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Biomedical subjects

J Shaw

Publications and source records attributed to J Shaw.

At least 109 records · Page 6Linked to original sources
PubMed1998

Allogeneic stem cell transplantation for Fanconi Anaemia. Severe Aplastic Anaemia Working Party of the EBMT and EUFAR. European Group for Blood and Marrow Transplantation.

Fanconi anaemia is a hereditary disorder characterised by chromosomal breaks increased by cross-linking agents. Bone marrow transplantation is the treatment of choice when a HLA identical sibling donor has been identified. The use of low-dose cyclophosphamide with thoraco-abdominal irradiation for the conditioning regimen of FA patients has lead to a dramatic improvement of survival, with a long-term survival of 75% at our institution. However, if most patients are completely cured of their haematological disease, there is concern about an increased frequency of secondary tumours, mostly head and neck squamous cell carcinomas of poor prognosis. Results of BMT using alternative donors (HLA mismatched related and unrelated donors) have also improved during the last decade. A better selection of the donor via high-resolution techniques for class-II HLA matching, and more recently the use of T cell depleted grafts are probably the main explanations. Despite a short follow-up and the small number of patients analysed, transplants using HLA matched family cord blood give some promising results. On the other hand, first results with unrelated cord blood remind that this approach is clearly an experimental one that has to be evaluated through international registries and prospective studies. New approaches including autologous stem cell transplantations and gene therapy are currently explored.

Fanconi Anemia↗
PubMed1997

Vacuole segregation in the Saccharomyces cerevisiae vac2-1 mutant: structural and biochemical quantification of the segregation defect and formation of new vacuoles.

The conditional vacuolar segregation mutant vac2-1 [Shaw and Wickner (1991) EMBO J. 10, 1741-1748] shifted to non-permissive temperature (37 degrees C), forms large-budded cells without a vacuole in the bud, and daughter cells without an apparent vacuole. Some cells still contain normal segregation structures. Structural and biochemical quantification of the segregation defect showed that (i) about 10% of the full-grown buds did not contain a vacuole, (ii) about 15% of the small cells washed out of a population growing in an elutriation chamber at 37 degrees C, did not contain a visible vacuole, and (iii) 15% of the cells per generation lost carboxypeptidase Y activity after proteinase A depletion. Thus, 10-15% of the daughter cells did not inherit vacuolar structures or vacuolar proteolytic activity from the mother cell. To investigate the fate of vacuole-less daughters, these cells were isolated by optical trapping. The isolated cells formed colonies on agar plates that consisted of cells with normal vacuoles, both at 23 and 37 degrees C. Thus, the vacuole-less cells that failed to inherit proteolytic activities from the mother cell apparently give rise to progeny containing structurally normal vacuoles. Time-lapse experiments showed that vacuole-less daughter cells formed vacuolar vesicles that fused into a new vacuole within 30 min. Although new buds only emerged after a vacuole had formed in the mother cell, the temporary lack of a vacuole had little effect on growth rate. The results suggest that an alternative pathway for vacuole formation exists, and that yeast cells may require a vacuole of some minimal size to initiate a new round of budding.

Carboxypeptidases↗
PubMed1997

Enhanced (cytomegalovirus) viral replication associated with septic bacterial complications in liver transplant recipients.

BACKGROUND: Complications of the biliary anastomosis are the principal cause of clinically serious bacterial sepsis in liver transplant recipients. Reported series suggest an association of bacterial and fungal infection with cytomegalovirus (CMV) infection, although the mechanism of this association is unclear. METHODS: We examined the association of serious bacterial sepsis with CMV replication in a cohort of 106 consecutive liver transplant recipients. Sequentially collected buffy coats were examined with a polymerase chain reaction (PCR) assay that has been shown to have good predictive value for the development of CMV infection. For selected patients, CMV-specific IgM response and serum tumor necrosis factor-alpha (TNF-alpha) were also measured. RESULTS: Ten of 13 patients with serious bacterial sepsis developed buffy coat PCR positivity, compared with 26 of 93 patients without bacterial sepsis (chi-square, P<0.001). Ten of 10 septic recipients with a seropositive liver donor developed PCR positivity. For 9 of 10 recipients, bacterial sepsis developed before PCR positivity. Bacterial sepsis was associated with high serum levels of TNF-alpha. Immune response to CMV (reflected by the appearance CMV-specific IgM) was apparently affected by bacterial sepsis, and IgM response was not observed for the three septic patients who died during the study period. CONCLUSIONS: We conclude that CMV replication is encouraged by serious bacterial sepsis. Replication may be promoted by high antecedent levels of TNF-alpha, and/or by poor immune response to CMV in the context of serious bacterial infection.

