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Biomedical subjects

S M Graham

Publications and source records attributed to S M Graham.

At least 127 records · Page 7Linked to original sources
PubMed1989

Cholecystokinin augmentation of 'surgical' pancreatitis. Benefits of receptor blockade.

The management of acute pancreatitis has not changed appreciably throughout several decades. Recent evidence has suggested that cholecystokinin (CCK) may play an important role in pancreatic disease. Investigations into the precise role of CCK in acute pancreatitis have been hampered by the lack of a specific CCK receptor antagonist. Using a newly described, highly potent and specific CCK receptor antagonist, L-364,718, the effect of CCK in two models of acute "surgical" pancreatitis was examined: (1) the bile salt ductal perfusion model in the rat and (2) a traumatic model in the guinea pig. At a suboptimal dose for pancreatic enzyme secretion (25 pmol/kg/h), CCK was found to potentiate the severity of the ensuing pancreatitis in both models. Continuous CCK receptor blockade with L-364,718 (25 nmol/kg/h) improved biochemical, morphologic, and survival indexes. This study suggests that physiologic levels of CCK play an important permissive role in the evolution of acute pancreatitis. The use of L-364,718 as an investigative probe or therapeutic tool for acute pancreatitis is worthy of further consideration.

Acute Disease↗
PubMed1988

Bleeding colonic ulcers secondary to atheromatous microemboli after left heart catheterization.

Atheromicroembolism after aortic or cardiac catheterization is frequently found at autopsy but rarely recognized in life, perhaps because many cases are asymptomatic. We report two patients who, after left heart catheterization, developed gastrointestinal hemorrhage from a solitary colonic ulcer caused by occlusive atheromicroemboli in submucosal vessels. We briefly review the spectrum and pathogenesis of atheromicroembolic injury to the gastrointestinal tract. Atheromicroemboli, which occlude vessels too small to be visualized by angiography, should be considered in the differential diagnosis of gastrointestinal bleeding in patients who have undergone aortic instrumentation.

Aged↗
PubMed1988

Cholangitis glandularis proliferans. A histologic variant of primary sclerosing cholangitis with distinctive clinical and pathological features.

This is the first report in the American literature of a recently described histologic variant of primary sclerosing cholangitis (PSC). Only six examples of this unique entity, called cholangitis glandularis proliferans (CGP), or proliferative cholangitis, have previously been reported. This disorder typically presents as painless jaundice but differs clinically from PSC by occurring predominantly in females and lacking an association with inflammatory bowel disease. The unique histological features are characterized by florid intramural proliferation of glandular elements in addition to an intense inflammatory component. Anatomically, the lesion is confined to the extrahepatic biliary tree, which enables its successful surgical extirpation since it does not appear to be progressive.

Adult↗
PubMed1987

Cecal diverticulitis. A review of the American experience.

The etiology of cecal diverticulitis remains unclear. The majority of diverticula are solitary and probably false and may be the result of the same degenerative process seen in the more common left-sided diverticulosis. A minority are true diverticula and may be of congenital origin. Cecal diverticulitis is clinically indistinguishable from acute appendicitis although patients with cecal diverticulitis tend to be older (average age, 40 years), have a longer duration of symptoms, and present less often with nausea and vomiting. In patients with previous appendectomy and in those with more indolent symptoms, barium enema may be helpful in making the diagnosis. If nonoperative treatment is chosen, careful follow-up with air contrast barium enema and colonoscopy should be carried out. The majority of patients require surgery and two types of cecal diverticulitis are encountered at laparotomy. The usual type, accounting for two thirds of cases, is easy to recognize, has an inflamed projection from the cecal wall, and is dealt with by a limited local diverticulectomy. Some authors advocate nonsurgical treatment for this first group of patients. Incidental appendectomy is advocated to avoid confusion should symptoms occur postoperatively. The hidden variant presents as a large, indurated phlegmon and is difficult to distinguish from a perforated cecal carcinoma. With the hidden variant, right hemicolectomy is the surgical treatment of choice and carries a 1.4 percent mortality.

Cecal Diseases↗
PubMed1987

Superior mesenteric artery syndrome following ileal J-pouch anal anastomosis. An iatrogenic cause of early postoperative obstruction.

