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Biomedical subjects

R Shah

Publications and source records attributed to R Shah.

At least 109 records · Page 6Linked to original sources
PubMed1997

Carcinoid tumour of the lung.

A retrospective analysis of 29 patients with carcinoid tumour of the lung treated between 1980 to 1995 is presented. There were 15 females and 14 males with a mean age of 57 years (range 28-72). Fourteen of the 29 carcinoids were peripheral and the remaining 15 were central. Preoperative histology was available in 17. Surgical resection was carried out in 27 patients, one patient was unfit whilst the other patient had multiple liver metastases at presentation. Surgical treatment offered were lobectomy (n = 19), pneumonectomy (n = 3), sleeve lobectomy (n = 3) and segmentectomy (n = 2). Twenty three patients were stage 1 tumours, 3 were stage II and one was stage III and 1 was stage IV. Postoperative histology confirmed typical carcinoids in 24 patients and the remaining 5 were atypical. There was one perioperative death from massive pulmonary embolism and there was no morbidity. Overall five year survival rate for patients with carcinoid was 96.4%. Five year survival for typical carcinoid and that of atypical carcinoid was 100% and 77.8% respectively. Typical carcinoids carry an excellent prognosis and should be offered conservative lung resection, whilst atypical carcinoids which behave aggressively should be treated by radical lung resections.

Carcinoid Tumor↗
PubMed1997

Continuous paravertebral block for post thoracotomy analgesia in children.

The use of continuous paravertebral analgesia was studied in 15 children with a mean age of 9.8 years (2-16 years). Nine patients received pre-emptive and postoperative paravertebral analgesia while six children studied earlier in the series received only post operative paravertebral analgesia. Excellent pain relief was attained in all patients, as assessed by the graded pictures of facial expression or visual analogue pain scores and morphine requirements. There were no pulmonary complications and no complications related to the continuous paravertebral infusion of bupivacaine. We conclude that continuous paravertebral block is an effective and safe method for post thoracotomy pain relief in children.

Adolescent↗
PubMed1996

Production of tumor necrosis factor-alpha as a result of glia-T-cell interaction correlates with the pathogenic activity of myelin basic protein-reactive T cells in experimental autoimmune encephalomyelitis.

Tumor necrosis factor-alpha (TNF-alpha) has attracted the greatest attention as a major factor in experimental autoimmune encephalomyelitis (EAE) pathogenesis. We compared rats undergoing EAE with manipulated but healthy animals by examining TNF-alpha gene expression in cells recovered from the brain. We used reverse transcriptase-polymerase chain reaction (RT-PCR) as a sensitive assay for detection and Northern blot hybridization as a reliable quantitative assay of TNF-alpha mRNA. TNF-alpha gene expression was consistently detected in rats immunized with myelin basic protein (MBP) emulsified in complete Freund adjuvant (CFA), but not in rats immunized with MBP emulsified in incomplete Freund adjuvant (IFA), which does not induce EAE. Similarly, brain-derived cells from rats injected with cloned encephalitogenic T cells contained increased amounts of TNF-alpha mRNA compared with rats injected with nonencephalitogenic T cell clones similar in antigen specificity and in vitro lymphokine-producing capacity. Considering that the differing pathogenic capacity of MBP-reactive T cells might result from differing patterns of interaction with glia, we examined the impact of T-cell-glia interaction in vitro on cytokine gene expression in both cell types. Glial components were efficient in inducing TNF-alpha expression in T cells; T cells and T-cell-derived cytokines could elicit expression of several lymphokine genes in glial cells. Comparison of RT-PCR and blot hybridization assays, however, suggested that cytokine expression was much more efficient, on a per cell basis, in T cells than in glia. TNF-alpha was shown to have direct cytotoxic effect on glial cells, which was greatly enhanced by small amounts of interferon-gamma (IFN-gamma).

Animals↗
PubMed1996

Novel insights into the biology of myelodysplastic syndromes: excessive apoptosis and the role of cytokines.

