Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy

PURPOSE: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy. METHODS: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies. RESULTS: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2-4.7]. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6-15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3-18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4-67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1-57.6). Offspring of mothers using > 1,000 mg VPA/day were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed < or =600 mg VPA/day (RR 6.8; 95% CI: 1.4-32.7). No difference in risk of MCA was found between the offspring exposed to 601-1,000 mg/day and < or =600 mg/day. CONCLUSIONS: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.     

Cultural orientation and use of cannabis and inhalants among secondary school children in Zimbabwe

A survey among 3061 secondary school children in four provinces in Zimbabwe was conducted in 1994. In the present paper, the relationships between cultural and social factors and use of inhalants and cannabis are explored. Respondents were selected by means of a two-stage sample design, first based on a complete list of schools in the four provinces and subsequently on lists of students at the randomly selected schools. Stratification was based on the identification of four different sociocultural groups. Data collection followed standardised procedures and was conducted by a research team from University of Zimbabwe. Cultural orientation was operationalised by means of a Likert-type 14-item scale on choice of media, language and music. Exploratory principal component analysis revealed a two-factor solution, representing a global or Western cultural orientation and a local or Zimbabwean cultural orientation. Drug use by older siblings and best friends represented social factors. A combined model of cultural and social variables was subject to a multiple logistic regression analysis. Results revealed that the social variables and global cultural orientation were significantly associated with increased use of both drugs, whereas a local cultural orientation was found not to be associated with use of these substances. Findings are discussed in the light of historical and cultural factors.     

Improved wrist fracture localization with digital overlay of bone scintigrams and radiographs

The diagnosis of scaphoid fracture is often difficult and of interest in traumatology. Because of the low sensitivity of repeated scaphoid radiographs, a bone scintigram is advocated and considered the gold standard. In this study, we tried to simplify the interpretation of the bone scintigram of hand and wrist in localizing the hot spot by the digital overlay of the radiograph and the bone scintigram, using a simple device, in patients after wrist trauma. METHODS: Twenty-one consecutive patients (22 wrists) with clinically-suspected scaphoid fracture and negative initial radiographs were included. The PA view of the wrist was obtained with the hand of the patient placed in an acrylic device with three lead markers. For the bone scan, a similar device was used with 57Co markers at the same positions. We called this device the "hand-fix." The PA radiograph was digitized with a videocamera and overlaid on the bone scan. Each bone scan was interpreted twice by each of three observers, one nuclear physician and two residents in nuclear medicine. The first interpretation was made without the digital overlay, and the second was made with the digital overlay. RESULTS: The bone scintigrams were positive in the scaphoid, distal radius and in other carpal bones. Out of the 22 bone scans, Observer 1 judged 19 correctly, Observer 2 judged 16 correctly and Observer 3 judged 10 correctly without the digital overlay images. All three observers gave a correct localization in the 22 wrists using the digital overlay images. CONCLUSION: The digital overlay of a radiograph and a bone scintigram, using the hand-fix, simplifies and improves interpreting and localizing the hot spot on bone scintigrams in patients with wrist injuries.     

Ultrasonic vocalization behavior differs between lines of ethanol-preferring and nonpreferring rats

To further understand the relationship between emotional state and alcohol intake in rats, the tendency to emit ultrasonic vocalizations in response to an aversive, but nonpainful, air puff stimulus was tested in several rat lines. Included in this group were Maudsley Reactive (MR) and Non-Reactive (MNR) rats, and several lines of rats with either high ethanol preference or a low ethanol preference: Preferring, (P), Alko-Alcohol (AA), and Fawn-Hooded (FH) animals; and Non-Preferring (NP), Alko-Non-Alcohol (ANA), and Flinders Resistant Line (FRL). MR rats emitted fewer ultrasonic vocalizations (USVs) and showed less preference for ethanol than did MNR animals. An overall analysis that included the P, NP, FH, FRL, AA, and ANA groups demonstrated a significant negative correlation between the total number of USVs emitted and ethanol consumption. NP, FRL, and especially ANA rats (low ethanol-preferring) emitted the most USVs--to an extent similar to that typically found for normal rats. The duration of vocalizing was higher only in the NP and the FRL rats the relative to their P and FH comparison groups, respectively. In the ethanol-preferring and nonpreferring lines, the numbers of USVs emitted correlated positively with the duration of vocalizing, but not with the latency to vocalize, which in turn did not correlate strongly with ethanol intake. The latency to vocalize did not correlate significantly with ethanol intake across all drinking lines or MR or MNR rats, but was found to be higher in FH and AA rats relative to their nondrinking comparison groups. These associations suggest that the relationship between emotional state and ethanol drinking is complex and cannot be attributed to a simple elevated state of anxiety or emotionality. Further examination of the central nervous system mechanisms mediating the difference in USVs between paired lines of ethanol-preferring and nonpreferring rats may identify neurochemical factors that predict ethanol preference.     

