Delayed onset of skin fibrosis after the ingestion of eosinophilia-myalgia syndrome-associated L-tryptophan.
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Biomedical subjects
Publications and source records attributed to A Hasan.
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BACKGROUND: Acute lipodermatosclerosis is characterized by pain and tenderness in the medial aspect of the leg. It is thought to be the result of venous insufficiency and to be the acute counterpart of chronic lipodermatosclerosis, a hallmark of venous disease. However, there is no direct evidence linking acute lipodermatosclerosis to venous disease. OBJECTIVE: Our purpose was to determine whether acute lipodermatosclerosis is associated with venous insufficiency. METHODS: With air plethysmography, we determined the venous filling index, the ejection fraction, and the residual volume fraction in 15 sequential patients with acute lipodermatosclerosis. RESULTS: Ten of the 15 patients (67%) had at least one abnormal result, eight (53%) had two, and two (13%) had three. In four patients (27%), abnormalities of both reflux and ejection were noted. Duplex venous ultrasonography, in two of the patients with normal results from air plethysmography, showed incompetent perforators at sites of lipodermatosclerosis. CONCLUSION: Acute lipodermatosclerosis is associated with objective findings of venous insufficiency in a high percentage of patients. It is likely that this condition is the result of venous disease.
OBJECTIVE: To review the results of bronchial healing in a consecutive series of 100 isolated pulmonary transplants, performed at one centre between 1987 and 1994. METHODS: A retrospective review of 123 assessable bronchi (61 in single lung and 62 in bilateral lung) transplants was carried out. All anastomoses were assessed by bronchoscopy at 7-10 days, and follow up was from one to seven years. The effect on bronchial dehiscence or stenosis requiring endobronchial stent, of suture technique, pre and post operative steroid administration, bronchial wrap, donor ischaemic time and time to first rejection episode was assessed. RESULTS: Complications of airways healing occurred in four patients: stenosis in two and dehiscence in two (1.6% of bronchi at risk in both groups). Airway complication was not affected by steroids, pre-operative diagnosis, presence of a wrap (34 with pericardium or omentum, 89 with peribronchial tissue alone) or any other variable. There was a higher incidence of dehiscence (2/36) with continuous rather then interrupted (0/87) suture, but this was not statistically significant. There was one airway-related death. Two patients who required anastomotic stenting remain alive and well. CONCLUSIONS: A very low complication rate can be achieved without recourse to bronchial wrapping, telescoping anastomoses or steroid avoidance. Combined heart-lung transplantation or bronchial revascularisation are not required to achieve reliable bronchial healing.
B-cell epitopes of the mycobacterial 65 kDa heat shock protein (HSP) were mapped in sera from patients with Behçet's Disease (BD). A series of 47 overlapping synthetic peptides (15ers) derived from the sequence of the Mycobacterium tuberculosis 65 kDa HSP was used in ELISA. Significant increases in IgA and IgG antibody levels were observed with peptides 111-125, 154-172 and 311-326 in sera from BD, compared with those from controls. Homologous peptides derived from the sequence of the human mitochondrial 60 kDa HSP were then examined. Peptides 136-150 and 336-351 showed comparable results to the homologous mycobacterial peptides 111-125 and 311-326, respectively. The B-cell epitopes defined in this investigation overlap with the T-cell epitopes the authors have previously reported in BD. Inhibition studies are consistent with the view that antibodies to each of the three B-cell epitope peptides represent a small proportion of the total B-cell epitope repertoire elicited by the 65 or 60 kD HSP. Sequential antibody studies suggest that IgA and IgG antibody titres to one or all three peptides tested may increase during exacerbation of ocular disease. The functional role of these antibodies needs to be determined, but the peptides may be involved in the immunopathogenesis of BD as they can induce experimental uveitis in Lewis rats, which is a principal manifestation of BD.
