Comparison of radionuclide lymphoscintigraphy and dynamic magnetic resonance lymphangiography for investigating extremity lymphoedema.

BACKGROUND: Lymphoscintigraphy is widely used to image the lymphatic system. The aim of this study was to compare lymphoscintigraphy and dynamic magnetic resonance lymphangiography (MRL) in the investigation of extremity lymphoedema. METHODS: Sixteen patients with primary extremity lymphoedema and two with Klippel-Trenaunay syndrome with lymphoedema were examined by lymphoscintigraphy using the tracer (99)Tc-labelled dextran, and by MRL using gadobenate dimeglumine as contrast agent. Morphological abnormalities and functional state of the lymphatic systems of affected limbs were compared between the two imaging methods. RESULTS: Lymphatic vessels were imaged in 14 of 18 limbs with lymphoedema using MRL, compared with one of 18 using lymphoscintigraphy. MRL detected the inguinal nodes in 16 of 17 patients, whereas lymphoscintigraphy revealed inguinal nodes in only nine. MRL revealed more precise information about structural and functional abnormalities of lymph vessels and nodes than lymphoscintigraphy by real-time measurement of lymph flow in vessels and nodes. CONCLUSION: Dynamic MRL was more sensitive and accurate than lymphoscintigraphy in the detection of anatomical and functional abnormalities in the lymphatic system in patients with extremity lymphoedema.

Impaired glucose tolerance and its relationship to ECG-indicated coronary heart disease and risk factors among Chinese. Da Qing IGT and diabetes study.

OBJECTIVE: To determine the prevalence of IGT and diabetes and identify the occurrence of CVD and its risk factors. RESEARCH DESIGN AND METHODS: This study was a population-based, cross-sectional study of 110,660 residents, 25-74 yr of age of DaQing, Hei Long Jiang Province, China. RESULTS: Using 1985 WHO criteria, 577 (5.5/1000) subjects with IGT and 630 (6.0/1000) with newly diagnosed diabetes were identified. In addition, 190 (1.7/1000) with previously known diabetes were identified. Hypertension, obesity, and abnormal albumin excretion were twice as frequent in those with IGT as in 279 men and 240 women of similar age and sex distribution who had normal OGTTs. Plasma cholesterol and TGs were higher, and HDL cholesterol was lower in subjects with IGT than in nondiabetic subjects. Those with IGT had a prevalence of electrocardiographically recognized CHD 9.5-fold greater than the normoglycemic subjects. Subjects with IGT had higher plasma insulin concentrations, but the 1-h insulin-glucose ratio after the 75-g glucose load was lower. In a forward stepwise multiple logistic regression analysis, IGT itself remained an independent factor associated with CHD after adjustment for age, sex, cigarette smoking, plasma cholesterol, BP, and obesity. CONCLUSIONS: Therefore, in China, IGT may occur with almost as high a frequency as diabetes and is accompanied by an increased frequency of CVD and its risk factors. Estimates from this study indicate that > 12.0% of all ECG-indicated CHD in the Da Qing population occurs in individuals with IGT and NIDDM. The IGT subjects identified in this survey form the cohort for a long-term follow-up and intervention study.

Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.

OBJECTIVE: Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. RESEARCH DESIGN AND METHODS: In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. RESULTS: The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8-75.2) in the control group compared with 43.8% (95% CI, 35.5-52.3) in the diet group, 41.1% (95% CI, 33.4-49.4) in the exercise group, and 46.0% (95% CI, 37.3-54.7) in the diet-plus-exercise group (P < 0.05). When analyzed by clinic, each of the active intervention groups differed significantly from the control clinics (P < 0.05). The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight (BMI < or > or = 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively. CONCLUSIONS: Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.

Coronary heart disease and diabetic retinopathy in newly diagnosed diabetes in Da Qing, China: the Da Qing IGT and Diabetes Study.

