Effect of variable hydraulic conductivity on transcapillary fluid exchange: Application to the microcirculation of rat intestinal muscle

A theoretical model has been developed to study the influence of variable hydraulic wall conductivity of single capillaries on transmural fluid exchange. A systematic study has been carried out to examine the factors which determine the direction of transcapillary fluid flow; i.e., filtration or absorption. One important result of this study is that, in addition to capillary pressure and plasma protein concentration, the shape of the axial distribution of the hydraulic conductivity of the capillary wall can affect the direction of transmural fluid movement. The experimental data for the axial distribution of the hydraulic conductivity of single capillaries in the rat intestinal muscle of R. W. Gore, W. Schoknecht, and H. G. Bohlen (In “Microcirculation,” J. Grayson and W. Zingg, eds., Vol. 1, pp. 331–332, Plenum, New York) were employed in the present model in order to predict axial and radial fluid flow. The comparison of the results with experimental data for capillary pressure and transmural flux at four axial positions showed excellent agreement. The results of the present model support the experimental finding of Gore et al. that the capillary bed in the rat intestinal muscle is absorptive.     

Comparing the effects of scopolamine on operant and aggressive responses in squirrel monkeys

The anticholinergic drug, scopolamine, causes disinhibition or an increase in response that an animal normally suppresses. Experiment 1 confirmed this effect in squirrel monkeys. Experiment 2 explored the implications of drug-produced disinhibition on aggressive interactions. In Experiment 1, scopolamine produced increased unreinforced responding on a DRL schedule and increased responding during unreinforced (Time Out) periods. In contrast, the peripheral control drug, methyl scopolamine, caused decreased responding in both situations. In Experiment 2, social rank and drug treatment interacted. When space was restricted so that the opportunity for social interactions was maximized, scopolamine consistently increased aggressiveness in the dominant monkey and decreased aggressiveness in a submissive monkey. When space was increased so that the opportunity for social interactions was minimized, scopolamine caused decreased aggressive responses in all monkeys. Neither the effective dosage nor the drug's effect on the operant task could be easily generalized to aggressive responses.     

Comparison of peripheral metabolic effects of insulin and metformin following severe burn injury

OBJECTIVE: Both insulin and metformin have been shown to attenuate hyperglycemia and reduce net muscle protein catabolism following burn injury. The purpose of this study was to compare the peripheral metabolic effects of insulin and metformin in severe burn patients. METHODS: Six adult patients with burns greater than 40% of their body surface underwent metabolic evaluation utilizing isotopic dilution of phenylalanine, femoral arterial and venous blood sampling, and sequential biopsies of leg muscle. Following baseline measurements, insulin was infused into the femoral artery at 0.45 mIU/min 100 mL leg volume. Patients were then given metformin (850 mg every 8 hours) for seven days with repeat metabolic evaluation before and during intra-arterial infusion of insulin. RESULTS: Intra-arterial administration of insulin significantly increased insulin concentrations within the femoral vein, creating hyperinsulinemia localized to the extremity. Metformin had no significant effect on either peripheral glucose clearance or the rate of glucose oxidation. Furthermore, the availability of ATP and energy charge within muscle was not overtly affected by either insulin or metformin. Metformin did significantly increase the fractional synthetic rate of muscle protein which increased even further with insulin administration. Both metformin and insulin separately increased the rate of muscle protein synthesis as calculated using three compartment modeling. CONCLUSION: This study demonstrates a significant anabolic effect on muscle protein with metformin and a modest response with insulin. Findings also suggest that metformin and insulin may work synergistically to further improve muscle protein kinetics.     

Mental health of low income uninsured men with prostate cancer

PURPOSE: We evaluated mental health outcomes in a cohort of low income, uninsured men with prostate cancer and identified factors that influence mental health. MATERIALS AND METHODS: We performed a retrospective cohort study of 277 subjects enrolled in a program that provides free care to men with prostate cancer who have an annual income of no more than 200% of the federal poverty level. We compared scores on the 5-item RAND Mental Health Inventory (MHI-5) to those in individuals with other chronic diseases. We also examined the relationship between MHI-5 scores and validated measures of general and disease specific health related quality of life. Disease specific quality of life included measures of distress related to urinary, sexual and bowel habits. Multivariate analyses were performed to evaluate factors associated with mental health score. RESULTS: Most men studied were Hispanic (51.6%) and had at most a high school education (85.9%). Mean MHI-5 score +/- SD was 68 +/- 23 on a 100-point scale, significantly worse than cohorts of men with diabetes, congestive heart failure and chronic pulmonary disease. Hispanic ethnicity, urinary bother and bowel bother were negatively associated with mental health. Spirituality and physical functioning were positively associated with mental health. CONCLUSIONS: Economically disadvantaged men with prostate cancer report worse mental health than people with other chronic diseases. Patients especially at risk are those with significant urinary or bowel distress, poor physical health, low spirituality and Hispanic ethnicity.     

