摘要:

Summary:The fragmentary knowledge of gastric ulcer aetiology is contrasted with the developing repertoire of short term drug treatments Reasons are also advanced for believing that gastric ulcer may be a disease of diminishing importance and that this is due to environmental changes rather than to the introduction of effective treatments.

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb04384.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb03330.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Summary:There are six drugs usually implicated in peptic ulceration and these are adrenal corticosteroids, aspirin, phenylbutazone, indomethacin, ethanol and caffeine. The types of data upon which these conclusions rest follows three lines of evidence. First, the production of ulcers in experimental animals; all the drugs mentioned above can produce experimental ulcers. Second, the cause and effect relationship in man, i.e. epidemiological evidence; the epidemiological evidence is very weak except for aspirin. Third, a mechanism suspected of participating in the pathogenesis; the pathogenesis of drug ulceration is not fully understood but aspirin may be the only one with a body of data to support its ulcerogenic effect.The pathogenesis of peptic ulcer is usually considered in terms of the equation, acid‐pepsin versus mucosal resistance. Caffeine is a moderately strong stimulus of acid secretion but corticosteroids, phenylbutazone, ethanol and indomethacin are very weak stimulants or have no effect. Aspirin decreases acid secretion. The lack of effect of these drugs on acid‐pepsin secretion has led investigators to study the mucosal resistance.Mucosal resistance may be due to the gastric mucus barrier or the gastric mucosal barrier. The evidence for the mucus barrier rests on data indicating that mucus secretion is decreased and altered in composition by some of the drugs. It is difficult to know what this means since mucus has virtually no buffer capacity or neutralizing power and does not offer a barrier to the free diffusion of hydrogen ion. Thus, alteration of the composition and secretory rate of mucus may have no bearing on drug induced ulceration.The other parameter is the gastric mucosal barrier which prevents the acid in the lumen from diffusing into the blood down a high concentration gradient and similarly prevents sodium from diffusing from interstitial fluid into the lumen down its concentration gradient. The barrier is thought to depend upon the lipo‐protein cellular lining. When the barrier is “broken”, acid rapidly leaves the lumen of the stomach, sodium enters the lumen of the stomach and the normal transmucosal potential difference (in man 40 mV, lumen negative to serosa) decreases.Unbuffered aspirin breaks the mucosal barrier but if buffered to pH 6–7 it has no effect. Indomethacin has variable effects in the dog but has no effect in man. Ethanol breaks the barrier in concentrations greater than 3 M (about 12%). Phenylbutazone, caffeine or adrenal corticosteroids have no effect. The effects of unbuffered aspirin and ethanol given together are additive. In 15 subjects on long term aspirin therapy (5.5 g/day for seven years) or long term prednisone therapy (20 mg/day for two months to six years) it was found that their electrical potential difference was normal and they behaved like normal subjects to a challenge with aspirin or prednisone. These studies suggest that aspirin causes episodes of acute damage which is potentially reversible.Of all the drugs, unbuffered aspirin is the most effective agent for breaking the barrier and causing erosions and occult bleeding. Limited studies with the other drugs indicate they usually do not cause erosions (except excessive ethanol ingestion) or occult bleeding (indomethacin causes a mild increase). These latter complications, i.e. erosions, occult bleeding, may be explained on the basis of the gastric mucosal bar

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb04385.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb03331.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Summary:A beta‐blocker‐based antihypertensive drug program guided by age and renin.From analyses of the effectiveness of beta‐blocker monotherapy in relation to the patient's age and to pre‐treatment renin determinations an antihypertensive drug program is proposed in which beta‐blockers form the cornerstone.Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%), or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall into two categories: younger patients with fairly mild hypertension and older patients with more severe hypertension and signs of renal disease.The antihypertensive efficacy of beta‐blocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, beta‐blockers normalized blood pressure (≤ 95 mmHg diastolic) in three‐quarters of the younger than 40‐year‐olds, in about half of those aged 40–60 years, but in only 20% of those aged over 60 years.On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state while those with a normal or high renin—for a given age and elevated pressure—have a relatively increased adrenergic nervous activity.Because the beta‐blockers have a potent suppressive action on the renin‐angiotensin system—and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms—their antihypertensive mode of action may be linked to an important extent, though no

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb03332.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Summary:A combined test of anterior pituitary reserve.

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb03288.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Summary:1.The initial site of damage in analgesic abuse is the renal medulla and the characteristic lesion is renal papillary necrosis. The papillary necrosis appears to be an ischaemic infarct. The cortical lesion of chronic interstitial nephritis is a non‐specific change and secondary to obstruction to tubules in the necrotic medulla.2.Medullary perfusion and the concentration mechanism appear to be important factors in the genesis of renal papillary necrosis.3.Experimental and clinical studies suggest that abuse of compound analgesics containing aspirin, phenacetin and caffeine result in renal papillary necrosis and the clinical syndrome of analgesic nephropathy. In the APC mixture aspirin appears to be the major nephrotoxic agent while phenacetin plays a synergistic but secondary role in the renal nephrotoxicit

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb04387.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Summary:Once daily dosage beta‐blockade: Antihypertensive efficacy of slow release oxprenolol as related to renin and age.A single daily dose antihypertensive therapy with a new slow‐release (SR) form of the beta‐adrenoceptor blocking agent oxprenolol was as effective as a standard tid beta‐blocker regimen in maintaining therapeutic effects over 24 hours. The good overall response rate (target ≤ 95 mmHg diastolic) of 67% was achieved in eight of the 11 high renin patients and 16 out of the 20 normal renin ones; the five low renin patients, who were also older, proved to be non‐responsive. In terms of age, 83% of the patients aged under 40 years showed a reduction in diastolic pressure to ≤ 95 mmHg, this percentage being significantly better than the 50% response rate in the 40–56‐year‐olds.In nine of the 12 beta‐blocker non‐responders the diastolic blood pressure was reduced to ≤ 95 mmHg by adding a diuretic, and in four of the nine, all of them low renin patients, this effect persisted in response to diuretics alone. Oxprenolol SR suppresses renin acutely (59%) and chronically (62%), and it blunts the renin stimula

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb03333.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb04389.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Summary:Renin unresponsiveness and the effects of oxprenolol, methyldopa and spironolactone in patients with essential hypertension.Plasma renin activity (PRA), supine, erect and post‐frusemide (1 mg/kg IV) was studied in 51 patients with previously untreated essential hypertension and their age‐and sex‐matched normotensive controls. Supine PRA, and the rise in PRA in response to the erect posture and frusemide, were significantly less in hypertensives compared to controls. When the hypertensives were arbitrarily divided into lower, mid, and upper subgroups according to supine PRA, the renin responsiveness was similar in each subgroup but significantly less in hypertensives compared to controls, subdivided in the same way. This does not support the existence of a separate “low renin” subgroup. The low supine PRA and reduced response to stimulation appears to be a feature of patients with essential hypertension.Thirty‐nine of these hypertensives entered a double‐blind cross‐over drug trial of oxprenolol, methyldopa and spironolactone. All three drugs were equally effective in lowering the systolic and diastolic blood pressures in all three renin subgroups. Spironolactone caused a greater fall in systolic pressure in the lower renin group than in the other groups. Oxprenolol was the best tolerated drug, with only 5% of patients withdrawing due to side‐effects compared to 13% on spironolactone and

ISSN:0004-8291    

DOI:10.1111/j.1445-5994.1976.tb03334.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY