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Biomedical subjects

S R Patel

Publications and source records attributed to S R Patel.

At least 109 records · Page 6Linked to original sources
PubMed1992

Interleukin-1 and interleukin-6 in breast cyst fluid: their role in regulating aromatase activity in breast cancer cells.

Gross cystic breast disease is a common benign disease which may be associated with an increased risk for breast cancer. Breast cyst fluid (BCF) contains many steroids, peptide growth factors and proteins. We have now identified interleukin-1 (IL-1) and IL-6 in BCF by specific radioimmunoassays. Concentrations of IL-1 were similar in BCF with low or high Na+/K+ ratios (ratio less than 3 vs greater than 3; 357 +/- 72 pg/ml vs 308 +/- 126 pg/ml). In contrast, IL-6 concentrations were significantly higher (P less than 0.01) in BCF with a Na+/K+ ratio greater than 3 (2.75 +/- 2.34 ng/ml) compared with BCF with a low electrolyte ratio (0.21 +/- 0.09 ng/ml). BCF (10%, v/v) stimulated aromatase activity when added to dexamethasone stimulated breast tumour-derived fibroblasts and there was a significant correlation between the stimulation of aromatase activity and BCF Na+/K+ ratio (r = 0.95, P less than 0.001). A significant correlation was also found between stimulation of aromatase activity and concentration of IL-6 in BCF (r = 0.80, P less than 0.01) but not IL-1 concentration (r = -0.39, not significant). Addition of IL-1 or IL-6 (50 ng/ml) to fibroblasts stimulated aromatase activity but was associated with a small (20%) decrease in cell growth. It is concluded that IL-6 may have an important role in regulating aromatase activity in breast cancer cells.

Aromatase↗
PubMed1991

Phase I-II study of pibenzimol hydrochloride (NSC 322921) in advanced pancreatic carcinoma.

Pibenzimol is a fluorescent molecule known to bind to double stranded DNA. It also induces prolongation of the G2 phase of the cell cycle, inhibition of DNA replication and cessation of the growth of some cells in late S phase after DNA content has been doubled. It has been shown to increase the life span of mice bearing intraperitoneally implanted L1210 and P388 leukemia. These factors coupled with the affinity of pibenzimol for pancreatic tissue led us to conduct a phase I-II trial of pibenzimol hydrochloride in patients with advanced pancreatic cancer. Twenty-six patients were treated with a five day continuous infusion of pibenzimol at a dose ranging from 6-28 mg/m2/d. There were no treatment related deaths. Major toxicity was hyperglycemia which was self-limited. No objective responses were noted.

Adult↗
PubMed1991

The short Synacthen test in acute hospital admissions.

OBJECTIVE: We wished to define the cortisol response to 250 micrograms intramuscular tetracosactrin (Synacthen) in acute hospital admissions, using a modern immunoassay for cortisol. DESIGN: We performed a prospective study of, as near as possible, a consecutive series of 161 admissions to a single unit. PATIENTS: We studied 50 patients (age range 67-98, mean 80.3 years, 31-female, 19-male) admitted as an emergency, from whom it was possible to obtain informed consent, and whom it was possible to study within 24 hours of admission. MEASUREMENTS: We measured baseline, increment and peak serum cortisol following administration of 250 micrograms intramuscular tetracosactrin between 0800 and 0900 hours. RESULTS: Baseline cortisol concentrations ranged from 288 to 1585 nmol/l (mean 706; median 665). Peak cortisol concentrations ranged from 602 to 2265 nmol/l (mean 1076; median 999). Baseline and peak cortisol concentrations showed a significant correlation (P less than 0.001). Increment varied from 10 to 747 nmol/l (mean 374; median 336) and did not correlate with baseline. CONCLUSIONS: In acute hospital admissions, baseline serum cortisol between 0800 and 0900 hours should exceed 250 nmol/l. Peak serum cortisol after 250 micrograms intramuscular tetracosactrin should exceed 600 nmol/l. Calculation of the increment is of no value.

Acute Disease↗
PubMed1991

Effects of purine derivatives on calcitriol metabolism in rats.

