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Biomedical subjects

J Cunningham

Publications and source records attributed to J Cunningham.

At least 91 records · Page 5Linked to original sources
PubMed1996

Cooperative hernia study. Pain in the postrepair patient.

BACKGROUND: The Cooperative Hernia Study assessed postoperative pain in a prospective trial as part of a larger study looking at the recurrence rate and other morbidity of the Bassini, McVay, and Shouldice repairs. METHODS: Patients were randomized to one of three surgical hernia repairs. Patients were seen in follow-up at 6, 12, and 24 months and were assessed for the presence of pain, numbness, paresthesia, and recurrence. RESULTS: Three hundred fifteen patients were seen in follow-up, with 276 seen at the 2-year mark. At 1 year, 62.9% of patients had groin or inguinal pain and 11.9% of patients had moderate to severe pain; 53.6% had pain and 10.6% of patients continued to report moderate to severe pain 2 years postoperatively. The predictors for long-term postoperative pain were as follows: absence of a visible bulge before the operation (p < 0.001); presence of numbness in the surgical area postoperatively (p < 0.05); and patient requirement of more than 4 weeks out of work postoperatively (p < 0.004). Three distinct chronic pains were identified. The most common and most severe pain was somatic, localized to the common ligamentous insertion to the public tubercle. The second was neuropathic and was referable to the ilioinguinal or genitofemoral nerve distribution. This was likely because of injury to the genitofemoral nerves, either at surgery or subsequently by encroachment of scar. The third pain was visceral, ejaculatory pain. Twenty-four percent of patients had postoperative numbness at 2 years, independent of the type of repair. Numbness was most common in the distribution of cutaneous branches of the ilioinguinal and iliohypogastric nerves. CONCLUSION: Pain or numbness are common late sequelae of traditional external surgical hernia repairs. Strategies need to be developed to reduce the risk of these complications.

Adult↗
PubMed1996

Fibula and its ligaments in load transmission and ankle joint stability.

A study was made of the role of the fibula in weightbearing and its contribution to ankle joint stability in 10 anatomic specimen lower limbs. On axial loading of the lower limb, the fibula was found to take an average of 17% of a 1500 N axial load. The proportion of the load carried by the fibula increased with the total loading. It also increased when the line of load was displaced laterally and when the ankle joint was in dorsiflexion and decreased when the line of loading shifted medially or the joint was plantar flexed. With loading, the lateral malleolus migrated distally relative to the medial malleolus, except after fibular osteotomy, when it migrated proximally. There was an approximately inverse relationship between proportional fibular loading and distal fibular migration. Cutting the inferior tibiofibular ligament reduced the proportional load in the fibula and increased its distal migration. The interosseous membrane modified the load distribution between the tibia and the fibula, with the distal fibula carrying a higher proportion of the axial load than did the proximal. Surgical repair of a ruptured inferior tibiofibular ligament, using either 1 or 2 screws, was associated with an abnormal pattern of load distribution and fibular displacement.

Ankle Joint↗
PubMed1996

Environmental tobacco smoke, wheezing, and asthma in children in 24 communities.

The association of exposure to environmental tobacco smoke (ETS) at home with asthma and several measures of wheeze was examined among 11,534 children aged 8 to 11 yr in 24 communities in the United States and Canada in 1988 through 1990. Information on the child's respiratory symptoms in the past year and history of exposure to ETS was provided by the child's mother on a questionnaire. After adjusting for potential confounders, children currently exposed to ETS were at greater risk of wheezing with colds (odds ratio [OR] = 1.7; 95% confidence interval [95% CI], 1.4 to 1.9), going to a hospital emergency room for wheeze (OR = 1.6; 95% CI, 1.2 to 2.2), and having persistent wheeze (OR = 1.4; 95% CI, 1.1 to 1.8). The relative odds of these symptoms increased with exposure level, and there was no evidence of a difference in the association with smoking by mother, father, or other adults. In contrast to wheeze symptoms, active doctor-diagnosed asthma and asthma medication use were not significantly associated with ETS exposure at home, possibly reflecting underdiagnosis of asthma, reporting bias, or smoking cessation by parents whose child is labeled asthmatic. We conclude that exposure to ETS is associated with wheezing symptoms, medical therapy for wheezing, and wheezing-related emergency department visits in U.S. and Canadian children.

