Incidence and outcome of chromosomal mosaicism found at the time of chorionic villus sampling

OBJECTIVE: Chromosomal mosaicism has been reported in about 1% to 3% of chorionic villus sampling specimens. This report provides incidence and outcome information that should be useful in counseling patients found to have mosaicism on chorionic villus sampling.STUDY DESIGN: A retrospective analysis of 11,200 consecutive patients undergoing chorionic villus sampling at the University of California, San Francisco, during the period from Jan. 1, 1984, to June 1, 1996, was undertaken.RESULTS: A total of 140 cases of mosaicism were identified for an incidence of 1.3%. Follow-up information was available for 130 cases, 26 of which (20%) were confirmed in fetal tissue. Confirmation rates for specific types of mosaicism were as follows: autosomal trisomy 7.6%, sex chromosome 25%, structural abnormality 27.3%, and marker chromosome 77.8%. Neonatal outcome was normal in all cases for which pregnancy continued.CONCLUSION: The data indicate that in most cases of chromosomal mosaicism found by chorionic villus sampling the mosaicism is unlikely to be clinically significant in the fetus. (Am J Obstet Gynecol 1997;176:1349-53.)     

Bone marrow micrometastases in 109 breast cancer patients: Correlations with clinical and pathological features and prognosis

Background: The presence in bone marrow of cells which react with monoclonal antibodies against tumor-associated antigens has been proposed over the last few years as a new prognostic factor in breast cancer patients. Patients and methods: Bone marrow aspirates were obtained from 109 stage I and II breast cancer patients during or 2–4 weeks after primary surgery. The samples were processed for leukocyte separation on a Ficoll-Hypaque gradient and then used to prepare cytospin slides for immunocytochemical analysis. The slides were stained with a pool of monoclonal antibodies (MoAbs) which recognize tumor associated antigens, using the alkaline phosphatase anti-alkaline phosphatase method. The median follow-up was 36 months (range 15–62); 22 patients relapsed and 7 died. Results: Thirty-four of the 109 patients (31.1%) had MoAb positive bone marrow cells. The bone marrow was positive in 28/74 (37.9%) patients who had the aspirate taken during surgery and in 6/35 (17.1%) who had it taken after surgery (p = 0.055). No association was found between bone marrow positivity and tumour size, nodal status, menopausal status, estrogen receptor positivity or the proliferative index. No association was found between bone marrow and prognosis: the log-rank test was 0.291 (p > 0.5) for OS and 0.023 for DFS; the hazard ratio (positive vs negative) was 1.51 for OS (95% CI: 0.33–6.86) and 0.93 for DFS (95% CI: 0.35–2.45). Conclusions: In our series, bone marrow positivity did not correlate with prognostic parameters or prognosis. Of interest is the relative excess of positivity when the bone marrow was obtained during surgery.     

In vitro and in vivo interaction between cisplatin and topotecan in ovarian carcinoma systems