The effects of theophylline and sodium urate on metabolic production (PR) and clearance rate (MCR) of calcitriol were determined by the constant isotope infusion method in normal rats. Calcitriol PR was significantly reduced after infusion for 20 h of either theophylline (1 mg/h, PR = 22.3 +/- 1.6 ng.kg-1.day-1, P less than 0.001, n = 5) or sodium urate (0.5 mg/h, PR = 18.6 +/- 1.2 ng.kg-1.day-1, P less than 0.001, n = 5) compared with control rats infused with saline (PR = 32.0 +/- 1.5 ng.kg-1.day-1, n = 5). Renal 1 alpha-hydroxylase activity of kidney homogenate was significantly inhibited in rats infused with theophylline or urate. Suppression of 1 alpha-hydroxylase activity was also observed when the kidney homogenate was preincubated for 3 h with various concentrations of xanthine (0.11-3.0 mg/dl). In addition, the MCR of calcitriol was decreased in rats infused with either theophylline (MCR = 21.0 +/- 0.88 microliter.min-1.100 g-1, P less than 0.005) or urate (MCR = 22.9 +/- 0.91 microliter.min-1.100 g-1, P less than 0.05) compared with saline-infused control rats (MCR = 25.2 +/- 0.41 microliter.min-1.100 g-1). Because calcitriol degradation is a receptor-mediated process that requires binding of the receptor-hormone complex to chromatin, we studied the binding affinity of labeled calcitriol receptor for DNA-cellulose in the presence of theophylline or urate. Both theophylline and urate inhibited receptor binding affinity for DNA-cellulose. We conclude that these purine derivatives suppress calcitriol synthesis and inhibit receptor binding affinity for DNA. The altered receptor binding affinity could explain the decreased MCR of calcitriol.

Animals↗
PubMed1991

Auscultated forced expiratory time as a clinical and epidemiologic test of airway obstruction.

OBJECTIVE: Seeking an inexpensive, readily available, clinical, screening, and field surveillance test of airway obstruction, we determined the validity of current dogma that forced expiratory time (FET) is a good clinical test of airway obstruction yet is of no epidemiologic use given excessive intrasubject variability. SUBJECTS AND METHODS: Two hundred twenty-nine white male plumbers and pipefitters were evaluated by spirometry, chest roentgenography, and a standardized respiratory questionnaire during a union-sponsored asbestos screening program. Subjects were classified as having large airway obstruction (LAO), small airway obstruction (SAO) alone, or no obstruction, on the basis of standard spirometric prediction equations. Two physicians, blinded to clinical and spirometric data, independently measured FET while auscultating the trachea with a stethoscope. The FET was defined as the time taken for an individual to forcefully exhale through an open mouth from total lung capacity until airflow became inaudible. Five such times were recorded for each subject. The mean of the three times having the narrowest range was deemed the FET for calculating test sensitivity and specificity. Based on previous literature, an FET greater than or equal to 6 s was considered abnormally prolonged. RESULTS: Two hundred five subjects completed both spirometry and FET testing; 67 had LAO, 5 SAO, and 133 no obstruction. A total of 83 percent had three FETs reproducible within a range of less than or equal to 1 s. The sensitivity and specificity of FET for LAO were 92 and 43 percent, respectively, while for SAO alone, 60 and 44 percent, respectively. Overall, FET misclassified 56 percent of nonobstructed subjects. Adjusting the normal-abnormal cutoff points for both FET and SAO minimally improved the performance of FET. CONCLUSION: Although FET is a simple, inexpensive, sensitive, and fairly reproducible clinical test of LAO, it cannot be recommended as a clinical or an epidemiologic tool because of its extremely low specificity.

Asbestosis↗
PubMed1991

Breast cancer.

Several issues of clinical importance were in the forefront of discussion during 1989. Heated debates continue regarding whether alcohol, oral contraceptives or hormonal replacement therapy modifies a patient's risk for developing breast cancer. It is quite apparent, and rightfully so, that a major impetus in the arena of research in breast cancer seems to be towards cure of the disease. The rationale for offering adjuvant systemic treatment to a larger group of primary breast cancer patients who have a potential for cure certainly seems justifiable. However, one still needs to individualize patients based on their prognosis and objectively weigh the potential benefits and risks of adjuvant therapy in a given clinical situation, especially in patients with less than 1 cm primary tumors and negative axillary nodes as they have been shown to have a 20-year recurrence-free survival of 86%. A better understanding of several molecular and genetic parameters has begun. Further developments in this area may lead to clinically appropriate means of preventing or treating this disease. Metastatic disease continues to remain an incurable entity. Efforts aimed at treating metastatic disease with more 'intensive dose chemotherapy' have not been demonstrated to be beneficial for affected patients.

Adult↗
PubMed1990

Papillary serous carcinoma of the peritoneum. A review of 33 cases treated with platin-based chemotherapy.

