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Biomedical subjects

K M Shakir

Publications and source records attributed to K M Shakir.

At least 37 records · Page 2Linked to original sources
PubMed1993

Association of multinodular goiter with breast carcinoma: Cowden's disease.

Cowden's Disease or multiple hamartoma syndrome is an autosomal dominant genodermatosis associated with abnormalities of the breast, thyroid gland, gastrointestinal tract and genitourinary system. A large percentage of these patients have goiters or other thyroid abnormalities. Physicians should consider the diagnosis of Cowden's disease in patients presenting with thyroid disease and skin lesions such as papules or skin tags and if present these subjects should be screened for other malignancies associated with this disease.

Adult↗
PubMed1993

Autoimmune hypothyroidism in a patient with generalized resistance to thyroid hormone.

Generalized resistance to thyroid hormone is a rare condition; affected individuals have elevated serum levels of free thyroxine and free triiodothyronine with inappropriately normal or slightly elevated levels of thyrotropin, yet are generally clinically euthyroid. However, responsiveness to thyroid hormone varies from tissue to tissue, and some patients may benefit from treatment with exogenous hormone. We have described the case of a patient with this disorder who initially had a mildly elevated serum thyrotropin level and was clinically euthyroid but in whom symptomatic autoimmune hypothyroidism subsequently developed. The serum free thyroxine level, although diminished from its previously elevated value, remained within the normal range. The patient required substantial doses of levothyroxine to return basal and stimulated TSH to their prior levels. Criteria for the treatment of adults with this disorder have not been firmly established. This case suggests that one indication for thyroid hormone supplementation may be the presence of high-titer serum antithyroid antibodies in patients who initially have mildly elevated thyrotropin values; they could be at increased risk for progression to overt hypothyroidism.

Aged↗
PubMed1992

Incidental adrenal nodules: association with exaggerated 17-hydroxyprogesterone response to adrenocorticotropic hormone.

The etiology of incidentally discovered, nonfunctional adrenal nodules was evaluated by using the 17-hydroxyprogesterone (17-OHP) response to synthetic adrenocorticotrophin (cosyntropin) (ACTH) administration. Patients who were discovered to have adrenal nodules and age-matched volunteers were studied. A total of 12 patients with adrenal nodules and 10 control subjects were studied. None of the patients with adrenal nodules had any evidence of hormonal hypersecretion consistent with pheochromocytoma, Cushing's syndrome or hyperaldosteronism. All subjects had serum 17-OHP and cortisol responses measured at baseline and at 30 and 60 min following the intravenous administration of 250 micrograms of ACTH. Baseline 17-OHP levels in patients with adrenal nodules were not significantly different from those of the normal controls (adrenal nodules 17-OHP: 75 +/- 13 vs control 68 +/- 11 ng/dl). After stimulation with ACTH, both 30 min and 60 min 17-OHP levels in patients with adrenal nodules (322 +/- 47 and 361 +/- 54 ng/dl, respectively) were significantly elevated over the responses seen with the controls (169 +/- 29 ng/dl at 30 min, p < 0.015, and 158 +/- 20 ng/dl at 60 min, p < 0.004). Baseline and post-ACTH serum cortisol levels were similar in both groups. Out of these twelve patients with adrenal nodules, nine were reevaluated twelve months later. In this group the basal 17-OHP remained comparable to normal levels (72 +/- 8.4 ng/dl) whereas the post-ACTH levels still remained exaggerated (30 and 60 min values 327 +/- 37 and 373 +/- 39 ng/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1991

The significance of gastrinomas found in peripancreatic lymph nodes.

A patient with Zollinger-Ellison syndrome (ZES) was found to have a solitary, extrapancreatic, extraintestinal gastrinoma in a peripancreatic lymph node. Preoperative studies did not show the location of the tumor. After excision of the gastrinoma the patient's fasting serum gastrin level dropped from preoperative levels of 596 pg/ml to 120 pg/ml (normal, less than 200 pg/ml). Fasting and stimulated gastrin levels have remained within the normal range at 18 months follow-up. This patient had previously undergone antrectomy, so it could not be determined if this tumor represented a primary lymph node gastrinoma or metastasis from an unrecognized tumor that may have been present in the resected stomach or duodenum. The outcome of this case confirms the previous reports that ZES can be controlled after resection of gastrinomas that were contained within abdominal lymph nodes, even if a primary enteropancreatic tumor is not found. Our results also support the use of an aggressive operative search aimed at eradication of the tumor in patients with ZES even if preoperative localization studies fail to identify the site of the gastrinoma.

