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Biomedical subjects

N O Atuk

Publications and source records attributed to N O Atuk.

At least 19 recordsLinked to original sources

Circulating dihydroxyphenylglycol and norepinephrine concentrations during sympathetic nervous system activation in patients with pheochromocytoma.

Although increased plasma norepinephrine (NE) concentrations mediate vasoconstriction during episodic hypertension and hypertensive crises in patients with pheochromocytoma (Pheo), the precise origin of this circulating NE (tumor or sympathetic nerves) is not known. Dihydroxyphenylglycol (DHPG), a deaminated metabolite of NE, is formed principally in sympathetic nerve endings. Under basal conditions, plasma NE and DHPG concentrations correlate closely, and during sympathetic nervous system activation, both plasma NE and DHPG concentrations increase. This observation suggests that plasma DHPG concentrations may reflect the source of circulating NE (tumor or sympathetic nerves) during hypertensive episodes in patients with Pheo. Plasma NE and DHPG concentrations were measured simultaneously, and the NE/DHPG ratio was calculated in seven patients with Pheo during 20 min of sympathetic nervous system activation (treadmill exercise) before and after surgical resection of the tumor. Age- and sex-matched normal subjects were also studied. Exercise resulted in a significant increase in plasma NE and DHPG concentrations in patients with Pheo and in normal subjects (Pheo: basal NE, 1827 +/- 639; peak NE, 3016 +/- 769 pg/mL (P = 0.02); normal subjects: basal NE, 266 +/- 27; peak NE, 1166 +/- 197 pg/mL (P = 0.01); Pheo: basal DHPG, 1521 +/- 280; peak DHPG, 2313 +/- 252 pg/mL (P = 0.007); normal subjects: basal DHPG, 870 +/- 50; peak DHPG, 1630 +/- 180 pg/mL (P = 0.01)]. The NE/DHPG ratio increased with exercise in normal subjects (basal, 0.30 +/- 0.02; peak, 0.83 +/- 12; P = 0.005), but did not change in patients with Pheo (basal, 1.22 +/- 0.32; peak, 1.54 +/- 0.27). Exercise also increased plasma NE and DHPG concentrations and the NE/DHPG ratio in five patients studied after surgical resection of the tumor. Systolic blood pressure and heart rate increased significantly during exercise in all three study groups. The increase in plasma NE and HDPG concentrations during exercise-induced sympathetic nervous system stimulation in patients with Pheo is similar to that in normal subjects and may indicate that the sympathetic nervous system plays an important role in the pathogenesis of hypertension and hypertensive crises in patients with Pheo.

Adolescent

Insertion of subclavian hemodialysis catheters in difficult cases: value of fluoroscopy and angiographic techniques.

Double-lumen hemodialysis catheters designed to be placed via a subclavian vein approach have gained rapid acceptance over the past several years. Several studies have shown a significant rate of subclavian vein stenosis or occlusion after placement of these catheters. A large number of these patients require repeat placement of catheters with access often becoming increasingly difficult to obtain. Over the past 5 years, we have been asked to place 38 catheters in 34 patients that could not be placed at the bedside. Our procedure consists of obtaining a preliminary venogram to evaluate the reason for difficulty. The subclavian vein is then cannulated under direct fluoroscopic visualization while the peripheral venous line is injected with contrast material. Percutaneous angiographic techniques are then used to position the catheter. Satisfactory placement was obtained in all 38 cases. There were no complications, which is surprising considering the number of complications seen with the standard methods of insertion. This represents a new role for the interventional radiologist, one that can be important in minimizing the number of new dialysis sites in any one patient.

Angiography

Disparate urinary catecholamine patterns in secondary hypertension due to unique sequential development of pheochromocytoma and neuroblastoma.

A 43-year-old white woman had a pheochromocytoma removed from her left adrenal gland, and one year later she developed a new left upper abdominal mass that was found to be a neuroblastoma. On both occasions, urinary vanillylmandelic acid level was elevated. However, urinary norepinephrine and epinephrine levels were increased only during the pheochromocytoma episode, while the urinary homovanillic acid level was elevated only when neuroblastoma developed. Despite a high suspicion of pheochromocytoma recurrence, the urinary catecholamine profile was suggestive of neuroblastoma, which was revealed by histopathologic analysis of the tumor tissue.

