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Biomedical subjects

M Hudson

Publications and source records attributed to M Hudson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Expression of apoptosis-related genes in human head and neck squamous cell carcinomas undergoing p53-mediated programmed cell death.

Human head and neck squamous cell carcinoma (HNSCC) lines infected with a replication-defective Ad5CMV-p53 vector bearing a wild-type human p53 gene were used to examine alterations in the production of proteins implicated in regulating apoptosis. Because HNSCC lines express abundant levels of c-myc, and simultaneous expression of c-myc and p53 is known to trigger apoptosis in other cells, cooperation between these two genes was examined. Surprisingly, levels of c-myc mRNA and protein were rapidly and profoundly suppressed after infection with wild-type p53. Suppression of c-myc using antisense oligodeoxynucleotides (in the absence of p53) was sufficient to trigger apoptosis in Tu-138 cells, raising the possibility that the reduction of c-myc may be involved in at least one of the cell death pathways mediated by p53. Expression of a panel of Bcl-2 homology proteins was also examined in HNSCC lines undergoing p53-mediated apoptosis. No changes in Bcl-2, Bak, or Bcl-xS were found after p53 expression. Increased levels of the apoptosis-accelerating protein Bax were found in HNSCC lines after infection with Ad5CMV-p53. Induction of the apoptosis-inhibiting protein Bcl-xL was observed in Tu-167 cells and may account for the delayed onset of apoptosis in these cells. These studies suggest that multiple pathways may regulate apoptosis after transient overexpression of p53.

Apoptosis↗
PubMed1999

Locum doctors in general practice: motivation and experiences.

BACKGROUND: There is evidence of dissatisfaction with locum doctors' performance, but little is known about doctors who work as locums in general practice or about their experiences of this work. AIM: To describe the motivations and experiences of doctors providing locum cover in general practices. METHOD: A postal questionnaire survey distributed to locums through organizations such as locum groups, commercial agencies, and general practices. RESULTS: Questionnaires were returned by 111 doctors currently working as locums in general practice. Four main reasons for working as a locum GP were: as a short-term option while between posts, to gain experience of different practices before commitment to one practice, to balance work and family or other commitments, to continue part-time work after retirement. One-quarter of responders intended to continue working as a locum indefinitely. The drawbacks of locum work included frustration with low status, lack of security, and difficulty accessing structured training and education. CONCLUSION: Locum doctors in general practice are a heterogeneous group that includes those who have chosen this type of work. The doctors who intend to continue as locums indefinitely represent a useful resource in primary care whose ability to provide short-term cover could be maximized. The need to control the quality of 'freelance' doctors should not overshadow the need to control the quality of their working environments.

Attitude of Health Personnel↗
PubMed1999

Preface

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Journal Article↗
PubMed1998

Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin's disease.

Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) is effective prophylaxis and treatment of EBV-positive immunoblastic lymphoma in immunocompromised patients. In 50% of patients with Hodgkin's disease, the tumor cells are EBV antigen-positive and may therefore also be suitable targets for treatment with virus-specific CTLs. However, Hodgkin's disease may produce several inhibitory effects on immune induction and effector function in vivo, which may preclude the generation or effector function of CTLs reactive against EBV viral proteins, including those expressed by the tumor cells. We have investigated whether EBV-specific CTLs could be generated ex vivo from 13 patients with Hodgkin's disease: nine with active relapsed disease and four who were in clinical remission after a first or subsequent relapse. CTL lines were successfully generated from nine of 13 patients (five active disease, four remission). Although these lines had an abnormal pattern of expansion comparable to EBV-specific CTLs generated from normal donors, their phenotype was normal except for reduced expression of the zeta chain of the T-cell receptor (TCR). Their cytotoxicity was also compared to EBV-specific lines generated from normal donors and included activity against LMP2a, one of the three weakly immunogenic viral antigens expressed by Hodgkin's tumor cells. To assess the activity of the CTLs in vivo, they were gene-marked and infused into three patients with multiply relapsed disease. The CTLs persisted for more than 13 weeks postinfusion and retained their potent antiviral effects in vivo, thereby enhancing the patient immune response to EBV. This approach may therefore have value in the treatment of EBV-positive Hodgkin's disease.

