Waiting to exhale: Retrieval of an unusual bronchial foreign body.

ABSTRACT: Foreign-body aspiration in adults is considerably less common than in children. The clinical course can be life-threatening but often presents in a more indolent manner, leading to difficulties with diagnosis. We report the retrieval of a buprenorphine-naloxone wrapper by flexible bronchoscopy in a 44-year-old male patient with COVID-19 who was on mechanical ventilation. Following removal, the patient completed treatment for COVID-19, his respiratory status improved, and he was discharged from the hospital. Flexible bronchoscopy is an effective means of diagnosis and retrieval of foreign bodies in the distal airway.

Use of the Internet by patients and their families to obtain genetics-related information.

OBJECTIVE: To characterize use of the Internet by patients and their families referred to general genetics clinics. PATIENTS AND METHODS: We developed a survey to assess Internet use among patients visiting urban and rural clinics in Colorado and Wyoming. One hundred eighty-nine surveys were distributed to patients and their family members visiting outpatient general genetics clinics in spring 2000. The 8-page anonymous survey instrument asked about use of the Internet to obtain genetics-related information (GRI). All participants were asked whether a physician or health professional had referred them to the Internet for GRI. Subjects who had previously used the Internet to search for GRI were asked to rate whether they considered the GRI they encountered to be accurate, inaccurate, easy to understand, confusing, or trustworthy. RESULTS: One hundred fifty-seven surveys (83%) were returned (52% urban; 48% rural). Ninety (60%) of 149 respondents were at the clinic for a new-patient visit, and 59 (40%) were follow-up visits. All respondents were older than 17 years; 141 (91%) of 155 respondents were the patient's parent or guardian. Seventy-three (47%) of 155 respondents had searched the Internet for GRI prior to their clinic visit. The patients and families themselves initiated the majority of such efforts; only 8 (5%) of 148 respondents had been referred to a site on the World Wide Web by a physician. Interestingly, 136 (92%) of 147 respondents indicated that they would be likely to visit a Web site that was recommended by a geneticist. The most compelling reasons for searching the Internet for GRI were to get information in layperson's terms (60/131 [46%]); to get information about treatment (16/131 [12%]); and to get information about genetic research (16/131 [12%]). Among respondents who reported visiting GRI Web sites, 24 (41%) of 58 agreed that information was confusing or difficult to understand, 35 (53%) of 66 agreed that information was accurate and trustworthy, and 44 (77%) of 57 agreed that using the Internet was a positive experience. CONCLUSION: Internet use among patients referred to general genetics clinics and their family members appears to be widespread. Respondents reported that they found some of the information confusing and questioned its accuracy. Referral to Web sites by physicians was reported rarely, although the majority of respondents said they would visit a Web site recommended by a genetics physician. Further studies are needed to establish the accuracy of Internet information and how best to integrate and/or accommodate the data into the genetics clinic.

Towards the development of brain injury specialists.

Brain injury presents a hugely complex, and sometimes daunting arena for the rehabilitation professional. With disruption to a person's core sense of self being almost the sine qua non of brain injury, rehabilitation can cover physical, psychological, social, philosophical and psychiatric realms. Those with brain injury can also be amongst the most vulnerable people in our society. Their rehabilitation has profound implications socio-politically, both in how we seek to understand disturbance in others, and also how we strive to ameliorate it. Whilst both theory and practice have grown exponentially over the last two decades, there is still no formal training or qualification within the brain injury rehabilitation field. This paper discusses the need for such formal training at both a theoretical and practical level not only for clinicians but also for front line staff, families and primary care services. The difficulties inherent in providing co-ordinated and structured training in such a complex area are discussed, and finally a model that attempts to meet user needs is outlined.

Ethnic variability in the allelic distribution of human aryl hydrocarbon receptor codon 554 and assessment of variant receptor function in vitro.

