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Biomedical subjects

S Isaacs

Publications and source records attributed to S Isaacs.

At least 19 recordsLinked to original sources
PubMed2002

Germline mutations in the ribonuclease L gene in families showing linkage with HPC1.

Although prostate cancer is the most common non-cutaneous malignancy diagnosed in men in the United States, little is known about inherited factors that influence its genetic predisposition. Here we report that germline mutations in the gene encoding 2'-5'-oligoadenylate(2-5A)-dependent RNase L (RNASEL) segregate in prostate cancer families that show linkage to the HPC1 (hereditary prostate cancer 1) region at 1q24-25 (ref. 9). We identified RNASEL by a positional cloning/candidate gene method, and show that a nonsense mutation and a mutation in an initiation codon of RNASEL segregate independently in two HPC1-linked families. Inactive RNASEL alleles are present at a low frequency in the general population. RNASEL regulates cell proliferation and apoptosis through the interferon-regulated 2-5A pathway and has been suggested to be a candidate tumor suppressor gene. We found that microdissected tumors with a germline mutation showed loss of heterozygosity and loss of RNase L protein, and that RNASEL activity was reduced in lymphoblasts from heterozyogous individuals compared with family members who were homozygous with respect to the wildtype allele. Thus, germline mutations in RNASEL may be of diagnostic value, and the 2-5A pathway might provide opportunities for developing therapies for those with prostate cancer.

Adenine Nucleotides↗
PubMed2001

Characterization of Salmonella associated with pig ear dog treats in Canada.

In the summer of 1999, the incidence of Salmonella enterica serotype Infantis infections in Alberta rose dramatically. Subsequent laboratory and epidemiological investigations established that an outbreak of human disease caused by this organism was occurring across Canada and was associated with pet treats for dogs produced from processed pig ears. Laboratory investigations using phage typing and pulsed-field gel electrophoresis (PFGE) established that isolates of Salmonella serotype Infantis from pig ear pet treats and humans exposed to pig ear pet treats comprised a well-defined subset of all isolates analyzed. Of the 53 subtypes of Salmonella serotype Infantis obtained around the time of the outbreak as defined by PFGE and phage typing, only 6 subtypes were associated with both human infection and isolation from pig ears. Together with information from epidemiological studies, these investigations established pig ear pet treats as the cause of the Salmonella serotype Infantis outbreak. The results are consistent with a model in which contaminated pig ear pet treats constitute a long-term, continuing vehicle for infection of the human population rather than causing temporally delimited point-source outbreaks. During the course of this outbreak, several other Salmonella serotypes were also isolated from pet treats, suggesting these products may be an important source of enteric infection in both humans and dogs. Though isolates of Salmonella serotypes other than Salmonella serotype Infantis from pet treats were also subjected to PFGE and phage typing, no link with human disease could be definitively established, and the contribution of pig ear pet treats to human disease remains unclear. Elimination of bacterial contamination from pet treats is required to reduce the risk of infection from these products.

Alberta↗
PubMed2001

The power distance between users of information technology and experts and satisfaction with the information system: implication for cross cultural transfer of IT.

There is a need for research into Information Technology (IT) transfer from one culture to another. Two of the more important cultural factors which affects IT transfer are power distance and uncertainty avoidance. The IT expert, by virtue of specialized knowledge is in a position of power. The user of information technology may or may not accept the authority of the IT professional. When the user and the expert is in agreement on the issue of power-distance the IT systems provided will be viewed in a more positive light. This hypothesis is tested and confirmed in the present study. A list of twelve statements expressing special IT knowledge and authority was constructed and a sample of IT experts and users were asked to rate their level of agreement with these on a scale 0 to 5. The simple sum of respondent rating was used as a measure of acceptance of IT authority and power. Users were also asked to rate their level of satisfaction with the progress of a new Hospital Information System been implemented. The IT acceptance score of users who were satisfied with implementation progress did not differ from IT personnel but differed significantly from users who were not satisfied with progress. This study has implications for cross culture transfer of IT.

Attitude to Computers↗
PubMed2000

Illness outbreak associated with Escherichia coli O157:H7 in Genoa salami. E. coli O157:H7 Working Group.

