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Biomedical subjects

J Mohr

Publications and source records attributed to J Mohr.

At least 19 recordsLinked to original sources
PubMed2007

Helicobacter pylori-induced apoptosis in T cells is mediated by the mitochondrial pathway independent of death receptors.

BACKGROUND: Chronic infection with Helicobacter pylori is related to the pathogenesis of the noncardia carcinoma of the stomach. In this study we investigated the mechanisms of H. pylori-induced apoptosis in T lymphocytes, which could explain a mechanism of immune evasion facilitating chronic inflammation of the mucosa and gastric carcinogenesis. MATERIALS AND METHODS: The supernatant of H. pylori culture was used to study the mechanism of apoptosis induction in human leukaemia T cell lines Jurkat and CEM and in primary T cells. The cytotoxin associated gene A (CagA) and vacuolating cytotoxin A (Vac A) positive bacterial strain H. pylori 60190 (CagA(+), VacA(+)) and as a control the less toxic H. pylori strain Tx30a (CagA(-), VacA(-)) were used to produce the supernatant. Cell death was determined by DNA fragmentation and protein expression by Western blot. RESULTS: H. pylori 60190-induced apoptosis was neither blocked by inhibition of the death ligands TRAIL (TNF-related apoptosis-inducing ligand), CD95L/FasL and TNF-alpha (tumour necrosis factor-a) in wild type Jurkat cells nor in FADD(def) (Fas-associated death domain protein) and caspase-8(def) subclones of the Jurkat cell line. Yet, the pancaspase inhibitor zVAD-fmk could inhibit up to 90% of H. pylori-induced apoptosis. Stable transfection of Jurkat wild type cells with Bcl-x(L and) Bcl-2 resulted in marked reduction of H. pylori-induced apoptosis, showing that the mitochondrial pathway is the key regulator. This is supported by the finding that surviving primary human lymphocytes upregulate Bcl-2 when exposed to H. pylori supernatant. CONCLUSIONS: H. pylori-induced apoptosis of T cells is mediated by the mitochondrial pathway and could create a local environment that facilitates life-long infection by immune evasion.

Apoptosis↗
PubMed2004

Integrating patient safety into the clinical microsystem.

Healthcare institutions continue to face challenges in providing safe patient care in increasingly complex organisational and regulatory environments while striving to maintain financial viability. The clinical microsystem provides a conceptual and practical framework for approaching organisational learning and delivery of care. Tensions exist between the conceptual theory and the daily practical applications of providing safe and effective care within healthcare systems. Healthcare organisations are often complex, disorganised, and opaque systems to their users and their patients. This disorganisation may lead to patient discomfort and harm as well as much waste. Healthcare organisations are in some sense conglomerates of smaller systems, not coherent monolithic organisations. The microsystem unit allows organisational leaders to embed quality and safety into a microsystem's developmental journey. Leaders can set the stage for making safety a priority for the organisation while allowing individual microsystems to create innovative strategies for improvement.

Efficiency, Organizational↗
PubMed2001

Hemodilution - an overview of current canadian practices.

Background. Transplant teams evaluate potential organ and tissue donors to exclude donation of tissues at risk for disease transmission. Standards dictate that serological tests be performed on every donor to assess the presence of transmissible diseases including: Human Immunodeficiency Virus 1 & 2, Human T Lymphotropic Virus 1 & 2, Hepatitis C, Hepatitis B surface Antigen, Hepatitis B core Antibody and Syphilis. A limitation of serological testing is the risk of false negative results due to the dilution of the serum. Hemodilution results from the transfusion of fluids (blood products, colloids and/or crystalloid). Confidence in the accuracy and sensitivity of donor serology testing is of utmost importance to ensure the provision of safe organs and tissues for transplantation.Methods. In order to determine the preferred and validated methodology for determining hemodilution, if any; and to determine the level of hemodilution that jeopardizes serologic test results, we reviewed the literature and current testing practices. Tissue banks throughout Canada as well as accrediting bodies were contacted regarding the hemodilution algorithm they utilize.Results. In the absence of a pretransfusion sample, hemodilution calculations are the prevalent methodology for assessing sensitivity of serology testing. A literature search and personal communications provided no documentation on the validation of any hemodilution algorithm or evidence that 50% hemodilution is an acceptable level for accurate serology testing.Conclusion. A validation of hemodilution algorithms and the acceptable or unacceptable rate of hemodilution is required. The utilization of a validated algorithm should be mandated in standards to ensure continuity of practice by all transplantation centres. If validation cannot be obtained, alternative methodologies for serology testing should be investigated.

