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Biomedical subjects

A Hasan

Publications and source records attributed to A Hasan.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1997

Dermal fibroblasts from venous ulcers are unresponsive to the action of transforming growth factor-beta 1.

Failure to reepithelialize is the major clinical problem in venous ulcers. It is not clear whether the problem resides with keratinocytes or with inadequate and improper formation of extracellular matrix. In this study, we characterized the biosynthetic activity and response to transforming growth factor-beta 1 (TGF-beta) of dermal fibroblast cultures isolated from biopsies of venous ulcers and from normal thigh skin (controls) of seven patients. We found that baseline 3H-proline incorporation was similar in fibroblasts from venous ulcers and control skin (p= 0.1716). No difference was detected by ELISA between ulcer and control fibroblasts in the synthesis of total TGF-beta (p = 0.2309), and the mRNA levels for alpha 1(I) procollagen and TGF-beta were comparable in both groups. However, TGF-beta (0.1-5 ng/ml) enhanced collagen protein synthesis by more than 60% and in a dose-dependent manner (r = 0.997) in control fibroblast cultures, while failing to stimulate collagen production by venous ulcer fibroblasts (p = 0.0001). This unresponsiveness to TGF-beta was associated with up to a fourfold decrease in TGF-beta Type II receptors. We conclude that fibroblasts from the edge of non-healing venous ulcers are unresponsive to the action of TGF-beta, and that this blunted response may cause faulty deposition of the extracellular matrix needed for reepithelialization and wound healing.

Cells, Cultured↗
PubMed1997

The use of 99Tcm-DTPA aerosol and caesium iodide mini-scintillation detectors in the assessment of lung injury during cardiopulmonary bypass surgery.

Lung injury is a well-documented adverse effect of cardiopulmonary bypass. The mechanism of injury is not fully understood, but pulmonary hypoxia may be a factor. Post-operative pulmonary epithelial permeability (PEP) in ventilated versus non-ventilated lungs was measured within 2 h of return to the intensive care unit using a 99Tcm-diethylenetriamine pentaacetate aerosol technique. A portable scintillation detector system was required. Sodium iodide detectors have been used previously with this technique but are cumbersome. This study used mini caesium iodide detectors (Oakfield Instruments, Oxon, UK), which can be attached directly to the patient and are more suited to the intensive care setting. The clearance half-time from lung to blood (T1/2LB) was measured in 31 patients (62 lungs). The mean (+/- S.E.M.) clearance half-times were 42.3 +/- 2.7 and 45.7 +/- 3.8 min for non-ventilated and ventilated lungs respectively, with a mean difference of 3.4 +/- 3.1 min (P > 0.05). We conclude that, using this technique, no significant difference in PEP is observed between ventilated and non-ventilated lungs in patients undergoing cardiopulmonary bypass.

Adult↗
PubMed1997

The effects of Escherichia coli sepsis and short-term ischemia on coronary vascular reactivity and myocardial function.

Ischemia and reperfusion stun the myocardium and the coronary vasculature. We have previously shown that a short period (15 min) of global ischemia in the isolated rat heart causes impaired coronary constriction in response to a thromboxane analog U46619 during reperfusion. Sepsis has also been shown to affect myocardial and vascular function. In the present study, we determined whether Escherichia coli-induced sepsis would exacerbate the effects of ischemia on the coronary circulation. Sepsis prolonged the impairment in the coronary constriction response to U46619 following short term ischemia. We hypothesized that sepsis-induced increases in nitric oxide (NO) production caused the delay in the recovery of the contractile response to U46619. Perfusion with NO synthase inhibitors however indicated that the impaired response was not due to NO. However, NO did appear to have a significant role in the development of myocardial ischemic contracture and on the recovery of diastolic function after ischemia. Inhibitors of NO synthase also caused a significant increase in basal coronary perfusion pressure as well as in the maximum coronary pressure generated in response to U46619, suggesting a role of NO in regulating basal coronary vascular resistance in the isolated rat heart. Some of these effects were more pronounced in septic rat hearts than in the sham surgical rat hearts, consistent with altered nitric oxide production in the septic rat hearts.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

TGF-beta3 stimulates and regulates collagen synthesis through TGF-beta1-dependent and independent mechanisms.

