Renal growth and function 11–28 years after treatment of Wilms' tumour

In order to obtain more information on the long-term effects of treatment of Wilm's tumour we investigated 30 subjects treated at the Children's Hospital between 1960 and 1976. All had been nephrectomized and in 4 the length of the remaining kidney was subnormal. In the other subjects kidney length was related to follow up time and age at follow up. Blood pressure was elevated in 5 subjects. Urinary albumin excretion deviated only slightly from normal. Tubular functions were well preserved in all subjects. In this small series we were unable to establish any relation between the abnormalities observed and the treatment given. Our results suggest that, despite wide interindividual variation those who survive Wilm's tumours seldom have long-term renal complications.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after renal transplantation

Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged 6.3 – 24.3 (median 15.0) years who had been transplanted 1.5 – 8.4 years previously. Daytime values were compared with the mean of 10 concomitant casual blood pressure recordings. At the time of the study, antihypertensive drugs were given to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per 1.73 m². Ambulatory blood pressure monitoring confirmed hypertension or normotension determined by casual blood pressure measurements in 63% of patients. The physiological nocturnal dip in blood pressure was attenuated or reversed in 8 of 27 patients. It was reduced in all 3 patients with renal artery stenosis of the graft, in 3 of 4 patients with chronic rejection, in the only patient with recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past acute rejection. The dipping was not related to inulin clearance. In conclusion, casual blood pressure measurements do not accurately reflect blood pressure in pediatric patients transplanted more than 1.5 years previously. A reduced nocturnal dip in blood pressure may indicate an underlying renovascular or renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly be applied in patients with renal transplants. Received May 23, 1995; received in revised form June 18, 1996; accepted June 20, 1996     

Stereotactic brain biopsy in AIDS

Summary In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrastCT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.     

Proteinuria and other renal functions in Wilson’s disease

Renal lesions have repeatedly been described in Wilson’s disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-β-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6 – 37 (mean 17) years who had been treated for a period of 0 – 15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of β₂-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD. Received October 26, 1995; received in revised form August 27, 1996; accepted September 20, 1996     

Reconstruction of the anterior cruciate ligament with a cyropreserved ACL allograft

Summary. The ACL in the rabbit is innervated by three types of nerve fibres. These subserve vasoconstriction, nociceptive and proprioceptive purposes. The aim of this paper was to investigate the revascularisation and reinnervation of cyropreserved ACL allografts in 22 New Zealand white rabbits. Cyropreserved grafts were used as they may excite less host immune response. Both microangiographic and immunohistochemical methods were used. We found that cryopreserved allografts exhibited little immune response, revascularisation was considerable by the 24th postoperative week and reinnervation was essentially complete by then. No mechanoreceptors were found in ACL allografts. In rabbits, the anatomical basis for the participation of ACL allografts in sensorimotor reflexes is not given before the twelfth week after transplantation.

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Résumé. Nous avons examiné par méthodes micro-angiographiques et immuno-histo-chimiques la revascularisation et l’innervation d’un allogreffon cryopréservé (os – ligament croisé antérieur – os), chez 22 lapins de Nouvelle Zélande. Au sein de la greffe, existe une hypervascularisation maximale à 6 semaines, persistante à 12 semaines et se normalisant 24 semaines après la transplantation. Le panicule adipeux du genou était une source importante pour la revascularisation du greffon. L’immuno-histo-chimie a montré la présence de 3 types de fibres nerveuses au sein du ligament croisé: des afférents sensoriels mécano-réceptifs, des afférents sensoriels nociceptifs et des efférents sympathiques vaso-moteurs. Les contr?les ont montré l’existence de plusieurs fibres des 3 types de nerf; les terminaisons sensitives étaient toutes des corpuscules de Ruffini. Il n’y avait pas de fibre nerveuse au sein de l’allogreffe du ligament croiséà 3 et 6 semaines après la transplantation. Des fibres d’aspect cicatriciel étaient détectées à 12 semaines, tandis que des contr?les plus tardifs montraient un nombre et une distribution presque normale des filets nerveux. Aucun récepteur mécanique ne fut trouvé dans l’allogreffe. Chez le lapin, les bases anatomiques de la participation sensitivo-motrice de l’allogreffe du ligament croisé antérieur n’existent pas avant la 12ème semaine après la transplantation.

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Accepted: 11 May 1995     

Drogen und Arzneimittelabusus in der Frauenheilkunde

Addiction in women has many implications in the field of obstetrics and gynecology. Particularly in obstetrical care, the health needs of the unborn as well as of the pregnant patients have to be considered. Therefore, early somatic and psychosocial help should be offered to pregnant women with addiction disorders. The main elements of this concept will be presented along with a summary of typical comorbidity issues in these patients, the handling of drug-related emergencies, and the management of perioperative replacement therapy.