Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes

The association of bone with the metabolic syndrome and its features, visceral fat accumulation or insulin resistance, remains unclear. We determined visceral and subcutaneous fat areas (V and S) by computed tomography on 187 men (28–83 years) and 125 postmenopausal women (46–82 years) with type 2 diabetes. Men whose V was 100 cm² or more had significantly lower urinary N-terminal cross-linked telopeptide of type-I collagen (p = 0.005), higher femoral neck bone mineral density (FN-BMD) (p = 0.004), and lower prevalence of vertebral fractures (VFs) (p = 0.04) than controls. Fat mass, V, S, and lean body mass positively correlated with FN-BMD in men and with lumbar (L) and FN-BMD in women. When adjusted for weight, these correlations became negative. Urinary C-peptide positively correlated with FN-BMD in both genders. Multivariate logistic regression analysis adjusted for age, height, weight, L-BMD, duration of diabetes, and diabetes therapies identified V in men and urinary C-peptide in women as factors inversely associated with the presence of VFs [odds ratio (OR) = 0.61 per SD increase, p = 0.04, and OR = 0.32, p = 0.01, respectively]. These findings suggest that, of the components of the metabolic syndrome, body fat in gravity and hyperinsulinemia could increase FN-BMD in diabetic subjects. Visceral fat in men and hyperinsulinemia in women may protect against VFs independent of weight, L-BMD, diabetes duration, or therapies.     

The mechanism of action of tumor necrosis factor (TNF) on tumor vascularity--study using a transparent chamber

Effects of human recombinant TNF on the tumor blood vessels and on the thrombus formation were investigated in relation to its mode of antitumor action against Meth-A sarcoma transplanted in BALB/c mice. The extent of the blood vessel lesion was evaluated by using transparent chamber placed in the mouse skin. Bleeding, hyperemia and congestion were observed at 1-2h, 4-6h and 24h after TNF (1 X 10(4)U/mouse) administration, respectively. In contrast, no histological changes in the normal blood vessels were observed microscopically following TNF injection. Thrombus formation was evoked in the tumor vessels 4h after TNF injection. However, when thrombus formation was prevented by heparin, no difference was observed among antitumor action of TNF against Meth-A fibrosarcoma necrotic response and the rate of complete cure. These results suggest that the direct effects of TNF causing lesions in the tumor blood vessels plays an important role in its antitumor action.     

The effect of bismuth subnitrate on cisplatin toxicity

Bismuth subnitrate (BSN), a bismuth compound medically used for antidiarrheics, was orally administered to see whether it can reduce CDDP nephrotoxicity or not. Thirteen patients aged 19 approximately 60 with ovarian cancer entered this BSN-CDDP trial. A total of thirty three courses of BSN-CDDP treatment was undergone. BSN was administered orally at a dose of 50 mg/kg for five days before CDDP therapy. CDDP was infused for two hours. No vigorous hydration or diuresis was performed. Only 2,000 ml of saline with 20 mEq per liter of KCl was given for post-hydration. The median dose of CDDP was 100 mg/m2. The renal toxicity of BSN-CDDP treatment was minimum. 82% of the courses at the sixth day after the treatment had creatinine clearance levels which were more than 80% of those before the treatment. But twenty-four hour NAG and beta 2-microglobulin excretion were significantly increased. Bone marrow suppression and gastrointestinal disturbance were commonly observed. The results of our study indicate that BSN pretreatment reduces the renal toxicity of CDDP to some extent.     

Surgical management of insulinoma: Diagnosis of tumor location and high incidence of malignancy

The findings in twenty-two patients with insulinoma were reviewed, as continuous efforts should be made to establish preoperative localization of the tumor. Superselective arteriography and percutaneous, transhepatic portal vein and pancreatic venous catheterization are highly recommended approaches. At the time of surgical intervention, a cautious exploration of the pancreas after thorough mobilization is most important. Recent use of intraoperative ultrasonography increases the likelihood of finding these occult tumors which locate deeply in the head of the pancreas. Apart from the diagnostic problems, we wish to emphasize the high incidence of malignancy (7/22, 31.8 per cent) in our series. Althout patients with malignant isulinoma had a much better prognosis compared to those with a pancreatic ductal malignancy, pancreatic resection with regional lymphnode dissection seems to be a rational procedure. Enucleation can be done when intraoperative findings of the tumor and regional lymphonode indicate no malignant features and no multiple lesions. However, at the first operation, enucleation is still a procedure of choice, even for the malignant insulinoma in the head with a well-defined capsule and no metastatic lesions, the objective being to avoid a duodenopancreatectomy or total pancreatectomy. These data were reported at the 30th Congress of Société Internationale de Chirurgie, Hamburg, Germany, 1983     

