Peritoneal defense in continuous ambulatory versus continuous cyclic peritoneal dialysis

Peritoneal defense in continuous ambulatory peritoneal dialysis versus continuous cyclic peritoneal dialysis. Several centers have reported a lower rate of peritonitis among adult patients on continuous cyclic peritoneal dialysis (CCPD) as compared to those undergoing continuous ambulatory peritoneal dialysis (CAPD). Preliminary results of our ongoing prospective randomized study comparing CAPD-Y with CCPD also suggest a lower peritonitis incidence among CCPD-treated patients. To investigate whether the two dialysis regimens could result in differences in local host defense, we studied peritoneal macrophage (PMO) function and effluent opsonic activity in eight patients established on CAPD-Y matched with eight chronic CCPD patients. Since short and long dwell times are inherent to both dialysis modalities, and we previously found that dwell time has an impact on PMO function and effluent opsonic activity, patients were studied after both a short (4hr) and a long (15hr) dwell time. In both patient groups PMO phagocytic capacity increased significantly with dwell time (39 ± 3.3% at 4hr vs. 58 ± 4.2% at 15hr in CAPD patients, and 40 ± 3.9 vs. 72 ± 3.3% in CCPD patients; P < 0.01), as did PMO peak chemiluminescence response (31 ± 4.9 vs. 77 ± 7.2 counts · min-1/104 cells in CAPD, and 22 ± 3.9 vs. 109 ± 21.2 counts · min-1/104 cells in CCPD; P < 0.01) and effluent opsonic activity (41 ± 7.6 vs. 73 ± 5.8% in CAPD and 39 ± 6.2 vs. 70 ± 5.9% in CCPD; P < 0.01). However, no significant difference was found in either variable between CAPD and CCPD patients when dwell times were equal. In conclusion, no differences were observed in PMO function or effluent opsonic activity between matched CAPD-Y and CCPD patients when dwell times were equal. In both patient groups prolongation of dwell time enhanced PMO function as well as effluent opsonic activity, thereby providing a better host defense. The improvement in peritoneal defenses may, in part, be responsible for the lower peritonitis incidence observed among CCPD-treated patients

Combination of insulin and metformin in the treatment of type 2 diabetes

WSTĘP. Celem pracy była ocena działania metabolicznego metforminy w porównaniu z placebo, u chorych na cukrzycę typu 2, leczonych według schematu intensywnej insulinoterapii. MATERIAŁ I METODY. Metformina poprawia kontrolę glikemii u osób ze źle wyrównaną cukrzycą typu 2. Dotychczas nie zbadano jej wpływu u chorych na cukrzycę typu 2, leczonych metodą intensywnej insulinoterapii. Grupa 390 chorych na cukrzycę typu 2, stosujących insulinę, uczestniczyła w randomizowanym, kontrolowanym, przeprowadzonym metodą podwójnie ślepej próby badaniu z zaplanowaną pośrednią analizą po 16 tygodniach leczenia. Uczestników badania wybrano z 3 przyszpitalnych przychodni i losowo przydzielono do grup, przyjmujących placebo lub metforminę w uzupełnieniu insulinoterapii. Podczas badania prowadzono intensywną kontrolę glikemii z natychmiastowym dostosowaniem dawki insuliny, zgodnie ze ścisłymi wytycznymi. Określano wskaźniki kontroli glikemii, zapotrzebowanie na insulinę, masę ciała, ciśnienie tętnicze, stężenie lipidów, incydenty hipoglikemii i inne działania niepożądane. WYNIKI. Sposród 390 osób 37 nie ukończyło badania (12 w grupie otrzymującej placebo i 25 w grupie leczonej metforminą). U osób, które ukończyły 16-tygodniowy okres leczenia zastosowanie metforminy w porównaniu z placebo powodowało poprawę kontroli glikemii (średnia glikemia podczas 16 tygodni 7,8 vs. 8,8 mmol/l, p = 0,006; średnie stężenie HbA1c 6,9 vs. 7,6%, p < 0,0001), zmniejszone zapotrzebowanie na insulinę (63,8 vs. 71,3 j.; p < 0,0001), mniejszy przyrost masy ciała (-0,4 vs. +1,2 kg; p < 0,01) i zmniejszenie stężenia cholesterolu frakcji LDL (-0,21 vs. -0,02 mmol/l; p < 0,01). Ryzyko wystąpienia hipoglikemii było podobne. WNIOSKI. U chorych na cukrzycę typu 2, leczonych intensywnie insuliną, skojarzenie insuliny z metforminą powoduje lepsze wyrównanie glikemii w porównaniu z monoterapią insuliną, a jednocześnie zmniejsza zapotrzebowanie na insulinę i ogranicza przyrost masy ciała.INTRODUCTION. To investigate the metabolic effects of metformin, as compared with placebo, in type 2 diabetic patients intensively treated with insulin. MATERIAL AND METHODS. Metformin improves glycemic control in poorly controlled type 2 diabetic patients. Its effect in type 2 diabetic patients who are intensively treated with insulin has not been studied. A total of 390 patients whose type 2 diabetes was controlled with insulin therapy completed a randomized controlled double-blind trial with a planned interim analysis after 16 weeks of treatment.The subjects were selected from three outpatient clinics in regional hospitals and were randomly assigned to either the placebo or metformin group, in addition to insulin therapy. Intensive glucose monitoring with immediate insulin adjustments according to strict guidelines was conducted. Indexes of glycemic control, insulin requirements, body weight, blood pressure, plasma lipids, hypoglycemic events, and other adverse events were measured. RESULTS. Of the 390 subjects, 37 dropped out (12 in the placebo and 25 in the metformin group). Of those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with improved glycemic control (mean daily glucose at 16 weeks 7.8 vs. 8.8 mmol/l, P = 0.006; mean GHb 6.9 vs. 7.6%, P < 0.0001); reduced insulin requirements (63.8 vs. 71.3 IU, P < 0.0001); reduced weight gain (&#8211;0.4 vs. +1.2 kg, P < 0.01); and decreased plasma LDL cholesterol (&#8211;0.21 vs. &#8211;0.02 mmol/l, P < 0.01). Risk of hypoglycemia was similar in both groups. CONCLUSIONS. In type 2 diabetic patients who are intensively treated with insulin, the combination of insulin and metformin results in superior glycemic control compared with insulin therapy alone, while insulin requirements and weight gain are less