Abdominal Neoplasms

Rabies pre-exposure prophylaxis using intradermal human diploid cell vaccine: immunologic efficacy and cost-effectiveness in a university medical center and a review of selected literature.

The authors studied the antigenicity of intradermal human diploid cell rabies vaccine administered to 40 laboratory workers considered to be at-risk at the University of Virginia Medical Center. A 1-year postvaccination serology was determined for 20 of those 40, all of whom demonstrated an antirabies titer greater than or equal to 1:50 by the raped fluorescent focus inhibition test. By 2 years' postvaccination, 5 of 40 subjects had "unprotective levels" (less than 1:5), whereas 35 had titers greater than or equal to 1:5, and none had a titer greater than or equal to 1:50. Booster doses given to four subjects whose titers had declined produced a 1-month postvaccination antirabies titer greater than or equal to 1:50 in all cases. Vaccine administration by the intradermal rather than the intramuscular route resulted in a cost savings of $120 (U.S.) per employee. This data indicate that the intradermal administration of human diploid cell vaccine for rabies pre-exposure prophylaxis achieves an immunologic response thought to be protective while providing a substantial cost savings when compared with the intramuscular route of administration. Those who receive primary pre-exposure rabies vaccination should have serologic confirmation of immunologic protection every 2 years with a booster dose given to subjects demonstrating a titer less than 1:5.

Adolescent

Increased uptake and accumulation of catecholamines by red blood cells in phaeochromocytoma.

Red blood cell (RBC) and plasma catecholamine content were determined by high performance liquid chromatography in 18 patients suspected of having phaeochromocytoma on the basis of clinical manifestations, especially hypertension and laboratory findings. Eight normotensive health individuals served as controls. The fivne patients with tumours had strikingly greater RBC catecholamine concentrations (C) than in plasma and reached CRBS/Cplasma ratios approximating 5, significantly different from the ratios in controls and in hypertensive patients without tumours. One tumour patient had a normal RBC catecholamine content as well as repeatedly normal plasma and urinary catecholamine levels. The other 12 patients, who had no ++tumours, had only slight elevations in plasma and RBC catecholamine levels. There is an accelerated uptake of catecholamines against a concentration gradient by the RBC in phaeochromocytoma, which indicates that RBC play a major role in the clearance of catecholamines after they are secreted into circulation.

Adrenal Gland Neoplasms

Pheochromocytoma: diagnosis, localization, and treatment.

Pheochromocytoma is curable in 90% of cases, yet its diagnosis and localization are among the most challenging problems in clinical medicine. Although only 10% of these tumors are malignant, others may be lethal because of excessive circulating catecholamines. The clinical hallmark of pheochromocytoma is hypertension, but some patients are normotensive and may even be hypotensive.

Adrenal Gland Neoplasms

Cutaneous histoplasmosis after renal transplantation.

A 21-year-old woman with a renal allograft presented with cellulitis of the right foot as the first manifestation of disseminated histoplasmosis. Disseminated histoplasmosis is more common in immunosuppressed hosts, and there is a trend toward more frequent cutaneous manifestations in transplant recipients (47%). Biopsy of cellulitis in these patients may lead to early diagnosis and curative amphotericin therapy.

Adult

Biorhythms of the nonpregnant human uterus.

Uterine activity was monitored continuously for periods of three or five days in two subjects. Biorhythms in the spontaneous variations of intrauterine pressure and frequency of contraction were demonstrated in both phases of the menstrual cycle. Statistically, the patterns conformed to 24-hour Fourier curves, with higher values synchronized by the periods of light. Positive statistical correlations were present between uterine activity and the circadian patterns of intrauterine temperature and norepinephrine concentrations in both urine and peripheral arterial plasma.

Activity Cycles

Familial pheochromocytoma, hypercalcemia, and von Hippel-Lindau disease. A ten year study of a large family.

