Randomized trial of low-dose interleukin-2 vs cyclosporine A and interferon-gamma after high-dose chemotherapy with peripheral blood progenitor support in women with high-risk primary breast cancer.

High-risk primary breast cancer patients treated with high-dose chemotherapy (HDC) and stem cell support (SCS) have shown prolonged disease-free survival (DFS) in many studies; however, only one trial has demonstrated an overall survival benefit (OS). We hypothesize that the period following myeloablative therapy is ideal for immunologic manipulation and studied the effects of two different methods of immunotherapy following HDC with SCS aimed at the window of immune reconstitution. Seventy-two women with high-risk stage II or III breast cancer were randomized following HDC to receive either interleukin 2 (IL-2) at 1 million units/m(2) SQ daily for 28 days or combined cyclosporine A (CsA) at 1.25 mg/kg intravenously daily from day 0 to +28 and interferon gamma (IFN-gamma) 0.025 mg/m(2) SQ every 2 days from day +7 to +28. At a median follow-up of 67 months, no significant difference was observed in DFS or OS between the two treatment groups. The IL-2 arm had a 59% DFS (95% CI (0.45, 0.78)) and a 72% OS (95% CI (0.58, 0.88)) at 5 years. The CsA/INF-gamma arm had a similar outcome with a 55% DFS (95% CI (0.40, 0.76)) and a 78% OS (95% CI (0.65, 0.94)) at 5 years. Treatment was well tolerated, without increased toxicity.

Disopyramide-induced ventricular tachycardia.

A patient with ischemic cardiomyopathy and congestive heart failure was treated with disopyramide phosphate for ventricular arrhythmias. The development of ventricular tachycardia was associated with elevated plasma disopyramide levels and prolongation of the QRS and QT intervals, suggesting a disopyramide-induced depression of ventricular conduction and a prolongation of recovery. Thus, in patients with congestive heart failure, as well as in patients with renal and/or hepatic dysfunction, special care must be exercised with respect to the use of disopyramide.

Spontaneous activity and barosensitivity of the barosensitive neurons in the rostral ventrolateral medulla of hypertensive rats induced by transection of aortic depressor nerves.

In order to determine the role of the rostral ventrolateral medulla (RVLM) in the development of neurogenic hypertension, the aortic depressor nerves of rats were transected (tADN) to produce neurogenic hypertension. The rate and pattern of firing of the barosensitive RVLM neurons of the treated rats were studied. In neurogenic hypertensive rats, the RVLM barosensitive neurons exhibited a faster firing rate and a shorter interspike interval (ISI) than the corresponding values of the control and sham groups, indicating an enhanced spontaneous activity of these neurons in the hypertensive rats. The coefficient of variation (cv) and skewness (sk) of the ISI histogram, parameters reflecting the regularity of neuronal firing, were smaller in neurogenic hypertensive than in the control and sham-operated rats. Following tADN, the responsiveness of these neurons to blood pressure changes was attenuated, suggesting a reduced intrinsic barosensitivity of neurons and/or a reduced baroreceptor input. The increase in spontaneous activity and firing regularity of RVLM barosensitive neurons imply an enhancement in the efficacy of outflow from these neurons. The increased efficacy of the outflow from the RVLM barosensitive neurons and the resetting of the baroreflex may contribute to the genesis of neurogenic hypertension.

Fractionation of fulvic acids: characteristics and complexation with copper.

Two fulvic acid samples isolated from Suwannee river (International Humic Substance Society) and Feeitsuey reservoir were subjected to gel filtration chromatography (GFC) for molecular size fractionation. The GFC-eluted samples were separated into three groups corresponding to the molecular weight ranges: < 220, 220-1000, and 1000-4000. Fluorescence quenching techniques were employed for determining the conditional stability coefficient and kinetic parameters of copper complexation with the three fractions of fulvic acids. Experimental conditions were pH 6, 5 x 10(-5)m total copper and 5 mg C litre(-1) of fulvic acids. The conditional stability coefficients of the fulvic acid fractions were in the order of 0.9-3.3 x 10(5)m(-1), and the forward and reverse rate constants were in the order of 6.9-12.4 x 10(3)m(-1) s(-1) and 3.5-8.0 x 10(-2) s(-1). Information could be useful in modelling copper transport in the hydrosphere.

Platelet apoptosis by cold-induced glycoprotein Ibα clustering.