In contrast to the TGF-beta1 and beta2 isoforms, TGF-beta3 has shown the ability to downregulate scarring and fibrosis in vivo under certain experimental conditions. In this study, we determined the direct effects of TGF-beta3 on cultures of human dermal fibroblasts. TGF-beta3 (0.1 to 100 pg per ml) increased DNA synthesis up to 50% (p < 0.01, r = 0.970), collagen protein synthesis up to 200% (dose range of 0.1 to 5 ng per ml, p < 0.001, r = 0.990), and increased alpha1(I) procollagen mRNA levels (r = 0.999), with maximal effects (200% of control) observed by 24 h. Collagen lattice contraction was increased by more than 50% in response to TGF-beta3 (p < 0.001), and to a similar extent as the TGF-beta1 isoform. Stimulation of collagen synthesis and of alpha1(I) procollagen mRNA levels in response to TGF-beta3 was partially blocked by a TGF-beta1-specific anti-sense oligonucleotide but was still detectable (35% greater than baseline) when TGF-beta3 was added to dermal fibroblasts from TGF-beta1 knock-out mice. In contrast with these stimulatory effects, however, downregulation of alpha1(I) procollagen, alpha1(III) procollagen, and TGF-beta1 mRNA levels toward baseline occurred when TGF-beta3 (0.1 to 5 ng per ml) was added simultaneously and in combination with TGF-beta1. We conclude that stimulation of collagen synthesis by TGF-beta3 occurs through TGF-beta1-dependent and independent pathways. By downregulating the response to TGF-beta1 and by shifting from one pathway to the other, TGF-beta3 can dampen and provide fine-tuning to the overall TGF-beta's induced program of collagen deposition.

Animals↗
PubMed1997

Durometer measurements of skin induration in venous disease.

BACKGROUND: The degree of skin induration (lipodermatosclerosis) around venous ulcers has prognostic significance; however, objective measurements are needed to assess the induration. The durometer, an engineering instrument used to measure the hardness of metals and plastic, has recently been adapted to assess skin induration. OBJECTIVE: The purpose of this study was to measure skin induration and its relationship to skin ulceration by the use of a durometer, and to determine the influence of edema, if any, on durometer measurements. METHODS: The degree of skin induration on the medial leg was determined in six sequential, nonselected patients with lipodermatosclerosis and leg ulcers, and in five normal volunteers by using a blinded observer's clinical score (0 = normal to 3 = maximal induration) and a hand-held Type 0 durometer. In addition, durometer readings in 14 patients with edema and eight control subjects were taken on the tibia, the dorsum of the foot, and behind the ankle. RESULTS: Durometer readings in patients with leg ulcers and lipodermatosclerosis diminished as one measured from the superior edge of the ulcer to the knee (r = 0.925). The higher the clinical skin score the higher were the durometer readings (P = 0.0062). The presence of edema did not influence durometer measurements. CONCLUSION: The durometer is an effective and reliable instrument for measuring the degree of skin induration in venous ulceration and its readings are not affected by edema. Ulcers occur in skin most affected by lipodermatosclerosis.

Dermatology↗
PubMed1997

Differential pulmonary flow after heart transplantation in patients with malposition of the great arteries.

In transposition of the great arteries the right lung is preferentially perfused, and this may be due to the orientation of the right pulmonary artery when the main pulmonary artery comes off in a posterior position. In this study the mean perfusion of the right lung was 61% in six patients who had "correction" of the great artery malposition at the time of heart transplantation. This suggests that anatomic correction of pulmonary artery orientation does not correct the preferential perfusion to the right lung.

Adult↗
PubMed1996

Base-boronated dinucleotides: synthesis and effect of N7-cyanoborane substitution on the base protons.

Boron-modified nucleic acids comprise a new set of DNA mimics that have potential biological and therapeutic applications. A series of nine dinucleotides containing N7-cyanoborane-2'-deoxyguanosine ((7b)dG) at the 3', 5' or both positions of the phosphodiester linkage have been synthesized using solution phase phosphoramidite chemistry. Fmoc was used as the 5'-protecting group because of incompatibility of the cyanoborane moiety with 5'-DMT cations generated during the deprotection step. The presence of the cyanoborane group was confirmed on the basis of Fab-MS and 1H NMR spectroscopy. The H-8 proton of (7b)dG in the dinucleotides shifted 0.35-0.80 p.p.m. downfield relative to that of unmodified dG. A comparison of the D20 exchange kinetics of the H-8 proton at 60 degrees C showed that H-8 of (7b)dG is very labile relative to unmodified dG, indicating that the N7-cyanoborane modification increases the acidity of the H-8 proton of (7b)dG. These studies illustrate the feasibility of synthesizing boron-containing oligonucleotides which are modified at the N7-guanine to block Hoogsteen pairing in the DNA major groove.

