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Biomedical subjects

J M Feldman

Publications and source records attributed to J M Feldman.

196 records · Page 11Linked to original sources
PubMedDate not supplied

Therapeutic doses of cyproheptadine do not inhibit monoamine oxidase in man.

Cypro, a serotonin and histamine antagonist, has been shown to be a moderately potent reversible inhibitor of tissue monoamine oxidase (MAO) obtained from hamsters and rabbits. In the present study, Cypro inhibits MAO obtained from human platelets with the same potency as harmine (Ki = 5 x 10(-5) M). However, when ten normal volunteers received conventional therapeutic doses of Cypro (16 mg/day) for two days, there was no alteration in their urinary excretion of tryptamine, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxymandelic acid, epinephrine, or norepinephrine. We conclude that, when used in conventional clinical doses, Cypro does not inhibit MAO in man.

Adult↗
PubMedDate not supplied

Glyburide: a second-generation sulfonylurea hypoglycemic agent. History, chemistry, metabolism, pharmacokinetics, clinical use and adverse effects.

Glyburide, a second-generation hypoglycemic sulfonylurea, is 200 times as potent as tolbutamide. This increase is due to greater intrinsic hypoglycemic potency of the molecule rather than to a prolonged biologic half-life. Glyburide is inactivated by the liver to 4-trans-hydroxyglyburide and 3-cis-hydroxyglyburide; 50% of these compounds is excreted in the urine and 50% in the bile. Although the serum concentration of glyburide can be measured by radioimmunoassay and high-performance liquid chromatography, the importance of its serum concentration in the reduction of hyperglycemia is not yet established. Glyburide has a therapeutic effectiveness comparable to that of the first-generation sulfonylurea chlorpropamide; however, it has a lower frequency of adverse effects. To date it has a low frequency of clinically significant interactions with other drugs. Glyburide should not be prescribed for patients with liver disease or significant renal disease. Because glyburide is a potent hypoglycemic agent, it should be prescribed in small initial doses, particularly for elderly patients with diabetes. At the present time there is no definite evidence that it modifies the increased risk of cardiovascular disease of diabetic patients. Although glyburide is a potent stimulator of pancreatic insulin secretion after short-term administration, an additional mechanism of action during long-term administration is to decrease the resistance of muscle and liver to the action of insulin. It is a useful medication for patients with type II diabetes whose hyperglycemia is not adequately reduced by dietary management and exercise. It can be used as the initial drug in these patients or as the replacement drug for those with primary or secondary failure during therapy with first-generation sulfonylureas.

Animals↗
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Limitations of angiography for mesenteric ischemia caused by midgut carcinoid tumors.

Mesenteric ischemia associated with carcinoid tumors often presents with nonspecific abdominal pain and is usually due to mesenteric branch artery occlusion caused by elastic vascular sclerosis. Mesenteric ischemia was defined by the operative findings of cyanosis or infarction. Eleven patients with intraabdominal metastatic carcinoid tumor were evaluated by angiography. Angiographic narrowing and occlusion of multiple peripheral jejunal and ileal intramesenteric branch arteries was present in 3 patients with mesenteric ischemia, but also occurred in 5 of 8 patients without mesenteric ischemia. Other angiographic abnormalities included staining of the primary tumor (5) or metastases (6), tenting of small mesenteric vessels (5), and occlusion of draining mesenteric veins (2). We conclude that in patients with midgut carcinoid tumors, angiographic narrowing and occlusion of peripheral mesenteric arteries most likely represents elastic vascular sclerosis, is indicative of mesenteric invasion of tumor, but correlates poorly with the presence of ischemia in the subtended bowel. Alternatively, a normal selective arteriogram should exclude mesenteric ischemia as the cause of abnormal pain.

Adult↗
PubMedDate not supplied

Preparation of islets of Langerhans from rabbits and hamsters by the collagenase digestion technique.

