Journal of internal medicine. Supplement最新文献

We randomized 352 patients with suspected acute myocardial infarction (AMI) to treatment with rt-PA (n = 177) or placebo (n = 175). Patients were eligible if evaluated within 2 h and 45 min from onset of chest pain, and if aged less than 75 years. There were no ECG criteria for inclusion. A mobile coronary-care unit with a cardiologist present was used to initiate treatment at home in 29% of cases. During 1 year of follow-up the mortality in patients treated with rt-PA was 10.2%, as compared with 14.3% in patients the initial ECG, the mortality during the first year was 8% in the rt-PA group vs. 18% in the placebo group (P less than 0.05). Among patients without ST-elevation the mortality was 9% for the rt-PA group vs. 12% for the placebo group (NS). Requirement for rehospitalization, symptoms of angina pectoris and congestive heart failure, time of return to work and requirement for various medications did not differ significantly between the two groups, regardless of the initial ECG pattern.

In a randomized, double-blind study, rt-PA vs. placebo treatment in early suspected acute myocardial infarction (AMI) was evaluated in patients both in hospital and prehospitally. The inclusion criteria were as follows: (a) age less than 75 years; and (b) chest pain indicative of AMI, of no longer than 2.75 h duration before first examination. In the prehospital setting a mobile coronary-care unit, accompanied by a cardiologist, was sent out by the ambulance services to 350 patients, of whom 205 (59%) were classified as non-eligible when examined by the cardiologist. Of the 145 patients who fulfilled the inclusion criteria, 44 were excluded due to contraindications to thrombolytic treatment. Thus 101 patients were randomized to blinded treatment outside hospital. The median time interval between onset of pain and treatment was 75 min, 45 min less than for those subjects who were randomized in hospital. The prevalence of confirmed AMI was 42% in the prehospital group, compared to 66% in the hospital group. Bleeding and cardiac complications for prehospital treatment were few, and similar to those for hospital treatment. In conclusion, prehospital thrombolysis was feasible, and delay times prior to treatment were significantly reduced. However, the specificity and diagnostic accuracy were lower than those achieved with in-hospital therapy.

Epidemiological evidence suggests that there is a close association between obesity, non-insulin-dependent diabetes (NIDDM) and hypertension. Obesity and NIDDM are the classical insulin-resistant states. Even in the absence of these conditions, essential hypertension is associated with insulin resistance. In view of the acute effects of insulin on renal sodium reabsorption, the sympathetic nervous system, the renin-angiotensin-aldosterone system, the transmembranous cation transport, the cardiovascular reactivity, the atrial natriuretic peptide and the kallikrein-kinin system, hyperinsulinaemia may contribute to the development of hypertension in these diseases. Preliminary evidence suggests that sensitivity to these possible blood-pressure-elevating action(s) of insulin is still present despite the resistance to the glucose-lowering action of the hormone. However, extrapolation of the epidemiological data and results of acute experiments indicate that the impact on blood pressure is rather small. The pathophysiological mechanisms of hypertension in the above-mentioned conditions are also not always consistent with insulin action(s). Moreover, some data suggest that insulin resistance, and not hyperinsulinaemia per se, underlies the blood pressure elevation, while the possibility cannot be excluded that both hypertension and insulin resistance are co-inherited, but unrelated, abnormalities.

The prohormone form of insulin is contained in the secretory granules of the pancreatic beta-cell and released as the mature peptide sequence by exocytosis. One of the factors believed to trigger the movement of the secretory granules to the cell surface and their fusion with the plasma membrane is an increase in the cytosolic Ca2+ concentration [Ca2+]i. Extracellular glucose depolarizes the cells and favours the opening of voltage-dependent Ca2+ channels, which results in a rise in [Ca2+]i and activation of protein kinases. The phosphorylation of proteins associated with the functions of the secretory granules will influence the movement of the granules towards the plasma membrane. Due to their effects on voltage-dependent Ca2+ channels, it is suspected that calcium antagonists influence glucose-stimulated insulin release. Current information on calcium antagonists suggests that they may have different effects on glucose tolerance in non-diabetic and diabetic subjects. In non-diabetic hypertensives, fasting blood glucose is generally not affected by verapamil, diltiazem or nifedipine taken in therapeutic doses, although some reports indicate that high-dose nifedipine or diltiazem may deteriorate glucose homeostasis. Studies of the effect of single doses of calcium antagonists on the response to a glucose challenge have yielded somewhat conflicting results. The general picture, however, is that under these circumstances glucose tolerance in non-diabetic individuals remains largely unaffected, although higher doses of verapamil and nifedipine have impaired glucose tolerance slightly in some studies. In patients with non-insulin-dependent diabetes mellitus (NIDDM), acute administration of calcium antagonists with or without glucose challenge does not generally cause any changes in the blood glucose or insulin profiles. During short-term calcium antagonist therapy, conflicting results have been obtained. Overall, the data suggest that these drugs do not significantly modify glucose homeostasis. However, some reports do suggest that diabetic patients may deteriorate on nifedipine treatment. There are as yet no clear indications of any consistent changes in glucose homeostasis during long-term administration of verapamil, diltiazem or nifedipine. However, isolated case reports have indicated unfavourable changes in glucose homeostasis in patients treated with calcium antagonists of the dihydropyridine type, such as nifedipine.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrastructural studies performed on pigs revealed that numerous cytoplasmic tubulovesicles were present in resting pancreatic duct cells. Elevation of systemic arterial PCO2 from 5.5 to 11 kPa increased the number of vesicles more than twofold. Following secretin administration, concurrent with the onset of HCO3- secretion (JHCO3), the cytoplasm became devoid of vesicles, and the basolateral plasma membrane surface area more than doubled. Similar phenomena were observed in bile duct cells. After pretreatment with the microtubules-inhibiting drug colchicine, secretin failed to reduce duct cell vesicle density, and JHCO3 was reduced by c. 50% compared to the control. These ultrastructural changes resemble those described in other H+/HCO3(-)-transporting organs such as the distal nephron and the urinary bladder. Our findings are compatible with the notion that cytoplasmic vesicles containing H(+)-ATPases are incorporated into the basolateral plasma membrane of secretory cells during secretin stimulation. Active transport of H+ into interstitial fluid might therefore be the driving force underlying JHCO3.

When the integrity of the gastric mucosa is destroyed, there is a large passive diffusion of interstitial HCO3- from the nutrient side to the luminal side of the tissue. In the absence of nutrient HCO3-, rapid repair of superficial mucosal injuries is slowed markedly down or does not take place at all. The effects of a high degree of luminal acidification, which prevents rapid repair, can be counteracted by high concentrations of nutrient HCO3-. The importance of nutrient HCO3- is emphasized by the finding that luminal acid may destroy both the fibrin network beneath which restitution occurs and the basal lamina along which viable cells must migrate to re-establish epithelial continuity. At the present time, it is not known whether the preventive effects of HCO3- against ulceration in a variety of systems are dependent upon leakage of HCO3- toward the surface, or whether nutrient HCO3- actually enters cells in order to regulate intracellular pH.