Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

Postoperative analgesia: pain by choice? The influence of patient attitudes and patient education

Postoperative pain control can be unsatisfactory for a variety of reasons, including patients' attitudes towards pain treatment itself. To assess patients' expectations and their influence on postoperative analgesia, as well as the prevalence of pain following common gynaecological surgery, a prospective study was performed in 166 patients with either adbominal hysterectomy, mastectomy, laparoscopy or uterine curettage. After a first postoperative period with routine on-demand analgesia, a nurse specialised in pain treatment discussed the purposes and risks of pain treatment with the patients and cared for these patients in the second, subsequent study period. Following this discussion, 30 of 40 patients refusing analgesics in the first study period agreed to be given pain medication. In the groups with hysterectomy or mastectomy, pain control improved in the second postoperative period, even though the doses of analgesics administered were generally lower. Education of patients regarding the aims and risks of pain therapy is an essential part of pain control and can lead to an improvement of postoperative analgesia.     

无环鸟苷亲脂性前体药物脂质体的制备及体外抗病毒活性(英文)

本文通过将无环鸟苷(acyclovir,简称ACV)2’位羟基分别与月桂酰氯或棕榈酰氯进行酯化反应,制得亲脂性前体药物无环鸟苷月桂酸酯和无环鸟苷棕榈酸酯(分别简称为C₁₂-ACV和C₁₆-ACV),使脂质体包封率从ACV的29.9%提高到C₁₂-ACV的95.6%和C₁₆-ACV的97.1%;漏泄实验表明在4℃透析60h后,一半以上的ACV从脂质体中漏泄,而C₁₂-ACV和C₁₆-ACV的滞留率分别为70%和80%;体外抗疱疹病毒的试验中,在最低试验浓度0.044μmol/L时,ACV不显示抗病毒活性,而C₁₆-ACV脂质体抑制细胞病变率达75%,说明前体药物通过与脂质体脂膜的结合增加了药物的进入细胞能力,从而提高了ACV的抗病毒能力。     

Individual and group dose-responses to intravenous omeprazole in the first 24 h: pH-feedback-controlled and fixed-dose infusions.

1. Individual responses to intravenous boli of omeprazole have shown considerable variability. Data on the individual responses to the new omeprazole infusion formulation are lacking. 2. Individual dose-responses in the first 24 h of fixed-dose and pH-feedback-controlled infusions of omeprazole were assessed in two randomised, third-party blinded, cross-over studies, using two separate groups of eight healthy subjects. In study A, feedback-controlled infusions of omeprazole (target pH 5, dose range 0-12 mg h-1) and fixed-dose infusions (8 mg h-1) were compared, both with an initial bolus of 80 mg. Omeprazole plasma concentrations were measured. Study B assessed the effect on individual pH-control of a loading bolus of either 40 mg or 80 mg omeprazole, followed by feedback-controlled infusions. 3. Study A: the median % time of pH > 5 was 71.2 (total range: 48.9-83.2) with feedback infusions and 57.9 (28.0-95.3) with fixed-dose infusions (P = 0.06). The mean 24 h infusion doses were 173.1 mg (44.5-253.1) in the feedback group and 192 mg in the fixed-dose group. The AUC of omeprazole plasma concentrations ranged widely, but correlated with the % time of pH > 5 during fixed-dose infusions. Study B: initial boli of 40 mg and 80 mg of omeprazole resulted in similar 24 h median % of time with pH > 5, 69.2 (49.9-78.8) and 69.6 (44.4-87.7), respectively. Mean omeprazole doses infused by feedback pump were 187.6 mg (83.1-253.6) after 40 mg boli and 159.9 mg (61.8-227.0) after 80 mg boli.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management of bacterial peritonitis and exit‐site infections in continuous ambulatory peritoneal dialysis*

SUMMARY: Peritonitis and exit‐site infections remain the most important limitations to the delivery of continuous ambulatory peritoneal dialysis (CAPD). Contamination of the peritoneum, from endogenous or exogenous sources, is responsible for most peritonitis episodes. Patients usually present with a cloudy bag, although other causes should be distinguished. Clinical suspicion of peritonitis should be followed rapidly by microbiological examination and empirical treatment. Microbiological confirmation allows for subsequent treatment based on sensitivities. Other interventions such as catheter removal may be appropriate in some patients. Exit‐site infections should also be identified and treated early. Peritonitis may be further prevented by adequate exit‐site care, hygienic methods, and techniques to minimise early contamination of the exit site. Mupirocin may also have a role in preventing infections caused by Staphylococcus aureus.     

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.