Comparison of a modified microagglutination technique for HBsAg with the standard technique and a new RIA system.

A further modification of the standard RPHA technique (Hepatest, Wellcome Reagents) for the detection of HBsAg is described. This modification does not require a centrifugation step which is required by the other modifications that have been described previously and consequently takes a little longer to perform. It does, however, retain the advantages of increased sensitivity and decreased costs which are also features of the other modifications. A series of 939 routine clinical specimens were used to evaluate the method described and to evaluate a new RIA kit for the detection of HBsAg (Hepatube, Wellcome Reagents). Of 53 specimens found to be positive for HBsAg by RIA, 50 (94% were detected by the modified Hepatest RPHA as opposed to 47 (89%) by the standard technique.     

An unusual clinical presentation of bilateral schizencephaly

Summary We present a case with a characteristic magnetic resonance image (MRI) of bilateral open-lipped schizencephaly and atypical clinical presentation. The patient is still alive and in good health in her forties, she has never presented seizures, and although the motor dysfunction is well correlated with cerebral lobe involvement, neurobehavioral dysfunction is not proportional to the MR image of the cerebral malformation.

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Un cas inhabituel de schizencéphalie bilatérale

Résumé Nous présentons un cas de schizencéphalie bilatérale ouverte caractérisé par une présentation clinique atypique et une imagerie par résonance magnétique nucléaire caractéristique. La patiente est encore vivante, en bonne santé, à plus de 40 ans, elle n'a jamais présenté de crise comitiale et, bien que les troubles moteurs soient bien corrélés aux altérations cérébrales, les troubles neuro-comportementaux ne sont pas proportionnels aux images IRM de cette malformation cérébrale.

     

A quantitative method for measuring in vitro synthesis of IgA and IgG by human rectal mucosa: studies on normal controls and patients with hypogammaglobulinaemia.

A quantitative technique has been developed for measurement of immunoglobulin production by human rectal mucosa in vitro. The technique overcomes the problem of serum proteins trapped in the tissue by parallel measurements of Ig and human serum albumin (HSA) over a 6 day period. IgG, IgA, IgM and HSA were measured in supernatant fluids using sensitive radioimmunoassays. The technique has demonstrated IgG and IgA synthesis by rectal mucosa in vitro. The conclusion that the observed IgA and IgG was synthesized in vitro was supported by the demonstration that the production could be increased by pokeweed mitogen and blocked by emetine. This culture system has been applied to measure Ig synthesis by the rectal mucosa of immunodeficient patients.     

The effects of haemorrhage in the unanaesthetized rabbit

1. The circulatory response following acute loss of 26% of the blood volume was examined in unanaesthetized rabbits. The groups of animals studied were normal rabbits; adrenalectomized rabbits; animals subjected to prolonged treatment with guanethidine in which peripheral adrenergic nerve transmission is blocked, but which can reflexly liberate adrenal medullary hormones; animals subjected to combined adrenalectomy and guanethidine treatment with no functional adrenergic effectors; in each case with or without administration of atropine. The responses of animals with section of the carotid sinus and aortic nerves were also examined.

2. The spontaneous rate of replacement of the blood volume after haemorrhage by reabsorption of extravascular fluid was the same in all the above preparations, the blood volume returning to normal 3-4 hr after bleeding.

3. The `passive' effects of haemorrhage were examined in animals without functioning autonomic effectors and include a large fall in right atrial pressure and cardiac output, arterial hypotension, no significant change in total peripheral resistance, and a bradycardia of gradual onset. Reflex autonomic effector activity in normal animals minimizes the fall in atrial pressure, cardiac output and arterial blood pressure, and produces a significant increase in total peripheral resistance and tachycardia. Increased sympathetic nerve activity and secretion of adrenal medullary hormones each play an important and complementary part in the normal circulatory response to haemorrhage of the rabbit. There is also reflex reduction in vagal efferent activity.

4. Reflexes from the carotid sinus and aortic arch limit the fall in arterial pressure for the first 4 hr after haemorrhage. These reflexes also account for the tachycardia normally observed after haemorrhage. The baroreceptor reflexes rather than the chemoreceptors appear to be dominant in these responses.

5. Twenty-four hours after haemorrhage the haemodynamic pattern is similar in all preparations irrespective of their autonomic effector status: blood volume, right atrial pressures and cardiac outputs are all elevated, and the arterial pressure has virtually recovered, consistent with the development of hypervolaemic anaemia at this time.

     

Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis.

AIM--To determine the effects of a three month course of low dose cyclosporin on the expression of epidermal cell adhesion molecules. METHODS--Eighteen patients with psoriasis were treated for 12 weeks with either 2.5 or 5 mg/kg/day of oral cyclosporin. Biopsy specimens taken from skin before, during, and after cyclosporin treatment were stained immunohistochemically for CD 54 (ICAM-1), CD 29 (beta-1 integrins), and CD18 (beta-2 integrins). RESULTS--There was a highly significant (p < 0.01) clinical response after 12 weeks of cyclosporin as assessed by the Psoriasis Area and Severity Index (PASI) score. The staining of CD 29 on keratinocytes of affected and unaffected psoriatic skin was not affected by cyclosporin. Epidermal CD54 was variably expressed in active psoriatic plaques and changed unpredictably after cyclosporin (p = NS). Staining for CD18 on large epidermal dendritic cells was reduced after cyclosporin (p < 0.02). The expression of CD18 by large epidermal dendritic cells during treatment correlated strongly with the PASI score at that time and one month after stopping cyclosporin (p < 0.02). CONCLUSIONS--Persistence of epidermal staining for CD 54 in psoriasis is compatible with a good clinical response to cyclosporin. Residual staining for CD 18 on large epidermal dendritic cells may be a useful marker for early clinical relapse.     

Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity

Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal- reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.      

Bias in treatment assignment in controlled clinical trials

Controlled clinical trials of the treatment of acute myocardial infarction offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment. A group of 145 papers was divided into those in which the randomization process was blinded (57 papers), those in which it may have been unblinded (45 papers), and those in which the controls were selected by a nonrandom process (43 papers). At least one prognostic variable was maldistributed (P less than 0.05) in 14.0 per cent of the blinded-randomization studies, in 26.7 per cent of the unblinded-randomization studies, and in 58.1 per cent of the nonrandomized studies. Differences in case-fatality rates between treatment and control groups (P less than 0.05) were found in 8.8 per cent of the blinded-randomization studies, 24.4 per cent of the unblinded-randomization studies, and 58.1 per cent of the nonrandomized studies. These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration.     

Clinical trials of hepatitis B immune globulin. Development of policies and materials for the 1972-1975 studies sponsored by the National Heart and Lung Institute.

Plasma from persons with high titers of hepatitis B antibody (anti-HBs) was used to manufacture one lot of hepatitis B "immune" globulin sufficient for four interlocking clinical trials of prevention or modification of hepatitis B infections. The trials were carried out in renal dialysis units, in medical personnel with accidental exposures to hepatitis B, in transfused patients, and in patients with fulminant hepatitis. A single policy board developed protocols that allowed comparisons among the four studies while respecting the unique requirements of each.