Antibodies, Viral↗
PubMed1997

Stereotactic radiosurgery for the treatment of brain metastases. Results of a single institution series.

BACKGROUND: Stereotactic radiosurgery is being used with increasing frequency for the treatment of brain metastases. Optimal patient selection and treatment factors continue to be defined. This study provides outcome data from a single institutional experience with radiosurgery and identifies parameters that may be useful for the proper selection and treatment of patients. METHODS: Eighty-four patients underwent stereotactic radiosurgery for brain metastases between September 1989 and November 1995. Seventy-nine patients (93%) were treated at recurrence after previous whole brain radiotherapy. Patients had between 1 and 6 lesions treated with a median minimum tumor dose of 1600 centigrays (cGy). Thirty-eight patients (45%) had active extracranial disease at the time of radiosurgery. RESULTS: Median survival for the entire group was 43 weeks from the date of radiosurgery and 71 weeks from the original diagnosis of brain metastases. Patients with 1 or 2 metastases had significantly improved survival compared with patients with > or = 3 metastases (P = 0.02), and patients without active extracranial tumor survived longer than those with extracranial disease (P = 0.03). Median time to failure for 145 evaluable lesions was 35 weeks. Local control was significantly improved for radiosurgery doses of > 1800 cGy, and for melanoma histology. CONCLUSIONS: These results are comparable to reports of patients treated with resection and significantly superior to results observed after whole brain radiotherapy. The authors conclude that stereotactic radiosurgery is an effective, low risk treatment for extending the survival of patients with recurrent brain metastasis. Although survival is best for patients with < or = two lesions and no active extracranial disease, selected patients with > two lesions or active extracranial tumor may benefit as well.

Actuarial Analysis↗
PubMed1997

Patterns of viremia in liver transplant recipients with symptomatic cytomegalovirus infection.

Cytomegalovirus (CMV) titer in blood seems to be the principal determinant of clinical symptoms in immunosuppressed patients. We have developed an assay for quantitation of CMV DNA in serum. The assay requires the coamplification by polymerase chain reaction (PCR) of extracted serum DNA with 1000 molecules of mutated internal standard DNA, and then an ELISA detection system. We examined 133 paired buffy coats and sera from 15 patients with symptomatic infection. Sera were examined by quantitative PCR, and buffy coats were examined by qualitative PCR (with a detection threshold of approximately 40 copies per 150,000 cells). Serum viral titers peaked during the seventh week after transplant (median day 40, range 26-58) at about the time of symptom onset. Mean viral titer measured during the seventh week was 1.2 x 10(5) copies per milliliter of serum (standard error 6.5 x 10(4). Buffy-coat PCR results were generally concordant with results of serum PCR (overall concordance 103/133=77.4%). Serum CMV titer fell, as symptoms resolved with reduction of immunosuppression and specific antiviral therapy. High titers and poor response to antiviral therapy were observed in the context of excessive immunosuppression and bacterial sepsis. Measurement of serum CMV titer may be useful for the management of immunosuppressed transplant recipients, and provides a tool for the better understanding of factors that enhance or inhibit viral replication.

Antibodies, Viral↗
PubMed1997

Enhanced (cytomegalovirus) viral replication after transplantation for fulminant hepatic failure.

