Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR.

The rate of net hepatic glycogenolysis was assessed in humans by serially measuring hepatic glycogen concentration at 3- to 12-hour intervals during a 68-hour fast with 13C nuclear magnetic resonance spectroscopy. The net rate of gluconeogenesis was calculated by subtracting the rate of net hepatic glycogenolysis from the rate of glucose production in the whole body measured with tritiated glucose. Gluconeogenesis accounted for 64 +/- 5% (mean +/- standard error of the mean) of total glucose production during the first 22 hours of fasting. In the subsequent 14-hour and 18-hour periods of the fast, gluconeogenesis accounted for 82 +/- 5% and 96 +/- 1% of total glucose production, respectively. These data show that gluconeogenesis accounts for a substantial fraction of total glucose production even during the first 22 hours of a fast in humans.

Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study.

UNLABELLED: To quantitate hepatic glycogenolysis, liver glycogen concentration was measured with 13C nuclear magnetic resonance spectroscopy in seven type II diabetic and five control subjects during 23 h of fasting. Net hepatic glycogenolysis was calculated by multiplying the rate of glycogen breakdown by the liver volume, determined from magnetic resonance images. Gluconeogenesis was calculated by subtracting the rate of hepatic glycogenolysis from the whole body glucose production rate, measured using [6-3H]glucose. Liver glycogen concentration 4 h after a meal was lower in the diabetics than in the controls; 131 +/- 20 versus 282 +/- 60 mmol/liter liver (P < 0.05). Net hepatic glycogenolysis was decreased in the diabetics, 1.3 +/- 0.2 as compared to 2.8 +/- 0.7 mumol/(kg body wt x min) in the controls (P < 0.05). Whole body glucose production was increased in the diabetics as compared to the controls, 11.1 +/- 0.6 versus 8.9 +/- 0.5 mumol/(kg body wt x min) (P < 0.05). Gluconeogenesis was consequently increased in the diabetics, 9.8 +/- 0.7 as compared to 6.1 +/- 0.5 mumol/(kg body wt x min) in the controls (P < 0.01), and accounted for 88 +/- 2% of total glucose production as compared with 70 +/- 6% in the controls (P < 0.05). IN CONCLUSION: increased gluconeogenesis is responsible for the increased whole body glucose production in type II diabetes mellitus after an overnight fast.

13C-nuclear magnetic resonance spectroscopy studies of hepatic glucose metabolism in normal subjects and subjects with insulin-dependent diabetes mellitus.

To determine the effect of insulin-dependent diabetes mellitus (IDDM) on rates and pathways of hepatic glycogen synthesis, as well as flux through hepatic pyruvate dehydrogenase, we used 13C-nuclear magnetic resonance spectroscopy to monitor the peak intensity of the C1 resonance of the glucosyl units of hepatic glycogen, in combination with acetaminophen to sample the hepatic UDP-glucose pool and phenylacetate to sample the hepatic glutamine pool, during a hyperglycemic-hyperinsulinemic clamp using [1-13C]-glucose. Five subjects with poorly controlled IDDM and six age-weight-matched control subjects were clamped at a mean plasma glucose concentration of approximately 9 mM and mean plasma insulin concentrations approximately 400 pM for 5 h. Rates of hepatic glycogen synthesis were similar in both groups (approximately 0.43 +/- 0.09 mumol/ml liver min). However, flux through the indirect pathway of glycogen synthesis (3 carbon units-->-->glycogen) was increased by approximately 50% (P < 0.05), whereas the relative contribution of pyruvate oxidation to TCA cycle flux was decreased by approximately 30% (P < 0.05) in the IDDM subjects compared to the control subjects. These studies demonstrate that patients with poorly controlled insulin-dependent diabetes mellitus have augmented hepatic gluconeogenesis and relative decreased rates of hepatic pyruvate oxidation. These abnormalities are not immediately reversed by normalizing intraportal concentrations of glucose, insulin, and glucagon and may contribute to postprandial hyperglycemia.

Splanchnic and peripheral disposal of oral glucose in man.

