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Biomedical subjects

A Hasan

Publications and source records attributed to A Hasan.

At least 19 recordsLinked to original sources
PubMed2000

Donor organ transmission of varicella zoster due to cardiac transplantation.

BACKGROUND: We report a case of donor-transmitted varicella zoster viral (VZV) infection in a cardiac transplant recipient. A 15-month-old girl developed primary VZV infection 12 days after cardiac transplantation. The donor suffered from varicella 2 weeks before death from pneumococcal meningitis. METHODS: Despite treatment of the seronegative recipient with intravenous acyclovir from the time of surgery, she developed symptoms of fever, a nonspecific macular rash, and small palatal vesicles. RESULTS: After rapid diagnostic confirmation by direct immunofluorescence on vesicular fluid, high-dose intravenous acyclovir was commenced. In addition, the cyclosporine dose was reduced by 25%. The child made a quick and uncomplicated recovery. CONCLUSIONS: Donor organ transmission of VZV has not, to our knowledge, been previously reported. It occurred despite treatment with acyclovir and resulted in an atypical cutaneous eruption. It responded to an increased dose of acyclovir and a reduced level of immunosuppression.

Acyclovir↗
PubMed2000

The major in vivo modifications of the human water-insoluble lens crystallins are disulfide bonds, deamidation, methionine oxidation and backbone cleavage.

This investigation of the water-insoluble crystallins from human lenses has used multiple chromatographic separations to obtain proteins of sufficient purity for mass spectrometric analysis. Each fraction was analysed to determine the molecular masses of the constituent proteins as well as peptides in tryptic digests of these proteins. The major components of the water-insoluble crystallins were identified as alphaA- and alphaB-crystallins. In addition, gammaS-, betaB1-, gammaD-, betaA3/A1- and betaB2-crystallins were found, in order of decreasing abundance. Although there was evidence of some backbone cleavage, the predominant forms of alphaA-, alphaB, betaB2-, gammaS- and gammaD-crystallins were the intact polypeptide chains. The major modifications distinguishing the water-soluble crystallins were increased disulfide bonding, oxidation of Met, deamidation of Gln and Asn and backbone cleavage. Of the many reactions hypothesized to lead to crystallin insolubility and cataract, these results most strongly support metal-catalysed oxidation, deamidation and truncation as initiators of conformational changes that favor aggregation.

Aged↗
PubMed2000

Results in the operative treatment of elderly patients with intracranial meningioma.

With life expectancy in the industrial nations increasing during recent years, the number of patients older than 70 years with intracranial tumours and, especially, meningiomas is rising. To evaluate the indications for operative treatment, we reviewed 66 patients older than 70 years who were operated upon for intracranial meningioma in our department between 1991 and 1997. The mean age was 75 years. The oldest patients were 86 years old. Thirteen patients with recurrent meningiomas were operated upon. The mortality rate was 7.6%. Neurological symptoms improved in 38 patients (57.6%), were unchanged in 11 (16.6%), and deteriorated in 12 (18.2%). Patients with recurrent meningiomas seem to have a higher operative risk and their outcome is worse than after a primary operation. In general, there were good postoperative results in patients with few concomitant diseases, small meningiomas, small edema, short time of operation, and accessible location (convexity rather than skull base). Age in general is not a contraindication for operation. In cases of incidental findings of small meningiomas, we recommend observation and MRI follow-up. Symptomatic meningiomas should be removed whenever there is an acceptable risk from an internal or anaesthesiological point of view.

Aged↗
PubMed1999

Synthesis of 5-substituted 2'-deoxycytidine 5'-(alpha-P-borano)triphosphates, their incorporationinto DNA and effects on exonuclease.

