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N M Williams

Publications and source records attributed to N M Williams.

At least 37 records · Page 2Linked to original sources
PubMed2000

Emergent causes of placentitis and abortion.

The clinical signs, laboratory findings, diagnosis, epidemiology, treatment, and prevention and control of two emerging causes of placentitis and abortion in horses are described in this article. Leptospirosis has been reported as a significant cause of fetal loss in horses in Kentucky, Northern Ireland, and England. Most abortions result from infection by serovars kennewicki or bratislava. Nocardioform placentitis has become the most common cause of placentitis in central Kentucky horses. Nocardioform placentitis is associated with infection by unnamed, gram-positive, filamentous, branching bacteria, and is characterized by distinctive changes in the placental membranes.

Abortion, Veterinary↗
PubMed2000

Thoughts on the source of tissue on subsequent cell culture success.

This paper describes attempts to initiate equine adipocyte cultures from necropsy cases with varying intervals from time of death to isolation and culture. Equine adipocytes were isolated from 21 necropsy cases, regardless of the interval from time after death to establishment in primary ceiling cultures. However, while all cultures produced adipocytes, only 2 attempts to produce long-term equine adipocyte cultures from the subcutaneous rump fat depots were successful and not contaminated. Findings from these experiments indicate that it is possible to collect and culture equine adipocytes from necropsy cases with varying intervals of time of death to culturing provided that the issue of contamination is addressed. Viable cells were produced from tissue with an interval of 38.5 hours as well as 45 minutes. This result encourages the continuation of research using equine necropsy cases as a source of adipose tissue.

Adipose Tissue↗
PubMed2000

No evidence for association between a non-synonymous polymorphism in the gene encoding human metabotropic glutamate receptor 7 and schizophrenia.

The cDNA sequence of the gene encoding human metabotropic glutamate receptor type 7 (mGluR7) contains the single nucleotide polymorphism 1536A > T [GenBank sequence X94552 (Makoff et al., 1996)]. This sequence variation is predicted to result in an amino acid change (F433Y) in the gene product and thus has the potential to affect receptor function. Since disturbances in glutamate function have been implicated in the pathophysiology of schizophrenia, we have used a novel and robust polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to genotype this polymorphism in a case-control sample comprising 181 schizophrenic patients and 182 group-matched unaffected individuals. No evidence was found for association between this polymorphism and schizophrenia. We have also localised mGluR7 to chromosome 3p25-22 using radiation hybrid (RH) mapping.

Alleles↗
PubMed1999

CAG repeat length in the hKCa3 gene and symptom dimensions in schizophrenia.

BACKGROUND: Long CAG repeats in the hKCa3 potassium channel gene have been associated with schizophrenia. We sought evidence for associations between this polymorphism and aspects of the schizophrenia phenotype. METHODS: Associations were investigated between CAG repeat length and gender, age of illness onset, and psychotic symptom dimensions in 203 unrelated individuals with DSM-IIIR schizophrenia. RESULTS: No association was found between CAG repeat length and gender or age of onset. Long CAG repeats were associated with higher negative symptom dimension scores. CONCLUSIONS: This study provides preliminary evidence that genetic liability to negative symptoms in schizophrenia may be partly mediated through the hKCa3 gene.

Adult↗
PubMed1999

Autosome search for schizophrenia susceptibility genes in multiply affected families.

We have analysed 298 polymorphic markers in 13 families multiply affected with schizophrenia and related disorders using a combination of radiolabelled and fluorescent-based methodologies. The markers were distributed throughout the autosomes at an average spacing of 12.8 cM. The data were analysed with two-point linkage analysis (MLINK) and heterogeneity testing (HOMOG). Several genetic models were used ranging from near dominant to fully recessive. Multi-point analysis was performed for 27 regions demonstrating either contiguously positive lod scores in two or more consecutive markers, and in regions with two-point lod score(s) of 1.0 or above in a single marker. A proportion of the multi-point regions have been implicated in previous studies, thereby decreasing risk of false-positive results. However neither our two-point, nor multi-point scores reached the threshold value for significance of 3. 6. Nevertheless three regions were suggestive of linkage.

