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Biomedical subjects

A Hill

Publications and source records attributed to A Hill.

At least 73 records · Page 4Linked to original sources
PubMed2000

Clinical features associated with a delayed diagnosis of cystic fibrosis.

BACKGROUND: The majority of patients with cystic fibrosis (CF) are diagnosed in the first decade of life. In a small number of patients, the diagnosis is not made until later. OBJECTIVE: In this study, the clinical and genetic features of patients diagnosed after the age of 10 were examined. METHODS: All living patients in Northern Ireland diagnosed prior to 1983, when neonatal screening was introduced, were studied. A total of 103 patients were identified of whom 18 were diagnosed after the age of 10. The relationships between late diagnosis and clinical presentation, sputum microbiology, pancreatic sufficiency, nutritional status, genotype and distance from the regional CF centres was determined by multiple regression analysis. RESULTS: All 18 late-diagnosed patients had a sweat (chloride >70 mmol/l). Late diagnosis was significantly related to carriage of the R117H mutation (r(2) = 0.45) and pancreatic sufficiency (r(2) = 0.37). There was a weak relationship with pulmonary function (r(2) = 0.09). CONCLUSIONS: In Northern Ireland, late diagnosis in mainly associated with pancreatic function and carriage of the R117H mutation.

Adolescent↗
PubMed2000

Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension.

Therapeutic strategies against free radicals have mostly focused on the augmentation of antioxidant defenses (eg, vitamins C and E). A novel approach is to prevent free radical generation by the enzyme system xanthine oxidase. We examined whether the inhibition of xanthine oxidase with allopurinol can improve endothelial function in subjects with type 2 diabetes and coexisting mild hypertension compared with control subjects of a similar age. We examined 23 subjects (11 patients with type 2 diabetes and 12 healthy age-matched control subjects) in 2 parallel groups. The subjects were administered 300 mg allopurinol in a randomized, placebo-controlled study in which both therapies were administered for 1 month. Endothelial function was assessed with bilateral venous occlusion plethysmography, in which the forearm blood flow responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators were measured. Allopurinol significantly increased the mean forearm blood flow response to acetylcholine by 30% (3.16+/-1.21 versus 2.54+/-0.76 mL. 100 mL(-1). min(-1) allopurinol versus placebo; P=0.012, 95% CI 0.14, 1.30) but did not affect the nitroprusside response in patients with type 2 diabetes. There was no significant impact on either endothelium-dependent or -independent vascular responses in age-matched control subjects. Allopurinol improved endothelial function to near-normal levels. Regarding markers of free radical activity, the level of malondialdehyde was significantly reduced (0.30+/-0.04 versus 0. 34+/-0.05 micromol/L for allopurinol versus placebo, P=0.03) in patients with type 2 diabetes but not in control subjects. The xanthine oxidase inhibitor allopurinol improves endothelial dysfunction in patients with type 2 diabetes with mild hypertension but not in matched control subjects. In the former group, allopurinol restored endothelial function to near-normal levels.

Age Factors↗
PubMed2000

Bartonella henselae infection in British Columbia: evidence for an endemic disease among humans.

Human bartonellosis in North America is mainly associated with Bartonella henselae, and the availability of laboratory diagnostic tools has significantly heightened awareness of the spectrum of human disease that is caused by this bacterium. We detail herein examples of illness in a pediatric population which serve to confirm that B. henselae-associated disease exists in British Columbia. Seroprevalence studies among asymptomatic adults and among children with symptomatic respiratory illness of other causation demonstrated that 36.8% and 18.5% of sera, respectively, had IFA-IgG titres > or = 1:256. IFA-IgG titres did not vary significantly whether B. henselae ATCC 49793 or a local wild-type B. henselae isolate were used as substrate. An assessment of IgM response was consistent with the proposal that endemic seroprevalence is a function of past rather than recent exposure. Both clinical and serological studies are concordant in providing evidence that B. henselae is endemic in British Columbia.

Adolescent↗
PubMed1999

Localized male breast carcinoma and family history. An analysis of 142 patients.