Long-term epidemiological and laboratory studies were carried out in a kindred with familial pheochromocytoma associated with von Hippel-Lindau disease. Thirteen members were affected by the syndrome and the trait appears to be transmitted in an autosomal dominant fashion. Of 13 patients, 7 had pheochromocytoma alone. Of the remaining six patients, one had pheochromocytoma combined with von Hippel-Lindau disease, four had pheochromocytoma with retinal disease only, and a single patient had a retinal lesion without pheochromocytoma. In four patients, pheochromocytoma antedated the development of retinal lesions. Ten members also had mild hypercalcemia without accompanying elevations of PTH in the 4 patients in whom this was determined. In all, hypercalcemia was corrected with removal of tumors, and no patient had a return of hypercalcemia in the absence of recurrent increases in urinary catecholamines. The clinical presentations in 12 patients varied markedly, as did their urinary excretion rates of norepinephrine, epinephrine and their metabolites. However, an analysis of the data revealed significant correlations not previously described between the urinary excretion of free catecholamines (norepinephrine plus epinephrine), blood pressure, the free catecholamine content of the tumor and the age of the patient. Urinary excretion of free norepinephrine plus epinephrine appear to be decreased with advancing age (p less than 0.001). Both systolic and diastolic blood pressures and the age of the patient were inversely correlated (p less than 0.01). A significant inverse relationship between the tumor content of free catecholamines and the age of the patients was, although to a lesser degree, also present (p less than 0.05). As a whole, the size of the tumors and their norepinephrine content were not correlated. We present a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the clinical presentations of the disease.

Adolescent

Study of chemical sympathectomy in endotoxin-induced lethality and fibrin depostion.

Shock and the generalized Shwartzman reaction are well known features of endotoxin which have been shown to involve the sympathetic nervous system. The mechanism of sympathetic nervous system involvement with endotoxin injection was studied in rabbits chemically sympathectomized with 6-hydroxydopamine. Endotoxin, in doses producing a spectrum of morbidity and mortality in normal rabbits, was administered i.v. to chemically sympathectomized, normal, and unilateral renal surgically sympathectomized animals. Chemical sympathectomy produced a significant depletion of tissue norepinephrine which, in endotoxin recipient animals, was associated with a significantly lower mortality rate and greatly decreased fibrin deposition in the lungs and kidneys, despite intravascular coagulation. Unilateral renal sympathectomy afforded protection to the ipsilateral kidney, but data on mortality and systemic fibrin deposition were similar to those reported for normal rabbits given endotoxin. Six-hydroxydopamine prevents significant tissue injury secondary to endotoxin in this experimental model. In addition, the data provide direct evidence that an intact reactive sympathetic nervous system is essential for development of lethal toxicity and generalized Shwartzman reaction due to endotoxin.

Animals

Nephrotoxic nephritis in rabbits. The role of the sympathetic nervous system.

The sympathetic nervous system and catecholamines play a major role in fibrin deposition in organs in rabbits after endotoxin administration. Glomerular fibrin deposition is also a key factor in the pathogenesis of nephrotoxic nephritis in rabbits, but the role of the sympathetic nervous system in this type of fibrin deposition has not been defined. We investigated sympathetic nervous system involvement in nephrotoxic nephritis using a model of isolated chemical sympathectomy with 6-hydroxydopamine. Different quantities of pooled nephrotoxic serum were injected intravenously into control and sympathectomized rabbits to produce a known spectrum of pathology in normal rabbits. Animals were killed and their organs were analyzed to ascertain that sympathectomy had been accomplished. Biochemical, immunohistologic, and histopathologic evaluation of the animals, comparing controls and sympathectomized rabbits, revealed no differences in the degree of renal damage for a given quantity of nephrotoxic serum. We conclude that, in the rabbit model, the sympathetic nervous system plays no significant role in the pathogenesis of fibrin deposition and glomerular damage in nephrotoxic nephritis.

Animals

Therapy of the idiopathic nephrotic syndrome with alternate day steroids.

