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Biomedical subjects

S R Ahmed

Publications and source records attributed to S R Ahmed.

At least 19 recordsLinked to original sources
PubMed2004

Human saphenous vein and coronary bypass surgery: ultrastructural aspects of conventional and "no-touch" vein graft preparations.

Coronary artery bypass graft surgery (CABG) is routinely used to restore blood flow to diseased cardiac muscle due to coronary artery disease. The patency of conventional grafts decreases with time, which is due to thrombosis and formation of neointima. A primary cause of graft failure is the mechanical damage inflicted to the graft during harvesting, including removal of surrounding tissue accompanied by high pressure saline distension to overcome vasospasm (both causing considerable mechanical trauma). The aim of this study was to compare the ultrastructural features of human saphenous vein (SV) grafts harvested conventionally and grafts prepared using an atraumatic 'no-touch' harvesting technique introduced by Souza (1996). The results of this study showed a better preservation of the lumenal endothelium and medial vascular smooth muscle (SM) in 'no-touch' versus conventional grafts. A 'fast' (within 30 min) response of SM cells to conventional harvesting was noted where features of both SM cell division and apoptosis were observed. It is concluded that the 'preserved' nature of the 'no-touch' aortocoronary SV grafts renders them less susceptible to thrombotic and atherosclerotic factors than grafts harvested conventionally. These features are suggested to contribute to the improved early patency rate described using the no-touch technique of SV harvesting.

Aged↗
PubMed1999

External hydrocephalus in primary hypomagnesaemia: a new finding.

This paper reports a new finding in two siblings with primary hypomagnesaemia as a result of renal magnesium wasting, namely, rapidly increasing head size. External hydrocephalus and brain shrinkage in primary hypomagnesaemia seen on computed tomography of the brain with reversibility after magnesium treatment has not been reported previously.

Female↗
PubMed1993

Necrotizing infundibulo-hypophysitis: a unique syndrome of diabetes insipidus and hypopituitarism.

Clinical, radiological, histological, and anatomical features in 2 patients with necrotizing infundibulo-hypophysitis are reported. The patients presented with a combination of diabetes insipidus and hypopituitarism. Each was found to have a sellar mass lesion with an abnormally thickened enlarged pituitary stalk that intensively enhanced on contrast magnetic resonance imaging. They were suspected to have pituitary tumors with suprasellar extension. However, tissue obtained at transphenoidal surgery revealed necrosis, fibrosis, and chronic inflammation; there was no evidence of infiltrative, infective, or neoplastic disease processes. Postoperatively, they continued to have diabetes insipidus and hypopituitarism despite radiological improvement and steroid therapy. Several clinical and anatomical features distinguish these 2 cases from classical lymphocytic hypophysitis, the most common entity in the differential diagnosis. Specifically, diabetes insipidus has not been observed preoperatively in 30 cases of lymphocytic hypophysitis, but was present in the 2 cases reported. Histological evidence of tissue necrosis present in these 2 cases is not a feature of lymphocytic hypophysitis. Pituitary stalk involvement on magnetic resonance imaging or computed tomographic scan present in these 2 cases is highly unusual in lymphocytic hypophysitis. Finally, 29 of 30 cases of lymphocytic hypophysitis were females, whereas the 2 cases reported are men. On the basis of these disparate findings, we suggest that these 2 cases represent a unique syndrome, which may be recognized clinically and radiologically.

Adult↗
PubMed1991

Role of transforming growth factor-alpha (TGF-alpha) in basal and hormone-stimulated growth by estradiol, prolactin and progesterone in human and rat mammary tumor cells: studies using TGF-alpha and EGF receptor antibodies.

