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Biomedical subjects

M Shuster

Publications and source records attributed to M Shuster.

At least 19 recordsLinked to original sources
PubMed2000

Chromosomal instability and cytoskeletal defects in oral cancer cells.

Oral squamous cell carcinomas are characterized by complex, often near-triploid karyotypes with structural and numerical variations superimposed on the initial clonal chromosomal alterations. We used immunohistochemistry combined with classical cytogenetic analysis and spectral karyotyping to investigate the chromosomal segregation defects in cultured oral squamous cell carcinoma cells. During division, these cells frequently exhibit lagging chromosomes at both metaphase and anaphase, suggesting defects in the mitotic apparatus or kinetochore. Dicentric anaphase chromatin bridges and structurally altered chromosomes with consistent long arms and variable short arms, as well as the presence of gene amplification, suggested the occurrence of breakage-fusion-bridge cycles. Some anaphase bridges were observed to persist into telophase, resulting in chromosomal exclusion from the reforming nucleus and micronucleus formation. Multipolar spindles were found to various degrees in the oral squamous cell carcinoma lines. In the multipolar spindles, the poles demonstrated different levels of chromosomal capture and alignment, indicating functional differences between the poles. Some spindle poles showed premature splitting of centrosomal material, a precursor to full separation of the microtubule organizing centers. These results indicate that some of the chromosomal instability observed within these cancer cells might be the result of cytoskeletal defects and breakage-fusion-bridge cycles.

Antigens, Nuclear↗
PubMed1999

Frequent allelic loss and homozygous deletion in chromosome band 8p23 in oral cancer.

Frequent loss of heterozygosity on chromosome 8p in a variety of human malignancies, including head and neck cancers, has suggested the presence of a tumor suppressor gene (or genes) associated with the pathogenesis of these cancers. To test the role of genetic alterations at 8p23 in oral carcinogenesis, we studied 51 squamous cell carcinomas of the head and neck and 29 oral squamous cell carcinoma cell lines for allelic loss using 7 microsatellite markers spanning approximately 5 cM of chromosome band 8p23. Twenty-three of 51 tumors (45%) and 23 of 29 cell lines (79%) showed allelic loss at 1 or more loci. Three cell lines showed homozygous deletion of loci within a 3 cM region defined by the markers D8S1781 and D8S262. Our results suggest that a tumor suppressor gene (or genes) is located in 8p23 and is associated with the development and/or progression of oral carcinomas.

Carcinoma, Squamous Cell↗
PubMed1999

Prereduction radiographs in clinically evident anterior shoulder dislocation.

The main study objective was to determine if experienced emergency physicians can accurately identify a subgroup of patients with anterior shoulder dislocation for whom prereduction radiographs do not alter patient management. Our prospective study evaluated 97 patients who presented to 2 ski-hill clinics and to our rural emergency department with possible shoulder dislocation between November 1996 and May 1997. Emergency physicians were certain of shoulder dislocation by clinical examination alone in 40 of 59 cases (67.8%) of possible dislocation. All 40 cases were found to have a dislocation (100%; 95% Cl, 91.19% to 100%), and the prereduction radiograph did not affect management of the injury. Prereduction radiographs added 29.6 +/- 12.68 minutes to treatment. We conclude that shoulder dislocation is often readily apparent from history and physical examination. When the experienced emergency physician is certain of the diagnosis of anterior shoulder dislocation, prereduction radiography delays treatment and does not alter management.

Adolescent↗
PubMed1998

Parental alleles of an imprinted mouse transgene replicate synchronously.

Molecular features of imprinted genes include differences in expression, methylation, and the timing of DNA replication between parental alleles. Whereas methylation differences always seem to be associated with differences in expression, differences in the timing of replication between parental homologs are not always seen at imprinted loci. These observations raise the possibility that differences in replication timing may not be an essential feature underlying genomic imprinting. In this study, we examined the timing of replication of the two alleles of the imprinted RSVIgmyc transgene in individual embryonic cells using fluorescence in situ hybridization (FISH). The cis-acting signals for RSVIgmyc imprinting are within RSVIgmyc itself. Thus, allele-specific differences in replication, if they indeed govern RSVIgmyc imprinting, should be found in RSVIgmyc sequences. We found that the parental alleles of RSVIgmyc, which exhibit differences in methylation, replicated at the same time. Synchronous replication was also seen in embryonic cells containing a modified version of RSVIgmyc that exhibited parental allele differences in both methylation and expression. These findings indicate that maintenance of expression and methylation differences between alleles does not require a difference in replication timing. The differences in replication timing of endogenous imprinted alleles detected by FISH might therefore reflect structural differences between the two alleles that could be a consequence of imprinting or, alternatively, could be unrelated to imprinting.