Effects of Psychiatric Consultation on Medical Consumption in Medical Outpatients With Abdominal Pain

A randomized controlled clinical trial was conducted in an outpatient clinic of internal medicine to test the hypothesis that a protocol of cooperation and communication between internist and general practitioner, sustained with psychiatric consultation, would reduce medical consumption in a group of medical outpatients with abdominal pain (N = 106). A reduction in medical consumption could not be demonstrated. However, a great variation in protocol adherence was found, partly related to the severity of the psychological problems. There is some evidence that the protocol, if restricted to cases with more severe psychiatric comorbidity, might reduce medical consumption

Analysis of twenty-four-hour ambulatory blood pressure monitoring: What time period to assess blood pressures during waking and sleeping?

Objective: To study whether two widely used methods of analysis of ambulatory blood pressure monitoring (ABPM), which calculate means for fixed periods, provide accurate estimates of blood pressure during the true waking and sleeping periods. Design and methods: Ninety-five ABPM recordings were retrospectively analysed. Mean systolic and diastolic blood pressures during waking and sleeping were calculated in three ways: the waking and sleeping period according to the diary of the patient (diary method); the waking period from 0700 to 2200 h and the sleeping period from 2200 to 0700 h (9h); and the waking period from 1000 to 2300 h and the sleeping period from 0100 to 0700 h (6 h). Results: Systolic and diastolic blood pressures during the waking period were not different among the three methods of analysis. Compared with the diary method, the 9h sleeping period method overestimated systolic blood pressure during sleep by 3.74 mmHg [99% confidence interval (Cl) 2.70-4.77] and diastolic blood pressure by 2.44 mmHg (99% Cl 1.75-3.14). In contrast, there was no significant difference between the diary method and the 6h sleeping period method. Conclusions: The 6h sleeping period method gave accurate estimates of blood pressure during sleep. The use of the long (9 h) sleeping period method should be avoided in studies in which sleeping-waking differences will be part of the analysis

Reliability of clinical oral examinations re-examined

Many medical schools still use oral examinations for the evaluation of clinical competence of students in their clerkship, although it has been proven that orals have poor reliability. This study investigates the feasibility and reliability of multiple oral examinations. Students in the last week of their Internal Medicine clerkship in an outpatient clinic were given several patient-based oral examinations. The student's performance was rated on a list of items reflecting clinical competence. A global judgement of the student's performance was also given. The results indicate that it is possible to increase the number of orals and the number of examiners in the day-to-day practice of an outpatient clinic moderately. The reliability when using a number of orals is better than the reliability of the common single oral examination. The reliability using global judgements appeared to be better than the reliability of averaged item scores

Effects of insulin on glucose uptake and leg blood flow in patients with sickle cell disease and normal subjects