The paradox of myelodysplastic syndromes (MDS) which present with pancytopenias despite cellular bone marrows (BM) was investigated by conducting detailed studies of proliferation and apoptosis in 89 MDS patients. Our results demonstrated a rapid rate of both proliferation as well as apoptosis. Levels of three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and interleukin-1 beta (IL-1 beta) were measured in the same patients. High levels of TNF-alpha were found to correlate with high levels of apoptosis in 83 MDS patients (P = 0.0045). We propose a dual role for TNF-alpha (or other cytokines) in the pathogenesis of MDS. On the one hand, TNF-alpha induces apoptosis in the maturing cells causing pancytopenia while on the other, it stimulates the proliferation of the primitive progenitors accounting for the hypercellular BM frequently seen in MDS. A new model for MDS is presented. The initial abnormality probably affects a primitive hemopoietic progenitor which acquires a growth advantage leading to monoclonal hemopoiesis, which in turn makes these cells susceptible towards acquiring additional mutations and appearance of cytogenetically marked (or unmarked) clones. Cytokines such as TNF-alpha whose source is presently unknown, then contribute towards the clinical syndrome of pancytopenia and hypercellularity.

Antigens, CD34↗
PubMed1996

Stenting in malignant obstruction of superior vena cava.

The treatment of patients with malignant superior vena caval obstruction with minimal morbidity has been made possible by the recent introduction of expandable metal stents as the sole palliative treatment or as an adjunct to other treatment modalities. To alleviate the distressing symptoms of superior vena caval obstruction, self-expanding metal stents were used successfully in 12 (Wallstent device in 6 and Gianturco device in 6 patients) of 13 patients. The diagnoses were small cell carcinoma (n = 4), squamous cell carcinoma (n = 4), non-Hodgkin's lymphoma (n = 1), and mesothelioma (n = 1), and a diagnosis of malignancy was not confirmed (although strongly suspected) in the remaining three cases. Eleven patients had immediate relief of obstruction and there was no change in one patient. Mean follow-up was 3.7 months (range 1 to 10 months). Excellent palliation was obtained in all but one patient in whom recurrent superior vena caval obstruction developed 3 months after stenting. Mean survival was 4.8 months (range 1 to 10 months). The ease of insertion with the use of local anesthesia with radiologic control, the self-expanding nature of the stent, and the lack of major complications on follow-up of up to 10 months are particular advantages. The self-expanding superior vena caval stents are a useful addition to our armamentarium in the management of malignant superior vena caval obstruction.

Aged↗
PubMed1996

Flow cytometric and ultrastructural aspects of the synergistic antitumor activity of vitamin C-vitamin K3 combinations against human prostatic carcinoma cells.

Transmission and scanning electron microscopy and flow cytometry were employed to characterize the cytotoxic effects of vitamin C (VC), vitamin K3 (VK3), or VC-VK3 combinations on a human prostate carcinoma cell line (DU145) following a 1-h vitamin treatment and a 24-h incubation in culture medium. Cells exposed to VC exhibited membranous blebs, aberrant microvillar morphology, mitochondria with swollen cristae and intramitochondrial deposits, as well as nucleoli with segregated components. VK3-treated cells displayed a damaged cytoskeleton and membranes, a cytoplasm which contained large lumen, condensed polysomes, and severely damaged mitochondria with residual bodies, and nuclei which exhibited chromatic condensation, pyknosis, and karyolysis. VC-VK3-treated cells exhibited characteristics consistent with necrosis, i.e. swollen mitochondria and swollen, achromatic nuclei with marginated chromatin and intact envelopes, while other cells displayed characteristics consistent with apoptosis, i.e. expulsion of organelle-containing blebs, margination of nuclear chromatin, and segregation of nucleolar components. Vitamin treatment also decreased DNA synthesis, induced a S/G2 block in the cell cycle, and resulted in the accumulation of fragmented DNA. These results suggested that increased oxidative stress, subsequent membrane damage, and DNA fragmentation were responsible for enhanced cytotoxicity of the vitamin combination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Mechanism of UVB-induced suppression of the immune response to Mycobacterium bovis bacillus Calmette-Guerin: role of cytokines on macrophage function.