BACKGROUND: Increasing evidence suggests that fibrin deposition is an important pathogenic component of venous ulceration and that fibrin removal could accelerate ulcer healing. OBJECTIVE: We sought to determine whether topical application of recombinant tissue plasminogen activator (tPA) compounded in 1% hyaluronate acid (HA) can be used safely in venous ulcers and whether it can accelerate healing. METHODS: Twelve patients were randomized in a double-blind fashion in three sequential groups of four subjects each, so as to receive daily topical application of either placebo (HA alone, one patient) or tPA/HA (three patients) at escalating doses of 0.25, 0.5, and 1.0 mg/ml of tPA for 4 weeks. RESULTS: No safety problems occurred, and we found a close direct correlation between mean ulcer reepithelialization, fibrin removal, and the dose of topically applied tPA (r = 0.991). CONCLUSION: In this first study to examine its usefulness, topically applied tPA appears to be a safe and promising agent for treating venous ulcers.
Thermal injury is known to induce alterations in the immune system. Sixty-four patients of thermal burns have been studied for serum immunoglobulins. Concentrations of IgG, IgA and IgM were decreased immediately after injury and gradually increased up to normal limits on the 30th postburn day.
The management of patients who present with penetrating thoracic trauma but are haemodynamically stable may be subjective and imprecise. We report our initial experience with the use of video-assisted thoracoscopy in a series of five patients in whom accurate assessment was achieved and unnecessary thoracotomy avoided.
Ischemia and reperfusion have been shown to cause damage to the endothelium as well as to the cardiac myocyte. Although the vasodilator response has been shown to be impaired following ischemia and reperfusion, the effect of a short period of global ischemia on the contractile response of the coronary vasculature is not clear. In the present study, coronary vasoconstriction in response to U46619, PGF2 alpha, 5-HT, and KCl was found to be depressed for at least 15 min following 15 min of in vitro global ischemia in rats hearts. Vasodilator blockers or inactivators were used in an effort to restore this depressed coronary response. Indomethacin (5 microM) was used to block production of vasodilator prostaglandins, L-NAME (30 microM) to block production of nitric oxide (NO), and adenosine deaminase (2.4 units/ml of coronary flow) to inactivate adenosine. None of these agents restored the normal coronary constrictor response following ischemia. When superoxide dismutase and catalase (both 20 micrograms/ml of coronary flow) were infused for 5 min before and after ischemia, the coronary response recovered more than 100% of its preischemic value by 15 min of reperfusion, but still remained depressed at 5 min reperfusion. These data suggest that free radicals produced during ischemia and/or reperfusion may be at least partly responsible for this temporary "stunning" of the coronary vasculature. Since the impaired contractile response was still present at 5 min reperfusion when the buffer was supplemented with oxygen radical scavengers, another mechanism must also be involved in this "stunning" process.
Besides rutin, quercetin 3-rhamnoside and kaempferol 3-rhamnosyl(1-->6) galactoside, a new flavonol glycoside, quercetin 3-glucosyl(1-->4)galactoside, and 1,6,8-trihydroxy-3-methyl anthraquinone (emodin) have been characterized from leaves of Rumex chalepensis. The structures were established on the basis of Rf values, acid hydrolysis to aglycone and sugar and UV, EI and FAB-mass spectra, 1H NMR, 13C DEPT NMR, NOE difference measurement, 1H-H COSY and 1H-13C COSY spectral data.
Right ventricular failure secondary to elevated pulmonary vascular resistance (PVR) following orthotopic cardiac transplant is a complication with a high mortality; and patients with high resistance are often not accepted on transplant waiting lists. We describe six cases of right ventricular failure after cardiac transplant managed by right ventricular assist device (RVAD), four of whom died and two patients who survived following life-threatening complications.