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcriptional regulator of several genes including the cytochrome P4501 (CYP1) family as well as genes encoding factors involved in cell growth and differentiation. In mice, several polymorphic forms of the AHR are known, some of which have altered affinity for toxic and carcinogenic ligands. Remarkably little genetic variation has been detected in the human AHR gene. In studies on human AHR, Kawajiri et al. (Pharmacogenetics 1995; 5:151-158) reported a variation at codon 554 that results in an amino acid change from arginine to lysine; the frequency of the variant allele in a Japanese population (n = 277) was 0.43. We investigated the Lys554 allele in 386 individuals of various ethnic origins and found the frequency to be: 0.58 in Ivory Coast Africans (n = 58); 0.53 in a mixed African group (n = 20); 0.39 in Caribbean-Africans (n = 55); 0.32 in Canadian Chinese (n = 41); 0.14 in North American Indians (n = 47); 0.12 in French Canadian Caucasians (n = 20); 0.11 in a mixed ethnicity North American group (n = 45); 0.09 in Canadian Inuits (n = 22); and 0.07 in German Caucasians (n = 78). We expressed the human Lys554 allele in an in-vitro transcription-translation system and found that the receptor bearing the R554L substitution had an equivalent ability to that of the wild-type receptor to bind to a dioxin-responsive element following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The Lys554 allele also was equivalent to the wild-type receptor at stimulating CYP1A1 mRNA expression when transfected into TCDD-treated receptor-deficient mouse Hepa-1 cells. It is not yet known if any of the wide variations in allele frequency at codon 554 are related to ethnic differences in susceptibility to adverse effects of environmental chemicals.

PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome.

Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway. CS is characterized by multiple hamartomas and an increased risk of benign and malignant disease of the breast, thyroid and central nervous system, whilst the presence of cancer has not been formally documented in BRR. The partial clinical overlap in these two syndromes is exemplified by the hallmark features of BRR: macrocephaly and multiple lipomas, the latter of which occur in a minority of individuals with CS. Additional features observed in BRR, which may also occur in a minority of CS patients, include Hashimoto's thyroiditis, vascular malformations and mental retardation. Pigmented macules of the glans penis, delayed motor development and neonatal or infant onset are noted only in BRR. In this study, constitutive DNA samples from 43 BRR individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both CS and BRR, were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) BRR cases. Genotype-phenotype analyses within the BRR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, BRR or BRR/CS overlap family ( P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family ( P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRR patients ( P = 0.028). In contrast to a prior report, no significant difference in mutation status was found in familial versus sporadic cases of BRR ( P = 0.113). Comparisons between BRR and a previously studied group of 37 CS families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CS alone or both CS and BRR when compared with BRR alone ( P = 0.002). Among CS, BRR and BRR/CS overlap families that are PTEN mutation positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS and BRR may be different presentations of a single syndrome and, hence, both should receive equal attention with respect to cancer surveillance.

Fragile X syndrome and an isodicentric X chromosome in a woman with multiple anomalies, developmental delay, and normal pubertal development.

We report on an individual with developmental delays, short stature, skeletal abnormalities, normal pubertal development, expansion of the fragile X triplet repeat, as well as an isodicentric X chromosome. S is a 19-year-old woman who presented for evaluation of developmental delay. Pregnancy was complicated by a threatened miscarriage. She was a healthy child with intellectual impairment noted in infancy. Although she had global delays, speech was noted to be disproportionately delayed with few words until age 3.5 years. Facial appearance was consistent with fragile X syndrome. Age of onset of menses was 11 years with normal breast development. A maternal male second cousin had been identified with fragile X syndrome based on DNA studies. The mother of this child (S's maternal first cousin) and the grandfather (S's maternal uncle) were both intellectually normal but were identified as carrying triplet expansions in the premutation range. S's mother had some school difficulties but was not identified as having global delays. Molecular analysis of S's fragile X alleles noted an expansion of more than 400 CGG repeats in one allele. Routine cytogenetic studies of peripheral blood noted the presence of an isodicentric X in 81of 86 cells scored. Five of 86 cells were noted to be 45,X. Cytogenetic fra(X) studies from peripheral blood showed that the structurally normal chromosome had the fragile site in approximately 16% of the cells. Analysis of maternal fragile X alleles identified an allele with an expansion to approximately 110 repeats. FMRP studies detected the expression of the protein in 24% of cells studied. To our knowledge, this is the first patient reported with an isodicentric X and fragile X syndrome. Whereas her clinical phenotype is suggestive of fragile X syndrome, her skeletal abnormalities may represent the presence of the isodicentric X. Treatment of S with 20 mg/day of Prozac improved her behavior. In the climate of cost con trol, this individual reinforces the recommendation of obtaining chromosomes on individuals with developmental delay even with a family history of fragile X syndrome.