Thirty-three patients were identified who had papillary serious carcinoma of the peritoneum (PSCP). The gross operative specimens, histopathologic condition, and treatment records were reviewed. The median age at presentation was 60 years (age range, 22 to 78 years). Abdominal pain and distention were the most common presenting symptoms. All patients had a total abdominal hysterectomy and bilateral salpingo-oophorectomy, and all but two had debulking surgery. All patients had disease involving the omentum, the abdominal and pelvic peritoneum, and the surface of the ovaries, but none had intrinsic disease of the ovaries. Eight patients had disease outside of the abdominal cavity. Seven of these patients had malignant pleural effusions. All patients received platin-based chemotherapy. Sixteen patients underwent second-look laparotomy, two had no evidence of disease, and one had microscopic disease only. The median survival time for all patients was 17 months. Three patients are alive 6 to 7 years after the initial diagnosis. In conclusion, long-term survival can be achieved in some PSCP patients by debulking surgery and platin-based chemotherapy.

Abdominal Pain↗
PubMed1990

A phase II randomized trial of megestrol acetate or dexamethasone in the treatment of hormonally refractory advanced carcinoma of the prostate.

The results of a randomized, multicenter, cooperative group trial evaluating hormonal therapy with either megestrol acetate or dexamethasone in advanced, hormonally refractory prostate cancer are reported. Three of 29 patients (approximately 10%) on the megestrol acetate arm experienced an objective response lasting 41, 84, and 202 days, respectively, whereas two of 29 patients (approximately 7%) on the dexamethasone arm achieved an objective response lasting 359 and 512 days, respectively. Twenty of 29 patients (approximately 69%) on the megestrol acetate arm had stable disease lasting for a median duration of 117 days, whereas 21 of 29 patients (72%) on the dexamethasone arm had stable disease for a median duration of 86 days. Median survival of all patients was 9 months from initiation of treatment. The median survival of all patients on the megestrol acetate arm was 268 days compared to 246 days for patients on the dexamethasone arm (P = 0.2). Neither dexamethasone nor megestrol acetate would seem to be of substantive value in altering the progression of advanced, hormonally refractory prostate cancer.

Aged↗
PubMed1990

Synchronous and metachronous bilateral testicular tumors. Mayo Clinic experience.

The authors report a retrospective review of their experience with bilateral testicular cancers over two 10-year periods, one each from the prechemotherapy era (1935-1944) and the postchemotherapy era (1977-1986). Three of 295 patients (1.02%) evaluated at Mayo Clinic (Rochester, MN) for testicular germ cell malignancy between 1935 and 1944 had evidence of bilateral testicular malignancy. Two of these were synchronous and one metachronous occurring 3 years after the first diagnosis. In all three, the histology was pure seminoma. None of these three had a history of undescended testes. Both patients with synchronous tumours died within 2 years (6 months and 2 years, respectively) in spite of appropriate treatment at that time, and the one with metachronous tumor survived long-term (47 years). During the modern chemotherapy era, 16 of 500 (3.2%) patients evaluated at the Mayo Clinic Rochester between 1977 and 1986 for testicular germ cell malignancy had evidence of bilateral testicular cancers (four of these were synchronous and 12 metachronous [eight seminomas, four non-seminomas]) occurring between 1 to 15 years after the first diagnosis. Only two of 16 had a history of undescended testes surgically corrected while the patients were in their teens. All patients did well after appropriate treatment. This study reemphasizes the small but definite risk for development of a second testicular malignancy and suggests a recent increase in incidence of bilateral testicular tumors as possibly related to improved treatment modalities with a higher cure rate of the original tumor.

Adolescent↗
PubMed1990

Familial testicular cancer: report of six cases and review of the literature.

The cause of testicular cancer, like most other cancers, is unknown. Certain risk factors such as cryptorchidism, carcinoma in situ, and a preceding contralateral testicular germ cell neoplasm are known to predispose a person to the subsequent development of a testicular malignant lesion. Familial testicular cancer has been debated as a potential and possibly independent risk factor. Evidence in favor of such a hypothesis, based on various genetic studies reported during the past few decades, is reviewed. We add to the existing literature our experience with six cases of familial testicular cancer encountered during a 10-year period, consisting of four father-and-son pairs, one pair of nontwin brothers, and a 23-year-old man who had a maternal uncle with a history of testicular cancer.

Adult↗
PubMed1990

Observation after orchiectomy in clinical stage I nonseminomatous germ cell tumor of testis. Mayo Clinic experience.

