranolol or propranolol and hydrallazine in three patients. 5. In a double-blind study in three patients with desmethylimipramine 25 mg three times daily, mianserin 20 mg three times daily did not antagonize the hypotensive action of either guanethidine or bethanidine.


Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo.

1. Eighteen healthy male volunteers were treated at random in double-blind conditions with mianserin, amitriptyline, or placebo for 8 days. Measurements were made of various parameters indicative of anticholinergic and blood pressure effects. 2. Mianserin showed no significant anticholinergic effects on any of the measures used. Compared with placebo, mianserin significantly reduced pupil diameter and tended to increase salivary production and increase the distance of the near point. 3. Amitriptyline showed evidence of anticholinergic effects in that salivary production fell to a level significantly lower than that of the mianserin- or placebo-treated subjects. The distance of the near point tended to increase during amitriptyline treatment. Compared with placebo, amitriptyline also significantly reduced pupil diameter on some occasions. 4. Amitriptyline produced postural hypotension to a statistically significant degree, whereas this effect was not observed during mianserin treatment. 5. In conclusion, mianserin in doses of up to 60 mg daily given to healthy males seemed to lack the anticholinergic effects and postural hypotension associated with amitriptyline treatment.


Clinical study of mianserin, imipramine and placebo in depression: blood level and MHPG correlations.

1. The clinical efficacy of mianserin, a tetracyclic compound, was compared with imipramine and placebo in 47 hospitalized depressed patients. 2. The clinical ratings showed that the three treatment groups improved equivalently during hospitalization. 3. Plasma levels of mianserin correlated with changes in the Hamilton Rating Scale for depression, total score and two of its factors (anxiety/somatization, and retardation) and the item 'late insomnia'. 4. Drowsiness was a more frequent side-effect among mianserin patients on day 4; no other side-effect distinguished the treatments. 5. No relationship between MHPG levels and treatment or treatment outcome were observed.


Electroencephalogram study of mianserin in depressed patients.

1. Electroencephalogram (EEG) recordings and blood level assessments were included in a clinical comparison of the effects of mianserin (GB-94), imipramine and placebo in depressed, hospitalized patients during a 3-week observation period. 2. Temporal changes in behavioural ratings were observed, but these failed to be distinguished among the active drugs and placebo. EEG measures also showed temporal changes, but these also failed to distinguish among the drug conditions, except at 2 h after administration of the first dose. 3. Plasma levels of mianserin were obtained with EEG recordings in a temporal relationship to the behavioural assessments. There were no correlations between the changes in EEG variables and plasma levels of mianserin, or between EEG and behavioural variables, except on acute administration. The lack of discrimination for the EEG variables may be related to the quality of the EEG recordings and the poor control of the temporal relationships of behavioural assessments to EEG recording and drug dosing.


Effects of amitriptyline and mianserin on psychomotor skills and memory in man.

1. Twenty volunteers were treated with amitriptyline 25 mg, mianserin 10 mg, and placebo, three times daily for 2 weeks each, in a double-blind cross-over study. Tests of psychomotor function and of learning and memory, were carried out after consumption of alcohol or a placebo drink at intervals during each treatment period. 2. Coordinative and reactive skills were affected by mianserin on the first day only, but by amitriptyline up to day 7 in most of the tests. Both drugs seemed to interact additively with alcohol. 3. Amitriptyline impaired short-term memory span and acquisition, and alcohol enhanced these effects. Mianserin did not affect learning and memory, and did not interact with alcohol in this respect. 4. The differing effects of amitripyline and mianserin are considered in relation to anticholinergic properties.


Comparative double-blind trial of mianserin hydrochloride (Organon GB94) and diazepam in patients with depressive illness.