Fulminant hepatic failure (FHF) is an established indication for liver transplantation. A pretransplant diagnosis of FHF may be a risk factor for subsequent development of cytomegalovirus (CMV) infection, although the mechanism of this association is not understood. FHF is associated with very high levels of tumor necrosis factor alpha (TNF-alpha), and TNF-alpha may directly promote viral replication. We have used the polymerase chain reaction (PCR) to examine sequentially collected buffy coats from 106 consecutive adult liver transplant recipients. PCR evidence of CMV replication was found for 13 of 18 patients who underwent transplantation for FHF (c.f. 23/88 non-FHF patients; P < .01). Ten of 12 patients who received transplants transplanted for fulminant seronegative hepatitis were buffy-coat PCR-positive, sometimes during the first posttransplant week. TNF-alpha was measured by enzyme-linked immunosorbent assay in selected sera, and results were examined in the context of a quantitative PCR assay. Serum TNF-alpha levels increased and decreased in concert with viral titers. High levels of TNF-alpha were not found in the early posttransplant period. We conclude that FHF (in particular, seronegative hepatitis) is associated with enhanced CMV replication in the posttransplant period. Results also suggest that viral replication may be enhanced before transplantation. These patients may be at special risk for development of symptomatic CMV infection.

Cytomegalovirus↗
PubMed1997

The cost-effectiveness of a cardiovascular risk reduction program in general practice.

An economic evaluation was conducted alongside a randomised controlled trial of two lifestyle interventions and a routine care (control) group to assess the cost-effectiveness of a general practice-based lifestyle change program for patients with risk factors for cardiovascular disease. Routine care was the base case comparator because it represents 'current therapy' for cardiovascular disease (CVD). A 'no care' control group was not considered a clinically acceptable alternative to lifestyle interventions. The interventions consisted of an education guide and video for GPs to assess individual patient risk factors and plan a program for risk factor behavior change. Each patient received a risk factor assessment, education materials, a series of videos to watch on lifestyle behaviors and some patients received a self-help booklet. Eighty-two general practitioners were randomised from 75 general practices in Sydney's Western Metropolitan Region to (i) routine care (n = 25), (ii) video group (n = 29) or (iii) video + self help group (n = 28). GPs enrolled patients into the trial who met selection criteria for being at risk of CVD. There were 255 patients in the routine care (control) group, 270 in the video (intervention) group and 232 in the video + self help (intervention) group enrolled in the trial. Outcome measures included patient risk factor status: blood pressure, body mass index, cholesterol and smoking status at entry to trial and after 1 year. Changes in risk factors were used to estimate quality adjusted life years (QALYs) gained. One hundred and thirty patients in the routine care group, 199 in the video group and 155 in the video + self help group remained in the trial at the 12-month review and had complete data. The cost per QALY for males ranged from $AUD152,000 to 204,000. Further analysis suggests that a program targeted at 'high risk' males would cost approximately $30,000 per QALY. The lifestyle interventions had no significant effect on cardiovascular risk factors when compared to routine patient care. There remains insufficient evidence that lifestyle programs conducted in general practices are effective. Resources for general practice-based lifestyle programs may be better spent on high risk patients who are contemplating changes in risk factor behaviours.

Australia↗
PubMed1997

High-dose chemotherapy, autologous bone marrow or stem cell transplantation and post-transplant consolidation chemotherapy in patients with advanced breast cancer.

This study was designed to determine the complete response (CR) rate, event-free survival (EFS) and overall survival (OS) in patients with metastatic breast cancer treated with an adriamycin-based induction regimen, high-dose chemotherapy consisting of cyclophosphamide and thiotepa with autologous bone marrow or stem cell reinfusion, followed by post-transplant 5-fluorouracil and cisplatin. Forty-eight consecutive patients were enrolled and 35 received two to four cycles of a cytoreductive chemotherapy regimen followed by high-dose chemotherapy which included cyclophosphamide and thiotepa. Thirty-three patients with non-progressive disease received at least one cycle of post-transplant 5-fluorouracil and cisplatin. Fifty percent of patients with evaluable disease responded to induction chemotherapy. Three of the 34 patients (9%) evaluable for response to high-dose chemotherapy achieved CR, eight (24%) achieved partial response (PR), 12 (35%) had stable disease (SD) and 11 (32%) had progressive disease (PD). The median time to neutrophil recovery was 11.5 days (range, 8 to 40 days) post- reinfusion. The median time to platelet independence was 14.5 days (range, 8 to 44 days). The median follow-up is 24.5 months (range, 1 to 96 months). The actuarial probability of EFS for all patients is 17% at 4 years. The EFS for patients receiving all four cycles of post-transplant chemotherapy is 27% at 4 years, compared to 36% at 1 year for patients not receiving any post-transplant chemotherapy. Ten of the 48 patients (21%) are alive, and seven of these (15%) have no evidence of disease. High-dose chemotherapy with autologous bone marrow or peripheral blood-derived stem cell transplantation followed by post-transplant consolidation chemotherapy in patients with metastatic breast cancer results in a proportion of patients without evidence of disease at 4 years.

