B. H. Belohradsky

Cellular interactions: Scanning electron microscopy of human thymus-derived rosette-forming lymphocytes

Abstract Scanning electron microscopy was used to study morphologic features of the surface of human T-lymphocytes which were incubated with sheep red blood cells without antibody or complement and then separated into rosette forming cells and nonrosette forming cells. Microvilli, 1800–2300 A in diameter and of variable length, were demonstrated on the surface of all lymphocytes. Microvilli formed the attachment with sheep red blood cells suggesting that the receptor sites for this interaction are located on the microvilli. Microvilli on some rosette forming lymphocytes were unequally distributed with the higher density being adjacent to the red blood cells. Rosette forming cells had far more microvilli than did nonrosette forming cells.

Meeting report of the Second International Workshop on Primary Immunodeficiency Diseases in Man.

Abstract The Second International Workshop on the Primary Immunodeficiency Diseases in Man, sponsored by the National Foundation—March of Dimes, was held in St. Petersburg, Florida, February 4–8, 1973. This short review attempts to summarize the most important findings reported at the Workshop. The complete papers and discussions will be published by the National Foundation; however, brief reports of new diagnostic criteria, recently discovered disorders of the immune system, and new information about animal models may be of value immediately to those responsible for therapy of patients with these diseases. The condensed information below is derived from notes taken by the authors; it is not an official proceedings of the workshop. Detailed inquiries regarding topics discussed here should be directed to the appropriate investigators.

Unmasking by antimetabolites of receptors for sheep red blood cells on human lymphocytes

Abstract The action of antimetabolites (puromycin, cycloheximide) and cold was studied in the human rosette system. We found that the number of detectable receptors for sheep red blood cells on peripheral blood lymphocytes was increased in presence of some concentration of these drugs. A similar finding was noted when the blood lymphocytes were left at 4 °C. The possibility that both cold and antimetabolites, by modifying the cell membrane mobility, increase the receptor affinity and thus the number of detectable receptors is discussed. Another attractive possibility is also presented. We propose that the unmasking effect by antimetabolites is due to inhibition of protein synthesis which is necessary to better express the receptors for sheep red blood cells on human lymphocytes. This concept of decreased protein synthesis affecting the expression of surface receptors may be a more general phenomenon.

Control of mitogen-induced lymphocyte activation: II. Analysis of cell populations and metabolic events involved in cyclic AMP-mediated recovery of DNA synthesis suppressed by mitogens

Abstract Exposure of human peripheral blood lymphocytes to increased doses of PHA (0–2000 μg/ml PHA) leads to a decrease in thymidine incorporation. The addition of exogenous cyclic AMP (10 −3 –10 −4 M ) to lymphocyte cultures exposed to such high levels of PHA results in a recovery of the ability to incorporate both thymidine and uridine. Using this system as a model for the study of cyclic nucleotide metabolism, experiments have demonstrated a differential sensitivity to changes in cyclic nucleotide levels among lymphocyte subpopulations exposed to PHA, concanavalin A, or pokeweed mitogen. Further evidence for differential sensitivity is also obtained using lymphocyte populations separated on the basis of rosette formation. Measurement of intracellular cAMP and cGMP levels in lymphocyte cultures exposed to PHA, concanavalin A, or pokeweed mitogen suggests that while cGMP is the mitogenic signal, cAMP may control deactivation, thereby exerting an overide effect on cGMP mediated events. In addition, metabolic studies suggest that exogenous cAMP may influence PHA-induced transformation up to 67 hr after culture initiation and that the effects of Ca 2+ ions and cyclic nucleotides are interrelated in the activation of lymphocytes by PHA.

Comparison of long- and short-term treatment of recurrent urinary tract infection