Topotecan, a camptothecin analogue, is a␣specific inhibitor of topoisomerase I approved for use in the treatment of patients with refractory ovarian carcinoma. The drug's mechanism of action suggests a potential efficacy of drug combinations incorporating DNA-damaging agents. In an attempt better to define a␣rational basis for drug combination we examined the effect of topotecan on the cytotoxicity and antitumor activity of cisplatin in an ovarian carcinoma system growing in vitro and in vivo as a tumor xenograft. The in vitro cell system included a cisplatin-sensitive cell line, IGROV-1, and a cisplatin-resistant subline, IGROV-1/Pt0.5, which is characterized by p53 mutation and loss of normal function of the wild-type gene of the parental cell line. This cell system was chosen since the cell sensitivity to DNA-damaging agents appears to be dependent on p53 gene status. Cytotoxicity was assessed by the growth inhibition assay using different schedules: (a) a 1-h period of cisplatin exposure followed by a 24-h topotecan treatment and (b) a 1-h period of simultaneous exposure to cisplatin and topotecan. In the case of the sequential schedule, an additive interaction was observed in IGROV-1 and IGROV-1/Pt0.5 cells. When the simultaneous schedule was used, a synergistic interaction, more evident for the cisplatin-sensitive cells, was found. On the basis of these observations at a cellular level, the effect of concomitant administration of the two drugs (i.e., the most favorable schedule) was studied in the IGROV-1 tumor xenograft, which is moderately responsive to cisplatin and topotecan. Suboptimal doses of each drug (with a low dose of topotecan, 5.1 mg/kg) achieved an antitumor effect comparable with or superior to that of the optimal dose of a single treatment (tumor weight inhibition, 60%), thus indicating a␣pharmacological advantage of the combination over the single treatment. However, an increase in the topotecan dose (7.1 mg/kg) was associated with an evident increase in the toxicity of the combination, thereby suggesting that the drug interaction was not tumor-specific. Although the molecular basis of the drug interaction is not clear, it is likely that inhibition of topoisomerase I affects the ability of cells to repair cisplatin adducts. Such findings may have pharmacological implications since they suggest the potential clinical interest of topoisomerase I inhibitors in combination with cisplatin. Received: 14 June 1997 / Accepted: 18 September 1997     

Peracetic acid in the disinfection of a hospital water system contaminated with Legionella species.

OBJECTIVE: To assess the efficacy of an alternative disinfection method for hospital water distribution systems contaminated with Legionella. METHODS: Disinfection with peracetic acid was performed in a small hospital contaminated with L. pneumophila serotype 1. The disinfectant was used at concentrations of 50 ppm (first three surveillance phases) and 1,000 ppm (fourth surveillance phase) for 30 minutes. RESULTS: Environmental monitoring revealed that disinfection was maintained 1 week after treatment; however, levels of recontamination surpassing baseline values were detected after approximately 1 month. Comparison of water temperatures measured at the distal outlets showed a statistically significant association between temperature and bacterial load. The circulating water temperature was found to be lower in the two wards farthest away from the hot water production plant than in other wards. It was thought that the lower water temperature in the two wards promoted the bacterial growth even after disinfection. CONCLUSION: Peracetic acid may be useful in emergency situations, but does not provide definitive protection even if used monthly.     

Cerebral autoregulation in pediatric traumatic brain injury.

OBJECTIVE: The aims of this study were to document the incidence of impaired cerebral autoregulation in children with traumatic brain injury using transcranial Doppler ultrasonography and to examine the relationship between autoregulatory capacity and outcome in children following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Harborview Medical Center (level I pediatric trauma center) in Washington state. PATIENTS: Thirty-six children <15 yrs old with traumatic brain injury: Glasgow Coma Scale score <9 (n = 12, group 1), Glasgow Coma Scale score 9-12 (n = 12, group 2), and Glasgow Coma Scale score 13-15 (n = 12, group 3). INTERVENTIONS: Cerebral autoregulation testing was conducted during extracranial surgery. Mean middle cerebral artery flow velocities were measured using transcranial Doppler as mean arterial pressure was increased to whichever variable was greater: 20% above baseline or a set value (80 mm Hg for <9 yrs and 90 mm Hg for 9-14 yrs). Autoregulatory capacity was quantified by the Autoregulatory Index. Autoregulatory Index <0.4 was considered impaired cerebral autoregulation. Discharge outcome using the Glasgow Outcome Scale score was considered good if the Glasgow Outcome Scale score was > or =4. MEASUREMENTS AND MAIN RESULTS: Twenty-four (67%) of 36 children had an Autoregulatory Index > or =0.4. The incidence of impaired cerebral autoregulation was 42% (five of 12) in group 1, 42% (five of 12) in group 2, and 17% (two of 12) in group 3. Ten (42%) of the 24 children with intact cerebral autoregulation had a good outcome compared with only one of 12 (8%) children with impaired cerebral autoregulation (p =.04). Six of 12 (50%) children with impaired cerebral autoregulation had hyperemia compared with one of 24 (4%) children with intact cerebral autoregulation (p <.01). Hyperemia was associated with poor outcome (p =.01). CONCLUSIONS: The incidence of impaired cerebral autoregulation was greatest following moderate to severe traumatic brain injury. Impaired cerebral autoregulation was associated with poor outcome. Hyperemia was associated with impaired cerebral autoregulation and poor outcome.     