Halothane Suppression of Spinal Sensory Neuronal Responses to Noxious Peripheral Stimuli Is Mediated, in Part, by Both GABAA and Glycine Receptor Systems

Background: A major effect of general anesthesia is lack of response in the presence of a noxious stimulus. Anesthetic depression of spinal sensory neuronal responses to noxious stimuli is likely to contribute to that essential general anesthetic action. The authors tested the hypothesis that [gamma]-aminobutyric acid receptor type A (GABAA) and strychnine-sensitive glycine receptor systems mediate halothane depression of spinal sensory neuronal responses to noxious stimuli.

Methods: Extracellular activity of single spinal dorsal horn wide dynamic range (WDR) neurons was recorded in decerebrate, spinal cord transected rats. Neuronal responses to noxious (thermal and mechanical) and nonnoxious stimuli were examined in the drug-free state. Subsequently, cumulative doses (0.1-2.0 mg/kg) of bicuculline (GABAA antagonist) or strychnine (glycine antagonist) were administered intravenously in the absence or presence of 1 minimum alveolar concentration (MAC) of halothane.

Results: Halothane, 1.1%, depressed the response of WDR neurons to both forms of noxious stimuli. Antagonists, by themselves, had no effect on noxiously evoked activity. However, bicuculline and strychnine (maximum cumulative dose, 2.0 mg/kg) partially but significantly reversed the halothane depression of noxiously evoked activity. Similar results were seen with most, but not all, forms of nonnoxiously evoked activity. In the absence of halothane, strychnine significantly increased neuronal responses to low threshold receptive field brushing.     

Effects of age on susceptibility of chickens to delayed neurotoxicity due to triphenyl phosphite

Triphenyl phosphite (TPP), which is widely used in the chemical industry, is known to produce delayed neurotoxicity in some experimental animals. The effects of aging on the susceptibility to TPP, its disposition and pharmacokinetics, and its in vitro degradation by liver homogenate were studied in chickens. Chickens aged 60 days or less at administration were not affected, but 10 of 15 chickens aged 90 to 180 days developed ataxia 10 to 12 days after the intravenous injection of TPP (50 mg/kg). TPP clearance from the blood and most of the tissues examined was faster in 45-day-old chickens than in 135-day-old chickens. The biological half-life of TPP in the blood was 23.2 min. in the younger group and 30.5 min. in the older group. In the in vitro experiment, the initial TPP concentration of 1.6 x 10(-5) M fell to less than half this level within 60 min. during incubation with liver homogenates from 45-day-old chickens, whereas with homogenates from 135-day-old chickens the level remained high. These results suggested that the age-specific susceptibility to TPP was related to the differences of the tissue load, which derived in part from differing levels of metabolic activity in the liver.     

MRI and ultrasonography of atherosclerosis of the thoracic aorta and carotid arteries in elderly hypercholesterolemic patients]

In 53 elderly participants aged more than 60 the thoracic aorta and bilateral carotid arteries were observed with noninvasive techniques, MRI and ultra-sonography, in order to elucidate the relationship between hypercholesterolemia and atherosclerosis in the elderly. Hypercholesterolemic subjects were classified as group H (serum total cholesterol (TC) greater than 220 mg/dl), group H-I (220 mg/dl less than TC less than 250 mg/dl) and group H-II (TC greater than or equal to 250 mg/dl). Atherosclerotic changes of the thoracic aorta were observed in 46% of group H, 27% of group H-I, 60% of group H-II and 37% of normolipidemic subjects (group NL). Carotid atherosclerotic changes were observed in 19% of group H, 9% of group H-I, 27% of group H-II and 18% of group NL. In group H-I, the percentages of atherosclerotic changes in both thoracic aorta and carotid arteries were lower than those in group NL. However, atherosclerotic changes of thoracic aorta and carotid arteries were detected in 43% and 29% of the subjects showing higher apo B/Apo Al ratio than 1.0 among group H-I + NL (TC less than 250 mg/dl). These changes occurred in 32% and 13% of the subjects showing lower apo B/Apo Al ratio than 1.0 among the same groups. Namely, atherosclerotic changes of the thoracic aorta and carotid arteries were observed more frequently in the subjects showing a higher apo B/Apo Al ratio than 1.0 even if their serum cholesterol values were not higher than 250 mg/dl. We should use not only the serum cholesterol value but also the apo B/Apo Al ratio as an indicator to evaluate the roles of lipids in the development of atherosclerosis.