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Abstracting and Indexing↗
Biomedical subjects
C Colburn
Publications and source records attributed to C Colburn.
Evidence that the brain of the conscious dog is insulin sensitive.
The aim of this study was to determine whether a selective increase in the level of insulin in the blood perfusing the brain is a determinant of the counterregulatory response to hypoglycemia. Experiments were carried out on 15 conscious 18-h-fasted dogs. Insulin was infused (2 mU/kg per min) in separate, randomized studies into a peripheral vein (n = 7) or both carotid and vertebral arteries (n = 8). This resulted in equivalent systemic insulinemia (84 +/- 6 vs. 86 +/- 6 microU/ml) but differing insulin levels in the head (84 +/- 6 vs. 195 +/- 5 microU/ml, respectively). Glucose was infused during peripheral insulin infusion to maintain the glucose level (56 +/- 2 mg/dl) at a value similar to that seen during head insulin infusion (58 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and similar hypoglycemia; steady state plasma epinephrine (792 +/- 198 vs. 2394 +/- 312 pg/ml), norepinephrine (404 +/- 33 vs. 778 +/- 93 pg/ml), cortisol (6.8 +/- 1.8 vs. 9.8 +/- 1.6 micrograms/dl) and pancreatic polypeptide (722 +/- 273 vs. 1061 +/- 255 pg/ml) levels were all increased to a greater extent during head insulin infusion (P < 0.05). Hepatic glucose production, measured with [3-3H]glucose, rose from 2.6 +/- 0.2 to 4.3 +/- 0.4 mg/kg per min (P < 0.01) in response to head insulin infusion but remained unchanged (2.6 +/- 0.5 mg/kg per min) during peripheral insulin infusion. Similarly, gluconeogenesis, lipolysis, and ketogenesis were increased twofold (P < 0.001) during head compared with peripheral insulin infusion. Cardiovascular parameters were also significantly higher (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog (a) the brain is directly responsive to physiologic elevations of insulin and (b) the response includes a profound stimulation of the autonomic nervous system with accompanying metabolic and cardiovascular changes.
3-Hydroxybutyric Acid↗
Smoking ban's juggling act. Pro.
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Humans↗
Clonal expansions of activated gamma/delta T cells in recent-onset multiple sclerosis.
Multiple sclerosis (MS) is a chronic disease characterized by focal demyelination of the white matter of the brain and spinal cord. Central nervous system damage appears to be mediated by infiltrating T lymphocytes and macrophages, and a central role for autoreactive CD4+ T cells has been proposed. However, the initial immune events that lead to the chronic process of MS remain unidentified. We now present evidence that a subset of T lymphocytes bearing gamma/delta T-cell antigen receptors has been activated in patients with recent-onset disease. Cells recovered from the cerebrospinal fluid of subjects with MS were cultured for short periods of time in medium supplemented with T-cell growth factors. Expansions of V delta 1 and V delta 2 T-cell receptor-bearing lymphocytes were found only in cell populations obtained from subjects with recent-onset disease. Similar populations were not expanded in subjects with chronic MS or other neurological diseases. Junctional region sequencing showed the expanded gamma/delta T cells to be oligoclonal in nature, suggestive of specific stimulation by antigen. These results reveal a fundamental difference in the immunopathogenesis of acute vs. chronic disease and provide additional insight into the autoimmune nature of MS.
Base Sequence↗
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↗
Effects of differing insulin levels on response to equivalent hypoglycemia in conscious dogs.
The aim of this study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent hypoglycemia. Insulin was infused intraportally into normal 18-h-fasted conscious dogs at 2 (low, 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 the high dose to maintain plasma glucose similar to low (50 +/- 1 mg/dl). Despite similar plasma glucose levels, epinephrine (2,589 +/- 260, 806 +/- 180 pg/ml), norepinephrine (535 +/- 60, 303 +/- 55 pg/ml), cortisol (12.1 +/- 1.5, 5.8 +/- 1.2 micrograms/dl), and pancreatic polypeptide (1,198 +/- 150, 598 +/- 250 pg/ml) were all increased in the presence of high-dose insulin (P < 0.05). Glucagon levels were similar during both insulin infusions. Hepatic glucose production, measured with [3-3H]-glucose, rose from 2.6 +/- 0.2 to 4.7 +/- 0.3 mg.kg-1.min-1 in response to high insulin (P < 0.01) but remained unchanged, 3.0 +/- 0.5 mg.kg-1.min-1, during low-dose infusions. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. By the final hour of the high-dose euglycemic clamps, cortisol (2.4 +/- 0.4 to 4.8 +/- 0.8 micrograms/dl) and norepinephrine (125 +/- 34 to 278 +/- 60 pg/ml) had increased (P < 0.05) compared with baseline. Plasma epinephrine levels remained unchanged during both series of euglycemic studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Accuracy of rhythm classification using a data log system in implantable cardioverter defibrillators.
Because the presence or absence of symptoms alone may be insufficient to correctly diagnose the rhythm for which implantable cardioverter defibrillator therapy is delivered, we hypothesized that the addition of data log information available in Telectronics ATP 4210 may improve the accuracy of rhythm classification. With this system the recorded ventricular electrogram cycle length is reported on a beat-to-beat basis immediately before, during, and after the tachyarrhythmia is detected. Using this information recorded from the data log in 32 separate tachyarrhythmia episodes in 20 patients, we compared the sensitivity, specificity, and predictive accuracy of rhythm classification on the basis of symptoms alone, data log alone, and data log combined with symptoms. While classification based on symptoms alone is highly specific (10/10 episodes), it is insensitive and has an overall predictive accuracy of 53%. By contrast, data log is sensitive (90%) and specific (91%) with better predictive accuracy (94%) than symptoms alone (P = 0.002). The addition of symptoms to information on beat-to-beat cycle length from data log resulted in a slight increase in predictive accuracy.
Data Collection↗