Biomedical subjects

L Cobb

Publications and source records attributed to L Cobb.

At least 19 recordsLinked to original sources

PubMed1998

Investigation of lung tumour induction in C3H/HeH mice, with and without tumour promotion with urethane, following paternal X-irradiation.

In series of papers Nomura has reported that parental irradiation can lead to an enhanced incidence of lung and other tumours. However, in a recent study with BALB/cJ mice, using optimum conditions as defined by Nomura, we were unable to confirm this. We have now repeated the investigation using a different inbred strain, C3H/HeH, with and without tumour promotion in the F1 by urethane, again using protocols defined by Nomura. In a series of replicate studies spanning over 2 years, males were exposed to single, acute doses of 0, 250 and 500 cGy X-rays and thereafter placed with two females each in each of two consecutive weeks. Half the offspring from each treatment group and each week of mating were given 5 mmol/kg body weight of the urethane, while the remainder remained untreated. Most of the offspring produced were killed and scored for lung tumours at 6 months of age, while the rest were examined at 12 months of age. The proportion of fertile females and litter size provided evidence of a dose-dependent mutational response to the paternal irradiation, but no trace of a radiation-enhanced lung tumour incidence was detected among the progeny, whether in the urethane or non-urethane groups at 6 or 12 months of age, and whether assessed by numbers of mice with tumours, clusters of tumours, or cluster size. As seen in the BALB/cJ study, significant differences among different replicates were found, again suggesting a cyclical or seasonal variation in tumour incidence, but the variations seen with the two strains were not the same. The need for concurrent controls for tumour work was, nevertheless, again indicated. The overall findings do not therefore accord with those of Nomura. Furthermore, they do not support the causal association between the raised incidence of childhood leukaemia and non-Hodgkins lymphoma near Sellafield and the father's recorded radiation exposure during employment in the nuclear industry, as suggested by the Gardner report.

Animals↗

PubMed1998

Public locations of cardiac arrest. Implications for public access defibrillation.

BACKGROUND: The purpose of this study was to describe the public locations of cardiac arrest and to estimate the annual incidence of cardiac arrest per site to determine optimal placement of automatic external defibrillators (AEDs). This was a retrospective cohort study. METHODS AND RESULTS: Locations of cardiac arrest were abstracted from data collected by emergency medical service programs in Seattle and King County, Washington, from January 1, 1990, through December 31, 1994. Types of commercial and civic establishments were tallied and grouped into 23 location categories consistent with Standard Industrial Codes, and the number of sites within each location category was determined. With the addition of "public outdoors" and "automobiles" as categories, there were 25 location categories. During the study period, 7185 arrests occurred, 1130 (16%) of which were in public locations. An annual incidence of cardiac arrest per site was calculated. Ten location categories with 172 sites were identified as having a higher incidence of cardiac arrest (> or = .03 per year per site). Thirteen location categories had a lower incidence of arrest (< or = .01 per year per site). There were approximately 71,000 sites within these categories. CONCLUSIONS: Placement of 276 AEDs in the 172 higher-incidence sites would have provided treatment for 134 cardiac arrest patients in a 5-year period, 60% of whom were in ventricular fibrillation. We estimate between 8 and 32 lives could be saved in 5 years. To cover the remaining 347 arrests occurring in public in a 5-year period, defibrillators would have to be placed in 71,000 sites, not including outdoors and automobiles. Placement of AEDs in public locations can be guided by the site-specific incidence of arrest.

Electric Countershock↗

PubMed1998

Imprinting of distal mouse chromosome 2 is associated with phenotypic anomalies in utero.