BACKGROUND: An outbreak of Escherichia coli O157:H7 infection was identified in the spring of 1998, with a 7-fold increase in the number of laboratory-confirmed E. coli O157:H7 cases in southern Ontario. This prompted an intensive investigation by local, provincial and federal public health officials. METHODS: Case interviews of 25 people from southern Ontario were conducted using a broad food history and environmental exposure survey. Laboratory investigations involved both case and food sampling. Specimens of foods sold locally and reportedly consumed by those affected were tested. Common suppliers of suspected foods were identified by cross-referencing suppliers' lists with stores frequented by those who fell ill. A case-control study involving 25 cases and 49 age-matched controls was conducted. This was followed by a comprehensive environmental investigation of the meat processing plant identified as the source of the E. coli. RESULTS: Thirty-nine outbreak-related cases occurred between April 3 and June 2, 1998. Of the 36 case specimens tested all were positive for E. coli O157:H7. The case-control study identified Genoa salami as the most probable (odds ratio 8 [confidence interval 2-35]) source of the outbreak. Samples of Genoa salami produced by the most commonly identified supplier later tested positive for E. coli O157:H7, and the pathogen matched the same pulsed-field gel electrophoresis pattern and phage type of the case specimens. INTERPRETATION: Our investigation, which led to a national recall of the brand of dry fermented Genoa salami identified as the source of the outbreak, supports an adherence to stringent manufacturing requirements for fermented meat products. A review of the Canadian standards for fermented meat processing and the effectiveness of their implementation is warranted.

Adolescent↗
PubMed2000

Expression of p53 and p21waf1/cip1 in gastric carcinoma: lack of inter-relationship or correlation with prognosis.

AIMS: The cell cycle regulators p53 and p21waf1/cip1 are expressed variably in human cancers. We investigated their expression in gastric carcinoma and determined their inter-relationship and prognostic significance. METHODS: Immunohistochemistry was used to determine their expression in material from 100 resected specimens of gastric carcinoma, and comparison was then made of the degree of expression between each, with conventional clinicopathological indices and with survival. RESULTS: Positivity was found with p53 (40%) and p21 (75%). There was no significant correlation between the expression of each individual marker, nor between each marker and 5-year survival. There appeared to be an association between p53 expression and lymph node metastases, and a higher frequency of p21waf1/cip1 expression in males. CONCLUSIONS: The expression of p53 and p21waf1/cip1 as detected by immunohistochemistry were of no value in predicting the prognosis of patients with gastric carcinoma.

Biomarkers, Tumor↗
PubMed2000

Tonsillectomy and tonsillitis in Cape Town--age and sex of patients.

OBJECTIVES: To assess the sex and age of patients undergoing tonsillectomy in the Cape Town metropolitan area. METHODOLOGY: A retrospective audit was conducted from 1991 to 1995 comparing the sex and age of patients undergoing tonsillectomy with patients admitted to hospital for acute tonsillitis and the general population. RESULTS: A total of 7,250 tonsillectomies were performed for recurrent tonsillitis, and 111 adult patients were admitted with acute tonsillitis. When the data for the adult tonsillectomy patients were isolated, the female/male ratio was 3.22:1, which is highly significant when compared with the data for the general population (Cornfield's 95% confidence limit: 2.82, 3.68) and for patients with acute tonsillitis (Cornfield's 95% confidence limit: 1.14, 2.65). CONCLUSION: Recurrent tonsillitis requiring tonsillectomy occurs more commonly in female than male patients.

Adolescent↗
PubMed1999

Parathyroid and thyroid function five years after treatment of laryngeal and hypopharyngeal carcinoma.

The proximity of the thyroid and parathyroid glands to the larynx and hypopharynx puts them at risk from treatment of squamous cell carcinoma (SCC) of this region. Consequently parathyroid and thyroid function was evaluated in patients surviving at least 5 years following treatment of primary SCC of the larynx or hypopharynx. Twenty-eight patients, initially treated from 1990 to 1992, were assessed and divided into four groups according to treatment received. Hypoparathyroidism (partial and hypocalcaemic) occurred in 88% and hypothyroidism (clinical and subclinical) in 50% in Group 1 (radiotherapy only) Group 2 (salvage laryngectomy for failed radiotherapy) had 66% hypoparathyroid and 33% hypothyroid. Group 3 (surgery + radiotherapy combined) had 89% hypoparathyroid and 89% hypothyroid. Group 4 (surgery only) had 63% hypoparathyroid and 63% hypothyroid. Significant endocrine hypofunction therefore occurs following the treatment of laryngopharyngeal carcinoma, more so with radiotherapy and combined therapy than with surgery alone.