Adenoma, Islet Cell↗
PubMed1991

Endocrine crises. Hypoglycemia.

Hypoglycemia is defined as the occurrence of a wide variety of symptoms in association with a plasma glucose level of 40 mg/dL or less. The conditions associated with hypoglycemia in hospitalized patients include exogenous insulin administration, ethanol, drugs (especially chlorpropamide), renal insufficiency, liver disease, infections, total parenteral nutrition, treatment of hyperkalemia with insulin, extensive burns, neoplasia, pregnancy, and a wide variety of less common causes. Although clinical features are helpful in making a diagnosis, a significant proportion of the patients are either asymptomatic or present with symptoms of altered mental status. The diagnosis of hypoglycemia should be considered in all hospitalized patients presenting with adrenergic or neuroglycopenic symptoms and signs suggestive of hypoglycemia. A detailed history along with a physical examination and appropriate laboratory investigations usually identify the specific cause of the hypoglycemia. An episode of hypoglycemia, especially if severe, should be treated with prolonged intravenous infusion of glucose. Prompt recognition and management of hypoglycemia are necessary to prevent significant morbidity and mortality.

Aged↗
PubMed1990

Pheochromocytoma associated ventricular tachycardia blocked with atenolol.

Ventricular tachycardia in patients with phenochromocytoma is rare. We report a patient with a norepinephrine-secreting extra-adrenal pheochromocytoma who had exercise induced ventricular tachycardia. Prior to diagnosis, the patient was treated with a selective beta 1 blocker, atenolol, which resulted in suppression of the dysrhythmia and amelioration of the hypertension. This is the first reported case of selective beta blockade suppressing ventricular tachycardia in a patient with a pheochromocytoma. Electrocardiographic abnormalities described in patients with pheochromocytoma are reviewed.

Adrenal Gland Neoplasms↗
PubMed1990

Decreased free fraction of thyroid hormones after prolonged Antarctic residence.

We investigated the effects of Antarctic residence (AR) on serum thyroid hormone and cardiovascular responses to a 60-min standard cold air (0 degree C) test (SCAT). Serum total thyroxine (TT4) and serum total triiodothyronine (TT3), free T4 (FT4) and T3 (FT3), thyrotropin (TSH), and percent free fraction of T4 (%FT4) and T3 (%FT3) were measured in normal men (n = 15) before and after each of three SCATs. The SCAT was first carried out in California and then repeated after 24 and 44 wk AR. Mean arterial pressure (MAP) and sublingual oral temperature (Tor) were measured before and during each SCAT. The SCAT did not alter thyroid hormones before or after AR. The %FT4 decreased from 0.0334 +/- 0.0017 to 0.0295 +/- 0.0007% (P less than 0.002) with 44 wk AR but without a significant change in TT4 or FT4 for the same period. The %FT3 also decreased from 0.2812 +/- 0.0128 to 0.2458 +/- 0.0067% (P less than 0.005) after 44 wk AR. FT3 decreased (P less than 0.003) but TT3 and TSH were unchanged with 44 wk AR. The decrease in %FT4 and %FT3 may be theoretically accounted for by a 10% increase in either the capacity or the affinity of the serum binding proteins. The SCAT in California increased MAP and did not change Tor. After 44 wk AR, the SCAT no longer increased MAP but did lower Tor. The shift in the Tor and MAP response to the SCAT is consistent with the associated occurrence of cold adaptation during AR. We describe for the first time a decrease in the free fraction of both serum T3 and T4 present with extended polar residence and independent of a SCAT, further characterizing the recently reported "polar T3 syndrome."

Adaptation, Physiological↗
PubMed1990

Changes in serum triiodothyronine (T3) kinetics after prolonged Antarctic residence: the polar T3 syndrome.