In this report we describe some modifications of the collagenase digestion technique for the preparation of pancreatic islets, that we have found helpful in preparing isolated islets of Langerhans from rabbits and hamsters. These modifications include disrupting the pancreatic acinar tissue by directly infiltrating it with Hanks' solution, periodically monitoring the progress of the collagenase digestion of the pancreatic tissue with the dissecting microscope, and purifying the islets by serial passage of the digested tissue through three Petri dishes containing Hanks' solution. This technique results in the successful isolation of the fragile and irregular rabbit islets as well as the isolation of the sturdier and more uniformly shaped hamster islets. The isolated respond to a glucose stimulus with an increase in radioimmunoassayable insulin secretion. We also describe a filtration technique for the preparation of isolated islets for histological examination. Isolated islets are retained on Millipore filters. The filters are then fixed, stained and mounted. Finally, we present realistic photographs of rabbit and hamster islets, as they appear under the dissecting microscope, during various stages of purification and isolation.

Animals↗
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Effects of food restriction on mice with the hereditary obese-hyperglycemic syndrome.

The purpose of this study was to compare the organ weights of obese-hyperglycemic (ob/ob) mice with the organ weights of their normal litter-mates. The absolute weights of the epididymal fat pads (white fat), interscapular fat pads (brown fat) and liver were greater in ob/ob mice than in normal mice. The weights of the kidneys and heart were similar in the 2 groups. The weights of the brain and testes were decreased in ob/ob mice when compared with normal mice. The weight gain of a second group of ob/ob mice was decreased by chronic food restriction resulting in a 26% reduction in weight when compared with ob/ob mice having unrestricted access to food. This substantially reduced the weight of the liver, but resulted in a minimal reduction in the weight of the epididymal fat pad. Food restriction did not alter the weight of the interscapular fat pads. It caused a relative reduction in kidney weight and a further absolute and relative reduction in testis weight.

Adipose Tissue↗
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Reliability of copper reduction methods for quantitation of glucosuria.

In the present study we evaluated the reliability of the "2-drop" Clinitest method in determining the 24-h glucose spill of a diabetic patient. The urine glucose content over the 33 day study period was measured with a Beckman glucose analyzer that employed a glucose oxidase method. There was no statistical difference between the glucose content determined by the two methods. There was a mean error of +4.4 +/- 3.6% between the values obtained with the "2-drop" method and values obtained with glucose analyzer. The mean coefficient of variation for determining the glucose content of urine with the "2 drop" method was 19%. In a group of 10 normal volunteers we found that there was a falsely elevated glucose value in urines with osmolality of less than 295 mosm/kg when the "5-drop" method was used. The "2-drop" Clinitest and the Beckman analyzer could accurately determine glucose concentration even in these dilute urines. The "2-drop" Clinitest method is a useful and reasonably reliable method for evaluationg 24-h glucosuria.

Adult↗
PubMedDate not supplied

Growth hormone and prolactin secretion in the carcinoid syndrome.

We evaluated plasma growth hormone (GH) and plasma prolactin (PRL) levels in ten patients with metastatic carcinoid tumors and the carcinoid syndrome ("active tumors") and seven patients with metastatic carcinoid tumors without the carcinoid syndrome ("inactive tumors"). The patients with active tumors had elevated serum serotonin levels and increased urinary 5-hydroxyindoleacetic acid (5-HIAA) while these values were normal in patients with inactive tumors. Forty-five per cent of patients with active tumors had elevated fasting plasma GH levels that were either not suppressed or showed a paradoxical increase in response to I.V. glucose. There was a positive correlation between the plasma GH levels and serotonin production by the tumor. Twenty-eight per cent of patients with inactive tumors had elevated fasting plasma GH levels. GH levels were decreased by the administration of serotonin antagonists in some but not all of the patients. Parachlorophenylalanine (PCPA) an inhibitor of serotonin synthesis caused a paradoxical rise in GH levels. GH release in response to insulin hypoglycemia was normal. Plasma prolactin levels were normal in most of the patients with metastatic carcinoid tumors. PCPA administration did not systematically alter plasma prolactin levels. We conclude that elevated plasma GH levels are frequently present in patients with the carcinoid syndrome. Both serotonin produced by the tumors and the tumor itself may be responsible for the elevated GH levels.

