Induction of sister chromatid exchanges by transformation with simian virus 40.

The frequency of sister chromatid exchange (SCE) has been followed sequentially after the addition of SV40 to human diploid fibroblast cultures. The SCE frequency was nearly the same in uninfected controls and in infected cultures before they became tumor antigen positive. When cells exhibited tumor antigen, the SCE frequency increased over a wide range, and changes in chromosome number and structure were observed simultaneously. Cells with induced chromosome abnormalities without increased SCE's and the reverse present the possibility that the two phenomena have different viral mechanisms. This increase in SCE can be added to the previously demonstrated change in chromosome number and increase in chromosome breakage and rearrangement as indicators of genetic damage associated with viral transformation.

Quantitative 99mTc-DMSA uptake in experimental pyelonephritis.

UNLABELLED: Quantitative 99mTc-dimercaptosuccinic acid (DMSA) renal uptake was studied in unilateral reflux-related pyelonephritis in pigs. The changes to absolute % dose uptake and differential uptake occurring with induction and after treatment of pyelonephritis were correlated with the DMSA images and renal pathology. METHODS: Quantitative uptake in 53 young pigs was obtained from planar images acquired 6 h after injecting the dose. Baseline studies were made (Q1), and studies were made again after urinary infection was established (Q2), when 8 pigs had normal (no defect) renal images (group A), 23 had photon-deficient (reversible) focal defects (group B) and 22 had photon absent (irreversible) focal defects (group C). Q3 studies were made in 21 animals from groups B and C after 3-wk antimicrobial treatment. RESULTS: At Q2 the affected kidney differential uptake was unchanged for group A and reduced for groups B and C (respective mean changes -1.7%, P < 0.01; and -5.5%, P < 0.01). The absolute % dose uptake was unchanged in pyelonephritic kidneys, but increased in the contralateral nondiseased kidneys in groups B and C (respective mean increases +1.4%, P < 0.05; and +5.4%, P < 0.01), while remaining unchanged for group A. In group C, global renal accumulation was actually increased above the Q1 values. After treatment (Q3) the reduced pyelonephritic kidney differential uptake persisted in groups B and C. In group C, however, the increased absolute % dose uptake by the contralateral kidney was less marked and not significantly different from Q1 values in this small group. CONCLUSION: Induction of unilateral pyelonephritis produced a small reduction in diseased kidney differential uptake that was greatest in the group with irreversible imaging defects. The method did not discriminate individuals with reversible and irreversible imaging defects. The decrease in pyelonephritic kidney differential uptake resulted from increased DMSA accumulation (absolute % dose uptake) by the nondiseased contralateral kidney, while that in pyelonephritic kidneys remained unchanged. After treatment, the reduced pyelonephritic kidney differential uptake persisted, but the elevated global DMSA accumulation seen for group C (with irreversible imaging defects) was not sustained and was variable.

Rationale and statistical methodology for the VISA studies.

After examination of the epanolol ('Visacor') clinical package it became clear that, although efficacy and safety of epanolol were equivalent to efficacy and safety with other antianginal therapies, tolerability was improved. It was decided to initiate 2 studies with 500 patients in each to quantify the improved tolerability and examine patient preference for antianginal treatments. One study was a comparison of epanolol 200mg daily with metoprolol 100mg twice a day and the other compared epanolol 200mg daily with nifedipine retard 20mg twice a day. The rationale, design and statistical methodology are presented, together with a summary of the geographical spread of the study.

An international collaborative study of 'genetic drift' in Salmonella typhimurium strains used in the Ames test.