Surgical excision of isolated renal-bed recurrence after radical nephrectomy for renal cell carcinoma

OBJECTIVE: To present our results on managing loco-regional recurrence of renal cell carcinoma (RCC) with surgical excision, as local recurrence at the site of a previous nephrectomy is resistant to both systemic therapy and radiotherapy. PATIENTS AND METHODS: In all, 16 patients were operated on between 1994 and 2003 for local recurrence of RCC. The median (mean, range) age at the time of local recurrence was 57.9 (57.4, 28.9-71.7) years, and the median interval from primary surgery 2.22 (3.88, 0.27-14.46) years. Before surgery eight patients had been given systemic immunotherapy, with no response of their local recurrence. RESULTS: Two patients were deemed inoperable because of direct invasion of the great vessels and the liver by tumour. The remaining 14 patients had recurrence in residual adrenal tissue (two), para-aortic nodes (three), para-caval nodes (two), retrocaval nodes (one), renal bed (six), liver, spleen and stomach (one each), and diaphragm (two). Although complete macroscopic en-bloc clearance was achieved in these patients, only eight had tumour-free margins on histological examination. The histology was consistent with RCC recurrence in all cases. All of the patients were followed with computed tomography at regular intervals. At a median follow-up of 1.0 (1.65, 0.25-6.5) years, five patients remain disease-free, four have local and distant relapse, and five developed distant metastasis only. The presence of tumour at the resection margin was a significant factor in predicting local and distant disease-free survival (P < 0.05). CONCLUSIONS: En bloc excision of isolated locally recurrent RCC is possible, and complete surgical extirpation can lead to prolonged disease-free survival.     

Pulmonary artery catheterization in acute coronary syndromes: insights from the GUSTO IIb and GUSTO III trials

PURPOSE: To correlate pulmonary artery catheterization (PAC) use and 30-day outcomes and to characterize the use of pulmonary artery catheters among patients with acute coronary syndromes (ACS). SUBJECTS AND METHODS: We retrospectively studied 26437 ACS patients from two large multicenter, international randomized clinical trials. Multivariable and causal inference analyses were applied to adjust for differences in baseline risk. RESULTS: PAC was performed in 735 patients (2.8%), with a median time to insertion of 24 hours. Patients undergoing PAC were older (median, 67 vs. 64 years), more often diabetic (25.7% vs.16.2%), and more likely to present with ST-segment elevation (81.6% vs. 70.2%) or Killip class III or IV (7.9% vs. 1.4%). US patients were 3.8 times more likely than non-US patients to undergo PAC. Patients managed with PAC also underwent more procedures, including percutaneous intervention (40.7% vs. 18.1%), coronary artery bypass grafting (12.5% vs. 7.7%), and endotracheal intubation (29.3% vs. 2.2%). Mortality at 30 days was substantially higher among patients with PAC for both unadjusted (odds ratio [OR] 8.7; 95% confidence interval [CI] 7.3-10.2) and adjusted analyses (OR 6.4; 95% CI 5.4-7.6) in all groups except in patients with cardiogenic shock (OR 0.99; 95% CI 0.80-1.23). CONCLUSIONS: PAC was associated with increased mortality, both before and after adjustment for baseline patient differences and subsequent events that may have led to PAC use, except in patients with cardiogenic shock. The definitive role of PAC in managing patients with ACS is still to be determined.     

Atenolol eye drops in glaucoma: a double-masked, controlled study.

Guttae atenolol 4% (Tenormin), a pure beta1-blocking (i.e., cardioselective) drug, produced a median overall fall of 5-6 mmHg (range 3-2 to 13-2 mmHg) in the first tonometrised eyes of 7 patients with open-angle glaucoma or ocular hypertension and 1 with closed-angle glaucoma (off any treatment for the whole of the day preceding each test day) after allowance for an 'effect' of guttae saline 0-9%, in a double-masked, cross-over trial. By a Wilcoxon matched pairs rank test this was significant at the P less than 0-05 level. The median overall fall of 3-5 mmHg (range 0-8 to 10-8 mmHg) in the second-tonometrised eyes of 7 patients (1 of the 8 contributed only 1 eye) was also significant (P less than 0-05). In 2 patients who had been treated with guttae atenolol 4% daily 3 X for 1 and 2 months there is evidence that, on replacing the atenolol 4% with saline 0-9%, a rise of pressure of around 3 mmHg occurred 2 and 3 and 5 days later, i.e., the drug still retained its effectivity (slightly reduced) after 1 and 2 months.