Oral glucose (92 g) was administered to 22 healthy, young volunteers undergoing hepatic vein catheterization, and net splanchnic glucose output (SGO) was measured during the basal period and for 4 h after glucose ingestion. In the basal state, SGO averaged 1.90 +/- 0.11 mg/min X kg. After glucose, SGO rose to a peak value of 6.65 +/- 0.83 mg/min X kg at 30 min and returned to baseline by 3 h. Total SGO over 4 h was 69 +/- 4 g; assuming complete absorption of the load, this amount represented 75% of the oral glucose. In a subgroup of six subjects, leg glucose uptake was simultaneously quantitated by femoral vein catheterization and leg blood flow measurement. In the postabsorptive state, glucose uptake by one leg was 24 +/- 8 mg/min and increased to a mean value of 76 +/- 7 mg/min during the 4 h after glucose ingestion. Overall, 18 +/- 2 g/4 h of glucose were taken up by one leg, which extrapolates to a total body muscle uptake of 65 +/- 4 g over 4 h. We conclude that in normal man, well over 2/3 of an oral glucose load escapes splanchnic removal, and that the peripheral tissues quantitatively play the dominant role in glucose disposal.

Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration.

The contribution of net hepatic glycogenolysis to overall glucose production during a physiological increment in the plasma glucagon concentration was measured in six healthy subjects (18-24 years, 68-105 kg) after an overnight fast. Glucagon (approximately 3 ng.kg-1.min-1), somatostatin (0.1 microgram.kg-1.min-1), and insulin (0.9 pmol.kg-1.min-1) were infused for 3 h. Liver glycogen concentration was measured at 15-min intervals during this period using 13C-labeled nuclear magnetic resonance spectroscopy, and liver volume was assessed from magnetic resonance images. The rate of net hepatic glycogenolysis was calculated from the decrease in liver glycogen concentration over time, multiplied by the liver volume. The rate of glucose appearance (Ra) was calculated from [3-3H]glucose turnover data using a two-compartment model of glucose kinetics. Plasma glucagon concentration rose from 136 +/- 18 to 304 +/- 57 ng/l and plasma glucose concentration rose from 5.6 +/- 0.1 to 10.4 +/- 0.9 mmol/l on initiation of the infusions. Mean baseline Ra was 11.8 +/- 0.4 mumol.kg-1.min-1, increased rapidly after the beginning of the infusions, reaching its highest value after 20-40 min, and returned to baseline by 140 min. Liver glycogen concentration decreased almost linearly (from 300 +/- 19 mmol/l liver at baseline to 192 +/- 20 mmol/l liver at t = 124 min) during 2 h after the beginning of the infusions, and the calculated mean rate of net hepatic glycogenolysis was 21.7 +/- 3.6 mumol.kg-1.min-1. Mean Ra during the same time period was 22.8 +/- 2.3 mumol.kg-1.min-1. Thus, net hepatic glycogenolysis accounted for 93 +/- 9% of Ra.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced basal ganglia volumes in Tourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images.

Using a 1.5-tesla GE Signa MR scanner, we imaged the brains of 14 right-handed Tourette's syndrome (TS) patients (11 men, three women), aged 18 to 49 years, who had minimal lifetime neuroleptic exposure. We also studied an equal number of normal controls individually matched for age, sex, and handedness and group-matched for socioeconomic status. We circumscribed basal ganglia on sequential axial images from spin-echo proton density-weighted acquisitions (TR 1,700, TE 20; slice thickness, 3 mm with 1.5-mm skip) and submitted the images for three-dimensional processing at a computer graphics workstation. Our hypothesis of lenticular nucleus volume reduction in TS was confirmed for the left- but not the right-sided nucleus. Post hoc analyses revealed smaller mean volumes of the caudate, lenticular, and globus pallidus nuclei compared with controls on both the right and left. Further analyses of basal ganglia asymmetry indices suggest that TS basal ganglia do not have the volumetric asymmetry (left greater than right) seen in normal controls. These findings confirm and extend prior phenomenologic, neuropathologic, and neuroradiologic studies that implicate the basal ganglia in the pathogenesis of TS.

