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Biomedical subjects

J Hull

Publications and source records attributed to J Hull.

At least 37 records · Page 2Linked to original sources
PubMed1998

Severe viral respiratory infections in infants with cystic fibrosis.

Limited data in children with cystic fibrosis (CF) suggest that respiratory viral infections during infancy result in substantial morbidity. Eighty of 101 (79%) infants with CF diagnosed by neonatal screening during 1991-1996 were recruited into a prospective, multiple-birth cohort study. We aimed to perform an initial, then annual bronchoalveolar lavage (BAL) for bacterial and viral culture, cytology, IL-8, and elastolytic activity over the following 2 years. When possible, BAL was also performed during any hospitalization for a pulmonary exacerbation, and additional specimens for viral culture were collected by nasopharyngeal aspiration. Thirteen infants undergoing bronchoscopy for congenital stridor served as disease controls. During infancy, 31 children (39%) were hospitalized for respiratory disease and 20 (65%) cases had an etiologic agent identified. Respiratory viruses were detected in 16/31 (52%) cases, including four with simultaneous bacterial infection. Another four were infected with Staphylococcus aureus. Respiratory syncytial virus predominated and was found in seven infants. In the absence of bacteria, those with viral infections had acute onset of respiratory distress, were not treated with antibiotics, and had an uncomplicated hospital course. Compared to noninfected CF subjects and controls, infected infants had elevated BAL inflammatory indices (P < 0.01). Eleven of 31 (35%) hospitalized infants followed for 12-60 months acquired Pseudomonas aeruginosa, compared with only three of 49 (6%) subjects not hospitalized for respiratory symptoms during infancy (risk ratio 5.8, CI 1.9, 24). We conclude that respiratory viruses are important causes of hospitalization in CF infants. While viral infections were self-limited, they were accompanied by airway inflammatory changes, and admission to hospital was associated with early acquisition of Pseudomonas aeruginosa and persistent respiratory symptoms.

Bronchoalveolar Lavage↗
PubMed1998

Contribution of genetic factors other than CFTR to disease severity in cystic fibrosis.

BACKGROUND: Disease severity in patients with cystic fibrosis shows marked variability. Attempts to explain this phenotypic heterogeneity on the basis of CFTR genotype have had limited success. A study was undertaken to test the hypothesis that naturally occurring variants of the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) and the detoxifying enzyme glutathione S-transferase M1 (GSTM1) could influence disease severity in cystic fibrosis. METHODS: Fifty-three children with cystic fibrosis were studied. To allow for the effect of age, all clinical details were collected during the eighth year of age. The subjects were divided into groups, both according to the presence or absence of the TNF2 TNF-alpha -308 promoter polymorphism (n = 20), and by homozygosity for the null allele of GSTM1 (n = 26). RESULTS: Percentage predicted forced expiratory volume in one second (FEV1) and weight z scores were significantly lower in the TNF2 group (mean difference (95% confidence intervals) for FEV1 11.6% (1.7 to 21.5) and 0.59 (0.06 to 1.12) for weight z score). The Chrispin-Norman chest radiographic score was significantly higher and the Shwachman score was significantly lower in patients homozygous for the GSTM1 null allele. CONCLUSIONS: Two independent genetic factors have been identified which appear to influence disease severity in cystic fibrosis. These results support the contention that inflammation in cystic fibrosis contributes to tissue damage. Isolation of further such factors may lead to identification of patients at risk of more severe disease and allow targeted aggressive therapy in this group.

Alleles↗
PubMed1998

Elemental content of airway surface liquid from infants with cystic fibrosis.

We tested the hypothesis that airway surface liquid (ASL) electrolyte composition is altered in infants with cystic fibrosis (CF) and that the presence of airway inflammation affects ASL composition. We measured the tracheal ASL sodium and chloride concentration and examined bronchoalveolar lavage (BAL) fluid cytology, interleukin-8 (IL-8) concentrations, and quantitative bacterial culture in 19 infants and young children with CF. Seven infants undergoing bronchoscopy for the evaluation of stridor served as non-CF controls. In addition, we measured nasal ASL sodium and chloride concentrations from 10 young adults with CF and from 10 control subjects. On the basis of the BAL findings, the infants with CF were divided into three groups: one with little evidence of pulmonary inflammation (CF-NI, n = 5); one with obvious pulmonary inflammation (CF-I, n = 7); and an intermediate group (CF-MI, n = 7). We found the ASL sodium was not different among any of the four groups (means mM +/- SE, 85 +/- 10 controls; 78 +/- 16 CF-NI; 83 +/- 9 CF-MI, 84 +/- 9 CF-I). In contrast the ASL chloride was lower in the CF-NI group when compared with control subjects (108 +/- 5 control subjects; 77 +/- 7 CF-NI, p < 0.01). In the CF-I and CF-MI groups, the ASL chloride concentrations were of intermediate values (CF-I 95 +/- 10 mM; CF-MI 96 +/- 9 mM) and not significantly different from controls. Results from the nasal ASL analysis showed no significant differences in sodium and chloride concentrations in the CF group compared with control subjects. These results suggest that the primary abnormality of ASL composition is a reduction in chloride concentration. ASL composition appears to be affected by the presence of airway inflammation.