1. The antidepressant action of mianserin was tested in a double-blind clinical trial lasting 6 weeks. Forty-six patients with moderate to severe degrees of depression were treated at random with mianserin or diazepam. Patients who failed to improve by week 3 were taken out of the trial. 2. Mianserin was more effective than diazepam in reducing scores on the Hamilton Rating Scale for depression. Fewer patients allocated to mianserin had to be withdrawn from the trial on account of failure to improve. Mianserin was more effective than diazepam in reducing symptoms of 'retarded depression' and as effective as diazepam in reducing symptoms of 'anxious depression'. 3. Mianserin did not cause any more side-effects than diazepam, very few side-effects being encountered with either drug. 4. The design of this trial on antidepressant drugs is commended on ethical grounds.


Relationship between mianserin plasma levels and antidepressant effect in a double-blind trial comparing a single night-time and divided daily dose regimens.

1. Twenty-six in-patients and 24 out-patients suffering from moderate or severe primary depressive illness were randomly allocated to either a single night-time dose of mianserin 60 mg or a three times daily regimen in a double-blind controlled trial. 2. There was no significant difference in antidepressant effect between the two dosage regimens in either patient group measured using Hamilton Rating Scale (HRS), the Beck Self-Rating Inventory (BSRI) and the new Montgomery and Asberg Depression Scale (MADS). 3. A significant negative correlation (-0.36 P less than 0.05) was found between plasma levels and clinical response using the MADS. A trend for patients with low levels to do worse was also observed suggesting a curvilinear relationship. A highly significant poorer clinical response in patients with levels above 70 microgram/1 was observed using the MADS (t = 3.33, P less than 0.005). This was also seen with the HRS (t = 2.42, P less than 0.02). 4. A significant correlation (r = 0.29, P less than 0.05) with age is reported, and a highly significant increased variability (F = 7.07, P less than 0.001) of mianserin plasma levels in patients over 55 was demonstrated.


Mianserin in the treatment of depressive illness and anxiety states in general practice.

1. In an initial study in general practice, mianserin was shown to be of similar antidepressant efficacy to imipramine. 2. A subsequent placebo-controlled study confirmed that mianserin is an effective as imipramine, and also demonstrated that both mianserin and imipramine are superior to placebo in the treatment of depression in general practice. 3. In a third trial, mianserin was found to be as effective as diazepam in the treatment of anxiety states in general practice. 4. The overall incidence of side-effects in this series of studies, either with mianserin or with the comparison drugs, was very low.


A double-blind multicentre trial comparing mianserin with imipramine.

1. Fifty-four depressive in-patients aged 18-45 yr, were treated at random, in double-blind conditions, with mianserin 60 mg daily or imipramine 150 mg daily in three divided doses for 4 weeks. Nitrazepam and diazepam were also allowed if necessary. 2. There was no significant difference in antidepressant efficacy between the two groups, as assessed by the rating scales of Hamilton, Beck and Overall, the Brief Psychiatric Rating Scale, and a global clinical rating. 3. The overall frequency of side-effects was significantly lower with mianserin than with imipramine. Autonomic symptoms increased in severity during treatment with imipramine, but not with mianserin. 4. the patients treated with imipramine had a fall in blood pressure which was not observed during mianserin treatment.


A comparison of ampicillin, erythromycin and erythromycin with sulphametopyrazine in the treatment of infective exacerbations of chronic bronchitis.

A comparative study of ampicillin (500 mg four times daily), erythromycin (500 mg four times daily) and sulphametopyrazine (1 g at start of exacerbation) followed by erythromycin (500 mg four times daily) was carried out in infective exacerbations of chronic bronchitis. Ampicillin and erythromycin were found to be equally effective, but the combination of erythromycin and sulphametopyrazine was significantly less effective. Unwanted effects were more frequent with ampicillin and with erythromycin plus sulphametopyrazine than with erythromycin alone.


House dust mite hyposensitization.

