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Biomedical subjects

J Jacobs

Publications and source records attributed to J Jacobs.

At least 91 records · Page 5Linked to original sources
PubMed1995

Paradoxical insulin-induced increase in gluconeogenesis in response to prolonged hypoglycemia in conscious dogs.

The aim of this study was to determine the effects of differing insulin concentrations on the gluconeogenic response to equivalent prolonged hypoglycemia. Insulin was infused intraportally, for 3 h, into normal 18-h fasted conscious dogs at 2 (lower, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady-state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during high dose to maintain the hypoglycemic plateau (50 +/- 1 mg/dl) equivalent to lower. Epinephrine (806 +/- 180 vs. 2,589 +/- 260 pg/ml), norepinephrine (303 +/- 55 vs. 535 +/- 60 pg/ml), cortisol (5.8 +/- 1.2 vs. 12.1 +/- 1.5 micrograms/dl), and pancreatic polypeptide (598 +/- 250 vs. 1,198 +/- 150 pg/ml) were all increased (P < 0.05) in the presence of high-dose insulin. Net hepatic glucose production increased significantly from 2.2 +/- 0.3 to 3.8 +/- 0.5 mg.kg-1.min-1 (P < 0.05) during high-dose infusion but remained at basal levels (2.3 +/- 0.4 mg.kg-1.min-1) during lower-dose insulin. During the 3rd h of hypoglycemia, gluconeogenesis accounted for between 42 and 100% of glucose production during high-dose infusion but only 22-52% during lower-dose insulin. Intrahepatic gluconeogenic efficiency, however, increased similarly during both protocols. Lipolysis, as indicated by arterial blood glycerol levels, increased by a greater amount during high- compared with lower-dose insulin infusion. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. Gluconeogenesis remained similar to basal levels, but lipolysis was significantly suppressed during both series of hyperinsulinemic euglycemic studies. In summary, these data suggest that 1) the important counterregulatory processes of gluconeogenesis and lipolysis can be significantly increased during prolonged hypoglycemia despite an eightfold increase in circulating insulin levels and 2) the amplified gluconeogenic rate present during the hypoglycemic high-dose insulin infusions was caused by enhanced substrate delivery to the liver rather than an increase in intrahepatic gluconeogenic efficiency.

Animals↗
PubMed1995

Impact of infection on hepatic disposal of a peripheral glucose infusion in the conscious dog.

The effect of infection on hepatic uptake and disposal of a continuous (180-min) intravenous glucose infusion (8 mg.kg-1.min-1) was examined in conscious, 54-h-fasted, chronically catheterized dogs. Thirty-six hours before a study, either infection was induced by implantation of an Escherichia coli-containing (INF; 2 x 10(9) organisms/kg body wt; n = 6) fibrinogen clot, or a sterile (SH; n = 6) clot was implanted into the peritoneal cavity. Hepatic glucose metabolism was assessed using tracer ([3-3H]glucose and [U-14C]glucose) and arteriovenous difference techniques. Infection increased the basal rate of glucose appearance (45%); glucose levels were not altered. In response to glucose infusion, average blood glucose levels increased to similar levels (140 +/- 9 vs. 147 +/- 11 mg/dl in INF and SH, respectively), whereas arterial insulin levels were higher in the infected group during the last hour of the glucose infusion (77 +/- 10 vs. 41 +/- 5 microU/ml in INF vs. SH). Infection impaired net hepatic glucose uptake (0.6 +/- 0.5 and 2.7 +/- 0.7 mg.kg-1.min-1 in INF and SH; P < 0.05). The liver remained a persistent lactate consumer (4.1 +/- 1.8 mumol.kg-1.min-1), whereas the sham group became a net producer of lactate (-3.8 +/- 1.3 mumol.kg-1.min-1). Infection decreased net hepatic glycogen deposition by 53%. In conclusion, infection impairs net hepatic glucose uptake and glycogen deposition despite an exaggerated increase in insulin levels.