Adult↗
PubMed1997

An audit of the diagnostic usefulness of PRL and TSH responses to domperidone and high resolution magnetic resonance imaging of the pituitary in the evaluation of hyperprolactinaemia.

BACKGROUND AND OBJECTIVE: The usefulness of dynamic tests of PRL release in determining underlying pathology in hyperprolactinaemic patients is not well recognized by endocrinologists, only 15% of whom routinely perform such tests. High resolution pituitary magnetic resonance imaging (MRI) has become more widely available during the past 5 years and is now generally regarded as the pituitary imaging method of choice. Since few prolactinoma patients are now submitted to surgery, it is important to ascertain the usefulness of these techniques in suggesting a pathological diagnosis. DESIGN: A 3 year retrospective audit of the information derived from measurement of PRL and TSH responses to the dopamine antagonist domperidone and from high resolution pituitary MRI in patients being investigated for hyperprolactinemia in regional endocrine unit. PATIENTS: Eighty-four patients (10 male, 74 female) whose investigation of hyperprolactinaemia included a domperidone test and high resolution pituitary MRI. Patients who had domperidone tests performed after pituitary surgery or who did not have pituitary MRI were excluded from the analysis. MEASUREMENTS: PRL and TSH were measured basally and at 30 and 60 minutes following domperidone (10 mg i.v.) and gadolinium-enhanced pituitary MRI was performed in all patients. RESULTS: 20 patients had a normal PRL response to domperidone (defined as PRL30/PRL0 > 3) and this group included five patients in whom hyperprolactinaemia was not sustained. Pituitary MRI showed evidence of a microadenoma in only two patients, imaging being unequivocally normal in the majority. Sixty-four patients had an abnormal PRL response to domperidone and 18 of these had a macrolesion (nine prolactinomas, nine other tumours). Pituitary MRI was performed in the remaining 46 patients with abnormal PRL response to domperidone and suggested microadenoma in 29 (63%), identified other structural abnormalities in six cases but was entirely normal in 11 cases. Neither the basal PRL level nor the TSH response could refine the diagnosis further because of overlap between the various subgroups. CONCLUSIONS: The majority of patients with a normal dynamic response of PRL to domperidone had a normal or near normal pituitary MRI scan. In the two cases where an abnormality was detected it could have been an incidental microadenoma or cyst, thus suggesting that pituitary scanning could normally be omitted in patients whose PRL response to domperidone is normal (24% of our total). The group of patients with an abnormal dynamic response of PRL to domperidone was not generally amenable to further diagnostic refinement by considering the degree of hyperprolactinaemia or the TSH response to domperidone because of overlap of these parameters between the diagnostic subgroups. Therefore any degree of hyperprolactinaemia associated with a blunted PRL response to domperidone warrants pituitary imaging.

Adolescent↗
PubMed1997

The incidence of chronic headache in children with shunted hydrocephalus.