Previous studies have shown that the distal region on mouse chromosome (Chr) 2 is subject to imprinting as mice with maternal duplication/paternal deficiency (MatDp.dist2) and the reciprocal (PatDp.dist2) for this region exhibit phenotypic anomalies at birth and die neonatally. We show here that imprinting effects are detectable in utero. Notably PatDp.dist2 embryos show an increase in wet weight compared with normal, which peaks at 16.5 d post coitum (dpc), and diminishes by birth, whereas the wet weight of placenta is slightly reduced in the latter half of gestation. Newborns have increased length of the long bones. By contrast, the wet weight of MatDp.dist2 embryos decreases during the second half of gestation. Measurements of dry weights of embryos at 16.5 dpc have indicated that there is no difference in either PatDp.dist2 or MatDp.dist2 compared with normal so that the wet weight differences are due to fluid retention in PatDp.dist2 but fluid loss in MatDp.dist2. In PatDp.dist2 embryos excess fluid is particularly prominent in the subcuticular skin layer, whereas by birth fluid is evident around the neck and tongue. At 16.5 dpc the PatDp.dist2 embryos are severely oedematous, as the average fluid content per unit dry weight per embryo was increased by 40%, whereas the MatDp.dist2 embryos are dehydrated as the average water content per unit dry weight per embryo was reduced by 6%. A preliminary conclusion is that there is neither growth enhancement in PatDp.dist2 nor growth retardation in MatDp.dist2 offspring.

Animals↗

PubMed1998

Covering the "open abdomen": a better technique.

"Damage control" in severe abdominal trauma, abdominal compartment syndrome, necrotizing fasciitis of the abdominal wall, and necrotizing pancreatitis often preclude closure of the fascia after laparotomy. Many techniques have been reported for temporary coverage of the exposed viscera, but most have had documented problems. We report the successful use, since 1989, of a temporary sutureless coverage. The viscera are covered with omentum when possible, then with a clear plastic sheet. Sump drains are placed over this layer. The entire abdomen is then covered with two layers of iodophor-impregnated adhesive plastic drape. The last 50 patients managed with this technique are reported. The most common indication (27 patients) was for treatment of severe abdominal trauma. There were no wound infections, fasciitis, or bowel obstruction. Eighteen patients died; no deaths were related to abdominal closure. Temporary abdominal covering with adhesive plastic sheeting is a rapid, safe, and readily available method for managing the open abdomen. This technique provides a physiologic milieu for the abdominal viscera, simplifies nursing care, and promotes safe closure of the abdomen at a later time.

Abdomen↗

PubMed1996

Diastolic blood pressure and the risk of primary cardiac arrest among pharmacologically treated hypertensive patients.

BACKGROUND: Previous studies have raised the concern that the reduction of diastolic blood pressure below 85 mm Hg among treated hypertensive patients may have cardiac hazards. However, these reports have not fully assessed potential confounding from coexisting cardiovascular disease. METHODS: We conducted a population-based case-control study to examine the relation between treated diastolic blood pressure and the risk of primary cardiac arrest among hypertensive patients free of clinically diagnosed cardiovascular disease. Cases were hypertensive enrollees of the Group Health Cooperative of Puget Sound, an HMO, who had primary cardiac arrest between 1977 and 1990 (n = 80). Control patients were a stratified random sample of hypertensive enrollees (n = 426). Ambulatory-care records were reviewed to assess blood pressures and other clinical characteristics. Medication use was assessed through the HMO computerised pharmacy database. RESULTS: Logistic regression models suggested a curvilinear relation between the level of treated diastolic blood pressure and the risk of primary cardiac arrest, after adjustment for pretreatment diastolic blood pressure, antihypertensive therapy, and other potential confounders. Compared with a treated diastolic blood pressure of 85 mm Hg, a treated diastolic blood pressure of 80 mm Hg was associated with a small increase in risk (relative risk [RR] 1.2; 95% confidence interval [CI] 1.0, 1.6), 75 mm Hg was associated with a modest increase in risk [RR 1.6; 95% CI 1.2, 2.1], and 70 mm Hg was associated with more than a twofold increase in the risk of primary cardiac arrest [RR 2.3; 95% CI 1.4; 3.8). There was little evidence of effect modification by pretreatment diastolic blood pressure. CONCLUSIONS: Our findings support available evidence that among hypertensive patients a treated diastolic blood pressure level below 85 mm Hg is associated with cardiac hazards.