This is the first case report of the superior mesenteric artery syndrome developing in a patient following total proctocolectomy and ileal J-pouch anal anastomosis. In addition, this is the first demonstration of this syndrome using abdominal CT scan. A 22-year-old veteran underwent total proctocolectomy for left-sided ulcerative colitis because of failure of medical therapy. At operation an ileal J-pouch anal anastomosis was constructed. Following operation, the patient developed an intestinal obstruction. Abdominal CT scan demonstrated scant retroperitoneal fatty tissue, massive dilatation of the duodenum proximal to the midline, and tapered narrowing of the duodenum between the superior mesenteric artery and aorta. These findings indicated superior mesenteric artery syndrome: arteriomesenteric obstruction of the duodenum. Based on the experience of this case, the authors believe that compression of the duodenum by the superior mesenteric artery may be a common but unsuspected cause of prolonged postoperative ileus or early postoperative obstruction following ileal pouch anal anastomosis.

Adult↗
PubMed1987

Provocative testing for occult medullary carcinoma of the thyroid: findings in seven children with multiple endocrine neoplasia type IIa.

A rise in the serum calcitonin (CT) following provocative testing has facilitated making the diagnosis of occult medullary carcinoma of the thyroid (MCT) or C cell hyperplasia (CCH) in asymptomatic children of kindred with multiple endocrine neoplasia (MEN) type IIa. Findings were reviewed for seven children varying in age from 3 to 16 years screened at our institution between 1976 and 1986. Three had elevated basal calcitonin (S-CT). Six had significant elevation of calcitonin (delta-CT) after stimulation. Total thyroidectomy was performed in all seven. Five had MCT with bilobar involvement in three. CCH was present in all five. Two patients had no gross, microscopic, or immunohistochemical evidence of MCT or CCH. One of three had an elevated S-CT. The other had a significant delta-CT. All patients have normal postoperative S-CT and delta-CT. Our experience indicates the importance of beginning stimulation tests of affected kindred at less than 3 years of age. It appears, however, that neither elevated S-CT or positive delta-CT are perfect predictors of parafollicular cell pathology. Solitary parathyroid enlargement, second thyroid malignancy, and branchial pouch anomalies may occur with MEN IIa. One patient with MCT had a focus of papillary carcinoma. One patient with primary hyperparathyroidism had a solitary enlarged parathyroid adenoma. Additional findings were the presence of nodules of ectopic thymus in close association with the thyroid gland in three patients.

Adolescent↗
PubMed1987

Age-associated alterations in hepatic beta-adrenergic receptor/adenylate cyclase complex.

The effect of age on catecholamine regulation of hepatic glycogenolysis and on hepatic adenylate cyclase was studied in male rats up to 24 mo of age. Epinephrine and norepinephrine stimulated glycogenolysis in isolated hepatocytes at all age groups studied. Isoproterenol, however, stimulated glycogenolysis only at 24 mo. In isolated liver membranes, usual activators of adenylate cyclase increased the activity of the enzyme considerably more in membranes from 24-mo-old rats than in membranes from either 3- or 21-mo-old rats. The Mn2+-dependent activity of the cyclase was increased by 2.9-fold in 3-mo-old animals and approximately 5.7-fold in 24-mo-old rats, indicating a substantial age-dependent increase in the intrinsic activity of the catalytic unit. The density of the beta-adrenergic receptor, as measured by the binding of [125I]-iodocyanopindolol to plasma membranes, was 5-8 fmol/mg protein in rats aged 3-12 mo but increased to 19 fmol/mg protein in 24-mo-old rats. Computer-aided analysis of isoproterenol competition of the binding indicated a small age-dependent increase (from 30% at 3 mo to 43% at 24 mo) in the proportion of beta-receptors in the high-affinity state. These observations suggest that beta-receptor-mediated hepatic glycogenolysis in the aged rat is predicated upon increases in the density of beta-receptors as well as increased intrinsic activity of the catalytic unit of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1987

High and low affinity sites associated with the binding of [3H]guanyl-5'-yl imidodiphosphate to liver plasma membranes.

Scatchard plots of the binding of [3H]Gpp(NH)p to rabbit and guinea pig liver plasma membranes were curvilinear, and could be resolved by computer-assisted non-linear regression analysis into two sites which exhibit high and low affinities. The two sites appear to be of equal capacities. The Kd values for binding to rabbit liver membranes were 5.6 +/- 0.5 nM and 133 +/- 20 nM for the high and low affinity sites, respectively. The Kd values for binding to similar sites on guinea pig liver membranes were 7.6 +/- 0.9 nM and 289 +/- 75 nM. In addition to Ns and Ni which have been identified in liver membranes, one or more of the other GTP-binding proteins may contribute to the observed binding.

Adenylyl Cyclases↗
PubMed1987

Gastric epithelioid leiomyomatous tumors.