A double-blind controlled trial of house dust mite hyposensitization was carried out in 14 patients with asthma, who were hypersensitive on skin testing to the house dust mite alone. Measurements were made, using a Wright's peak flowmeter, during the 15-month trial period. Precautions were taken in the home to reduce the mite population. At the end of the trial, no clinical improvement was noted subjectively or objectively, despite a reduced bronchial sensitivity to allergen in the treated group. The role of the house dust mite as a cause of asthma is discussed.


Immuno-electron microscopic studies of surface receptors and antigens of human Langerhans cells.

A heteroantiserum, prepared in rabbits against fractionated cell membranes of a human B-lymphoblastoid cell line, was used to study the distribution of Ia antigen(s) in human epidermis. Indirect immunofluorescence staining demonstrated specific reactivity of dendritic supra-basal cells, consistent in location with Langerhans cells. Basally located cells were noted in biopsy specimens from vitiliginous skin and from the leukodermatous regions of halo naevi. The specificity of the reaction was confirmed at the ultrastructural level by means of ferritin labelling methods. Cell surface staining was confined in the epidermis to Langerhans cells. Fc and C3' receptors were studied by means of rosetting methods. Negative results were obtained on frozen sections, while 2-3% of cells formed rosettes when applied to an epidermal cell suspension.


Immunopathological studies on the cutaneous lesions in sarcoidosis.

We examined the immunohistology of the cutaneous granulomas in sarcoidosis. By direct immunofluorescence immunoglobulin deposits were found in the skin lesions of 5 to 8 patients. These consisted of IgM within blood vessel wall (5 patients), IgM at the epidermal-dermal junction (2 patients) and IgG within and around the granuloma (2 patients). A fibrin network was present within the granulomas. Biopsy of a Kveim test site but not of uninvolved skin or of an erythema nodosum lesion showed similar immunofluorescence findings. Sheep erythrocytes sensitized with IgG antibody adhered to epithelioid cells within the granuloma indicating the presence of surface Fc receptors. At the periphery of the granulomas were B-lymphocytes. These findings are similar to those described in nodal and pulmonary sarcoid granulomas, and suggest that humoral antibodies may be important in the pathogenesis of the sarcoid granuloma.


The long term treatment with beta-carotene in erythropoietic protoporphyria: a controlled trial.

The efficacy of oral beta-carotene for the prevention of photosensitivity symptoms in erythropoietic protoporphyria was studied in a controlled cross-over trial in which it was compared with a placebo. No significant difference was found between the 2 preparations. Patients' symptoms showed statistically significant association with sunlight hour records.


Streptococcal impetigo and acute glomerulonephritis in children in Cairo.

Impetigo contagiosa in Cairo affected young children of both sexes, the face being the main site. Post-impetigo nephritis, confirmed by a low serum C3 level and by urinalysis, occurred in only 11% of cases. Streptococcus pyogenes strains were recovered from 84% of the skin lesions. Sixteen types were identified according to their T-protein, and most infections were associated with T3/B3264, T13/B3264, T5, T11, T12, T8/25/Imp 19 and T14/49; the majority of these types were also recovered from houseflies. The types isolated from cases of post-impetigo nephritis were T4 (M 60), T14/49 (M49), T8/25/Imp 19 (mostly M 55) and T11. Seventy percent of the patients infected with T4 (M 60) and 40% of those infected with T14/49 (M 49) developed nephritis. Strains isolated from the skin bore a closer resemblance to those isolated from the nose than to those found in the throat. The ASO response was poor in uncomplicated impetigo but the titre rose more aften in post-impetigo nephritis.


An immunoenzyme histochemical technique for the detection of platelet antibodies from the serum of patients with idiopathic (autoimmune) thrombocytopenic purpura (ITP).

The resent report describes a simple, reproducible, semi-quantitative immunohistochemical assay for the detection of antiplatelet antibody. Evaluation of the technique in 10 children with active idiopathic (autoimmune) thrombocytopenic purpura (ITP), seven children with thrombocytopenia due to other causes, and 12 normal individuals revealed that the assay consistently and reliably distinguished children with ITP from the other groups. Individuals who had had multiple platelet transfusions and individuals with systemic lupus erythematosus (SLE) also had antiplatelet antibodies detectable using this technique although the levels were less than those of individuals with ITP. The method can be used effectively to monitor the course of ITP and the effects of therapy.