Antihypertensive Agents↗

PubMed1995

Perinuclear anti-neutrophil cytoplasmic antibodies are spontaneously produced by mucosal B cells of ulcerative colitis patients.

Approximately 60% of sera from ulcerative colitis (UC) patients contains Igs reactive with neutrophil components, raising the question of the origin of these anti-neutrophil cytoplasmic Abs (ANCA). Our assertion that ANCA is a marker for a mucosal disease-related immune response predicts the existence of ANCA producing B cell clones in the lamina propria lymphocyte (LPL) fraction of UC patients. This hypothesis was tested by examining 12-day culture supernatants of LPL ANCA expression. LPL were isolated from surgically removed mucosa from patients with UC, Crohn's disease (CD), and diverticulitis. Normal mucosa was obtained from accident victims or normal margins of colon cancer resections. Supernatants were assayed by a fixed neutrophil ELISA. The ANCA staining pattern of supernatants expressing ANCA, as determined by ELISA, was assessed by indirect immunofluorescent staining of alcohol-fixed neutrophils. ANCA was found in 70% of culture supernatants from UC LPL fractions. In contrast, only approximately 11% of supernatants from CD and diverticulitis/normal (noninflammatory bowel disease (IBD)) LPL displayed ANCA binding. A perinuclear (pANCA) staining pattern was obtained with 70% of ANCA-expressing UC LPL supernatants, whereas ANCA-expressing CD and non-IBD LPL supernatants displayed a cytoplasmic reaction. PBL and mesenteric lymph node lymphocytes lacked spontaneous pANCA production, and pANCA production from PBL was not inducible. These findings indicate the existence of pANCA-producing B cell clones in mucosal lesions of UC patients and support our hypothesis that pANCA production is a consequence of a mucosal immune response specific to UC.

Autoantibodies↗

PubMed1995

Segregation of pANCA antigenic recognition by DNase treatment of neutrophils: ulcerative colitis, type 1 autoimmune hepatitis, and primary sclerosing cholangitis.

Antineutrophil cytoplasmic antibodies (ANCA) have been identified in the serum of 50-80% of ulcerative colitis (UC) patients. UC-associated ANCA yield a perinuclear staining pattern (pANCA) with alcohol-fixed neutrophils. More recently, pANCA have been detected in the serum of patients with primary sclerosing cholangitis (PSC) and other autoimmune liver diseases. Up to 70% of PSC patient sera and up to 92% of sera from patients with well-defined type 1 autoimmune hepatitis (type 1 AIH) were found to express pANCA. Such expression by patients with PSC and type 1 AIH raises questions concerning the relationship of these pANCA to each other and to that of UC. Differences and similarities in pANCA characteristics are found among the three diseases, suggesting the use of pANCA to define specific disease subgroups. Our recent finding that the UC-associated pANCA reactive antigen was localized within the nuclear domain prompted an examination of whether DNase treatment of neutrophils would alter antigenic recognition by the pANCA of UC, PSC, and type 1 AIH. While loss of antigenic recognition after DNase digestion of neutrophils was a dominant feature of the UC-associated pANCA, the majority of PSC and type 1 AIH pANCA recognized cytoplasmic constituents. These results further support the feasibility of defining and/or distinguishing disease subgroups based on the characterization of respective pANCA.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1995

Investigation of lung tumour induction in BALB/cJ mice following paternal X-irradiation.

