Low-dose doxorubicin in the management of advanced carcinoma of the prostate

Twenty-one patients with advanced metastatic carcinoma of the prostate, no longer responsive to conventional therapy, were treated with weekly low-dose doxorubicin (Adriamycin). Twelve had an impressive subjective response in terms of pain relief and improved performance status and in nine this was maintained for 3 or more months.     

A case of mosaic trisomy 2 diagnosed at amniocentesis in an abnormal fetus and confirmed in multiple fetal tissues

Pseudomosaicism for trisomy 2 is a relatively common finding at amniocentesis. However, genuine trisomy 2 mosaicism is extremely rare. As a result, very few cases have been described and little information is available with which to counsel the parents of an affected fetus. We describe a case of mosaic trisomy 2 diagnosed at amniocentesis in a fetus with multiple anomalies on ultrasound scan. Following termination of pregnancy, the fetus was found to have mild dysmorphic features, together with an absent gall bladder, cystic left kidney, a 13th left rib and mild unilateral talipes. The presence of trisomy 2 cells was confirmed by both standard cytogenetic analysis and fluorescent in-situ hybridisation techniques in multiple fetal tissues, as well as in the cord and placenta.     

Prospective study of the complications of endoscopic laryngeal surgery

Patients undergoing 204 endoscopic laryngeal operations were studied prospectively to determine the incidence of complications. Twelve patients were considered to be at high risk of postoperative airway obstruction. Two of these patients had an elective tracheostomy. One required temporary reintubation in the recovery room. No case of respiratory obstruction occurred in a patient not considered to be in the high risk group. Mucosal haemorrhage or oedema was seen on postoperative indirect laryngoscopy in 31 per cent of patients. The commonest abnormality found was mucosal haemorrhage in the oropharynx.     

A portable system for measuring cutaneous thresholds for warming and cooling.

Measurement of cutaneous thermal thresholds is a valuable technique for detecting small fibre neuropathy. A robust and portable microcomputer controlled system, which separately measures thresholds for warming and cooling, is described. Thresholds at three sites have been measured; the cheek, the dorsum of the hand and the sole of the foot. Regional variability and a correlation with age have been found, indicating the sensitivity of this system.     

Mechanism of increased collateral airway resistance during inhomogeneous inflation of excised dog lungs

Collateral airway resistance was measured during inflation of an excised lung lobe or a segment within the lobe. Gas blown into the outer lumen of a double lumen catheter (Vcoll) inflated the segment and exited via collateral airways. Pressure at the catheter tip (Pct) was measured through the inner lumen of the catheter, and transpulmonary pressure (Pao) was measured at the lobar bronchus. A pleural capsule measured pressure in the segmental subpleural alveoli (Ps). The segment was inflated with helium (He), air, or sulfurhexafluoride; the lobe was ventilated with air. Collateral airway resistance [Rcoll = (Pct-Pao)/Vcoll], intrasegmental airway resistance [Rs = (Pct-Ps)/Vcoll], and resistance of airways passing through the segment-lobar interface [Ri = (Ps-Pao)/Vcoll] were calculated. Rcoll, Rs, and Ri were decreased by lobar inflation and increased by segment inflation. The latter increase was due to nonlaminar flow in intrasegmental airways. The major resistance was Ri when Vcoll was laminar or transitional. Moody plots suggested that lobar inflation caused intrasegmental airway dilation whereas segment inflation did not affect segment airway geometry.     

Generation and characterization of a human monoclonal antibody that neutralizes diverse HIV-1 isolates in vitro.

OBJECTIVE: The purpose of this study was to develop and characterize human monoclonal antibodies (HuMAb) that neutralize HIV-1. DESIGN: Based upon previous studies involving the generation of HuMAb that neutralize other enveloped viruses, we thought it feasible to generate HuMAb that might neutralize HIV-1. METHODS: A HuMAb was generated by fusing splenic B-cells from an HIV-positive patient with a mouse myeloma cell line. Flow cytometry was used to determine surface reactivity of the HuMAb on HIV-infected and non-infected cells. Radioimmunoprecipitation was employed to elucidate the antigen recognized by the HuMAb. A cell survival assay was used to determine the ability of the HuMAb to neutralize divergent isolates of HIV-1 in the presence or absence of complement. A gp120-CD4 inhibition enzyme-linked immunosorbent assay (ELISA) was developed in order to initiate studies to determine the mechanism of neutralization by the HuMAb. RESULTS: An anti-HIV HuMAb was generated that neutralized two HIV-1 isolates (IIIB and MN) without complement and which neutralized one divergent isolate (RF) and one clinical isolate in the presence of complement. This HuMAb, designated S1-1, was found, by flow cytometric analysis, to react with the surface of HIV-1-infected but not with uninfected cells. Radioimmunoprecipitation analysis demonstrated that S1-1 binds to native HIV gp120, but not dithiothreitol (DTT)-treated gp120. In addition, HuMAb S1-1 did not bind to denatured HIV antigens in Western blot analysis. HuMAb S1-1 effectively inhibited the binding of gp120 to soluble CD4 in ELISA. CONCLUSIONS: These results suggest that the epitope recognized by S1-1 is conformational and conserved among diverse HIV-1 isolates and may represent an uncharacterized HIV neutralizing domain within or close to the CD4 binding domain on gp120. HuMAb S1-1 might have a role to play in vaccine development or passive immunotherapy.     

Fetal heart rate response to milk predicts expression of the stretch response.

On the day before birth, rat fetuses respond to an intraoral infusion of milk with a stretch response that resembles the behavior of suckling pups at the nipple. Unlike the postnatal response, which occurs coincident with milk ejection, the fetal stretch occurs 3-5 min after milk infusion. Measurement of fetal heart rate (HR) is useful as a predictor of the fetal stretch response. Expression of the stretch response was preceded by a reduction in HR variability and a transient episode of bradycardia. Fetuses that did not stretch showed a delayed reduction in HR variability and no evidence of HR deceleration. Systematic changes in fetal HR may be indicative of changes in fetal state associated with milk infusion and the stretch response.     

Rising mortality from motor neurone disease in Sweden 1961–1990: the relative role of increased population life expectancy and environmental factors

Recent studies of mortality from motor neurone disease (MND) in Sweden have demonstrated rising levels of mortality from the disease, especially amongst older age groups. Case-control investigations have suggested that certain environmental factors are significantly related to variations in mortality from the disease, and are associated with a probable individual susceptibility to MND. This study applies an innovative epidemiological technique to longitudinal and cohort analysis of Swedish mortality from MND during the period 1961 to 1990. Survival modelling shows that a subpopulation susceptible to MND exists in Sweden, as has been demonstrated in other countries. The increased life expectancy of the Swedish population since 1961 has resulted in more of that susceptible population living to the ages at which MND is expressed, explaining the majority of the increase in mortality from the disease. However, environmental factors may play a role in accelerating the course of MND and may affect the timing of death within the susceptible sub-population.