Gastric epithelioid leiomyomatous tumors can present in three patterns; intramural, endogastric and exogastric based upon the relation to the gastric muscular wall. Patients may experience no symptoms from this tumor or may complain of symptoms suggesting peptic ulcer disease. Upper gastrointestinal tract series are the most reliable diagnostic tests but important additional information can be obtained by ultrasound and abdominal computerized tomography. The overwhelming majority of epithelioid leiomyomatous tumors are found in the gastric antrum. Round or polygonal cells are seen histologically. Often these cells have a clear zone that surrounds the nuclei. The origin of these tumors is debated. Less than one-third of these tumors metastasize. Complete surgical excision can often achieve cure. The exogastric lesions are the ones most readily cured by resection. Prognosis also correlates with clinical parameters including size of tumor, duration of symptoms and weight loss. Adjuvant therapy has not proved beneficial.

Humans↗
PubMed1987

Gastric epithelioid leiomyosarcoma: a curable gastric neoplasm.

This is the first case report of the preoperative diagnosis of a gastric epithelioid leiomyosarcoma by percutaneous needle biopsy. Preoperative diagnosis facilitated curative surgical resection. Patients may present without symptoms or may report symptoms of peptic ulcer disease or gastrointestinal bleeding. Upper gastrointestinal series is the most useful radiological tool for detecting these lesions. Ultrasound and CT play a useful role in documenting the origin of these large masses, as well as their spread. Endoscopy is being used with increasing frequency, but because these are submucosal lesions diagnosis cannot easily be made through the endoscope. Pathologically, these tumors can be subdivided histologically into a benign epithelioid leiomyoma and two varieties of malignant epithelioid leiomyosarcoma. Prognosis correlates with histological features. Complete surgical resection is the treatment of choice. Chemotherapy or radiotherapy have no proven efficacy in treating epithelioid leiomyosarcoma. Unlike most other gastric malignancies, a favorable prognosis follows successful resection.

Aged↗
PubMed1986

Beta-adrenergic receptors in guinea-pig liver plasma membranes and thermal lability of [3H]dihydroalprenolol binding sites.

beta-Adrenergic receptors in guinea-pig liver plasma membranes were characterized by radioligand binding, using l-[3H]dihydroalprenolol ([3H]DHA), l-3-[125I]iodocyanopindolol ([125I]CYP) and dl-[3H]4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzimidazole-2- one hydrochloride [( 3H]CGP-12177). The binding of both [125I]CYP and [3H]CGP-12177 to membranes exhibited high affinity (Kd = 3.5 +/- 0.2 pM for [125I]CYP and 0.75 +/- 0.10 nM for [3H]CGP-12177) and stereospecificity; the maximal binding sites were 130 +/- 15 and 137 +/- 8 fmoles/mg protein respectively. Catecholaminergic agonists competed for these binding sites in the order l-isoproterenol greater than l-epinephrine greater than l-norepinephrine, which is typical for beta 2-adrenergic receptors. The binding data are supported by parallel experiments on adenylate cyclase activation by catecholamines, and on antagonism of this activation by beta 1- and beta 2-selective blockers. The binding of [3H]DHA was excessive (Bmax = 21.4 pmoles/mg protein), exhibited low affinity (Kd = 34.6 nM), and lacked stereospecificity. When liver membranes were incubated at 50 degrees for 40 min in the presence of an agonist, l-isoproterenol, the binding of [3H]DHA to the heat-treated membranes exhibited high affinity (Kd = 1.07 +/- 0.17 nM) and the Bmax was reduced to 139 +/- 22 fmoles/mg protein. In such membranes, as opposed to native membranes, stereospecificity was evident and catecholaminergic agonists competed for the binding sites in the order typical for beta 2-adrenergic receptors. However, agonist competition of the binding to the heat-treated membranes could not be modulated by guanine nucleotides, indicating a loss of communication between the receptor and the guanine nucleotide regulatory protein.

Adenosine Diphosphate Ribose↗
PubMed1985

Hepatic adenylate cyclase. Development-dependent coupling to the beta-adrenergic receptor in the neonate.