Evidence of an enhanced incidence of lung tumours (benign adenomas and adenocarcinomas) was sought in the BALB/cJ mouse following paternal germ cell X-irradiation. In a series of replicate studies spanning approximately 1 year, males were exposed to single, acute X-ray doses of 0, 250 and 500 cGy. In each of the 2 consecutive weeks immediately thereafter they were placed with two females to generate progeny that were derived from irradiated post-meiotic cells (spermatozoa to late spermatids). These animals were then examined at 8 or 12 months for lung tumours. While the proportion of fertile females and mean litter size was affected by the radiation, showing a dose-dependent, dominant lethal response, and while cases of mutant offspring were detected, the paternal radiation did not affect lung tumour incidence in the offspring. The incidence did not vary significantly between germ cell stages irradiated (week of mating), sex of offspring, or radiation dose. However, significant differences between lung tumour incidence (mostly representing benign adenomas) were found between different replicates, these being high at the start of the study, declining and then rising to yet higher levels at its close. The finding that lung tumour incidence in BALB/cJ mice is not affected by paternal germ cell irradiation does not accord with Nomura's reports using other strains of mice. This, in turn, weakens biological support for a causal association between the raised incidence of childhood leukaemia and non-Hodgkin lymphoma near Sellafield and the father's recorded radiation exposure during employment by the nuclear industry.

Adenoma↗

PubMed1995

Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus.

The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased expression and result in yellow coat color. Other associated effects are obesity, diabetes, and increased susceptibility to tumors. To try to define important functional domains of the agouti protein, we have analyzed the molecular defects present in a series of recessive viable agouti mutations. In total, six alleles (amJ, au, ada, a16H, a18H, ae) were examined at both the RNA and DNA level. Two of the alleles, a16H and ae, result from mutations in the agouti coding region. Four alleles (amJ, au, a18H, and ada) appear to represent regulatory mutations that down-regulate agouti expression. Interestingly, one of these mutations, a18H, also appears to cause an immunological defect in the homozygous condition. This immunological defect is somewhat analogous to that observed in motheaten (me) mutant mice. Short and long-range restriction enzyme analyses of homozygous a18H DNA are consistent with the hypothesis that a18H results from a paracentric inversion where one end of the inversion maps in the 5' regulatory region of agouti and the other end in or near a gene that is required for normal immunological function. Cloning the breakpoints of this putative inversion should allow us to identify the gene that confers this interesting immunological disorder.

Agouti Signaling Protein↗

PubMed1995

Nuclear localization of the antigen detected by ulcerative colitis-associated perinuclear antineutrophil cytoplasmic antibodies.

Antineutrophil cytoplasmic antibodies (ANCAs) identified in the serum of 50 to 80% of ulcerative colitis (UC) patients yield a perinuclear staining pattern (pANCA) with alcohol-fixed neutrophils. The ANCAs of UC are distinguishable from those described for Wegener's granulomatosis and other vasculitidies. These various non-UC ANCAs recognize neutrophil granule constituents, but the antigenic moiety specific for the UC pANCA remains unknown. Although the perinuclear nature of some ANCA reactions is an artifact of the alcohol fixation of neutrophils, which causes cytoplasmic granules to redistribute around the nucleus, the UC pANCA reaction has been found not to be similarly affected. We postulated a nuclear localization for the UC-associated pANCA antigen and used both confocal laser microscopy and immunoelectron microscopy to examine the neutrophil reaction of UC-associated pANCA-containing sera. Confocal microscopy revealed a nuclear reaction for 88% (22/25) of the sera with 72% (18/25) showing the reaction localizing to the inner side of the nuclear (membrane) periphery. Immunoelectron microscopy showed that the UC-associated pANCA reaction localized primarily over chromatin concentrated toward the nuclear periphery, although the sera did not recognize double-stranded DNA. These results confirm the nuclear localization of the UC-associated pANCA antigen.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1994

Diuretic therapy for hypertension and the risk of primary cardiac arrest.

