Urinary sodium excretion in patients with nephrotic syndrome, and its circadian variation

We analysed sodium excretion and its circadian variation in70 patients with nephrotic syndrome and 19 healthy controlsover 1–3 days, with a regimen of bed rest and constantsodium intake around the clock. We sampled urine and blood andtook their blood pressure every 3 h. We also scored 60 renalbiopsies for presence of interstitial fibrosis and tubular atrophy.Peripheral oedema was estimated in 37 patients. Fifty-nine patients excreted >10mmol sodium per 24 h, inequilibrium with dietary intake. In group A (n = 24), sodiumexcretion followed a normal circadian rhythm, with a daytimepeak. In group B (n = 35), 29 had reversed circadian rhythmwith a night-time peak, and 6 had no apparent rhythm. Nephroticsyndrome was more severe in group B than in A (serum albumin19.5 vs. 24.1 g/l, p<0.05; oedema 7.0 vs. 3.8 kg, p<0.01).Group B also had signs of more advanced renal disease (GFR 49vs. 99 ml/min; number of biopsies with tubulo-interstitial damage:20/28 vs. 4/23; p< 0.001). Reversed sodium rhythm was associatedwith reversed circadian rhythms for GFR, effective renal plasmaflow and urine flow, and blunting or reversal of the day-nightdifferences in blood pressure and plasma renin activity. Elevenpatients had urinary sodium excretion <1 mmol/24 h. Withrespect to severity of nephrosis, they resembled group B, butGFR and incidence of tubulointerstitial lesions were like groupA. Half of the patients with nephrotic syndrome had reversed circadianrhythm for sodium excretion. This nocturnal peak in natriuresis(and diuresis) may be due to re-entry of oedema fluid into thecirculation, with a subsequent increase in renal blood flowand GFR, and especially occurs in patients with structural tubulointerstitialdamage, where sodium reabsorption is incomplete.     

Traumatic or septic aortic regurgitation: diagnosis by oesophageal echocardiography

Severe aortic regurgitation was discovered in a young man 21 days after blunt chest trauma and after a prolonged febrile state with positive blood cultures. Using transoesophageal echocardiography (TEE), it was possible to make the differential diagnosis between traumatic rupture and endocarditis as the cause of valvular insufficiency. The use of TEE in the initial evaluation of severe thoracic trauma with an unclear clinical picture is recommended. This method is easy to use at the bedside and gives precise information on the aortic valve and the ascending aorta.     

Psychological well-being of informal caregivers of elderly people with dementia: Changes over time

Psychological well-being of caregivers of demented elderly people was investigated during two years of follow-up. Three groups of caregivers were distinguished: those providing care for two years after baseline; those whose care-recipient died within the first year after baseline, and those whose care-recipient was institutionalized within the first year. Compared to general population norms, all groups of caregivers showed a great amount of psychological distress, especially those whose elder suffering from dementia deceased within the first year after baseline. The course of psychological well-being of caregivers who continued to provide care during follow-up supported the wear-and-tear model: an overall deterioration of psychological well-being was found (measured by the GHQ-12, SCL-90-R and SWLS) as elders' functioning declined and caregiving at home continued. Specific increases were found on total amount of psychological distress, but also on the SCL-90-R subscales: Depression, Anxiety, Interpersonal Sensitivity and Paranoid Ideation and Difficulty with Cognitive Performance. No overall changes were found for caregivers whose demented care-recipient had died or was institutionalized in the first year after baseline. These data suggest that the high level of psychological distress and the deterioration in psychological well-being among informal caregivers of dementia patients is a reason to reconsider the merits of the current trend to have demented older people live on their own as long as possible. Additional support should be considered.     