Journal Article↗
PubMed2000

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

BACKGROUND: Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. OBJECTIVE: To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. DESIGN: Prospective, observational study. SETTING: HIV clinics in a Veterans Affairs medical center and a university medical center. PATIENTS: 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). MEASUREMENTS: Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). RESULTS: During the study period, 45,397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. CONCLUSIONS: Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.

Adult↗
PubMed1999

Quality of life in patients with human immunodeficiency virus infection: impact of social support, coping style and hopelessness.

We aimed to determine whether the quality of life (QOL) in the patients infected with human immunodeficiency virus (HIV) infection was influenced by satisfaction with social support, coping style and hopelessness. One hundred and thirty-eight HIV-infected patients were prospectively studied in this multicentre, longitudinal study. The QOL was assessed by Medical Outcome Study Health Survey SF-36, social support by Sarason Social Support Questionnaire, hopelessness by Beck Hopelessness Scale, and coping by Billing and Moos Inventory of coping with illness. The QOL did not correlate with age, sex, race, HIV risk factor, education or marital status. Employment (P = 0.0001), higher income (P = 0.03), satisfaction with social support (P = 0.04), regardless of the source of that support, and problem-focused coping (P = 0.03) were associated with a significantly better QOL, while, emotion-focused coping (r = -0.19, P = 0.04), avoidant coping (r = 0.40, P = 0.0001), hopelessness (r = -0.64, P = 0.0001) and AIDS (P = 0.09) were predictors of poorer QOL. Physical functioning correlated positively with employment (P = 0.0001), and inversely with AIDS (P = 0.0002), hopelessness (P = 0.03), avoidant coping (P = 0.03), and age (P = 0.10). At 6 months follow up, QOL score had changed in 20% of the patients; older age (P = 0.01), and lesser satisfaction with social support (P = 0.15) were associated with a decline in QOL, while adherence with antiretroviral therapy (P = 0.006) was associated with an increase in QOL score. Seven of 138 patients died during follow up; these patients had significantly lower QOL at baseline than all other patients (P = 0.003). Interventions to alleviate hopelessness, maladaptive coping, and enhancement of satisfaction with social support may improve overall QOL in HIV-infected patients. Older patients with HIV were less satisfied with their social support, were more likely to utilize unhealthy coping styles, and experienced a greater decline in QOL over time.

Adult↗
PubMed1997

Does a cheaper mask save money? The cost of implementing a respiratory personal protective equipment program.

OBJECTIVE: To determine the annual cost of implementing and maintaining a respiratory personal protective equipment (PPE) program at an urban hospital. SETTING: St Clare's Hospital and Health Center, a 250-bed hospital in Manhattan that treats 60 to 100 cases of tuberculosis annually. METHODS: Review of Purchasing Department records for all masks acquired by the hospital from 1992 to 1995, and an estimate of administrative time spent developing and implementing the guidelines recommended by various agencies during the study interval. RESULTS: Respiratory isolation was provided for 6,360 to 10,883 days annually during the 4-year interval. Yearly costs for the PPE program ranged from $86,560 to $175,690. Of note, the daily cost for a respiratory isolation day decreased dramatically between 1994 and 1995 ($25/day to $13/day), when the high-efficiency particulate air-filter (HEPA) respirator was used by all staff. The decrease occurred because of lower administrative costs and a sharp decrease in the numbers of HEPA units purchased. Objective measures of worker compliance with HEPA respirators demonstrated the decrease was not due to less HEPA use but rather that employees were using each HEPA unit for several weeks, as recommended. CONCLUSION: We found a significant decrease in cost in the second year of our HEPA program due to increasing employee familiarity with the program. Newly approved, cheaper, but less durable, N-95 masks are unlikely to withstand multiple wearings and may be discarded after a few uses. Thus, cheaper masks may result in a more expensive PPE program.