Chromosome Mapping↗
PubMed1999

DNA pooling identifies QTLs on chromosome 4 for general cognitive ability in children.

General cognitive ability (g), which is related to many aspects of brain functioning, is one of the most heritable traits in neuroscience. Similarly to other heritable quantitatively distributed traits, genetic influence on g is likely to be due to the combined action of many genes of small effect [quantitative trait loci (QTLs)], perhaps several on each chromosome. We used DNA pooling for the first time to search a chromosome systematically with a dense map of DNA markers for allelic associations with g. We screened 147 markers on chromosome 4 such that 85% of the chromosome were estimated to be within 1 cM of a marker. Comparing pooled DNA from 51 children of high g and from 51 controls of average g, 11 significant QTL associations emerged. The association with three of these 11 markers ( D4S2943, MSX1 and D4S1607 ) replicated using DNA pooling in independent samples of 50 children of extremely high g and 50 controls. Furthermore, all three associations were confirmed when each individual was genotyped separately ( D4S2943, P = 0. 00045; MSX1, P = 0.011; D4S1607, P = 0.019). Identifying specific genes responsible for such QTL associations will open new windows in cognitive neuroscience through which to observe pathways between genes and learning and memory.

Adolescent↗
PubMed1999

A two-stage genome scan for schizophrenia susceptibility genes in 196 affected sibling pairs.

We undertook a systematic search for linkage in 196 affected sibling pairs (ASPs) with DSMIV schizophrenia. In stage 1 we typed 97 ASPs with 229 microsatellite markers at an average inter-marker distance of 17.26 cM. Multipoint affected sib pair analysis identified seven regions with a maximum lod score (MLS) at or above the level associated with a nominal pointwise significance of 5%, on chromosomes 2q, 4p, 10q, 15q, 18p, 20q and Xcen. In stage 2 we genotyped a further 54 markers in 196 ASPs together with parents and unaffected siblings. This allowed the regions identified in stage 1 to be typed at an average spacing of 5.15 cM, while the region of interest on chromosome 2 was typed to 9.55 cM. Analysis was performed on the whole data set. Simulation studies suggested that we would expect one multipoint MLS of 1.5 per genome scan in the absence of linkage. An MLS of 3 would be expected only once in every 20 genome scans and thus corresponds to a genome-wide significance of 0.05. We obtained three multipoint MLSs >1.5 and, on this basis, the results on chromosomes 4p, 18q and Xcen can be considered suggestive. However, none approached a genome-wide significance of 0. 05. The power of this study was >0.95 to detect a susceptibility locus of lambda(s)= 3 with a genome-wide significance of 0.05, but only 0.70 to detect a locus of lambda(s)= 2. Our results suggest that common genes of major effect (lambda(s)> 3) are unlikely to exist for schizophrenia.

Chromosome Mapping↗
PubMed1998

Further support for an association between a polymorphic CAG repeat in the hKCa3 gene and schizophrenia.

A recent study has suggested that a polymorphism in the hKCa3 potassium channel may be associated with raised susceptibility to schizophrenia. Despite its modest statistical significance, the study is intriguing for two reasons. First, hKCa3 contains a polymorphic CAG repeat in its coding sequence, with large repeats more common in schizophrenics compared with controls. This is interesting in view of several repeat expansion detection (RED) studies that have reported an excess of large CAG repeats in psychotic probands. Second, the hKCa3 gene is a functional candidate gene because studies of antipsychotic and psychotogenic compounds suggest that glutamatergic systems modulated by SKCa channels may be important in schizophrenia pathogenesis. In the light of the above, we have tested the hypothesis of an association between schizophrenia and the hKCa3 CAG repeat polymorphism using a case control study design. Under the same model of analysis as the earlier study, schizophrenic probands had a higher frequency of alleles with greater than 19 repeats than controls (chi 2 = 2.820, P = 0.047, 1-tail). Our data therefore provide modest support for the hypothesis that polymorphism in the hKCa3 gene may contribute to susceptibility to schizophrenia.