Adolescent↗
PubMed1998

Intravenous bisphosphonate prevents symptomatic osteoporotic vertebral collapse in patients after liver transplantation.

Osteoporosis is common in patients with chronic cholestatic liver disease, and atraumatic spinal fracture is a recognized complication after orthotopic liver transplantation. Bisphosphonates are potent inhibitors of osteoclast bone resorption and have been successfully used to treat postmenopausal osteoporosis. We examined whether preoperative bone mineral density can predict the risk of fracture after orthotopic liver transplantation and whether intravenous bisphosphonate can prevent fractures in high-risk patients. Beginning in February 1993, standard bone mineral density measurements of the lumbar spine were performed as part of routine pretransplantation assessment. On the basis of a preliminary analysis from January 1995, patients with a lumbar spine bone mineral density of <0.84 g/cm2, or <84% of the predicted value (age/sex), were treated with intravenous bisphosphonate (pamidronate disodium) every 3 months before and for 9 months after liver transplantation. Bone mineral density measurements were available in 90 of 136 consecutive first transplants performed in our unit from February 1993 to September 1996. Before the use of pamidronate, 7 patients sustained symptomatic vertebral fractures. Their mean spine bone mineral density was lower than in the 38 patients with no clinical evidence of fracture (81.8% +/- 12.3% v 94.2% +/- 10.2%; P = .006). Since the introduction of pamidronate, no symptomatic vertebral fractures have occurred. Of 29 surviving patients with bone mineral density <0.84 g/cm2 before transplantation, 38% who did not receive treatment with pamidronate suffered spontaneous fracture, whereas 0 of 13 who received treatment suffered such a complication. A low lumbar spine bone mineral density is associated with a high risk of symptomatic vertebral fracture after liver transplantation. These results suggest that this risk is considerably reduced by the administration of intravenous bisphosphonate before and after transplantation.

Absorptiometry, Photon↗
PubMed1998

Post-regraft supra-hepatic caval obstruction in liver transplantation: a successful outcome with expandable stents. A case report.

Supra-hepatic inferior vena cava (IVC) obstruction is an unusual complication following an orthotopic liver transplantation (OLT) and is seen more often in hepatic regrafts. Dilatation of these stenotic lesions and the use of endovascular stents has been described in the past. Although the results of this technique are unquestionably superior to surgical correction, their use in the very early post-operative period is not without danger. Herein we describe a case where this modality was used successfully within 24 h of an OLT.

Dilatation↗
PubMed1998

Late vascular occlusion of central lines in pediatric malignancies.

OBJECTIVE: To determine whether thrombi or vascular occlusion represent a late complication persisting several years after removal of central venous lines (CVLs) in children and adolescents treated for childhood cancer. METHODS: Children whose treatment for malignancy included placement of a CVL that had been removed at least 2 months previously were studied during scheduled follow-up that included contrast-enhanced computed tomography. Spiral volume acquisition was used to obtain 3-mm images from the chest apices through the right hilum, and three-dimensional reconstruction of angiograms was performed. Thrombosis/occlusion was defined as narrowing, obstruction, or filling defect of the deep venous system, with or without the formation of collateral veins. Charts were reviewed to document patient characteristics, previous CVL complications, administration of hyperalimentation, use of urokinase, and family history of venous thrombosis. RESULTS: Twenty-three patients treated for solid tumors and 2 treated for B-cell acute lymphocytic leukemia or lymphoma were studied. Lines had been in place from 0.2 to 36 months (median, 7.4) and were removed at 2.3 to 121.8 months (median, 32.5) before study. Nine patients received hyperalimentation for periods ranging from 2 to 38 weeks (median, 12). Four patients had required urokinase instillations, and one developed superior vena cava syndrome; 4 had a CVL-related infection (two superficial and two Candida line infections). Occlusion was seen on computed tomography angiograms in 3 of the 25 patients (12%; 95% confidence interval: 4.5-31%). One of the patients with occlusion had superior vena cava syndrome; none had a family history of thrombosis, use of a double lumen CVL, or multiple instillations of urokinase. CONCLUSIONS: Persistent asymptomatic vascular occlusion does occur as a late complication of CVL placement for treatment of childhood malignancies, although the frequency appears low among patients treated primarily for solid tumors. Prospective studies of large numbers of patients with a broader spectrum of diagnoses are necessary to define the incidence of and risk factors for this complication and to assess the need for prevention with anticoagulation or other therapy. Pediatricians caring for patients with a history of cancer and CVLs should be aware that these patients may have persistent vascular occlusion that could predispose them to recurrent thrombosis or postphlebitic syndrome.