Adult↗
PubMed1996

Health effects of acid aerosols on North American children: respiratory symptoms.

We examined the respiratory health effects of exposure to acidic air pollution among 13,369 white children 8 to 12 years old from 24 communities in the United States and Canada between 1988 and 1991. Each child's parent or guardian completed a questionnaire. Air quality and meteorology were measured in each community for a 1-year period. We used a two-stage logistic regression model to analyze the data, adjusting for the potential confounding effects of sex, history of allergies, parental asthma, parental education, and current smoking in the home. Children living in the community with the highest levels of particle strong acidity were significantly more likely [odds ratio (OR) = 1.66; 95% confidence interval (CI) 1.11-2.48] to report at least one episode of bronchitis in the past year compared to children living in the least-polluted community. Fine particulate sulfate was also associated with higher reporting of bronchitis (OR = 1.65; 95% CI 1.12-2.42). No other respiratory symptoms were significantly higher in association with any of the air pollutants of interest. No sensitive subgroups were identified. Reported bronchitis, but neither asthma, wheeze, cough, nor phlegm, were associated with levels of particle strong acidity for these children living in a nonurban environment.

Aerosols↗
PubMed1996

Race, asthma, and persistent wheeze in Philadelphia schoolchildren.

OBJECTIVES: Many studies show asthma to be more common in Black than in White children. This study assessed how much of this difference remains after adjustment for other potentially race-associated predictors of asthma. METHODS: We assessed the predictors of active diagnosed asthma and persistent wheeze in 1416 Black and White Philadelphia children aged 9 to 11 years, as reported by parents. RESULTS: Black race remained a significant predictor of active diagnosed asthma (odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.3, 4.1) but not of persistent wheeze (OR = 1.0; 95% CI = 0.6, 1.8). The excess risk of asthma in Black children was not appreciably altered by adjustment for other demographic and environmental factors. CONCLUSIONS: Black race is an important risk factor for active diagnosed asthma in these urban children, a relationship not explained by social factors. This finding and the lack of an association of race with persistent wheeze after adjustment for social factors suggest that race may be more important to the acquisition of an asthma diagnosis than to the prevalence of the symptoms.

Asthma↗
PubMed1995

Comparative allelotype of in situ and invasive human breast cancer: high frequency of microsatellite instability in lobular breast carcinomas.

To better understand the timing for presentation of allelic losses in human breast carcinogenesis, we compared the allelotypic profile of 23 in situ ductal carcinomas with that of 29 invasive ductal carcinomas. We also compared the allelotype of the invasive ductal breast carcinomas with that of 23 invasive lobular breast carcinomas. These studies were performed by means of microsatellite length polymorphisms from microdissected paraffin sections. We observed that involvement of chromosome arms 1p, 3p, 3q, 6p, 16p, 18p, 18q, 22q, and possibly 6q and 11p appear to be late events in breast cancer progression because allelic losses or imbalances affecting these areas were observed with very low frequency at the in situ stage. On the other hand, allelic imbalances and losses affecting chromosome arms 7p, 16q, 17p, and 17q appear to be early abnormalities because they were observed in approximately 25-30% of ductal carcinoma in situ lesions. Allelic losses and imbalances affecting the 8p arm were frequently observed in invasive lobular breast carcinomas. It was also interesting that microsatellite instability, also known as replication error (RER) phenotype, was found to occur at a high frequency in invasive lobular breast carcinomas because 9 of 23 (39%) were RER+, compared with 7 of 52 (13.5%) RER+ of breast cancers with ductal differentiation (P = 0.012, chi 2 test). Our findings provide for the first time molecular evidence suggesting that invasive lobular breast carcinomas may arise by a different mechanism of carcinogenesis than ductal carcinomas.

Adult↗
PubMed1995

p53 gene mutations inside and outside of exons 5-8: the patterns differ in breast and other cancers.

