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Biomedical subjects

J Jones

Publications and source records attributed to J Jones.

At least 127 records · Page 7Linked to original sources
PubMed2001

Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function.

Disruption of the signaling pathways mediated by the receptor tyrosine kinase Tek/Tie2 has shown that this receptor plays a pivotal role in vascularization of the developing embryo. In this report, we have utilized the tetracycline-responsive binary transgenic system to overcome the early lethal cardiovascular defects associated with the tekDeltasp null allele in order to investigate the role of Tek in later stages of vessel growth. We show for the first time in vivo that synchronized loss of tek expression correlates with rapid endothelial cell apoptosis in hemorrhagic regions of the embryo, demonstrating an ongoing requirement for Tek-mediated signal transduction in vascular maintenance.

Actins↗
PubMed2001

The Community Partnerships Experience: a report of institutional transition at East Tennessee State University.

The Community Partnerships Program, sponsored by the W. K. Kellogg Foundation, served as a catalyst for significant changes within East Tennessee State University (specifically its schools of medicine, nursing, and public and allied health) and the rural communities involved. The authors describe the development and implementation of the program and its effects on the students, faculty, communities, and the three participating schools over the period 1992-1999. They also review the changes the program fostered in health professions education and the resulting institutional changes at their university. The primary motivation for change at East Tennessee State University was the desire to develop primary care providers who could more effectively function in an interdisciplinary and interprofessional health care system and who would be sensitive to community needs in rural and underserved areas. The planning process, curricular transformation, implementation of inquiry-based learning, community collaboration, and interdisciplinary education involving students from the three health professions schools are described, including challenges and difficulties (e.g., student attrition; retention of volunteer community-based clinical preceptors; initial faculty resistance; a climate of competition rather than cooperation). Outcomes are described, including students' enrollment and attrition in the program over time, performances on the U.S. Medical Licensing Examination, program graduates' career choices, and the types and locations of their practices. The program's students performed as well on professional licensing examinations as did their peers enrolled in traditional programs. Program graduates have been much more likely to select primary care careers and to practice in rural locations than have their non-program peers. The development strategies and experience gained could give useful insights to other universities contemplating a community-based component for health professionals within their existing curricula.

Community Participation↗
PubMed2001

Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: a Southwest Oncology Group Study.

PURPOSE: Patients with locally advanced bladder cancer or who are not medically fit for surgery are a therapeutic dilemma. Radiotherapy with or without single agent cisplatin has been the major therapeutic modality. A phase II Southwest Oncology Group trial investigated the efficacy and feasibility of 5-fluorouracil, cisplatin and radiation in this patient subset. MATERIALS AND METHODS: Eligible patients had muscle invasive bladder cancer (clinical stages T2-T4) with nodal involvement at or below the level of bifurcation of the iliac vessels, were medically or surgically inoperable, or refused cystectomy. Patients underwent pretreatment cystoscopy and detailed tumor mapping, and were treated with 75 mg. /m.2 cisplatin on day 1 and 1 gm./m.2 daily, 5-fluorouracil on days 1 to 4 and definitive radiotherapy. Chemotherapy was repeated every 28 days, twice during and twice after radiation. RESULTS: From October 1993 to April 1998, 60 patients were enrolled in study. Of the 56 eligible patients 34% had unresectable tumors, 21% were not medically fit for surgery and 45% refused cystectomy. Overall, 68% of the patients had clinical T3 tumors or greater and 22% had nodal metastasis. Treatment was completed as planned in 32 of 56 (57%) patients. The most frequent grade 3 or 4 toxicities were neutropenia, stomatitis or mucositis, diarrhea, neuropathy and nausea. There were 53 patients who were evaluable for response, although response was not determined for 18. The overall response rate was 51% (95% confidence interval [CI] 37 to 65) based on intent to treat with a complete response rate of 49% (95% CI 35 to 63). Estimated median survival of the 56 patients was 27 months (95% CI 21 to 40 months) with an overall 5-year survival of 32%. The 5-year survival of the 25 patients who refused surgery was 45%. CONCLUSIONS: Concurrent 5-fluorouracil, cisplatin and radiation therapy is feasible. Despite a promising complete response rate, the overall 5-year survival suggests the need for more effective systemic therapy. The 5-year survival of patients who refused cystectomy suggests that this combined modality may provide another alternative to cystectomy for these patients.

Aged↗
PubMed2001

Biochemical markers of maternal bone turnover are elevated in pre-eclampsia.