Platelet Autoimmunity.

Autoimmunity to platelets was looked for by complement fixation, antiglobulin consumption, transformation and migration-inhibition techniques. Only the migration-inhibition method gave consistently positive results. The test was positive in nine out of 14 patients with idiopathic thrombocytopenic purpura and all five patients with glandular fever.


Immunological evidence that human factor VIII is composed of two linked moieties.

The relationship between the three measurable components of the factor VIII complex, procoagulant activity (VIII:C), Ristocetin cofactor (VIIIR:WF) and  factor VIII related antigen (VIIR:AG), has been investigated using a solid phase immunoadsorption system in which homologous antibodies specific for VIII:C are insolubilized onto Sepharose beads. The VIII:C component of partially purified factor VIII can be completely separated from the Willebrand factor (VIIIR:WF/VIIIR:AG) by this technique. The loss of VIII:C has no detectable effect on the molecular size, antigenicity or electrophoretic mobility of the original molecule. The Willebrand factor (WF) recovered from these immunoadsorption columns was used to absorb heterologous antisera to factor VIII. A specific heterologous antiserum to VIII:C, which no longer neutralized VIIIR:WF nor precipitated VIIIR:AG, was obtained. Heterologous antisera to WF were prepared which potently neutralized VIIR:WF and precipitated with VIIIR:AG, but also weakly neutralized VIII:C (titre I u/ml). This study is compatible with the theory that VIII:C and VIIIR:WF/VIIIR:AG are two different but linked entities.


Myelotoxicity of methotrexate in animals with pyogenic infection.

Rats stimulated into prolonged increased neutrophil production by the induction of a unilateral pyo-hydronephrosis showed consistent profound neutropenia when methotrexate (MTX) was given during the first 2 d of infection. Thereafter greater neutropenia than that observed in non-infected rats was only observed in occasional animals. There was a significant correlation between the degree of neutropenia induced by MTX and the day after MTX upon which this occurred. The main target for myelotoxicity by MTX appears to be the myelocyte. Its precursors seem relatively insensitive.


Induction of labour by pharmacological and physiological doses of intravenous oxytocin.

In addition to membrane rupture, pharmacological doses of oxytocin (2.6 mU/minute rusing stepwise to 422.4 mU/minute) were used in 134 patients and the results compared to those obtained in 144 patients given only physiological doses of oxytocin (2.6 to 13.2 mU/minute). Pharmacological doses of oxytocin gave better results in terms of induction-delivery intervals, incidence of failed inductions and puerperal morbidity. The incidence of hypertonus was similar in both groups and unrelated to oxytocin doses. A uterine activity of 276 Montevideo units, modified to 200 to 220 Montevideo units for grande multiparae, is defined as the goal of oxytocin treatment in induction of labour. A sign of imminent uterine tetany in the intrauterine pressure curve (the 'damping sign') is described.


Panretinal photocoagulation in central retinal vein occlusion: A randomised controlled clinical study.

A randomised controlled study of photocoagulation compared with no treatment in central retinal vein occlusion is reported. Forty-eight patients were allocated into treated and control groups by a random procedure 3 months after their first visual symptoms. For the analysis they were subdivided into (1) ischaemic type, and (2) hyperpermeability-response macular-oedema type of central retinal vein occlusion. In neither group did treatment confer benefit as far as visual acuity was concerned. However, iris, disc, and retinal neovascularisation improved after treatment in the ischaemic group. In addition none of the treated patients progressed to neovascular glaucoma. Macular-oedema improved in treated patients with the hyperpermeability response, but the visual field was affected and atrophic changes at the macular precluded visual improvement. It is concluded that photocoagulation should be used only to prevent complications in the ischaemic type of central retinal vein occlusion. It does not appear to be of value in the hyperpermeability group.