An international collaborative study of the response of 5 Salmonella typhimurium strains (TA1535, TA1537, TA1538, TA98 and TA100) to 4-nitroquinoline-N-oxide was performed. A laboratory's 'in-house' stock of these strains was compared with a set of reference strains, using a standardized protocol. The prime objective of this study was to investigate whether the ability of these strains to produce spontaneous or induced mutants had changed during their prolonged cultivation in different laboratories, i.e. to investigate their 'genetic drift'. Any observed change in mutability might contribute to the variations between laboratories in the results of the Ames test. A second objective was to obtain information on the extent of intra- and inter-laboratory variation when a standardized protocol was used. 38 laboratories participated in this study. The data were analysed statistically by 3 groups using different models and the same conclusion was reached: genetic drift is found in some strains in some laboratories, but does not contribute significantly to inter-laboratory variation in the Ames test. When the inter-laboratory variation was analysed there was considerable correlation between results for the 'in-house' and the reference strain, and between results for different strains in the same laboratory (Margolin et al., accompanying paper).

Case management services for adolescent substance abusers: a program description.

A case management model for adolescent substance abusers whose problems are severe enough to warrant residential treatment is presented, based on the experience of a demonstration project. The five integral functions of case management (assessment, planning, linking, advocacy, and support) are described within the framework of each phase of an adolescent's treatment program (screening, residential treatment, and continuing care). Detailed descriptions of case management activities and the philosophy underlying case management are addressed. The integrated client tracking and program evaluation monitoring system developed for the case management project is described, and evaluation data are presented. Among the advantages case managers are able to offer to the entire treatment process include encouragement of family involvement in the youth's recovery; providing support; tracking substance abuse relapse episodes following treatment; connecting the youth with school, work, and community resources; and helping youth to fulfill legal obligations.

99Tcm-DMSA as a dynamic imaging agent for estimating renal blood flow. A comparison with 99Tcm-DTPA.

A technique for estimating fractional renal blood flow (RBF) from the early part of the 99Tcm-diethylenetriaminepentaacetate (DTPA) renogram has been described previously and its reproducibility validated in the pig model. The technique is assumed to be applicable to any recirculating gamma-emitting tracer compound. The aim of this study was to determine whether the same method could be applied to 99Tcm-dimercaptosuccinic acid (DMSA) which has been largely neglected as a dynamic imaging agent. Paired estimates of fractional RBF were obtained in Large White (n = 16) and Göttingen miniature pigs (n = 6) in three groups: group 1, paired 99Tcm-DTPA studies; group 2, paired 99Tcm-DMSA studies; group 3, alternate 99Tcm-DTPA and 99Tcm-DMSA studies. The results showed good agreement between paired results independent of whether 99Tcm-DTPA or 99Tcm-DMSA was used, supporting the assumption that the technique is applicable to any recirculating gamma-emitting tracer compound. The demonstration that fractional RBF can be reliably estimated from the DMSA renogram means that, if required, it may be combined in a single nuclear medicine procedure with conventional static DMSA renal imaging.

Renal imaging with 99Tcm-labelled DMSA in the detection of acute pyelonephritis: an experimental study in the pig.

Serial renal 99Tcm-labelled dimercaptosuccinic acid (DMSA) scintigrams were acquired 2-58 days after the introduction of urinary tract infection in 33 pigs with experimentally induced vesicoureteric reflux (VUR). In 29 animals VUR was unilateral and in four bilateral, a total of 37 refluxing systems. Animals were killed either at varying intervals after a scintigraphic defect was noted (24 refluxing kidneys) or after a period when sequential scintigrams were normal (13 refluxing kidneys). The appearance of the scintigram acquired on the day prior to death was compared with the renal pathology, each kidney and renal image being divided into three zones (upper, middle, lower) for separate consideration. Of the 37 refluxing systems pyelonephritic lesions were seen in 27, in a total of 61 zones. In the remaining ten kidneys no scintigraphic defect was detected and no pathological lesions were identified either macroscopically or microscopically. Where an abnormality was detected on the scintigram a lesion was always identified in the kidney (sensitivity 100%). Small pyelonephritic lesions in a total of 12 zones in six kidneys were not detected on the scintigram (specificity 82%). Of the lesions undetected by scintigraphy only one occurred in the upper pole.

The relationship between renal parenchymal mass and absolute quantitation of 99Tcm-DMSA uptake. An experimental study in the growing pig.

Five Gottingen minipigs from the same litter aged 1 month entered the study and right nephrectomies were performed at staggered intervals between weeks 1 and 5. Absolute renal uptake of 99Tcm-DMSA, expressed as a percentage of the administered dose, was recorded in each animal weekly before right nephrectomy and at weekly intervals for 5 weeks post-nephrectomy. Before nephrectomy absolute renal uptake of 99Tcm-DMSA ranged between 16.8 and 21.5% (mean 18.6%) per kidney with no difference between right and left kidneys. After right nephrectomy, uptake in the left kidney approximately doubled within 1 week. No correlation was shown between renal parenchymal mass and absolute 99Tcm-DMSA uptake in paired or solitary normal kidneys undergoing growth or compensatory growth.

Alcoholism treatment by disulfiram and community reinforcement therapy.

Traditional disulfiram treatment has often been ineffective because of a failure to maintain usage. The present study with 43 alcoholics compared: (1) a traditional disulfiram treatment, (2) a socially motivated Disulfiram Assurance program and (3) a Disulfiram Assurance program combined with reinforcement therapy. About five sessions were given for each program. At the 6-month follow-up, the traditional treatment clients were drinking on most days and no longer taking the medication. The Disulfiram Assurance treatment resulted in almost total sobriety for married or (cohabitating) clients but had little benefit for the single ones. The combined program produced near-total sobriety for the single and married clients. These results indicate a promising integration of chemical, psychological and social treatment of alcoholism.

Experimental short-term partial fetal bladder outflow obstruction: II. Compliance and contractility associated with urinary flow impairment.

PURPOSE: Posterior urethral valves (PUV) is the commonest cause of congenital bladder outlet obstruction. Despite valve ablation in the neonatal period, up to 70% of patients develop renal failure by their teenage years, and progressive bladder dysfunction. This study forms part of a continuing project examining the relationship between severity and duration of obstruction and urinary tract dysfunction. Here is the assessed result of short-term (9-day) obstruction. MATERIALS AND METHODS: Fourteen male fetal lambs at 75 days' gestation were assigned to one of three groups: urachal ligation, urachal ligation with partial urethral obstruction, sham-operated controls. Pregnancy proceeded for 9 days. At autopsy, filling cystometry was performed with the urinary tract in situ and the bladder harvested for nerve counts using PGP 9.5 immunohistochemistry, or in vitro measurement of contractile function. RESULTS: Obstruction was associated with an increase in bladder:fetal weight ratio. Compliance was variable in the obstructed bladders, but the calculated wall stress per unit strain was either similar or less than controls. Nerve-mediated or agonist-induced contraction magnitude in tissue from obstructed bladders and nerve counts did not differ from controls. CONCLUSIONS: Nine days of outflow obstruction at mid-gestation generated a bladder of increased weight but without evidence of contractile failure. An increase in bladder compliance as a function of bladder growth was observed even at this stage, and represents one of the initial responses to outflow tract obstruction.

Experimental short-term fetal bladder outflow obstruction: I. Morphology and cell biology associated with urinary flow impairment.

PURPOSE: In fetal sheep, combined urethral and urachal obstruction initiated at 75 days' gestation and maintained for 30 days led to dysmorphic bladders, similar to those found in humans with prune belly syndrome, and uniformly disrupted kidney development. We aimed to create a less severe model of fetal bladder outlet obstruction, more closely resembling infants with posterior urethral valves, and additionally to further our understanding on the role of the urachus. We hypothesized that milder morphological renal tract changes would occur after shorter term experimental obstruction. MATERIALS AND METHODS: Male fetal lambs were assigned to urachal and urethral ligation, urachal ligation only or sham operations. Analyses were performed after 9 days. RESULTS: Concurrent urachal and urethral obstruction resulted in increased bladder weight, and protein and DNA content. Detrusor smooth muscle was well maintained, as assessed by light and electron microscopy, although urothelia showed basal apoptosis. Bladder obstruction led to hydronephrosis but failed to produce significant perturbations in urine osmolality. The nephrogenic cortex was either well preserved or was replaced by glomerular cysts; the latter group tended to have heavier bladders. Urachal obstruction alone produced similar changes suggesting that the male sheep fetal urethra is a high-resistance conduit in mid-gestation. CONCLUSIONS: Concurrent urachal and urethral obstruction, or urachal obstruction alone, initiated in mid-gestation and maintained for 9 days leads to bladder overgrowth but preserved renal tubular function. In future, it will be interesting to determine whether bladder decompression around this stage leads to reversal of bladder overgrowth and/or ameliorates severe renal tract damage described after longer term fetal bladder outflow obstruction.