Guanine nucleotide-dependent modulation of agonist binding to the beta-receptor reflects coupling of the receptor to the nucleotide regulatory protein. Similarly, guanine nucleotide-dependent stimulation of adenylate cyclase can be used as an index of coupling between the regulatory protein and the catalytic unit of the cyclase. Using both approaches we have studied coupling in the beta-adrenergic receptor-adenylate cyclase system in rabbit liver during neonatal development. With [3H]dihydroalprenolol as ligand, the Bmax was relatively unchanged (200-300 fmol/mg of protein) between birth and end of day 1 and was similar to adult values. Guanyl-5'-yl imidodiphosphate-dependent shift in agonist (l-isoproterenol) competition curves was biphasic, decreasing from 10-fold in membranes isolated from animals at term to about 6-fold in membranes from 6-h-old neonates, and increasing progressively in older animals to a maximal measurable value of 42-fold in the adult. The ability of guanyl-5'-yl imidodiphosphate, GTP, GTP plus isoproterenol, NaF, or forskolin to activate adenylate cyclase was also biphasic and age-dependent. With Mn2+ the measured activity was not at any time greater than the activity at term. Pretreatment of membranes with cholera toxin resulted in differential levels of enhancement of adenylate cyclase activity wherein much lower enhancement was observed in membranes from neonatal animals. With [32P]NAD as substrate, cholera toxin-catalyzed ADP-ribosylation of membranes indicated development-dependent accumulation of Ns peptides. From these results we suggest that there is a decreased efficiency in the coupling of the beta-adrenergic receptor to hepatic adenylate cyclase in early neonatal life. The molecular basis for the biphasic nature of the coupling is presently unclear.

Adenylyl Cyclases↗
PubMed1980

Metabolic resource allocation vs. mating attractiveness: Adaptive pressures on the "alba" polymorphism of Colias butterflies.

The sex-limited "alba" genetic polymorphism in wing color of Colias butterflies has been studied with respect to potential selective pressures on this locus. Alba female pupae, carrying at least one dominant A allele, redirect resources, used by aa pupae for pigmentation, to other metabolic ends. Associated with this reallocation, alba, A-, female adults eclose earlier, retain more larva-derived resources in their fat bodies for somatic maintenance and for reproduction, and, in some conditions, mature their eggs faster than do aa females. Alba females are also less attractive to males than are aa females and mate less frequently. Evolutionary implications of these results are discussed.

Journal Article↗
PubMedDate not supplied

Neurotoxicity in a phase I trial of continuous infusion cisplatin with hyperfractionated radiotherapy for locally advanced head and neck cancer.

BACKGROUND: Both twice daily fractionated radiotherapy and concurrent cisplatin with once-daily radiotherapy have been shown to improve local disease control in patients with head and neck cancer. The objective of this phase I trial was to determine the maximum tolerated dose of cisplatin which could be given as a continuous infusion concurrent with twice-daily radiotherapy to patients with locally advanced head and neck cancer. METHODS: Patients were treated with radiotherapy at doses of 110 cGy twice daily for 5 days per week to a total dose of 7040-7590 cGy. Concurrent with radiotherapy, patients received continuous-infusion cisplatin for 5 days per week. Groups of 3-6 patients were treated with doses of 1-3 mg/m2/day. RESULTS: Central nervous system toxicity became dose-limiting. At 1 mg/m2, 2 mg/m2, and 3 mg/m2 confusion was observed and one patient had a seizure. At 3 mg/m2, another patient suffered severe sensory and motor neuropathy. Despite bulky tumors, 12 of the 14 patients had an objective response and 3 achieved a complete response. CONCLUSION: the combination of twice-daily fractionated radiotherapy and concurrent cisplatin by continuous infusion is severely toxic and achieves results similar to less toxic programs. It is not recommended for further investigation or therapy.

Adult↗
PubMedDate not supplied

Anomalies of forearm vascular anatomy encountered during elevation of the radial forearm flap.

BACKGROUND: The radial forearm flap has gained considerable popularity over the past 10 years. With the increasing number of forearm flaps being used in head and neck reconstruction, it is likely that anomalous forearm vascular anatomy will be encountered by more head and neck surgeons performing this procedure. METHODS: We reviewed our experience with 52 forearm flaps; four different anomalies of forearm vascular anatomy were encountered in four patients. In this article we present each of our cases and discuss the incidence, preoperative diagnosis, and recommended management of these and the more common forearm vascular anomalies. RESULTS: The anomalies encountered in our series include: one case of distal takeoff of the radial artery deep to the pronator teres muscle, two cases of a superficial dorsal antebrachial artery, one case of bilateral hypoplastic ulnar arteries, and one case of high takeoff of the radial artery. CONCLUSIONS: There are a number of anomalies of forearm vascular anatomy of clinical significance to the surgeon performing these procedures. Most of these anomalies can be identified with a careful preoperative examination. Surgeons performing this procedure should be familiar not only with the normal vascular anatomy of the forearm flap, but also with the more common anatomic variants. Failure to recognize or appropriately manage these anomalies of forearm vascular anatomy may result in a compromised surgical outcome.

Adolescent↗