Previously we demonstrated that treatment of mice with either UVB radiation or supernatants derived from UVB-irradiated PAM 212 keratinocytes decreased the induction of the delayed-type hypersensitivity (DTH) response to Mycobacterium bovis bacillus Calmette-Guerin (BCG), impaired the clearance of bacteria from their lymphoid organs and also altered macrophage functions. In order to characterize the cytokines involved in these phenomena, UV-irradiated mice were injected with antibodies to interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-beta 1), or tumor necrosis factor-alpha (TNF-alpha). Injection of UVB-irradiated mice with anti-IL-10 immediately after UV irradiation restored the DTH response and reversed the UV-induced inhibition of bacterial clearance. Injection of UV-irradiated mice with anti-TGF-beta only partially restored the DTH response although it allowed a better clearance of BCG than injection of mice with the control antibody. In contrast, injection of anti-TNF-alpha did not affect the UVB-induced suppression of DTH or impaired bacterial clearance. Similarly, the ability of macrophages to phagocytose BCG and kill the intracellular organisms was restored to almost normal levels after injecting UV-irradiated mice with antibodies specific for IL-10 or TGF-beta. Injection of mice with either recombinant IL-10 or TGF-beta mimicked the effect of whole-body UV irradiation on immune function. These results suggest that IL-10 has a major role in UV-induced suppression of both DTH to BCG and impairment in the clearance of bacteria and that TGF-beta has a more significant role in blocking bacterial clearance. Furthermore, these cytokines seem to modulate immune responses by altering macrophage functions in UVB-irradiated mice.

Animals↗
PubMed1996

Predicting etoposide toxicity: relationship to organ function and protein binding.

PURPOSE: To investigate the effect of organ function on total and free etoposide pharmacokinetics and hematologic toxicity. PATIENTS AND METHODS: Seventy-two patients who received single-agent intravenous (i.v.) etoposide over 5 or 8 days (total dose, 500 mg/m2) were studied. Pharmacokinetic parameters were derived after analysis of total plasma etoposide by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection, and etoposide protein binding by ultrafiltration of an etoposide-spiked, pretreatment serum sample, followed by HPLC analysis. Free etoposide area under the concentration-time curve (AUC) was derived from the total AUC and protein binding. RESULTS: Patients with renal impairment (serum creatinine level > 130 mumol/L) had a lower plasma etoposide clearance (13.6 v 18.5 mL/min/m2; P = .016), resulting in an increased total-drug and free-drug AUC (total etoposide AUC 615 v 452 micrograms/mL.hr; P = .016; free etoposide AUC 26.0 v 17.6 micrograms/mL.hr; P = .026) and increased hematologic toxicity (nadir neutrophil count 0.3 v 1.9 x 10(9)/L; P = .005). Patients with albumin levels less than 35 g/L had no change in total etoposide kinetics but had an increase in unbound etoposide (5.2% v 4.1%; P = .01), resulting in an increase in free etoposide AUC (27.5 v 16.5 micrograms/mL.hr; P = .003) and more profound toxicity (nadir neutrophil count 0.6 v 1.9 x 10(9)/L; P = .004). In patients with normal albumin and creatinine, increased toxicity in those older than 65 years was associated with a reduced drug clearance, and in those with increased liver enzymes by a trend toward an increase in free etoposide AUC. CONCLUSION: Increased hematologic toxicity after etoposide in patients with abnormal organ function is mediated by an increase in free etoposide AUC. A reduction in dose is clearly indicated in such patients.

Adult↗
PubMed1996

Effects of low concentrations of benzene on mouse hematopoietic cells in vivo: a preliminary report.

