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The rising incidence of stroke, congestive heart failure (CHF) and end stage renal disease (ESRD) has signalled a need to increase awareness, treatment and control of hypertension. There continues to be a need for effective antihypertensive medications since hypertension is a major precursor to various forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system (RAAS) is a key component to the development of hypertension and can be one target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the most recent class of agents available to treat hypertension, which work by by inhibiting ATII at the receptor level. Currently, national consensus guidelines recommend that ARBs should be reserved for hypertensive patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however, are moving to the forefront of therapy with a promising role in the area of renoprotection and CHF. Recent trials such as the The Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val-HeFT) adds to the growing body of evidence that ARBs may improve morbidity and mortality in CHF patients. As a class, ARBs are well tolerated and have a lower incidence of cough and angioedema compared to ACEIs. This article reviews the differences among the ARBs, existing efficacy data in hypertension, and explores the role of ARBs in CHF and renal disease.
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PMID:Angiotensin II receptor blockers for the treatment of hypertension. 1182 17

The macrolide antibiotic erythromycin has been known to be associated with increased gastrointestinal motility since its introduction more than 35 years ago. Investigators have, thus, sought to take advantage of this side effect in patients with gastric stasis secondary to long-standing insulin-dependent diabetes mellitus (IDDM). The hormone motilin induces phase 3 contractions of the migrating motor complex (MMC) to induce peristalsis and facilitate gastric emptying in normal subjects. Patients with diabetic gastroparesis lack adequate phase 3 activity to effectively empty gastric contents. Exogenous motilin administered to animals and patients with diabetic gastroparesis has proven useful for promoting gastric emptying. However, motilin is expensive to produce and must be given intravenously. Erythromycin has been shown to induce premature phase 3 activity via stimulation of motilin receptors, so investigators evaluated its efficacy for the treatment of diabetic gastroparesis. Early studies in animals with experimental gastroparesis indicated that erythromycin may be a useful prokinetic agent. Human studies of both intravenous erythromycin and chronic oral erythromycin in patients with diabetic gastroparesis resistant to other prokinetic agents showed that gastric retention was indeed reduced and symptomatic improvement achieved. Even though erythromycin lost some of its prokinetic activity with chronic oral dosing, gastric retention was still significantly reduced compared to placebo or baseline. Although prokinetic agents like metoclopramide, domperidone and cisapride are effective for the treatment of patients with diabetic gastroparesis, tachyphylaxis and adverse effects are obstacles to their use. Erythromycin appears to be both effective and well tolerated in clinical studies. At this time it should be reserved for the treatment of patients with diabetic gastroparesis who are resistant to or intolerant of other prokinetic agents. Future research on erythromycin's long-term safety and comparative efficacy will further define its role.
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PMID:Erythromycin in the Treatment of Diabetic Gastroparesis. 1183 2

Recent trials have helped to clarify indications for the initial pharmacological therapy of hypertension. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World Health Organization-international Society of Hypertension (WHO-ISH) recommendations should be revised. The more recent trials indicate that: (1) diuretics and beta-blockers appear to be as effective in reducing overall morbidity/ mortality as other agents (Swedish Trial in Old Patients with Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS], Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events, especially congestive heart failure, when compared with a diuretic (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer myocardial infarctions and episodes of heart failure than calcium channel blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic patients; (4) overall cardiovascular events are similar with calcium channel blockers compared with a diuretic - however, there are fewer strokes with non-dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase in heart failure and myocardial infarctions with either a dihydropyridine or non-dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT, NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and slow progression of renal disease in type 2 diabetic patients when compared with regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High-risk hypertensive patients should probably be treated initially with combination therapy, one of which should be a diuretic. The use of diuretics and beta-blockers as well as ACE-inhibitors alone or with a diuretic should be considered as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be considered as preferred therapy in hypertensive diabetic patients. Some data suggest equal or greater reduction in strokes with a calcium channel blocker than other medications.
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PMID:Current recommendations for the treatment of hypertension: are they still valid? 1199 97