Eighty-one adult patients with the idiopathic nephrotic syndrome were treated with prednisone, 60 to 120 mg, on alternate days. Treatment was continued with diminishing drug doses for up to 10 years. Biopsy specimens were categorized as showing lipoid nephrosis 36 per cent, focal sclerosis 12 per cent, diffuse proliferative 22 per cent and membranous nephropathy 30 per cent. Patients with systemic causes of the nephrotic syndrome were excluded. Proteinuria decreased to normal or to less than or equal to 3 g with a greater than or equal to 50 per cent decrease from base line in 83 per cent of the patients with lipoid nephrosis, 30 per cent of the patients with focal sclerosis, 50 per cent of the patients with diffuse proliferative nephritis and 71 per cent of the patients with membranous nephropathy. Improvement occurred in those with focal sclerosis, diffuse proliferative nephritis and membranous nephropathy only after prolonged treatment (14 to 15 months). Stable or improved renal function occurred in 97 per cent of those with lipoid nephrosis, 50 per cent of those with focal sclerosis, 73 per cent of those with diffuse proliferative nephritis and in 83 per cent of those with membranous nephropathy. Death or dialysis occurred in 12 per cent of the patients, and complications coincident with treatment occurred once every 12 patient years. Compared to other series of patients with the idiopathic nephrotic syndrome, therapy of our patients with prolonged alternate day steroids resulted in (1) decreased protein excretion, (2) maintenance of good renal function and (3) decreased number of complications of therapy.

Adolescent

Close monitoring is essential during isoniazid prophylaxis.

A three-year prospective study during the entire course of preventive therapy with isoniazid (INH) for recently infected hospital employees was undertaken to evaluate the risk of developing INH-related hepatic injury. Results of clinical and laboratory tests at 1, 2, 6, and 12 months were correlated to ascertain the significance and value of monitoring procedures. Thirty-two (32%) of 100 employees developed elevated SGOT levels: one (1%) patient developed clinical hepatitis in the first month of therapy; four (4%) subjects with SGOT elevations (82-378 units) became clinically symptomatic at one to four months and INH was discontinued; one (1%) individual with minimal increases in serum bilirubin and SGOT levels was symptomatic at eight months and the drug was stopped. Twenty-four (24%) otherwise asymptomatic subjects who developed SGOT elevations (70-480 units) were followed at closer intervals to complete INH therapy without further progression of liver function abnormality. The intervals between the beginning of treatment and the elevation of SGOT levels varied widely, with elevations occurring throughout the 12-month course of isoniazid therapy.

Adult

Catecholamine uptake, accumulation, and release in acute porphyria.

Hypertension and tachycardia are well known features of acute porphyria and have been shown to be related to increased circulating catecholamines. The mechanism by which circulating catecholamines are increased was studied using the isolated perfused rat heart and human platelets as a model of adrenergic neuronal function. It was found that neither delta-aminolevulinate (ALA) nor porphobilinogen (PBG) blocked uptake or caused release in the isolated perfused rat heart. Platelets from six patients with acute prophyria, three in remission and three latent, with matching normal controls were studied with regard to their uptake of [(3)H]norepinephrine in the presence of ALA or PBG. It was found that ALA and PBG significantly reduced uptake and accumulation of [(3)H]-norepinephrine in patients with acute porphyria; however, no similar reduction in uptake and accumulation was observed in the platelets of normal controls. Therefore, it appears that there is a latent defect in the catecholamine uptake and (or) accumulation of platelets of patients with acute prophyria which only manifests itself in the presence of ALA or PBG. If platelet uptake serves as a model of adrenergic neuron uptake, this suggests that elevated circulating catecholamine levels during acute attacks of acute porphyria are caused at least partially by blockade of re-uptake into the sympathetic neurons.

Acute Disease

Avasucular necrosis of pheochromocytoma followed by spontaneous remission.

Following an acute spontaneous hypertensive crisis and shock a patient with pheochromocytoma was found to have an exceedingly high catecholamine excretion rate. After this episode, the patient remained normotensive and urinary excretion of catecholamines returned to normal. During surgery, a large pheochromocytoma was found and removed that showed avascualr necrosis. In phenochromocytoma, a sudden and exceedingly high rate of catecholamine release may cause intense vasoconstriction both generally and within the tumor itself. In this patient, avascular tumor necrosis led to a spontaneous remission of clinical symptoms.

Adolescent