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Biomedical subjects

G Dolan

Publications and source records attributed to G Dolan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prothrombin complex concentrate for oral anticoagulant reversal in neurosurgical emergencies.

The incidence of spontaneous intracranial haemorrhage has increased markedly in line with the increased use of oral anticoagulant agents. Recent guidelines for reversal of this acquired coagulation defect in an emergency have been established, but they are not adhered to in all centres. Our unit is referred between 20 and 60 patients per year (1994-1999) who are anticoagulated and require urgent neurosurgical intervention. In order to investigate this, we performed a prospective study using prothrombin complex concentrate (PCC). PCC was given to the first six patients with intracranial haemorrhage admitted to the neurosurgical unit requiring urgent correction of anticoagulation (Group 1) and compared with patients receiving standard treatment with fresh frozen plasma and vitamin K (Group 2). Mean International Normalised Ratios of Group 1 were 4.86 pretreatment and 1.32 posttreatment, and of Group 2 were 5.32 and 2.30, respectively. Results for complete reversal and reversal time were significant for PCC with p < 0.001. We recommend PCC for rapid and effective reversal of warfarin in life-threatening neurosurgical emergencies.

Adult↗
PubMed1999

Coil embolization of cerebral aneurysms in patients with sickling disorders.

In patients with sickle cell disease cerebral aneurysm formation is thought to be a complication of recurrent red cell sickling, and multiple aneurysms have been reported in these patients. Management of patients with suspected cerebral aneurysm has traditionally involved cerebral vessel angiography followed by craniotomy and aneurysmal clipping. In patients without sickle cell disease, non-operative intervention in the form of endovascular coil embolization is increasingly being used to ablate aneurysms, but has not thus far been reported in patients with sickle cell disease. We report two patients with sickling disorders who have undergone coil embolization of cerebral aneurysms with good functional and radiological outcomes. These patients illustrate that endovascular coiling is useful in the treatment of cerebral aneurysms associated with sickling disorders, although, as with surgical intervention, preparation with exchange transfusion is appropriate.

Adult↗
PubMed1999

Operational and resource management of an RCT: some of the pitfalls and lessons learned.

Nurses frequently fulfil important functions within a research team involved in clinical trials. This paper describes the challenges inherent in developing and managing a large clinical trial involving the evaluation of homoeopathy and asthma. Teamwork, a clear and comprehensive understanding of the research protocol, marketing the project, and the ability to manage human resources within both a primary and secondary care environment are all essential aspects of clinical research. Our experience in establishing and managing this project has suggested to us that a high standard of clinical research demands an open approach to problem-solving as well as the realization that efficient research is as much about the management of people as it is about scientific rigour.

Adolescent↗
PubMed1998

Coeliac axis thrombosis associated with the combined oral contraceptive pill: a rare cause of an acute abdomen.

We report a case of coeliac axis thrombosis and splenic infarction presenting in a girl of 14 years who had been on the oral contraceptive pill (OCP), Marvelon (ethinyloestradiol 30 microg plus desogestrel 150 microg, Organon, Cambridge, UK), for 3 weeks. She had no other risk factors for thrombo-embolism. Diagnosis was made with duplex Doppler ultrasound and confirmed with dynamically-enhanced comput-ed tomography and magnetic resonance angiography, thus avoiding the need for percutaneous arteriography. Though mesenteric thrombo-embolic disease is recognised in association with use of the combined OCP, it has not previously been reported to affect the coeliac axis. Paediatricians and surgeons should be aware of the risks to young girls on the OCP, and consider it in their differential diagnosis of the acute abdomen.

Abdomen, Acute↗
PubMed1998

A phase II study of liposomal doxorubicin in the treatment of HIV-related Kaposi's sarcoma.