Carcinoma, Squamous Cell↗
PubMed1999

Ethnicity and patterns of spondyloarthritis in South Africa--analysis of 100 patients.

OBJECTIVE: To determine the spectrum and ethnic differences of spondyloarthritis disease patterns in patients attending the Rheumatic Diseases Unit, University of Cape Town, South Africa. METHODS: A retrospective survey of case records of 100 patients with spondyloarthritis seen between January 1988 and January 1995. RESULTS: Of these 100 patients, 71 were male, 53 were Colored [mixed race descendants of Khoisan (Hottentot and Bushmen), Whites, Malays and Black Africans], 40 White, 5 Black and 2 Indian (descendants of immigrants from the Indian subcontinent). Our results show that the prevalence and disease patterns of spondyloarthritis in this South African cohort are comparable to those seen in Europe and North America with respect to clinical and radiological features, as well as therapeutic and orthopedic surgical requirements. No major ethnic differences in disease patterns were observed in White and Colored patients studied. CONCLUSION: The spectrum of spondyloarthritis in South Africa is similar to that seen elsewhere in the world. Our study confirmed the rarity of these conditions in Black South Africans.

Age of Onset↗
PubMed1998

Hypoparathyroidism after the treatment of laryngopharyngeal carcinoma.

Thirty patients with squamous cell carcinoma of the laryngopharynx were treated with surgery (total laryngectomy and hemithyroidectomy) and radiotherapy. Group 1 (n = 7) patients had surgery only; Group 2 (n = 7) had radiotherapy followed by salvage surgery while Group 3 (n = 16) had surgery followed by radiotherapy. Parathyroid hormone and calcium levels were measured pre- and post-operatively and post-radiotherapy. In Group 1 no patients were hypoparathyroid. In Group 2, 29 per cent of patients preoperatively and 57 per cent post-operatively, were hypoparathyroid. In Group 3, no patients were hypoparathyroid pre-operatively, while 25 per cent were hypoparathyroid post-operatively and post-radiotherapy. Parathyroid hormone and calcium levels were averaged and compared within and between each group. There was no significant difference within each group, when comparing levels post-operatively and post-radiotherapy from those of pre-operatively. There was no significant difference in levels between each of Groups 1, 2 or 3 (p > 0.05).

Aged↗
PubMed1998

Evidence for a prostate cancer susceptibility locus on the X chromosome.

Over 200,000 new prostate cancer cases are diagnosed in the United States each year, accounting for more than 35% of all cancer cases affecting men, and resulting in 40,000 deaths annually. Attempts to characterize genes predisposing to prostate cancer have been hampered by a high phenocopy rate, the late age of onset of the disease and, in the absence of distinguishing clinical features, the inability to stratify patients into subgroups relative to suspected genetic locus heterogeneity. We previously performed a genome-wide search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a second prostate cancer susceptibility gene, which by heterogeneity estimates accounts for approximately 16% of HPC cases. This HPC locus resides on the X chromosome (Xq27-28), a finding consistent with results of previous population-based studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28 was observed in a combined study population of 360 prostate cancer families collected at four independent sites in North America, Finland and Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113, theta=0.26, in the combined data set. Parametric multipoint and non-parametric analyses provided results consistent with the two-point analysis. Significant evidence for genetic locus heterogeneity was observed, with similar estimates of the proportion of linked families in each separate family collection. Genetic mapping of the locus represents an important initial step in the identification of an X-linked gene implicated in the aetiology of HPC.

Adult↗
PubMed1998

Suicide in the Northwest Territories: A descriptive review.

The incidence of suicide among the populations of the Northwest Territories (NWT) is notably higher than in the rest of Canada. A comparison of three five-year time periods between 1982 and 1996 reveals an increasing incidence rate, particularly for Nunavat, the eastern half of the NWT, occupied primarily by Inuit people. This is largely attributable to a rising use of hanging as opposed to other methods of suicide. A coroner's record review of suicides occurring between 1994 and 1996 demonstrates the preponderance of young males and of Inuit among those who committed suicide, the majority of whom committed suicide in familiar settings, usually their own homes, and often while others were on the premises. Thirty-six percent of those who committed suicide had experienced a recent family or relationship breakup, and twenty-one percent were facing criminal proceedings. Understanding the impact of these and other reported circumstances on the imminent risk of suicide requires further investigation.

Adolescent↗