A large cholera outbreak in Kano City, Nigeria: the importance of hand washing with soap and the danger of street-vended water

The aim of this study was to identify the risk factors for cholera during an outbreak in Nigeria. Cases were defined as recent onset of acute diarrhoea with dehydration in a patient hospitalised at the Infectious Diseases Hospital in Kano City. Meningitis patients admitted concurrently at the same hospital were recruited as unmatched controls. Data were collected on age, sex, place of residence, hygienic practices, and on food and water consumption. A total of 5600 cholera cases and 340 cholera deaths were reported between December 1995 and May 1996 (attack rate = 86.3 per 100,000 population) in the state of Kano. Compared to the 77 controls, the 102 cases were more likely to have drunk street-vended water (age-adjusted odds ratio (AAOR) = 3.2; 95% confidence interval (CI): 1.4-7.1) and less likely to have drunk tap water in their homes (AAOR = 0.2; 95% CI: 0.1-0.7) or to have washed hands with soap prior to eating food (AAOR = 0.2; 95% CI: 0.1-0.6). While no data suggested that the municipal water supply was contaminated, safe water systems and hand hygiene practices might have prevented a high proportion of cases if implemented early during this outbreak.     

Vaccination in emergencies

Nongovernmental organisations (NGOs) are the main actors of vaccine delivery during complex humanitarian emergencies such as large population displacements. This paper discusses the use of vaccinations against measles, cholera and meningitis in this context. The role of NGOs in the advocacy for making new and more effective vaccines available to the most vulnerable populations is also emphasised.     

Beta-substituted cyclohexanecarboxamide: a nonpeptidic framework for the design of potent inhibitors of cathepsin K

A new series of nonpeptidic cathepsin K inhibitors that are based on a beta-substituted cyclohexanecarboxamide motif has been developed. Lead optimization yielded compounds with sub-nanomolar potency and exceptional selectivity profiles against cathepsins B, L, and S. Use of fluorine atoms to block metabolism on the cyclohexyl ring led to compounds with excellent pharmacokinetic properties. Considering the well-established role of cathepsin K in osteoclast-mediated bone turnover, compounds such as (-)-34a (hrab Cat K IC(50) 0.28 nM; >800-fold selectivity vs Cat B, L, and S; PK data in dogs: F 55%, t(1/2) = 15 h) exhibit great potential for development as an orally bioavailable therapeutic for treatment of diseases that involve bone loss.     

Intellectual Impairment in School-Age Children Exposed to Manganese from Drinking Water

Background

Manganese is an essential nutrient, but in excess it can be a potent neurotoxicant. Despite the common occurrence of manganese in groundwater, the risks associated with this source of exposure are largely unknown.

Objectives

Our first aim was to assess the relations between exposure to manganese from drinking water and children’s intelligence quotient (IQ). Second, we examined the relations between manganese exposures from water consumption and from the diet with children’s hair manganese concentration.

Methods

This cross-sectional study included 362 children 6–13 years of age living in communities supplied by groundwater. Manganese concentration was measured in home tap water (MnW) and children’s hair (MnH). We estimated manganese intake from water ingestion and the diet using a food frequency questionnaire and assessed IQ with the Wechsler Abbreviated Scale of Intelligence.

Results

The median MnW in children’s home tap water was 34 μg/L (range, 1–2,700 μg/L). MnH increased with manganese intake from water consumption, but not with dietary manganese intake. Higher MnW and MnH were significantly associated with lower IQ scores. A 10-fold increase in MnW was associated with a decrease of 2.4 IQ points (95% confidence interval: −3.9 to −0.9; p < 0.01), adjusting for maternal intelligence, family income, and other potential confounders. There was a 6.2-point difference in IQ between children in the lowest and highest MnW quintiles. MnW was more strongly associated with Performance IQ than Verbal IQ.

Conclusions

The findings of this cross-sectional study suggest that exposure to manganese at levels common in groundwater is associated with intellectual impairment in children.     

Chemotherapy by fotemustine in cerebral metastases of disseminated malignant melanoma

Summary A total of 42 patients with cerebral metastases of malignant melanoma were included in this study of the nitrosourea fotemustine. The treatment plan consisted of a 1-h i. v. infusion of 100 mg/m² fotemustine every week for 3–4 weeks, followed by a 4- to 5-week rest period. Responding or stabilised patients then received 100 mg/m² fotemustine every 3 weeks. Among the 39 evaluable patients, 2 complete responses and 9 partial responses were documented, leading to an overall response rate of 28.2%. Most of the responses were obtained in previously untreated patients and/or those presenting with a single cerebral metastasis. Toxicity was mild and mainly hematological, especially in patients previously treated by polychemotherapeutic regimen. Our study confirms the activity of fotemustine in cerebral metastases of disseminated malignant melanoma.Others institutions involved in this trial: A. Bernadou, Hôtel Dieu, Paris; J. Clavier, CHR de Brest; M. Delaunay, Hôpital Pellegrin Tripode, Bordeaux; J. P. Escande, Hôpital Tarnier, Paris; P. Fargeot, Centre George François Leclerc, Dijon; P. Lauret, Hôpital Charles Nicolle, Rouen; R. Leblay, Hôpital Sud, Rennes; P. Litoux, CHR de Nantes; G. Lorette, Hôpital Trousseau, Tours; R. Metz, Centre Alexis Vautrin, Nancy; A. Monnier, CHR Boulloche, Montbelliard; M. Mousseau, CHR de la Tronche, Grenoble; J. P. Olivier, Hôpital Dupuytren, Limoges; R. Touraine, Hôpital Henri Mondor, Créteil; F. Truchetet, Hôpital de Thionville, France     