OBJECTIVES: To evaluate the toxicity and clinical efficacy of liposomal encapsulated doxorubicin (DOX-SL) in the treatment of HIV-related Kaposi's sarcoma (KS). METHODS: DOX-SL 20-40mg/m2 was administered by intravenous infusion over 30-60 minutes every two weeks. Toxicity was assessed in all patients and response assessed in patients who completed two or more cycles of therapy. RESULTS: Twenty-five patients with KS were enrolled. Nine had received previous KS chemotherapy but only one prior anthracycline therapy. Eighteen patients had CD4 counts < 50/mm3. Eight had pulmonary and/or visceral KS. A total of 191 cycles were given, median 6, range 1-33. Twenty patients completed two or more cycles and were considered evaluable for efficacy. A defined response occurred in 11 patients, nine achieving a partial response and two a complete response. The median duration of response was 120 days and the median time to disease progression was 187 days. Acute toxicity was minimal, except in one patient who had generalised erythema, hypotension and diaphoresis within ten minutes of starting DOX-SL infusion. Grade 3 or 4 neutropenia occurred in 13.6 and 3.7% of cycles respectively. Neutropenic sepsis secondary to drug therapy was not reported. Alopecia and gastrointestinal symptoms were mild and infrequent. No cardiac toxicity was seen. Nine/25 patients developed HIV-associated illnesses while on study (three Pneumocystis carinii pneumonia, two systemic Cytomegalovirus infection, three cryptosporidiosis, one Mycobacterium avium intracellulare--(MAC) infection). Median survival in the evaluable patients was 219 days. CONCLUSIONS: DOX-SL is an effective and well tolerated palliative therapy in AIDS-related KS.

Adult↗
PubMed1998

Precise carrier diagnosis in families with haemophilia A: use of conformation sensitive gel electrophoresis for mutation screening and polymorphism analysis.

Causative mutations in the factor VIII gene of seven unrelated patients with severe haemophilia A were identified using the mutation screening procedure conformation sensitive gel electrophoresis (1) and characterised by direct sequencing. Female family members of all patients had requested either carrier status determination or prenatal diagnosis. However, lack of the factor VIII gene inversion, a prior family history or informative polymorphisms prevented diagnosis in these families. Identification of a mutation in each family enabled female carrier status to be determined in all cases. Six mutations were previously unreported. One Afro-Caribbean patient had two sequence changes; A670 2G and A6769G. The latter, resulting in Met2238Val and previously reported as a FVIII mutation, was shown to be polymorphic with a 42% heterozygosity rate in an Afro-Caribbean population. Conformation sensitive gel electrophoresis was found to be technically simple and efficient at locating previously unknown FVIII gene mutations.

Blotting, Southern↗
PubMed1997

Parvovirus-induced pancytopenia in a child with acquired haemolytic anaemia.

A 14-year-old boy, with acquired haemolytic anaemia secondary to paravalvular leak from a prosthetic aortic valve, presented with severe pancytopenia. Subsequent investigation showed serological evidence of recent parvovirus B19 infection. The patient required transfusion and subsequently improved rapidly, with maintenance of pre-infective haemoglobin levels. To our knowledge this is the first reported case in which infection with parvovirus has caused pancytopenia in an acquired chronic mechanical haemolytic anaemia.

Adolescent↗
PubMed1996

Efficacy of recombinant interferon-alpha (rIFN-alpha) in polycythaemia vera: a study of 17 patients and an analysis of published data.

The efficacy and tolerability of rIFN-alpha has been evaluated in 17 selected patients with symptomatic polycythaemia vera, diagnosed according to the PRV Study Group criteria. Complete disease control (CR) was achieved, after 1-12 months, in nine patients, with partial control in a further five cases. Three patients failed to respond. Pruritus significantly improved in 83% (10/12) of cases, following 1-28 weeks of treatment. Six patients (35%), however, were unable to tolerate rIFN-alpha, on account of weight loss, myalgia and mental changes. Overall, alpha-interferon therapy significantly improved venesection requirements, MCV and PCV values, platelet counts, pruritus scores and the degree of splenomegaly. Analysis of pooled published data (100 evaluable patients, including the present study) revealed an overall CR of 60%, a PR of 27%, and a failure rate of 13%. Significant pruritus control (> 50% improvement) occurred in 77% of cases. rIFN-alpha appears to be an effective therapy for PV-associated myeloproliferation and/or pruritus, although side-effects remain a concern. Long-term studies are now indicated to determine if the natural history of the disease is altered, in particular whether the incidence of myelofibrosis and/or leukaemic transformation is reduced.