Promoting cancer screening among the first-degree relatives of breast and colorectal cancer patients: the design of two randomized trials.

BACKGROUND: In this paper two large nationwide trials are described, both of which will test a comparable telephone-based counseling intervention to promote cancer screening among the first-degree relatives (FDRs) of breast and colorectal cancer patients. The unit of randomization will be the family unit of eligible FDRs. Access to FDRs will be obtained from their relatives with cancer. Selected intervention and design issues are reviewed, including how both projects will respond to FDRs who exhibit significant levels of cancer-specific anxiety or distress and how potential high-risk cancer families will be accommodated. METHODS: Pursuant to the development of both studies, two feasibility surveys were conducted to determine whether patients would grant access to their FDRs and whether the FDRS identified by these patients would be receptive to the telephone intervention. RESULTS: Approximately 80% (106 of 132) of breast cancer patients agreed to provide access to their eligible FDRs when contacted on-site at participating hospitals and clinics. Of those subsequently selected for telephone follow-up (n = 95 or 90%), 80% (n = 76) were successfully contacted by telephone, and of these 97% (n = 74) provided the names and telephone numbers of their FDRs. Among colorectal cancer patients contacted on-site (n = 46), 96% (n = 44) agreed to provide access to their FDRs, and of those contacted by telephone (n = 33 or 75%), 91% (n = 30) provided the requested information about their FDRs. Once contacted, 95% of breast cancer FDRs (55 of 58) and 91% of colorectal cancer patients (51 of 56) endorsed the intervention strategy. CONCLUSIONS: It is argued that this intervention, if proven effective, could provide an exportable strategy for reaching large numbers of high-risk individuals to promote cancer screening.

Polycyclic aromatic hydrocarbon-DNA adducts in human placenta and modulation by CYP1A1 induction and genotype.

This study investigated the relationship in human placenta between polycyclic aromatic hydrocabon (PAH)-DNA adduct levels and two biomarkers of cytochrome P4501A1 (CYP1A1): gene induction evidenced by CYP1A1 mRNA, and a genetic polymorphism, the CYP1A1 MspI RFLP. CYP1A1 codes for an inducible enzyme system that catalyzes the bioactivation of PAHs. Prior research found a high correlation in human lung tissue between CYP1A1 activity and DNA damage from PAHs. The CYP1A1 Mspi RFLP has been linked in some studies to risk of lung cancer. The relationships in human placenta between DNA damage, CYP1A1 activity and genotype have not been well characterized and may be relevant to risks from transplacental PAH exposure. The study cohort consisted of 70 newborns from Krakow, Poland, a city with elevated air pollution, and 90 newborns from nearby Limanowa, an area with lower air pollution but greater indoor coal use. Contrary to results seen previously in lung tissue, CYP1A1 mRNA was not significantly correlated with PAH-DNA adduct levels in the placenta. Smoking (self-reported maternal and infant plasma cotinine) was significantly associated with CYP1A1 mRNA levels (P < 0.01), but not with PAH-DNA adduct levels. Placental PAH-DNA adduct levels were significantly higher in infants with the CYP1A1 MspI restriction site compared with infants without the restriction site (P < 0.01), implicating a genetic factor in inter-individual variation in DNA damage in human placenta. Further studies are needed to determine the relevance of this finding to risk of transplacental carcinogenesis.

Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2+-dependent signaling protein which is mutated in human X-linked neuronal migration defects.