Animals↗
PubMed1995

Metastatic basal cell carcinoma of the head and neck.

Metastases are occasionally associated with cutaneous squamous cell carcinoma but only rarely with basal cell carcinoma. There are approximately 200 cases of metastases from basal cell carcinoma reported in the world literature. We describe 6 additional cases. All of our patients demonstrated recurrence at the primary site before they developed their metastases. Metastases presented in subcutaneous tissue, cervical lymph nodes, bone, and lung between 1.5 and 14 years after initial treatment of the primary lesion. The long interval seen in these patients between the initial treatment of the primary and the development of metastases underscores the need for long-term follow-up in what is often thought to be a nonaggressive, nonmetastasizing malignancy.

Aged↗
PubMed1994

The effect of perioperative blood transfusion on survival in head and neck cancer.

This Head and Neck Intergroup analysis was undertaken to evaluate further previously reported observations linking blood transfusions, which were given to patients with head and neck cancer, to a worse prognosis. This study population represents those patients registered to the Head and Neck Intergroup Trial 0034 for previously untreated resectable squamous cell carcinoma. Additional transfusion data were obtained by one of us (D.E.S.) on 217 patients and added to the Head and Neck Intergroup data set, providing an opportunity for assessing the impact of survival by other variables. The study group was separated using 13 variables. Analysis demonstrated that transfusion did not significantly decrease the locoregional control (P = .60). Multivariate analysis indicated that T stage (P = .015), N stage (P = .004), treatment received (P = .004), and Karnofsky Performance Scale (P = .031) were the only factors that did significantly influence survival. This multivariate analysis controlling for these variables demonstrated no significant effect on survival for those patients receiving transfusion during surgery (P = .55) or after surgery (P = .39). This study of 217 patients, controlled for other variables, does not demonstrate any significant negative relation between blood transfusions and either locoregional control or survival.

Activities of Daily Living↗
PubMed1994

Growth and protein status of term infants fed soy protein formulas differing in protein content.

OBJECTIVE: The purpose of this study was to compare growth and protein status of healthy term infants from 2 to 112 days of age fed a commercially available soy-based formula (IS) and a similar formula (EF) containing less protein (2.91 vs 2.45 g/100 kcal). DESIGN: A controlled, randomized, blind parallel clinical trial was conducted in 32 male and 32 female infants. Infants were enrolled at 2 days of age, and their assigned formula was their only feeding to 112 days of age. At this time their weight, length, and head circumference were measured. Weight, length, and head circumference were measured and formula intake, formula intolerance and stool characteristics were recorded at 8, 28, 56, and 112 days of age. Plasma urea nitrogen (PUN), total protein, albumin, and transthyretin were determined at 56 and 112 days. RESULTS: There were no statistically significant differences in weight, length, head circumference, or gains in these measures. PUN concentration was significantly lower in infants fed EF than IS at 56 and 112 days. Plasma total protein, albumin, and transthyretin concentrations were not different between the two feeding groups at the two testing periods. Tolerance to the two formulas was similar. Stool characteristics did not differ between the two groups. CONCLUSION: A soy-based formula containing 2.45 g protein/100 kcal and approximately 640 mumol of total sulfur containing amino acids/100 kcal adequately meets the protein needs of term infants from 2 to 112 days of age.

Anthropometry↗
PubMed1994

Pure motor demyelinating neuropathy: deterioration after steroid treatment and improvement with intravenous immunoglobulin.

Within one month of starting oral prednisolone treatment weakness unexpectedly increased in four patients aged 34 to 75 years with purely motor forms of acquired chronic demyelinating neuropathy. By contrast, steroids produced the expected improvement in 11 other patients with symmetric sensorimotor chronic inflammatory demyelinating polyneuropathy. Two of the patients with purely motor demyelinating neuropathy were subsequently treated with high dose IVIg (0.4 g/kg/day for five days) with prompt improvements in strength measurements and motor nerve conduction. Thus IVIg seems to be the treatment of choice and steroids should be used with extreme caution, if at all, in patients with purely motor forms of acquired demyelinating polyneuropathy.