Adult↗
PubMed1996

The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria.

Tumor necrosis factor (TNF) is thought to play a key role in the pathogenesis of cerebral malaria. A double-blind, placebo-controlled trial of an anti-TNF monoclonal antibody (B-C7) comprised 610 Gambian children with cerebral malaria, with mortality and residual neurologic sequelae as primary study end points. Sixty (19.9%) of 302 children who received B-C7 died compared with 64 (20.8%) of 308 children who received placebo (adjusted odds ratio [OR], 0.90; 95% confidence interval [CI], 0.57-1.42). Residual neurologic sequelae were detected in 15 (6.8%) of 221 survivors from the B-C7 group and in 5 (2.2%) of 225 survivors of the placebo group (adjusted OR, 3.35; 95% CI, 1.08-10.4). The monoclonal antibody used in this study did not improve survival in cerebral malaria and was associated with a significant increase in neurologic sequelae. A possible explanation of the latter observation is that the antibody acts to retain TNF within the circulation and thereby prolongs its effects on vascular endothelium.

Antibodies, Monoclonal↗
PubMed1996

Development of a rapid DNA screening procedure for the Factor V Leiden mutation.

Aim-To develop a rapid, simple and highly specific DNA screening procedure based on the amplification refractory mutation system (ARMS) to detect the Leiden mutation in whole blood.Methods-ARMS PCR amplification primers with additional mismatches at either -2 or -3, which greatly improves specificity, were constructed to detect the normal Factor V gene and the Leiden mutation in whole blood samples from patients with abnormal clotting results.Results-Construction of ARMS primers with either an additional mismatch at -2 or -3 at the 3' end of the primer could be used to detect the Leiden mutation in 0.5 mu1 whole blood in under three hours. Primers destabilised at position -3 could be used at a lower annealing temperature, which gave greater sensitivity and are now routinely used. A control set of primers was included in the same reaction to act as a positive control.Conclusions-This rapid and specific assay for the factor V Leiden mutation is a useful addition to the investigation of patients with or at risk from thrombovascular disease.

Journal Article↗
PubMed1995

Hepatitis C virus infection in multi-transfused children with haematological malignancy.

Transmission of hepatitis C virus (HCV) is an important hazard of blood transfusion and may result in chronic liver disease. 98 children from Nottingham and Sheffield with haematological malignancies were studied to determine the prevalence of HCV infection by enzyme immunoassay and RT/PCR techniques. The children had been exposed to up to 184 donors through red cell and platelet transfusion, the majority prior to routine testing for HCV infection in blood donors. Only one sample showed evidence of HCV infection being both ELISA and RT/PCR positive. None of the samples taken since donor screening were positive. This provides reassurance as to the low rate of HCV acquisition in multi-transfused patients in this part of the U.K. compared to other parts of the world.

Adolescent↗
PubMed1995

Bone marrow and serum connective tissue polypeptides in idiopathic myelofibrosis.

The distribution of collagen type VI and tenascin has been determined in both normal and myelofibrotic bone marrow by immunohistological techniques. In normal sections positivity was demonstrated in the periosteum (collagen type VI and tenascin) and in the walls of small blood vessels (tenascin). In contrast, myelofibrotic bone marrow showed an increased deposition of both proteins, especially collagen type VI, although this increase was restricted to the later fibrotic stages of the disease. Serum concentrations of collagen type I (PICP), collagen type III (PIIIP) and laminin (laminin P1) related polypeptides were determined in a further 26 patients. PIIIP levels were significantly raised, in contrast to PICP and laminin P1 concentrations. All three markers, however, were significantly elevated in patients with active/transforming disease. Laminin P1 and PICP levels showed a strong correlation, indicating a relationship between basement membrane and interstitial collagen metabolism, although they do not appear to offer any advantage over PIIIP for the monitoring of disease activity.

Aged↗