Subcortical band heterotopia (SBH) and classical lissencephaly (LIS) result from deficient neuronal migration which causes mental retardation and epilepsy. A single LIS/SBH locus on Xq22.3-q24 was mapped by linkage analysis and physical mapping of the breakpoint in an X;2 translocation. A recently identified gene, doublecortin ( DCX ), is expressed in fetal brain and mutated in LIS/SBH patients. We have identified four novel missense mutations in the gene, one familial mutation with LIS in a male and SBH in the carrier females, one de novo mutation in an SBH female, and two mutations in sporadic SBH female patients. The DCX gene is found to be expressed exclusively at a very high level in the adult frontal lobe. We have also cloned the X-linked mouse doublecortin (Dcx) gene. It encodes isoforms of a highly hydrophilic 40 kDa protein, homologous to its human counterpart and containing several potential phosphorylation sites. Both human and mouse DCX proteins are homologous to a CNS protein containing a Ca2+/calmodulin kinase domain, suggesting that the DCX protein may belong to a novel class of intracellular proteins involved in neuronal migration through Ca2+-dependent signaling.

Relationship between ambient air pollution and DNA damage in Polish mothers and newborns.

Industrialized regions in Poland are characterized by high ambient pollution, including polycyclic aromatic hydrocarbons (PAHs) from coal burning for industry and home heating. In experimental bioassays, certain PAHs are transplacental carcinogens and developmental toxicants. Biologic markers can facilitate evaluation of effects of environmental PAHs on the developing infant. We measured the amount of PAHs bound to DNA (PAH-DNA adducts) in maternal and umbilical white blood cells. The cohort consisted of 70 mothers and newborns from Krakow, Poland, an industrialized city with elevated air pollution. Modulation of adduct levels by genotypes previously linked to risk of lung cancer, specifically glutathione S-transferase MI (GSTM1) and cytochrome P4501A1 (CYP1A1) Msp restriction fragment length polymorphism (RFLP), was also investigated. There was a dose-related increase in maternal and newborn adduct levels with ambient pollution at the women's place of residence among subjects who were not employed away from home (p < or = 0.05). Maternal smoking (active and passive) significantly increased maternal (p < or = 0.01) but not newborn adduct levels. Neither CYP1A1 Msp nor GSTM1 polymorphisms was associated with maternal adducts. However, adducts were significantly higher in newborns heterozygous or homozygous for the CYP1A1 Msp RFLP compared to newborns without the RFLP (p = 0.04). Results indicate that PAH-induced DNA damage in mothers and newborns is increased by ambient air pollution. In the fetus, this damage appears to be enhanced by the CYP1A1 Mspl polymorphism.

Recent developments in molecular epidemiology: A study of the effects of environmental polycyclic aromatic hydrocarbons on birth outcomes in Poland.

The authors briefly review the current potential and limitations of molecular epidemiology. This approach uses biomarkers to measure the internal and bioeffective dose of toxicants, early biologic effects likely to be predictive of cancer, and variations in individual susceptibility. The most frequent application of biomarkers has been in assessment of exposure/dose and susceptibility due to genetic and nongenetic factors. More research is needed to establish the predictive significance of biomarkers in terms of disease risk. To illustrate that molecular epidemiology has potential in identifying etiologic factors in disease, this article presents data from a recent study of the developmental effects of fetal exposure to polycyclic aromatic hydrocarbons (PAH) via ambient pollution. The study was carried out in an industrialized area of Poland with relatively high levels of PAH pollution from coal burning. PAH-DNA adducts in leukocytes and plasma cotinine were measured in umbilical cord blood as dosimeters of transplacental PAH and cigarette smoke, respectively. The study subjects were 70 newborns from the industrialized city of Krakow and 90 newborns from Limanowa, a rural town with far greater use of coal for home heating. Newborns whose levels of PAH-DNA adducts were above the median (3.85/10[8] nucleotides) had a significantly decreased birth length, weight, and head circumference. Cotinine was significantly inversely associated with birth weight and length. Although preliminary, these results provide a new molecular link between PAH exposure and developmental effects, generating initial data and hypotheses for further study.

Meiotic segregation, recombination, and gamete aneuploidy assessed in a t(1;10)(p22.1;q22.3) reciprocal translocation carrier by three- and four-probe multicolor FISH in sperm.

