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Biomedical subjects

D N Danforth

Publications and source records attributed to D N Danforth.

At least 37 records · Page 2Linked to original sources
PubMed1985

Melatonin and malignant disease.

A possible role for the pineal and melatonin in malignant disease is suggested by the studies of hormone-dependent tumours presented here. The most dramatic observation of the effect of the pineal and melatonin in malignancy is that melatonin protects against, while pinealectomy enhances, 7,12-dimethylbenz[a]anthracene-induced mammary tumours in rats. Melatonin may protect against tumours through a suppressive effect on prolactin secretion or an action on oestrogen receptors. Melatonin can change the concentration of oestrogen receptors in hamsters, both juvenile and adults, and in a human breast cancer cell line. The long-term effect of melatonin in the ovariectomized adult hamster and in human breast cancer cells is to inhibit oestrogen-stimulated growth. A possible relationship between melatonin and oestrogen receptors was examined in women with breast cancer. An inverse correlation was observed between the oestrogen receptor concentration in each patient's tumour and her peak plasma melatonin level, suggesting that the more hormone dependent the breast cancer the more blunted the daily melatonin rhythm. Thus, the more robust the daily melatonin rhythm the greater the protective effect on hormone-dependent breast cancer. Unfortunately, this hypothesis is not easily tested as shown in a study of women at high risk for developing breast cancer. These women had daily melatonin profiles that did not differ from those of a normal population. Thus, the use of plasma melatonin as a screening tool for breast cancer risk is not reasonable; however the basic and clinical data argue that the role of melatonin in endocrine-related cancers requires more extensive clinical investigation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Plasma melatonin and the hormone-dependency of human breast cancer.

We studied the 24-hour plasma melatonin profile in three groups of women: normal individuals, women with breast cancer, and women at high risk for breast cancer, to determine the relationship of plasma melatonin to this malignancy. The mean daytime (nadir) and mean nighttime (peak) plasma levels for the normal subjects were 9.1 pg/mL and 70.9 pg/mL, respectively. The mean daytime and nighttime plasma levels, and the range of melatonin day to night differences for women with breast cancer and women at high risk for breast cancer were comparable to each other and to the normal subjects, with no statistically significant differences noted. The patients with breast cancer demonstrated a striking correlation between the melatonin diurnal rhythm and the steroid receptor content of the primary tumor. Women with estrogen (ER) or progesterone (PR) receptor-positive tumors had a significantly lower mean plasma melatonin day to night difference than did patients with ER- or PR-negative tumors. Further, a strong inverse correlation was observed between the plasma melatonin concentration and the quantities of ER and PR in the primary tumor: the lower the plasma melatonin concentration the greater the amount of either receptor in the primary tumor. Plasma melatonin did not correlate with tumor glucocorticoid receptor content or stage of breast cancer among these patients, or with menopausal status, age, parity, or the plasma levels of estrone, estradiol, progesterone, follicle-stimulating hormone (FSH), or luteinizing hormone (LH) among all individuals studied. Plasma melatonin was also independent of the degree of risk for breast cancer among the high-risk patients. These findings suggest an important relationship between the plasma melatonin diurnal rhythm and the hormone dependency of human breast cancer, and may have implications for both the prognosis and treatment of this malignancy.

Adolescent↗
PubMed1984

Evaluation of abdominal pain in the AIDS patient.

Acquired immune deficiency syndrome (AIDS) is a recently recognized entity characterized by a deficiency in cell mediated immune response. The syndrome is manifested by the development of otherwise rare malignant neoplasms and severe life-threatening opportunistic infections. Case histories of five AIDS patients evaluated for abdominal pain are presented to demonstrate the unusual spectrum of intra-abdominal pathology that may be encountered in the AIDS patient. As the number of patients with AIDS continues to escalate, surgical evaluation and intervention will be required more frequently. An understanding of this syndrome and its complications is mandatory for the surgeon to adequately evaluate AIDS patients with abdominal pain.

Abdomen↗
PubMed1984

Metastatic insulin-secreting carcinoma of the pancreas: clinical course and the role of surgery.