Alleles↗
PubMed1998

Dynamic contrast-enhanced magnetic resonance imaging in a model of splenic metastasis.

RATIONALE AND OBJECTIVES: The use of rapid dynamic magnetic resonance (MR) imaging after bolus intravenous contrast injection, to improve detection and delineation of parenchymal disease, was evaluated in an experimental model of splenic metastasis. METHODS: An experimental model for splenic metastasis was first developed in the New Zealand White rabbit. Magnetic resonance studies were then obtained at 1.5 tesla in six animals. A 25 ga needle was used to penetrate the spleen and inject 0.1 mL of minced, screened VX2 adenocarcinoma (obtained from a carrier rabbit). The injections were performed by two techniques, percutaneously using ultrasound guidance (n = 3) and at the time of abdominal laparotomy (n = 3). The animals were imaged at 1.5 tesla on day 10 after implantation. Breath-hold T2-weighted and T1-weighted scans were acquired prior to contrast injection. A dose of 0.3 mmol/kg gadoteridol (ProHance) was then administered intravenously using an MR-compatible power injector, with both dynamic and delayed postcontrast scans obtained. The lesion was confirmed in each animal by gross pathologic and microscopic exam. RESULTS: On region of interest analysis of T2-weighted scans, the lesions could not be differentiated by signal intensity (with any statistical significance) from normal surrounding splenic parenchyma. Lesion conspicuity, assessed by signal difference/noise ratio on dynamic turbo-FLASH scans, increased from 6+/-5 precontrast to a peak of 16+/-5 at 31 seconds postcontrast, with P < 0.003 (n = 6). Lesion conspicuity steadily diminished from this time to 5 minutes postinjection, although it was still improved at 5 minutes over precontrast scans. CONCLUSIONS: On early dynamic contrast enhanced breath-hold MR, marked improvement in the differentiation of splenic metastases from surrounding normal parenchyma is achieved. The capability of dynamic MR in this regard is analogous to that demonstrated for helical computed tomography.

Adenocarcinoma↗
PubMed1998

Magnetic resonance imaging in a spinal abscess model. Preliminary report.

RATIONAL AND OBJECTIVES: Magnetic resonance (MR) scan technique and lesion detectability were evaluated using a newly developed spinal abscess model in the New Zealand White rabbit. METHODS: To create the lesion, an epidural needle was inserted under fluoroscopic guidance in the lumbar region and advanced to penetrate the ligamentum flavum. Next, polyethylene tubing was fed through the needle into the epidural space. A mixed suspension of Staphylococcus aureus (Cowan I) and blue polystyrene microspheres then was injected. Lesions were evaluated by MR imaging in four animals at multiple time points (3, 6, and 9 days). Imaging was performed at 1.5 tesla using a surface coil. Precontrast T2-and T1-weighted scans were first obtained. The T1-weighted scans were acquired both with and without fat saturation, and were repeated after intravenous contrast administration. The contrast agent used was gadoteridol (gadolinium HP-DO3A or ProHance) at a dose of 0.3 mmol/kg. RESULTS: On prospective film review, postcontrast scans proved superior for lesion detection. A spinal abscess could be identified postcontrast in all cases, irrespective of the use of fat saturation. The next best imaging technique for lesion detection was the T2-weighted scan, with 5 of 8 lesions noted thereon. Visualization of lesion margins proved to be a primary factor in prospective lesion identification. Region of interest image analysis demonstrated the postcontrast scans to be superior to all precontrast scan techniques for conspicuity of the interface between the abscess and the compressed spinal cord, with these results statistically significant. The lesions were characterized histologically by infiltrates of heterophils into the meninges and outer spinal cord with accompanying mild hemorrhage, fibrin exudation, and bacterial colonies. The lesions in three animals were confirmed to be in the epidural space, with the lesion in one animal in the subdural space. CONCLUSIONS: The current animal model was developed to study spine infection and, specifically, imaging characteristics and lesion detectability on MR. With the increased use of epidural catheters for pain management and the large number of acquired immunodeficiency syndrome cases, epidural infection is becoming an increasingly important clinical problem. Imaging technique, in particular the use of intravenous contrast, is critical for lesion detection and evaluation.