BACKGROUND: Cold-storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα-distribution indicative of receptor clustering and initiates thromboxane A(2) -formation. GPIbα is associated with 14-3-3 proteins, which contribute to GPIbα-signaling and in nucleated cells take part in apoptosis regulation. OBJECTIVES AND METHODS: We investigated whether GPIbα-clustering induces platelet apoptosis through 14-3-3 proteins during cold (4 h 0 °C)-rewarming (1 h 37 °C). RESULTS: During cold-rewarming, 14-3-3 proteins associate with GPIbα and dissociate from Bad inducing Bad-dephosphorylation and activation. This initiates pro-apoptosis changes in Bax/Bcl-x(L) and Bax-translocation to the mitochondria, inducing cytochrome c release. The result is activation of caspase-9, which triggers phosphatidylserine exposure and platelet phagocytosis by macrophages. Responses are prevented by N-acetyl-D-glucosamine (GN), which blocks GPIbα-clustering, and by O-sialoglycoprotein endopeptidase, which removes extracellular GPIbα. CONCLUSIONS: Cold-rewarming triggers apoptosis through a GN-sensitive GPIbα-change indicative of receptor clustering. Attempts to improve platelet transfusion by cold-storage should focus on prevention of the GPIbα-change.

Familial Ebstein's anomaly.

2 adult siblings with Ebstein's anomaly are presented in this report. The second sibling was found to have the anomaly 20 years after the first sibling was diagnosed. The use of echocardiography in screening for Ebstein's anomaly and the diagnostic features are emphasized. Documentation by electrode catheter recording intracardiac electrocardiogram and pressures in the right heart were made.

Necrotizing fasciitis due to Vibrio alginolyticus following an injury inflicted by a stingray.

We describe the case of a patient with necrotizing fasciitis due to Vibrio alginolyticus in a patient with cirrhosis following an injury inflicted by a stingray. The patient was successfully treated with aggressive surgical debridement and a combination of ciprofloxacin and amoxicillin-clavulanate. Cases of invasive V. alginolyticus reported in the literature were reviewed.

An autologous blood donation program for paediatric scoliosis patients in Hong Kong.

A retrospective audit was conducted to determine the safety, efficacy and patient satisfaction related to a preoperative autologous blood donation program for children and teenagers undergoing corrective surgery for scoliosis. Forty-five of the 77 patients donated the requested amount of blood. These 45 compliant patients had been requested to donate fewer units of blood than noncompliant patients (mean 4.0 vs 4.6 respectively, P = 0.02). Twelve patients required allogeneic blood transfusion. Two patients had surgery delayed making the collected autologous blood unavailable. The extent of the operation was associated with the need for allogeneic blood transfusion. Six and a half percent of all donated units of blood were discarded. No major complications were reported. Overall, 93% of patients were satisfied with the program. With careful patient selection, good inter-departmental coordination and teamwork, preoperative autologous blood donation in paediatric patients undergoing extensive corrective surgery for scoliosis is safe and effective.

Characterization of the pathogenicity of members of the newly established H9N2 influenza virus lineages in Asia.

The reported transmission of avian H9N2 influenza viruses to humans and the isolation of these viruses from Hong Kong poultry markets lend urgency to studies of their ecology and pathogenicity. We found that H9N2 viruses from North America differ from those of Asia. The North American viruses, which infect primarily domestic turkeys, replicated poorly in inoculated chickens. Phylogenetic analysis of the hemagglutinin and nucleoprotein genes indicated that the Asian H9N2 influenza viruses could be divided into three sublineages. Initial biological characterization of at least one virus from each lineage was done in animals. Early isolates of one lineage (A/Chicken/Beijing/1/94, H9N2) caused as high as 80% mortality rates in inoculated chickens, whereas all other strains were nonpathogenic. Sequence analysis showed that some isolates, including the pathogenic isolate, had one additional basic amino acid (A-R/K-S-S-R-) at the hemagglutinin cleavage site. Later isolates of the same lineage (A/Chicken/Hong Kong/G9/97, H9N2) that contains the PB1 and PB2 genes similar to Hong Kong/97 H5N1 viruses replicated in chickens, ducks, mice, and pigs but were pathogenic only in mice. A/Quail/Hong Kong/G1/97 (H9N2), from a second lineage that possesses the replicative complex similar to Hong Kong/97 H5N1 virus, replicated in chickens and ducks without producing disease signs, was pathogenic in mice, and spread to the brain without adaptation. Examples of the third Asian H9N2 sublineage (A/Chicken/Korea/323/96, Duck/Hong Kong/Y439/97) replicated in chickens, ducks, and mice without producing disease signs. The available evidence supports the notion of differences in pathogenicity of H9N2 viruses in the different lineages and suggests that viruses possessing genome segments similar to 1997 H5N1-like viruses are potentially pathogenic in mammals.