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H Imam

Publications and source records attributed to H Imam.

9 recordsLinked to original sources
PubMed2001

Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele.

Several theories have been advanced to explain the mechanisms by which varicocele impairs male fertility. These theories include scrotal hyperthermia, retrograde flow of adrenal or renal metabolites, Leydig cell dysfunction and hypoxia. Varicocele is reported to be associated with elevated reactive oxygen species (ROS) production in spermatozoa and diminished seminal plasma antioxidant activity. The aim of this study was to investigate whether surgical correction of varicocele might reduce ROS or increase the antioxidant capacity of seminal plasma from infertile patients with varicocele. The study group consisted of 68 infertile males, selected from patients scheduled for varicocelectomy at Cairo University Hospital during the year 1999. Seminal plasma levels of two ROS [malondialdehyde (MDA), hydrogen peroxide (H2O2)] and one ROS radical [nitric oxide (NO)] were estimated as well as six antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), vitamin C (Vit C), vitamin E (Vit E), albumin) on the day prior to varicocelectomy. For comparison, the same parameters were measured again 3 and 6 months post-operatively. A statistically significant reduction in the 3 month post-operative levels of MDA, H2O2 and NO was observed when compared with the pre-operative values. A further significant reduction took place during the following 3 months. Four of the six antioxidants tested (SOD, CAT, GPx, and Vit C) showed a significant increase in seminal levels when comparing 3-month post-operative with pre-operative values. A further significant increase of the four antioxidant levels took place during the following 3 months. No significant change in the level of seminal plasma albumen took place during the first 3 months after varicocelectomy, however, a significant increase was noted during the next 3 months. In contrast to other antioxidants, seminal plasma levels of Vit E showed a significant decrease when comparing 3-month post-operative with pre-operative values. A further significant decrease took place during the following 3 months. It is concluded that varicocelectomy reduces ROS levels and increases antioxidant activity of seminal plasma from infertile men with varicocele.

Adult↗
PubMed2000

Expression of CD44 variant isoforms and association to the benign form of endocrine pancreatic tumours.

BACKGROUND: The expression of CD44 and its isoforms have been shown in many neoplastic tissues to serve as prognostic indicators, therefore, the feasibility of using these as prognostic markers in endocrine pancreatic tumour patients was examined. PATIENTS AND METHODS: Immunohistochemistry (IHC) was performed on 26 tumour samples (5 gastrinomas, 3 glucagonomas, 10 non-functioning tumours, 6 insulinomas, 2 mixed insulinoma and glucagonomas) with monoclonal antibodies against CD44s (standard form) and variant isoforms (v4, v5, v6, v7, v7-8, v9, v10). Staining was correlated to the tumour proliferation, malignancy, metastasis and patients survival. RESULTS: There was variable expression of CD44s. All tumours showed complex expression of many isoforms. CD44v6 and CD44v9 were down regulated in malignant tumours. There was statistical significance of CD44v6 expression in benign tumours (P < 0.05) compared to malignant tumours and near significance in CD44v9 expression (P = 0.0574). Survival of the patients with CD44v6 positive staining was higher than those who were negative (P = 0.0822). Moreover, the expression was well correlated to the patients without any distant metastases (CD44v6, p < 0.001; CD44v9, P < 0.01). Tumour proliferation (Ki67 index) correlated directly to the malignancy (P < 0.05) and there was inverse correlation between Ki67 index and CD44v6 (P < 0.05) as well as v9 (P < 0.05). CONCLUSIONS: Endocrine pancreatic tumours express CD44s and isoforms differentially. Expression of the two isoforms of CD44, namely v6 and v9 seem to be related more to benign form of the tumour and could serve as a predictor of good prognosis.

Adenoma, Islet Cell↗
PubMed2000

Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use.

BACKGROUND: To evaluate the efficacy of streptozocin and o.p'DDD (SO) in adrenocortical cancer (ACC) patients since other chemotherapeutic regimens have limited effects. PATIENTS AND METHODS: We performed a phase II study with SO therapy in 40 ACC patients (median age 44 years). Oral o,p'DDD administration (1-4 g/d, every day) was given together with intravenous streptozocin (1 g/d for five days, thereafter 2 g once every three weeks). 5HT3-receptor blocker was used as standard premedication for streptozocin. RESULTS: The SO therapy was found to have significant effects on disease-free interval (P = 0.02) as well as on survival (P = 0.01) in adjuvantly treated cases (n = 17) in comparison to the patients who did not get any therapy after complete resection (n = 11). Complete or partial response was obtained in 36.4% of patients with measurable disease (n = 22). The overall two-year and five-year survival rates were 70% and 32.5%, respectively. The presence of metastases at diagnosis was identified as a poor prognostic factor (P = 0.02). CONCLUSIONS: The present study necessitates further randomized clinical study of SO therapy in the treatment of ACC, mainly as adjuvant treatment immediately after curative intended surgery, and could be developed into a regular treatment regimen.