Most studies of mutations in the p53 tumor suppressor gene in tumors have examined only exons 5-8. Our laboratory previously found 64 mutations in exons 5-8 of the p53 gene in 194 primary breast cancers. Herein, we report 18 additional mutations found outside of exons 5-8. Mutations are present in exons 4, 9 and 10, and flanking splice junctions, but not in the promotor region or in exons 1, 2, 3 and 11. No missense mutations are found outside of exons 5-8. Instead, there is a predominance of frameshift mutations with lesser numbers of nonsense and splice site mutations. In contrast, the majority of mutations in exons 5-8 in this sample are missense changes and all of these are at amino acids that are identical in the 11 known p53 sequences that represent about 1.6 billion years of evolutionary divergence. The difference in mutational pattern between these two regions of the p53 gene is due to a lack of missense mutations and inframe microdeletions outside of exons 5-8. A review of our database of p53 mutations (De Vries et al., in preparation) shows that the patterns of mutation inside and outside of exons 5-8 differ in other types of cancers as well. The paucity of missense mutations in exons 2-4 and 9-11 in breast and other cancers (even at amino acids identical throughout p53 gene evolution) suggest that at least some missense mutations result in a phenotype other than malignant transformation. These data also illustrate the importance of examining identical exons when comparing the pattern of p53 gene mutations in different populations.

Adult↗
PubMed1995

Elevated plasma ceruloplasmin in insulin-dependent diabetes mellitus: evidence for increased oxidative stress as a variable complication.

Ceruloplasmin (Cp) is an acute-phase-responsive oxidase enzyme. Prior reports suggest that Cp is increased in diabetes mellitus, perhaps reflecting greater oxidant stress. However, the situation in insulin-dependent diabetes mellitus (IDDM) per se remains unclear. Furthermore, vitamin C can interfere with one indirect assay for Cp, and vitamin C metabolism is altered in IDDM. We measured Cp levels by both a direct radial immunodiffusion (RID) assay and an indirect oxidase assay in 10 subjects with IDDM and 10 nondiabetics, both at baseline and after 30 days of vitamin C supplementation (100 or 600 mg daily, five subjects per group). Plasma copper level was measured independently also. Our data show that circulating levels of Cp are significantly increased in IDDM subjects as a group, and specifically that Cp is abnormally high in a subset of IDDM individuals. Vitamin C supplementation at either dose interfered with the oxidase assay for Cp in both groups, but vitamin C did not alter the RID assay. The observed increase in plasma copper suggests that circulating holo-Cp is increased. The finding of increased Cp in some individuals with IDDM supports the hypothesis of increased oxidant stress as a variable factor in the spectrum of chronic complications in diabetes. Measurements of Cp level by the oxidase assay must be considered unreliable for subjects taking vitamin C supplements of > or = 100 mg/d.

Acute-Phase Reaction↗
PubMed1995

Detection of oxidants in uremic plasma by electron spin resonance spectroscopy.

Depletion of antioxidants and the presence of products of free radical damage in plasma suggest that oxidative stress is increased in uremia. We have developed an application of electron spin resonance spectroscopy, and used this method to show that a stable oxidizing component or components of plasma accumulate in uremia. No oxidizing activity was detectable in plasma from subjects with normal renal function. The oxidant was detected by its capacity to oxidize the spin trap 3,5-dibromo-4-nitrosobenzene sulphonate (DBNBS). The oxidant was dialyzable from plasma, had an upper molecular weight limit of about 3,000 Daltons and was stable over many months. Physiological plasma concentrations of vitamin C, a water soluble congener of vitamin E and reduced glutathione were unable to inhibit the oxidizing capacity of uremic plasma. Thus, uremia is associated with accumulation of an endogenous oxidizing activity at much higher concentrations than in subjects with normal renal function.

Adult↗
PubMed1995

Racial differences in the association between maternal smoking during pregnancy and lung function in children.

We recently reported that suburban white schoolchildren whose mothers smoked during pregnancy have significantly reduced lung function. Because inner-city and minority children may be at greater risk for respiratory morbidity, we evaluated the relationship between maternal smoking during pregnancy and lung function in 493 white and 383 black schoolchildren 9 to 11 yr of age in three areas of Philadelphia. The child's passive smoking history was determined from reports by the mother. Spirometry was performed at school. After adjusting for height, weight, age, sex, area of city, race, socioeconomic status, and current exposure to environmental tobacco smoke at home, maternal smoking during pregnancy was associated with significant deficits in FEF25-75 (-8.1%) and FEV1/FVC (-2.0%). The observed deficits were larger for black children than for white children, and they were larger for boys than for girls. These results provide additional evidence of an association between maternal smoking during pregnancy and reduced pulmonary function in children, and they suggest that the association may be modified by race and/or sex.

Black People↗
PubMed1995

The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults.