The hemodynamic concept of insulin resistance assumes that vasodilatory effects of insulin determine glucose uptake. Sickle cell disease (SCD) is characterized by microangiopathy and microvascular occlusion. Therefore, we hypothesized that patients with SCD have a reduced insulin-mediated glucose uptake. In 8 patients with SCD and 8 matched normal controls, we studied the effects of a 4-hour insulin infusion (50 mU/kg/h) on glucose uptake and leg blood flow (LBF) using the euglycemic clamp technique and venous occlusion plethysmography. Time-control experiments were performed in the same subjects. Insulin-mediated glucose uptake (M value, mg/kg/min) did not differ between patients with SCD and control subjects during the second (6.3 ± 4.6 and 7.6 ± 2.6, P = .5), third (7.5 ± 4.6 and 9.3 ± 3.4, P = .4) and fourth hour (8.6 ± 4.7 and 11.0 ± 2.9, P = .2) of the clamp. At baseline, LBF was higher in the patients with SCD than in the controls (3.28 ± 1.68 and 1.37 ± 0.47 mL/min/dL, respectively; P = .005). Insulin-induced increases in LBF in patients with SCD and in normal subjects were not different (P = .9). Respectively, 56% and 24% of the changes in glucose uptake could be explained from changes in LBF in the course of the insulin infusion in the patients with SCD and controls. We suppose that the comparable insulin sensitivity between both groups is due to a compensatory hemodynamic state in SCD characterized by vasodilation and increased flow

Direct evidence for insulin-induced capillary recruitment in skin of healthy subjects during physiological hyperinsulinemia

It has been proposed that insulin-mediated changes in muscle perfusion modulate insulin-mediated glucose uptake. However, the putative effects of insulin on the microcirculation that permit such modulation have not been studied in humans. We examined the effects of systemic hyperinsulinemia on skin microvascular function in eight healthy nondiabetic subjects. In addition, the effects of locally administered insulin on skin blood flow were assessed in 10 healthy subjects. During a hyperinsulinemic clamp, we measured leg blood flow with venous occlusion plethysmography, skin capillary density with capillaroscopy, endothelium-(in)dependent vasodilatation of skin microcirculation with iontophoresis of acetylcholine and sodium nitroprusside combined with laser Doppler fluxmetry, and skin vasomotion by Fourier analysis of microcirculatory blood flow. To exclude nonspecific changes in the hemodynamic variables, a time-volume control study was performed. Insulin iontophoresis was used to study the local effects of insulin on skin blood flow. Compared to the control study, systemic hyperinsulinemia caused an increase in leg blood flow (-0.54 ± 0.93 vs. 1.97 ± 1.1 ml · min-1 · dl-1; P < 0.01), an increase in the number of perfused capillaries in the resting state (-3.7 ± 3.0 vs. 3.4 ± 1.4 per mm2; P < 0.001) and during postocclusive reactive hyperemia (-0.8 ± 2.2 vs. 5.1 ± 3.7 per mm2; P < 0.001), an augmentation of the vasodilatation caused by acetylcholine (722 ± 206 vs. 989 ± 495%; P < 0.05) and sodium nitroprusside (618 ± 159 vs. 788 ± 276%; P < 0.05), and a change in vasomotion by increasing the relative contribution of the 0.01- to 0.02-Hz and 0.4- to 1.6-Hz spectral components (P < 0.05). Compared to the control substance, locally administered insulin caused a rapid increase (∼13.5 min) in skin microcirculatory blood flow (34.4 ± 42.5 vs. 82.8 ± 85.7%; P < 0.05). In conclusion, systemic hyperinsulinemia in skin 1) induces recruitment of capillaries, 2) augments nitric oxide-mediated vasodilatation, and 3) influences vasomotion. In addition, locally administered insulin 4) induces a rapid increase in total skin blood flow, independent of systemic effects

Microvascular function relates to insulin sensitivity and blood pressure in normal subjects

Background - A strong but presently unexplained inverse association between blood pressure and insulin sensitivity has been reported. Microvascular vasodilator capacity may be a common antecedent linking insulin sensitivity to blood pressure. To test this hypothesis, we studied 18 normotensive and glucose-tolerant subjects showing a wide range in insulin sensitivity as assessed with the hyperinsulinemic, euglycemic clamp technique. Methods and Results - Blood pressure was measured by 24-hour ambulatory blood pressure monitoring. Videomicroscopy was used to measure skin capillary density and capillary recruitment after arterial occlusion. Skin blood flow responses after iontophoresis of acetylcholine and sodium nitroprusside were evaluated by laser Doppler flowmetry. Insulin sensitivity correlated with 24-hour systolic blood pressure (24-hour SBP; r= -0.50, P < 0.05). Capillary recruitment and acetylcholine-mediated vasodilatation were strongly and positively related to insulin sensitivity (r = 0.84, P < 0.001; r = 0.78, P < 0.001, respectively), and capillary recruitment was inversely related to 24-hour SBP (r = -0.53, P < 0.05). Waist-to-hip ratio showed strong associations with insulin sensitivity, blood pressure, and the measures of microvascular function but did riot confound the associations between these variables. Subsequent regression analysis showed that the association between insulin sensitivity and blood pressure was not independent of the estimates of microvascular function, and part of the variation in both blood pressure (R2 = 38%) and insulin sensitivity (R2 = 71%) could be explained by microvascular function. Conclusions - Insulin sensitivity and blood pressure are associated well within the physiological range. Microvascular function strongly relates to both, consistent with a central role in linking these variables