Meiotic segregation, recombination, and aneuploidy was assessed for sperm from a t(1;10)(p22.1;q22.3) reciprocal translocation carrier, by use of two multicolor FISH methods. The first method utilized three DNA probes (a telomeric and a centromeric probe on chromosome 1 plus a centromeric probe on chromosome 10) to analyze segregation patterns, in sperm, of the chromosomes involved in the translocation. The aggregate frequency of sperm products from alternate and adjacent I segregation was 90.5%, and the total frequency of normal and chromosomally balanced sperm was 48.1%. The frequencies of sperm products from adjacent II segregation and from 3:1 segregation were 4.9% and 3.9%, respectively. Reciprocal sperm products from adjacent I segregation deviated significantly from the expected 1:1 ratio (P < .0001). Our assay allowed us to evaluate recombination events in the interstitial segments at adjacent II segregation. The frequencies of sperm products resulting from interstitial recombination in chromosome 10 were significantly higher than those resulting from interstitial recombination in chromosome 1 (P < .006). No evidence of an interchromosomal effect on aneuploidy was found by use of a second FISH method that simultaneously utilized four chromosome-specific DNA probes to quantify the frequencies of aneuploid sperm for chromosomes X, Y, 18, and 21. However, a significant higher frequency of diploid sperm was detected in the translocation carrier than was detected in chromosomally normal and healthy controls. This study illustrates the advantages of multicolor FISH for assessment of the reproductive risk associated with translocation carriers and for investigation of the mechanisms of meiotic segregation of chromosomes.

Prolonged, severe behavioural disturbance following traumatic brain injury: what can be done?

At the end of 1994 the New South Wales Department of Health identified the need for a specialized unit for people with a brain injury who exhibited aggressive and violent behaviour at such a level that they could not be cared for in standard rehabilitation programmes and who were not mentally ill as defined by the Mental Health Act. An interim unit based on the principles of neurobehavioural rehabilitation was opened in the grounds of Lidcombe Hospital, and in January 1995 the first patient (SA) was admitted. Following intervention weekly aggression decreased from a peak of 159 incidents to zero after ten months. Other maladaptive behaviours also decreased markedly. Simultaneous attempts to improve adaptive behaviours were successful. At 11 months follow-up in the community, these gains were all noted to have been maintained. This article discusses the need for specialized units dealing with severe behavioural problems following head injury, presents the case of SA for illustrative purposes, and addresses some of the more common criticisms of such environments.

Mutations in the delta-sarcoglycan gene are a rare cause of autosomal recessive limb-girdle muscular dystrophy (LGMD2).

The dystrophin-based membrane cytoskeleton of muscle fibers has emerged as a critical multi-protein complex which seems to impart structural integrity on the muscle fiber plasma membrane. Deficiency of dystrophin causes the most common types of muscular dystrophy, Duchenne and Becker muscular dystrophies. Muscular dystrophy patients showing normal dystrophin protein and gene analysis are generally isolated cases with a presumed autosomal recessive inheritance pattern (limb-girdle muscular dystrophy). Recently, linkage and candidate gene analyses have shown that some cases of limb-girdle muscular dystrophy can be caused by deficiency of other components of the dystrophin membrane cytoskeleton. The most recently identified component, delta-sarcoglycan, has been found to show mutations in a series of Brazilian muscular dystrophy patients. All patients were homozygous for a protein-truncating carboxy-terminal mutation, and showed a deficiency of the four sarcoglycan proteins. To determine if delta-sarcoglycan deficiency occurred in other world populations, to identify the range of mutations and clinical phenotypes, and to test for the biochemical consequences of delta-sarcoglycan gene mutations, we studied Duchenne-like and limb-girdle muscular dystrophy patients who we had previously shown not to exhibit gene mutations of dystrophin, alpha-, beta-, or gamma-sarcoglycan for delta-sarcoglycan mutations (n = 54). We identified two American patients with novel nonsense mutations of delta-sarcoglycan (W30X, R165X). One was apparently homozygous, and we show likely consanguinity through homozygosity for 13 microsatellite loci covering a 38 cM region of chromosome 5. The second was heterozygous. Both were girls who showed clinical symptoms consistent with Duchenne muscular dystrophy in males. Our data shows that delta-sarcoglycan deficiency occurs in other world populations, and that most or all patients show a deficiency of the entire sarcoglycan complex, adding support to the hypothesis that these proteins function as a tetrameric unit.

A non-aversive approach to reducing hospital absconding in a head-injured adolescent boy.