The biological role of transforming growth factor-alpha (TGF-alpha) in basal and hormone-stimulated proliferation of primary human and rat mammary tumor cells was studied using antibodies against TGF-alpha and its receptor. A monoclonal antibody, MAb-425 against human EGF receptor was added to in vitro soft agar, clonogenic cultures of human breast carcinoma cells under basal and estradiol(E2)-stimulated conditions. The antibody had an antagonist effect on colony growth in 4 of 10 tumors and an agonist effect in 4 (72 and 153% of control). E2-stimulated colony growth in 5 tumors (167% of control) and the antibody blocked E2-stimulation in 3 of the 5. Inhibition of E2-stimulated growth in 3 and basal growth in 4 other tumors by the EGF receptor antibody suggest that endogenously secreted TGF-alpha has a role as an autocrine/paracrine growth factor in constitutive and E2-stimulated tumor cell proliferation in a majority of human tumors. A polyclonal antibody against TGF-alpha was used to study the role of TGF-alpha in E2-, prolactin(Prl)- and progesterone(Prog)-stimulated proliferation of NMU(nitrosomethylurea)-induced rat mammary tumor cells under similar culture conditions. TGF-alpha, E2, Prl and Prog stimulated colony growth equally to 176, 187, 168 and 181% of control. The antibody produced significant and similar inhibition of TGF-alpha and E2-stimulated growth (95 and 83%). In contrast, inhibition of Prl- and Prog-stimulated growth by the antibody was only 24 and 37%. The TGF-alpha ligand antibody did not have an agonist or antagonist effect when added alone. Thus, TGF-alpha seems to be a major stimulatory growth factor mediating E2-induced tumor cell proliferation in rat mammary tumors. It is less important in Prl- and Prog-induced tumor growth and not essential for basal growth in these tumors. We conclude that TGF-alpha is a biologically important autocrine/paracrine growth factor in primary human breast cancer cell proliferation and in E2-induced rat mammary tumor growth.

Animals↗
PubMed1990

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease.

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low-dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low-dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505-1150 ng/l). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy.

Adolescent↗
PubMed1989

Hypopituitarism following external radiotherapy for pituitary tumours in adults.

The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.

Adolescent↗
PubMed1988

Role of polyamines in the growth of hormone-responsive experimental breast cancer in vivo.

We have provided evidence for a critical role of polyamines in the growth of the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor in vitro. The present experiments were designed to test whether polyamines are involved in the growth of this experimental tumor in vivo. To test this hypothesis, groups of rats bearing NMU-induced mammary cancers were randomly allocated to receive no treatment or escalating doses of the polyamine biosynthesis inhibitor alpha-difluoromethyl-ornithine (DFMO) (0.5%, 1%, 2%, 3% in drinking water). DFMO inhibited tumor growth in a dose-dependent fashion and consistently reduced tumor putrescine level. To evaluate the time dependency of this effect, additional groups of rats received either no treatment or 2% DFMO for 3, 7, 14, and 21 days. At all times DFMO suppressed tumor putrescine level as well as spermidine to spermine ratio. Finally, exogenous administration of putrescine (200 mg/kg/i.p./day x 21 days) given concomitantly with DFMO restored tumor growth, partially repleted tumor putrescine level, and raised the spermidine to spermine ratio to control levels. Putrescine, given alone, had no significant effect on either tumor polyamine levels or tumor growth. Except for modest weight loss, no major toxicity was encountered. These results indicate that polyamines play an important role in the growth of the NMU rat mammary tumor in vivo. The interaction between polyamines and hormones in supporting NMU mammary tumor growth in vivo remains to be elucidated.

Animals↗
PubMed1988

Species-specificity of estradiol regulated growth factors in breast cancer.

Recent evidence indicates that autocrine/paracrine mechanisms may mediate the mitogenic effect of estradiol (E2) both in human and experimental breast cancer. However, the species-specificity of E2-regulated growth factors with regard to their biologic action has not been evaluated. To test this issue, we examined, in the soft agar clonogenic assay, the colony-stimulating activity in human breast cancers of conditioned media obtained from rat mammary carcinomas exposed to E2 (rat E2-CM). Of 22 primary human breast cancers plated in soft agar in the absence of serum, 18 (82%) successfully grew with a mean colony number of 62.4 +/- 9.8 (S.E.M.) (range 14-193). Rat E2-CM significantly stimulated colony formation in 10/18 (56%) human breast cancers to 155 +/- 11% (S.E.M.) of control. E2 administration (10(-9) M) in these tumors had a virtually identical overall effect (154 +/- 13% of control colony number). In the remaining eight tumors (44%), neither rat E2-CM nor E2 had, in general, a significant colony-stimulating effect. The growth-promoting action of rat E2-CM and E2 was not influenced by the hormone receptor status of the tumor. These results suggest that E2-regulated growth factors may not be species-specific, at least with regard to their colony-stimulating effects in soft agar.

Adult↗
PubMed1988

Transdermal testosterone therapy in the treatment of male hypogonadism.