Acalculous cholecystitis represents 2% to 14% of cholecystectomies performed for acute cholecystitis. Its main etiology is ischemia of the gallbladder wall, which mainly occurs in critically ill patients, particularly in case of cardiovascular previous disease or diabetes. Acalculous cholecystitis associated with VIH are rare and have a better prognosis. Other etiologies are exceptional. Diagnosis of acalculous cholecystitis is difficult, with a lack of specificity of abdominal ultrasound for the diagnosis of ischemic cholecystitis. In all cases, cholecystectomy is a definitive treatment allowing certain diagnosis. Percutaneous drainage must be reserved to patients whose general condition does not allow general anesthesia. Medical treatment alone is not indicated in acalculous cholecystitis.
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PMID:[Alithiasic cholecystitis in the adult: etiologies, diagnosis and treatment]. 1209 14

Intermittent claudication (IC) is a common, debilitating symptom of atherosclerotic peripheral arterial disease. There are two therapeutic objectives in patients with IC: relief of symptoms and secondary prevention of acute thrombotic complications. Among patients with Fontaine stage II disease, surgical revascularization for symptom relief is reserved for those in whom exercise/lifestyle modification and medical therapy has failed. To improve exercise tolerance in IC requires favourable alteration in the oxygen supply/demand relationship in the lower limb. Following the largest ever clinical trials programme in patients with IC, cilostazol, a phosophodiesterase III inhibitor, has been licensed for symptom relief in the UK. In double-blind, randomized, placebo-controlled trials involving over 2000 patients, cilostazol 100 mg b.d. produced significant and sustained improvements in pain-free and maximal walking distances as well as improved subjective assessments of quality of life. In particular, comparative studies with pentoxifylline (oxpentifylline) showed that cilostazol had significantly greater effects on functional outcome and exhibited good patient tolerance.
Diabetes Obes Metab 2002 Mar
PMID:Evidence-based symptom relief of intermittent claudication: efficacy and safety of cilostazol. 1218 Mar 54

About 600 injections per year are administered in a Luxembourg family planning center using 3 types of long acting progestatives: Depo Provera 150 and 450 and Norigest. The method is no longer reserved for women with completed families and the mentally handicapped since its reversibility has been proven. Patients seeking this type of contraception must meet the same criteria as for oral contraceptives except that women with contraindications for estrogens may tolerate progestatives. Long acting progestatives offer the safety of minipills along with high effectiveness since the risk of forgetting a pill is removed. Some women with cardiac disease, diabetes, and circulatory problems are able to use injectables, but caution should be exercised with hypertensives and the obese because of possible weight gain. Women with coagulation problems or suspected fibromas should be excluded. Administered postpartum, pure progestatives do not affect lactation. Menstrual cycles are completely disturbed, with irregular and unpredictable bleeding until amenorrhea appears after 3-6 months. Women who are psychologically unable to accept amenorrhea should not use this method, as they are more likely to experience undesirable side effects. Return of fertility upon termination of use poses no problem and usually occurs after 6-10 months, even after a single injection. Treatment with a sequential contraceptive beginning on the day when the next injection would have been given may help to reestablish menstruation. The physician should determine through a preliminary interview the couple's psychological readiness for this type of contraception. A careful medical history and gynecological examination should be done to rule out contraindications, and treatment should begin in the 1st 3 days of the cycle. Irregular and prolonged bleeding after 6 months of use can be treated with oral administration of estrogen, or by proceeding to the next injection ahead of schedule. Administration of a mild diuretic is rarely necessary for water retention. Pregnancy during use of the method is very rare but usually occurs after the 2nd or 3rd treatment and may be detected only in the 3rd or 4th month. Uterine size should be assessed at each treatment for the 1st year. Short term local treatment with estrogen rapidly restores vaginal lubrication when necessary. No serious incidents have occurred with use of long acting progestatives at this clinic.
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PMID:[Indications and medical survey of long acting progestatives used for contraception (author's transl)]. 1233 49

Thoracic radiculopathy represents an uncommon spinal disorder that is frequently overlooked in the evaluation of spinal pain syndromes. Degenerative disc disease and diabetes mellitus may frequently cause radiculopathy at the thoracic level. Electromyography and magnetic resonance imaging are useful in the evaluation of radiculopathy and thoracic spinal pain syndromes. Percutaneous vertebroplasty is a procedure that may be used in the treatment of thoracic spinal pain syndromes. Surgical intervention for thoracic radiculopathy usually is reserved for patients with progressive myelopathy and neurologic compromise.
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PMID:Thoracic radiculopathy. 1238 May 52

