Colposcopic examination of the cervix of cebus monkeys.

A total of 410 colposcopic examinations were performed on 188 female cebus monkeys that were under study to determine the oncogenic potential of herpes simplex virus type 2 in this genus. A split-cone vaginal speculum was developed that permitted good observation of the vaginal cervix in the cebus monkey. The cervical anatomy of cebus monkeys was found to differ from that of humans in that the surface of the animal cervix was more papilliform, with thinner squamous epithelium, and the squamocolumnar junction lay within the endocervical canal. Therefore, the ability to detect abnormalities in the cervical epithelium by colposcopic examination in the cebus monkey was restricted to vascular changes in the squamous epithelium. After 100 examinations, several vascular patterns were distinguishable and interpretations of these patterns were compared with cytologic findings on the same animals. Findings by both cytology and colposcopy were mild in nature; no carcinoma was detected. Colposcopic and cytologic findings correlated at a level of 84%. More abnormalities were detected with colposcopy than with use of cytologic techniques.     

Monitoring renal allograft rejection with duplex sonography

Thirty-six renal allograft recipients were monitored by serial duplex Doppler ultrasound studies post-transplant and during early rejection. A separate reproducibility study demonstrated no significant inter- or intra-operator variability in measurements of resistive index of an interlobar artery (RI) (2.1% [1.5%] and 3.2% [2.3%] respectively, mean [standard error] of coefficients of variance). Twenty-one patients had rejection within 3 weeks of transplantation. These grafts showed greater overall rises in the RI, from day 2 to day 5 post-transplant, than the grafts which had no rejection. Eleven of the 21 patients required more than one course of methyl-prednisolone for persistent or recurring rejection. These grafts had higher RI on the day rejection was diagnosed (81 [7.3], median [interquartile range]) compared with the remaining 10 patients (68.6 [8.7]). The 11 grafts with persistent rejection had higher RI (p less than 0.005, Mann-Whitney U-test) on day 2 post-transplant (76 [3.9]) compared with the 10 grafts successfully treated with a single course of methyl-prednisolone (63.2 [10.9]). This study demonstrates that grafts with an RI of greater than 70 on day 2 post-transplant are likely to have rejection requiring additional treatment (sensitivity--100%, specificity--80%). These patients may be candidates for earlier or alternative anti-rejection therapy.     

A new fracture of the forearm adjacent to a healing fracture

A 10-year-old girl sustained closed fractures of the distal radius and ulna. This was manipulated and she was treated in an above-elbow plaster for 4 weeks. Two weeks later she was discharged, only to have a second injury to the same forearm. X-ray showed a new fracture distal to undisrupted callus.

---

Résumé  Une fille agée de dix ans a soutenu des fracture fermées du radius et du cubitus distaux. Ceci a été manipulé et a été traitée dans un plaitré pendant quatre semaines. Deux semaines plus tard elle a été déchargée, seulement pour avoir des deuxièmes dommages au même avant-bras. Radiographies a montré que une nouvelle fracture distale du callus.

---

---

Accepted: 17 January 2000     

Alterations of arterial function in end-stage renal disease

Cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Epidemiological and clinical studies have shown that this is most frequently related to damage of large conduit arteries. Macrovascular disease develops rapidly in uremic patients and is responsible for the high incidence of ischemic heart disease, sudden death, peripheral artery diseases, and congestive heart failure. The most frequent causes of these complications are occlusive lesions due to atherosclerosis. Nevertheless, atherosclerosis, a disease characterized by the presence of plaques, represents only one form of structural response to metabolic and hemodynamic alterations which interfere with the process of aging, i.e., arteriosclerosis, characterized by dilation/hypertrophy and stiffening of arteries. The vascular complications in ESRD are ascribed to two different but associated mechanisms, namely atherosclerosis and arteriosclerosis. Whereas the former principally affects the conduit function with ischemic lesions being the most characteristic consequence, the latter primarily disturbs the cushioning function of large arteries. Arteriosclerosis in ESRD patients is characterized by diffuse dilation and hypertrophy of large conduit arteries and stiffening of arterial walls and represents a clinical form of accelerated aging process. The main clinical characteristics of arterial stiffening concern changes in blood pressure with isolated increase in systolic pressure and normal or lower diastolic pressure. The consequences of these alterations are: (1) an increased left ventricular afterload with development of left ventricular hypertrophy and increased myocardial oxygen demand and (2) altered coronary perfusion and subendocardial blood flow distribution. Epidemiological studies have identified arterial remodeling and stiffening as independent predictors of overall and cardiac mortality in ESRD patients.     

Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891.