Amides↗
PubMed1996

Role of gamma delta T cells in pathogenesis and diagnosis of Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a multisystem disorder of unknown pathogenesis. The diagnosis is based on a set of international clinical criteria. Previous investigations have suggested that immunological cross-reactivity between peptides within streptococcal heat-shock proteins and human peptides might be involved in the pathogenesis of BD. We tested four peptides from mycobacterial heat-shock proteins to see if they specifically stimulated gamma delta T cells from BD patients. We then investigated this response to see whether it could be used as a laboratory test to diagnose BD. METHODS: We used a T-cell proliferative test to assay responses to four mycobacterial 65 kDa heat-shock-protein peptides and to four homologous peptides derived from the sequence of the human 60 kDa heat-shock protein. FINDINGS: We elicited significant gamma delta T-cell responses to the mycobacterial peptides in 25 (76%) of 33 patients with BD, compared with 2 (3.6%) of 55 controls with recurrent oral ulcers, systemic disease, or no disorders. The proportion of BD patients who had false-negative results decreased if the test was done during clinical manifestation of disease activity. There was a correlation between disease activity and T-cell responses. Four homologous peptides from human 60 kDa heat-shock protein also specifically stimulated T cells from patients with BD but with lower stimulation indices. INTERPRETATION: Activation of peripheral-blood mononuclear cells with the four heat-shock-protein peptides elicited significant T-cell proliferative responses by the gamma delta subset of T cells, which may regulate alpha beta T cells. Because these peptides have a high specificity for BD, this assay can be used as a laboratory diagnostic test for BD.

Adult↗
PubMed1996

Vascular complications of lung transplantation.

BACKGROUND: The data on vascular anastomotic complications after single-lung and bilateral lung transplantation are scant. METHODS: We reviewed the data on our patients having single and bilateral lung transplantation to examine our experience and management of vascular anastomotic complications. RESULTS: We retrospectively identified 5 of 109 consecutive patients undergoing lung transplantation who had postoperative pulmonary arterial or venous obstruction. There were 4 women and 1 man (age range, 32 to 53 years). Three patients had left single-lung transplantation, 1 patient had right single-lung transplantation, and 1 patient underwent bilateral sequential lung transplantation. Complications comprised two right-sided and two left-sided pulmonary artery stenoses and one combined left pulmonary arterial and venous obstruction. Isotope perfusion scanning was used in 3 patients and suggested a vascular stenosis in all of them. Pulmonary angiography was used in each as a confirmatory test and to demonstrate anatomic details. Transesophageal echocardiography was used in 1 patient and did not detect a right pulmonary artery stenosis. One patient underwent revision of a pulmonary artery stenosis with a period of warm ischemia and subsequent fatal lung injury. Two revisions were undertaken on cardiopulmonary bypass with a cold blood flush to the transplanted lung. One venous anastomotic angioplasty with stent insertion was performed. Two patients died before treatment. All 5 patients died between 5 and 630 days postoperatively. CONCLUSIONS: Vascular complications carry a high mortality. Reoperation, preferably using cardiopulmonary bypass and a cold blood flush technique to avoid further lung injury, is recommended. In high-risk patients, dilation or stent insertion can be considered.

Adult↗
PubMed1996

Evaluation of 1-azabicyclo[2.2.2]oct-3-yl alpha-fluoroalkyl-alpha-hydroxy-alpha-phenylacetates as potential ligands for the study of muscarinic receptor density by positron emission tomography.

Both 1-azabicyclo[2.2.2]oct-3-yl alpha-(1-fluoroeth-2-yl)-alpha-hydroxy-alpha-phenylacetate (FQNE, 5) and 1-azabicyclo[2.2.2]oct-3-yl alpha-(1-fluoropent-5-yl)-alpha-hydroxy-alpha-phenylacetate (FQNPe, 6) were prepared and evaluated as potential candidates for the determination of muscarinic cholinergic receptor (mAChR) density by positron emission tomography (PET). The results of in vitro binding assays demonstrated that although both 5 and 6 had high binding affinities for m1 and m2 mAChR subtypes, 6 displayed a higher affinity (nM, m1; KD, 0.45, m2; KD, 3.53) as compared to 5 (nM, m1; KD, 12.5, m2; KD, 62.8). It was observed that pretreatment of female Fisher rats with either 5 or 6 prior to the i.v. administration of Z-(-)(-)-[131I]-IQNP, a high-affinity muscarinic ligand, significantly blocked the uptake of radioactivity in the brain and heart measured 3 h postinjection of the radiolabeled ligand. These new fluoro QNB analogues represent important target ligands for evaluation as potential receptor imaging agents in conjunction with PET.

Animals↗
PubMed1996

Two flavonol triglycosides from flowers of Indigofera hebepetala.

Two new flavonol triglycosides, kaempferol 3-omicron-alpha-L-rhamnopyranosyl(1->2)-beta-D-galactopyranoside-7-O- alpha-L-arabinofuranoside and kaempferol 3-O-alpha-rhamnopyranosyl(1-->6)-beta-D-galactopyranoside-7-O- alpha-L-arabinofuranoside were isolated from the flowers of Indigofera hepepetala, together with three known glycosides, kaempferol 3-omicron-alpha-L-arabinopyranoside-7-O-alpha-L-rhamnopyranoside, kaempferol 3-O-alpha-L-rhamnopyranoside-7-O-alpha-L-arabinopyranoside and kaempferol 7-rhamnoside. The structures were determined by means of Rf values, UV, EI-mass spectrometry, FAB-mass spectrometry, 1H NMR, 13C (B.B and DEPT) NMR, NOE difference measurement and 1H-1H COSY spectral data.

Flavonoids↗