Direct PCR sequencing with boronated nucleotides provides an alternative to current PCR sequencing methods. The positions of boranophosphate-modified nucleotides incorporated randomly into DNA during PCR can be revealed directly by exonuclease digestion to give sequencing ladders. Cytosine nucleotides, however, are especially sensitive to exonuclease digestion and provide suboptimal sequencing ladders. Therefore, a series of 5-substituted analogs of 2'-deoxycytidine 5'-(alpha-P-borano)triphosphates (dCTPalphaB) were synthesized with the hope of increasing the nuclease resistance of deoxycytosine residues and thereby enhancing the deoxycytosine band intensities. These dCTP analogs contain a boranophosphate modification at the alpha-phosphate group in 2'-deoxycytidine 5'-triphosphate (dCTP) as well as a 5-methyl, 5-ethyl, 5-bromo or 5-iodo substitution for the 5-hydrogen of cytosine. The two diastereomers of each new dCTP derivative were separated by reverse phase HPLC. The first eluted diastereomer (putatively Rp) of each dCTP analog was a substrate for T7 DNA polymerase (Sequenase) and had an incorporation efficiency similar to normal dCTP and dCTPalphaB, with the 5-iodo-dCTPalphaB analog being the least efficient. Substitution at the C-5 position of cytosine by alkyl groups (ethyl and methyl) markedly enhanced the dCTPalphaB resistance towards exonuclease III (5-Et-dCTPalphaB >5-Me-dCTPalphaB >dCTPalphaB approximately 5-Br-dCTPalphaB >5-I-dCTPalphaB), thereby generating DNA sequences that better define the deoxycytosine positions. The introduction of modified dCTPalphaB should increase the utility of direct DNA sequencing with boronated nucleoside 5'-triphosphates.

Boron Compounds↗
PubMed1999

Significance of Epstein-Barr virus status and post-transplant lymphoproliferative disease in pediatric thoracic transplantation.

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a serious complication of organ and bone marrow transplantation. The importance of EBV matching between recipient and donor remains unclear. Between October 1987 and December 1997, 64 pediatric cardio-pulmonary transplants were performed at this center (58 hearts, two heart/lungs, four sequential single lungs). The EBV viral capsid antigen (VCA) immunoglobulin G (IgG) status of both donor and recipient was determined at the time of transplant. Of 56 patients from whom paired sera was available for analysis, 27 (50%) were recipient and donor EBV IgG positive, four (7%) were recipient EBV IgG positive and donor EBV IgG negative, and 12 (20%) were recipient EBV IgG negative and donor EBV IgG negative. The remaining 13 (23%) patients were EBV IgG negative but received organs from EBV IgG-positive donors. The EBV immunoglobulin M (IgM) status was determined from 6 weeks post-transplant in the 11 mismatches who survived for longer than 28 d. Seven became EBV IgM positive, two remained EBV IgM negative; the status of the remaining two remains unknown. The EBV IgM status was also determined retrospectively in patients who were EBV IgG negative pretransplant and received organs from EBV IgG-negative donors. Nine became EBV IgM positive; the rest remained negative. PTLD was diagnosed in two of 56 patients from whom paired sera was available; one was donor and recipient EBV IgG negative; the other was donor and recipient EBV IgG positive. No cases of PTLD were diagnosed in the remaining eight patients from whom paired sera was not available. Our experience suggests that PTLD does not occur with any greater frequency in the 'mismatch' group, and does not justify EBV matching in pediatric thoracic transplantation where there is a higher proportion of EBV-negative recipients than in adults.

Adolescent↗
PubMed1999

Changing cyclosporin A formulation: an analysis in paediatric cardiac transplant recipients.

Cyclosporin A is the primary immunosuppressive agent used in cardiac transplantation to maintain chronic immunosuppression. Absorption may be erratic and major side-effects include nephrotoxicity. A recently introduced formulation (Neoral) improves absorption in cystic fibrosis heart-lung transplant recipients, but episodes of rejection have been reported on conversion from the oil-based formulation. A retrospective analysis of 21 paediatric cardiac transplant recipients who had been converted from the oil-based formulation to the micro-emulsified formulation was performed. No clinical rejection episodes occurred following conversion. There was a significant reduction in dose following conversion (p < 0.001). The mean trough level was less on the new formulation (p = 0.04), but there was no difference in coefficient of variation or standard deviation. Mean glomerular filtration rate (GFR) was significantly less, but there was no difference in the rate of change of GFR on the new formulation. Erratic absorption and deteriorating renal function remain as significant problems in paediatric cardiac transplant recipients despite conversion to the new formulation.

Adolescent↗
PubMed1999

Early results with the Carbo-seal composite valve conduit for aortic root replacement.