BACKGROUND: The results of trials of the primary prevention of coronary heart disease have suggested that treating hypertension with high doses of thiazide diuretic drugs might increase the risk of sudden death from cardiac causes. In contrast, treatment with low doses of thiazide reduces the risk of coronary heart disease. METHODS: To examine the association between thiazide treatment for hypertension and the occurrence of primary cardiac arrest, we conducted a population-based case-control study among enrollees of a health maintenance organization. The case patients were 114 persons with hypertension who had a primary cardiac arrest from 1977 through 1990. The control patients were a stratified random sample of 535 persons with hypertension. The patients' treatment was assessed with the use of a computerized pharmacy data base. Records of their ambulatory care were reviewed to determine other clinical characteristics. RESULTS: The risk of primary cardiac arrest among patients receiving combined thiazide and potassium-sparing diuretic therapy was lower than that among patients treated with a thiazide without potassium-sparing therapy (odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). As compared with low-dose thiazide therapy (25 mg daily), moderate-dose therapy (50 mg daily) was associated with a moderate increase in risk (odds ratio, 1.7; 95 percent confidence interval, 0.7 to 4.5), and high-dose therapy (100 mg daily) was associated with a larger increase in risk (odds ratio, 3.6; 95 percent confidence interval, 1.2 to 10.8) (P value for trend, 0.02). The addition of a potassium-sparing drug to low-dose thiazide therapy was associated with a reduced risk of cardiac arrest (odds ratio, 0.4; 95 percent confidence interval, 0.1 to 1.5). CONCLUSIONS: Both the dose of thiazide drugs and the addition of potassium-sparing drugs influence the risk of primary cardiac arrest. These results may explain the differences in the effect of antihypertensive therapy on mortality from coronary heart disease in previous clinical trials.

Aged↗

PubMed1993

Analysis of childhood pedestrian deaths in New Mexico, 1986-1990.

STUDY OBJECTIVE: To determine if the mechanism of fatal childhood pedestrian injuries correlated with location, injury pattern, and age of the pedestrian and to determine ethnic differences in fatality rates. DESIGN: Retrospective review of state medical investigator reports and autopsies from 1986 to 1990. Logistic regression and chi 2 were used to test for statistically significant differences between the groups in our data set. TYPE OF PARTICIPANTS: New Mexican children, 0 to 14 years old fatally injured by moving vehicles. RESULTS: Sixty-four children died for an overall fatality rate of 3.8 (per 100,000). Native American children and children younger than 5 years experienced the highest fatality rates. Children younger than 5 years were more likely to be crushed under the wheels of a slow-moving vehicle in both a nontraffic and a traffic location, whereas older children were found more often to have died from injuries from a high-speed impact event in a traffic location (P < .001). Leg fractures (P = .001) and spinal fractures (P = .02) occurred more frequently in impact than crush injuries. CONCLUSION: Young children are at risk for a crush injury in both the traffic and nontraffic environment.

Accidents, Traffic↗

PubMed1993

Socioeconomic status and prediction of ventricular fibrillation survival.

OBJECTIVES: The association between socioeconomic status and cardiac arrest is less well known than some other associations with cardiac arrest. We used property tax assessments as a measure of socioeconomic status in a study of victims of out-of-hospital cardiac arrest found in ventricular fibrillation. METHODS: We studied patients attended by the Seattle Fire Department's emergency medical services system between May 1986 and August 1988. During the period studied, 356 episodes met the study criteria; 114 (32%) of these patients survived without major neurologic deficit. Residential property tax assessments were available for 253 of the patients. RESULTS: After adjustments were made for age, witnessed collapse, bystander-initiated cardiopulmonary resuscitation, time from call to paramedic arrival, activity, location of collapse, and chronic morbidity, an association of survival with greater assessed value per living unit was observed. An increase of $50,000 in value per unit was associated with a 1.6-fold increase in survival rate. CONCLUSIONS: Not only are persons in the lower socioeconomic strata at greater risk for cardiac mortality, but they are also less likely to survive an episode of out-of-hospital cardiac arrest.

Aged↗

PubMed1993

Pseudomyxoma peritonei.