BACKGROUND: Male breast carcinoma is rare; therefore, the effect of family history on the course of the disease has not been well described. Germ-line mutations in breast carcinoma susceptibility genes, particularly BRCA2, are associated with an increased risk of male breast carcinoma. The authors sought to correlate significant family history with clinical phenotype in males with breast carcinoma. METHODS: One hundred forty-two men with breast carcinoma were treated at Memorial Sloan-Kettering Cancer Center or the Ochsner Clinic from 1973 to 1994. The authors reviewed the effect imparted by a family history of breast carcinoma on the duration of symptoms, the age at diagnosis, and the survival of men with this disease. RESULTS: Fifteen percent of male breast carcinoma patients had a first-degree relative with the disease. Fifty-eight years was the mean age at diagnosis for those with a family history, compared with 61 years for those without (P = not significant [NS]). The mean duration of symptoms was 23 months for those with a family history, compared with 22 months for those without. Three of 22 patients (13.6%) with a family history, compared with 11 of 90 patients (12%) without a family history, had Stage III disease (P = NS) at presentation. The overall 5-year and 10-year survival rates were 86% and 64%. Survival was not affected by family history. Lymph node positivity reduced 5-year and 10-year survival rates to 73% and 50% (P = 0.0004). CONCLUSIONS: For men with breast carcinoma, the presence of a family history did not affect the age at presentation, the duration of symptoms, the stage of disease at presentation, or the overall survival. In multivariate analysis, the most powerful predictor of outcome for these men was the status of the axillary lymph nodes.

Adult↗
PubMed1999

Equatorius: a new hominoid genus from the Middle Miocene of Kenya.

A partial hominoid skeleton just older than 15 million years from sediments in the Tugen Hills of north central Kenya mandates a revision of the hominoid genus Kenyapithecus, a possible early member of the great ape-human clade. The Tugen Hills specimen represents a new genus, which also incorporates all material previously referable to Kenyapithecus africanus. The new taxon is derived with respect to earlier Miocene hominoids but is primitive with respect to the younger species Kenyapithecus wickeri and therefore is a late member of the stem hominoid radiation in the East African Miocene.

Animals↗
PubMed1999

Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy.

OBJECTIVE: HIV-induced CD4 lymphocyte depletion is partially reversed by antiretroviral therapy but it is unclear if the degree to which the CD4 count rises depends on viral suppression (if so, the extent of viral suppression required to achieve a maximal CD4 count rise), whether the rise is sustainable and whether it occurs in patients with CD4 count <10 x 10(6) cells/l. We aimed to address these issues. METHODS: We studied CD4 count and plasma HIV RNA values every 4 weeks for 72 weeks in 154 patients starting indinavir-containing regimens. RESULTS: Mean baseline HIV RNA and CD4 count were 4.8 log10 copies/ml and 180 x 10(6) cells/l, respectively. Overall, there was a mean increase in CD4 count of 143 x 10(6) cells/l by 72 weeks. The adjusted mean increase (adjusted for initial viral load, CD4 count and age) was strongly related to the mean viral suppression over the follow-up period (P < 0.0001). Importantly, there was a highly significant difference (P = 0.0004) in the rise in CD4 count between those with 2-3 log suppression (161 x 10(6) cells/l) and those with > 3 log suppression (314 x 10(6) cells/l; mean 3.6 log suppression in this group), suggesting that with even greater suppression the rise in CD4 lymphocytes may be still larger. We also studied whether CD4 counts were still rising after 72 weeks in patients with sustained suppression of at least 3 log in viral load. There was a significant (P = 0.004; paired t-test) rise in count of 43 x 10(6) cells/l between weeks 64 and 72 in these patients, suggesting that regeneration continues at least up to 72 weeks after therapy, provided virus replication continues to be suppressed. Patients with initial CD4 counts < 10 x 10(6) cells/l experienced no smaller rises than those at higher levels, even after adjustment for other factors. CONCLUSION: These results strongly support a direct causal relationship between HIV replication and CD4 lymphocyte count depletion. The rise in those with > 3 log suppression provides the best available indicator of the potential for natural CD4 regeneration in HIV-infected patients. However, since still greater CD4 count rises may be seen with more suppressive regimens, it may not be possible to study the intrinsic CD4 regenerative capacity until such regimens are available.

Adult↗
PubMed1999

Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the alpha2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma.

A region of 150 kb has been analysed around a previously isolated, lymphoma associated, translocation breakpoint located at chromosome band 11q23. This balanced and reciprocal translocation, t(11;14)(q32;q23), has been shown to result in the fusion between chromosome 11 specific sequence and the switch gamma4 region of the IGH locus. The LPC gene, encoding a novel proprotein convertase belonging to the furin family, has been identified in this region. In order to characterize further the region surrounding the translocation, we have determined the detailed structure of LPC. Here we show that LPC consists of at least 16 exons covering 25 kb, and that there is a partial duplication, involving mobile genetic elements and containing LPC exons 13-17 in a tail-tail configuration at 65 kb downstream. Since the chromosomal breakpoint lay between these two structures, the intervening region was further analysed and shown to contain at least two unrelated genes. The previously known SM22 gene was localized close to the 3' tail of LPC. Furthermore, we identified the gene encoding the alpha2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) at the chromosomal breakpoint. The position of another previously identified breakpoint was also located to within the first intron of this gene. Altogether, our results give evidence of a genomic instability of this area of 11q23 and show that Pafah1a2 and not LPC is the gene disrupted by the translocation, suggesting that deregulated Pafah1a2 may have a role in lymphomagenesis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Virological response to protease inhibitor therapy in an HIV clinic cohort.