Long Term Variceal Sclerotherapy: Is Endoscopic Sclerosis a Unique Therapeutic Approach and a True Alternative to Surgery?

Endoscopic sclerotherapy has been used to control acute variceal haemorrhage which persists despite conservative therapy, prevent recurrent variceal haemorrhage in patients with a history of oesophageal haemorrhage, and to prevent a haemorrhage in patients with oesophageal varices who never bled. In this short paper I will cover our personal experience with more than 2000 patients receiving particularly paravariceal endoscopic sclerotherapy of bleeding esophageal varices, and especially present the results of our prospective and controlled randomized trials (Table 1) and underline the thesis that endoscopic sclerotherapy and surgical procedures for patients with portal hypertension are complementary supporting measures or options.     

Investigation of the portal perfusion index after low diameter mesocaval interposition and distal splenorenal shunt — a prospective study

Summary In 50 consecutive patients portal blood flow was determined using computed liver perfusion scintigraphy preoperatively and at 6, 12, 24, 36, 48, 60, 72, and 84 months postoperatively between 1 January 1983 and 1 January 1990. All 25 subjects had undergone placement of a distal splenorenal shunt (DSRS) and 25, insertion of low-diameter PTFE mesocaval interposition shunt (LDMIS) between 15 January 1983 and 1 January 1988. Indications for shunt operation included recurrent variceal hemorrhage in spite of long-term endoscopic sclerotherapy, a Child-Pugh classification of A or B, a sonographically determined liver volume of between 1000 and 2500 ml, exclusion of the activity and progression of liver disease by biopsy and stenosis of the hepatic artery or coeliac trunk. DSRS was performed when the portal perfusion index (PPI) was >30% (normal values 56±5%) and LDMIS was carried out when the PPI was 10% to 30%. In all cases the underlying disease was liver cirrhosis of alcoholic (n = 34, 68%) or hepatic (n = 12, 24%) etiology. Five patients who underwent LDMIS had originally scheduled for DSRS at a PPI of >30%; because the DSRS would have been technically difficult due to severe chronic pancreatitis, a LDMIS was performed. One in-hospital death due to liver failure had occurred in each group by 1 January 1990. One patient in the DSRS group and two in the LDMIS group died later, and in each group one patient was lost to follow-up. In the DSRS group, no case of encephalopathy or rebleeding was encountered, and in the LDMIS group, one case each of encephalopathy (4%) and rebleeding (4%) were recorded. In the DSRS group, the PPI value showed a steady reduction from 38% (preoperatively) to 15% (after 7 years); the same tendency could be demonstrated in the LDMIS group from 24% to 0). The difference between the preoperative and late postoperative PPI values obtained for both shunt types was statistically significant. We concluded that a reduction in portal blood flow to the liver develops during the period following the surgical implantation of a selective or non-selective shunt. LDMIS maintains portal perfusion for at least 6 years post-surgery. Thus, LDMIS constitutes an excellent alternative in patients in whom the insertion of a Warren shunt is either not possible or not indicated due to an insufficient PPI value (<30%).     

Working memory impairments in first-episode psychosis and chronic schizophrenia

Working memory (WM) impairments are core cognitive deficits in patients with schizophrenia linked to prefrontal cortical dysfunctions. Determining the differences between early phases of illness allows a better understanding of its course and constitutes an important guide for treatment. The present cross-sectional study examined differences of working memory functions between 33 first-episode and 29 chronic schizophrenic patients, as well as 64 healthy controls. On the basis of a two-back visual–verbal computerized working memory task, reaction time was slower and accuracy was worse in both patient groups than in controls. Test variables, however, were not significantly different between the patient groups, suggesting stability of the deficits over time. Effect size accuracy variables nevertheless showed larger deficits in chronic patients.     

Preimplantation genetic diagnosis for myotonic dystrophy type 1: upon request to child

Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis for patients at risk of transmitting an inherited disease such as myotonic dystrophy type 1(DM1) to their offspring. In this paper, the clinical application of preimplantation diagnosis for DM1 upon request to children born is described in a large cohort of risk couples. PGD could be offered to all 78 couples opting for PGD regardless of the triplet repeat size. The incidence of major complications was minimalised following a careful assessment in affected DM1 females anticipating possible cardiological, obstetrical and anaesthetical problems. A live-birth delivery rate per cycle with oocyte retrieval of 20% was the outcome. Forty-eight of the 49 children born are in good health and have normal psychomotor development.