COMPARISON OF NITROGLYCERINE, VERAPAMIL AND NIFEDIPINE IN THE MANAGEMENT OF ARTERIAL PRESSURE DURING CORONARY ARTERY SURGERY

The efficacy of nitroglycerine, verapamil and nifedipine incontrolling post-sternotomy hypertension was compared in fourgroups of 20 patients anaesthetized with fentanyl 100 µgkg^–1 undergoing elective coronary artery surgery. Vasodilatorswere started before surgery and adjusted to maintain systolicarterial pressure < 120% of pre-infusion values, the mean(±SEM) requirements being: nitroglycerine (group II)3.6±0.6 µg kg^–1 min^–1; verapamil groupIII) 31.1 ±2.6 µg kg^–1 min¹ nifedipine (groupIV) 1.7±0.2 µg kg^–1 min^–1 Systolicpressure decreased significantly by 5 min after starting infusionsin groups II and III. In the control group (I: no vasodilator)arterial pressure increased significantly following skin incisionand sternotomy. Pulmonary arterial and capillary wedge pressuresincreased significantly following sternotomy in groups I andIII. Heart rate increased after sternotomy in all groups, butonly reached significance in groups III and IV. There were nosignificant changes in cardiac index or vascular resistance,although the latter remained lower than pre-infusion valuesat all times in groups III and IV. The P-Q interval increasedsignificantly in group III. It is concluded that nifedipineis a suitable alternative to nitroglycerine for the controlof arterial pressure during coronary artery surgery, but verapamilis not recommended because of its negative inotropic effectand its depressant effect on A-V conduction.     

THE PHARMACOLOGICAL ROLE OF P-GLYCOPROTEIN IN THE INTESTINAL EPITHELIUM

P-glycoprotein, a membrane-associated transport protein, has recently been recognised as an important element of the intestinal epithelium. This paper summarises thein vivodata on the pharmacological role of intestinal P-glycoprotein. These data show that P-glycoprotein contributes to the elimination of many drugs by mediating their direct secretion from the blood into the intestinal lumen. In addition, there is also evidence that this protein can limit oral drug absorption. Hence, inhibition of intestinal P-glycoprotein, e.g. by a reversal agent like cyclosporin A, may be a promising strategy for improving the oral bioavailability of P-glycoprotein substrate drugs. Indeed, several preclinical and clinical studies have shown that coadministration of drugs with a reversal agent can substantially increase oral drug absorption.     

34例淋巴瘤骨髓浸润患者治疗与预后分析

目的 探讨淋巴瘤骨髓浸润患者的治疗与预后。方法 34例淋巴瘤骨髓浸润患者分为单纯化疗组、化疗+放疗组、大剂量化疗+自体干细胞移植组进行治疗,长期随访,分析其预后状况。结果 全组中位生存期为20个月;1年和3年生存率分别为76.47％和26.47％,最初疗效为完全缓解和部分缓解患者的1年和3年生存率均大于未缓解患者(P<0.05);大剂量化疗+自体干细胞移植组的3年生存率大于单纯化疗组和化疗+放疗组(P<0.05)。结论 淋巴瘤骨髓浸润患者的生存率与最初疗效有关;大剂量化疗+自体干细胞移植能提高其生存率,改善预后。     

Mechanisms and patient compliance of dust-mite avoidance regimens in dwellings of mite-allergic rhinitic patients

We report on the mechanisms, the environmental changes and patient compliance with regard to conventional and new dust and mite avoidance measures to prevent allergic symptoms caused by mite allergens, taking into account both allergen contamination and the developmental success of pyroglyphid Acari. Twenty patients with persisting rhinitic complaints were selected and matched. Although the patients had performed some conventional dust and mite avoidance measures (patient compliance was 90%), the dwellings proved to be a stimulus for mite development. Moisture problems due to faulty construction and excessive moisture production were common. Since humidity conditions could not be changed at short notice, the 20 homes were subjected to the new variants of mite allergen avoidance based on intensive cleaning without (control) and with an acaricide incorporated (acaricidal cleaner [Acarosan]). After the carrying out of conventional avoidance measures, these patients still had allergic symptoms, and dust from only 23 to 52% of their textile objects was under the proposed guanine (mite faeces indicator) risk level. Only the acaricidal cleaner was able to decrease the allergenic mite load (and the burden of the patients) significantly in this 12 month period. With respect to mite-extermination, acaricidal cleaning was 88% better than intensive cleaning. Reduction of guanine was 38% better in the Acarosan treatment group. Clinical results have been reported elsewhere. A significant difference in favour of the acaricidal cleaning was seen in both subjective (as regards symptoms) and in objective data (total IgE). Another 50 patients were questioned. About 90% were willing to spend two weekends (70%), or at the most one weekend (20%) per year sanitizing the dwelling by cleaning it with the whole family. The authors of this report consider acaricidal cleaning to be a significant improvement in the management of mite-allergic diseases, such as rhinitis. Compared with the replacement of home textiles, this treatment is less expensive and more effective. Patient compliance is acceptable, but depends on acceptance by physicians and the initial motivation and consequent burden on the patient.     

