Modulatory action of noradrenergic system on spinal motoneurons in humans.

Previous findings in animals demonstrated that the noradrenergic coeruleospinal system exerts a tonic facilitation on spinal reflexes and that activation of alpha2-autoinhibitory receptors can be responsible for a disfacilitation of the spinal activity. To investigate this issue further, we examined whether this system is also involved in descending facilitatory control of spinal motoneurons in healthy humans. The H-reflex technique was utilized to assay the motoneuronal excitability. The ratio between the maximal reflex response (H) and maximal direct response (M) was determined in each subject and was calculated at 10 min intervals before and after i.v. administration of the alpha2-agonist clonidine (0.5 microg/kg). In all subjects a marked decrease of the H/M ratio, due to depression of the H response, occurred 10 min following the clonidine injection and reached its maximum within 30 min. No significant changes of blood pressure values were provoked by drug injections. These results suggest that an autoinhibitory action may be induced by alpha2-receptor activation of locus coeruleus neurons in humans, and that this device may serve as a mechanism for a myotonolytic action on spinal motoneurons.     

N-Acetylcysteine does not artifactually lower plasma creatinine concentration.

BACKGROUND: All randomized controlled trials of N-acetylcysteine (NAC) in contrast media-induced nephropathy used creatinine as a marker of renal function. However, it has been suggested that NAC may lower plasma creatinine levels independent of any effects on glomerular filtration rate (GFR). METHODS: At a tertiary hospital 110 cardiac surgical patients were randomly allocated to peri-operative infusion of NAC (300 mg/kg over 24 h, N = 30) or placebo (N = 80). We compared the plasma concentrations of creatinine, cystatin C and urea, the plasma creatinine/plasma cystatin C ratio and the estimated GFR at baseline and at 24 and 72 h after commencement of the infusion. We measured urinary creatinine concentration at 24 h. RESULTS: At baseline, the plasma creatinine/plasma cystatin C ratio did not differ between the NAC and placebo group (0.90 versus 0.92; P = 0.94). There was no significant difference in the plasma creatinine/plasma cystatin C ratio for the NAC and placebo group either during or after NAC infusion at 24 h (1.03 versus 1.00; P = 0.78) and 72 h (0.94 versus 0.89; P = 0.09). Those allocated to NAC showed no difference in urinary creatinine excretion when compared to placebo (P = 0.24). CONCLUSIONS: The results of our study do not demonstrate that NAC artifactually lowers creatinine measured using the Jaffé method. (ClinicalTrials.gov, NCT00332631, NCT00334191).     

Telangiectases [corrected] of the anterior chest in homosexual men

Physical examination by a single clinician showed that 17 of 51 asymptomatic homosexual men and 19 of 26 men with persistent lymphadenopathy had linear telangiectasias in a broad, crescent distribution across the chest. The telangiectasias were commonly associated with erythema in the same distribution. Of the 36 men with telangiectasias, 25 were positive for serum antibody to the human immunodeficiency virus (HIV), whereas only 15 of 41 men without telangiectasias were seropositive (p = 0.001). Biopsy studies of supraclavicular skin from 6 of the men with HIV antibody and telangiectasias showed a characteristic pattern of dilated blood vessels with a perivascular small-cell infiltrate; no endothelial proliferation was noted. This histopathologic pattern was not consistently observed in HIV-seronegative men regardless of whether they had telangiectasias. These data show that telangiectasias of the upper chest are a relatively common finding in homosexual men and that they are significantly, although not exclusively, associated with HIV infection.     

Correlation of several methods for recording esophageal sphincteral pressures

Summary Three balloons of different size were used to obtain pressures in the esopha-geal sphincters of 21 healthy young subjects. In 12 of these we had the opportunity to repeat the studies using perfused open-tip methods, and in 10 of these 12, three methods were correlated. The constantly perfused open-tip tubes were pulled through the sphincter intermittently and continuously. The balloons were pulled through the sphincter continuously.The pressures in the inferior sphincter varied with the size of the balloon tip and with respiration but not with rate of perfusion or the lumen from which pressures were recorded. The pressures in the superior sphincter varied with all four parameters. If the four parameters were properly chosen, similar mean values and correlation of the values obtained by the various methods in an individual patient were obtained. The advantages and disadvantages of the various methods were discussed briefly.Supported by the Mount Carmel Research and Education Corporation.     

Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension

OBJECTIVE: To test the hypothesis that Vegf-B contributes to the pulmonary vascular remodelling, and the associated pulmonary hypertension, induced by exposure of mice to chronic hypoxia. METHODS: Right ventricular systolic pressure, the ratio of right ventricle/[left ventricle+septum] (RV/[LV+S]) and the thickness of the media (relative to vessel diameter) of intralobar pulmonary arteries (o.d. 50-150 and 151-420 microm) were determined in Vegfb knockout mice (Vegfb(-/-); n=17) and corresponding wild-type mice (Vegfb(+/+); n=17) exposed to chronic hypoxia (10% oxygen) or housed in room air (normoxia) for 4 weeks. RESULTS: In Vegfb(+/+) mice hypoxia caused (i) pulmonary hypertension (a 70% increase in right ventricular systolic pressure compared with normoxic Vegfb(+/+) mice; P<0.001), (ii) right ventricular hypertrophy (a 66% increase in RV/[LV+S]; P<0.001) and (iii) pulmonary vascular remodelling (a 27-36% increase in pulmonary arterial medial thickness; P<0.05). In contrast, in Vegfb(-/-) mice hypoxia did not cause any increase in either right ventricular systolic pressure or pulmonary arterial medial thickness; also right ventricular hypertrophy (41% increase in RV/[LV+S]; P<0.001) was less pronounced (P<0.05) than in Vegfb(+/+) mice. CONCLUSION: Vegf-B may have a role in the development of chronic hypoxic pulmonary hypertension in mice by contributing to pulmonary vascular remodelling. If so, the effect of Vegf-B appears to be different from that of Vegf-A which is reported to protect against, rather than contribute to, hypoxia-induced pulmonary vascular remodelling.     

Interferon β-1a alone or in combination with ribavirin: A randomized trial to compare efficacy and safety in chronic hepatitis C

AIM: To compare the efficacy and safety of recombinant human IFN β-1a alone or in combination with ribavirin in treatment-naive subjects with chronic hepatitis C. METHODS: Open, randomized trial was performed in 6 Italian tertiary centers: 102 of the 108 patients screened were randomized to receive 6 MIU of recombinant human IFN β-1a subcutaneously daily for 24 wk, alone (Group 1, n = 51) or in combination with ribavirin 1000 to 1200 mg/d (Group 2, n = 51). RESULTS: The end-of-treatment virologic response rate was 29.4% in Group 1 and 41.2% in Group 2 (nonsignificant). Twenty-four weeks after stopping therapy, sustained virologic response rate was 21.6% in Group 1 and 27.4% in Group 2 (non-significant). All subjects in Group 1 completed treatment, while two subjects in Group 2 stopped therapy due to treatment-related adverse events. CONCLUSION: Recombinant human IFN β-1a, alone or in combination with ribavirin, has an excellent safety profile and, may represent an alternative for chronic hepatitis C patients who are unable to tolerate pegylated α-interferon.     

Understanding Interactions of Smoking on Prognosis of HPV-Associated Oropharyngeal Cancers

The new 8th edition AJCC/UICC staging system for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), developed to account for improved survival outcomes over HPV-negative cancers, includes anatomic features strictly associated with tumor-node-metastasis (TNM) and does not account for patient-specific characteristics that may impact prognosis. This commentary evaluates the evidence of smoking as an adverse prognostic factor in HPV-associated OPSCC. We review the multifactorial biological, clinical, and social/behavioral characteristics of smokers with OPSCC that impact outcomes, discuss current challenges with incorporating smoking history in prognostic classifications, and consider opportunities for future investigation.