We reviewed our personal experience with insulin-secreting carcinoma of the pancreas to determine the clinical course and the role of surgery in this disease. Seventeen patients with high-grade metastatic carcinoma were treated at our institution between 1957 and 1982. To this series we have added 45 cases of metastatic carcinoma reported in the literature. All patients had symptoms with manifestations of hypoglycemia. Patients with metastatic insulin-secreting carcinoma had an average age of 48.5 years, with male predominance. The average duration of symptoms at presentation was 2.0 years. The tumors were usually single and averaged 6.2 cm. All tumors had metastases, most commonly to the liver and/or lymph nodes. The median disease-free survival after curative resection was 5 years. The recurrence rate was 63%, with the median interval to recurrence 2.8 years, and the median survival with recurrent tumor was 19 months. Palliative resection was associated with a median survival of 4 years, and biopsy only, 11.0 months. Insulin-secreting carcinomas are slow-growing tumors with significant metastatic potential. Surgical resection of primary and metastatic tumors represents the treatment of choice when possible. Long-term follow-up is required.

Adenoma, Islet Cell↗
PubMed1983

Malignant Brenner tumor of the ovary. Electron microscopic study of a case responsive to radiation and chemotherapy.

A patient with malignant Brenner tumor of the ovary is presented. The tumor responded to combined therapy with radiation plus doxorubicin + cyclophosphamide despite earlier failure on a single alkylating agent (levophenylalanine mustard). The patient next exhibited a brief response to chemotherapy with hexamethylmelamine + cyclophosphamide + amethopterin + 5-fluorouracil. The histologic findings and ultrastructure of the tumor are discussed in detail. The morphologic features are consistent with the proposed origin of Brenner tumors from coelomic epithelium through a process of secondary urothelial metaplasia.

Aged↗
PubMed1983

The morphology of the human cervix.

The normal human cervix is a collagenous structure that undergoes a dramatic and probably unique metamorphosis in late pregnancy and labor, effacing and dilating without injury to permit the baby to pass through and, thereafter, returning in the course of a few weeks to its former state. In addition to collagen, the cervix contains small amounts of smooth muscle and elastic tissue, and it is unreasonable to presume they would be found here if they were not to have some function. Whatever this function may be, it appears to be secondary, and possibly supportive, to the role of the collagenous system. Coordinated uterine contractions are involved in the processes of effacement and dilatation of the cervix. However, they appear to be incidental rather than causative, being initiated by the same factors that are also responsible for the cervical changes. When these influences are withdrawn after delivery, remodeling processes begin and the cervix returns to its nonpregnant morphologic and functional state.

Abortion, Spontaneous↗
PubMed1983

Melatonin-induced increase in cytoplasmic estrogen receptor activity in hamster uteri.

The pineal gland hormone, melatonin, has been shown to influence the growth and metabolism of uterine tissue in the Syrian hamster. Because the uterus is an estrogen-responsive target tissue, we studied the effect of melatonin on the unoccupied estrogen receptor (ER) activity of immature hamster uteri in vivo and in vitro. A single sc injection of 2.5 micrograms melatonin increased the ER activity of uterine cytosol (Rc) 30% within 60 min [from 147.4 +/- 14.1 (SE), to 191.8 +/- 18.5 fmol/mg protein]. Scatchard analysis showed the induced population of receptor to be homogeneous and of high affinity, with an equilibrium dissociation constant (Kd = 0.08 nM) similar to that for uteri for vehicle-treated animals. The induction of Rc by melatonin persisted for 90 min, but Rc returned to control levels by 2 h after injection. Scatchard analysis of unoccupied nuclear receptor showed no significant differences either in the quantity of receptor (vehicle = 379.7 +/- 46.7, melatonin = 396.9 +/- 76.7 fmol/mg protein) or in the Kd (vehicle = 0.75 nM, melatonin = 0.60 nM) between these two groups. In vitro incubation of fresh whole uteri for 60 min in media containing 10(-5) M melatonin increased Rc by 83% (from 41.3 +/- 10.7 to 75.4 +/- 11.0 fmol/mg protein), supporting a direct effect of melatonin on uterine tissue. The Rc induced by melatonin both in vivo and in vitro was sensitive to the degree of homogenization used in preparation of the cytosol. Whereas conservative homogenization (two 10-sec bursts with an intermittent 40-sec cooling period) of uteri from melatonin-treated animals was associated with a significant increase in Rc, homogenization for 60 sec without intermittent cooling showed a significant decrease (from 251.1 +/- 17.4 to 182.7 +/- 5.8 fmol/mg protein) as compared with uteri from vehicle-treated animals. Whole organ analysis of uteri from animals injected with melatonin followed by [3H]estradiol, in which no homogenization was used, demonstrated a 26% increase in Rc specific binding, confirming induction as the primary response to melatonin. These findings demonstrate the ability of melatonin to modulate ER activity in hamster uteri, and may help explain the effects of melatonin on uterine growth and metabolism.