The characteristics of facial nerve electromyography at various levels of neuromuscular blockade are unclear. Partial blockade is well known to facilitate anesthetic safety and management. However, the use of neuromuscular blockage in many skull base procedures is avoided to allow intraoperative facial nerve monitoring.We studied the influence of various levels of neuromuscular blockade on facial nerve stimulation in the New Zealand white rabbit. The facial nerve was exposed in the middle ear of six rabbits. Using electromyographic-type facial nerve monitor, we recorded the facial electromyography signals in these rabbits at increasing levels of vecuronium-induced neuromuscular blockade. All animals demonstrated reliable facial electromyography response at all levels of partial neuromuscular blockade (P < .02). Five of the six animals could be monitored throughout complete blockade. These results clearly demonstrate that rabbit facial electromyography monitoring is possible under neuromuscular blockade. The effect of neuromuscular blockers on facial electromyography monitoring deserves further study, as partial blockade would greatly facilitate the management of anesthesia in otologic, neurotologic, and skull base surgery.
Pentoxifylline (PTX) is a methylxanthine that exhibits multiple biologic activities, including the inhibition of collagen synthesis by dermal fibroblasts. Because some PTX activities have recently been linked to transcription factor-mediated regulation of gene transcription, we have investigated if PTX acts to inhibit collagen synthesis at a transcriptional locus by measuring procollagen mRNA levels by assaying for the presence of an activator of procollagen gene promoters, nuclear factor (NF)-1. The effects of another methylxanthine, pentifylline (PTF), shown herein to be a tenfold more potent inhibitor of collagen synthesis than PTX, and interferon-alpha, -beta, and -gamma were studied in parallel. Analysis of extracellular protein and RNA from 48-h-treated fibroblasts showed that PTX, PTF, and interferons decreased alpha 1(I), alpha 2(I), and alpha 1(III) procollagens by reducing the steady-state levels of the corresponding procollagen mRNA transcripts. Reduction of procollagen mRNA levels appeared to be dependent on new protein synthesis, as it was prevented by treatment with cycloheximide. Assay for the presence of nuclear NF-1 by gel mobility shift analysis showed that extracts from interferon, PTX, and PTF-treated fibroblasts lacked proteins recognizing the consensus DNA binding sequence for NF-1. Taken together, these observations suggest interferons and methylxanthines may inhibit fibroblast collagen synthesis by a common mechanism requiring new protein synthesis that suppresses procollagen gene transcription through down-regulation of NF-1.
It is thought that normal fibrotic repair progresses to dermal fibrosis when fibroblasts are activated persistently by chronic exposure to cytokines such as transforming growth factor-beta. However, additional cytokines and mechanisms may play a role in the development of fibrosis. Thus, we examined a recently described T-lymphocyte/macrophage-derived cytokine, oncostatin M, for its effect on the production of collagen and glycosaminoglycan by microcultures of normal dermal, sclerodermal, and keloidal fibroblasts. Treatment with oncostatin M for 48 h induced dose-dependent (1-100 ng/ml) increases in the collagen and glycosaminoglycan production of nine normal fibroblast strains, which in the absence of fetal bovine serum at 100 ng/ml averaged 196% and 244%, respectively. Oncostatin M treatment increased both types I and III procollagens and their mRNA transcripts, as well as levels of hyaluronic acid, chondroitin-4/6 sulfates, and dermatan sulfate, but not fibronectin or general noncollagenous protein synthesis. In contrast, the collagen production of six of eight sclerodermal and keloidal fibroblast strains was essentially unresponsive to oncostatin M treatment, with 100 ng/ml inducing an average increase of only 34% for the eight fibrotic strains. Oncostatin M stimulation of fibrotic fibroblast glycosaminoglycan production was also hyporesponsive, as 100 ng/ml of oncostatin M induced an average increase of only 101%. These results indicate that oncostatin M could function as a stimulator of normal fibrotic repair via activation of fibroblast collagen and glycosaminoglycan synthesis and that the persistent activation of sclerodermal and keloidal fibroblasts is accompanied by a loss of sensitivity to oncostatin M stimulation.
