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Biomedical subjects

J M Falko

Publications and source records attributed to J M Falko.

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

Combination insulin/glyburide therapy in type II diabetes mellitus. Effects on lipoprotein metabolism and glucoregulation.

A randomized double-blind, placebo-controlled trial of insulin plus glyburide was carried out in 22 insulin-treated patients with poorly controlled type II diabetes mellitus. Glycemic control and lipoprotein responses were assessed for 16 weeks. Oral glucose tolerance testing was performed at weeks 0, 4, and 16. Clinical characteristics and glycemic control were similar at week 0 in the placebo/insulin group (n = 12) and the glyburide/insulin group (n = 10). Throughout the study, the dose of insulin was fixed. The placebo group had no change in any metabolic parameter throughout the protocol period. After four weeks, glyburide significantly lowered fasting blood glucose and integrated glucose areas (p less than 0.01) after oral glucose testing compared with week 0 (fasting blood glucose 225 +/- 20 mg/dl versus 286 +/- 27 mg/dl, p less than 0.02). Associated with this were mean fasting, stimulated, and integrated C-peptide levels that were significantly higher (p less than 0.02) at week 4 versus week 0. After 16 weeks, mean fasting blood glucose remained significantly lower compared with baseline values (252 +/- 25 mg/dl versus 286 +/- 27 mg/dl, p less than 0.05). Glycosylated hemoglobin (hemoglobin A1c) levels decreased significantly (p less than 0.05) at weeks 4 to 16 compared with the baseline value. Although integrated areas were no different after oral glucose, fasting and stimulated C-peptide levels were significantly higher (p less than 0.05) at week 16 versus week 0. Total cholesterol, triglycerides, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol did not change during the study. After the code was broken, comparisons were made between those with response to combination therapy (reduction of fasting blood glucose by at least 50 mg/dl or fasting blood glucose of 140 mg/dl or less at the end of the first week of treatment that persisted for four consecutive weeks) and those without response. Baseline clinical and laboratory characteristics were identical in both groups. Mean fasting and stimulated serum C-peptide levels after oral glucose, however, were significantly higher in the patients with response at week 4 compared with the patients without response. The mean maximal incremental C-peptide level was 1.50 +/- 0.19 ng/ml at week 0 in the patients with response compared with 0.67 +/- 0.28 ng/ml in the patients without response (p less than 0.01). Lipoproteins were not different in the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗
PubMed1985

Serum C-peptide levels determine glycemic responses in type II diabetic patients treated with combined insulin and sulfonylurea agent.

Type II diabetes mellitus is a heterogeneous disease. Selection of either insulin or a sulfonylurea agent in addition to diet is usually made empirically. In patients who fail to respond to either agent alone, the potential benefit of combined insulin and sulfonylurea therapy is unclear. We therefore evaluated nine poorly controlled insulin treated type II diabetic patients after addition of a sulfonylurea agent--glyburide--for four weeks. Glycosylated hemoglobin (HbA1c), serum glucose, and C-peptide responses to oral glucose were evaluated. Based on a reduction of at least 50 mg/dl in the fasting serum glucose (FSG) at the end of the first week of the combination therapy or a FSG of less than 140 mg/dl, two groups were arbitrarily identified: responders (n = 5) and nonresponders (n = 4). Clinical characteristics including mean age, weight, duration of diabetes, daily dose of insulin, and duration of insulin treatment were not statistically different between the two groups. Mean baseline FSG and HbA1c levels were also not statistically different in both groups. An improvement in mean FSG and glucose tolerance occurred in the responders at the end of four weeks of combined therapy (FSG: 291 +/- 25 vs. 189 +/- 6 mg/dl, p less than 0.05; HbA1c 10.76 +/- 0.80 vs. 9.40 +/- 0.21%, p = NS). The nonresponders had no change in glucose tolerance. The mean fasting and stimulated serum C-peptide levels were significantly higher in the responders at week 4 compared with that of the nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Concomitant insulin and sulfonylurea therapy in patients with type II diabetes. Effects on glucoregulation and lipid metabolism.