Adult↗
PubMedDate not supplied

Gastrointestinal and metabolic function in patients with the carcinoid syndrome.

We evaluated gastrointestinal absorption in six consecutive patients with metastatic serotonin-secreting carcinoid tumors. One patient had a consistent defect in fat absorption and two other patients malabsorbed fat during spontaneous or dopamine-induced exacerbation of the carcinoid syndrome. The steatorrhea of the patient with the persistent defect in fat absorption was reduced when tumor serotonin production was reduced by the tryptophan hydroxylase inhibitor parachlorophenylalanine. The six patients had normal hemoglobin levels and the serum concentration of the following urinary constituents was normal in most of the patients: albumin, carotene, 25-hydroxycalciferol, parathyroid hormone, calcitonin, calcium, phosphorous, osteogenous alkaline phosphatase, cholesterol, triglycerides, and serum lipoproteins. The excretion of the following urinary constituents was also normal in most of the patients: creatinine clearance, tubular reabsorption of phosphorous, calcium, D-xylose, cyclic 3'5' monophosphate and hydroxyproline. We conclude that patients with the carcinoid syndrome may have steatorrhea, and that their hyperserotoninemia plays a role in this process.

Aged↗
PubMedDate not supplied

Serotonin metabolism and platelet monoamine oxidase activity in patients with medullary carcinoma of the thyroid and pheochromocytoma.

Occasional patients with medullary carcinoma of the thyroid (Multiple Endocrine Neoplasia Type II [MEN II]) are reported to have excessive serotonin (5-HT) production from the MCT; almost all patients with metastatic MCT have elevations in plasma concentration of the amine oxidase, histaminase. The elevated 5-HT production is thought ot contribute to the troublesome diarrhea experienced by patients with MEN II. We compared the urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the principle metabolite of 5-HT, of 33 patients with MCT with the urinary excretion of 5-HIAA in 33 control subjects. Six of the 33 MCT patients (18%) had severe diarrhea. The 5-HIAA excretion of the MCT patients did not differ from that of normal subjects. We also compared the platelet monoamine oxidase (MAO) activity of 27 MCT patients and 27 control subjects. The platelet MAO activity of the two groups did not differ. The 5-HT content and MAO activity of 6 of the MCTs was similar to normal thyroid tissue. The MAO activity of two follicular adenomas of the thyroid was greater than the MAO activity of MCTs. In contrast to the uniform elevation of plasma histaminase in patients with MCT, the platelet MAO activity is not altered and the majority of MCTs do not produce excessive amounts of 5-HT.

Adolescent↗
PubMedDate not supplied

Urinary free cortisol excretion in patients with metastatic cancer.

Many patients with metastatic carcinoma have an increase in urinary excretion of 17-hydroxycorticosteroids (17-OHCS), plasma concentrations of 17-OHCS, plasma total cortisol, plasma nonprotein-bound cortisol, or cortisol production rate. A small portion of circulating cortisol is excreted in the urine as unaltered or free cortisol. This urinary free cortisol, which is believed to reflect the average unbound plasma cortisol circulating during the day, is an excellent measure of adrenal cortical function. In this study, we compared the urinary free cortisol of 35 patients with metastastic cancer (10 small cell carcinomas of the lung, 8 other types of carcinoma of the lung, 8 breast carcinomas, and a miscellaneous carcinomas) with a group of 15 healthy age-matched volunteers. There were no significant changes in urinary free cortisol excretion in the patients with cancer.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Diagnostic and therapeutic considerations in a hypercalcemic dog with multiple endocrine neoplasia.

Hypercalcemia was found in a dog examined for episodic weakness and disorientation. A right adrenal mass identified on abdominal ultrasonographic examination was diagnosed as a pheochromocytoma based on increased 1231-metaiodobenzylguanidine uptake and characteristic histopathological features. Serum intact parathyroid hormone (iPTH), total serum calcium, and ionized serum calcium were increased prior to surgery. Although both total and ionized serum calcium concentrations decreased to within normal reference ranges following surgery through postoperative day 17, subsequent high concentrations with increased serum iPTH concentrations confirmed concurrent primary hyperparathyroidism. A right parathyroid tumor was suspected based on a technetium-99m-sestamibi (99mTc-sestamibi) scan.