Alleles↗
PubMed1998

Preparation, attitudes and behaviour in nonhospital cardiac emergencies: evaluating a community's readiness to act.

OBJECTIVE: To determine how people in a moderately sized Ontario city believe they will react if they witness someone colapsing. DESIGN: Telephone survey. SETTING: The cities of Kitchener and Waterloo, part of the Regional Municipality of Waterloo, Ontario, with a combined population of 378,000. PARTICIPANTS: Households were randomly contacted and a questionnaire was administered, provided the respondent was over 44 years of age and agreed to be interviewed. Of 2479 households with eligible respondents, 811 (33%) completed the questionnaire. OUTCOMES: Age, sex, educational level, cardiac risk factors and cardiopulmonary resuscitation (CPR) training of respondents were determined, as well as actions they would take if cardiac arrest occurred in a family member at home or in stranger in the street, and associated emotions and barriers to implementing actions. RESULTS: Among the first three actions that respondents who were not prompted with possible responses said they would take, 311 (72%) witnessing a collapse at home, compared with 166 (44%) witnessing a collapse on the street, would call 911, the police or an ambulance. Other 'first three actions' in home collapse were checking for breathing (120 [28%]), checking for pulse (91 [21%]) and administering CPR (34 [8%]); these actions were less commonly selected in response to a strangers collapse and when respondents were not prompted. Respondents felt they would be more likely to perform CPR on a friend than on a stranger (OR 1.38, 95% CI 1.10 to 1.58). When asked how likely they would be to perform specific acts when witnessing a collapse, 254 (69%) of respondents thought they would call their family doctor and 179 (48%) thought they were likely to begin chest compressions. Barriers to performing CPR centred around legalities and disease transmission. CONCLUSION: Older people do not know how to act effectively in a cardiac emergency. Traditional CPR and public awareness programs have been ineffective in reaching this population; alternative means are required to help the public respond more effectively to cardiac emergencies.

Accidents↗
PubMed1996

FHIT gene alterations in head and neck squamous cell carcinomas.

To determine whether the FHIT gene at 3p14.2 is altered in head and neck squamous cell carcinomas (HNSCC), we examined 26 HNSCC cell lines for deletions within the FHIT locus by Southern analysis, for allelic losses of specific exons FHIT by fluorescence in situ hybridization (FISH) and for integrity of FHIT transcripts. Three cell lines exhibited homozygous deletions within the FHIT gene, 55% (15/25) showed the presence of aberrant transcripts, and 65% (13/20) showed the presence of multiple cell populations with losses of different portions of FHIT alleles by FISH of FHIT genomic clones to interphase nuclei. When the data obtained by FISH and by reverse transcriptase-PCR analyses are combined, 22 of 26 cell lines showed alterations of at least one allele of the FHIT gene. Our data indicate that the FHIT gene is disrupted in HNSCCs and hence, loss of FHIT function may be important in the development and/or progression of head and neck cancers.

Acid Anhydride Hydrolases↗
PubMed1995

Intra-uterine infection in women with preterm premature rupture of membranes: maternal and neonatal characteristics.

OBJECTIVE: Our purpose was to determine the prevalence of intra-uterine infection in patients with preterm premature rupture of membranes and to evaluate the clinical characteristics of women and neonates according to the presence or absence of intrauterine infection. STUDY DESIGN: Trans-abdominal amniocentesis was performed in 90 consecutive patients admitted with preterm premature rupture of membranes. Maternal clinical parameters evaluated included maternal age, origin, gravidity, parity, habitual abortion, previous perinatal death, previous preterm birth, urinary tract infection, fetal distress, abruptio placentae, gestational diabetes, admission-delivery interval and cesarean rate. Neonatal clinical parameters evaluated were gestational age at delivery, birth weight, Apgar score, neonatal gender, perinatal death and neonatal sepsis. RESULTS: The prevalence of intra-uterine infection was 66.6% (60/90). No differences between patients with intra-uterine infection and those without intra-uterine infection were observed in maternal age, origin, gravidity, parity, habitual abortion, previous perinatal death, fetal distress, abruptio placentae, gestational diabetes, admission-delivery interval, cesarean section, neonate's gender, Apgar score at 5 min and neonatal sepsis. On the other hand, gestational age at delivery, birth weight and Apgar score at 1 min were significantly different between the groups. CONCLUSION: An intra-uterine infection was found in two thirds of women presenting with preterm premature rupture of membranes. Women presenting with preterm premature rupture of membranes and intra-uterine infection had a lower gestational age at delivery and consequently had a lower neonatal birth weight than those without intra-uterine infection.

