Immunoprecipitation of biosynthetically-labelled proteins from different Papua New Guinea Plasmodium falciparum isolates by sera from individuals in the endemic area

The human serum antibody response to Plasmodium falciparum infection in Papua New Guinea has been studied by electrophoretic analysis of immunoprecipitated biosynthetically-labelled malaria proteins from three different isolates maintained in long-term in vitro culture. Differences in protein antigenic composition in different lines have been described and simplified by examination of antigens recognized only by hyperimmune serum. An in vitro assay has been used to screen various human sera containing antimalarial antibody for their ability to inhibit parasite growth and the immunoprecipitation profiles of non-inhibitory sera have been compared with those of a hyperimmune serum pool. In the discussion, emphasis is placed on the value of immunoprecipitation analyses using clinically-defined sera with known in vitro function in the identification of antigens which may be responsible for the induction of host-protective immunity.     

Treatment of verruca vulgaris with topical cidofovir in an immunocompromised patient: a case report and review of the literature

Lesions caused by verrucus vulgaris are commonly refractory to therapy and may become large, painful, or disfiguring in immunocompromised patients. Cidofovir is a potent nucleoside analog antiviral agent shown to have in vitro and in vivo activity against a broad spectrum of DNA viruses. We report a successful use of topical cidofovir to treat verruca vulgaris lesions in a highly immunocompromised patient, who was not considered a candidate for conventional therapy.     

Post-systolic shortening: a marker of potential for early recovery of acutely ischaemic myocardium in the dog

Regional diastolic wall motion was studied with sonomicrometry in 30 open chest anaesthetised dogs after left anterior descending stenosis or occlusion. Post-systolic shortening and thickening, defined as the magnitude of segment shortening or wall thickening that occurred after end systole, was measured in peripheral and central ischaemic segments. These post-systolic events developed concurrently with impaired systolic shortening or thickening, either immediately after acute coronary occlusion or during progressive stenosis, and persisted with the development of dyskinesis and during reperfusion. The magnitude of these events in dyskinetic segments of 24 dogs was considerable, reaching 50(2)% (mean(SEM)) and 33(3)% of shortening or thickening that was present before coronary occlusion. Post-systolic shortening and thickening were maximum at 100(2) ms after peak negative dP/dt. Significant correlations were found between systolic shortening or thickening before coronary occlusion and post-systolic shortening (r = 0.74, 56 segments) or thickening (r = 0.84, 19 segments) after occlusion, but there was no correlation between post-systolic shortening or thickening and dyskinetic lengthening or thinning. In seven dogs followed for 4 h after coronary occlusion post-systolic shortening fell by 15% in peripheral segments and by 70% in central segments (p less than 0.002). In 17 dogs reperfused after 60 (n = 9) or 90 (n = 8) min of coronary occlusion the maximal recovery of systolic shortening early after reperfusion was significantly related to the magnitude of post-systolic shortening immediately before reperfusion (60 min occlusion r = 0.84, 90 min occlusion r = 0.88). These data show that post-systolic shortening is a marker of potential for early recovery of function of acutely ischaemic myocardium and suggest that it is due, at least in part, to an active process.     

Instantaneous mitral valve leaflet velocity and its relation to left ventricular wall movement in normal subjects.

Echocardiograms showing mitral valve leaflets, interventricular septum, and posterior wall of the left ventricle simultaneously were recorded at a paper speed of 100 mm/s in 20 normal subjects. These records were manually digitized and a computer was used to derive mitral valve velocity, left ventricular dimension, and its rate of change continuously throughout a single cardiac cycle. The pattern of instantaneous mitral valve velocity with respect to time was similar in all subjects studied, showing a peak opening rate of 400 +/- 60 mm/s (mean +/- 1 SD), and continuously changing velocity throughout the period of mid-diastolic closure. The peak diastolic closure rate was 250 +/- 60 mm/s and thus appreciably higher than average velocities obtained by manually measuring the slope. A close time relation existed between mitral valve and left ventricular wall movement in early diastole. Forward movement of the anterior leaflet began 1 +/- 6 ms after the onset of outward wall movement, and peak velocity was reached 2 +/- 7 ms after the maximum rate of change of dimension. Later, a discontinuity in wall movement at the end of rapid filling preceded a corresponding discontinuity in the mitral valve velocity tracing by 5 +/- 10 ms. The technique, therefore, allows continuous measurement of mitral valve velocity, and demonstrates its close relation to left ventricular wall movement during diastole.     