Animals↗
PubMed1982

Hormonal status of patients with primary malignant melanoma: a review of 313 cases.

We studied 313 patients with a confirmed diagnosis of primary malignant melanoma who presented to The University of Texas System Cancer Center between 1976 and 1980, to determine the relationship of endocrine status to the presentation of this tumor. There were 171 women and 142 men, a ratio of 1.20:1. Age, age range, race, and residence distribution were comparable for both sexes. The women married and had their first pregnancy at ages at least comparable to the population in general. They tended to have multiple pregnancies (average, 2.64), to nurse their children, to have an aggregate 32 years of menstrual activity, and to use exogenous hormones (73%). The female patients in this study had more favorable lesions than their male counterparts in all five microstaging categories: type of melanoma, location, level of invasion, thickness, and stage. Analysis of the hormonal subgroups among the women revealed the morphology of the primary tumor to be independent of menopausal status, parity, or the use of exogenous hormones. These findings suggest that hormonal background does not effect the acquisition of malignant melanoma, but may influence its subsequent spread.

Adult↗
PubMed1980

Pressure effects of urinary reflux studied with renal autotransplantation and pyelocystostomy.

The pressure effects of urinary reflux on renal structure and function were studied using a canine model in which the kidney was autotransplanted to the iliac fossa and the urine drained through a pyelocystostomy. This provided grade III reflux of urine (distention of the renal pelvis and calyces). A control group of nonrefluxing animals with the ureter and ureterovesical valve intact was studied in an identical fashion, and all animals were observed for one year. The reflux of sterile urine was not associated with any impairment of the inulin clearance or transport maximum of para-aminohippuric acid. There were no histologic abnormalities of glomeruli, tubules, or interstitium noted in the animals exposed to sterile reflux, nor were any differences found between the study and control groups. The transmission of bladder pressures into the renal pelvis and calyces during reflux is considered an unimportant factor in explaining the renal damage noted from sterile reflux of short duration in adults. The pyelocystostomy provides a satisfactory means of urinary drainage, and may be used effectively to study the properties of urinary reflex.

Animals↗
PubMed1978

Endodermal sinus tumor of the ovary. The orphan tumor.

The endodermal sinus tumor of the ovary is a rare and highly lethal germ cell tumor. At least 10 different names have been applied to it, and so long as its name remains unsettled the collection of information will continue to be greatly impeded. One of the patients who came under our observation died after 21 months despite surgical removal of all evident disease followed by radiation and chemotherapy; the other patient, whose tumor could be removed only partially, and who received intensive chemotherapy for 4 months but refused all treatment thereafter, is well without evidence of disease 3 years after the initial diagnosis was made. Despite the dismal outlook for patients with this tumor, a few encouraging features emphasize the need to report new cases as they appear, and to continue the search for agents that will control it.

Adolescent↗
PubMed1977

Renal changes in primary aldosteronism.

The clinical presentations and renal biopsy specimens of 18 patients with primary aldosteronism were reviewed to determine the characteristic pathologic features of the kidney in this syndrome. All patients were hypertensive with a mean blood pressure of 192 nm. Hg systolic and 122 mm. Hg diastolic. The average duration of hypertension was 6.88 years. The mean serum potassium was 2.88 mEq. per l. and the mean plasma carbon dioxide was 31.4 mEq. per l. A significant history of urinary tract disease was noted in 8 patients. Laboratory and diagnostic studies evaluating renal structure and function were abnormal in 11 patients. Renal biopsies from all 18 individuals showed evidence of parenchymal damage. Hypertensive and hypokalemic changes were the most significant abnormalities and were considered moderate to severe in 78 and 89 per cent of the patients, respectively. Histologic evidence of pyelonephritis was noted in 2 patients only and no renal specimens contained characteristic changes of metabolic alkalosis. The preoperatively hypertensive and renal evaluations did not reflect the severity of the renal changes noted histologically. The extent of renal injury caused by hypertension and hypokalemia in these patients emphasizes the consequences of primary aldosteronism. Early diagnosis and treatment of this disorder are essential if these consequences are to be avoided.