OBJECTIVE: New antiretroviral strategies aim to reduce plasma HIV RNA (viral load) to below the limits of detectability of assays with the objective of reducing viral replication in order to stop or reverse the pathogenic process and prevent development of drug resistance. First use of a protease inhibitor might offer the most realistic chance of achieving this aim. Our objective was to study the virological response to protease inhibitors in patients taking them for the first time. METHODS: A total of 901 patients from a large outpatient clinic were followed a mean of 15 months from the time of starting a protease inhibitor until 1 May 1998. Viral load and CD4 cell count measurements were made on average every 34 days. RESULTS: Overall there was a 79% [95% confidence interval (CI), 76-82] probability of the patients achieving a viral load < 500 copies/ml by 24 weeks after starting the protease inhibitor. In a multiple Cox regression model, those with lower initial viral load [relative hazard (RH), 0.72; P < 0.0001], higher CD4 cell count (RH, 1.07; P = 0.002), those starting other new drugs at same time as the protease inhibitor (RH, 1.46 for two versus none; P = 0.003), those who were antiretroviral-naive, and those using indinavir or nelfinavir were more likely to achieve such levels. In those 651 patients achieving viral load < 500 copies/ml within 24 weeks, there was an estimated 53% (95% CI, 51-55) probability of rebound of viral load to > 500 copies/ml by 52 weeks from the first undetectable value. Again, those who had started other new drugs at the same time as the protease inhibitor (RH, 0.57; P = 0.003 for starting two versus none) tended to experience a lower probability of viral load rebound, as did those with higher initial CD4 cell count (RH, 0.87 per 100 x 10(6)/l higher; P = 0.0007). Those who took saquinavir achieved less durable virological responses than those who took other protease inhibitors. CONCLUSIONS: Starting protease inhibitor therapy with two other new antiretroviral drugs simultaneously with protease inhibitor therapy offers a better best chance of achieving sustained viral load < 500 copies/ml than starting fewer new drugs.

Adult↗
PubMed1999

Phantom limb pain: a review of the literature on attributes and potential mechanisms.

This study presents a review of the literature on the attributes and potential mechanisms involved in phantom limb pain, encompassing studies describing pain in the residual limb, phantom sensation and phantom limb pain, and the difficulties that may arise when making these distinctions. A variety of theories have been proposed to explain causal mechanisms for phantom limb pain. Conceptually, research into phantom limb pain is informed by the particular theory of chronic pain that is dominant at the time the research is undertaken. For example, early physiological theories on the etiology of phantom limb pain were grounded in specificity or pattern theories of pain. Later physiological research was based on the framework provided by Gate Control Theory and focused on identifying peripheral, spinal, and central neural mechanisms. Psychological explanations were grounded in psychoanalytic or personality theories of chronic pain which propose that phantom limb pain results from pre-amputation psychological disturbance. Despite numerous studies examining phantom limb pain, much of this research has both conceptual and methodological shortcomings. As such, the application of these research findings to clinical practice has limited utility.

Amputation Stumps↗
PubMed1999

Newborn radial nerve palsy: report of four cases and review of published reports.

Four newborns presented with isolated radial nerve palsy during the first 2 days of life. In three, there was a history of failure of progression of labor, which may have resulted in prolonged radial nerve compression. Furthermore, three infants had fat necrosis of the upper arm above the elbow, suggestive of compression of the radial nerve in the region of the spiral groove. Significant recovery of function was evident within 1 month in all four infants. The authors review published reports about the rare condition of isolated radial nerve palsy in the newborn.

Arm↗
PubMed1999

Low frequency of germline E-cadherin mutations in familial and nonfamilial gastric cancer.

Little is known about the relative contributions of genetic and environmental factors to the development of gastric cancer. Mutations in the cell adhesion molecule E-cadherin are recognized to be associated with the development of undifferentiated, diffuse and invasive gastric cancers. A recent study of two gastric cancer families has shown that germline mutations in the E-cadherin gene can be causative (Guilford P et al, Nature 1998; 26: 402-405). We have examined the E-cadherin gene for constitutive mutations in a systematic series of 106 gastric cancer patients, 10 with a family history of the disease and 96 sporadic cases. No pathogenic mutations were observed in any of the 106 patients. The results indicate that germline mutations in E-cadherin will not account for more than 3% of gastric cancers.

Adenocarcinoma↗
PubMed1999

Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial.