In 1986, 110,660 of 281,589 residents aged 25-74 years in Da Qing, Hei Long Jiang Province of China, were surveyed. Based on the results of a 75-g oral glucose tolerance test, 630 subjects were found to have previously undiagnosed diabetes according to 1985 WHO criteria. Among them, 600 diabetics aged 35-74 years (288 men, 312 women) and 410 non-diabetics of similar age with normal glucose tolerance (207 men, 203 women) were examined to determine the prevalence of retinopathy and coronary heart disease (CHD) and to evaluate associated characteristics. Retinal examinations of 423 newly diagnosed diabetics showed that 15.4% had several microaneurysms and/or small intraretinal haemorrhage, 5.5% soft exudates, 7.1% hard exudates, and 2.3% proliferative retinopathy. Among 220 non-diabetics, 13.6% had one or two microaneurysms and/or small intraretinal haemorrhage, and only 1.4% had a few soft exudates; half of the non-diabetics with retinopathy had hypertension. CHD, according to Minnesota coding (1.1-1.3, 5.1-5.3 and 7.1) of resting electrocardiograms, was ten times more frequent in the diabetics (3.59%) than in the controls (0.32%), after adjusting for age and sex. Multiple regression analysis showed that plasma glucose concentration was a risk factor for retinopathy after adjusting for age, sex, body mass index (BMI), smoking and blood pressure. Two-hour plasma glucose concentration (after adjusting for age, sex, BMI, smoking and blood pressure) and blood pressure (after adjusting for age, sex BMI, smoking and 1-h or 2-h plasma glucose level) were associated with CHD among the diabetics and non-diabetics and among the diabetics alone. Thus, both micro- and macrovascular complications occur frequently in previously undiagnosed Chinese diabetics and the frequency of CHD is markedly increased compared to the low frequency among Chinese non-diabetics.

Crosslinking of the nearest membrane protein neighbors in ATP depleted, calcium enriched and irreversibly sickled red cells.

ATP depleted or Ca2+ (0.1 mM) enriched normal red cells (greater than 80% echinocytes III) subjected to crosslinking by catalytic oxidation contain a greater than 1,000,000 daltons spectrin rich polymer cleavable by dithiothreitol (DTT) reduction. Similar complex is seen after glutaraldehyde crosslinking suggesting spectrin rearrangement into closer contacts or aggregation. In addition, a non-reducible greater than 1,000,000 daltons polymer is produced in fresh rbc or ghosts by high (greater than 0.5 mM) Ca2+ conc. and ionophore A23187. This complex is attributed to endogenous membrane protein crosslinking, catalyzed by a Ca2+ stimulated rbc transglutamidase. ISCs exhibiting a 4 fold increase in Ca2+ and a decrease in ATP do not exhibit these polymers. However, ISCs have an increased propensity to form the spectrin rich polymer during a subsequent ATP depletion and this is associated with a transformation of greater than 60% ISCs into spheroechinocytes. Similar cells are occasionally noted (greater than 4%) in the densest ISC rich fractions separated from fresh blood. We conclude that neither Ca2+, ATP dependent spectrin aggregation nor a spontaneous irreversible crosslinking underlie the membrane lesion of ISCs. Accelerated calcium gain and ATP depletion in ISCs leads to spectrin rearrangement and transformation of ISCs into spheroechinocytes which may represent an end stage ISC lesion resulting in an ISC removal from circulation.

Protein kinases and membrane protein phosphorylation in normal and abnormal human erythrocytes: variation related to mean cell age.

Protein kinase activities and membrane autophosphorylation reactions of normal and abnormal human erythrocytes were analyzed. Erythrocytes from patients with high reticulocytosis due to sickle cell anemia and other disorders (n = 13) exhibited elevated activities of total and membrane-bound cAMP-independent casein kinase and cAMP-stimulated histone kinase. Relative to normal controls (n = 10), the average total activities in these abnormal cells were increased 50% and 81%, respectively. The casein and histone kinase activities of normal and abnormal erythrocytes declined significantly with increasing age and buoyant density in Stractan density gradients. Casein kinase activity was highly correlated (r = 0.88; n = 23) with the percentage of reticulocytes in the fraction, consistent with either a progressive loss of activity in mature erythrocytes or an abrupt decline during reticulocyte maturation. The cAMP-independent and cAMP-stimulated autophosphorylation activities of isolated membranes also declined with increasing erythrocyte age. On average, the initial rate of spectrin labeling was 36% lower in ghosts from Stractan gradient bottom fractions, relative to ghosts from top fractions similarly incubated with gamma-32P-ATP. Incorporation into the "band 4.5 zone" (primarily labeling bands 4.8 and 4.9, mol wt 47,800 and 44,600) was also age-dependent. In membranes of unfractionated sickle cells, spectrin autophosphorylation was within normal limits, while 4.5 zone autophosphorylation was increased. Membranes from high reticulocytosis controls (vitamin B-12 deficiency) exhibited similar autophosphorylation patterns, suggesting that the altered autophosphorylation pattern of sickle cell membranes may be attributed to the predominance of very young cells.