Cost-Benefit Analysis↗
PubMed1996

Dombrock blood group (DO): assignment to chromosome 12p.

The Dombrock blood group system (DO) is a common polymorphism in Caucasians, represented by two red cell antigen alleles. In a linkage study in our family material of 832 families from the Copenhagen area, we found a strong indication of tight linkage with the two flanking DNA polymorphisms D12S358 (z = 7.66; at theta M = 0.001, theta F = 0.031) and D12S364 (z = 8.53; at theta M = 0.068, theta F = 0.031). DO is assigned to the region 12p13.2-12p12.1 by physically localised markers.

Blood Group Antigens↗
PubMed1996

Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis.

BACKGROUND & AIMS: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within affected families. The purpose of this study was to assess the age-specific cancer risk in a large series of gene carriers. METHODS: Thirty-four families were studied by mutation analysis. In 19 of these families, pathogenic mutations were found at hMSH2 or hMLH1. Of 382 relatives, 124 had a mutation in hMLH1 and 86 in hMSH2. RESULTS: The lifetime risk of colorectal cancer was the same in both groups of gene carriers (80%). The risk of endometrial cancer was greater in hMSH2 gene carriers compared with hMLH1 gene carriers (61% vs. 42%), but the difference was not statistically significant. A very high relative risk of cancer of the small bowel (relative risk of >100) was observed in carriers of either gene. Only the carriers of hMSH2 mutations had a significantly increased relative risk of cancer of the urinary tract (kidney and ureter) (relative risk of 75.3), stomach (relative risk of 19.3), and ovaries (relative risk of 8.0). CONCLUSIONS: This study provides estimates of cancer risk that may contribute to the appropriate management of gene carriers within families with hereditary nonpolyposis colorectal cancer.

Adolescent↗
PubMed1996

Assignment of genes coding for brown eye colour (BEY2) and brown hair colour (HCL3) on chromosome 15q.

Brown eye colour (BEY), or total brown iris pigmentation is one of the most common phenotypes of iris colour. Data of eye colour as well as hair colour were obtained for linkage analysis through an enquiry in our family material of 832 families from Copenhagen area. By exclusion mapping with 80 markers in 120 segregating families and 290 markers in 5 segregating families, we obtained some indication of a locus BEY2 for brown eye colour on chromosome 15. For possible confirmation, we selected a total of 45 families from our DNA bank segregating for BEY. All these were tested for chromosome 15 markers in the area between D15S11 and CYP19. We found a strong indication of tight linkage with the DNA polymorphism D15S165 (Z = 24.25; theta M = F = 0.010) and with the flanking markers D15S156 (Z = 14.04; theta M = F = 0.0.029) and D15S144 (Z = 12.99; theta M = F = 0.060). BEY2 is assigned to the region 15q11-15q21 by physically localized markers. A new locus for brown hair colour (HCL3) was localized by indication of linkage to BEY2 in our 45 families segregating for BEY (Z = 9.93; theta M = F = 0.10). The gene (DN10 or P) homologous to the pink-eye-dilution gene (p) in mice could be a candidate gene for BEY2 or for HCL3.