Suspected nutritional deficiency causing anaemia in llamas (Lama glama)

A case of poor condition and recumbency in a 14-month-old female llama and a case of poor condition and ataxia in a 23-month-old male llama are described. Both animals were anaemic and had low plasma copper levels. An increased intake of feed with a higher copper level and treatment with copper injections and an oral mineral solution resulted in a successful recovery. Two other young llamas also had low plasma copper levels. The problem was probably due to a nutritional, particularly copper, deficiency and the animals recovered as their copper levels increased.     

The changing face of emphysematous cholecystitis

Emphysematous cholecystitis is a variant of acute cholecystitis characterized by the presence of gas in the gall bladder lumen, wall or pericholecystic tissues in the absence of an abnormal communication between the biliary system and the gastrointestinal tract. In the past, the diagnosis has relied on the plain abdominal radiograph (AXR), since there are no clinical features to separate this condition from simple acute cholecystitis. The apparently high mortality and morbidity associated with emphysematous cholecystitis has previously emphasized the importance of emergency cholecystectomy. We have reviewed eight cases of emphysematous cholecystitis presenting to this hospital over the last 5 years. The diagnosis was made on AXR in only one of these cases. Ultrasound (US) scans were performed in all eight cases, of which five were positive and three negative, due to non-visualization of the gall bladder. In the three negative cases, the diagnosis was made on subsequent CT scans. On initial clinical examination, only one of the eight patients appeared systemically unwell and conservative management was employed in five of the patients. The remaining three patients underwent cholecystectomy within 3-5 days because of continuing signs or symptoms. It is concluded that the AXR is relatively insensitive in the diagnosis of emphysematous cholecystitis. As a result of the regular use of US in suspected hepatobiliary disease, emphysematous cholecystitis is being diagnosed with increased frequency, uncovering a broad spectrum of disease ranging from mild to severe. Previously, failure to separate milder cases from simple acute cholecystitis may have been responsible for reports of unremitting severity and progression requiring emergency cholecystectomy. Based on clinical assessment, conservative surgical management is possible in a significant proportion of patients.     

Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinemic women

OBJECTIVE: To assess the effect on various aspects of carbohydrate and lipid metabolism of administering a quick-release formulation of bromocriptine (Ergoset) to obese, nondiabetic, hyperinsulinemic women. RESEARCH DESIGN AND METHODS: Hourly concentrations of prolactin, glucose, insulin, free fatty acid (FFA), and triglyceride were measured for 24 h before and after approximately 8 weeks of treatment with Ergoset. In addition, fasting lipid and lipoprotein concentrations and the steady-state plasma glucose (SSPG) concentration in response to a continuous infusion of somatostatin, insulin, and glucose were determined before and after Ergoset administration. RESULTS: Circulating prolactin concentrations were dramatically decreased (P < 0.001) following treatment, associated with a significant fall (P < 0.05) in 24-h-long plasma glucose, FFA, and triglyceride concentrations. Neither circulating plasma insulin concentrations nor the ability of insulin to mediate glucose disposal changed with treatment. Finally, fasting total cholesterol fell (P < 0.05) and the ratio of total to HDL cholesterol decreased (P = 0.06) in association with Ergoset treatment. CONCLUSIONS: The fact that significant metabolic improvement was seen in the obese nondiabetic hyperinsulinemic women studied suggests that Ergoset could be of therapeutic benefit in clinical conditions of hyperglycemia and/or dyslipidemia.