Adolescent↗
PubMed1998

Effects of psychoeducational intervention for married patients with bipolar disorder and their spouses.

The relative benefit of adding a structured psychoeducational intervention to standard medication treatment for married patients with bipolar disorder and their spouses was assessed. Patients were randomly assigned to receive either medication management or medication management plus a marital intervention with their spouses for an 11-month period. Patients' symptoms, functioning, and adherence to their medication regimens were measured at study entry and at 11 months. Significant effects favoring the combined treatments were observed for overall patient functioning but not for symptom levels. The marital intervention was associated with improved medication adherence. Combined psychosocial and medication treatment does not affect patients' symptom levels beyond the effects of medication alone, but it does result in significant incremental gains in overall patient functioning.

Bipolar Disorder↗
PubMed1997

The relationship between personality and quality of life in persons with schizoaffective disorder and schizophrenia.

The goal of this study was to examine the effects of personality traits as measured by the NEO-PI on the quality of life (QOL) of persons with schizoaffective disorder and schizophrenia. The premise of this research is that personality traits may be important in shaping one's outlook and satisfaction with life. In a prior pilot study, personality traits were measured in persons with schizoaffective disorder and schizophrenia. In this study, the relationship between QOL and specific personality domains as assessed by the NEO-PI were studied in 21 patients. Global QOL as measured by the Lehman QOL instrument was positively correlated with Extroversion (E) and Agreeableness (A), and negatively correlated with the domain of Neuroticism (N). Global satisfaction scores were not correlated with ratings of psychoticism, paranoia or depression. These data suggest that even in psychotic conditions such as schizoaffective disorder or schizophrenia, intrapsychic factors influence one's sense of QOL. In addition, these data suggest that personality variables may differentially affect patients' satisfaction and QOL with different treatment settings.

Adult↗
PubMed1997

Biparental psychopathology and borderline personality disorder.

The pathology of parents is thought to be associated with the emergence of Borderline Personality Disorder (BPD) among offspring by both genetic and environmental pathways (Links and Blum 1990). In an effort toward clearer delineation, not only reliable diagnoses of patients, but also direct study of families, are recommended (Gunderson 1990; Gunderson and Zanarini 1989; Links and Blum 1990; Ogata et al. 1990; Zanarini et al. 1990). With this in mind, we conducted a pilot, retrospective study of parental psychiatric status, developmental events, and family climate during the developmental years of 30 young women hospitalized for BPD, to be reported here. In studying these three dimensions of family life, we hoped to shed light on environmental underpinings (Gunderson 1990; Gunderson and Zanarini 1989; Links 1992; Rutter and Quinton 1984). Even though our cohort is small and select, and the data on a comparison group not yet available, our research approach holds promise of yielding fresh insights.

Adolescent↗
PubMed1997

BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and ovarian cancer.

The strongest risk factors currently known for inherited predisposition to breast and ovarian cancer are mutations in BRCA1 and BRCA2. Two mutations in BRCA1 and one mutation in BRCA2 have been identified that are present to a particularly high degree in the Ashkenazi Jewish population due to ancient founder effects. To clarify the role of ancient and novel BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population, families with a strong history of breast and ovarian cancer were examined. Seventeen Ashkenazi Jewish families with four or more breast or ovarian cancers were analyzed for ancient and novel mutations in BRCA1 and BRCA2. Ancient mutations existed in 9 families; 7 had the BRCA1 185 del AG mutation, 1 had BRCA1 5382 ins C, and 1 had BRCA2 6174 del T. A novel mutation, BRCA2 6425 del TT, was discovered in 1 of the remaining 8 families. Seven families with four or more cases of breast and ovarian cancer cannot be accounted for by either the ancient or novel mutations. Therefore, ancient mutations in BRCA1 and BRCA2 are present in approximately half of Ashkenazi Jewish families in this series, suggesting the possibility of novel mutations, either in BRCA1, BRCA2, or in currently unidentified gene(s), responsible for the remainder.