We report the final results of a prospectively randomized study that compared the combination of epirubicin, cisplatin and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin and methotrexate (FAMTX) in previously untreated patients with advanced oesophagogastric cancer. Between 1992 and 1995, 274 patients with adenocarcinoma or undifferentiated carcinoma were randomized from eight oncology centres in the UK and analysed for response and survival. The overall response rate was 46% (95% confidence interval (CI), 37-55%) with ECF, and 21% (95% CI, 13-28%) with FAMTX (P = 0.00003). The median survival was 8.7 months with ECF and 6.1 months with FAMTX (P = 0.0005). The 2-year survival rates were 14% (95% CI, 8-20%) for the ECF arm, and 5% (95% CI, 2-10%) for the FAMTX arm (P = 0.03). Histologically complete surgical resection following chemotherapy was achieved in ten patients in the ECF arm (three pathological complete responses to chemotherapy) and three patients in the FAMTX arm (no pathological complete responses). The ECF regimen resulted in a response and survival advantage compared with FAMTX chemotherapy. The probability of long-term survival following surgical resection of residual disease is increased by this treatment. The high response rates seen with ECF support its use in the neoadjuvant setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

The association of energy intake bias with psychological scores of women.

OBJECTIVE: Assess the association between reporting bias of dietary energy intake and the behavioral and psychological profiles in women. DESIGN: At baseline a series of questionnaires were administered to 37 women, (the Marlowe-Crowne Social Desirability Scale, Weinberger Adjustment Inventory (WAI), the Eating Disorder Inventory (EDI), the Restraint Scale and Sorensen-Stunkard's silhouettes). Subjects received training on how to record dietary records. Subjects recorded three days of dietary records to measure energy intake (EI) during a study to determine total energy expenditure (TEE) using doubly labeled water. Reporting accuracy (RA = EI/TEE x 100) was determined for each subject. Statistical analysis of the data used a mixed effects model accounting for within subject variability to determine if the psychological scores were associated with reporting accuracy. SETTING AND SUBJECT: Women were recruited with local advertisements in Tucson, Arizona. The women had a mean ( +/- 1 s.d.) age of 43.6 +/- 9.3 yrs, body mass index (BMI) of 28.7 +/- 8.5 kg/m2 and total body fat (%TBF) of 31.9 +/- 7.3%. RESULTS: Age and %TBF were significantly and inversely associated with RA. Furthermore, Social Desirability was negatively associated with RA. Body dissatisfaction and associating a smaller body size than one's own as being more healthy were also associated with a lower RA. CONCLUSIONS: These results suggest that Social Desirability and self image of body shape are associated with RA. Modifications in subject training may reduce the effect of these factors on RA.

Adult↗
PubMed1999

The molecular basis of malonyl-CoA decarboxylase deficiency.

We characterized a 2.1-kb human cDNA with a 1362-bp (454-amino acid) open reading frame showing 70.3% amino acid identity to goose malonyl-CoA decarboxylase (MCD). We have identified two different homozygous mutations in human MCD (hMCD) by using RT-PCR analysis of fibroblast RNA from two previously reported consanguineous Scottish patients with MCD deficiency. The first mutation is a 442C-->G transversion resulting in a premature stop codon (S148X) in the N-terminal half of the protein. The second is a 13-bp insertion in the mature RNA, causing a frameshift with predicted protein truncation. This insertion is the result of an intronic mutation generating a novel splice acceptor sequence (IVS4-14A-->G). Both mutations were found to segregate appropriately within the families and were not found in 100 normal unrelated individuals. These mutations would be predicted to cause MCD deficiency, thus confirming this transcript as the hMCD ortholog. The peptide sequence of hMCD revealed a C-terminal peroxisomal targeting sequence (-SKL). This targeting signal appears to be functional in vivo, since the distribution of MCD enzymatic activity in rat liver homogenates-as measured by means of subcellular fractionation-strongly suggests that MCD is localized to peroxisomes in addition to the mitochondrial localization reported elsewhere. These data strongly support this cDNA as encoding human MCD, an important regulator of fatty acid metabolism.

Adolescent↗
PubMed1999

CD4 lymphocyte count as a predictor of the duration of highly active antiretroviral therapy-induced suppression of human immunodeficiency virus load.

The association between CD4 cell count and duration of virus load suppression was investigated in 558 patients in the Frankfurt HIV Clinic Cohort who had begun highly active antiretroviral therapy and who had virus load declines to </=500 copies/mL. The Kaplan-Meier method estimated viral rebound in 42.5% of patients by 24 weeks and in 64.3% by 84 weeks. Risk of viral rebound was independently associated with baseline and changes from baseline CD4 cell count. The achieved CD4 cell count was the most important factor for prediction of viral rebound (relative hazard, 5.4 for an updated CD4 cell count of <20 vs. >500 copies/mL; P=.0001). Baseline virus load was not associated with virus load rebound. Lower baseline CD4 cell counts were associated with increased risk of viral rebound; however, this risk was significantly reduced in persons with low baseline CD4 cell counts who experienced substantial increases in CD4 cell counts during follow-up.

Adult↗