3-Iodobenzylguanidine↗
PubMedDate not supplied

Midgut carcinoid tumors: CT findings and biochemical profiles.

OBJECTIVE: Our goal was to describe the abdominal CT findings in 52 patients with midgut carcinoid tumors and correlate these findings with their biochemical profiles. MATERIALS AND METHODS: Abdominal/pelvic CTs of 52 patients with midgut carcinoid tumors were reviewed retrospectively for the presence of liver metastases, mesenteric and peritoneal disease, bowel changes, lymphadenopathy, and the presence of the primary tumor. Logistic regression models were used to evaluate the association between these findings and the serum and platelet serotonin and urine 5-hydroxyindolacetic acid levels. RESULTS: The most common finding was hepatic metastases (34/52). Nonspecific mesenteric soft tissue stranding was present in 26 of 52 and a discrete mesenteric mass was present in 25 of 52. These masses had linear, radiating soft tissue spokes in 16 of 25 and contained calcification in 10 of 25. Retroperitoneal and mesenteric lymphadenopathy was present in 14 of 52 and 11 of 52 cases, respectively. Carcinomatosis was present in 11 of 52. Bowel wall thickening was seen in 9 of 52. Six patients had a small bowel obstruction. Elevated serum serotonin, platelet serotonin, and urine 5-hydroxyindolacetic acid levels were significantly associated with the presence of liver metastases (p = 0.0032, 0.0098, and 0.0450, respectively). Elevated platelet serotonin levels were also significantly associated with the presence of a mesenteric mass (p = 0.0101). CONCLUSION: In our population, the most common findings of a midgut carcinoid tumor are liver metastases, nonspecific mesenteric soft tissue changes, a discrete mesenteric mass with radiating soft tissue spokes, often containing calcification, and lymphadenopathy. As expected, liver metastases correlate strongly with the presence of elevated biochemical levels. A new observation is the correlation of elevated platelet serotonin levels and mesenteric masses. We hypothesize that platelet serotonin may be the factor that stimulates stromal cells to produce mesenteric fibrosis and mass formation.

Adult↗
PubMedDate not supplied

Do agents used for epidural analgesia have antimicrobial properties?

BACKGROUND AND OBJECTIVES: Local anesthetics inhibit bacteria growth in culture although this effect diminishes as the concentration of the drug is reduced. The antimicrobial properties of opioids are unknown. This study was designed to determine the ability of lidocaine and bupivacaine, with or without fentanyl or sufentanil, to inhibit bacteria growth in culture at concentrations typically used to provide analgesia. METHODS: Potential bacteria pathogens were cultured in agar media containing: agar alone, 2%, 1.5%, and 1% lidocaine, 0.5%, 0.25%, and 0.125% bupivacaine, 0.125% bupivacaine + fentanyl 2 mcgs/mL, 0.125% bupivacaine + sufentanil 0.3 mcgs/mL, and fentanyl 5 mcgs/mL, fentanyl 2 mcgs/mL or sufentanil 0.3 mcgs/mL. Organisms were deemed sensitive to the study agent if no growth was apparent after incubation for 24 hours. RESULTS: Both lidocaine and bupivacaine significantly reduced bacteria growth at all concentrations studied compared to the growth observed in agar alone (P < .0001). This growth inhibition diminished as the concentration of local anesthetic was reduced especially for certain bacteria species for example. Staphylococcus aureus (P < .0001). Neither fentanyl nor sufentanil inhibited any bacterial growth in culture. CONCLUSIONS: Since the growth in culture of common pathogens, especially S. aureus, is not inhibited as the concentration of local anesthetic is reduced, the local anesthetics tested are unlikely to help prevent epidural-catheter-related infection due to common pathogens. More study is necessary to determine if local anesthetics help prevent infection from less common pathogens in patients at increased risk for infectious complications.

Analgesia, Epidural↗