Bilateral cataract: extraction in classic haemophilia with retrobulbar anaesthesia and peripheral iridectomy.

A 47-year-old factor VIII deficient haemophiliac successfully underwent bilateral cataract extraction. The use of cryoprecipitates to achieve haemostasis permitted retrobulbar anaesthesia and a peripheral iridectomy without complication. We consider that the use of cryoprecipitated factor VIII concentrate allows safe elective ocular surgery in patients with classic haemophilia.


Endothelial cell loss and corneal thickness after intracapsular extraction and iris clip lens implantation: a randomised controlled trial (interim report).

Patients in a randomised controlled trial were chosen either to have iris clip lens implantation after intracapsular cataract extraction or intracapsular extraction only. They were assessed in terms of corneal thickness, postoperative epithelial oedema, and endothelial cell counts. All patients had 1 eye submitted to operation, which was carried out by the same surgeon. There was significantly greater increase in corneal thickness (P less than 0.05) on the 5th postoperative day in eyes which had lens implants (23 patients with intracapsular extraction and 19 with implant), but the difference between the 2 groups became insignificant at 1 month (17 patients in each group). Daily corneal thickness measurements and observations of epithelial oedema in a subgroup (20 patients divided equally into 2 groups) showed that postoperatively there was greater and more widespread corneal oedema after implant surgery. When the operated eye was compared with the unoperated eye, endothelial cell loss was significantly greater in those with implants (P less than 0.01) than in those with simple intracapsular extraction.


Photoinduced affinity labeling of the Escherichia coli ribosome puromycin site.

The photoincorporation of puromycin into Escherichia coli ribosomes has been studied in detail. Incorporation into protein L23 as a function of puromycin concentration follows a simple saturation curve and is specifically blocked by structural and functional analogues of puromycin, thus demonstrating that such incorporation proceeds via an affinity labeling process. Incorporation into L23 becomes more specific as the light fluence is reduced, indicating that such incorporation takes place from a native rather than light-denatured puromycin site. L23 remains the major labeled protein using ribosomes prepared by several procedures, suggesting the conservative nature of the site. In addition evidence is presented for affinity labeling of S14 and of a site in the RNA fraction of the 50S particle. Specific incorporation appears to proceed with an anomalously high quantum yield. The detailed photochemical mechanism is not understood, although 8-alkylation of purine moiety has been excluded. Incorporation is largely inhibited in the presence of thiol reagents.


Altered topography of 16S RNA in the inactive form of Escherichia coli 30S ribosomal subunits.

We have studied the topography of 16S RNA in the inactive form of the 30S ribosomal subunit (Ginsburg, I., et al. (1973) J. Mol. Biol. 79, 481), using the guanine-specific reagent kethoxal. Oligonucleotides surrounding reactive guanine residues were isolated and quantitated by means of diagonal electrophoresis and sequenced. Comparison of these results with experiments on active or reactivated subunits reveals the following: (1) Most of the sites which are reactive in active 30S subunits are much more reactive (average 13-fold) in inactive subunits. Upon reactivation, these sites return to a less reactive state. Thus, a reversible increase in accessibility of specific 16S RNA sites parallels the reversible loss of protein synthesis activity of 30S subunits. (2) The number of kethoxal-reactive sites in inactive subunits is about twice that of active subunits. The nucleotide sequences and locations of the additional accessible sites in inactive subunits have been determined. (3) Sites that can be located in the 16S RNA sequence are distributed throughout the RNA chain in inactive subunits, in contrast to the clustering observed in active subunits. (4) The sites of kethoxal substitution are single stranded. Yet, of the 30 sites that can be located, 23 were predicted to be base paired in the proposed secondary structure model for 16S RNA (Ehresmann, C., et al. (1975), Nucleic Acids Res. 2, 265).