Adolescent↗
PubMed1994

Asthma in Gaza refugee camp children and its relationship with house dust mites.

Three hundred asthmatic children aged 3 to 15 years, and 100 age-sex-neighborhood matched controls, were studied for environmental risk factors for asthma during 1986 to 1987. In 98% of the asthmatic patients, exposure to house dust aggravated the symptoms. In 97% of the cases, the symptoms were more severe at home; in more than 50%, the symptoms persisted throughout the year. Significantly more cigarettes were smoked in the homes of the allergic children than in the control homes. House dust samples from homes of 20 asthmatic and 20 nonasthmatic children were examined for the presence of house dust mites. Twelve species of mites were identified, of which Dermatophagoides pteronyssinus, the most prevalent (97%), was found in all samples examined. The average number of mites per gram dust was 447 in homes of children with asthma, and 399 in homes of controls. Although dust and mites seem to be the most important factors causing allergies in Gaza and most of the children are exposed to large numbers of mites in their homes, it appears that those who are genetically predisposed and who are exposed to environmental tobacco smoke are at greater risk for allergic symptoms.

Adolescent↗
PubMed1994

Treatment of acute childhood diarrhea with homeopathic medicine: a randomized clinical trial in Nicaragua.

OBJECTIVE: Acute diarrhea is the leading cause of pediatric morbidity and mortality worldwide. Oral rehydration treatment can prevent death from dehydration, but does not reduce the duration of individual episodes. Homeopathic treatment for acute diarrhea is used in many parts of the world. This study was performed to determine whether homeopathy is useful in the treatment of acute childhood diarrhea. METHODOLOGY: A randomized double-blind clinical trial comparing homeopathic medicine with placebo in the treatment of acute childhood diarrhea was conducted in León, Nicaragua, in July 1991. Eighty-one children aged 6 months to 5 years of age were included in the study. An individualized homeopathic medicine was prescribed for each child and daily follow-up was performed for 5 days. Standard treatment with oral rehydration treatment was also given. RESULTS: The treatment group had a statistically significant (P < .05) decrease in duration of diarrhea, defined as the number of days until there were less than three unformed stools daily for 2 consecutive days. There was also a significant difference (P < .05) in the number of stools per day between the two groups after 72 hours of treatment. CONCLUSIONS: The statistically significant decrease in the duration of diarrhea in the treatment group suggests that homeopathic treatment might be useful in acute childhood diarrhea. Further study of this treatment deserves consideration.

Acute Disease↗
PubMed1993

Autoimmunity in depression: increased antiphospholipid autoantibodies.

Some groups have recently reported higher titers of autoantibodies in depressed subjects than in normal controls. The present study investigates whether depressed patients exhibit increased antiphospholipid antibody titers compared with normal controls. The authors measured the binding index (BI) of antiphosphatidylserine (APSA), antipartial thromboplastin (APTA) and anticardiolipin (ACA) in 22 minor, 23 simple major and 20 melancholic depressives, 10 healthy controls and 104 normal controls with negative autoantibody sera. Depressed subjects exhibited significantly higher APSA and APTA antibody titers compared with normal controls. A large number of depressed subjects (+/- 54%) showed APTA and APSA positivity, defined as BI > or = 2 standard deviations above the mean BI of normal controls. There was a significant discrimination (> or = 2.8 standard deviations) between melancholic subjects and healthy controls with respect to BI of ACA, APSA and APTA. However, by using a more conservative value for phospholipid positivity (i.e., BI > or = 5 standard deviations above the mean BI of a reference sample of normal sera), the subject's autoantibody titers were, on the whole, within the normal range. Our results point towards a higher expression of antiphospholipid antibodies during depression but a much lower incidence of positive patients than in classical autoimmune disorders, such as systemic lupus erythematosus.

