Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.     

The five amino acid-deleted isoform of hepatocyte growth factor promotes carcinogenesis in transgenic mice

Hepatocyte growth factor (HGF) is a polypeptide with mitogenic, motogenic, and morphogenic effects on different cell types including hepatocytes. HGF is expressed as two biologically active isotypes resulting from alternative RNA splicing. The roles of each HGF isoform in development, liver regeneration and tumorigenesis have not yet been well characterized. We report the generation and analysis of transgenic mice overexpressing the five amino acid-deleted variant of HGF (dHGF) in the liver by virtue of an albumin expression vector. These ALB-dHGF transgenic mice develop normally, have an enhanced rate of liver regeneration after partial hepatectomy, and exhibit a threefold higher incidence of hepatocellular carcinoma (HCC) beyond 17 months of age. Moreover, overexpression of dHGF dramatically accelerates diethyl-nitrosamine induced HCC tumorigenesis. These tumors arise faster, are significantly larger, more numerous and more invasive than those appearing in non-transgenic littermates. Approximately 90% of female dHGF-transgenic mice had multiple macroscopic HCCs 40 weeks after injection of DEN; whereas the non-transgenic counterparts had only microscopic nodules. Liver tumors and cultured tumor cell lines from dHGF transgenics showed high levels of HGF and c-Met mRNA and protein. Together, these results reveal that in vivo dHGF plays an active role in liver regeneration and HCC tumorigenesis.     

Humoral immune responses in murine pregnancy. I. Anti-paternal alloantibody levels in maternal serum

The kinetics and properties of anti-paternal alloantibody produced by female C57BL(H-2^b) mice in response to mating with CBA(H-2^k) males have been investigated using an immunobead adsorption assay. No alloantibody was ever detected in the first pregnancy or post-partum period. 72% of females exhibited a humoral response in their second pregnancy, detectable from day 16 or 17 post-coitum, and almost all females responded in their third pregnancy. Column chromatographic and immunoelectrophoretic analysis showed that the alloantibody was IgG. Although passive transfer experiments suggested similar stability characteristics to those of cytotoxic antibody induced by experimental hyperimmunization, the pregnancy-induced alloantibody did not exhibit complement-dependent cytotoxicity. The findings are discussed in relation to the nature of the immunogenic stimulus from the conceptus and the regulation and possible function of the humoral immune response in allogeneic pregnancy.     

Contraceptive knowledge and practice among undergraduates at a Canadian university.

A total of 509 undergraduate students aged 17 to 23 years, were tested to assess the adequacy of their knowledge of methods of birth control. A level of adequate knowledge was arbitrarily defined a priori as one standard deviation below the mean score of a random sample of second-year medical students, who were assumed to have more than adequate knowledge on the basis of prior courses in reproductive physiology and human sexuality. Of the undergraduate population sampled, 34 per cent were found to have inadequate knowledge. This population is in need of birth control information. Of nonvirgins in the sample, 20.2 per cent risk unwanted pregnancy, the majority (78.3 per cent) in spite of adequate knowledge. This suggests that lack of motivation, rather than purely lack of information, is an important factor contributing to the unwanted pregnancy rate of the college student population.     

A pilot study investigating the role of NAT1 and NAT2 polymorphisms in gastric adenocarcinoma

In humans, aromatic and heterocyclic amine carcinogens may be acetylated by the expression products of either of the N-acetyltransferase genes, NAT1 or NAT2. This conjugation reaction can result in either activation or detoxication of these carcinogens depending on the tissue involved. Recent studies suggest that polymorphisms in NAT1 or NAT2 may modulate cancer risk. To determine if genetic differences in NAT1 and NAT2 could alter risk of gastric cancer, we tested for the presence of polymorphic N-acetyltransferase alleles (both NAT1 and NAT2) in a preliminary study of 94 gastric adenocarcinoma patients and 112 control subjects from North Staffordshire, England. We used established PCR protocols to genotype for NAT2 and NAT1 alleles (NAT2*4, NAT2*5, NAT2*6, NAT2*7, NAT2*14; NAT1*3, NAT1* 4, NAT1*10, and NAT1*11), and implemented an oligonucleotide ligation assay (OLA) to test for low-activity NAT1 alleles [NAT1*14 (G560A), NAT1*15 (C559T), and NAT1*17 (C190T)]. No significant increased risk was observed for NAT2 acetylation genotypes. However, among all cases, we found that individuals inheriting a variant NAT1 allele, NAT1*10, have a significantly elevated risk for gastric cancer (OR = 2.2, 95% CI 1. 2-3.9, P < 0.01). Interestingly, the risk observed for NAT1*10 appears to be solely associated with advanced-stage tumors (OR = 4.8, P < 0.001), suggesting a possible role in progression to advanced disease. This preliminary finding needs confirmation in a larger, detailed epidemiological study.     