Abscess↗
PubMed1998

Is the incidence of acute appendicitis really falling?

To determine if there has been a genuine fall in the incidence of acute appendicitis, an epidemiological study using HAA and Korner datasets for the years 1975-1994 was carried out to identify those children and young adults undergoing appendicectomy for acute appendicitis. The overall incidence of acute appendicitis fell from 1.84/1000 to 1.17/1000. This fall was statistically significant (R2 = 0.74, P < 0.01). The decrease was significant in both males (overall reduction, 34%) and females (overall reduction, 40%). No significant reduction was observed in either males or females between 15 and 19 years of age. The overall reduction remains essentially unexplained, but may have implications for health planning and provision of services.

Acute Disease↗
PubMed1998

The diagnostic value of symptoms and signs in childhood abdominal pain.

The assessment and diagnosis of abdominal pain in childhood continues to be a clinical challenge. We audited the presenting symptoms and signs in a consecutive series of 447 children presenting to a paediatric surgical unit in an attempt to quantify the value of particular symptoms and signs in differentiating acute appendicitis (AA) from non-specific abdominal pain (NSAP). The onset of pain in the centre of the abdomen and radiation of pain was not sufficient to differentiate between NSAP and AA. Progression of pain, nausea, vomiting, anorexia and diarrhoea were significantly more common in children with AA (P < 0.01). Similarly, facial flushing, tachycardia (pulse > 100 beats/min), guarding and rebound tenderness were significantly more common in children with AA (P < 0.001). Knowledge of this quantitative data could help clinicians adjust the weighting given to the presence of a particular symptom or sign in children with acute abdominal pain.

Abdomen, Acute↗
PubMed1997

Linkage study of chromosome 6p in sib-pairs with schizophrenia.

Following reports of linkage between schizophrenia and markers in the chromosomal region 6p24-22 we have studied nine microsatellite markers spanning 40 cM of this region in our sample of 102 affected sibling pairs from 86 families. Allele sharing identity by descent was examined using likelihood based sib-pair analysis as implemented by the program SPLINK. No evidence for linkage was obtained and the highest lod score was only 0.192 for D6S309. We conclude that if there is a susceptibility locus for schizophrenia in this region then its effect size is so small as to render our study insufficiently powerful to detect it.

Adult↗
PubMed1997

No evidence for an allelic association between schizophrenia and markers D22S278 and D22S283.

We report a case control association study using markers D22S278 and D22S283 in 90 unrelated patients with DSMIII-R schizophrenia and 90 controls matched for ethnicity, age and sex. No differences between allele frequencies for either marker were observed when the two groups were compared (D22S278: chi 2 = 6.53, df = 7, P = 0.51; D22S283: chi 2 = 14.73, df = 15, P = 0.48). These findings fail to support previous work by others suggesting the presence of allelic association between the markers D22S278 and D22S283 and schizophrenia.

Alleles↗
PubMed1997

Successful management of external duodenal fistula in a specialized unit.

BACKGROUND: High-output external duodenal fistula remains a challenging condition to treat. Despite advances in metabolic and nutritional care, mortality rates remain high. METHOD: Retrospective casenote review of patients managed on a specialised unit. RESULTS: Thirteen of 388 admissions (3.4%, 11 males, median age 51 years) had an external duodenal fistula. Management was by eradication of abdominal and systemic sepsis and maintenance of nutritional status by the administration of total parenteral nutrition. The majority of fistulas followed surgery for peptic ulcer disease. Eight of 13 fistulas closed spontaneously, and of those requiring operative closure, surgery was successful in 4 of 5 cases. There were 2 mortalities. CONCLUSION: High-output external duodenal fistula may be successfully managed in a specialised unit.

Adult↗