Five hypogonadal men were treated with transdermal testosterone therapy, using a testosterone patch applied to the scrotal skin. Daily application of the patch, which contained 10 mg testosterone, produced an increase in serum testosterone concentrations from a pretreatment value of 45 +/- 12 (+/- SE; 1.5 +/- 0.4) to 436 +/- 80 ng/dL (15.1 +/- 2.8 nmol/L; P less than 0.001) after 4 weeks of treatment. Normal serum testosterone concentrations were achieved in all men after 6-8 weeks of therapy and were maintained during continued long term therapy for 9-12 months with a patch containing 15 mg testosterone. All men reported a subjective increase in libido and sexual function during therapy, and three men preferred it to testosterone injections. The serum testosterone and estradiol levels did not rise above the normal adult male range at any time during therapy. However, elevated serum dihydrotestosterone (DHT) concentrations occurred during treatment; the pretreatment DHT concentration was 95 +/- 3 ng/dL (3.3 +/- 0.1 nmol/L), and it increased to 228 +/- 40 ng/dL (7.8 +/- 1.4 nmol/L) after 4 weeks of treatment and remained elevated thereafter. The individual mean DHT to testosterone ratio increased from a pretreatment value of 0.2 (range, 0.1-0.3) to 0.6 (range, 0.4-0.7) after 2 weeks of therapy and remained high thereafter. Comparison of the serum DHT levels in patients during therapy with those in normal men who had similar testosterone concentrations [531 +/- 62 vs. 566 +/- 72 ng/dL (18.4 +/- 2.1 vs. 19.6 +/- 2.5 nmol/L); P greater than 0.05] revealed that the mean serum DHT concentration was significantly higher in the patients [315 +/- 69 vs. 87 +/- 6 ng/dL (10.8 +/- 2.4 vs. 2.9 +/- 0.2 nmol/L); P less than 0.001], as was the mean DHT to testosterone ratio [0.6 (range, 0.25- 1.1) vs. 0.16 (range, 0.09- 0.24); P less than 0.001]. The high serum DHT levels presumably were due to increased metabolism of testosterone to DHT by the 5 alpha-reductase in the scrotal skin. Serum 3 alpha-androstanediol glucuronide levels were not elevated in the patients. We conclude that transdermal testosterone therapy is an effective long term treatment for hypogonadism in men. It is, however, associated with high serum DHT levels, whose potential long term effects on the prostate and other tissues need to be investigated.

Administration, Cutaneous↗
PubMed1987

Effects of progestins on growth of experimental breast cancer in culture: interaction with estradiol and prolactin and involvement of the polyamine pathway.

The role of progesterone either alone or in combination with other hormones in breast cancer growth is not well established. In these experiments, using the hormone-responsive N-nitrosomethylurea-induced rat mammary tumor grown in the soft agar clonogenic assay, we tested the colony-stimulating effect of progesterone and the synthetic progestin R5020 over a wide range of physiological and pharmacological concentrations (from 0.1 nM to 10 microM). Both progesterone and R5020 were found to have a significant colony-stimulating effect which was more pronounced in the absence of serum. The action of progesterone appeared to plateau at concentrations of 10 or 100 nM, whereas R5020 was maximally effective at lower concentrations (approximately 1 nM). A biphasic dose-dependent effect was occasionally seen both with progesterone and R5020 with a loss of colony-stimulating effect at high concentrations. The combined administration of varying doses of progesterone (0.1, 1, 10, and 100 nM) and estradiol (10(-10) M and 10(-9) M) was found at times to potentiate and at times to decrease colony formation over that observed with the individual treatments. The former effect, when present, was usually seen with low doses of progesterone, while the latter was frequently observed with high concentrations (100 nM). No major potentiation or suppression of colony formation over individual treatments was observed when varying doses of progesterone (1, 10, and 100 nM) were added together with prolactin (50 ng/ml). The administration of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine completely blocked the colony-stimulating effect of progesterone. The inhibitory effect of alpha-difluoromethylornithine was completely reversed in a dose-dependent fashion by exogenous administration of spermidine, thus implying a critical involvement of the polyamine pathway in progesterone action.

Animals↗
PubMed1987

Role of polyamines in the synthesis of prolactin-regulated growth factors by experimental breast cancer in culture.