GH deficiency is associated with increased cardiovascular morbidity, which may be determined by alterations in vascular risk factors. We report the effect of partially treated hypopituitarism and subsequent GH replacement (mean dose, 0.2 IU/kg.week) on putative cardiovascular risk factors in 22 nondiabetic hypopituitary subjects in a 6-month, double blind, controlled study (active/placebo ratio, 11:11). All patients were subsequently treated with GH for a further 6 months. Total fat, percent body fat, and central fat were measured by dual energy x-ray absorptiometry. The hypopituitary patients had increased percent fat (P = 0.03) and central fat (P < 0.01) compared with body mass index-matched controls. Before GH treatment, fasting (total) and specific insulin positively correlated with body mass index (P = 0.02 and P < 0.001, respectively), waist/hip ratio (P = 0.05 and P = 0.01), and central fat (P = 0.03 and P = 0.003). Specific insulin and insulin sensitivity (IS), calculated by homeostatic model of assessment, were related to total fat (P < 0.001 and P = 0.02). GH treatment for 6 months led to a reduction in total fat (P < 0.02), percent fat (P = 0.002), central fat (P = 0.012), waist/hip ratio (P < 0.05), total cholesterol (P = 0.03), and apolipoprotein-B (P = 00001), as well as a decrease in the IS from 36.9% (range, 12-100%) to 25% (range, 2.5-55%; P = 0.0002). This was paralleled by a rise in fasting (total) and specific insulin (P = 0.016 and P = 0.002). The degree of correlation among indices of IS, body composition, and fat distribution increased after GH treatment. Fasting plasma glucose rose significantly, but was within the reference range. During 12 months of GH therapy, a significant increase in serum lipoprotein-(a) was observed (P < 0.05). Although GH has beneficial effects on central adiposity and lipid fractions, it is also associated with a decrease in IS; these effects may vary between individuals.

Adipose Tissue↗
PubMed1995

Granisetron in the prevention of irradiation-induced emesis.

A double-blind double-dummy, comparative study was carried out in 30 patients receiving highly emetogenic fast dose rate, single fraction total body irradiation prior to bone marrow transplantation. Patients were randomised into one of two groups, receiving either granisetron, a specific 5-HT3 antagonist or a combination of metoclopramide, dexamethasone phosphate and lorazepam to assess the comparative efficacy of the two regimens in the control of irradiation-induced nausea and vomiting. After 24 h eight patient (53%) treated with granisetron showed a complete response compared with two patients (13%) in the comparator group. The control of vomiting by granisetron, over both 24 h and 7-day periods (P = 0.001 and P = 0.004), was significantly better than that seen with the comparator and required significantly fewer rescue doses. The safety profiles in the two groups appeared similar, with the exception that granisetron produced less drowsiness than the comparator.

Adult↗
PubMed1994

Maternal smoking during pregnancy as a predictor of lung function in children.

Recent studies have suggested that prenatal exposure to environmental tobacco smoke may lead to lower lung function in infants. The authors examined the relation of maternal smoking during pregnancy to persistent deficits in the lung function of older children. Subjects were 8,863 nonsmoking white children aged 8-12 years from 22 North American communities. Information on maternal smoking was provided by the child's mother. Pulmonary function testing of the children was conducted at school in 1988-1991. Children whose mothers smoked during pregnancy, whether or not they still smoked in the year prior to the study, had significantly lower lung function than did children whose mothers did not smoke in either period. On average, forced expiratory flow between 65 and 75 percent of forced vital capacity (FEF65-75%), forced expiratory flow between 25 and 75 percent of forced vital capacity (FEF25-75%), and forced expiratory volume in 3/4 of a second (FEV0.75) were 5.7%, 4.9%, and 1.7% lower, respectively, for children whose mothers smoked during pregnancy. After adjusting for maternal smoking during pregnancy, the authors found that current maternal smoking was not associated with significant differences on any lung function measure. These results show a persistent deficient in lung function associated with maternal smoking during pregnancy that is not explained by current maternal smoking alone. The strongest effects were observed with pulmonary function measures of flow in the small airways. The authors conclude that the effects of exposure to tobacco smoking by the mother during pregnancy and/or environmental tobacco smoke exposure in the first few years of life persist into childhood and may affect the pulmonary function attained throughout the child's life.

Child↗