BACKGROUND AND AIMS OF THE STUDY: Composite graft replacement of the aortic root is still a complex operation, transgraft hemorrhage being one of the most severe complications. The aim of the study was to evaluate early results with the Carbo-seal composite conduit for aortic root replacement. METHODS: A retrospective review of 21 patients operated on for ascending aortic aneurysm and/or dissection with the open technique between August 1993 and February 1998 is presented; 12 patients had Marfan syndrome and nine were non-Marfan. RESULTS: There were two operative deaths (9.5%) due to low cardiac output. Two patients were re-explored for bleeding which was not due to transgraft hemorrhage. Postoperative complications were one hemothorax, one pneumothorax and two pericardial effusions. During the follow up, one patient died of rupture of a descending aortic aneurysm, and one patient in atrial fibrillation had a transient ischemic attack. At the closing of the follow up, the remaining patients were well and free of complications. CONCLUSIONS: Carbo-seal may be considered a reliable device for use in aortic root replacement, though a longer follow up and a larger patient population are necessary to confirm these positive early results.

Adolescent↗
PubMed1999

The Ross procedure in children under ten years of age.

BACKGROUND AND AIMS OF THE STUDY: The potential advantages of the Ross procedure in children under 10 years of age have yet to be validated. Concerns remain regarding progressive dilatation of the pulmonary autograft and potential homograft stenosis. We present our experience in this age population. METHODS: A retrospective analysis of aortic root replacement using the Ross procedure in 11 young children (nine males, two females; median age 84 months; range 3 months to 10 years) between January 1996 and January 1999 was performed jointly in two pediatric surgical centers. RESULTS: There were no operative deaths. Mean hospital stay was 12 +/- 4 days, and mean follow up 14.5 +/- 8 months. The event-free survival (death, reoperation, endocarditis, arrhythmia) was 100%. Currently, nine children are in NYHA functional class I, and two in class II. The autograft and homograft were evaluated by serial echocardiography. There was no sign of progressive dilatation of the autograft. Aortic regurgitation was trivial in four children and mild in seven. No growth of the autograft was noted; this was consistent with minimal somatic growth. Homograft peak gradients remained low during the follow up. CONCLUSIONS: Although the pulmonary autograft procedure is more complex than other types of aortic valve replacement, it can be safely applied in children. Early follow up indicates satisfactory performance of the autograft. If dilatation will not occur, pulmonary root autograft may be an attractive substitute for diseased aortic valves in children.

Aortic Valve↗
PubMed1998

Effect of immunosuppression after cardiac transplantation in early childhood on antibody response to polysaccharide antigen.

BACKGROUND: Three children who had cardiac transplantation before age 4 years later presented with recurrent sinopulmonary infection caused by organisms including Streptococcus pneumoniae, in which capsular polysaccharide plays an important part, one developed bronchiectasis. We therefore studied responses to polysaccharide antigen after immunosuppression started in early childhood. METHODS: Antibodies against pneumococcal and haemophilus polysaccharides, and total IgG, IgG1, IgG2, and IgA concentrations were measured in 33 cardiac-transplant recipients transplanted before the age 4 years (group 1) and after that age (group 2). Patients with low pneumococcal and haemophilus antibody concentrations were immunised with 23 polyvalent pneumococcal and tetanus-haemophilus conjugate vaccines and antibody responses were measured. FINDINGS: Five patients from group 1 and seven from group 2 were transplanted for congenital heart disease and ten patients in each group had heart transplants because of cardiomyopathy; none were asplenic. Group 1 (16 patients) were aged 2-10 years when investigated, group 2 (17 patients), were 6-16 years. Four of 16 patients in group 1 responded to pneumococcal polysaccharide vaccine compared with 14 of 17 in group 2 (p=0.0016). This difference remained when those in group 1, aged less than 4 years at investigation, were excluded (p=0.0060). Response to haemophilus-conjugate vaccine was similar in both groups (14 of 16 vs 14 of 17, p=1.0). Significantly more patients who failed to respond to pneumococcal vaccine had low IgG2 concentrations (p=0.0269). INTERPRETATION: Children who had a transplantation and immunosuppression in early childhood before they had developed antibody responses to pneumococcal polysaccharide, still failed to show a response when older-ie, when such responses are the norm. Ongoing immunosuppression prevents the maturation of antipolysaccharide responses leaving children susceptible to severe and recurrent damaging infection.