Amniotic Fluid↗
PubMed1995

Effects of prehospital care on outcome in patients with cardiac illness.

STUDY OBJECTIVE: To compare outcomes of patients with acute cardiac illness transported by ambulance for whom prehospital care was provided by emergency medical technician-paramedics (EMT-Ps) or EMTs trained in defibrillation (EMT-Ds). DESIGN: A prospective chart review carried out over 3.5 years. SETTING: The Hamilton-Wentworth region of Ontario, Canada, which covers 1,136 km2 and includes five receiving hospitals. PARTICIPANTS: We prospectively identified 8,720 potentially eligible patients from approximately 30,000 who presented to the ambulance service. We reviewed hospital charts to confirm eligibility. The group of 8,720 patients yielded 3,066 patients with acute cardiac illness who met all other eligibility requirements. We excluded patients in cardiac arrest. RESULTS: Incidence of myocardial infarction (MI), length of hospital stay, and mortality were evaluated. Analysis was performed with chi 2 tests for association, linear regression, and logistic regression. Of the eligible patients who received prehospital EMS care, 783 sustained MIs. The proportions of people discharged alive with the diagnosis of MI did not differ between crew types (P = .16). Average hospital stay was 13 days in both groups for patients with the discharge diagnosis of MI; hospital stay ranged from 9 (EMT-D) to 11 days (EMT-P) for any patient with a discharge diagnosis other than MI. These values were statistically similar. The odds ratio of having had an MI after treatment by an EMT-D crew was 1.02 (95% confidence interval, .86 to 1.21) compared with that for treatment by an EMT-P crew. CONCLUSIONS: In an urban setting with short (less than 10 minutes) average transport times, the availability of prehospital paramedic care does not affect occurrence of MI, length of hospital stay, or mortality of patients presenting to the EMS system with cardiac illness.

Aged↗
PubMed1994

Differential prehospital benefit from paramedic care.

STUDY OBJECTIVES: To determine whether prehospital outcome of patients who receive care from emergency medical technicians-paramedic (EMT-Ps) differs from that of patients who receive care from emergency medical technicians-defibrillation (EMT-Ds), as rated by the treating EMTs using standardized scales, and to determine whether the patient's seriousness of illness is relevant to any differential benefit of one level of care over the other. DESIGN: Historical (retrospective) cohort. SETTING: An urban and semiurban region of southwest Ontario comprising an area of 1,136 square kilometers (438 square miles) with a population of more than 445,000. TYPE OF PARTICIPANTS: Patients (10,291) who were transported by the Hamilton-Wentworth EMS system between January 1, 1991, and December 31, 1991. METHODS AND MEASUREMENTS: EMTs rated the prehospital outcome of their own patients, using scales that had been tested in a previous study. Comparisons between EMT-P- and EMT-D-treated patients were made by chi 2, chi 2 by trend, and Fisher's exact test as appropriate. RESULTS: More seriously ill or injured EMT-P-treated patients were rated as improved and fewer EMT-P-treated patients were rated as worsened compared with similar patients who were cared for and rated by EMT-Ds. The differential benefit from EMT-P to EMT-D care ranged from 8% to 25% for patients rated as "severe" and from 27% to 49% for patients rated as "life-threatened." CONCLUSION: According to the ratings of prehospital care providers, patients classified as "severe" or "life-threatened" had their conditions "improve" by the time they arrived at the hospital more often when care was provided by an EMT-P team than when it was provided by an EMT-D team.

Adult↗
PubMed1993

Reliability of prehospital rating scales for case severity and status change.