Adrenal Cortex Neoplasms↗
PubMed1997

High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumors: clinical and biological effects.

BACKGROUND: Neuroendocrine tumors usually present with inoperable metastatic disease and severe hormonal symptoms. Specific chemotherapy, alpha-interferon and the somatostatin analog octreotide are established therapies in these patients but all of them eventually fail. Other somatostatin analogs, e.g., RC-160 and lanreotide, are currently being studied in different doses and modes of administration. PATIENTS AND METHODS: Nineteen patients with advanced neuroendocrine gastrointestinal tumors [13 carcinoids and six endocrine pancreatic tumors (EPT)], liver metastases being present in 18, most of them heavily pretreated, were included. Seventeen out of 18 patients had somatostatin receptors demonstrated by octreotide scintigraphy. Lanreotide was given as four daily subcutaneous injections, starting with 750 microg/d, then increasing every week up to 12,000 microg/d after six weeks, a dose which was maintained, if tolerated, for 12 months, or until progression. RESULTS: There was a significant tumor size response (>50%) in one patient (5%), whereas 12 patients (70%) had tumor stabilization for 12 months. Bichemical tumor markers were significantly reduced at six months (urinary 5-hydroxyindoleacetic acid and plasma chromogranin) and 12 months (chromogranin) and the overall biochemical response rate was 58% with this high dose of lanreotide. Adverse events were observed and four patients stopped the treatment due to adverse events. Studies of tumor biopsies before and during treatment indicated induction of apoptosis in patients with tumor stabilization and biochemical response. CONCLUSION: High-dose treatment with lanreotide (12,000 microg/d) produced tumor size response in 5%, stabilization in 70% and a biochemical response in 58% of patients. These results should be related to the advanced stage of the disease as indicated by the mean duration of disease of more than four years, but they do not appear to be better than those achieved with standard doses of somatostatin analogs. However, in responding patients we observed induction of apoptosis in the tumors, a phenomenon not seen with regular doses of somatostatin analogs, but often produced by chemotherapeutic agents.

Adult↗
PubMed1997

Induction of apoptosis in neuroendocrine tumors of the digestive system during treatment with somatostatin analogs.

The extent of apoptosis identified by in situ DNA nick end labelling (TUNEL) on tissue samples obtained from patients with neuroendocrine tumors was correlated with the clinical outcome in patients treated with high-dose somatostatin analog (lanreotide 12 mg/day), n = 8, or other biotherapy including interferon-alpha (IFN-alpha), n = 4, low-dose somatostatin analog (octreotide or lanreotide), n = 3, or a combination of both, n = 1. Biopsies were obtained before the start of treatment and/or after 6 months and 12 months. After 6 months of treatment, 5 patients receiving high-dose somatostatin analog showed a biochemical response (decrease in different neuroendocrine tumor markers) and 4 of these showed an increase in apoptotic index (AI: percentage of apoptotic cells) by 1.94 +/- 1.71%. At 12 months, AI was also increased in patients with a biochemical response (4.22 +/- 3.93%). However, none showed a decrease in tumor size on computerized tomography (CT) and none of the patients treated with low-dose somatostatin analog or IFN-alpha showed any significant increase in AI during treatment. In an experimental model, nude mice were xenografted with the neuroendocrine cell line (BON-1). From the 2nd day of tumor implantation, they received treatment with either placebo, high-dose octreotide, IFN-alpha, or a combination of both, for 28 days. In mice receiving treatment with high-dose octreotide (300 microg/kg, t.i.d) there was a threefold increase in apoptotic cells as compared to the placebo group (p = 0.0084), while the combination group had few cells with ultra-structural changes indicating apoptosis and the IFN-alpha treated group showed no significant changes. However, tumor growth inhibition was more pronounced in the combination group (p = 0.0011). This probably denotes that tumor growth inhibition could be achieved more efficiently by blocking the cell cycle than by inducing apoptosis. We concluded that treatment with high-dose somatostatin analogs may induce apoptosis in neuroendocrine tumors, while this is not found during treatment with low-dose somatostatin analogs or IFN-alpha. We also found that an increase in AI during high-dose somatostatin analog treatment was correlated with the biochemical response, but not with the tumor size as detected by CT in patients or with the tumor mass in the experimental model.