Storage temperature and differing methods of sample preparation in the measurement of urinary albumin

Summary Microalbuminuria is a predictor of persistent proteinuria, renal failure and cardiovascular disease and therefore accurate determination of urinary albumin concentration is important. We examined the stability of albumin in urine under different conditions of storage, temperature and sample preparation. There was no significant difference in urinary albumin concentration between fresh urine and urine stored at either 4°C or 20°C for up to 7 days. Similarly in urine samples from diabetic patients there was no significant difference in albumin concentration at levels ranging from 1.3 to 1999.3 mg/l between fresh urine at 4°C and urine stored frozen for 1 week, 1 month or 6 months. Neither storage temperature (−20°C or −40°C) nor centrifugation of sample prior to assay made a significant difference to the albumin concentration. Multiple freezing and thawing of urine samples during 6 weeks of storage at −20°C made no difference to albumin concentrations. Storage of urine samples in either polypropylene, polystyrene or borosilicate glass tubes did not result in a significant change in urinary albumin concentration after either 1 week or 1 month at −20°C although, after 1 month of storage, urinary albumin concentrations tended to be lower by an average of approximately 7%. In tubes to which gelatine had been added this was reduced to 4%. We conclude that fresh urine can be kept at 4°C or 20°C for up to 7 days. Frozen urine samples can be stored for up to 6 months before assay without any loss of albumin concentration. Polypropylene, polystyrene or borosilicate glass tubes are acceptable containers for short-term storage and samples can simply be thoroughly thawed and vortex mixed immediately prior to assay.     

Combined modality treatment of small cell carcinoma of the lung

Ninety patients with extensive and 61 with limited small cell carcinoma of the lung were treated with three courses of intravenous chemotherapy (cyclophosphamide, doxorubicin hydrochloride, and vincristine sulfate) followed by radiotherapy to intrathoracic disease, and a second three-drug oral combination consisting of lomustine, procarbazine, and methotrexate for one year. Among the 147 patients who were evaluated, 55 of 66 (83%) with limited disease and 53 of 81 (65%) with extensive disease showed response after three courses of chemotherapy. The complete response rate in patients with limited disease prior to radiotherapy was 24%, but increased to 58% when evaluated following radiotherapy. The median survival was 47 weeks for patients with limited disease and 36 weeks for those with extensive disease. A 24% two-year survival is projected for complete responders. Important prognostic factors for survival are performance status, extent of disease, and sex, with female subjects doing somewhat better than male subjects. Among patients with limited disease, 45% failed within the CNS despite the use of chemotherapeutic agents that cross the blood-brain barrier. The initial induction regimen and radiotherapy were well tolerated; the oral three-drug combination was more toxic and did not prevent CNS metastases.     

Circulating immune complexes in Hodgkin's disease

Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 μg/ml ± 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (< 15 μg/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific Raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.     

beta2-adrenoceptor gene polymorphisms and blood pressure variations in East Anglian Caucasians

OBJECTIVE: The amino-terminal polymorphisms, Arg16Gly and Gln27Glu, of the beta2-adrenergic receptor (beta2AR) have been shown to affect regulation of the receptor expression by an agonist in cell culture studies. The Arg16Gly polymorphism has also been recently shown to be associated with essential hypertension. We therefore evaluated whether the amino-terminal polymorphisms of beta2AR are associated with hypertension in a Caucasian population. SUBJECTS AND METHODS: We performed an association study in 298 hypertensive patients and an equal number of age-matched normotensive controls from the East Anglian region, with blood pressure assessed categorically and quantitatively. We also examined the influence of the amino-terminal polymorphisms on blood pressure response to beta-blockade in 144 of the patients randomly assigned to this class of drug. Genotyping of the Arg16Gly polymorphism was undertaken by a newly designed mismatched polymerase chain reaction (PCR) and digestion with Nde I, whereas the Gln27Glu polymorphism was genotyped by PCR followed by Fnu4H I cleavage. RESULTS: We found no differences in the genotype or allele frequencies of the beta2AR polymorphisms between hypertensive and normotensive participants. There was also no association between the beta2AR genotypes and variations in either basal blood pressure or the blood pressure response to a beta-blocker. CONCLUSION: These findings suggest that the amino-terminal polymorphisms of the beta2AR gene are unlikely to constitute major susceptibility for essential hypertension in the East Anglian population.