Moderate-intensity aerobic training improves glucose tolerance in aging independent of abdominal adiposity.

OBJECTIVE: To test the hypothesis that training-related improvements in glucose and insulin responses to an oral glucose tolerance test (OGTT) are independent of changes in abdominal adiposity. DESIGN: Adiposity and responses to an OGTT were measured before and after a 4-month randomized, controlled aerobic training program. SETTING: An academic medical institution. PARTICIPANTS: Sixteen healthy older (73+/-1 year) men and women. INTERVENTION: Both the training (T) (n=9) and control (C) (n=7) groups exercised 4 times a week for 60-minute sessions. T exercised on mini-trampolines at 55 to 65% of HRmax (determined from a graded treadmill test) for 1 month and then at 75% for 3 months; C engaged in supervised stretching and yoga. MEASUREMENTS: At baseline and follow-up, we estimated abdominal fat (from computed tomography and anthropometry), plasma glucose, and serum insulin responses to the OGTT and fasting concentrations of free fatty acids (FFA). RESULTS: Aerobic training resulted in a 16% increase in VO2 peak and a 24% decrease in FFA in the T group (P < .05), but training had no effect on abdominal fat. In the T group, the glucose response curve shifted to the left, and the incremental area under the glucose curve decreased by 25% (P < .05). This improvement in glucose response occurred, however, only in those with impaired glucose tolerance at baseline and without any observed change in insulin response. No change in any variables occurred in the C group. CONCLUSIONS: Our data suggest that moderate-intensity aerobic training has a favorable effect on glucose tolerance in older people, independent of changes in abdominal adiposity.

The disposal of an oral glucose load in patients with non-insulin-dependent diabetes.

Following glucose ingestion, tissue glucose uptake is enhanced and endogenous glucose production is inhibited, thus contributing to the maintenance of normal glucose tolerance. To examine whether these responses are disturbed in diabetes, glucose kinetics after oral glucose administration were studied in 12 non-insulin-dependent diabetic and 10 age- and weight-matched control subjects. A double tracer approach was used, whereby the endogenous glucose pool was labeled with 3-3H-glucose and the oral load with 1-14C-glucose. The two glucose tracers were separated in plasma by a two-step chromatographic procedure, and the two sets of isotopic data were analyzed according to a two-compartment model for the glucose system. Basally, glucose production was slightly higher in diabetics than in controls (2.51 +/- 0.24 v 2.28 +/- 0.11 mg/kg.min, NS) even though the former had higher plasma glucose (189 +/- 19 v 93 +/- 2 mg/dL, P less than .001) and insulin (23 +/- 4 v 12 +/- 1 microU/mL, P less than .05) concentrations. Following the ingestion of 1 g/kg of glucose, oral glucose appeared in the peripheral circulation in similar time-course and amount in the two groups (75 +/- 2% of the load over 3.5 hours in the diabetics v 76 +/- 3% in controls). Endogenous glucose production was promptly inhibited in diabetic and normal subjects alike, but the mean residual hepatic glucose production after glucose ingestion was significantly greater in the diabetic group (17 +/- 2 v 10 +/- 3 g/3.5 h, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo glucose metabolism in the awake rat: tracer and insulin clamp studies.

The goals of this study were twofold: (1) to determine the in vivo dose-response relationship in the conscious, unstressed rat between the plasma insulin concentration and total body glucose uptake, and between plasma insulin and suppression of endogenous glucose production; and (2) to develop a physiologic compartmental model to describe the kinetics of plasma glucose in the rat in the basal state. In order to perform repeat insulin clamp studies in the same rat, chronic catheters were implanted in the aortic arch (via the carotid artery) and in the cardiac atrium (via the jugular vein), exteriorized, and fixed to the back of the skull with a dental cement cap. Insulin was infused at rates of 1.2, 2.4, 4.8, 12, and 24 mU/min.kg, and the plasma glucose was held constant at the basal level by a variable glucose infusion (euglycemic insulin clamp). The resulting steady-state plasma insulin concentrations ranged from 40 to 1,300 microU/mL. The dose-response curve for glucose uptake was sigmoidal in shape: in the basal state, total glucose utilization averaged 6.8 mg/min.kg at an insulin concentration of 9 microU/mL, half-maximal glucose uptake (18.3 mg/kg.min) occurred at a plasma insulin concentration between 70 and 80 microU/mL, and maximal uptake (36.6 mg/kg.min) was seen at an insulin level in excess of 100 microU/mL. Residual endogenous glucose production was evaluated by a prime-continuous infusion of (3-3H)-glucose. The dose-response curve for suppression of endogenous glucose output also was sigmoidal.(ABSTRACT TRUNCATED AT 250 WORDS)

MR arthrography of the hip.

