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Biomedical subjects

J Cox

Publications and source records attributed to J Cox.

At least 19 recordsLinked to original sources
PubMed2006

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Amino Acid Sequence↗
PubMed2005

Validation of the Maltese version of the Edinburgh Postnatal Depression Scale.

This paper reports the validation of the Maltese translated Edinburgh Postnatal Depression Scale against Diagnostic Criteria for Research (DCR-10) diagnosis for severe, moderate and mild depression during pregnancy (antenatally) and at 8 weeks postnatally. A random sample of 239 pregnant women were interviewed at booking and at 8 weeks postnatally using a detailed sociodemographic history, the Revised Version of the Clinical Interview Schedule (CIS-R) and Maltese translation of the Edinburgh Postnatal Depression Scale (EPDS). The Maltese translated EPDS had good face validity and had satisfactory sensitivity and specificity for identifying depression both antenatally and postnatally. Cut-off scores of 13/14 antenatally and 11/12 postnatally are recommended when using the Maltese EPDS. Controversial issues surrounds the use of the EPDS in clinical practice. However, introducing the EPDS in pregnancy will help to identify women who are at high risk of depression so as to treat appropriately and early in the antenatal period.

Adult↗
PubMed2005

Estimating medium- and long-term trends in malaria transmission by using serological markers of malaria exposure.

The implementation and evaluation of malaria control programs would be greatly facilitated by new tools for the rapid assessment of malaria transmission intensity. Because acquisition and maintenance of antimalarial antibodies depend on exposure to malaria infection, such antibodies might be used as proxy measures of transmission intensity. We have compared the prevalence of IgG antibodies with three Plasmodium falciparum asexual stage antigens in individuals of all ages living at varying altitudes encompassing a range of transmission intensities from hyper- to hypoendemic in northeastern Tanzania, with alternative measures of transmission intensity. The prevalence of antibodies to merozoite surface protein-1(19) was significantly more closely correlated with altitude than either point-prevalence malaria parasitemia or single measures of hemoglobin concentration. Analysis of age-specific seroprevalence rates enabled differentiation of recent (seasonal) changes in transmission intensity from longer-term transmission trends and, using a mathematical model of the annual rate of seroconversion, estimation of the longevity of the antibody response. Thus, serological tools allow us to detect variations in malaria transmission over time. Such tools will be invaluable for monitoring trends in malaria endemicity and the effectiveness of malaria control programs.

Adult↗
PubMed2005

Haematological cancers in the breast and axilla: a drop in an ocean of breast malignancy.

We have reviewed imaging findings of 32 female patients with a proven haematological malignancy in the breast and axilla presenting to two breast units over a 13-year period. Nineteen patients had screen-detected lesions, and 13 presented to symptomatic services. The most common histological diagnosis was of non-Hodgkins lymphoma. Of the 12 patients who presented with disease in the breast, six (all with primary breast lymphoma) presented with a well-defined mass on mammography. The range of radiological appearances is, however, highly variable.

Aged↗
PubMed2005

Malaria in the southern highlands of Tanzania: a review of hospital records.

Outpatient attendance and inpatient admission records were examined to assess malaria situation in ten hospitals in Mbeya and Iringa Regions in southern highlands of Tanzania for a period of fifteen years from 1986-2000. Generally, records were deficient, some hospitals with entire annual records missing for one or several years. However, malaria maintained a high profile as the leading cause of admissions and deaths among hospital attendees. Of the ten hospitals, seven recorded malaria as the leading cause of admissions for at least ten years; in three of these, it was also the top ranking cause of child death. Although the respective magnitude of malaria morbidity and mortality burdens was not directly correlated with altitude (P>0.5), three hospitals (Uwemba, Bulongwa and Ikonda) at above 2,000m, had relatively lower malaria morbidity and mortality burden compared to three worst affected facilities (Ilembula, Chimala and Mbozi) in the lower range of altitude, located in the flat plains. In conclusion, malaria is the major public health problem in the highlands districts of Mbeya and Iringa Regions in Tanzania that need the attention of health authorities and immediate intervention. However, more research is required to establish the true picture of the problem among the communities.

Child↗
PubMed2004

Neutron capture cross section measurement of 151Sm at the CERN neutron time of flight facility (n_TOF).

The151Sm(n,gamma)152Sm cross section has been measured at the spallation neutron facility n_TOF at CERN in the energy range from 1 eV to 1 MeV. The new facility combines excellent resolution in neutron time-of-flight, low repetition rates, and an unsurpassed instantaneous luminosity, resulting in rather favorable signal/background ratios. The 151Sm cross section is of importance for characterizing neutron capture nucleosynthesis in asymptotic giant branch stars. At a thermal energy of kT=30 keV the Maxwellian averaged cross section of this unstable isotope (t(1/2)=93 yr) was determined to be 3100+/-160 mb, significantly larger than theoretical predictions.