BRCA2 Protein↗
PubMed1997

Stability of personality traits in schizophrenia and schizoaffective disorder: a pilot project.

This study was performed in an effort to begin characterization of personality traits in schizophrenia. Specific concerns included personality profiles relative to normal adults, personality profile stability over time, and trait-state issues. The authors administered the NEO Personality Inventory as well as symptom ratings at two time points to 21 patients. Patients were all stabilized outpatients attending an adult continuing day treatment program and diagnosed with either schizophrenia or schizoaffective disorder. Personality profiles were determined for all patients. Compared with a normal adult sample, this sample's scores on three out of five of the personality domains assessed were not distinguishable from normal adults. Test-retest correlations were highly significant over an average 28.2-week time interval. In general, the presence of positive symptoms did not appear related to NEO-PI stability, while negative symptoms did show a relationship to the stability of personality profiles. These data suggest that personality profiles can be looked at in schizophrenia, that these profiles do appear stable over time, and that negative symptoms have a strong influence on profile stability and appear to be "trait-like."

Adult↗
PubMed1997

Hormone replacement therapy with dydrogesterone and 17 beta-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up.

OBJECTIVE: To assess serum lipid and lipoprotein concentrations and oral glucose tolerance in postmenopausal women treated with 17 beta-oestradiol (2 mg/day) and cyclical dydrogesterone (10 mg/day for 14 days per 28 day cycle). DESIGN: A 24 month prospective study of 29 women acting as their own controls. On-treatment samples were taken during the combined (oestrogen-progestogen) phase of therapy. SETTING: Metabolic research unit in London. POPULATION: Postmenopausal women with no previous exposure to hormone replacement therapy attending a menopause clinic in a London hospital. METHODS: Fasting serum sampling and oral glucose tolerance testing. MAIN OUTCOME MEASURES: Serum lipids and lipoprotein concentrations and plasma glucose, insulin and C-peptide responses to an oral glucose load. RESULTS: Restricting the analysis to the 17 women who completed the study, no effect was seen on serum triglyceride concentrations. There was a mean fall of 5.9% (95% CI 1.2 to -13.0) in concentrations of serum total cholesterol, reflecting the balance of a 10.7% fall (95% CI 4.3 to -25.8) in low density lipoprotein cholesterol concentrations and a 16.3% increase (95% CI 7.3 to -25.3) in those of high density lipoproteins. Fasting glucose concentrations and glucose tolerance test responses were unchanged. Fasting insulin concentrations fell substantially (-41.6%, 95% CI -23.4 to -59.8) with falls also being seen in insulin responses to glucose. Fasting C-peptide concentrations increased by 36.2% (95% CI 9.17 to 63.3), with no consistent effect on C-peptide responses to glucose. CONCLUSIONS: Dydrogesterone did not appear to oppose the potentially beneficial effects of oestradiol on insulin or either low or high density lipoproteins, making the combination with 17 beta-oestradiol a potentially useful option for postmenopausal women particularly those at risk of cardiovascular disease or diabetes mellitus.

Adult↗
PubMed1997

Chronic idiopathic bronchiolitis of infancy.

The clinical and morphological features are presented of eight infants who developed a chronic respiratory illness in the first year of life characterised by tachypnoea and inspiratory crackles on auscultation. The median age at the onset of symptoms was 1 month (range 1 day to 7 months). Five of the infants required supplemental oxygen. Chest radiographs showed only non-specific perihilar alveolar shadowing and generalised hyperinflation. Investigations into the cause of the illness in these infants, including studies for infection, cardiac disease, and gastrooesophageal reflux, were negative, and an open lung biopsy sample was subsequently taken from each infant. Histological examination showed mild lymphocytic bronchiolar infiltration only in six of the eight infants. The other two biopsy samples were normal. Seven of the infants were given a trial of steroids by mouth (mean duration of treatment four months) without any apparent benefit. These infants have now been followed up for a median duration of 21 months (range 1-9 years). All have shown continuous improvement, with either the end of oxygen treatment (three patients) or the use of low flow oxygen only at night (two patients). All have normal development and all but one have normal growth. Chest examination has become normal in four subjects. In the remainder the inspiratory crackles have persisted, although they have decreased markedly in all patients. It is proposed that these infants have a previously unreported respiratory entity and that the clinical and lung biopsy sample findings reported here predict a favourable medium term prognosis.

