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H Fox

Publications and source records attributed to H Fox.

At least 19 recordsLinked to original sources
PubMed2002

Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure.

BACKGROUND: Primary antiphospholipid antibody syndrome (PAPS) is an established cause of recurrent pregnancy loss, traditionally presumed to be due to 'intraplacental thromboses'. This study examines products of conception (POC) from early pregnancy failures to investigate the mechanism of pregnancy loss. METHODS: POC from patients attending a recurrent miscarriage clinic and from terminations of pregnancy for non-medical reasons were examined histologically with particular regard to the presence or absence of vascular or intervillous thromboses and decidual endovascular trophoblast invasion. RESULTS: There were 31 PAPS-positive, 50 PAPS-negative, 34 aneuploid and 20 control cases at 6-14 weeks gestation. Villous morphology and frequency of intervillous thrombosis were not different among groups. Normal intradecidual endovascular trophoblast invasion was identified significantly less frequently in PAPS+ cases (24%), compared with controls (75%), aneuploid (53%), or PAPS- cases (61%; Z = -3.0, P < 0.01). In all cases there was apparently normal interstitial extravillous trophoblast invasion. CONCLUSIONS: Defective decidual endovascular trophoblast invasion, rather than excessive intervillous thrombosis, is the most frequent histological abnormality in PAPS+ associated early pregnancy loss. Furthermore, endovascular trophoblast invasion is not significantly reduced in the majority of fetal aneuploidy-associated pregnancy failures.

Abortion, Habitual↗
PubMed2001

Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland.

The NOTCH4 gene was recently reported to be associated with schizophrenia based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls.

Alleles↗
PubMed2001

The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics.

The clinical benefit and steroid-sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with moderate-to-severe allergic asthma. After a run-in period, 546 allergic asthmatics (aged 12-76 yrs), symptomatic despite inhaled corticosteroids (500-1,200 microg daily of beclomethasone dipropionate), were randomized to receive double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body weight and serum total IgE) subcutaneously for 7 months. A constant beclomethasone dose was maintained during a 16-week stable-steroid phase and progressively reduced to the lowest dose required for asthma control over the following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma exacerbations represented the primary variable. Compared to the placebo group, the omalizumab group showed 58% fewer exacerbations per patient during the stable-steroid phase (p<0.001). During the steroid-reduction phase, there were 52% fewer exacerbations in the omalizumab group versus the placebo group (p<0.001) despite the greater reduction of the beclomethasone dosage on omalizumab (p<0.001). Treatment with omalizumab was well tolerated. The incidence of adverse events was similar in both groups. These results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in corticosteroid requirement.

Acute Disease↗
PubMed2001

Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality.

AIM: Add-on therapy with omalizumab, an anti-immunoglobulin E antibody, is effective in improving disease control in patients with allergic asthma of varying severity. The aim of the present study was to determine the efficacy of omalizumab in a subgroup of patients at high risk of serious asthma-related morbidity and mortality. METHODS: A meta-analysis was performed of three randomised, double-blind, placebo-controlled studies (studies 1, 2 and 3) that enrolled 1412 patients with moderate or severe allergic asthma, all requiring daily treatment with inhaled corticosteroids (ICS). Omalizumab was administered subcutaneously every 2 or 4 weeks at a total 4-weekly dose of at least 0.016 mg/kg/IgE [IU/ml]. Each study consisted of a 16-week steroid-stable phase and a 12-16-week steroid-reduction phase, followed by a 24-week extension phase (studies 1 and 2 only). The primary outcome measure was the annualised rate of significant asthma exacerbation episodes (sAEEs) during the steroid-stable phase for the pooled subgroup of 254 high-risk patients (omalizumab, n = 135; placebo, n = 119). sAEEs were those requiring a doubling of baseline ICS dose (studies 1 and 2 only) or use of systemic steroids (all three studies). RESULTS: Overall, the number of patients with at least one sAEE during the steroid-stable phase was reduced from 35% (42/119) with placebo to 18% (24/135) with omalizumab. Mean sAEE rates were 1.56 and 0.69 per patient-year, respectively, a reduction of 56% with omalizumab (p = 0.007). Similar reductions in exacerbations in favour of omalizumab were observed for the whole study period and for all AEEs. In those with a history of hospitalisation in the last year, 6/49 (12%) on placebo vs. 2/44 (4.5%) on omalizumab were re-hospitalised during the study period. Patients treated with omalizumab also showed significantly greater improvements from baseline in PEFR (p = 0.026), overall AQoL (p = 0.042) and mean nocturnal (p = 0.007) and mean total (p = 0.011) asthma symptom scores compared with placebo. CONCLUSIONS: In patients at high risk of serious asthma-related morbidity and mortality, treatment with omalizumab offers the potential to halve the rate of asthma exacerbations and improve disease control.