PURPOSE: To determine whether children with localized gonadal malignant germ cell tumors (MGCT) stage II testicular and stages I and II ovarian treated with four cycles of standard-dose cisplatin combined with etoposide and low-dose bleomycin (PEB) have an event-free survival (EFS) of at least 85% without significant toxicity. PATIENTS AND METHODS: Between May 1990 and July 1995, eligible pediatric patients with stage II or recurrent from stage I (as a stage II) testicular MGCT and stages I and II ovarian MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. PEB chemotherapy consisted of bleomycin 15 U/m2 on day 1, cisplatin 20 mg/m2/d on days 1 to 5, and etoposide 100 mg/m2/d on days 1 to 5. Patients received four cycles of therapy at 21-day intervals. RESULTS: Seventy-four patients with a median age of 10.5 years (range, 8.7 months to 16.7 years) were enrolled. Primary sites included: stage II testicular (n = 17), stage I ovarian (n = 41), and stage II ovarian MGCT (n = 16). Treatment with standard PEB resulted in 6-year EFS of 95% and overall survival (OS) of 95.7%. EFS and OS by primary site were as follows: stage II testicular, 100% and 100%; stage I ovarian, 95.1% and 95.1%; and stage II ovarian, 87.5% and 93.8%, respectively. Two patients died from recurrent disease, and one patient died of secondary acute myelocytic leukemia. Infrequent grade 3 to 4 hematologic toxicity was reported. No grade 3 to 4 renal, pulmonary, or ototoxicity was observed. CONCLUSION: Combination chemotherapy with PEB results in excellent EFS and OS with minimal toxicity in children and adolescents with localized gonadal MGCT.     

Cardiac anomalies in chronic renal failure

PRINCIPAL CARDIOVASCULAR COMPLICATIONS IN END STAGE RENAL DISEASE: Cardiovascular diseases are the leading causes of morbidity and mortality in end stage renal disease patients. Very often, complications observed are left ventricular hypertrophy and various forms of arterial degenerative lesions involving coronary arteries, less frequently pericarditis and calcifying valvulopathy are diagnosed. THE REASONS ARE COMPLEX: Risk factors can be either specific of uremia per se such as anemia, overhydration, fistula or the same as in the general population. Hemodynamic alterations including tensile stress or blood flow play a major role associated to various locally or generally generated substances whose role remains currently to be determined. THEIR TREATMENTS: Treatments of cardiovascular complications are not specific in this end stage renal disease population but are more often the treatment of the etiology: reduction of fistula blood flow, increase of hemoglobin, best control of weight gain between two hemodialysis sessions or blood pressure control.     

Group and case study of the dysexecutive syndrome in alcoholism without amnesia

OBJECTIVES: To test the dysexecutive syndrome (DES) hypothesis of chronic alcoholism by the neuropsychological group and case study approaches. METHODS: A comprehensive neuropsychological assessment, including the "behavioural assessment of dysexecutive syndrome", a battery of tests recently designed to be "ecologically valid", was administered to 17 patients with chronic alcoholism without amnesia to examine executive functions, intelligence, and memory. In terms of each neuropsychological measure, reciprocal analyses of group means and individual case profiles were conducted: for the first contrasting the alcoholic patients with 17 age matched healthy subjects; and for the second making intersubject and intrasubject comparison of the patients, according to percentile basis impairment indices obtained from the control subjects. RESULTS: Despite relatively unimpaired memory and intelligence, the patients as a whole had the impairment of a wide range of executive domains, extending to "everyday" problem solving as well as more elementary aspects of executive functions, such as visuospatial performance, mental set shifting, and the inhibition of habitual behaviour. The profile analysis divided individual patients into four groups: the representative DES characterised by a clear dissociation between impaired executive functions and preserved intelligence and memory; the group of a modified dysexecutive pattern in which memory as well as executive functions were impaired with intelligence preserved; the group of general cognitive deterioration; and the group of unimpaired cognitive functioning. About two thirds of the patients were categorised into either the first or the second type of DES. CONCLUSION: DES characterised by the even more pronounced impairment of executive functions than of intelligence and memory afflicts a considerable proportion of patients with chronic alcoholism. Due to its subtlety, this would be potentially left out, unless appropriate behavioural measures were administered. This condition may prevent patients with alcoholism from achieving full recovery and benefiting from rehabilitation.     

Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non-missense, and 17 for two non-missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty-five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non-missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non-missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency.     

A Randomized Controlled Trial of the Clinical Utility of Genotypic Resistance Testing in Patients with Limited Prior Exposure to Antiretroviral Drugs

Abstract

Purpose: To assess the clinical utility of genotypic resistance testing among HIV-1-infected patients with limited prior exposure to antiretroviral drugs. Method: Patients experiencing virological failure were randomly allocated to either centralized genotypic resistance testing or to no testing and were followed for a minimum of 1 year. Results: 55 patients were recruited from 14 centers in the United Kingdom. There were no demonstrable differences between the groups in terms of virological or immunological response. For patients allocated to resistance testing, there was an increased tendency to recycle previously used drugs. Conclusion: The study did not demonstrate a benefit of genotypic resistance testing in this population, although statistical power was low. However, testing did alter prescribing behavior, and clinical effects may become manifest in the longer term.