Journal Article↗
PubMed2004

Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma.

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1-19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27-42) and 29% (95% CI 22-36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.

Acute Disease↗
PubMed2004

Spill-over of European bat lyssavirus type 1 into a stone marten (Martes foina) in Germany.

European bat lyssavirus type 1 (EBLV-1, genotype 5) is known to endemically circulate in insectivorous bat populations in Germany. In August 2001, a rabies suspect stone marten (Martes foina) was found in the city of Burg (Saxony-Anhalt, Germany) and was sent to the regional veterinary laboratory for routine rabies diagnosis. Whereas brain samples repeatedly tested negative in the fluorescent antibody test for classical rabies virus (genotype 1), the mouse inoculation test and the rabies tissue culture inoculation test yielded positive results. Rabies viral RNA was also detected in the stone marten brain sample both by nested and heminested RT-PCR specific for the nucleoprotein gene and for the nucleoprotein phosphoprotein junction of rabies virus. The amplification products were sequenced to genotype the isolate. Sequence data obtained from the first-round RT-PCR products were analysed and the suspect stone marten isolate was confirmed as a rabies related virus (EBLV-1a). Phylogenetic comparison with sequences from recent genotype five isolates from Germany and Denmark showed that it was closely related to a previous isolate of EBLV-1 from a serotine bat in Saxony-Anhalt obtained in the same year in an area adjacent to the place where the EBLV-1 infected stone marten was found. Both EBLV-1 isolates share a 99.5% identity. This is the first report of an EBLV-1a spill-over from an insectivorous bat into wildlife in Europe.

Animals↗
PubMed2004

Susceptibility of ferrets (Mustela putorius furo) to experimentally induced rabies with European Bat Lyssaviruses (EBLV).

Twenty ferrets (Mustela putorius furo) were inoculated by intramuscular (i.m.) injection with European Bat Lyssaviruses (EBLV) type-1 and 2 using 10(4.0) foci-forming units (FFU) EBLV-2 (n = 6), 10(4.0) FFU EBLV-1 (n = 7) and 10(6.0) FFU EBLV-1 (n = 7). Furthermore, 15 mice received 10(2.5) FFU EBLV-2 (n = 5), 10(2.5) FFU EBLV-1 (n = 5) and 10(4.5) FFU EBLV-1 (n = 5) by i.m. inoculation. All ferrets and mice receiving the higher dose of EBLV-1 succumbed to infection. In contrast, only three of seven ferrets and two of five mice inoculated experimentally with the lower EBLV-1 dose died. By comparison, all of the EBLV-2 infected ferrets and four of five mice survived infection. All 20 infected ferrets seroconverted. Using sensitive molecular tools, the virus was detected in different tissues, but it could not be found in any saliva samples taken during the 84-day observation period.

Animals↗
PubMed2004

Monoclonal antibody characterization of rabies virus isolates from Russia, Finland and Estonia.

Five different rabies virus variants were identified among rabies virus-positive samples from Russia, Finland and Estonia, using a panel of five anti-nucleocapsid monoclonal antibodies. Two rabies virus isolates showed a different reaction pattern, suggesting the presence of a new antigenic variant. The results were compared with the data obtained by other research groups.

Animals↗
PubMed2004

HIV status of sexual partners is more important than antiretroviral treatment related perceptions for risk taking by HIV positive MSM in Montreal, Canada.

OBJECTIVE: To examine the role of antiretroviral treatment related perceptions relative to other clinical and psychosocial factors associated with sexual risk taking in HIV positive men who have sex with men (MSM). METHODS: Participants were recruited from ambulatory HIV clinics in Montreal. Information on sociodemographic factors, health status, antiretroviral treatment related perceptions, and sexual behaviours was collected using a self administered questionnaire. At-risk sexual behaviour was defined as at least one occurrence of unprotected insertive or receptive anal intercourse in the past 6 months. Multivariate logistic regression was performed to evaluate the associations between at-risk sexual behaviour and covariates. RESULTS: 346 subjects participated in the study. Overall, 34% of subjects were considered at risk; 43% of sexually active subjects (n=274). At-risk sexual behaviour was associated with two antiretroviral treatment related perceptions: (1) taking antiretroviral treatment reduces the risk of transmitting HIV (adjusted odds ratio (OR), 2.10; 95% confidence interval (CI), 1.16 to 3.80); and (2) there is less safer sex practised by MSM because of HIV treatment advances (OR, 1.82; CI, 1.14 to 2.90). Other factors, however, were more strongly associated with risk. These were: (1) safer sex fatigue (OR, 3.23; CI, 1.81 to 5.78); (2) use of "poppers" during sexual intercourse (OR, 6.28; CI, 2.43 to 16.21); and (3) reporting a greater proportion of HIV positive anal sex partners, compared with reporting no HIV positive anal sex partners: (a) <50% HIV positive (OR, 16.79; CI, 4.70 to 59.98); (b) > or =50% HIV positive (OR, 67.67; CI, 15.43 to 296.90). CONCLUSION: Despite much emphasis on HIV treatment related beliefs as an explanation for sexual risk taking in MSM, this concern may play a relatively minor part in the negotiation of risk by HIV positive MSM. Serosorting, safer sex fatigue, and the use of poppers appear to be more important considerations in understanding the sexual risk behaviours of HIV positive MSM.