Trends in compliance with the national colposcopy guidelines.

This study aims to assess trends in compliance with current colposcopy guidelines in 10 gynaecological units in four English counties since 1996; to identify constraints on compliance and suggest change in practice. All 10 gynaecology units in Oxfordshire, Buckinghamshire, Northamptonshire and Berkshire participated. Data were collected prospectively by colposcopists from 23,500 new referrals across a 55-month period from September 1996 to March 2001. The Oxford Cancer Intelligence Unit performed collation, quality assurance and retrieval of data for incomplete records. Audit results were disseminated annually to colposcopists via the Regional Colposcopy Group. Colposcopy waiting times exceeded the standards, but waiting times for high-grade referrals showed statistically significant improvement. Six standards were achieved; relating to accuracy, appropriateness of management and outcomes. The seven unmet standards relate to waiting times, colposcopist's caseload, follow-up policy and the proportion of cervical epithelial neoplasia (CIN) on histology. Changes in practice are suggested, constraints on compliance are identified and the appropriateness of some guidelines is questioned.     

The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis.

PURPOSE: Tuberous sclerosis complex (OMIM 191100) is a multiorgan disease commonly associated with epilepsy refractory to anticonvulsants. Individual reports indicate that seizures in children with tuberous sclerosis might benefit from a ketogenic diet. We studied the effects of the diet introduced at 3.5 years of age in three boys with tuberous sclerosis and refractory partial seizures. METHODS: On admission a classical LCT ketogenic diet was initiated and patients were followed for 12 months. Antiepileptic drugs were maintained unless adverse effects required reduction. RESULTS: Two patients became seizure-free within 2 months on the diet. In the third patient drop attacks decreased significantly. On follow-up the diet was well accepted and without adverse effects. CONCLUSION: The ketogenic diet should be considered as a treatment option for children with tuberous sclerosis and partial seizures refractory to anticonvulsants. Our data support the need for further studies in larger cohorts to confirm the effectiveness of the ketogenic diet in this entity.     

Dapsone therapy for malaria during pregnancy: maternal and fetal outcomes.

The need to consider using dapsone in pregnant women for its antimalarial activity is becoming greater in areas where Plasmodium falciparum resistance to chloroquine and pyrimethamine-sulfadoxine is rapidly increasing. Dapsone in combination with other antimalarials might provide a valuable alternative for both treatment and prophylaxis. This review assesses the clinical pharmacology of dapsone and its adverse drug reactions in relation to haemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, blood dyscrasias and methaemoglobinaemia. Studies are summarised reporting its use in leprosy, dermatological and other conditions, and malaria, in relation to maternal and infant outcomes. A total of 924 pregnancies were identified during which dapsone therapy was taken. Only limited data are available and this precludes a meaningful quantitative benefit-risk analysis.Mild degrees of haemolysis consistently occur with continued therapy, although adverse effects may be less likely with intermittent treatment, as most reported adverse effects have occurred with long-term use of dapsone. There are a number of gaps in knowledge where more data are needed. These include no data on pharmacokinetics in pregnancy and whether these are altered with co-administration of chlorproguanil. Potential complications in women with severe anaemia are unknown and there is no information on haemolytic effects in women or the fetus with G6PD deficiency. The use of dapsone in HIV-infected women in malarious areas could carry increased risks because of the immunosuppressive actions of the drug. Trials of dapsone therapy in pregnancy should be considered in malarious areas where there is good reason for its deployment. Controlled trials have provided data on maternal tolerance, and dapsone in combination with other antimalarial drugs can offer clear benefit in terms of improved birthweight. The use of dapsone combinations should be considered when no good alternative is available and the threat of malaria is the greater risk.