Bronchiolitis↗
PubMed1997

Pulmonary oxidative stress response in young children with cystic fibrosis.

BACKGROUND: It has been suggested that oxidative stress contributes to lung injury in cystic fibrosis. There is, however, no direct evidence of increased pulmonary oxidative stress in cystic fibrosis nor of the effects of inflammation on the major pulmonary antioxidant, glutathione. A study was undertaken to measure these parameters in infants and young children in the presence or absence of pulmonary inflammation. METHODS: Thirty two infants and young children with cystic fibrosis of mean (SD) age 21.4 (15.3) months (range 2-54) and seven non-cystic fibrosis control subjects of mean (SD) age 21.0 (21.2) months (range 2-54) were studied using bronchoalveolar lavage (BAL). On the basis of the BAL findings the cystic fibrosis group was divided into those with (CF-I) and those without pulmonary inflammation (CF-NI). Levels of lipid hydroperoxide, total glutathione, and gamma-glutamyl transpeptidase (gamma-GT) were then measured in the BAL fluid. RESULTS: The concentrations of lipid hydroperoxide and gamma-GT in the epithelial lining fluid were significantly increased in the CF-I group compared with the control and CF-NI groups, each of which had similar values for these parameters (ratio of geometric means for CF-I group versus control for lipid hydroperoxide 5.4 (95% confidence interval (CI) 1.8 to 15.8) and for gamma-GT 5.2 (95% CI 1.4 to 19.4)). The glutathione concentration tended to be lower in the CF-I subjects but the difference did not reach statistical significance. CONCLUSIONS: These results demonstrate that the airways in patients with cystic fibrosis are exposed to increased oxidative stress which appears to be a consequence of pulmonary inflammation rather than part of the primary cystic fibrosis defect. The increase in gamma-GT in the CF-I group suggests a mechanism by which extracellular glutathione could be utilised by airway epithelial cells.

Bronchoalveolar Lavage Fluid↗
PubMed1997

Surfactant composition in infants and young children with cystic fibrosis.

We tested the hypothesis that the composition of bronchial surfactant is normal in infants with cystic fibrosis (CF) in the absence of active lung disease but that it is altered by lower respiratory tract infection and inflammation. We examined the total phospholipid (PL), disaturated phospholipid (DSP), surfactant protein-A (SP-A), surfactant protein B (SP-B), and surface activity in bronchoalveolar lavage fluid from 27 subjects with CF whose mean age was 22.7 (SD 14.5) mo. Six infants with stridor served as non-CF controls. Twelve of the subjects with CF (CF-I group) had evidence of active pulmonary infection or inflammation which was absent in the remaining 15 subjects (CF-NI group). We found no differences in the surfactant composition or activity between controls and the CF-NI group. In contrast, the DSP/PL ratio was lower in the CF-I subjects than in both the CF-NI subjects (p = 0.05) and controls (p < 0.01) suggesting a disturbance of surfactant function. SP-A concentrations were higher in the CF-I group compared to the other two groups (p < 0.05). These results suggest that the bronchial surfactant of infants with CF is altered following lower airway infection and inflammation and is not a primary abnormality associated with this disorder.

Bronchoalveolar Lavage Fluid↗
PubMed1997

Lower airway inflammation in infants and young children with cystic fibrosis.

Airway inflammation is an important component of cystic fibrosis (CF) lung disease. To determine whether this begins early in the illness, before the onset of infection, we examined bronchoalveolar lavage (BAL) fluid from 46 newly diagnosed infants with CF under the age of 6 mo identified by a neonatal screening program. These infants were divided into three groups: 10 had not experienced respiratory symptoms or received antibiotics and pathogens were absent in their BAL fluid; 18 had clear evidence of lower respiratory viral or bacterial (> or = 10(5) CFU/ml) infection; and the remaining 18 had either respiratory symptoms, taken antibiotics, or had < 10(5) CFU/ml of respiratory pathogens. Their BAL cytology, interleukin-8, and elastolytic activity were compared with those from 13 control subjects. In a longitudinal study to assess if inflammation develops or persists in the absence of infection, the results of 56 paired annual BAL specimens from 44 CF infants were grouped according to whether they showed absence, development, clearance, or persistence of infection. In newly diagnosed infants with CF, those without infection had BAL profiles comparable with control subjects while those with a lower respiratory infection had evidence of airway inflammation. In older children, the development and persistence of infection was accompanied by increased inflammatory markers, whereas these were decreased in the absence, or with the clearance, of infection. We conclude that airway inflammation follows respiratory infection and, in young children, improves when pathogens are eradicated from the airways.