Adolescent↗
PubMed2000

Can endometrial protection be inferred from the bleeding pattern on combined cyclical hormone replacement therapy.

OBJECTIVE: To investigate the relationship between the timing of withdrawal bleeding on hormone replacement therapy and the state of the endometrium. DESIGN: Double-blind, prospectively randomised dose-ranging study. SETTING: Menopause clinics in the UK and the Netherlands. SUBJECTS: Two hundred and seventy one postmenopausal women aged 40-60. INTERVENTIONS: Administration of six 28-day treatment cycles of a continuous daily dose of 2 mg of micronised 17beta oestradiol with a randomly allocated dose of 5-20 mg of dydrogesterone added for the last 14 days of each. METHODS: Comparison of the timing of the withdrawal bleed recorded in subject-held diaries with an endometrial biopsy obtained toward the end of the last cycle. RESULTS: There was a trend towards later withdrawal bleeding with secretory endometrium and earlier bleeding with inactive or atrophic endometrium, but with too much overlap for this to be of clinical relevance. There were two cases of proliferative and one of hyperplastic endometrium, with no characteristic bleeding pattern. CONCLUSION: Combined sequential HRT with progestogen given for 12-14 days very rarely fails to protect the endometrium. Such failures can not be detected by noting the bleeding pattern. The only suspicious pattern is non-cyclic bleeding, but this will not detect every case of hyperplasia or persistent proliferative endometrium.

Adult↗
PubMed2000

Expression of ErbB receptors during pancreatic islet development and regrowth.

We have characterized expression of the ErbB receptor family and one of its ligands, heregulin, in an effort to identify molecules associated with pancreatic development and regeneration. In addition to studying expression during fetal pancreatic development, we have also studied expression during pancreatic regeneration in the interferon-gamma (IFNgamma)-transgenic mouse, which exhibits significant duct cell proliferation and new islet formation. These studies demonstrate significant expression of the ErbB2, ErbB3, and ErbB4 receptors, in addition to heregulin isoforms, in the developing murine fetal pancreas. We also report significant ductal expression of these proteins during IFNgamma-mediated pancreatic regeneration. This striking expression was absent in 1-week-old neonates, but was clearly visible in pups by 5 weeks of age. These data therefore indicate that ErbB receptor and ligand expression decline by birth in both the IFNbeta-transgenic and non-transgenic mice, and that expression resumes early in postnatal life in the IFNbeta-transgenic mice. The expression of ErbB receptor family members at sites of islet development and regrowth suggests that these molecules might be relevant to these processes.

Animals↗
PubMed2000

Low incidence of endometrial hyperplasia with acceptable bleeding patterns in women taking sequential hormone replacement therapy with dydrogesterone.

A meta-analysis was undertaken to assess the incidence of endometrial hyperplasia during sequentially combined oral 17 beta-estradiol and dydrogesterone (Femoston) treatment in postmenopausal women. Bleeding pattern was assessed separately in each study. Two studies were double-blind, 6-month studies and two were open, long-term (1- or 2-year) studies. 17 beta-estradiol 2 mg daily was combined with dydrogesterone 10 mg for 14 days per 28-day cycle. Endometrial safety was assessed by endometrial biopsy in 369 women treated. In 236 women treated for one year or more, one simple hyperplasia was diagnosed (success rate: 99.61%; lower limit of one-sided 95% confidence interval: 98.16). The last observation carried forward analysis in 369 women also revealed one simple hyperplasia (success rate: 99.73%; lower limit of one-sided 95% confidence interval: 98.72). Cyclic bleeding occurred in approximately 90% of women; the duration and day of onset was highly predictable between cycles and the severity of bleeding was generally rated as slight. In conclusion, sequentially combined 17 beta-estradiol 2 mg and dydrogesterone 10 mg has very good endometrial safety and is associated with light and predictable bleeding of short duration.

Adult↗
PubMed1999

-141 C del/ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population.