Aged↗
PubMed1991

Interrelationships of liver and brain with special reference to Reye syndrome.

Reye syndrome is an acute non-inflammatory encephalopathy that can be precipitated by toxic, infective, metabolic or hypoxic upsets. The biochemical changes point to mitochondrial dysfunction and this is substantiated by structural changes in mitochondria on electron microscopy. The toxic metabolites that accumulate are similar to those incriminated in hepatic encephalopathy and other metabolic diseases. These metabolites exert their deleterious effects by direct neuronal damage, neurotransmitter blockade, vascular damage, cerebral oedema, hypoxic ischaemic damage, demyelination, retardation of brain growth and neuronal storage. Brain capillary endothelial cells are very rich in mitochondria and mitochondrial disorders can effect the central nervous system primarily, and not just as a consequence of systemic metabolic upset.

Animals↗
PubMedDate not supplied

Induction of MxA mRNA in patients with neuroendocrine tumors after interferon treatment. Lack of correlation with antitumor response.

We have investigated the possibility of using induction of MxA mRNA in patients with neuroendocrine tumors undergoing interferon-alpha(IFN-alpha) treatment as a predictive test for antitumor effect. A total of 122 patients with various types of neuroendocrine tumors were included in the study. Blood samples were drawn 12 hours after administration of either recombinant or natural IFN-alpha for analysis of induction of MxA mRNA in peripheral blood leukocyte (PBLs). Total RNA was isolated and slot-blot hybridization was performed using a MxA cDNA fragment as a probe. All patients displayed induction of MxA mRNA. Out of 13 untreated patients, 4 had MxA mRNA as well as 2 out of 11 patients treated with somatostatin analogue. All IFN-alpha treated patients showed induction of MxA mRNA and there was no difference between patients demonstrating partial remission, stable disease or progressive disease. Moreover, there was no difference between recombinant or natural leukocyte IFN-alpha in the ability to induce MxA mRNA. Six patients developed neutralizing IFN-alpha antibodies with 1 patient presenting a tire of 3200 NU/ml. Development of neutralizing antibodies did not abrogate the induction of MxA mRNA, but in 3 patients with high antibody titres the antitumor effect was lost. We therefore conclude that IFN-alpha is able to induce MxA mRNA in PBLs from patients with neuroendocrine tumors but we could not find any correlation with the therapeutic outcome. Furthermore, development of neutralizing IFN-alpha antibodies, although abrogating the antitumor effect, might not block the antiviral activity.

Adult↗
PubMedDate not supplied

Interferon-alpha induces bcl-2 proto-oncogene in patients with neuroendocrine gut tumor responding to its antitumor action.

We have studied the expression of apoptosis regulating genes bcl-2 and bax in neuroendocrine gut tumors. The expression pattern of these genes was compared with the clinical response (changes in the tumor markers and changes of the tumor size determined by radiology) after treatment with interferon-alpha (IFN-alpha, n = 13), somatostatin analog (octreotide, n = 3; lanreotide, n = 2) or a combination of both (n = 5). Immunohistochemistry and in situ RT-PCR were performed and expressions were scored from 0 (no staining) to 6 (strong and wide-spread staining). With regard to clinical outcome, the scores (mean +/- SEM) of immunohistochemical staining of bcl-2 and bax were 1.77 +/- 0.25 and 4 +/- 0.22 for patients with stable disease and, 0.54 +/- 0.28 and 4.68 +/- 0.21 for patients with progressive disease. The scores of bcl-2 and bax staining for IFN-alpha-treated patients were 1.96 +/- 0.35 and 4.12 +/- 0.31 and for untreated patients were 0.5 +/- 0.25 and 4.5 +/- 0.21, respectively. Expression of bcl-2 was observed in all IFN-alpha-treated patients who responded to the drug but not in nonresponsive patients (p = 0.0027). In contrast, bax, a promotor of apoptosis was expressed in all patients with higher degree of expression seen in patients with progressive disease (p = 0.0364). We have also detected bcl-2 expression by western blot analysis in neuroendocrine tumor tissue grown in nude mice, which were treated with IFN-alpha for 28 days. Our results indicate that, IFN-alpha can induce bcl-2. Thus, we, propose that bcl-2 may be used as a prognostic marker for IFN-alpha sensitivity of neuroendocrine tumors.

Animals↗