Chromosome Mapping↗
PubMed1996

Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant cancer susceptibility condition. Inherited mutations in at least four DNA mismatch repair genes, hMSH2, hMLH1, hPMS1, and hPMS2, are known to cause HNPCC. In this study we used denaturing gradient gel electrophoresis (DGGE) to screen for hMLH1 mutations in 34 unrelated HNPCC families (30 Dutch, 3 Italian, and 1 Danish). Ten novel pathogenic germ-line mutations (seven affecting splice sites, two frameshifts, and one in-frame deletion of a single amino acid) have been identified in 12 (35%) of these families. In a previous study, hMSH2 mutations were found in 21% of the same families. While the spectrum of mutations at the hMSH2 gene among HNPCC patients appears heterogeneous, a cluster of hMLH1 mutations has been found in the region encompassing exons 15 and 16, which accounts for 50% of all the independent hMLH1 mutations described to date and for > 20% of the unrelated HNPCC kindreds here analyzed. This unexpected finding has a great practical value in the clinical scenario of genetic services.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Executive function in children with Tourette syndrome and/or attention deficit hyperactivity disorder.

Tourette Syndrome (TS) in children is associated with various neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD). Children with TS and ADHD show some difficulties with neuropsychological tasks, but we do not know if children with TS alone have neuropsychological deficits. To assess specific cognitive differences among children with TS and/or ADHD, we administered a battery of neuropsychological tests, including 10 tasks related to executive function (EF), to 10 children with TS-only, 48 with ADHD-only, and 32 with TS + ADHD. Children in all groups could not efficiently produce output on a timed continuous performance task [Test of Variables of Attention (TOVA) mean reaction time and reaction time variability]. Children with TS-only appeared to have fewer EF impairments and significantly higher perceptual organization scores than children with TS + ADHD or ADHD-only. These findings suggest that deficiencies in choice reaction time and consistency of timed responses are common to all three groups, but children with TS-only have relatively less EF impairment than children with TS + ADHD or ADHD-only.

Adolescent↗
PubMed1995

Assignment of dominant inherited nocturnal enuresis (ENUR1) to chromosome 13q.

Nocturnal enuresis, or nightly bedwetting in children more than seven years of age affects about 10% of seven-year-old children, with a wide range of frequencies between populations. The affliction is often linked to major social maladjustments and occupies considerable time in general practice. From the age of seven there is a spontaneous cure rate of 15% per year, such that few remain affected after the age of 16 years. There are two types of nocturnal enuresis: type I (PEN1, primary) with at least three nightly episodes in children above seven years, where the child has always had the disorder and type II (secondary) where the child has been dry for at least six months, but enuresis has recurred. Among some 400 Danish, mostly three-generation families, we have found 17 families with nocturnal enuresis. Eleven of these family had type I nocturnal enuresis (PEN1) that appeared to follow an autosomal dominant mode of inheritance with penetrance above 90%. We now describe strong evidence of linkage with the DNA polymorphisms D13S291 (Z = 3.55; theta M = F = 0.07) and D13S263 (Z = 2.67; theta M = F = 0.08). Multipoint analysis indicates that these markers flank the disease locus at chromosome 13q13-q14.3.

Adolescent↗
PubMed1995

An analysis of two discrepancy-based models and a processing-deficit approach in identifying learning disabilities.

The incidence of learning disabilities (LD) in a research center sample of 107 boys and 103 girls between 6 and 12 years of age was calculated using Wechsler IQ and Woodcock-Johnson cluster scores in a regression model (REG) and a reliability model (REL). The REL method identified LD three times more often than the REG method, and all those identified by REG were also identified by REL. When stratified by IQ, REG and REL identified similar percentages in the lowest IQ group; however, REG identified at a lower rate as IQ increased. All 87 children identified with reading disabilities (both REL-RD and REG-RD) were weak to a similar extent on phonemic awareness. Comorbid elevated attention ratings were found in 62% of children with RD; 26% had elevated attention ratings but no linguistic processing deficits, and 21% had at least one linguistic processing deficit but no attentionally suspect rating.

Attention Deficit Disorder with Hyperactivity↗
PubMed1994

Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate.