Recent evidence suggests concomitant insulin and sulfonylurea therapy has a theoretical potential in the management of type II diabetes mellitus. In a long-term double-blind, randomized placebo-controlled study of combination therapy, serum glucose, C-peptide, total cholesterol, triglyceride, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations were evaluated in insulin-treated patients with poorly controlled, type II diabetes mellitus after addition of either glyburide (n = 10) or placebo (n = 12). Oral glucose tolerance testing was performed at weeks 0, 4, and 16. Clinical characteristics and glycemic control (fasting blood glucose and glycosylated hemoglobin values) were similar at week 0 in both groups. The placebo group had no change in any metabolic parameter throughout the study period. At week 4, glyburide significantly lowered fasting blood glucose and integrated glucose areas (p less than 0.01) compared with values at week 0 (fasting blood glucose 225 +/- 20 versus 286 +/- 27 mg/dl, p less than 0.02). Mean fasting, stimulated, and integrated C-peptide levels were significantly higher (p less than 0.02) at week 4 versus week 0. At week 16, mean fasting blood glucose values remained significantly lower compared with baseline values (252 +/- 25 versus 286 +/- 27 mg/dl, p less than 0.05). Glycosylated hemoglobin levels decreased significantly (p less than 0.05) at weeks 4 to 16 compared with the baseline values. Although glucose responses and integrated areas were no different after oral glucose tolerance testing, fasting and stimulated C-peptide levels were significantly higher (p less than 0.05) at week 16 versus week 0. Lipid and lipoprotein levels remained unchanged. In summary, combination therapy consisting of glyburide and insulin moderately improved glucose control in type II diabetes mellitus at the end of four weeks. Despite significantly lower fasting serum glucose and glycosylated hemoglobin levels after 16 weeks, combination treatment did not normalize glycemic control. Glucose tolerance decreased further after 16 weeks despite persistence of increased endogenous insulin secretion. The role of the combination therapy in the long-term care of patients with type II diabetes mellitus needs further investigation.

Aged↗
PubMed1984

Diabetogenic effect of pentamidine. In vitro and in vivo studies in a patient with malignant insulinoma.

Pentamidine can cause hypoglycemia followed by hyperglycemia. The mechanism of this biphasic response is not known but has been reported to be similar to that of streptozotocin and N-3-pyridyl-N-p- nitrourea (Vacor). Pentamidine (4 mg/kg per day for 12 days) was used in a patient with malignant insulinoma after several unsuccessful debulking procedures and chlorozotocin therapy. Mean glucose and immunoreactive insulin levels (+/- SEM) before and after therapy were 80 +/- 40 mg/dl versus 70 +/- 50 mg/dl and 216 +/- 12 microU/ml versus 198 +/- 22 microU/ml, respectively. These were not significantly different. The patient's five-month-old malignant insulinoma monolayer cell culture was incubated with pentamidine (60 micrograms/ml) in the presence or absence of supplemented stimulatory medium consisting of glucose (300 mg/dl) and theophylline (20 micrograms/ml). Chloroquine (60 micrograms/ml) was added to inhibit lysosomal degradation of immunoreactive insulin. Aliquots of media for immunoreactive insulin determination were obtained at 30 minutes, 20 hours, 72 hours, and three weeks. The cells were examined by high-power light microscopy at each time interval. At 30 minutes, pentamidine alone caused passive release of immunoreactive insulin, 23 percent higher than control (p less than 0.01). Stimulatory medium increased immunoreactive insulin 45 percent greater than control (p less than 0.01). Pentamidine plus stimulatory medium had no additive effect on immunoreactive insulin released within 30 minutes. At the end of 20 hours, immunoreactive insulin was no different with pentamidine and/or stimulatory medium. However, the addition of chloroquine increased immunoreactive insulin by 35 percent above the medium with pentamidine and stimulatory medium (p less than 0.01). At 72 hours, pentamidine suppressed immunoreactive insulin by 100 percent in all the media, irrespective of the presence or absence of stimulatory medium and/or chloroquine. At the end of three weeks, there was 50 percent suppression of immunoreactive insulin in the control medium, but pentamidine again completely suppressed immunoreactive insulin. High-power microscopy demonstrated intact cells in the control medium, whereas no cell structure could be detected in the media containing pentamidine at three weeks. In summary, pentamidine had no acute in vivo effect in a patient with malignant insulinoma. However, when used in an in vitro monolayer system, pentamidine caused (1) acute immunoreactive insulin release followed by inhibition of immunoreactive insulin secretion and (2) cytolysis of human malignant insulinoma cells in vitro.