SummaryIn accordance with general attempts to restrict medication to the necessary minimum, the length of chemotherapy in girls with recurrent urinary tract infection (UTI) attending our pyelonephritis outpatient clinic was shortened in recent years to 7 to 14 days. Long-term prophylaxis was usually dispensed with (with the exception of patients with below average renal growth, scarring of renal tissue, neurogenic bladder and UTI which had not responded to treatment). Thus it was possible, with some limitations, to compare patients undergoing long-term therapy from 1970 to 1972 (Group 1) with patients undergoing short-term therapy from 1976 to 1977 (Group 2). Group 1 consisted of 43 girls observed for a total of 771 months; Group 2 consisted of 24 girls observed for a total of 458 months. Significant bacteriuria recurred in about 1/2 of both groups shortly after cessation of treatment (after 3 to 5 days). In Group 2 37% of the girls had an episode again within 100 days. A 3–4 fold higher annual “relapse rate” could be established in Group 2 during the treatment-free period. Short-term therapy can be recommended in the majority of patients observed since prognostically neither clinical nor radiological differences were found apart from the repeated episodes. Neither the spectrum of the infecting organisms nor their antibiotic resistance differed to a marked degree.ZusammenfassungDen allgemeinen Bestrebungen folgend, keine über das notwendige Maß hinausgehende Medikation durchzuführen, wurde in unserer Pyelonephritisambulanz die Dauer der Chemotherapie bei Mädchen mit einer rekurrierenden Harnwegsinfektion (HWI) in den letzten Jahren auf 7 bis 14 Tage gekürzt und auf eine präventative Daueraplikation meist verzichtet (ausgenommen Patienten mit unter normalem Nierenwachstum, Nierengewebsnarben, neurogenen Blasen und nicht beherrschbarer HWI). So konnte unter gewissen Einschränkungen eine langzeitbehandelte Gruppe 1 (1970–72) einer nur den akuten Schub kurz behandelten Gruppe 2 (1976–77) gegenübergestellt werden. Gruppe 1 bestand aus 43 Mädchen mit insgesamt 771 Beobachtungsmonaten, Gruppe 2 aus 24 Mädchen mit 458 Beobachtungsmonaten. Unmittelbar nach dem Abbruch der Behandlung (nach 3 bis 5 Tagen) kam es bei etwa 1/2 der Patienten innerhalbbeider Gruppen zum Wiederauftreten einer signifikanten Bakteriurie. Bei Gruppe 2 kam es innerhalb von 100 Tagen bei 37% der Mädchen zu erneuten Schüben. Im Verlauf therapiefreier Zeit läßt sich das Zustandekommen der 3- bis 4mal höheren jährlichen „Rezidivrate“ der Gruppe 2 verfolgen. Da sich, abgesehen von den Schüben, weder in klinischer noch in radiologischer Hinsicht prognostische Unterschiede ergaben — alle Kontrolluntersuchungen ergaben normale Werte — dürfte eine Kurzzeitbehandlung bei einem Großteil der beobachteten Patienten unter ausreichender Überwachung zu verantworten sein. Weder die Zusammensetzung der Erreger, noch das Resistenzspektrum beider Gruppen unterschieden sich merklich.

Die Behandlung von Neu- und Frühgeborenen mit Cefoxitin

ZusammenfassungBei 14 schwererkrankten bzw. im Abdominalbereich operierten Neu- und Frühgeborenen wurde Cefoxitin in Kombination mit anderen Antibiotika verabreicht. Bei den Serumspiegelbestimmungen zeigten sich mittlere Spitzenwerte von etwa 100 mcg/ml. Die Halbwertszeiten lagen bei Beginn der Therapie zwischen zwei und vier Stunden, bei den untersuchten Schwerkranken im Rahmen der Gesamttherapie bei über sechs Stunden, jedoch wurde keine gravierende Kumulation festgestellt. Aufgrund des Wirkungsspektrums erscheint Cefoxitin für die Behandlung von besonders gefährdeten Neugeborenen und Frühgeborenen bei einer Exposition gegenüberBacteroides fragilis (z. B. durch OP) einschließlich anderer Indikationen für eine Cephalosporin- bzw. Cephamycin-Therapie wie z. B.Escherichia coli- undKlebsiella-Infektionen indiziert.SummaryCefoxitin was administered concomitantly with other antibiotics to 14 neonates and prematures who were severely ill and/or had undergone an abdominal operation. Determinations of the serum levels showed mean peak values of approximately 100 mcg/ml. Half-life intervals at the start of therapy were between two and four hours; after more than six hours, however, no adverse cumulation was observed in the severely ill patients investigated. On the basis of its spectrum of antimicrobial activity, cefoxitin appears indicated for the treatment of neonates and prematures especially susceptible when exposed toBacteroides fragilis (e. g. through surgery), as well as other indications for cephalosporin or cephamycin therapy, such as infections withEscherichia coli orKlebsiella.

Behandlung von Neugeboreneninfektionen mit Cefamandol

ZusammenfassungAnhand der aktuellen bakteriellen Resistenzsituation in einer Kinderklinik wird die Indikation von Cefamandol für die Behandlung der Neugeborenenperiode analysiert. Bei einer Dosierung von 100 mg/kg/Tag ist kein bedrohlicher kumulativer Effekt zu erwarten. Die tiefsten Spiegel während der Behandlung mit einer 3maligen Dosis pro Tag liegen zwischen 0 und 35µg/ml (Frühgeborene!), die Spitzenkonzentrationen um 100 µg/ml. Trotz der erheblichen Variationsbreite ähnelt die Halbwertszeit derjenigen bei Erwachsenen. Die günstigen MHKs bei dem häufigsten gramnegativen Erreger des Neugeborenenalters —Escherichia coli — und die Staphylokokkenempfindlichkeit gegen Cefamandol (die zwar bei Cephalotin in vitro graduell höher ist, aber in vivo aufgrund der günstigeren pharmakokinetischen Verhältnisse zumindest ausgeglichen wird), lassen Cefamandol für das Neugeborenenalter als besonders geeignet erscheinen.SummaryThe indication for treatment with cefamandole in neonates was studied in the light of the resistance situation in a childrens hospital. No dangerous cumulative effect is to be expected with a dosage of 100 mg/kg/day. The lowest concentrations during treatment with a dosage administered thrice daily was between 0 and 35 µg/ml (prematures); the highest concentrations were around 100 µg/ml. Despite the considerable variation, the half-life values were similar to those of adults. This antibiotic appears particularly suitable for treating neonates due to the relatively low MICs forEscherichia coli, the most frequently occurring gram-negative pathogen in neonates, and due to the susceptibility of staphylococci. Staphylococci susceptibility to cephalothin in vitro is higher measured in titer stages, but this is compensated by the favourable pharmacokinetic conditions for cefamandole in vivo.