Predictors of functional outcomes following limb salvage surgery for lower-extremity soft tissue sarcoma

BACKGROUND AND OBJECTIVES: Patient function has been conceptualized by clinical measures such as joint motion, muscle strength, disability, and general health status. The purpose of the current study was to evaluate tumor and treatment variables predictive of these conceptually different posttreatment functional outcomes in patients treated with limb preservation surgery for lower-extremity soft tissue sarcoma. METHODS: One hundred seventy-two patients with minimum 1-year follow-up were evaluated using the following outcomes: impairment, measured by the 1987 and 1993 versions of the Musculoskeletal Tumor Society Rating Scale (MSTS); disability, measured by the Toronto Extremity Salvage Score (TESS); and general health status, using the Short Form-36 (SF-36). Tumor and treatment-related variables (age, gender, presenting disease status, anatomic site, tumor size, grade, depth, prior excision, irradiation, bone resection, motor nerve sacrifice, and complications) were extracted from the STS database. RESULTS: Large tumor size, bone resection, motor nerve resection, and complications were predictive of lower MSTS 1987 and 1993 scores. Patients with large, high-grade tumors who required motor nerve resection were more disabled, as reflected by lower TESS scores. Only age and prior surgery were adverse predictors of SF-36 score. CONCLUSIONS: These results demonstrate that different factors are predictive of different patient outcomes, specifically, impairment, disability, and general health status. It is important to define function when counseling patients regarding their potential recovery based on tumor and treatment-related variables. J. Surg. Oncol. 2000;73:206-211.     

Successful pregnancy in transfusion-dependent thalassaemia

Successful pregnancy in a transfusion-dependent thalassaemic patient receiving subcutaneous desferrixaomine is reported. This is the first such case to be described.     

Fetal to maternal transfer of palmitic and linoleic acids across the sheep placenta.

Maternal and fetal blood samples were obtained at 2.5, 10 and 20 min after the injection of 3H-palmitic acid and 14C-linoleic acid into the fetal circulation of pregnant ewes. 3H-palmitic acid was easily detected in the maternal circulation within 2.5 min after its injection into the fetus resulting in an appreciable accumulation in the maternal plasma by the 20th min after injection. In contrast the presence of 14C-linoleic acid in the maternal circulation was barely detectable over the 20-min sampling period. The concentrations of total lipid and unesterified fatty acids within the fetal plasma were considerably lower than in the maternal plasma thereby providing an adverse concentration gradient for the passage of fatty acids between fetus and mother. The differential permeability of the placenta to the passage of the 3H-palmitic acid and 14C-linoleic acid is discussed in relation to their passage from fetus to mother in non-ruminant species and the adverse essential fatty acid status known to exist in the developing ruminant fetus.     

Anatomic confirmation of echocardiographic measurements in neonatal hearts.

Significant correlations were demonstrated between echocardiographic measurements of left ventricular wall thickness, right ventricular wall thickness, septal thickness, left ventricular mass, aortic valve excursion, pulmonary valve excursion, mitral valve excursion, and tricuspid valve excursion and the same measurements made directly on the same hearts at autopsy. A new regression formula was derived for the calculation of echocardiographic right ventricular mass in life and was found to correlate significantly with right ventricular mass measured as the sum of right ventricular wall and septal volumes at postmortem examination.     

Review article: the clinical role of anti-TNFalpha antibody treatment in Crohn's disease

The recent licensing of anti-TNFalpha antibody treatment offers the potential to radically alter the course of severe Crohn's disease using genetically-engineered drugs directed against a specific inflammatory mediator. Controlled randomized trials have demonstrated clinical benefit associated with tissue healing in patients with active intestinal disease and fistulae, often when conventional therapies were unsuccessful. This therapy is expensive, however, and long-term efficacy and safety data are still awaited. This review considers the nature of this therapy and the current evidence for its clinical benefit and adverse effects. The treatment is also considered in the context of available immunosuppressive agents, with suggestions about its practical application.