Aging↗
PubMed1998

Experimental mucosal induction of uveitis with the 60-kDa heat shock protein-derived peptide 336-351.

Subcutaneous (s.c.) immunization of rats with the human 60-kDa heat shock protein (HSP)-derived peptide 336-351 induced clinical and/or histological uveitis in 80 % of rats. Subsequent experiments to prevent the development of uveitis by oral or nasal administration of the peptide have failed. Instead, uveitis was induced in 74.6 % of rats given the peptide orally (5 times), in 75 % given the peptide nasally (5 times) or 91.7 % of those administered the peptide by both routes (10 times). Histological examination showed that any one route of administration of the peptide elicited iridocyclitis in 42.2 % but loss of photoreceptors only in 4.9 % of rats. In contrast, sequential administrations of the peptide by a combined mucosal-s.c. route resulted in iridocyclitis in only 25 % but loss of photoreceptors in 40 % of animals. Examination of mRNA from CD4-enriched splenic cells by reverse transcription-PCR failed to yield significant differences in Th1 or Th2 cytokines. Treatment with monoclonal antibody (mAb) to CD4 yielded a dose-dependent decrease in uveitis from 82 % to 25 %. Similarly, treatment with IL-4 significantly decreased the development of uveitis from 68 % to 30.4 %. Conversely, treatment of the rats with mAb to CD8 greatly enhanced the onset of uveitis (from about 22 days in the controls to 11 days) and all the rats developed uveitis by day 24. Thus, CD4+ cells mediate, whereas CD8+ cells suppress the development of uveitis. We suggest that this novel experimental mucosal model of induction of uveitis by the human 60-kDa HSP-derived peptide 336-351, which is specific in stimulating T cell responses in Behcet's disease, is consistent with the oro-genital onset of this disease and the development of uveitis.

Administration, Intranasal↗
PubMed1998

HSP-derived peptides inducing uveitis and IgG and IgA antibodies.

Heat shock protein (HSP) 65 kD-derived peptides, which specifically stimulate T cells from patients with Behçet's disease (BD), are capable of inducing uveitis in rats. Mycobacterial HSP 65 kD and BD-specific peptides were injected into Lewis rats and the development of uveitis was monitored clinically and histologically, and IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Rats immunized with HSP peptides that developed uveitis showed significantly higher serum IgG antibody levels to peptide 311-326 (P < 0.05) and the corresponding homologous human peptide 336-351 (P < 0.01) than rats without uveitis. Significant increases in serum IgA antibodies in rats with uveitis were also observed in those immunized with peptides 111-125, 311-326 and 336-351 (P < 0.05). Rats injected with HSP 65 kD showed a rise in IgG antibody levels to peptides 111-125, 154-172 and 311-326 and to a lesser extent, a rise in IgA antibody level to peptide 311-326. HSP showed almost complete inhibition of binding of IgG antibodies to HSP 65 kD, but peptides 111-125, 154-172, 311-326 and 336-351 showed inhibition to a lesser extent in a competitive assay. These results suggest that increases in IgG and IgA antibody levels to specific peptides within HSP, develop in rats with uveitis. The T and B cell epitopes responsible for the development of ocular disease in rats immunized with HSP-derived peptides, appear to be similar or identical to those found in patients with the ocular type of BD.

Animals↗
PubMed1998

Orthotopic cardiac transplantation for the failing Fontan circulation.