Adult↗
PubMed1993

Effects of hyperinsulinemia on the subsequent hormonal response to hypoglycemia in conscious dogs.

The aim of this study was to determine if differing periods of prior hyperinsulinemic nonhypoglycemia can modify the subsequent counterregulatory response to hypoglycemia. Experiments were carried out on 19 normal 18-h fasted conscious dogs. Insulin was infused intraportally at 8 mU.kg-1.min-1 for 3 h on two occasions and 3.5 h on a third separate occasion. This resulted in similar steady-state arterial insulin levels during each protocol (4,370 +/- 433 pmol/l). Each animal was maintained at a similar plasma glucose nadir (2.8 +/- 0.6 mmol/l) for 2 or 2.5h, depending on the protocol. In protocol I (n = 7) plasma glucose was allowed to fall to the desired hypoglycemic plateau by 30 min. In a second group of dogs (protocol II, n = 5) there was a 30-min period of euglycemic hyperinsulinemia followed by a 30-min fall (similar to protocol I) in plasma glucose. In a third group of dogs (protocol III, n = 7), there was an initial 15-min period of euglycemic hyperinsulinemia followed by a 45-min fall in plasma glucose. Differing periods of euglycemic hyperinsulinemia had distinct effects on subsequent counterregulation. During the final 2 h of hypoglycemia the incremental area under the curve (AUC) for glucagon was significantly greater in protocol I vs. II (3.0 +/- 1.0, -0.5 +/- 0.2 micrograms.l-1.min-1, P < 0.02, respectively). Conversely, catecholamine levels were increased in protocol II (30 min prior hyperinsulinemic euglycemia) compared with protocol I (epinephrine 1,448 +/- 268, 855 +/- 119 nmol.l-1.min-1; norepinephrine 244 +/- 30, 166 +/- 23 nmol.l-1.min-1, respectively, P < 0.05). During protocol III, glucagon and catecholamine levels were intermediate between protocols I (no euglycemic hyperinsulinemia) and II (30 min euglycemic hyperinsulinemia).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of insulin on the counterregulatory response to equivalent hypoglycemia in normal females.

The aim of this study was to determine if insulin could augment the counterregulatory response to equivalent hypoglycemia in normal females similarly to males. Experiments were carried out in nine normal lean overnight-fasted female subjects. Insulin was infused in two separate randomized protocols so that steady-state levels of 794 +/- 62 (low) and 3,620 +/- 476 pM (high) were obtained. Despite an identical plasma glucose level (2.8 +/- 0.1 mM), epinephrine (5.7 +/- 0.9 vs. 3.9 +/- 0.6 nM), norepinephrine (2.7 +/- 0.4 vs. 1.8 +/- 0.3 nM), cortisol (918 +/- 55 vs. 826 nM), and growth hormone (35.8 +/- 3.7 vs. 28.4 +/- 2.7 micrograms/l) were increased (P < 0.05) during high compared with low insulin infusion, respectively. Glucagon and pancreatic polypeptide levels increased significantly but were not different during the two insulin infusions. Hepatic glucose production was increased during the high-compared with low-dose infusions (9.5 +/- 1.1 vs. 5.1 +/- 2.2 mumol.kg-1 x min-1; P < 0.05). Lipolysis, as indicated by the blood glycerol level, increased significantly during high- compared with low-dose insulin infusions (121 +/- 29 vs. 65 +/- 13 microM; P < 0.05). The hormonal and metabolic responses to hypoglycemia were significantly different in females compared with previous results in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The effects of insulin on the counterregulatory response to equivalent hypoglycemia in patients with insulin-dependent diabetes mellitus.