OBJECTIVES: To investigate the hypothesis that bone turnover is reduced in pre-eclampsia compared with normal pregnancy. DESIGN: A prospective cross-sectional study. SETTING: Obstetric unit at the Chelsea and Westminster Hospital, London. METHODS: Third trimester maternal plasma levels of the cross-linked carboxyl-terminal telo-peptide of type I collagen (ICTP), (a marker of bone resorption) and the carboxyl terminal pro-peptide of type I pro-collagen (PICP), (a marker of bone formation) were compared in 25 women with pre-eclampsia and in 24 normal pregnant controls. The subjects were matched for maternal age, booking body mass index and gestational age. PICP and ICTP levels were measured by radio-immunoassay. RESULTS: ICTP and PICP levels were significantly increased in women with pre-eclampsia compared with the normal pregnant controls (P = 0.0001 and P = 0.004, for ICTP and PICP respectively, Wilcoxon signed ranked test). There was no significant correlation between either of the markers and booking body mass index, blood pressure, serum uric acid levels or platelet count. CONCLUSIONS: These data suggest that bone turnover is increased in established pre-eclampsia compared with normal pregnancy. Further studies are required to investigate whether this precedes the onset of the disease.

Adult↗
PubMed2001

Fetal bone metabolism in normal and rhesus isoimmunised pregnancies.

OBJECTIVE: To construct gestation-specific reference intervals for fetal concentrations of biochemical markers of bone metabolism and assess the effect of rhesus isoimmunisation on these. METHODS: Fetal blood samples were obtained by cordocentesis from 175 pregnancies (43 complicated by rhesus isoimmunisation) and assayed for carboxy terminal pro-peptide of type I pro-collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) which directly monitor the rate of bone formation and resorption respectively. RESULTS: Both plasma PICP and ICTP were negatively correlated with gestational age (r = -0.351 and -0.472 for PICP and ICTP, respectively, and P < 0.001 for both). In fetuses affected by rhesus isoimmunisation PICP levels were lower (P=0.030) and more variable (P <0.001) than expected, compared with normal unaffected fetuses. However, no such differences were found in the ICTP levels. In the fetuses affected by rhesus isoimmunisation there was a significant correlation between haemoglobin concentration and both PICP (r = 0.504, P = 0.001) and ICTP (r = 0.343, P = 0.030). CONCLUSIONS: Fetal bone turnover declines from early second trimester to term, and may be deranged in fetuses affected by rhesus isoimmunisation.

Adolescent↗
PubMed2001

The effect of the introduction of NHS Direct on requests for telephone advice from an accident and emergency department.

OBJECTIVES: To assess the effect of the introduction of NHS Direct on advice seeking calls to an accident and emergency (A&E) department. METHODS: Review of departmental telephone advice logbook before and after the introduction of NHS Direct together with recording of the number of calls redirected to NHS Direct by the hospital switchboard and the A&E department. RESULTS: The number of advice calls responded to within the department fell by 72.6% (84 in October 1998, 23 in October 1999). The number of calls redirected to NHS Direct was 242. The total number of calls to the hospital seeking advice thus increased by 315%. CONCLUSION: The introduction of NHS Direct has allowed for a mechanism to be put in place reducing the number of calls for advice being dealt with by the A&E department clinical staff with a concomitant time saving. At the same time the number of calls for advice made by the public to the hospital has dramatically increased.

Emergency Service, Hospital↗
PubMed2001

Synchronous bladder augmentation and living related kidney transplantation.

Ileocystoplasty for enlargement of bladder capacity in conjunction with renal transplantation has been described in several cases. However, the surgical approach has been accomplished as a two-stage procedure. We report the case of a 21-year-old female myelomeningocele patient with end-stage renal insufficiency who was treated with ileocytstoplasty and living related renal transplantation at a single stage. Convalescence remained uneventful. On follow-up 13 months after the operation, the renal parameters remained stable.

Adult↗
PubMed2001

Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis.