Hip arthroscopy can be performed on an outpatient basis and has a shorter period of rehabilitation than is necessary after an open hip arthrotomy or reconstruction. The procedure makes possible accurate diagnosis and treatment of acetabular labral tears and loose bodies. Further advancements are necessary in optical equipment; manual and motorized equipment; and simple, reliable traction devices specific for this procedure. Refinements in patient selection and the increased availability of specific outcome data will help to define the role of hip arthroscopy in orthopedic practice.

Human basal ganglia volume asymmetries on magnetic resonance images.

The brains of 19 healthy adults, ages 18-49, were imaged on a GE Signa 1.5 T MR scanner. Basal ganglia were circumscribed on sequential axial proton density-weighted images (TR 1700, TE 20) and submitted for 3-dimensional reconstruction and volumetric analysis at a computer graphics workstation. The 15 right-handed patients (12 men, 3 women) had significantly larger left total basal ganglia volumes, which included larger globus pallidus and lenticular nuclei on the left, but larger caudate nuclei on the right. In contrast, basal ganglia asymmetries were not seen in four left-handers. No sex differences were detected. The basal ganglia appear to belong to an increasing number of CNS structures that display anatomical hemispheric lateralization.

A non-invasive method for studying in vivo carpal kinematics.

Seven uninjured and three injured patients were studied using midsagittal computed tomographic (CT) images at 10 degrees increments from full extension to full flexion. Each injured patient had a confirmed scapholunate ligament tear and normal radiographs. CT bony contours were digitized, and incremental motion determined using a specifically designed automated contour-matching algorithm. We expressed wrist motion as a ratio of lunocapitate (midcarpal) motion, and radiolunate (radiocarpal) motion. In normal wrists, motion occurred equally at the midcarpal and radiocarpal joints. In wrists with scapholunate ligament disruption, lunocapitate motion increased significantly throughout the arc of motion.

Radiographic progression to dorsal intercalated segment instability.

We present a case of an acute hyper-extension wrist injury that progressed from normal carpal alignment to dorsal intercalated segment instability over a short period of time. Disruption of the scapholunate interosseous and radioscapholunate ligaments was proven arthroscopically, while the intercapsular ligaments were demonstrated to be intact. We have shown that lunate malalignment can occur over time, as secondary lunate ligamentous supports attenuate under abnormal carpal kinetics.

Neuritis ossificans of the tibial, common peroneal and lateral sural cutaneous nerves.

We describe a 23-year-old woman with neuritis ossificans involving the tibial, common peroneal and lateral sural nerves. She presented with chronic debilitating posterior knee pain. An MRI scan showed masses in these nerves, biopsy of which revealed a histological diagnosis of neuritis ossificans. Treatment with OxyContin and Neurotin for two years resulted in resolution of symptoms. Follow-up MRI demonstrated a resolution of two of the three masses. There was a persistent area of ossification without associated oedema in the common peroneal nerve. Neuritis ossificans has the histological appearance of myositis ossificans and follows a similar clinical course. The success of conservative treatment in this case suggests that the potential complications of surgical excision can be avoided.

Case report 571: Radiation-induced growth abnormalities.

A case of a 23-year-old man with deformities of the spine and hip is presented, demonstrating the bizarre long term effects of radiation on developing bone. The spectrum of radiation-induced growth abnormalities is reviewed. Multiple variables, including age of the patient, the quantity of radiation delivered, and the site of delivery, all effect the eventual radiographic appearance.

Intra-articular impaction fractures of the phalanges.