We previously demonstrated that hyperinsulinemia can amplify the counterregulatory response to hypoglycemia in normal subjects. The aim of the present study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent fixed hypoglycemia in insulin-dependent-diabetic subjects (IDDM). Experiments were carried out in seven lean, overnight-fasted, moderately controlled (hemoglobin A1c, 10.9%; normal range, 5-9) IDDM subjects with a disease duration of 13 +/- 3 yr. All were maintained normoglycemic overnight so that basal plasma glucose (5.6 +/- 0.2 and 5.4 +/- 0.2 mmol/L) and insulinemia (63 +/- 18 and 48 +/- 10 pmol/L) were similar at the start of each study. Insulin was infused for 120 min in two separate randomized protocols, so that steady state levels (mean +/- SE) of 742 +/- 212 pmol/L (low) and 3360 +/- 710 pmol/L (high) were obtained. Glucose was infused during both protocols to ensure that the rate of fall of plasma glucose (0.09 mmol/L.min) and the hypoglycemic plateau (2.8 +/- 0.1 mmol/L) were similar. In response to hypoglycemia, plasma levels of epinephrine, norepinephrine, cortisol, GH, and pancreatic polypeptide increased similarly during both insulin infusions. During the final 30 min, despite similar levels of counterregulatory hormones, hepatic glucose production was significantly reduced in the presence of high compared to low insulin levels (1.7 +/- 2.8 vs. 8.3 +/- 1.7 mumol/kg.min; P < 0.05). Similarly, plasma nonesterified fatty acids (472 +/- 94 vs. 787 +/- 105 mumol/L) and blood 3-hydroxybutyrate levels (30 +/- 12 vs. 106 +/- 29 mumol/L) were significantly reduced (P < 0.05) during high compared to low dose infusions. Cardiovascular parameters (heart rate and systolic, diastolic, and mean arterial pressures) responded similarly during both infusions. We conclude that 1) insulin per se does not amplify the counterregulatory response to equivalent hypoglycemia in individuals with moderately controlled, long duration IDDM; and 2) there may be a relative autonomic adrenomedullary deficit in some IDDM subjects that prevents the amplified epinephrine response to hyperinsulinemia during hypoglycemia.

Adult↗
PubMed1993

Cost effectiveness of beractant in the prevention of respiratory distress syndrome.

Beractant, a modified natural bovine surfactant extract, has been used successfully in the prevention of respiratory distress syndrome (RDS) in premature neonates. This analysis investigates the cost effectiveness of prophylactic surfactant therapy. Resource utilisation data were analysed retrospectively from 210 patients who had participated previously in a double-blind, placebo-controlled clinical trial. No baseline differences were apparent between the beractant and sham-air control groups. There was a significant difference in survival favouring the beractant-treated neonates. When the acquisition cost of the study drug was excluded, there was an incremental, daily cost-savings benefit for the beractant-treated group compared with the sham-air treated group. Costs per case per day were significantly lower for neonates treated with beractant ($US1442 beractant vs $US1544 sham-air; 1991 dollars p = 0.01). Costs for radiological and diagnostic procedures, respiratory care and drugs (excluding beractant) were all significantly lower. When the acquisition cost of beractant was included, the cost to produce a 28-day survivor was $US3319 less with beractant ($US41 020) than with sham-air ($US44 339). Thus, when viewed in terms of costs per year of life saved, beractant compares very favourably with other recently evaluated health technologies.

Cost-Benefit Analysis↗
PubMed1993

The effects of differing insulin levels on the hormonal and metabolic response to equivalent hypoglycemia in normal humans.

