Topical betamethasone-17-valerate inhibits heat-induced vasodilatation in man

Topical betamethasone-17-valerate inhibits the vasodilatation response to local non-pathological heating of rat skin.¹ We have shown that this effect can also be demonstrated in man. Topical betamethasone-17-valerate significantly inhibited the increase in human forearm cutaneous blood flow in response to heat of 44°C, as measured by laser-Doppler velocimetry. This suggests that the effects of topical steroids upon skin blood flow in the rat and in man are similar, and supports the use of the animal model as a paradigm for studying human skin blood flow, and changes in response to anti-inflammatory steroids.     

The presence of autoantibody to recombinant lipocortin-I in patients with psoriasis and psoriatic arthritis

Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kDa protein, lipocortin-I. Anti-lipocortin-I antibodies (ALA) were measured by enzyme-linked immunosorbent assay (ELISA) in 23 patients with plaque-type psoriasis alone (NAP), in 21 patients with psoriasis and arthritis (PA), and in 67 healthy controls. Only two of 23 NAP patients had elevated ALA, whereas six of 21 PA patients had raised levels of ALA (P = 0.2). Sero-negative polyarthritis was the most common pattern of joint disease in those PA patients with elevated ALA (4/6). ALA levels did not correlate with the extent or severity of cutaneous involvement, and are unlikely to be involved in the pathogenesis of cutaneous psoriasis.     

LONG-TERM CLINICAL AND ANGIOGRAPHIC RESULTS FOLLOWING PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY

The long-term results of percutaneous transluminal coronary angioplasty were evaluated in our first 42 patients, who had initial successful angioplasty and no restenosis on angiogram performed four months after angioplasty. Evaluation included repeat follow-up angiogram performed approximately two years after angioplasty in 22 of the 42 patients. All 42 patients had single vessel disease with severe angina pectoris refractory to medical treatment before angioplasty; at a mean follow-up of 28 months after angioplasty, 37 (88%) were asymptomatic. No patient died or underwent coronary artery bypass graft surgery during the follow-up period, although three patients (7%) suffered a myocardial infarction due to occlusion of a nondilated artery. In the 22 cases studied at a mean of 28 months after angioplasty, angiogram showed that successful coronary artery dilatation remained in all cases, with no deterioration of a dilated lesion between the four and 28 month angiograms. Progression of atherosclerosis, however, did occur in five of the 22 patients (23%), with development of either stenosis or occlusion of a non-dilated vessel. This study suggests that the development of restonsis between four and 28 months after percutaneous transluminal coronary angioplasty is unlikely. The results suggest an excellent long-term prognosis after angioplasty, in patients who have no evidence of restenosis at four months after an initially successful dilatation.     

P2T Purinoceptor Antagonists. A QSAR Study of Some 2-Substituted ATP Analogues

FPL67085MX represents the first in a class of novel, highly potent and selective P_2T purinoceptor antagonists which are inhibitors of adenosine diphosphate (ADP)-induced platelet aggregation in-vitro. In an early series of compounds we studied the effect of variation of the adenine 2-substituent on potency and derived quantitative structure-activity relationships (QSARs) between the properties of the molecules and their biological activity. This work has recently been revisited using comparative molecular-field analysis (CoMFA) and the comparison of the predictions from the two methods is discussed along with their relative merits in terms of compound design. The model suggests that the receptor for these molecules has a narrow lipophilic cleft, which is occupied by the adenine 2-substituent.     

Direct mutation analysis as the preferred method for carrier diagnosis in families with isolated cases of haemophilia B

Summary. Approximately one-third of haemophilia B cases are described as isolated due to their occurrence in families with no prior history of the disorder. In this report, two families with isolated haemophilia B were studied by the standard method of restriction fragment length polymorphism (RFLP) analysis coupled with factor IX activity and antigen levels with the aim of achieving carrier diagnoses. The limitations of using this approach in the determination of carrier status were highlighted by diagnostic problems arising in both families. The problems included difficulty in interpreting bioassay results, homozygosity for the RFLP marker in a key family member and the possibility of germline mosaicism. Unequivocal carrier diagnosis in the two families was ultimately achieved by direct mutation analysis.     

PERFORMANCE OF A SHELL-TYPE HEAT EXCHANGER IN EXTRACORPOREAL CIRCULATION

Tests were performed on a "shell" type heat exchanger used ina simulated extracorporeal circulation. The counter flow modewas the most efficient pattern and recommendations are madeon which flow pattern should be employed with low water flowrates.     

LIGHT AND ELECTRON MICROSCOPICAL STUDIES OF THE IMMUNOPEROXIDASE STAINING OF MULTIPLE SCLEROSIS PLAQUES USING ANTISERA TO A FELINE-DERIVED AGENT AND TO GALACTOCEREBROSIDE

Antibodies have been raised to two agents (CCA147 and MV631) that were isolated from central nervous tissue of cats. The cells co-cultivated with these agents are characterized by the presence of cytoplasmic inclusions consisting of 16-18 nm diameter tubular elements morphologically similar to inclusions seen in a demyelinating condition in cats and to inclusions described as 'curved linear profiles' in multiple sclerosis (MS) plaques. The peroxidase-labelled antibodies to CCA147 and MV631 stain these inclusions in MS plaques as well as small virus-like particles. The antisera do not stain normal white matter either in MS or non-MS brain tissue. The staining reaction of one agent is blocked by pretreatment with antisera to the other agent and also by pretreatment with MS sera but not by normal human sera. Peroxidase-labelled antibody to galactocerebroside stains normal myelin and myelin debris within MS plaques but does not stain the 'curved linear profiles' that are stained by the labelled antibodies to the feline-derived agents. The results show that the 'curved linear profiles' described in MS plaques are not myelin degradation products, but are comparable to the nucleocapsids of morbilliviruses. In addition, the small virus-like particles are morphologically similar to morbillivirus virions. The results are discussed with particular emphasis on the features of the morbilliviruses, canine distemper and measles viruses.     

A Case of Hepatocellular Carcinoma Complicating Hepatitis B Infection in a Nine-year-old Boy

A 9-year-old boy born of Chinese parents in England, and adoptedby English parents at an early age, presented with primary hepatocellularcarcinoma in a non-cirrhotic liver. His serum contained hepatitisB surface antigen and ‘e’ antibody, a probable resultof perinatal infection from an HBsAg carrier mother. The managementof infants at risk of perinatal hepatitis B virus transmissionshould now include active and passive immunisation.