Anti-Bacterial Agents↗
PubMed1997

BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2.

In order to evaluate the role of inherited BRCA2 mutations in American families--particularly the appearance in America of European founder mutations--the BRCA2 coding sequence, 5' UTR, and 3' UTR were screened in 22 Caucasian American kindreds with four or more cases of breast or ovarian cancer. Six mutations were found that cause a premature-termination codon; four of them have been reported elsewhere, and two are novel. In the four families with previously seen mutations, the distinct lineages at high risk of cancer were of Dutch, German, Irish, and Ashkenazi Jewish ancestry; mutations in Europe reflect these ancestries. The families with novel mutations were Puerto Rican Hispanic (exon 9 deletion 995delCAAAT) and Ashkenazi Jewish (exon 11 deletion 6425delTT). Among female BRCA2-mutation carriers, risks of breast cancer were 32% by age 50 years, 67% by age 70 years, and 80% by age 90 years, yielding a lifetime risk similar to that for BRCA1 but an older distribution of ages at onset. BRCA2 families also included multiple cases of cancers of the male breast (six cases), ovary (three cases), fallopian tube (two cases), pancreas (three cases), bladder (two cases), and prostate (two cases). Among 17 Ashkenazi Jewish families with four or more breast or ovarian cancers, 9 families (including 3 with ovarian cancer and 1 with male breast cancer) carried none of the three ancient mutations in BRCA1 or BRCA2. To date, both BRCA2 and BRCA1 have been screened by SSCA, supplemented by the protein-truncation test, in 48 families with four or more breast or ovarian cancers. Mutations have been detected in BRCA1 in 33 families, in BRCA2 in 6 families, and in neither gene in 9 families, suggesting both the probable cryptic nature of some mutations and the likelihood of at least one other BRCA gene.

Adult↗
PubMed1995

Isolation and structural analysis of the 5' flanking region of the gene encoding the human glucagon receptor.

The gene encoding the human glucagon receptor, including several kb of upstream sequence, was isolated from a bacteriophage lambda FIX II library constructed from human placental DNA. We report here the novel sequence of the 5' flanking region of the gene, the identification of a previously unreported intron of 5 kb, and the identification of the transcription start point of the glucagon receptor-specific transcript, which estimates the length of the first exon to be 300 bp.

Base Sequence↗
PubMed1994

Regulation of rat glucagon receptor expression.

This report describes the isolation of a cDNA for the rat glucagon receptor by using the glucagon-like peptide 1 receptor cDNA as a probe. Northern blot analysis using the cDNA clone showed that the message encoding the receptor is approximately 2.3 kb in size and is expressed only in liver and kidney among seven tissues tested. To study how glucagon receptor expression is regulated in vivo, the levels of hepatic glucagon receptor mRNA were measured in diabetic mouse model, db/db and control (db/+) mice. Interestingly, the receptor mRNA levels were similar between diabetic and control mice. In contrast, the number of hepatic glucagon receptors in diabetic mice measured by binding assays was significantly higher than that found in normal mice. These results suggest that the major regulation in hepatic glucagon receptor expression in vivo is at the posttranscriptional level.

Animals↗
PubMed1994

The stop mutation R553X in the CFTR gene results in exon skipping.

Stop or nonsense mutations are known to disrupt gene function in a number of different ways. We have studied the effects of the stop mutation R553X in exon 11 of the CFTR gene by analyzing mRNA extracted from nasal epithelial cells harvested from patients with cystic fibrosis. Four patients who were compound heterozygotes for the R553X mutation were studied. Ten non-CF control subjects were also studied. In all four patients, full-length CFTR mRNA was identified, but only a very small proportion of this was derived from the R553X allele. A smaller transcript, lacking exon 11, was also seen in the R553X patients but not in the controls. Most of this transcript was derived from the R553X allele. These results suggest that the R553X mutation results in skipping of the exon in which it is located.

Alleles↗