The nationwide Danish polyposis register includes all known Danish cases of familial adenomatous polyposis (FAP) and their relatives. By identifying all FAP patients born between 1920 and 1949, we found the frequency of the disease to be 1 in 13,528. By comparing the number of affected and nonaffected offspring born to affected parents during the same period we found the penetrance of the disease for inherited cases to be close to 100% at the age of 40 years. The mutation rate found by the direct method was 9 mutations per million gametes per generation and the proportion of new mutants was estimated to 25%. Fitness for patients between 15 and 29 years was found close to one, while for patients older than 30 the fitness was reduced, but increasing during the three decades (from 0.44 to 0.71) probably because treatment became more widespread and efficient. As we have used the overall fitness in the period, 0.87, to estimate the mutation rate by the indirect method, we found a lower value than by the direct method, namely 5 mutations per million gametes per generation.

Adenomatous Polyposis Coli↗
PubMed1994

Assignment of granular corneal dystrophy Groenouw type I (CDGG1) to chromosome 5q.

Granular corneal dystrophy Groenouw type I (CDGG1) is an autosomal dominant disease with complete penetrance. 124 blood samples were collected from a single Danish pedigree of seven generations. Linkage was discovered with markers on chromosome 5q, with IL9 (Z = 15.96; theta M = 0.027, theta F = 0.00) and D5S436 (Z = 11.75; theta M = 0.00, theta F = 0.081) flanking the disease locus most closely. The marker IL9 is located in the region 5q22-q32. By multilocus linkage analysis the most likely position of CDGG1 among 9 markers was: D5S396-IL9-CDGG1-D5S436-D5S210/D5S207++ +-D5S434-D5S119-D5S211 and CDGG1-D5S402-D5S434. In each of two independent small pedigrees, in which a milder form of CDGG1 occurs, the disease gene was also linked to IL9 (Z = 3.02 at theta = 0.0 in males and females); i.e. the severe and the milder forms may be allelic.

Child↗
PubMed1993

Use of ultrahigh frequency ventilation in patients with ARDS. A preliminary report.

STUDY OBJECTIVE: Our objective was to compare the efficacy of ultrahigh frequency ventilation (UHFV) (frequencies > 3 Hz) with respect to oxygenation, airway pressures, and hemodynamic parameters in patients with adult respiratory distress syndrome (ARDS) who were not responding to conventional ventilation. DESIGN: We used a prospective, multicenter, nonrandomized study design in which each patient served as his own control. SETTING: Three university-affiliated, tertiary-care medical centers participated. PATIENTS: Persons aged 16 to 79 years old with ARDS and unresponsive to conventional ventilation, as defined by a Food and Drug Administration (FDA) approved protocol, were included. INTERVENTIONS: Ninety patients who were not responding to conventional ventilation were changed to UHFV using a microcomputer-controlled device. MEASUREMENTS AND RESULTS: The patient's blood gas, hemodynamic, and airway pressure variables were measured just before, and at 1 and 24 h after the switch to UHFV. We demonstrated clinically significant improvements in arterial oxygen tension (PaO2) and reductions in peak and mean inspiratory pressures. CONCLUSIONS: In a multicenter study, UHFV improved respiratory gas exchange and reduced airway pressure variables at both 1 h and 24 h after the onset of UHFV when compared with conventional ventilation just prior to the change and without hemodynamic deterioration, in patients with severe ARDS.

Adolescent↗
PubMed1992

[Preclinical and prenatal diagnosis of familial adenomatous polyposis].

In order to investigate the possibility of preclinical and prenatal genetic diagnosis of familial adenomatous polyposis (FAP) by means of DNA-systems and other markers, blood samples were collected from 246 persons in 29 families, including 90 with the clinical diagnosis FAP and 73 clinically unaffected first degree relatives (persons at risk). The material was studied with up to 4 DNA-marker systems located in the region around the disease gene. Among the first degree relatives eight (11%) had probably inherited the disease gene, while 31 persons (42%) in this risk group had probably not inherited the gene. It was not possible to evaluate the risk in the remaining 34 persons (47%). In 45 (85%) out of 53 persons under 40 years the DNA-systems were informative, so that it would be possible to offer the option of prenatal diagnosis. It is concluded that preclinical and possibly prenatal genetic diagnosis may be offered; but the current practice of prophylactic proctosigmoidoscopic surveillance should be maintained.

Adenomatous Polyposis Coli↗