Adenoma, Islet Cell↗
PubMed1984

Pregnancy complicated by insulinoma.

Gestational hypoglycemia may result from either reactive hypoglycemia or complications related to the pregnancy. We report a 19-year-old pregnant patient with insulinoma who was treated successfully by distal pancreatectomy during the first trimester. A high index of suspicion was required for the diagnosis since abnormal immunoreactive insulin (IRI) and glucose (G) ratios (I/G) greater than 0.3 can be found in non-insulinoma normal pregnancy. The incidence of insulinoma complicating pregnancy is unknown, but it is important since gestational hypoglycemia can be associated with an increased perinatal mortality and morbidity similar to that of gestational hyperglycemia.

Abortion, Induced↗
PubMed1984

Solitary cold thyroid nodule: cost-ineffectiveness of ultrasonography.

We reviewed our experience with thyroid sonography of 60 patients with nonfunctioning (cold) solitary thyroid nodules proven by iodine 123 scan. Twenty-two patients had surgery; the remaining 38 had thyroid scan and ultrasound only. In the first group, the echograms did not demonstrate the surgically proven nodules in seven patients (32%). In the second group, the thyroid echograms were reported as negative in 12 patients (32%). Two of these patients had computerized tomography (CT) which confirmed the solitary nodule identified on the 123I scan. As a consequence, we no longer perform or recommend routine thyroid echograms on all scintigraphically cold solitary nodules. We believe that the extra cost of a thyroid echogram is not justified and that the most rational application of thyroid ultrasonography is in assessing the response of a nodule to suppressive hormonal therapy.

Cost-Benefit Analysis↗
PubMed1984

Serum lipids and lipoprotein composition in spontaneously diabetic BB Wistar rats.

Serum lipid and lipoprotein composition in spontaneously diabetic BB Wistar rats, nondiabetic littermates, and control Wistar rats was studied to elucidate diabetes-related abnormalities of lipoprotein composition. Serum total triglycerides and pre-beta-lipoprotein concentrations of insulin-treated spontaneously diabetic BB and nondiabetic littermate rats were significantly higher than those of control Wistar rats. Serum cholesterol and HDL cholesterol concentrations of spontaneously diabetic BB and nondiabetic littermate rats did not differ from controls. Concentrations of very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) of spontaneously diabetic BB and nondiabetic littermate rats were higher than those of normal rats. With sodium dodecylsulfate-polyacrylamide gel electrophoresis it was observed that the spontaneously diabetic BB and nondiabetic littermate rat VLDL contained higher percentages of apoE relative to total apoC when compared with control Wistar rats. With isoelectric focusing, apoC-II relative percentages in VLDL and HDL of both spontaneously diabetic BB and nondiabetic littermate rats were higher than apoC-II proportions in VLDL and HDL of controls. Apolipoprotein A-I of the control rat HDL showed four isoforms that focused at pI 5.8 (17.3%), 5.75 (30.6%), 5.65 (31.8%), and 5.55 (20.5%); however, the spontaneously diabetic BB and nondiabetic littermate rat HDL apoA-I was mainly represented by two isoforms that focused at pI 5.8 and 5.75. VLDL of both diabetic and nondiabetic BB rats contained higher levels of acidic apoE isoforms compared to their counterparts in control Wistar rats. Although HDL cholesterol concentrations of spontaneously diabetic BB rats remained normal, protein concentrations were higher resulting in a low cholesterol/protein ratio in HDL suggesting that the cholesterol-carrying capacity of spontaneously diabetic BB rat HDL could be less than normal and may be due to an abnormal apoA-I composition. Quantitative alterations of lipid and lipoprotein composition appear in the BB Wistar rat when compared to the Wistar rat, but some of the changes are more pronounced in the spontaneously diabetic BB Wistar rat.

