Peripheral and central arterial haemodynamic interactions are early abnormalities in young male cigarette smokers.

BACKGROUND: smoking, result in endothelial dysfunction and this affects systemic and local haemodynamics. The aim was to assess interactions of the left ventricle and arterial system of smokers at baseline and after a physiological stimulus--the cold pressor test (CPT) which causes a sympathetically driven vasoconstriction that counteracts the normal endothelial dependent vasodilatation. MATERIALS AND METHODS: male smokers and controls were compared using applanation tonometry. Parameters included systolic and diastolic blood pressure, ejection duration, heart rate, aortic augmentation index (AAI), and sub-endocardial viability ratio (SEVR). The CPT was performed at 1 and 3 min following immersion of the hand in ice. RESULTS: smokers have abnormal baseline cardiac timing (heart rate and ejection duration), systolic and diastolic blood pressures which are due to increased peripheral wave reflection (AAI) and thus affect the SEVR. Following CPT, the pressure wave differential, dP/dt, was significantly increased in smokers compared to non-smokers who had a decrease at 1 min in ice. Mean systolic and diastolic pressure was significantly increased in both groups at 1 and 3 min as was end systolic pressure in non-smokers. CONCLUSIONS: baseline ventriculo-vascular dynamics, are abnormal as was the evoked response to CPT. The blunted blood pressure increase of smokers compared to controls following CPT, may represent altered nitric oxide production in the macro and microcirculation through differential upregulation of endothelial nitric oxide synthase (eNOS) and inducible NOS respectively. The potential for therapeutic intervention and prevention of ongoing endothelial injury, requires further investigation.     

Acute intracerebroventricular injections of the mast cell degranulator compound 48/80 and behavior in rats

The intracerebroventricular (ICV) injection of the mast cell degranulator Compound 48/80 (2.5-2.0 micrograms/kg) produced a marked behavioral syndrome in normotensive rats. The behaviors included head and body shakes, paw tremor, excessive grooming, unusual posture and gait, mild diarrhoea, piloerection, extreme agitation and irritability to touch, and a later phase of sedation. The highest doses (15 and 20 micrograms/kg) also produced catalepsy and episodes of "barrel rolling" (continuous rolling of 1-8 turns around the longitudinal axis). These behaviors were observed for approximately 15-30 min although the sedation and catalepsy were maintained for 90-120 min. A second ICV injection of the 10 micrograms/kg dose of Compound 48/80 given 2 hr after an initial injection of this dose, produced a much reduced response and the numbers of head and body shakes, and episodes of paw tremor and grooming were between 20-30% of those produced by the first injection. The reduced effect of the second injection indicates that the behavioral effects of Compound 48/80 may arise from the acute degranulation of mast cells rather than direct effects on neuronal populations or the cerebral vasculature.     

Morbidity data collection in general practice: experience in the South Eastern Health Board 1998-1999

A joint project between general practitioners and the South Eastern Health Board resulted in the establishment of a network of computerised practices collecting morbidity data in 1998 - 1999. Five practices established age sex registers for public and private patients. The International Classification of Primary Care 2 (ICPC-2) was used to define inclusion criteria for a range of illnesses relevant to primary care and public health. Problems arose in validating and extracting data in three practices. Disease prevalence for 17 illnesses was established for two practices only. The project clearly established the problems associated with morbidity data collection in general practice which include absence of a national patient registration system, absence of a national electronic messaging standard, difficulties extracting data from practice software systems and the need for a high level of dedicated staff and resources to implement such a project.     

Withdrawal-like behaviour induced by inhibitors of biogenic amine reuptake in rats treated chronically with Δ 9-tetrahydrocannabinol

The effects of the biogenic amine reuptake inhibitors fluoxetine, clomipramine and imipramine on the behaviour of rats after chronic treatment with ⁹ tetrahydrocannabinol ( ⁹-THC) for 5 and 10 days were examined. Rats with permanently in-dwelling IV cannulae were injected twice daily with doses of ⁹-THC (2–6 mg/kg). ⁹-THC treatment reduced the rate of body weight gain and induced the typical biphasic modifications of behaviour. Tolerance developed to both of these effects. On days 6 and 11 of the experiment, rats were injected IP with 15 mg/kg imipramine HCl, clomipramine HCl or fluoxetine HCl, and behaviour, consisting of writhes, backward kicks, jumps and wet shakes, was observed for the next 30 min. Each of the amine reuptake inhibitors induced changes in behaviour, the severity of which appeared to correlate with their ability to inhibit the reuptake of 5-hydroxytryptamine (5-HT). It is suggested that tryptaminergic mechanisms are involved in the production of a withdrawal-like behaviour after chronic ⁹-THC treatment.     