Humans who live in Antarctica for greater than 5 continuous months demonstrate alterations in the hypothalamic-pituitary-thyroid axis. These changes are characterized by 1) increased pituitary release of TSH in response to iv TRH, 2) increased serum clearance of orally administered T3, and 3) normal serum total, free T4, and unstimulated TSH levels. To clarify the mechanism responsible for these findings, serum kinetic studies of 125I-labeled T4 and T3 were carried out in a group of normal men, first in California, then after 20 and 42 weeks of continuous Antarctic residence. The kinetic parameters were calculated by noncompartmental analysis. The mean T4 residence time (MRT) was not different before and after 42 weeks (5.54 +/- 0.50 and 5.08 +/- 0.43 days). The total T4 volume of distribution (TVd) tended to fall over the same period (4.30 +/- 0.12, 3.56 +/- 0.27 L/m2), but was not significantly different (P = 0.075). In contrast to T4, there was an increase from control values for the T3 MRT from 0.83 +/- 0.03 to 1.10 +/- 0.03 days (P less than 0.002) and a more than doubling of the T3 TVd from 15.55 +/- 0.52 to 47.24 +/- 5.09 L/m2 (P less than 0.002) after 42 wk of Antarctic residence. Energy intake increased approximately 40% throughout the study without a change in body weight. The changes in T3 kinetic parameters may be accounted for by increased extravascular tissue binding. The marked increase in T3 TVd and the small increase in MRT are associated with increased T3 production and clearance and only minor changes in T4 kinetics. This is the first description of a mechanism for the change in thyroid hormone economy occurring with extended residence in Antarctica.

Adult↗
PubMed1989

Phospholipase C activity in human polymorphonuclear leukocytes: partial characterization and effect of indomethacin.

Several hormones act at the cellular level to increase diacylglycerol via increased catabolism of phosphatidylinositol by phospholipase C. Diacylglycerol stimulates protein kinase C, leading to protein phosphorylation and hormone action. Since phospholipase C activity has not been well studied in man, we have established an assay for phospholipase C in human neutrophils. In this assay sonicates of neutrophils were incubated with L-3-phosphatidyl-[U 14C]-inositol and the incubation mixture extracted with chloroform/methanol. Following the additions of 2 mol/l KCl and chloroform, phospholipase C activity was determined by counting [14C] in the aqueous phase. The phospholipase C activity was linear with respect to time and the quantity of added enzyme. Optimum substrate concentration and pH were 2 mmol/l and 7.0, respectively. Optimal activity was dependent on Ca2+ (2 mmol/l) and deoxycholate (2 mmol/l). Naloxone, and PGD2, which affect various aspects of leucocyte function, had no significant effects on neutrophil PLC activity. The effects of various compounds with phospholipase A2 inhibitory activity were also tested on this enzyme. Of these, mepacrine, lidocaine and indomethacin inhibited the enzyme activity. The inhibition by indomethacin was of the noncompetitive type with an apparent Km of 0.17 X 10(-6) mol/l and apparent Ki of 3.6 X 10(-6) mol/l. From these data we conclude that indomethacin is capable of inhibiting phospholipase C activity in neutrophils at clinically significant levels and that this may be relevant in the therapeutic action of this drug.

Calcium↗
PubMed1989

Variable presentations of medullary carcinoma of the thyroid gland.

Although medullary carcinoma of the thyroid is rare, this disease generates considerable interest due to its unusual cellular origin from parafollicular C cells, ability to secrete calcitonin, and association with other endocrine adenomatosis. Pentagastrin-calcium stimulation continues to be the most valuable test for early diagnosis, in detecting recurrence of tumor, and for screening of family members. Total thyroidectomy along with central neck dissection is the treatment of choice. However, management of metastatic disease in the lateral neck remains controversial. We report three cases of medullary carcinoma of the thyroid to illustrate its various forms and the use of diagnostic tests.

Adult↗
PubMed1987

Phospholipase C activity in cultured human skin fibroblasts.

In this paper we report the detection of phospholipase C activity in cultured human skin fibroblasts by a rapid, sensitive method. Sonicates of fibroblasts were incubated with L-3-phosphatidyl-[U-14C]-inositol and the incubation mixture extracted with chloroform/methanol. The solvent components were then separated into 2 phases by the addition of 2 M KCl. Phospholipase C activity, determined from the amount of [14C] in the aqueous phase, agreed well with the enzyme activity assessed by other methods. The optimum pH for the enzyme was 7.0 and the enzyme was found to be dependent on Ca2+ and deoxycholate for optimal activity. The demonstration of phospholipase C activity by this method in cultured skin fibroblasts provides a useful means with which to study, in human tissues, the physiological control of this enzyme and its derangements in disease states in a controlled fashion.

Calcium↗
PubMed1986

Alterations in the hypothalamic-pituitary-thyroid axis after prolonged residence in Antarctica.

The human population which lives and works in polar environments has been increasing steadily over the last 15 years. Very little is known about how these residents adjust to their environment. Cold adaptation in man is a poorly understood phenomenon. Euthermic mammals maintain body temperature during cold exposure via non-shivering thermogenesis, a process which is hormonally mediated. We studied prospectively the response of the hypothalamic-pituitary-thyroid axis in 17 euthyroid men before, during and after assignment to duty in the Antarctic. Serum total and free T4 levels fell slightly but not significantly after very prolonged Antarctic residence. Serum total and free T3 decreased significantly from basal levels of 170 +/- 3 ng/dl and 388 +/- 19 pg/dl to 155 +/- 5 ng/dl and 319 +/- 14 pg/dl respectively after Antarctic duty. Serum T3 levels increased after 42 weeks of polar living, the end of the observation period, but the change did not attain statistical significance. The integrated TSH response to TRH administration increased by 50% to 734 +/- 58 microIU.min/ml over warm climate basal response levels of 456 +/- 33 microIU.min/ml by the end of the study. The daily circadian rhythm of serum cortisol was maintained throughout the study period. The alterations in thyroid hormones which we describe, are apparently related to the chronic cold exposure which our subjects experienced in this polar environment.

Adult↗
PubMed1986

Decreased phospholipase A2 activity in plasma and liver in uncontrolled diabetes mellitus. A defect in the early steps of prostaglandin synthesis?

Arachidonic acid metabolites and prostaglandins participate in numerous physiologic functions. An enzyme important in the control of prostaglandin production is phospholipase A2. In this study, we have investigated the changes in plasma and hepatic phospholipase A2 activity in diabetes mellitus. In uncontrolled diabetic patients, the postheparin plasma phospholipase A2 level was 18.7 +/- 4.1 U/ml; this value was significantly different from the enzyme activities in control subjects (106 +/- 9.8 U/ml) and in controlled diabetic patients (87 +/- 7.3 U/ml). In the streptozocin-induced diabetic rat model, the postheparin plasma phospholipase A2 level (1.9 +/- 0.45 U/ml) was also decreased when compared with normal (9.4 +/- 1.6 U/ml) and controlled diabetic rats (7.0 +/- 1.3 U/ml). The total hepatic enzyme activity in the uncontrolled diabetic rats was only 21.6% of that seen in control rats. Subcellular fraction studies demonstrated that the enzyme activity is decreased in all fractions in the liver. Liver perfusion studies showed that the heparin-releasable phospholipase A2 activity in the perfusate was significantly decreased in the diabetic rats when compared with control and controlled diabetic animals. We conclude that postheparin plasma and hepatic phospholipase A2 activities are decreased in uncontrolled diabetes mellitus, that the low plasma activity is related to decreased release from the liver, and that the alterations in phospholipase A2 activity in plasma and liver are restored to normal by controlling the diabetic status.

Adult↗
PubMed1985

Enhanced phospholipase A2 activity in rat plasma, liver, and intestinal mucosa following endotoxin treatment: a possible explanation for the protective effect of indomethacin in endotoxic shock.

Endotoxin administration in rats produced a significant increase in plasma, hepatic, and intestinal phospholipase A2 activity within three minutes after injection. The elevated phospholipase A2 activity seen in these tissues returned to normal levels six minutes after injection. The changes in phospholipase A2 activity were dose-dependent within the 0, 10, and 20 mg/kg range of treatment with Escherichia coli endotoxin. This increase in plasma, hepatic, and intestinal phospholipase A2 was abolished by prior treatment of the rats with 3 mg/kg indomethacin, a drug known to improve survival in endotoxic shock. The fact that the change in phospholipase A2 occurs soon after endotoxin administration and that the change in phospholipase is blocked by protective doses of indomethacin suggests that phospholipase A2 activation may be an important initial event in the lethal action of endotoxin, and that the protective effects of indomethacin may be directly related to inhibition of phospholipase A2 activity. Further, in vitro studies of the effects of indomethacin on hepatic phospholipase A2 activity showed that indomethacin significantly inhibited this enzyme. Indomethacin (25 mumol/L) produced 56% inhibition in phospholipase A2 activity and the apparent Ki for indomethacin was 9.2 mumol/L. Kinetic analysis using the Lineweaver-Burk method showed that the indomethacin inhibition was of the noncompetitive type.

Animals↗