Quantitation of vaginal discharge in healthy volunteers.

The mean quantity of vaginal discharge measured on four occasions during one menstrual cycle in 22 asymptomatic volunteers was 1.55 g/8 h although the amount varied significantly between different days of the cycle. The maximum occurred at mid-cycle (1.96 g/8 h) and low mean values were seen on day 7 (1.38 g/8 h) and day 26 (1.37 g/8 h), contrasting with the widely held view that the discharge increases premenstrually. This cyclical variation was statistically significant (P less than 0.02) in celibate women using no contraception but was less marked in sexually active women taking the combined oral contraceptive pill.

Use of LMA for awake intubation for caesarean section.

PURPOSE: This case report describes the use of a Laryngeal Mask Airway in a morbidly obese parturient with the H.E.L.L.P. syndrome. An urgent Caesarean section was required because of vaginal bleeding and fetal distress. CLINICAL FEATURES: The patient was a 32 year old G3, T1, P1, L1 who presented with epigastric pain, headache, vomiting, and diarrhoea. She was hypertensive (180/110 mmHg) and thrombocytopaenic (18 x 10(-9). L-1). Examination of the airway revealed a short neck, receded jaw, full dentition, large breasts and she was considered to be a potential intubation problem. The patient required an awake intubation using a technique that minimized hypertension, aspiration risk, airway trauma, and hypoxia. A laryngeal mask was used to facilitate tracheal intubation, and the patient tolerated the procedure with no adverse outcome. CONCLUSION: The LMA has a place to facilitate potentially difficult awake tracheal intubation with the pregnant patient.

Effect of unilateral vesicoureteric reflux on renal growth and the uptake of 99mTc DMSA by the kidney. An experimental study in the minipig.

The influence of unilateral vesicoureteric reflux (VUR) on renal growth and the uptake of 99mTc DMSA by the kidney has been investigated in a 2-kidney model in the growing minipig over a period of approximately 5 months. Animals with reflux in association with low voiding pressures and normal bladder function (n = 5), as well as those with raised voiding pressures and abnormal bladder function (n = 7), were investigated with appropriate non-refluxing controls (n = 12). Urinary infection and renal scarring were avoided since these factors may affect kidney function and growth independently. Statistical tests of difference failed to demonstrate any effect of VUR on renal growth or renal uptake of 99mTc DMSA even in the presence of elevated voiding pressures and abnormal detrusor function.

Effects of vesicoureteric reflux on renal growth and function as measured by GFR, plasma creatinine and urinary concentrating ability. An experimental study in the minipig.

The influence of vesicoureteric reflux (VUR) on renal growth and function measured by glomerular filtration rate (GFR), plasma creatinine concentration and urinary concentrating ability has been examined in a simple one-kidney model in the growing minipig over a period of approximately 5 months. Animals with reflux in association with low voiding pressures and normal bladder function (n = 6), as well as those with raised voiding pressures and abnormal bladder function (n = 5), were investigated together with appropriate non-refluxing controls (n = 12). Urinary infection and renal scarring were avoided since these factors may affect kidney function and growth independently. Statistical tests of difference failed to demonstrate any effect of VUR on 51Cr EDTA GFR or renal growth even in the presence of elevated voiding pressures and abnormal detrusor function. However, a significant association between VUR and reduced urinary concentrating ability was shown.