Adult↗
PubMed1976

Elevated plasma proglucagon-like component with a glucagon-secreting tumor. Effect of streptozotocin.

To determine the character of the glucagon secretion and its modification by streptozotocin, were studied the plasma of a patient with recurrent pancreatic alpha-cell carcinoma. The plasma immunoreactive glucagon level before treatment of 4.80 ng per milliliter. Biogel column separation of the plasma immunoreactive glucagon revealed four components; the predominant component had a molecular weight of 9000 daltons and was designated as proglucagon-like. This fraction constituted 60 to 90 per cent of the total circulating immunoreactive glucagon, and had a biologic activity of 32 percent of that of an immunoequivalent amount of normal (porcine) pancreatic glucagon. After treatment with streptozocin (1.5 g per square meter) the plasma immunoreactive glucagon level decreased to 0.24 ng per milliliter. Treatment was accompanied by a marked reduction in the proglucagon-like component and the appearance of pancreatic glucagon (molecular weight of 3500 daltons) as the major post-therapy fraction. These findings support the use of streptozotocin in the management of unresectable glucagon-secreting tumors.

Adenoma, Islet Cell↗
PubMed1976

Plasma immunoreactive glucagon fractions in four cases of glucagonoma: increased "large glucagon-immunoreactivity".

Immunoreactive glucagon (IRG) fractions from plasma of 8 normal subjects and 4 patients with glucagon secreting tumors were studied by gel filtration techniques on Bio Gel P--30 and Sephadex G--50 columns. The pancreatic glucagon specific anti serum (30K) of Unger was utilized to measure IRG. Columns were calibrated with labelled albumin, proinsulin, insulin and glucagon. Four peaks were defined in normal and tumor bearing patients: peak I (greater than 20 000 mol. wt.), peak II (primarily 9000 mol. wt.), peak III pancreatic glucagon (3500 mol. wt.) and peak IV small gucagon (less than 3500 mol. wt.). Glucagonoma patients differed from our normal and reported normal subjects in that peak II contained most of the circulating IRG. The percent of IRG associated with peak II was 9.5--31.5% in normals and 39.1--61.2% in glucagonomas. Glucagon-like biological activity in an isolated hepatocyte system was demonstrated for all peaks. However, relative to immunoreactivity, peak II showed reduced activity (25--33%). Immunoassay of dilutions of all peaks revealed the probability of immuno determinants identical with procine pancreatic glucagon. The presence of heterogenous IRG peaks with biological glucagon-like activity suggest that the larger molecules may be prohormones. Further, it is possible that specific elevation of peak II may be a diagnostic feature of glucagonomas.

Adenoma, Islet Cell↗
PubMed1976

Incidental splenectomy: a review of the literature and the New York Hospital experience.

981 consecutive splenectomies at The New York Hospital were reviewed. 18.9% were removed incidental to some other procedure, either to facilitate exposure or because of uncontrolled bleeding from capsular tears. The primary operation with which this was most frequently associated was gastric resection for peptic ulcer disease, accounting for 20.5% of the spleens so removed. Conversely, the incidental splenectomy was noted in only 0.91% of all gastrectomies and 1.4% of all left colectomies designated as nonradical procedures. It is therefore seldom a necessary procedure. Incidental splenectomy is more frequent when midline abdoiminal incisions are employed, less frequent with paramedian or left rectus splitting incisions. 85% of the spleens removed incidentally were grossly and microscopically unremarkable; lacerations most probably result from excessive manipulation rather than pathological changes predisposing to rupture. The postoperative morbidity and mortality is discussed and is felt to be increased significantly by the incidental splenectomy.

Gastrectomy↗
PubMed1975

Total unilateral renal destruction caused by irradiation for Hodgkin's disease.

Total unilateral renal destruction has been observed in a patient who previously received irradiation for Hodgkin's disease. The clinical features, after a six-year asymptomatic interval, included recurrent calculi and infection in what was subsequently demonstrated radiographically to be a nonfunctioning kidney. The gross and microscopic characteristics of the nephrectomy specimen have been described and correlated with the magnitude of irradiation and the clinical course.

Adult↗