Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer

It has previously been shown that the Copenhagen (COP) rat contains several genetic loci that contribute to its mammary tumor-resistant phenotype after 7,12-dimethylbenz(a)anthracene (DMBA) administration. One of these loci, mammary carcinoma susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidominant fashion. To confirm the existence and independent action of this locus and also aid in the identification of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto a Wistar Furth (WF) genetic background. Male carriers were genotyped using microsatellite markers spanning 20-30 cM of the Mcs1 locus. One of the congenic lines minimally retained the COP allele at D2Mit29 on the centromeric end of chromosome 2 and extended distally to D2Rat201. Heterozygous Mcs1 carrier rats were interbred, and the female offspring were treated with DMBA. The female rats from the Mcs1 congenic line that carried one or two COP alleles of the Mcs1 region had a significantly reduced (65 and 85%, respectively) tumor development (P < 0.001) compared with rats carrying zero COP alleles at this locus. A WF.COP-D2Mit29/D2Rat201 homozygous congenic strain derived at the N10 generation was treated with DMBA, and the COP homozygous rats developed 1.5 +/- 0.3 carcinomas/rat versus 6.3 +/- 0.5 in WF control rats (P < 0.0001). Fine mapping of this congenic interval using several recombinant lines identified three genetic loci within the Mcs1 congenic region that independently supported a tumor resistance phenotype. These genetic loci have been termed Mcs1a, Mcs1b, and Mcs1c. In rats for which each locus was homozygous for the COP allele, tumor development was reduced by approximately 60% compared with littermate controls. The identification of these independent loci within the Mcs1 COP allele provide a model of the genetic complexity of cancer.     

Effects of passive tilt and submaximal exercise on spectral heart rate variability in ventricular fibrillation patients without significant structural heart disease

It has been shown that tilt and exercise elicit significant changes in autonomic activity in normal subjects and that submaximal exercise causes a greater reduction in heart rate variability (HRV) in animals susceptible to ventricular fibrillation (VF). Whether there is an abnormal HRV response to tilt and exercise in patients at risk of sudden cardiac death (SCD) remains unknown. Short-term HRV before and during passive tilt and exercise was studied in 12 survivors of out-of-hospital cardiac arrest with documented VF and compared with 12 age- and sex-matched normal controls. No patient had significant structural heart disease or left ventricular dysfunction. HRV was computed as total-frequency (TF, 0.01 to 1.00 Hz), low-frequency (LF, 0.04 to 0.15 Hz) and high-frequency (HF, 0.15 to 0.40 Hz) components. There was no significant difference between normal controls and SCD survivors in HRV before or during tilt or submaximal exercise testing. The HF component was significantly decreased during tilt compared with that in the supine position in both normal controls (5.85 +/- 0.61 vs 5.08 +/- 0.95 In(msec2), p = 0.005) and patients (5.58 +/- 1.49 versus 4.74 +/- 1.18 In(msec2), p = 0.003). There was again no significant change in the TF or LF components during tilt in either patients or controls. All frequency components were significantly decreased during submaximal exercise testing in both patients and controls. However, there was no significant difference in any of these tilt- and exercise-induced changes in HRV between normal controls and SCD survivors.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of chronic high dose androgen or estrogen treatment on the human prostate [corrected

Prostate development and disease are androgen dependent. However, the nature of hormonal effects on the prostate of healthy young men is not clear. We, therefore, measured prostate size in males chronically exposed to high doses of androgens (AS; habitual anabolic steroid abusers; n = 15) or estrogens (E; male to female transsexuals; n = 11) and compared the results with those in age-matched healthy eugonadal men without known prostate disorders. Prostate size was measured by planimetric ultrasound as cross-sectional areas and maximal dimensions in three orthogonal dimensions with a 7.5-megahertz B-mode sector scanner biplane in a transrectal transducer at 2.5 mm steps from the base to the apex of prostate. Total prostate volume (TPV) was reconstructed from planimetric sections, central prostate volume (CPV) was calculated by the ellipsoidal formula from the appropriate three maximum dimensions, and peripheral prostate volume was determined by the difference between TPV and CPV. Compared with age-matched controls, TPV was normal (-2%) in AS (P = 0.752) and reduced by 31% in E (P = 0.002), whereas CPV was increased by 20% in AS (P = 0.002) and reduced by 46% in E (P = 0.002), and the ratio of CPV/peripheral prostate volume was increased by 77% in AS (P < 0.001) and decreased by 33% in E (P = 0.047). Blood sex hormone-binding globulin was elevated by nearly 500% in E (P < 0.001), but was reduced by 47% in AS (P = 0.003). Prostate-specific antigen was normal (-6%) in AS (P = 0.799) and decreased by 86% in E (P = 0.002). Prostatic acid phosphatase was increased by 26% in AS (P = 0.007), but was unchanged (-28%) in E (P = 0.106). Total and free testosterone levels were reduced to castrate levels in E, whereas LH, FSH, and total testosterone levels were significantly reduced in AS. We conclude that in the human prostate of young men, CPV is more hormonally sensitive than TPV, and during high dose treatment, CPV is preferentially increased by chronic androgen treatment and decreased by chronic estrogen treatment. The reduction of TPV by estrogens was less than expected if solely attributable to inhibition of endogenous gonadotropin and testosterone secretion, suggesting that estrogens also have a positive effect on the normal human prostate. The reversibility and long term significance of androgen-induced stimulation of CPV and, in particular, its relationship to the onset and severity of benign prostatic hyperplasia remain to be clarified.     

Acute aortic dissection: association with patent ductus arteriosus

The Cuban recombinant vaccine against the hepatitis B virus was applied to a group of individuals over 65 from a geriatric home in Havana City. Dose of 20 ìg were administered within a scheme from 0.1 to 6 months in order to study its immunogenicity, which was evaluated at 2, 7, and 12 months after the first dose. 47.1% of protective titres and geometrical mean of 6.04 UI/L were obtained after 60 days. 100% of seroconversion (UI/L) and seroprotection (10 UI/L) and geometric mean of 136.93 UI/L were obtained when the immune response was evaluated on the 7th month. Finally, after a year, seroconversion and seroprotection were also of 100%, and the geometric mean was of 204.61 UI/L. It was proved the high immunogenic power of this vaccine, which makes it recommendable to protect this age group from the hepatitis B virus.     

Do antral washouts have a place in the current management of chronic sinusitis?

Antral washouts have been widely used in the management of chronic sinusitis. With the advent of modern antibiotics and powerful topical nasal steroids, we sought to establish if a role remains for this procedure. One hundred and fourteen patients with chronic sinusitis were randomised into two groups. Patients in Group A received antral washouts followed by antibiotics and topical nasal steroids. Patients in the Group B received antibiotics and topical nasal steroids alone. In each group 51.6 per cent and 50 per cent of patients respectively improved with treatment. The outcome of treatment is also not influenced by endoscopic abnormality. The difference was not statistically significant (p = 0.86). The study indicates that half of patients with chronic sinusitis will improve with medical treatment but the addition of antral washout confers no additional benefits.