T cell epitopes of the 65-kD heat shock protein (hsp) were investigated in patients with recurrent oral ulcers (ROU). Peripheral blood mononuclear cells were stimulated with overlapping synthetic peptide (15ers), derived from the sequence of the 65-kD hsp of Mycobacterium tuberculosis. Specific lymphoproliferative responses were stimulated only with peptide 91-105 in ROU, compared with healthy or disease controls (P < 0.01). This was confirmed by studying 760 short term cell lines generated with the 65-kD hsp and then stimulated with the peptides. The frequency of short term cells lines responding to peptide 91-105 in ROU was significantly greater than in healthy (P < 0.0001) or disease controls (P < 0.01). A comparative investigation with the homologous human 60-kD hsp peptide 116-130 also showed significantly greater lymphoproliferative responses in ROU than in healthy (P < 0.01) or disease controls (P < 0.001). The potential involvement of the T cell epitope 91-105 in the pathogenesis of ROU is supported by finding a significant increase in the lymphoproliferative responses stimulated with peptide 91-105 during the stage of ulceration, compared with remission in 9/11 patients studied sequentially (P < 0.05). The results suggest that oral ulceration might be initiated by the microbial hsp peptide 91-105 stimulating the mucosal Langerhans cells, which may generate autoreactive T cell clones primed to the homologous peptide 116-130.
BACKGROUND: Bilateral sequential lung transplantation (BSLT) has been widely adopted as an alternative to combined heart and lung transplantation for the management of end stage septic lung disease in many transplant centres. METHODS: A retrospective review was undertaken of the first 32 consecutive patients with septic lung disease to undergo BSLT at the Freeman Hospital. RESULTS: Between April 1988 and October 1994 32 patients underwent BSLT. Survival at 30 days was 85% and actuarial survival at one year was 70%. Improved pulmonary function was seen in all surviving patients. CONCLUSION: BSLT for septic lung disease offers comparable survival to heart-lung transplantation, with excellent functional results. Long term results may be superior because the disadvantages of transplanting the heart are avoided.
Increasing evidence suggests that smooth pursuit eye movement (SPEM) dysfunction may serve as an endophenotype or genetic marker of schizophrenia. The authors tested SPEM and visual fixation (VF) in 31 patients with schizophrenia, 33 of their first-degree relatives, and 24 patients with major depressive disorder. A high rate of abnormal VF was found in schizophrenic patients and their first-degree relatives, but not in affective disorder patients with or without psychotic features. Rate of VF abnormality distinguished schizophrenic patients from acutely depressed mood disorder patients; SPEM did not. VF and SPEM performance correlated only moderately, suggesting that the pathophysiologies of these two eye movement abnormalities may be partially independent. Implications for identifying a schizophrenia endophenotype are discussed.
PATIENTS AND METHODS: Seven children of the same family with a possible variant of Diamond-Blackfan anemia (DBA) are reported. Five were male siblings, and the other two were their cousins, one male and one female. All were products of consanguineous marriages of healthy parents. All cases occurred within one generation. Anemia was present at birth or shortly after birth. Hepatosplenomegaly was present in all. Four had short stature. Hematological findings included normochromic, normocytic, or macrocytic anemia, marked reticulocytopenia, with initial normal white blood cell and platelet count, and absent or markedly decreased erythroid precursors on bone marrow examination. All were treated initially with prednisolone; in one patient oxymetholone was added. RESULTS: Three children failed to respond to the initial treatment, and also failed to respond to cyclosporin A and pulse doses of methylprednisolone. Myelofibrosis occurred in two siblings, 9 and 11 years from diagnosis. In two children the disease recurred 9 and 12 years after initial diagnosis. CONCLUSIONS: Our cases point to a possible variant of DBA characterized by the presence of normochromic normocytic anemia, hepatosplenomegaly, absent skeletal malformations, and unusual long- term complications.
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