The cutting balloon (CB) is a specialized device designed to create discrete longitudinal incisions in the atherosclerotic target coronary segment during balloon inflation. Such controlled dilatation theoretically reduces the force needed to dilate an obstructive lesion compared with standard percutaneous transluminal coronary angioplasty (PTCA). We report a multicenter, randomized trial comparing the incidence of restenosis after CB angioplasty versus conventional balloon angioplasty in 1,238 patients. Six hundred seventeen patients were randomized to CB treatment, and 621 to PTCA. The mean reference vessel diameter was 2.86 +/- 0.49 mm, mean lesion length 8.9 +/- 4.3 mm, and prevalence of diabetes mellitus in patients was 13%. The primary end point, the 6-month binary angiographic restenosis rate, was 31.4% for CB and 30.4% for PTCA (p = 0.75). Acute procedural success, defined as the attainment of <50% diameter stenosis without in-hospital major adverse cardiac events, was 92.9% for CB and 94.7% for PTCA (p = 0.24). Freedom from target vessel revascularization was slightly higher in the CB arm (88.5% vs 84.6%, log-rank p = 0.04). Five coronary perforations occurred in the CB arm only (0.8% vs 0%, p = 0.03). At 270 days, rates of myocardial infarction, death, and total major adverse cardiac events for CB and PTCA were 4.7% versus 2.4% (p = 0.03), 1.3% versus 0.3% (p = 0.06), and 13.6% versus 15.1% (p = 0.34), respectively. In summary, the proposed mechanism of controlled dilatation did not reduce the rate of angiographic restenosis for the CB compared with conventional balloon angioplasty. CB angioplasty should be reserved for difficult lesions in which controlled dilatation is believed to provide a better acute result compared with balloon angioplasty alone.
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PMID:Cutting balloon angioplasty for the prevention of restenosis: results of the Cutting Balloon Global Randomized Trial. 1242 7

To determine if the indications and numbers of the axillofemoral bypass have changed, a retrospective analysis was performed of all patients undergoing axillofemoral bypass over the past two decades. Group A (1980-89) and group B (1990-99) were compared using demographics, comorbid illness, perioperative outcomes, and indications for operation. There were 33 extraanatomic bypasses performed in group A and 24 extraanatomic bypasses in group B. The average age in both group A and group B was 69 years. Males comprised a higher percentage in group B (75%) than in group A (55%). The percentage of smokers was roughly equivalent (group A 76%, group B 71%). Coronary artery disease was more prevalent in group A (85%) than in group B (63%). Diabetes mellitus was also more common in group A (33%) than in group B (21%). All of the grafts in group B were composed of PTFE and there were 2 early (30 day) failures (6%). There were no perioperative deaths, strokes, or myocardial infarctions. At our institution, the axillofemoral bypass is now reserved almost exclusively for the treatment of graft infections and rarely for primary limb ischemia. This evolution is a reflection of the increase in interventional techniques used to improve inflow in high-risk patients who require revascularization.
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PMID:The evolution of the axillofemoral bypass over two decades. 1242 58

Adequate control of blood sugar has been repeatedly shown to translate into reductions in diabetic complications. Although insulin therapy in patients with type 2 diabetes can achieve and maintain near-normal glycemic goals associated with reductions in microvascular and macrovascular end points, it is often reserved for the later stages of management of these patients because of real or perceived concerns; these include fear and anxiety about worsening diabetes, failure of self-management, loss of quality of life, the pain of self-injection, and the possibility of multiple daily injections. Risks of hypoglycemia, weight gain, and cardiovascular disease may be concerns of physicians, but these risks are either manageable or, in the case of cardiovascular disease, unfounded. Taken together, the barriers to insulin therapy frequently compel physicians to consider it a treatment of last resort. Some of the more common barriers have been addressed through device options such as insulin pens and jet injectors, which may improve convenience but do not alleviate pain and discomfort. Transdermal delivery options using iontophoresis or ultrasound are in early stages of development, but methods based on transmucosal delivery-including buccal, nasal, and pulmonary routes-are further advanced. In particular, recent evidence shows that pulmonary forms of insulin are as safe and effective as rapid-acting injected insulin, and are well accepted by patients even over long-term periods of use. These innovative delivery systems may help overcome the barriers to insulin use.
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PMID:Evaluation of alternative strategies for optimizing glycemia: progress to date. 1243 59


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