Report of chronic headache amongst children with shunted hydrocephalus is frequent, and often leads to investigation for raised intra-cranial pressure and shunt malfunction, and much debate has appeared in the literature concerning possible cause. However headache is a common neurological symptom amongst children, and studies of prevalence indicate incidence of frequent non-migrainous headache to be 6.8%, and migrainous headache 4% in the general child population. A relationship between stress and anxiety and headache is recognised, and the hydrocephalic child has many reasons above those of his/her peers to be subject to stress. It is also hypothesised that this group may be more vulnerable than peers to developing a migraine-like condition in the face of adequate shunt function. The clinician dealing with complaint of chronic headache in a hydrocephalic child must therefore be wary of over-investigation in a child with a working shunt, or missing possible shunt malfunction when the only symptom is chronic headache. It was speculated therefore that incidence of non-shunt related chronic headache in this group would be high, and an attempt was made to document incidence of migrainous and non-migrainous headache in the medical notes, and in replies to postal questionnaire sent to a sample of 130 children with shunted hydrocephalus of varying aetiology. Incidence of migrainous headache was documented in the medical notes in 8.5% of cases, with incidence rising to 21.5% using self-report. Incidence of non-migrainous headache was also very high (15.4%) and the overlap between migraine and tension headache, combined with difficulty of diagnosis in children may indicate migraine to be more frequent still. The concept of "Shunt Migraine" is therefore worthy of consideration. Report of chronic headache led to investigation in a large proportion of cases, but symptomatology often continued. Even when shunt malfunction was indicated, shunt revision did not "cure" complaint of headache. Headache was not found to be related to diagnosis associated with hydrocephalus, to presence of seizure disorder, or to the sex of the child, although in common with other studies, there was a strong trend towards girls being statistically more likely to experience headache than boys. There was a relationship however between report of chronic headache, and the sort of school a child was likely to attend; children who attended mainstream school without the support of a Statement of Special Educational Need were more likely to report headache than their peers, and it is hypothesised that these children may be suffering sufficient stress to contribute to maintenance of headache. The importance of the multi-disciplinary team in assessment of children's physical, intellectual and emotional status is stressed, in order that medical interventions have the greatest chance of success.

Cerebrospinal Fluid Shunts↗
PubMed1997

How adequate are hospital records?--The first report of the North West Spina Bifida Registry.

The United Kingdom North West Regional Registry of patients with Neural Tube Defects was established in June 1996. The aims of the registry are to keep a record of all patients in a defined geographical location with neural tube defects and to ensure appropriate facilities and follow-up are available. During the first year of the registry 217 patients have been identified and the hospital records of 163 of these reviewed. This report deals with the shortcomings of hospital records identified during this exercise. We identified many inaccuracies and omissions when reviewing case notes. 3% of patients had unclear records as to the presence/absence of shunts. Bladder management was unclear in 17% of patients and bowel management in 26% of cases. There was no record as to the presence/absence of hydronephrosis or renal scarring in 24% and 34% of patients respectively, no blood pressure measurement in 50% of patients and no record of a serum creatinine in 56%. Mobility was not recorded in over 30% of patients. Developmental achievement and school placement were rarely if ever recorded. These results demonstrate the problems with the current medical record system. The potential consequences of this are discussed and means of improving record systems suggested.

Adolescent↗
PubMed1997

The spectrum of spinal cord dysraphism and bladder neuropathy in children.

The frequency of bladder neuropathy and its relationship to abnormalities of the neural axis on MR scan was examined in a group of 49 children with known occult spinal dysraphism and 148 children with daytime urinary incontinence. Of the patients with known spinal dysraphism 55% had bladder neuropathy. There was no relationship between either the type of abnormality or the number of abnormalities seen on MR scan and the presence or absence of bladder neuropathy. 5 of the 9 patients with a normal cord had neuropathic bladders. Four of the 148 patients with daytime wetting turned out to have spinal dysraphism. Of the rest, 51 patients required urodynamic studies and of these 12 had clearcut bladder neuropathy. 15 patients had MR scans, all of which were normal. The range of urodynamic findings in those with bladder neuropathy was identical to the range found in patients with spinal dysraphism. On the basis of these findings it is suggested that children with isolated bladder problems could well have spinal cord dysraphism as a cause of these - the lesions being beyond the resolution of MR scanning. For those children with clearcut spinal dysraphism the absence of any relationship between the bladder findings and the lesion places a question mark over the potential benefits of neurosurgical intervention.

Adolescent↗
PubMed1997

Feasibility of conducting cardiovascular outcome research in Australian general practice: results from the ANBP2 pilot study. Australian National Blood Pressure Study.

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was > or = 160 mmHg systolic or > or = 90 mmHg diastolic if systolic BP was > or = 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82,000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP > or = 160/90 mmHg. Forty-seven per cent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.

Aged↗