Dopamine has long been hypothesised to be involved in the pathogenesis of schizophrenia. The dopamine D2 receptor is a major site of action of neuroleptic agents used in the treatment of schizophrenia. Arinami et al. [1997; Human Mol Genet 6:577-582] have recently sequenced the dopamine receptor 2 (DRD2) gene in Japanese individuals and identified a novel polymorphism: a single cytosine deletion at position -141 disrupting a BstN1 restriction site with a frequency of 0.22 in their control group. They then found a strong association with this polymorphism and schizophrenia (p < 0.001) with an odds ratio of 0.60 in a Japanese population. We have attempted to verify their results by repeating the RFLP analysis on a sample of Scottish schizophrenics and controls. We then combined our data with those from another British sample recruited using similar procedures. The total combined sample size was 439 schizophrenics and 437 controls. We obtained a significant association--p = 0.02 with an odds ratio of 1.41. Schizophrenia is associated with the C insertion in the Japanese, but that association is reversed in Caucasians. Linkage disequilibrium with a causative polymorphism nearby is the most likely explanation for this reverse association.

Alleles↗
PubMed1999

Cervical dysplasia on cervicovaginal Papanicolaou smear among HIV-1-infected pregnant and nonpregnant women. Women and Infants Transmission Study.

OBJECTIVE: To assess the association of squamous intraepithelial lesions (SIL) on cervicovaginal Papanicolaou (Pap) smear among women infected with HIV-1 and their pregnancy status, and historical and clinical factors. METHODS: Study enrollment Pap smears of 452 pregnant and 126 nonpregnant HIV-infected women had cytologic evaluation. The rates of SIL were compared with pregnancy status, immunosuppression, presence of sexually transmitted diseases (STDs) and demographic features. RESULTS: Rates of low grade SIL were similar for pregnant and nonpregnant HIV-1-infected women (17% and 23.8%, respectively; p = .09). Of them, 12 women, 9 pregnant and 3 nonpregnant, had high grade SIL. None had invasive cervical cancer. Low CD4 percentage (odds ratio, [OR] = 3.8; 95% confidence interval [CI], 2.0-7.3) and inflammation (OR = 2.8; 95% CI, 1.8-4.3) were associated with SIL. An association between herpes simplex and SIL (OR = 3.3; 95% CI, 1.1-9.5) was less certain due to clinical diagnosis and low prevalence of herpes simplex (17 of 456 women). CONCLUSIONS: Pap smears for a cohort of HIV-infected pregnant and nonpregnant women revealed a high prevalence of LGSIL but a low prevalence of HGSIL and no cases of cervical cancer. Although pregnancy may not affect the rate of Pap smear abnormalities, SIL is associated with immunosuppression, cervical inflammation, and herpes simplex. Closer surveillance of HIV-1-infected women with these risk factors may be warranted.

Adolescent↗
PubMed1999

102T/C polymorphism of serotonin receptor type 2A gene is not associated with schizophrenia in either Chinese or British populations.

Several pieces of evidence implicate serotonin receptors in the aetiology of schizophrenia, and recently a number of studies have reported a genetic association between the 102T/C polymorphism of serotonin receptor type 2A gene and schizophrenia. Unfortunately a number of failures to replicate these positive associations in both Caucasian and Chinese populations have also been reported. We have examined the 102T/C polymorphism by PCR amplification and restriction analysis of DNA from: 202 schizophrenics and 202 controls from Shanghai; 112 schizophrenics and 224 parents from Chengdu, Cina; and 253 schizophrenics and 244 controls from the the UK. We find no evidence of association or transmission disequilibrium between the 102T/C polymorphism and schizophrenia in any of the groups we have examined. We conclude that either the original positive reports occurred by chance or any effect must be minimal, and urge caution in interpreting small positive results derived using data from different centres.

Carrier Proteins↗
PubMed1999

Present knowledge of gynecologic sarcoma management.

Sarcomas arising in the gynecologic pelvic organs encompass different diseases with very different prognoses. This article attempts to define the different pathologies that arise from tissues of different histologic origin (mesodermal, stromal, and epithelial), and reviews the actual therapeutic knowledge based on the intrinsic prognosis of the sarcoma.

Female↗
PubMed1999

Association study of the CACN1A4 (SCA6) triplet repeat and schizophrenia.