Six patients with acute impacted fractures of the base of the proximal or middle phalanges were treated with open reduction and internal fixation. Two of three patients who presented with chronic injuries also underwent surgical reconstruction. Contiguous 1.5-mm sagittal computed tomographic imaging was performed on each proximal interphalangeal joint fracture; the imaging documented an average impaction of 30% of the articular surface area. Metaphyseal bone grafting was necessary to support the articular surface in three acute and both late patients. Rigid internal fixation, most frequently employing a composite wire tension band technique, allowed immediate postoperative range of motion exercises. At an average follow-up period of 21 months, all six acute patients had restoration of an excellent painless range of motion. There was no loss of articular congruency on final x-ray films. Late or conservative treatment of these injuries was uniformly less successful.

Effect of epinephrine on renal potassium excretion in the isolated perfused rat kidney.

The effects of beta-agonists (epinephrine, isoproterenol, and ITP) and beta-antagonists (propranolol, metoprolol, and butoxamine) on renal potassium excretion were examined using the isolated perfused rat kidney preparation. Following 30 min of control perfusion, one of the above beta-adrenergic agonists or antagonists was added to the perfusion medium. Following epinephrine, a combined beta 1- and beta 2-agonist, urinary potassium excretion (UKV; 0.55 +/- 0.55 vs. 0.36 +/- 0.04 mueq/min, P less than 0.001) and fractional excretion of potassium (FEK; 24.6 +/- 2.4 vs. 18.2 +/- 2.0%, P less than 0.001) both decreased. When isoproterenol, a nonspecific beta-agonist, was added to the perfusate, UKV (0.49 +/- 0.10 vs. 0.27 +/- 0.04 mueq/min, P less than 0.02) and FEK (29.0 +/- 5.2 vs. 16.3 +/- 2.9%, P less than 0.01) again decreased. ITP, a specific beta 1-agonist also caused a decrease in UKV (0.60 +/- 0.13 vs. 0.39 +/- 0.04 mueq/min, P less than 0.02) and FEK (30.2 +/- 5.1 vs. 17.8 +/- 2.8%, P less than 0.02). In contrast, when propranolol, a nonspecific beta-antagonist, was added to the perfusate, the opposite effects on renal potassium handling were observed. UKV (0.45 +/- 0.05 vs. 0.70 +/- 0.07 mueq/min, P less than 0.001) and FEK (23.0 +/- 2.1 vs. 42.5 +/- 3.1%, P less than 0.001) both increased. Metoprolol (50 ng/ml), a specific beta 1-antagonist, increased UKV (0.56 +/- 0.10 vs. 0.68 +/- 0.15 mueq/min, P less than 0.02) and FEK (31.0 +/- 3.8 vs. 48.0 +/- 7.1%, P less than 0.02). A similar effect was observed when a higher dose of metoprolol (200 ng/ml) was employed.(ABSTRACT TRUNCATED AT 250 WORDS)

A method of palliation for obstructive carcinoma of the rectum.

The use of the resectoscope has several advantages in treating the patient with inoperable obstructive carcinoma of the rectum, particularly when compared with fulguration. It is immediate in its results, as often testified to by the sudden outpouring of blockaded feces. It is also safer in allowing greater amounts of tissue to be resected with less depth of tissue injury by the electrical output. It does, however, require the skills of someone able to handle the instrument, and the procedure should be a joint effort by the surgeon and urologist. The use of the urologic resectoscope should prove to be a useful addition in the surgeon's armamentarium in a selected number of patients.

Volvulus of the transverse colon: report of case and review of the literature.

A case of transverse colon volvulus is reported, bringing the total number of collected cases in the English language medical literature to 45. Although this type of volvulus is rare, a definite pattern can be appreciated. Patients tend to be young, female, and give a history of chronic or recurrent difficulty in having bowel movements. A triad of underlying factors predisposes to the development of the volvulus: a distal impediment (either organic or functional) to the evacuation of the bowel, a redundant bowel and mesocolon and a fixed point around which the bowel can twist. The best treatment is resection with either anastomosis or exteriorization, depending on bowel viability.