Here we report the effects of gentamicin treatment on cystic fibrosis transmembrane regulator (CFTR) production and function in CF airway cells and patients with CF with premature stop mutations. Using immunocytochemical and functional [6-methoxy-N- (3-sulfopropyl) quinolinium (SPQ)-based] techniques, ex vivo exposure of airway cells from stop mutation CF patients led to the identification of surface-localized CFTR in a dose-dependent fashion. Next, five patients with CF with stop mutations and five CF control subjects were treated with parenteral gentamicin for 1 wk, and underwent repeated in vivo measures of CFTR function (nasal potential difference [PD] measurements and sweat chloride [Cl(-)] testing). During the treatment period, the number of nasal PD readings in the direction of Cl(-) secretion was increased approximately 3-fold in the stop mutation patient group compared with controls (p < 0.001), and four of five stop mutation patients with CF had at least one reading during gentamicin treatment with a Cl(-) secretory response of more than -5 mV (hyperpolarized). A response of this magnitude was not seen in any of the CF control subjects (p < 0.05). In an independent series of experiments designed to test the ability of repeat nasal PDs to detect wild-type CFTR function, evidence of Cl(-) secretion was seen in 88% of control (non-CF) nasal PDs, and 71% were more than -5 mV hyperpolarized. Together, these results suggest that gentamicin treatment can suppress premature stop mutations in airway cells from patients with CF, and produce small increases in CFTR Cl(-) conductance (as measured by the nasal PD) in vivo.

Adolescent↗
PubMed2001

Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia.

Fibrous dysplasia (FD) of bone is characterized by focal replacement of normal bone and marrow with abnormal bone and fibrous tissue. It arises from postzygotic activating mutations of the GNAS1 gene. Hypophosphatemia due to renal phosphate wasting has been reported in association with FD as a part of the McCune-Albright Syndrome (MAS), which is characterized by FD, skin hyperpigmentation, and precocious puberty. To date, the prevalence and mechanism of phosphate wasting has not been well studied. We evaluated 42 patients with FD/MAS. Serum and urine samples were tested for indices of mineral metabolism, amino acid handling, and markers of bone metabolism. Twenty (48%) patients had some degree of renal phosphate wasting. Nephrogenous cyclic adenosine monophosphate (cAMP) was normal in FD patients, suggesting that the underlying cause of phosphate wasting is not the presence of activating GNAS1 mutations in the kidney. In addition, there was evidence of a more generalized renal tubulopathy as represented by the presence of abnormal vitamin D metabolism, proteinuria in 36 (86%) patients, and aminoaciduria in 39 (94%) patients. Renal phosphate wasting significantly correlated with the degree of bone involvement, as assessed by serum and urine markers of bone metabolism, suggesting that a circulating factor produced by FD bone and impacting on the kidney may be the mechanism. These data show that phosphaturia as part of a generalized renal tubulopathy represents the most common extraskeletal manifestation of FD and that the observed tubulopathy is similar to that seen in tumor-induced osteomalacia (TIO).

Adolescent↗
PubMed2001

Hypophosphatasia: molecular diagnosis of Rathbun's original case.

In 1948, Dr. John Campbell Rathbun characterized the disorder "hypophosphatasia" when he reported paradoxically low levels of alkaline phosphatase (ALP) activity in blood and in several tissues from an infant who died with rickets and epilepsy, which seemed to reflect "a new developmental anomaly." Hypophosphatasia is now recognized to be an inborn error of metabolism featuring deficient activity of the tissue-nonspecific isoenzyme of ALP (TNSALP) caused by deactivating mutations in TNSALP. Here, we show, more than 50 years after Rathbun's case report, that analysis of the parental DNA indicates compound heterozygosity involving two missense mutations (G340A and A881C) in TNSALP caused the death of Rathbun's patient.

Alkaline Phosphatase↗
PubMed2001

The effectiveness of outpatient pulmonary rehabilitation in chronic lung disease: a randomized controlled trial.

BACKGROUND: Patients with chronic pulmonary disease have been shown to benefit from pulmonary rehabilitation programs. Published work has often been from specialized teaching centers and has involved inpatient stay. We assessed an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic lung disease, using the St. George's Respiratory Questionnaire (SGRQ) (which measures health-related quality of life) as the primary outcome measure. METHODS: We undertook a randomized, prospective, parallel-group controlled study of an outpatient rehabilitation program in 65 patients with COPD (44 men and 21 women; mean age, 69.5 years [SD, 9.2 years]; FEV(1), 41% predicted [SD, 18.5%]). The active group (n = 36) took part in a 6-week program of education (2 h weekly) and exercise (1 h weekly). The control group (n = 29) were reviewed routinely as medical outpatients. The SGRQ was administered under supervision by a blinded observer at study entry, 12 weeks, and 24 weeks. RESULTS: The SGRQ in the active group was 59.9 (SE, 2.0) at study entry (n = 36), 47.4 (SE, 2.3) at 12 weeks (n = 32), and 50.6 (SE, 2.5) at 24 weeks (n = 24). The SGRQ in the control group was 59.3 (SE, 2.5) at study entry and did not change significantly over 24 weeks. There was a difference of 10.4 points (confidence interval [CI], 3.6 to 17.3) between the two groups at 12 weeks (p < 0.001) and of 8.1 points (CI, 1.4 to 14.9) at 24 weeks (p = 0.02) in favor of the active group. CONCLUSIONS: A 6-week outpatient-based program significantly improved quality of life in patients with moderate-to-severe COPD. Benefit was still evident after 24 weeks.