Adult↗
PubMed2004

Bioavailability of rifampicin in Indonesian subjects: a comparison of different local drug manufacturers.

To examine the bioavailability of rifampicin formulations produced in Indonesia, we conducted a single-dose, double-blind, cross-over bioavailability study. Antituberculosis drugs from three Indonesian manufacturers and one international manufacturer were compared in 12 healthy Indonesian subjects. Out of three local manufacturers, two showed equal bioavailability compared to the reference standard, and one showed slightly lower bioavailability (ratio 0.86; 90% confidence interval 0.80-0.91) and substandard rifampicin content of drug preparations. Plasma rifampicin concentrations in this study were more than three-fold higher than concentrations recently found in tuberculosis patients in Indonesia, which suggests that unknown (disease-related) determinants may reduce the bioavailability of rifampicin formulations.

Adult↗
PubMed2003

Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: an analysis from the Radiation Therapy Oncology Group protocol 86-10.

PURPOSE: The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. MATERIALS AND METHODS: Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. RESULTS: Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations. CONCLUSION: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.

Adult↗
PubMed2003

HA14-1 selectively induces apoptosis in Bcl-2-overexpressing leukemia/lymphoma cells, and enhances cytarabine-induced cell death.

The Bcl-2 oncoprotein is commonly overexpressed in hematological malignancy, where it promotes the survival of neoplastic cells. Recently, a small molecule (HA14-1) was reported to bind the surface pocket of Bcl-2 that mediates antiapoptotic interactions, triggering apoptosis in a Bcl-2-transfected cell line. We investigated the activity of this compound in a panel of malignant hematopoietic cell lines. Consistent with its proposed role as a Bcl-2 inhibitor, HA14-1 was most cytotoxic in lines expressing high levels of Bcl-2. In addition, at lower concentrations (5-12.5 muM), the compound predominantly triggered apoptosis. However, at concentrations two-fold higher than this and above, increasing primary necrosis was observed, suggesting the onset of interactions supplementary to Bcl-2 inhibition. In experiments on primary cells, 25 muM HA14-1 induced extensive apoptosis in acute leukemic blasts, but also suppressed normal hematopoietic colony formation to <50% of baseline. Importantly, low-concentration HA14-1 (5 muM) was nontoxic to normal colony-forming cells, whereas it enhanced the cytotoxicity of the antileukemia drug cytarabine in Bcl-2-positive lymphoblastic leukemia cells. In conclusion, our results indicate that HA14-1 at low concentration selectively triggers apoptosis in malignant hematopoietic cells that overexpress Bcl-2. Agents of this class may have particular utility in combination with cytotoxic chemotherapy drugs.

Apoptosis↗
PubMed2003

Type 2 diabetes presenting as diabetic ketoacidosis in adolescence.

We report two black adolescent subjects who presented with diabetic ketoacidosis, but who lacked autoimmune markers and demonstrated clinical and biochemical characteristics more typical of Type 2 diabetes, including obesity, acanthosis nigricans, positive family history for Type 2 diabetes, and Type 2 diabetic dyslipidaemia. Subsequent to acute presentation, insulin was discontinued in both subjects and excellent glycaemic control was achieved with metformin therapy alone. Four months following acute presentation, both had adequate C-peptide responses to intravenous glucagon. Type 2 diabetes can present as diabetic ketoacidosis in obese adolescent subjects.

Acanthosis Nigricans↗
PubMed2002

Revalidation of the isobaric multiplet mass equation.

We have determined the energy of the J(pi) = 1/2(+), T = 3/2 resonance in 32S(p,p) to be E(p) = 3374.7+/-0.8 keV. This disagrees with the previously accepted value of E(p) = 3370+/-1 keV by Abbondanno et al. [Nuovo Cimento 70A, 391 (1970)] and solves a problem raised by recent observations of unexpected deviations from the isobaric multiplet mass equation. This resonance is also important in calibrating the beta-delayed proton spectra from 33Ar and 32Ar, and our findings may modify previous conclusions.

Journal Article↗