We report a retrospective review of our experience with close observation after orchiectomy in clinical stage I nonseminomatous germ cell tumors (NSGCT) of the testis during a 10-year period. Twenty-four patients were followed between 1977 and 1986 for a median duration of 47 months (24-112 months). Six of 24 (25%) relapsed at a median of 3.5 months (2-46 months) after orchiectomy; all of these were treated with chemotherapy and are in complete remission at a median of 55 months (27-69 months) after diagnosis of recurrence. Eighteen other (75%) who did not relapse are without evidence of disease at a median of 39 months (24-112 months) after orchiectomy. Orchiectomy alone followed by close observation in clinical stage I NSGCT is a reasonable approach in reliable patient populations at well-equipped centers where adequate follow-up is possible.

Adolescent↗
PubMed1990

Moderate protection of renal function and reduction of fibrosis by colchicine in a model of anti-GBM disease in the rabbit.

A rabbit model of renal glomerulosclerosis induced by anti-glomerular basement membrane antibody was used to determine whether colchicine would protect renal function and reduce fibrosis. Initial studies established the time course of renal function changes and fibrosis. Colchicine at a dose of 0.02 to 0.04 mg/kg per day injected ip was begun at day 4 when injury had been initiated, and the experiment was ended at day 21 when fibrotic changes were established. Colchicine significantly reduced the rise in serum creatinine (serum creatinine = 2.7 +/- 0.3 mg% in vehicle-treated animals versus 1.8 +/- 0.1 mg% in colchicine-treated animals) and interstitial fibrosis (fibrosis score = 2.6 +/- 0.2 in vehicle-treated versus 1.5 +/- 0.2 in colchicine-treated animals). Colchicine treatment did not significantly affect weight, anti-guinea pig immunoglobulin level, % fibrocellular crescents formed, hydroxyproline per gram (dry weight) in tissue, or urine protein: creatine ratio. Regression analysis was performed to examine the interrelationships between variables for all animals and the effect of colchicine on pairs of variables. No clear-cut site of colchicine action could be identified. These data show that colchicine, in doses that could be used in humans, protected renal function by about 25% and reduced interstitial fibrosis in a model of severe crescentic nephritis.

Animals↗
PubMed1989

Monoclonal antibodies to human secretory "pregnancy-associated endometrial alpha 1-globulin," an insulin-like growth factor binding protein: characterization and use in radioimmunoassay, Western blots, and immunohistochemistry.

Monoclonal antibodies were raised against pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 32 KD insulin-like growth factor binding protein (IGF-BP), which represents a major secretory product of the human decidualized endometrium during pregnancy. This class of IGF-BP has been implicated in the modulation of action, inhibitory and stimulatory, of insulin-like growth factors. Immunization with the protein purified from pregnancy endometrium resulted after myeloma fusion in the isolation of six hybridoma clones and the antibodies produced were characterized. The Ka of the antibodies ranged between 4.75 x 10(9) M-1 and 0.7 x 10(8) M-1. In Western blots all monoclonal antibodies reacted with purified protein of molecular weight 32 KD and specifically detected this IGF-BP species in culture medium and cytosolic extracts of pregnancy endometrium and amniotic fluid. The monoclonal antibodies appear to define three epitope-bearing regions as evidenced by their reactivity to polypeptide fragments of the protein. After synthesis and secretion by tissue explants in vitro the protein is susceptible to cleavage into fragments possessing different monoclonal antibody-defined reactivity. Employing immunohistochemical techniques the protein was principally localized to decidual cells in tissue sections of pregnancy endometrium and solely to these cells after enzymic digestion of the tissue. The implications of these results are discussed with respect to potential role of IGF-BP in the action of IGF upon the IGF-1 receptor-bearing populations, including lymphocytes and trophoblast cells, D in the decidua.

Antibodies, Monoclonal↗
PubMed1988

Major secretory protein of human decidualized endometrium in pregnancy is an insulin-like growth factor-binding protein.

Pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG) is quantitatively the major secretory protein product, synthesized and secreted in vitro, of the human decidualized endometrium during pregnancy. This protein has been purified from cytosolic extracts of this tissue and has now been characterized as a 32 kDa somatomedin/insulin-like growth factor (IGF)-binding protein. Immunoreactive alpha 1-PEG isolated from amniotic fluid exhibited identical physiochemical properties and IGF-I-binding characteristics. In cytosolic extracts of pregnancy endometrium, in incubation medium of this tissue and in amniotic fluid, the 32 kDa protein represented the major alpha 1-PEG immunoreactive protein and major IGF-I-binding component. Purified alpha 1-PEG and incubation medium of pregnancy endometrium competed for IGF-I with placental membrane IGF receptors in vitro. The implications of the endometrial source of IGF-I-binding protein are discussed with reference to the origin of the amniotic fluid and serum small Mr IGF-binding protein and to the suggested paracrine effect upon trophoblast proliferation.

Affinity Labels↗