The present experiments were designed to test whether polyamines play an essential role in the synthesis of growth factors induced by ovine prolactin (oPRL), using the N-nitrosomethylurea (NMU)-induced rat mammary tumor cultured in the soft agar clonogenic assay. Conditioned media (CM) obtained from tumors treated with oPRL and the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) (1 mM) no longer exerted the colony-stimulating effect which was observed with oPRL-CM. Such growth-promoting activity was restored with conditioned media obtained from tumors treated with oPRL, DFMO, and increasing concentrations of spermidine from 1 to 500 microM. The colony-stimulating effect of the CM employed could not be accounted for by the contaminating presence in the media of oPRL, DFMO, and polyamines. These results indicate that in our system polyamines play an important role in the synthesis of oPRL-regulated growth factors.

Animals↗
PubMed1987

Studies on removal of malathion from water by means of activated charcoal.

The utility of activated charcoal for the removal of malathion from saline waters has been explored. The adsorption capacity of charcoal for malathion has been found to be 117 mg g-1. Adsorption follows the Freundlich adsorption isotherms, the value of k and 1/n for charcoal being 1.6 and 0.60, respectively. Malathion can be eluted with methanol or ethanolic potassium hydroxide.

Adsorption↗
PubMed1986

Effect of different salt leachates on the movement of some phosphorus containing pesticides in soils using thin layer chromatography.

The influence of pH, leachates of alkaline and saline salts, inorganic fertilizers, and surfactants on the movement of eight organophosphorus pesticides, viz., DDVP, diazinon, Ekatin, Folithion, malathion, metasystox, parathion methyl, and Rogor has been studied using soil thin layer chromatographic techniques. The variation in the movement of pesticides under different solvent amendments are expressed in terms of Rf, RB, and RM values and are explained on the basis of adsorption and leachability.

Carbonates↗
PubMed1986

Discordant responses of prolactinoma to two different dopamine agonists.

A 19-year-old woman presented with headaches, temporal lobe epilepsy and primary amenorrhoea. There was a family history of multiple endocrine adenomatosis. Investigation revealed normal visual fields and acuity, hyperprolactinaemia (48 000 mU/l) and a very large pituitary tumour with extrasellar spread. Treatment with bromocriptine reduced the tumour size and the prolactin level to 2440 mU/l. Six months after the start of therapy, resistance to bromocriptine developed and the prolactin concentration progressively rose to pretreatment levels, despite increasing the dose of bromocriptine to 40 mg/d. At this stage treatment with a second dopamine agonist, pergolide, was effective in reducing the prolactin concentration to normal within four months. Serial CT scans at 1, 6 and 12 months on dopamine agonist therapy showed a progressive decrease in tumour size, which seemed to be maintained even during the period of rising prolactin concentrations due to bromocriptine resistance. This case illustrates that during dopamine agonist therapy a discrepancy may exist in the clinical response as judged by reduction in tumour size and decrease in the circulating prolactin level. Furthermore, in patients with prolactinomas, pergolide may induce a response when resistance to bromocriptine develops.

Adult↗
PubMed1986

A new hormonal therapy for prostatic cancer: long-term clinical and hormonal response.

Twenty-four patients with advanced prostatic cancer were treated with daily injections of the LHRH analogue ICI 118630 (Zoladex) for up to 2 1/2 years. Successful long-term suppression of LH (luteinising hormone) and testosterone was observed without any escape of testosterone. Immunoreactive LH concentrations rose significantly following the daily injection of LHRH analogue but there was no corresponding rise in testosterone concentrations, suggesting altered bioactivity of the LH. A long-term clinical response was obtained in 10 patients (41.6%) and the median duration of response in these patients was 25 months. Eight of the 10 had well to moderately differentiated tumours. The actuarial median survival of all patients was 22 months.

Aged↗
PubMed1986

Testosterone and gonadotrophin profiles in patients on daily or monthly LHRH analogue ICI 118630 (Zoladex) compared with orchiectomy.

Diurnal profiles of circulating gonadotrophins and testosterone have been measured in patients with prostatic carcinoma on long-term treatment with the LHRH agonist analogue ICI 118630, which was administered either by subcutaneous daily injection or monthly injection of the depot preparation. These have been compared with profiles in patients who had undergone orchiectomy. Daily injection of the analogue induced a significant rise in the level of LH but this was not associated with a significant rise in circulating testosterone. There was no diurnal variation of LH or testosterone concentration in patients receiving the depot preparation and this did not differ in patients who were "mid-cycle" compared with those who were "end-cycle". The depot preparation did, however, induce significantly lower circulating levels of testosterone than did daily injection of the analogue and the levels were comparable with those achieved after orchiectomy.

Aged↗