Pseudomyxoma peritonei results from implantation of malignant tumors or irritation from ruptured benign cysts. This disease is traditionally characterized by accumulation of mucinous ascites, relatively long survival period and absence of extraperitoneal metastases. Disease progression is difficult to predict because of the spectrum of underlying pathologic entities. Four unusual instances of pseudomyxoma peritonei are presented. An instance of the neoplasm confined to the splenic parenchyma suggests potential for hematogenous dissemination. The tumor can be limited to and extend along the retroperitoneum. Retained rectal tissue after proctocolectomy may be a possible origin of disease. Enterobronchial fistula formation is a serious long term complication. Aggressive surgical approach with resection of the bulk of disease offers the optimal palliation and prognosis.

Female↗

PubMed1991

Comparison of CT, low-field-strength MR imaging, and high-field-strength MR imaging. Work in progress.

To assess objectively the sensitivity and specificity of low-field-strength (0.064 T) magnetic resonance (MR) imaging, a prospective blind study of 280 examinations was performed to compare low-field-strength MR imaging with computed tomography (CT) and with high-field-strength (1.5-T) MR imaging of the cranium. The sensitivity (defined as the true-positive rate) with high-field MR imaging was superior to that with low-field MR imaging and CT in helping detect overall abnormalities. Sensitivities were generally similar over a broad range of specific cranial central nervous system diseases. Low-field and high-field MR imaging were equivalent in the blind diagnoses of neoplasms and white matter disease, whereas low-field MR and CT were equivalent in the blind diagnoses of contusion, subdural and epidural hematoma, sinus disease, normality, and abnormality. The specificities with low-field MR imaging and CT were substantially better than those with high-field MR imaging.

Brain↗

PubMed1990

Age-related prognosis after acute myocardial infarction (the Multicenter Diltiazem Postinfarction Trial).

The basis for the excess mortality with age after acute myocardial infarction (AMI) is not clear, nor is it known whether the mode of death is altered with age. Age-related factors predictive of mortality and age-related mechanisms of the 333 deaths were examined in 2,466 patients who were enrolled in a placebo-controlled trial to determine the effect of diltiazem on mortality and reinfarction after AMI. There were 3 age groups with increasing mortality rates: ages 25 to 49 (n = 499), 50 to 64 (n = 1,228) and 65 to 75 years (n = 739). There was a significant age-related increase in the proportion of patients with baseline risk factors. These baseline characteristics did not differ by treatment (placebo vs diltiazem). However, multivariate survivorship analysis still identified age as an independent risk factor for cardiac death. The proportion of arrhythmic and myocardial failure deaths did not differ by treatment or age group.

Adult↗

PubMed1989

Power analysis of statistical methods for comparing treatment differences from limiting dilution assays.

Six different statistical methods for comparing limiting dilution assays were evaluated, using both real data and a power analysis of simulated data. Simulated data consisted of a series of 12 dilutions for two treatment groups with 24 cultures per dilution and 1,000 independent replications of each experiment. Data within each replication were generated by Monte Carlo simulation, based on a probability model of the experiment. Analyses of the simulated data revealed that the type I error rates for the six methods differed substantially, with only likelihood ratio and Taswell's weighted mean methods approximating the nominal 5% significance level. Of the six methods, likelihood ratio and Taswell's minimum Chi-square exhibited the best power (least probability of type II errors). Taswell's weighted mean test yielded acceptable type I and type II error rates, whereas the regression method was judged unacceptable for scientific work.

Cell Survival↗

PubMed1989

Comparison of statistical methods for the analysis of limiting dilution assays.

This study reports the results of a critical comparison of five statistical methods for estimating the density of viable cells in a limiting dilution assay (LDA). Artificial data were generated using Monte Carlo simulation. The performance of each statistical method was examined with respect to the accuracy of its estimator and, most importantly, the accuracy of its associated estimated standard error (SE). The regression method was found to perform at a level that is unacceptable for scientific research, due primarily to gross underestimation of the SE. The maximum likelihood method exhibited the best overall performance. A corrected version of Taswell's weighted-mean method, which provides the best performance among all noniterative methods examined, is also presented.

Cell Survival↗