Evaluation of benzene-induced hematotoxicity following exposure to low concentration is important for understanding mechanisms of toxicity and determining the dose response at benzene levels close to the current occupational exposure limit (1 ppm). Male B6C3F1 mice were exposed to 0, 1, 10, 100, or 200 ppm benzene by inhalation for 6 hr/day, 5 days/week, for 1, 2, 4, or 8 weeks. At each sampling time, we evaluated primitive and committed progenitor cells, differentiating and maturing lineage-specific cells, and stromal cells in the bone marrow; T and B lymphocytes of the spleen and thymus; micronucleated reticulocytes and erythrocytes; and standard blood parameters. At 100 and 200 ppm benzene, there were rapid and significant reductions in number of reticulocytes in the blood, B lymphocytes in the bone marrow and spleen, and an increased frequency of micronucleated reticulocytes in the bone marrow. At 10 ppm, the only parameter affected was a transient reduction in the number of splenic B lymphocytes. There were no significant effects induced by 1 ppm benzene in this study. The present study suggests numbers of B lymphocytes and maturing erythrocytes, and frequency of micronucleated reticulocytes are sensitive indicators of benzene-induced hematotoxicity and will be useful in further investigation of the hematotoxicity induced by 10 to 100 ppm benzene.

Animals↗
PubMed1996

The relationship of thoracic lymphadenopathy to pulmonary interstitial disease in diffuse and limited systemic sclerosis: CT findings.

OBJECTIVE: Mediastinal lymphadenopathy is frequently associated with interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). This study compared the extent of lymphadenopathy in diffuse and limited SSc with the presence and type of ILD found on CT scans. SUBJECTS AND METHODS: Seventy-three patients with diffuse and limited SSc underwent thoracic CT. The presence of lymphadenopathy was correlated with the frequency and type of ILD. RESULTS: Fifty-eight percent (18/31) of patients with diffuse cutaneous SSc and 40% (17/42) of patients with limited cutaneous SSc had lymphadenopathy. A significant relationship was found between lymphadenopathy and the presence of interstitial disease (p = .0002). Seventy-two percent (18/25) of patients with a ground-glass parenchymal pattern of interstitial disease and 74% (14/19) of patients with a honeycomb pattern had lymphadenopathy. CONCLUSION: Lymphadenopathy is prevalent in patients with SSc and ILD regardless of clinical subtype or interstitial pattern. Lymphadenopathy appears to increase as a function of the profusion rather than the morphology of ILD.

Female↗
PubMed1996

Results of surgical treatment of stage I and II lung cancer.

Pulmonary resection remains the most appropriate treatment for localised bronchogenic carcinoma, since prognosis and outcome are currently dependent on surgical resectability. A retrospective analysis of our experience with three hundred and thirteen stage I (n=250) and stage II (n=63) patients treated surgically form the basis of this report. The initial pulmonary resection was lobectomy in 173 patients, bilobectomy in 38, sleeve lobectomy in 12, pneumonectomy in 59, wedge excision or segmentectomy in 31. The overall operative mortality was 3.2%; 4.03% for lobectomy and 1.6% for pneumonectomy. Morbidity was observed in 21 (6.7%) patients. Four out of sixteen small cell carcinoma patients had postoperative adjuvant chemotherapy. Survival in patients with stage I tumours was 71% at 5 years and 61% at 10 years compared with 41% at 5 years and 35% at 10 years for patients with stage II disease. The five year survival after pneumonectomy was significantly (p<0.05) better for both stage I and stage II lung cancer than after lobectomy. Five year survival in stage I carcinoma was not influenced by histological type, while there was statistically significant difference (p<0.05) in survival between adenocarcinoma (0%) and squamous cell carcinoma (46%) in stage II disease. We conclude that an aggressive surgical approach can provide an excellent prognosis for recovery and long term cure in most patients with early stage lung cancer.

Carcinoma, Bronchogenic↗
PubMed1996

Tumor embolism to LAD during pneumonectomy. A case report.

Arterial embolization from bronchogenic carcinoma is a rare complication and more commonly occurs intraoperatively during pneumonectomy. We report an unusual case of intraoperative tumour embolism to LAD (left anterior descending artery) and aorta during left pneumonectomy due to tumour involvement of the inferior pulmonary vein. High risk cases should be evaluated by preoperative transesophageal echocardiography. If tumour involvement of the inferior pulmonary vein is demonstrated, a modification of the surgical technique or alternative modality of treatment should be used.

Adenocarcinoma↗