The purpose of this report is to determine the reliability and sensibility of the currently available prehospital rating scales by a prospective evaluation of ambulance call reports using generalizability methodology. Sequential samples of emergency call data from the Hamilton Base Hospital Paramedic program database were used to sample calls randomly for a two-phase study. Phase I and II used blinded ambulance call report forms presented to six rates during three sessions in each phase. Generalizability (reliability) coefficients were then generated to determine the degree of reliability for the scales in both phases of the study. The generalizability coefficients for all scales are substantial or excellent using the standards commonly applied to agreement statistics. The conclusion of the study is that all ambulance officers can use the prehospital scales reliably. The reliability of these general measures is one of the parameters that will allow us to evaluate where basic and advanced prehospital care have an impact on overall patient outcome.

Emergency Medical Technicians↗
PubMed1993

Effect of fire department first-responder automated defibrillation.

STUDY OBJECTIVE: To examine the effect of fire department first-responder defibrillation on time to defibrillation in a mid-sized community with two tiers of emergency medical services (EMS) ambulance response. DESIGN: Retrospective cohort. SETTING: The study area was the region of Hamilton-Wentworth, which has more than 445,000 inhabitants and covers 1,136 km2 (438 square miles). TYPE OF PARTICIPANTS: We studied 297 victims of out-of-hospital cardiac arrest presenting to the EMS system between May 1, 1990, and April 30, 1991. MEASUREMENTS AND MAIN RESULTS: The mean defibrillation interval was decreased from 11.96 minutes to 8.50 minutes (P < .001) by the introduction of fire first-responder defibrillation. Survival was significantly greater with bystander-witnessed arrest, initial rhythm of ventricular fibrillation, and presence of a pulse on arrival in the emergency department. CONCLUSION: In our EMS system, fire first-responders were able to provide defibrillation in significantly shorter times than ambulance attendants. Other EMS systems should review their response times and consider instituting first-responder defibrillation as one means of reducing defibrillation intervals.

Aged↗
PubMed1992

Mambin, a potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor structurally related to the short neurotoxins.

The purification, complete amino acid sequence, functional activity, and structural modeling are described for mambin, a platelet glycoprotein GP IIb-IIIa antagonist and potent inhibitor of platelet aggregation from the venom of the Elapidae snake Dendroaspis jamesonii (Jameson's mamba). Mambin is 59 residues in length and contains four disulfide linkages and an RGD amino acid sequence found in protein ligands that bind to GP IIb-IIIa. Mambin inhibits ADP-induced platelet aggregation (IC50 = 172 +/- 22 nM) and inhibits the binding of purified platelet fibrinogen receptor GP IIb-IIIa to immobilized fibrinogen (IC50 = 3.1 +/- 0.8 nM). Mambin has very little sequence similarity to the Viperidae family of platelet aggregation inhibitors, except for the RGD-containing region in the protein. However, mambin does have ca. 47% similarity to the short-chain postsynaptic neurotoxins found in other Elapidae venoms, which do not contain the RGD sequence and do not act as GP IIb-IIIa antagonists. On the basis of its circular dichroism spectrum, mambin has a beta-sheet structure characteristic of the neurotoxins. Molecular modeling of the mambin sequence onto the erabutoxin b structure predicts a very similar structure within the entire protein except for the loop containing the RGD sequence. Mambin may therefore represent a genetic hybrid of neurotoxic and hemotoxic proteins found in snake venoms.

Amino Acid Sequence↗
PubMed1992

Intradialytic parenteral nutrition as a therapy for malnourished hemodialysis patients.

B.H. did not consistently meet the expected outcomes related to maintenance of fluid balance and normal blood glucose levels. Interdialytic episodes of hypotension continued intermittently despite efforts of the multidisciplinary team to frequently assess the patient, alter the treatment plan, and avoid complications. Although postdialysis rebound hypoglycemia occurred, it was infrequent. B.H. did, however, meet the expected patient outcome related to nutrition. His nutritional parameters at the end of IDPN therapy correlated with dramatic improvement in his clinical status. Three months after the termination of the IDPN therapy, he showed continued improvement on oral intake only. Ongoing support from all nephrology professionals permitted this patient to obtain and maintain a desirable weight and nutritional status that eventually led to successful renal transplantation.

Humans↗