Aged↗
PubMed2001

Space radiation and cataracts in astronauts.

For over 30 years, astronauts in Earth orbit or on missions to the moon have been exposed to space radiation comprised of high-energy protons and heavy ions and secondary particles produced in collisions with spacecraft and tissue. Large uncertainties exist in the projection of risks of late effects from space radiation such as cancer and cataracts due to the paucity [corrected] of epidemiological data. Here we present epidemiological [corrected] data linking an increased risk of cataracts for astronauts with higher lens doses (>8 mSv) of space radiation relative to other astronauts with lower lens doses (<8 mSv). Our study uses historical data for cataract incidence in the 295 astronauts participating in NASA's Longitudinal Study of Astronaut Health (LSAH) and individual occupational radiation exposure data. These results, while preliminary because of the use of subjective scoring methods, suggest that relatively low doses of space radiation may predispose crew to [corrected] an increased incidence and early appearance of cataracts.

Aged↗
PubMed2001

Microvessel density and p53 overexpression in young women with breast cancer: a case-control study.

Several reports have indicated that young women (less than 40 years of age) with breast cancer have a worse prognosis than older women. We performed a case-control study in order to confirm this observation and to determine whether this was attributable to increased microvessel density (MVD) or p53 expression. Twenty-six young women (cases) with stage I-III breast cancer that had adequate paraffin-embedded archival tissue were identified by the Montefiore Medical Center Tumor Registry over a 24-year period. For each case, two or three control subjects at least 40 years of age or older were selected from the registry and matched for nodal status and tumor size. Immunohistochemistry was performed for MVD and p53 overexpression. A Cox proportional hazard model was performed to examine the influence of age, MVD, p53 overexpression, and recognized prognostic factors on disease-free and overall survival. There were 26 cases (median age, 36 years) and 72 controls (median age, 64 years). The groups were well matched for known prognostic variables. There was no significant difference in p53 overexpression or MVD in the cases and controls. In multivariate analysis, the only features associated with an increased risk of recurrence included young age (hazard ratio [HR] = 2.49; 95% confidence interval [CI]: 1.18-5.25; P = 0.02) and positive lymph nodes (HR = 2.44; 95% CI: 1.12-5.30; P = 0.02). We have confirmed previous reports demonstrating a worse prognosis for women younger than 40 years with invasive breast cancer but found no correlation between young age and MVD or p53 overexpression when adjusted for other variables.

Adult↗
PubMed2001

Discussing end-of-life issues with patients: reflections on developing an interviewing template to assist first-year medical students.

First-year medical students at the University of Ottawa currently use an interview template to work with patients who have chronic illnesses. A second-year medical student (JJ) modified the template to facilitate the discussion of death and end-of-life care by students who may have had little previous experience with such sensitive topics. The modification was accomplished using the following strategies: a systematic literature review on long-term care or nursing home residents' end-of-life needs; participation in a support group for families of dying patients; volunteering in a day hospice program for two months; piloting the template with two palliative care patients, one resident of a long-term care facility, and one family member. The paper summarizes and reflects on the process.

Aged↗
PubMed2000

Evidence for genetic linkage of Alzheimer's disease to chromosome 10q.

Recent studies suggest that insulin-degrading enzyme (IDE) in neurons and microglia degrades Abeta, the principal component of beta-amyloid and one of the neuropathological hallmarks of Alzheimer's disease (AD). We performed parametric and nonparametric linkage analyses of seven genetic markers on chromosome 10q, six of which map near the IDE gene, in 435 multiplex AD families. These analyses revealed significant evidence of linkage for adjacent markers (D10S1671, D10S583, D10S1710, and D10S566), which was most pronounced in late-onset families. Furthermore, we found evidence for allele-specific association between the putative disease locus and marker D10S583, which has recently been located within 195 kilobases of the IDE gene.

Age of Onset↗