OBJECTIVE: Modified Fontan procedures are now employed in several conditions unsuitable for bi-ventricular repair. Selection criteria have been relaxed. The procedure is palliative. Longterm outlook is unknown. This study evaluated factors associated with the development of a failing Fontan circulation and transplantation results. METHODS: Retrospective review of patients referred to a single centre for cardiac transplant assessment. RESULTS: Between 1985 and 1996, 46 of 448 cardiac transplants were performed for congenital heart disease. Nine of these were performed in patients with a failing Fontan circulation (four adults, five children). In six cases, the dominant ventricle had left ventricular (LV) morphology. Congenital anomalies included double outlet right ventricle (three cases), double inlet left ventricle (two cases), tricuspid atresia (two cases), and pulmonary atresia with intact ventricular septum (one case). Fontan procedures were performed in absence of sinus rhythm (four cases), atrio-ventricular (AV) valve regurgitation (two cases), aortic regurgitation and systolic LV dysfunction (one case), elevated mean pulmonary artery pressure (one case), and older age (>7 years, eight cases). Three patients required early re-operation and two needed permanent pacing. Subsequent deterioration associated with loss of sinus rhythm (four cases) and progressive AV valve regurgitation (seven cases) led to transplant assessment (at < 1 year, five cases; at 2-12 years, four cases). All patients were listed for transplantation. Three patients required intravenous inotropic support and three patients with lymphocytotoxic antibodies needed prospective crossmatching. Donor cardiectomy was modified to facilitate implantation. The recipient operation involved pulmonary artery reconstruction (using pericardium), modified atrial and direct caval anastomoses. Three patients died within 24 h of surgery (two graft failures, one haemorrhage). In operative survivors (n = 6), intensive care stay was 3-16 days, and hospital stay ranged from 14 to 32 days. There have been no subsequent deaths (follow up, 0.5-4.7 years). CONCLUSION: In high-risk Fontan candidates, transplantation may be preferable at the outset. Previous surgery, lymphocytotoxic antibodies, indeterminate pulmonary vascular resistance, emergency status, sub-optimal donor selection, and perioperative bleeding contribute to peri-operative mortality. In survivors, the outcome remains very encouraging.

Antilymphocyte Serum↗
PubMed1998

Thiamine deficiency mimicking acute rejection following cardiac transplantation.

We describe a recipient of an orthotopic cardiac transplant who developed severe ventricular dysfunction following an episode of sepsis. He had normal cardiac biopsies and responded to treatment with thiamine. Causes other than rejection should be considered in patients who have received a cardiac transplant and who present in cardiac failure.

Acute Disease↗
PubMed1998

Empyema thoracis: a role for open thoracotomy and decortication.

BACKGROUND: Thoracentesis and antibiotics remain the cornerstones of treatment in stage I empyema. The management of disease progression or late presentation is controversial. Open thoracotomy and decortication is perceived to be synonymous with protracted recovery and prolonged hospitalisation. Advocates of thoracoscopic adhesiolysis cite earlier chest drain removal and hospital discharge. This paper challenges traditional prejudice towards open surgery. METHODS: A five year audit of empyema cases referred to a regional cardiothoracic surgical unit analysing previous clinical course, surgical management, and outcome. RESULTS: Between February 1992 and February 1997, the number of referrals to this centre increased dramatically. Twenty-two children were referred for surgery (15 boys, seven girls; age range, 0.5-16 years). Before referral, patients had been unwell for 6-50 days (median, 15), had been treated with several antibiotics, and had undergone chest ultrasound (15 patients), computed tomography (five patients), pleural aspiration attempts (13 patients), and intercostal drainage (seven patients). The organism responsible was identified in only two cases (Streptococcus pneumoniae). Three patients had intraparenchymal abscess formation. Eighteen patients underwent open thoracotomy and decortication. Drain removal was performed on the first or second day. Fever resolved within 48 hours. Median hospital stay was four days. All patients had complete clinical and radiological resolution. CONCLUSIONS: Treatment must be tailored to the disease stage. In stage II and III diseases, open decortication followed by early drain removal results in rapid symptomatic recovery, early hospital discharge, and complete resolution. In the early fibrinopurulent phase, alternative strategies should be considered. However, even in ideal cases, neither fibrinolysis nor thoracoscopic adhesiolysis can achieve more rapid resolution at lower risk.

Adolescent↗
PubMed1998

Benign transient hyperphosphatasemia of infancy and early childhood following cardiac transplantation.

The phenomenon of a transient very high rise in serum alkaline phosphatase, associated with either trivial illness or no symptoms, in early childhood has been described previously in otherwise normal children. We describe here what we believe are the first published reports in two children who have previously undergone orthotopic cardiac transplantation. They were found to have a very high serum alkaline phosphatase, with features consistent with a diagnosis of transient hyperphosphatasemia of infancy and early childhood. The importance of early recognition and avoidance of overinvestigation are discussed.

Alkaline Phosphatase↗