Patients who abscond from hospital exclude themselves from therapy, and attempts to stop the person can quickly become confrontational with the inherent risk of aggression. Although information is available on absconding in psychiatric settings little is known about the type of person with a head injury who absconds, why such people do so, or how the problem might best be approached. This paper presents a non-aversive approach to hospital absconding in a head-injured adolescent male, discusses how his case relates to the psychiatric literature, and looks at the feasibility of adopting such interventions in general hospital wards.

Binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to AH receptor in placentas from normal versus abnormal pregnancy outcomes.

Binding of [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin to AH receptor was characterized in cytosol from human placentas in which the pregnancy outcome was normal compared with pregnancies in which there was some adverse outcome (premature birth; intrauterine growth retardation; structural abnormality). No significant difference was detected between normal and adverse outcomes in the concentration of AH receptor sites (Bmax) nor in the affinity with which [3H]TCDD bound to the receptor (Kd). Aryl hydrocarbon hydroxylase activity, a CYP1A1 enzyme regulated by the AH receptor, was elevated in placental microsomes from smokers; this elevation was associated with intrauterine growth retardation.

Hunter-McAlpine craniosynostosis phenotype associated with skeletal anomalies and interstitial deletion of chromosome 17q.

Hunter-McAlpine syndrome is an autosomal dominant disorder consisting of variable manifestations including craniosynostosis, almond-shaped palpebral fissures, small mouth, mild acral-skeletal anomalies, short stature, and mental deficiency. We report on a 9-year-old boy with this phenotype with more severe skeletal abnormalities than previously described. Chromosomes showed del(17)(q23.1-->q24.2); the more severe phenotype may be explained by the deletion. The deletion also suggests the possibility that the gene for Hunter-McAlpine syndrome might map to that region.

Sensitivity of somatic mutations in human umbilical cord blood to maternal environments.

To assess the potential effect of maternal environments on human embryonic/fetal somatic mutation, we measured the frequencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT, hprt gene), mutant T lymphocytes (Mf), and glycophorin A (GPA) variant erythrocytes (Vf) of both allele-loss (phi/N) and allele-loss-and-duplication (N/N) phenotypes in umbilical cord blood. The mean hprt Mf (1.40 +/- 1.11 x 10(-6), N = 66) and GPA Vf (phi/N 4.0 +/- 2.2 x 10(-6), N = 114; N/N 2.7 +/- 2.0 x 10(-6), N = 91) were significantly lower than those previously reported for adult populations. In addition, the hprt Mf was significantly higher than that of a published study of newborn cord blood samples from a geographically distant population (0.64 +/- 0.41 x 10(-6), N = 45, P < 0.01; t test, P < 0.01, Mann-Whitney U test). An examination of the demographic data from these two populations led to the sampling of 10 additional newborns specifically matched to the published study for maternal socioeconomic status. The hprt Mf (0.70 +/- 0.49 x 10(-6)) of this selected population was consistent with the published report and significantly lower than that of our initial population (P < 0.03, t test; P < 0.01, Mann-Whitney U test). These results indicate that there is an environmental effect related to maternal socioeconomic status on the frequency of embryonic/fetal somatic mutations. Molecular analyses of hprt mutants from this cohort with elevated Mf revealed a significant decrease in the relative contribution of gross structural mutations to the overall Mf (25 of 38, 66% vs. 34 of 41, 83%, P = 0.024, chi 2 test), suggesting that the higher Mf resulted from an elevated level of "point" mutations. No individual maternal demographic or environmental factor was identified as contributing more significantly than other any factor to the observed variability in hprt Mf or GPA Vf.

Neuroleptics, learning disability, and the community: some history and mystery.

Recent papers have again highlighted the consistently high use of neuroleptic agents among people with a learning disability, despite the lack of good evidence to support their role in this population for behaviour management and despite the risks of such medication. Evidence suggests, however, that prescribing habits have remained relatively unchanged; the reasons for this are poorly understood. Given the lack of understanding about the factors contributing to such drug use, and the possibility that use of neuroleptics will increase as people with learning disabilities move into the community, there seems a clear need for clinical guidelines to cover the prescribing and monitoring of neuroleptics within this group. Such guidelines should also ensure that reviews, using reliable measures of treatment efficacy, are carried out regularly.