Adolescent↗
PubMed1997

Epstein-Barr virus in pediatric Hodgkin disease: age and histiotype are more predictive than geographic region.

Epidemiologic studies have implicated Epstein-Barr virus (EBV) in the great majority (80%-100%) of Hodgkin disease (HD) cases in South American countries, versus only 30%-40% in the United States and other industrialized countries. Other EBV-related malignancies are known to be geographically localized, including nasopharyngeal carcinoma in south China and Burkitt lymphoma in equatorial Africa. Some studies, however, have suggested that age and histiotype, rather than geographic region, are the major determinants of the association between EBV and HD. To further characterize this relationship in children, we matched 26 cases of pediatric Hodgkin disease from south Brazil and 26 cases from the U.S.-forhistiotype and age. The Brazilian children (22 males, 4 females) had a median age of 9 years, while the median age of the U.S. group (11 males, 15 females) was 7.5 years. Formalin-fixed, paraffin-embedded biopsy material was examined for EBV early RNA1 (EBER1) expression by in situ hybridization. This antigen was detected solely in Reed-Sternberg cells or their variants in positive samples. The same proportion of cases was positive (15/26 or 58%) in both groups of children. After adjustment for histiotype and age, the association between EBV and HD remained independent of geographic location, but was more frequent in children aged < or = 10 years at diagnosis. These findings support the multiple-etiology hypothesis for Hodgkin disease.

Adolescent↗
PubMed1997

Resource utilization for minimally invasive direct and standard coronary artery bypass grafting.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MIDCABG) has been recently reintroduced into the cardiac surgical armamentarium for selected patients with suitable coronary anatomy. We hypothesized that MIDCABG had the potential for similar immediate results with decreased perioperative morbidity and decreased resource utilization compared with standard coronary artery bypass grafting (CABG). METHODS: From January 1996 to August 1996, 17 MIDCABG patients were compared with 33 patients with left ventricular ejection fraction greater than 0.50 who underwent CABG with standard technique. No significant differences were observed between the two groups for preoperative variables that are known to affect cost and resource utilization. Length of stay in the hospital was 2.5 +/- 0.8 days for MIDCABG and 5.9 +/- 2 days for CABG (p < 0.0001); length of stay in the intensive care unit was 12.3 +/- 3.3 hours for MIDCABG compared to 32.3 +/- 12.6 hours for the CABG group (p < 0.0001). RESULTS: Forty-one percent of MIDCABG patients were extubated in the operating room and 59% were discharged home on the first or second postoperative day versus none in the CABG group (p < 0.0001). Significantly less morbidity was observed in the MIDCABG group compared with CABG. Total ratio of cost-to-charge was $12,885 +/- $1,511 for MIDCABG and $21,260 +/- $5,497 for CABG (p < 0.0001), with an average savings of $8,375. CONCLUSIONS: Minimally invasive CABG is associated with significant reduction of resource utilization and morbidity related to inital hospitalization compared with CABG.

Aged↗
PubMed1997

Fertility and pregnancy in inflammatory bowel disease.

OBJECTIVE: A retrospective study of women with inflammatory bowel disease, aged 16-45 years during the 20-year period 1967-1986, was carried out in North East Scotland. METHOD: Five-hundred and three women were identified: 15 patients had died from unrelated causes and 22 had emigrated, but 409 of the remaining 466 patients (88%) replied to the study questionnaire. RESULTS: Women with ulcerative colitis and Crohn's disease had normal fertility when compared with the general population of north east Scotland. However, unresolved infertility problems were more frequent in women who had undergone surgery for inflammatory bowel disease compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for ulcerative colitis). Disease relapse rates did not increase in pregnancy. CONCLUSIONS: Overall, at conception women with active disease were as likely to have a normal full-term pregnancy as those in remission. However, spontaneous abortion occurred in five (36%) pregnancies of women who had undergone previous surgery for Crohn's disease and had evidence of recurrent disease. Three of these pregnancies were associated with active disease.