The aim of this study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent hypoglycemia in normal humans. Experiments were conducted in 9 normal, lean men, who had fasted overnight. Insulin was infused in two separate, randomized protocols so that steady-state levels of 486 +/- 33 (low) and 3056 +/- 236 pM (high) were obtained. Glucose was infused during both protocols to ensure that the rate of fall of plasma glucose (0.07 mM/min) and hypoglycemic plateau (2.8 +/- 0.1 mM) were similar. Despite similar plasma glucose levels, EPI (8.7 +/- 0.7 vs. 5.5 +/- 0.7 nM), NE (3.3 +/- 0.3 vs. 2.3 +/- 0.2 nM), and cortisol (811 +/- 36 vs. 611 +/- 72 nM) significantly increased during high compared with low insulin infusion, respectively (P < 0.05). Glucagon, growth hormone, and pancreatic polypeptide levels increased briskly and significantly but were not different during the two insulin infusions. HGP rose significantly from 12.1 +/- 0.3 to 18.1 +/- 1.1 mumol.kg-1 x min-1 in response to the high insulin level (P < 0.05) but remained unchanged (12.1 +/- 0.4 and 11.7 +/- 1.4 mumol.kg-1 x min-1) in the presence of th low insulin level. GRa increased significantly during high insulin levels (3.4 +/- 0.3 to 4.8 +/- 0.7 mumol.kg-1 x min-1, P < 0.05) but remained at a basal rate (3.0 +/- 0.3 to 2.7 +/- 0.6 mumol.kg-1 x min-1) in the presence of low insulin levels. sBP and heart rate increased more during high insulin infusion (18 +/- 5 vs. 6 +/- 5 mmHg and 18 +/- 4 vs. 7 +/- 2 beats/min, respectively, P < 0.05). In summary, the 6-fold higher insulin level resulted in significantly greater increases in catecholamine and cortisol secretion, HGP, lipolysis, heart rate, and sBP despite equivalent hypoglycemia. We conclude that at moderate hypoglycemia, high doses of insulin can augment certain aspects of the counterregulatory response in normal humans.

Adult↗
PubMed1993

Regulation of glucose uptake and metabolism by working muscle. An in vivo analysis.

To assess the mechanisms whereby muscular work stimulates glucose uptake and metabolism in vivo, dogs were studied during rest (-40-0 min), moderate exercise (0-90 min), and exercise recovery (90-180 min) with plasma glucose clamped at 5.0, 6.7, 8.3, and 10.0 mM (n = 5 at 5.0 mM and n = 4 at all other levels) using a variable glucose infusion. Basal insulin was maintained with somatostatin and insulin replacement. Whole-body glucose uptake, limb glucose uptake, and oxidative and nonoxidative glucose plus lactate metabolism, were assessed with tracers ([3H]glucose and [14C]glucose) and arteriovenous differences. The combined effects of glucose and exercise on the increment above resting values for limb glucose uptake, arteriovenous glucose difference, LGO, LGNO, and rate of glucose disappearance were synergistic (approximately 112, 90, 125, 76, and 90% greater than the additive values, respectively). Neither exercise nor recovery affected the Km for limb glucose uptake (4.7 +/- 1.1, 4.8 +/- 0.4, and 5.2 +/- 0.3 mM during rest, exercise, and recovery, respectively), but both conditions increased the Vmax (44 +/- 16, 217 +/- 30, and 118 +/- 14 mumol/min during rest, exercise, and recovery, respectively). Similarly, the Km for arteriovenous glucose differences were unaffected by exercise recovery (4.9 +/- 0.6, 5.0 +/- 0.4, and 5.3 +/- 0.3 mM during rest, exercise, and recovery, respectively), but the maximum rose (272 +/- 50, 650 +/- 78, and 822 +/- 111 microM during rest, exercise, and recovery, respectively). The LGO was unchanged by glycemia at rest (15 +/- 4 mumol/min at 10.0 mM). The Km for LGO during exercise was 5.1 +/- 0.3 mM, and the Vmax was 163 +/- 15. The capacity for LGO returned to basal during recovery. LGNO increased gradually with increasing glycemia during rest, exercise, and recovery and did not approach saturation (38 +/- 13, 105 +/- 36, and 132 +/- 45 mumol/min during rest, exercise, and recovery, respectively, at 10.0 mM). In general, the LGNO was elevated at every glucose level during exercise (approximately twofold) and recovery (approximately threefold) compared with rest. Arterial free fatty acid and glycerol levels decreased with increasing glycemia within all periods. Free fatty acids were suppressed by a greater amount during exercise compared with rest and recovery.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