Predictive role of PI-RADSv2 and ADC parameters in differentiating Gleason pattern 3 + 4 and 4 + 3 prostate cancer

Purpose

To compare the predictive roles of qualitative (PI-RADSv2) and quantitative assessment (ADC metrics), in differentiating Gleason pattern (GP) 3 + 4 from the more aggressive GP 4 + 3 prostate cancer (PCa) using radical prostatectomy (RP) specimen as the reference standard.

Methods

We retrospectively identified treatment-naïve peripheral (PZ) and transitional zone (TZ) Gleason Score 7 PCa patients who underwent multiparametric 3T prostate MRI (DWI with b value of 0,1400 and where unavailable, 0,500) and subsequent RP from 2011 to 2015. For each lesion identified on MRI, a PI-RADSv2 score was assigned by a radiologist blinded to pathology data. A PI-RADSv2 score ≤ 3 was defined as “low risk,” a PI-RADSv2 score ≥ 4 as “high risk” for clinically significant PCa. Mean tumor ADC (ADC_T), ADC of adjacent normal tissue (ADC_N), and ADC_ratio (ADC_T/ADC_N) were calculated. Stepwise regression analysis using tumor location, ADC_T and ADC_ratio, b value, low vs. high PI-RADSv2 score was performed to differentiate GP 3 + 4 from 4 + 3.

Results

119 out of 645 cases initially identified met eligibility requirements. 76 lesions were GP 3 + 4, 43 were 4 + 3. ADC_ratio was significantly different between the two GP groups (p = 0.001). PI-RADSv2 score (“low” vs. “high”) was not significantly different between the two GP groups (p = 0.17). Regression analysis selected ADC_T (p = 0.03) and ADC_ratio (p = 0.0007) as best predictors to differentiate GP 4 + 3 from 3 + 4. Estimated sensitivity, specificity, and accuracy of the predictive model in differentiating GP 4 + 3 from 3 + 4 were 37, 82, and 66%, respectively.

Conclusions

ADC metrics could differentiate GP 3 + 4 from 4 + 3 PCa with high specificity and moderate accuracy while PI-RADSv2, did not differentiate between these patterns.

     

Elevated plasma IGF 1 levels in stags prevented from growing antlers

We have previously shown that plasma IGF 1 concentration is positively correlated with the rate of antler growth and have proposed that IGF 1 is stimulatory for antler growth in the red deer stag. Therefore to partly resolve the question of whether the IGF 1 was of circulating or local origin in relation to its effect on antler growth, we surgically prevented stags from growing antlers. We recorded significantly elevated plasma levels of IGF 1 in the non-antlered stags compared with normal antlered stags during the antler growth periods. This result is consistent with a hypothesis that the antler is a target organ for IGF 1 and that prevention of antler growth removed a population of IGF 1 receptors. IGF 1 is already known to stimulate body growth but this work points strongly to the possibility that plasma IGF 1 may stimulate individual organ growth in an endocrine manner.     

Recurrent and acquired hepatitis C viral infection in liver transplant recipients.

To examine the postliver transplant recurrence of hepatitis C virus (HCV) infection in patients with pretransplant infection, as well as its acquisition in patients without prior infection, we used the polymerase chain reaction to amplify HCV RNA in serum and/or liver samples of 89 patients with alcoholic and cryptogenic cirrhosis undergoing liver transplantation. Results were correlated with histologic findings from posttransplant liver biopsies. Ninety-five percent of patients with pretransplant infection had posttransplant viremia. In contrast, 35% of patients without pretransplant infection acquired the virus (P less than 0.0001). Pretransplant HCV infection predisposed patients to hepatitis in the new graft. HCV RNA was present in serum of 96% of patients with posttransplant hepatitis. Fifty-six percent of patients with posttransplant HCV infection had no evidence of liver damage at least 1 year posttransplant. However, of those patients with histologic hepatitis, chronic active hepatitis was common. It is concluded that although HCV infection recurs posttransplant in almost all infected patients, acquisition of the HCV infection with transplant is common. Pretransplant HCV infection is an independent risk factor for the development of posttransplant hepatitis. HCV infection accounts for the majority of posttransplant hepatitis not due to cytomegalovirus, and although many patients with posttransplant viremia have little evidence of histologic hepatitis, significant hepatic damage may occur.