Abortion, Spontaneous↗
PubMed1997

Nicotiana plumbaginifolia hlg mutants have a mutation in a PHYB-type phytochrome gene: they have elongated hypocotyls in red light, but are not elongated as adult plants.

Two new allelic mutants of Nicotiana plumbaginifolia have been isolated which display a hypocotyl which is long (hlg) when seedlings are grown in continuous white light (W). This can be accounted for by the decreased response to red light (R) of the hypocotyl elongation rate in these mutants. Responses to other wavelengths are unaffected in the mutants. When grown in white light, mature hlg mutants are not elongated with respect to the wild-type; they also bolt and flower later. The shade-avoidance responses to red/far red ratio (R:FR) are intact in these mutants. Both mutants are deficient in phyB-like polypeptide that is immunodetectable in the wild-type; both have wild-type levels of a phyA-like polypeptide. These alleles are inherited in a partially dominant manner, and correspond to single-base missense mutations in a gene highly homologous to N. tabacum PHYB, which codes for a phytochrome B-type photoreceptor. One allele, hlg-1, has an introduced amino acid substitution; this may define a residue essential for phytochrome protein stability. The other allele, hlg-2, has a stop codon introduced C-terminal to the chromophore binding domain. As these phyB mutants are unaffected in shade-avoidance responses, but deficient in perception of R, it is concluded that the phyB absent in these mutants is responsible for R perception in the N. plumbaginifolia seedling, but is not a R:FR sensor in light-grown plants.

Amino Acid Sequence↗
PubMed1997

Therapeutic modalities in portal hypertension.

Optimal medical management is with octreotide or terlipressin (Glypressin) for acute variceal bleeding and combined beta-blocker and nitrate prophylaxis for prevention of rebleeding. Injection sclerotherapy is necessary to arrest acute bleeding, with variceal banding preferred for the obliteration of large varices. Transjugular intrahepatic portosystemic shunts (TIPS) are best used for uncontrolled or recurrent bleeding episodes which fail to respond to endoscopic or drug therapy. They can also rarely be used to treat refractory ascites. Surgical portosystemic shunting and devascularization techniques have now been superseded. Hepatic transplantation should be considered where overall hepatic function is poor.

Gastrointestinal Hemorrhage↗
PubMed1997

Transjugular intrahepatic portosystemic shunt: a limited role in refractory ascites.

OBJECTIVE: To evaluate the role of the transjugular intrahepatic portosystemic shunt (TIPS) in the management of patients with refractory ascites. DESIGN: A retrospective study of 25 consecutive patients for whom refractory ascites was the primary indication for TIPS insertion. SETTING: Regional liver unit at Freeman Hospital, Newcastle upon Tyne, UK. PARTICIPANTS AND INTERVENTIONS: Twelve male and 13 female patients with a mean age of 58 years and mean Child-Pugh score of 10, treated with TIPS for refractory ascites between July 1992 and September 1995. MAIN OUTCOME MEASURES: Effect of TIPS on mortality, ascites and hospital admission rate. RESULTS: TIPS was successfully placed in all patients with a 59% mean reduction in portosystemic pressure gradient. Response rate was 68%, 48% and 33% at 1, 3 and 12 months, respectively. Mortality was 48% at 3 months and 67% at 12 months, being higher in those patients older than 60, those with renal impairment and those with higher Child-Pugh score. Amongst nine patients surviving long term (> 12 months) the mean time spent in hospital in the 3 months before TIPS was 35 days and in the year following TIPS 30 days. Patients who died (16 in total) spent a mean of 19 days in hospital before TIPS, 10 never leaving hospital, and 6 who were discharged spent a mean of 19 days post procedure in hospital (mean survival 84 days). CONCLUSION: TIPS has a limited role in the management of patients with refractory ascites. It is not an appropriate treatment where patients are older than 60, have renal impairment (creatinine > 200 mumol/l) or have a Child-Pugh score greater than 10.

Ascites↗