Autoimmune reactions in patients with M-component and peripheral neuropathy.

A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, WaldenstrÖm's disease in one patient, and myeloma in three patients. Immunohistological examination with direct and indirect fluorescence showed binding of antibodies to nerve structures of the same class and light chain as seen in the M-component. In five cases of IgM M-component, the demyelinating neuropathy was caused by binding of the IgM M-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical and therapeutic difficulties are discussed; only two patients with an acute course responded to immunosuppression. A marked co-expression of other autoimmune phenomena is interpreted in the light of cross-reactions between the autoantibody and similar tissue autoantigens.     

Frusemide and Its Acyl Glucuronide Show a Short and Long Phase in Elimination Kinetics and Pharmacodynamic Effect in Man

The pharmacokinetics of 80 mg frusemide given orally were investigated in normal subjects using a direct HPLC method for parent drug and its acyl glucuronide conjugate. Two half-lives could be distinguished in the plasma elimination of both frusemide and its conjugate, with values of 1.25 ± 0.75 and 30.4 ± 11.5 h for frusemide and 1.31 ± 0.60 and 33.2 ± 28.0 h for the conjugate. The renal excretion rate-time profile showed two phases; the rapid elimination phase lasted from 0–15 h and the second and slow phase, from 15–96 h. During the first 15 h, 33.3 ± 4.8% of the dosed frusemide was excreted; in the remaining period 15–96 h, 4.6 ± 1.5% was excreted. In the same two periods the excretion of the glucuronide was 13.4 ± 4.7 and 1.9 ± 1.1%, respectively. The mean renal clearance of frusemide was 90.2 ± 16.9 mL min^?1 during the first period and 91.5 ± 29.3 mL min^?1 in the remaining period, during which the stimulation of urine production was absent. The renal clearance of the acyl glucuronide was 702 ± 221 mL min^?1 in the first period, but only 109 ± 51.0 mL min^?1 in the second period. The stimulated urine production in the first 6 h after administration amounted to 2260 ± 755 mL (measured urine production minus baseline value of 1 mL min^?1 (360 mL). During the second or rebound period (6–96 h after drug administration), the quantity of urine was 990 ± 294 mL lower than what would have been expected from the baseline production of 5400 mL. This reduced production (0.82 mL min^?1) is equivalent to an 18% reduction in the average urine flow rate of 1 mL min^?1.     

Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism

Abstract. The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of cholesterol in HDL and the subsequent transfer of cholesteryl ester towards apolipoprotein B-containing lipoproteins. Phospholipid transfer protein (PLTP) may be involved in the regulation of HDL particle size. We therefore measured the activities of LCAT, CETP and PLTP using exogenous substrate assays, as well as lipids, lipoproteins, insulin and C-peptide in fasting plasma from eight healthy obese men (body mass index >27 kg m^-2) and 24 non-obese subjects. The obese men had lower levels of HDL cholesterol (P<0·05) and higher levels of plasma triglycerides (P<0·05), insulin (P<0·05) and C-peptide (P<0·01), as compared to the quartile of subjects with the lowest body mass index (BMI <22·4 kg m^-2). CETP and PLTP activities were elevated in the obese men by 35% (P<0·01) and by 15% (P<0·05), respectively. LCAT activity was comparable among the quartiles. Linear regression analysis showed that CETP activity was positively correlated with body mass index (P<0·02), fasting blood glucose (P7lt;0·05) and plasma C-peptide (P<0·05). PLTP activity was positively related to body mass index (P<0·01), waist to hip circumference ratio (P<0·001), as well as to fasting blood glucose (P<0·05) and plasma C-peptide (P<0·05) It is concluded that the activities of CETP and PLTP are influenced by adiposity and possibly by insulin resistance. Elevated lipid transfer protein activities may provide a mechanism that contributes to alterations in HDL in insulin resistant states.