Animals↗
PubMed1983

Hypertensive crisis induced by eating in a patient with pheochromocytoma.

Catecholamines have an important effect on the gastrointestinal tract. Patients with pheochromocytomas frequently have gastrointestinal complaints. We report a 13-year-old girl with a 250-g intra-abdominal pheochromocytoma who presented with symptoms of excessive catecholamines release and hypertensive crisis that was provoked by eating. The patient's pheochromocytoma was so large that it was palpable and compressing the greater curvature of the stomach.

Adolescent↗
PubMed1983

Primary adrenal insufficiency manifesting as malignant lymphoma.

Primary adrenal insufficiency associated with a hematologic malignant neoplasm is a rare entity. Most malignant neoplasms with metastases to the adrenal gland are secondary to solid carcinomas of the lung and breast. A 55-year-old man was seen with clinical and biochemical evidence of primary adrenal insufficiency as the initial manifestation of his malignant lymphoma. At autopsy the architecture of both adrenal glands was completely effaced by malignant plasmacytoid cells. This case emphasizes that infiltrative lymphoma of the abdomen is a rare cause of primary adrenal insufficiency and may be the initial manifestation. Furthermore, it should be included in the differential diagnosis.

Adrenal Gland Diseases↗
PubMed1982

Improvement of high-density lipoprotein-cholesterol levels. Ambulatory type I diabetics treated with the subcutaneous insulin pump.

Twelve ambulatory patients (six women and six men; mean age, 29 years) with type I diabetes were treated with a continuous subcutaneous open-loop insulin pump in an attempt to effect better glucose control. Hemoglobin A1, mean blood glucose, total cholesterol, total triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and the cholesterol/HDL-C ratio were assessed monthly before and after glucoregulation from five to 14 months (mean, nine months). Mean HDL-C levels increased significantly (52 +/- 4 to 60 +/- 5 mg/dL); mean cholesterol/HDL-C ratios decreased significantly (4.46 +/- 0.43 to 3.89 +/- 0.39). Mean values for triglycerides, total cholesterol, and LDL-C, all initially normal, did not change. Both mean Hb A1 levels and glucose levels fell from 11.2% +/- 0.5% to 9.8% +/- 0.5% and 177 +/- 15 mg/dL to 128 +/- 12 mg/dL, respectively. Insulin requirements decreased from 0.80 +/- 0.08 to 0.61 +/- 0.05 units/kg/24 hr. These results may favorably alter the prediction for development of accelerated atherosclerosis in type I diabetics.

Adolescent↗
PubMed1982

Pseudomonas aeruginosa sepsis following retrograde cholangiopancreatography (ERCP).

Endoscopic retrograde cholangiopancreatography (ERCP) has become a routine examination in a number of medical centers within the past several years. We report a life-threatening case of acute pancreatitis with Pseudomonas aeruginosa sepsis immediately following ERCP. Cultures of the blood, the inner channel of the duodenoscope, and irrigating water bottles all were positive for Pseudomonas aeruginosa. The Pseudomonas aeruginosa isolated from the blood and endoscope both reacted to three common antisera: serotypes 2, 15, and 16, suggesting a common source of infection. Although it is obvious that the ERCP procedure cannot be sterile, attempts should be made to prevent transmission of nosocomial pathogens by this procedure.

Acute Disease↗
PubMed1982

"Pseudo" renal failure after isopropyl alcohol intoxication.

We have described a case of isopropyl alcohol intoxication with the confusing picture of normoglycemia and ketonuria, without evidence of metabolic acidosis. The patient also had a spurious elevation of serum creatinine caused by the high acetone level. The positive ketone test was secondary to high levels of acetone, the main metabolic product of isopropyl alcohol. This is the first case of isopropyl alcohol ingestion in which "pseudo" renal failure has been described.

1-Propanol↗