The P/Q type Ca2+ channel alpha 1-subunit (CACN1A4) gene on chromosome 19p13 is a promising candidate susceptibility locus for schizophrenia. Point mutations in CACN1A4 cause familial hemiplegic migraine and episodic ataxia. Expansion in a coding 3' CAG repeat causes spino-cerebellar ataxia type 6 (SCA6). The mouse mutant phenotype totterer has a form of petit-mal epilepsy. These are neurological conditions, all of which exhibit features in common with schizophrenia. The 19p13 area is also paralogous to other genomic regions of interest in schizophrenia genetics. For these reasons, we performed an association study with the CAG repeat and schizophrenia using 225 Scottish schizophrenia and 198 unrelated Scottish controls. The repeat was not associated with the disorder (P = 0.72) and neither did the schizophrenics have significantly longer alleles than the controls (P = 0.45). We conclude that the SCA6 CAG repeat is not associated with schizophrenia susceptibility. However, it remains possible that other variants in the region could be involved.

Alleles↗
PubMed1999

PDX-1 and Msx-2 expression in the regenerating and developing pancreas.

We have observed pancreatic duct cell proliferation and islet regeneration in transgenic mice whose pancreata produce interferon gamma (IFNg mice). We have previously demonstrated that new islet cells derive from endocrine progenitor cells in the pancreatic ducts of this model. The current study was initiated to define these endocrine progenitor cells further and to identify novel markers associated with pancreatic regeneration. Importantly, we have found that PDX-1, a transcription factor required for insulin gene transcription as well as for pancreatic development during embryogenesis, is expressed in the duct cells of IFNg mice. This striking observation suggests an important role for PDX-1 in the marked regeneration observed in IFNg mice, paralleling its critical function during ontogeny. Also demonstrated was elevated expression of the homeobox-containing protein Msx-2 in the pancreata of fetal mice as well as in adult IFNg mice, identifying this molecule as a novel marker associated with pancreatic development and regeneration as well. The identification of PDX-1 and Msx in the ducts of the IFNg transgenic pancreas but not in the ducts of the non-transgenic pancreas suggests that these molecules are associated with endocrine precursor cells in the ducts of the IFNg transgenic mouse.

Animals↗
PubMed1998

Plant-adapted green fluorescent protein is a versatile vital reporter for gene expression, protein localization and mitosis in the filamentous fungus, Aspergillus nidulans.

Green fluorescent protein (GFP) is a useful reporter to follow the in vivo behaviour of proteins, but the wild-type gfp gene does not function in many organisms, including many plants and filamentous fungi. We show that codon-modified forms of gfp, produced for use in plants, function effectively in Aspergillus nidulans both as gene expression reporters and as vital reporters for protein location. To demonstrate the use of these modified gfps as reporter genes we have used fluorescence to follow ethanol-induced GFP expression from the alcA promoter. Translational fusions with the modified gfp were used to follow protein location in living cells; plant ER-retention signals targeted GFP to the endoplasmic reticulum, whereas fusion to the GAL4 DNA-binding domain targeted it to the nucleus. Nuclear-targeted GFP allowed real-time observation of nuclear movement and division. These modified gfp genes should provide useful markers to follow gene expression, organelle behaviour and protein trafficking in real time.

Aspergillus nidulans↗
PubMed1998

An epidemiologic profile of children with special health care needs.

OBJECTIVE: To present an epidemiologic profile of children with special health care needs using a new definition of the population developed by the federal Maternal and Child Health Bureau. METHODS: We operationalized the new definition using the recently released 1994 National Health Interview Survey on Disability. Estimates are based on 30 032 completed interviews for children <18 years old. The overall response rate was 87%. RESULTS: Eighteen percent of US children <18 years old in 1994, or 12.6 million children nationally, had a chronic physical, developmental, behavioral, or emotional condition and required health and related services of a type or amount beyond that required by children generally. This estimate includes children with existing special health care needs but excludes the at-risk population. Prevalence was higher for older children, boys, African-Americans, and children from low-income and single-parent households. Children with existing special health care needs had three times as many bed days and school absence days as other children. An estimated 11% of children with existing special health care needs were uninsured, 6% were without a usual source of health care, 18% were reported as dissatisfied with one or more aspects of care received at their usual source of care, and 13% had one or more unmet health needs in the past year. CONCLUSIONS: A substantial minority of US children were identified as having an existing special health care need using national survey data. Children with existing special health care needs are disproportionately poor and socially disadvantaged. Moreover, many of these children face significant barriers to health care.

Adolescent↗