The effects of postmenopausal hormone replacement therapy on hemostatic variables: a meta-analysis of 46 studies.

The aim of the study was to summarize and reanalyze all available data from the literature to study the overall effect of postmenopausal hormone replacement therapy (HRT) and its various forms on hemostatic variables. Studies were identified from literature searches by Medline and Index Medicus, review articles and personal communications. Reference lists of all articles were checked to find additional studies. Principal investigators were contacted and asked to provide additional data if required. Data were collected separately for each factor of the hemostatic system. Studies written in any language were included. Each collection of studies was analyzed using standard methods for meta-analysis. A total of 76 arms of 48 studies were eligible for analysis. This included 6,119 women using HRT and 24,974 non-users. The age of investigated women was 40-68 years. HRT was associated with significantly decreased levels of fibrinogen, factor VIII, antithrombin III, and proteins C and S, but significantly increased plasminogen levels. HRT with estrogen alone or in combination with progestins, oral vs. transdermal regimens, different estrogen preparations and various progestins induced significantly different changes in many cases. In conclusion, HRT was associated with changes that could explain the increased rate of venous thrombotic events, and also with some changes that could account for beneficial vascular effects. Surprisingly, the addition of progestins induced favorable changes in many cases. Also, transdermal use was associated with more beneficial effects than oral regimens in some cases.

Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure.

OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.

Malignant thymic carcinoid in multiple endocrine neoplasia type I syndrome: case report and literature review.

OBJECTIVE: To describe a case of thymic carcinoid tumor in association with multiple endocrine neoplasia type I (MEN I) and discuss the various manifestations of this syndrome. METHODS: We present the clinical and laboratory data, including histopathologic and immunocytochemical findings, for our current patient and also review the literature on MEN I syndromes. RESULTS: In a 46-year-old Caucasian man with no family history of multiple endocrine neoplasia, numerous MEN I lesions developed over time. The patient had gastrinoma of the duodenum, Zollinger-Ellison syndrome, hyperparathyroidism, a nonfunctioning adrenal mass, and foregut carcinoid tumors, including gastric and malignant thymic carcinoids. He sequentially underwent partial gastrectomy in conjunction with Billroth II anastomosis, a four-gland parathyroidectomy, and palliative radiotherapy for malignant carcinoid tumor, as well as endoscopic excision of accessible tumors. CONCLUSION: The involvement in MEN I can be clinically complex. Early detection of MEN I lesions will facilitate timely implementation of treatment and help minimize complications.

Selecting antihypertensive drug therapy: the JNC-V controversy.

OBJECTIVE: To present both the supporting and the opposing arguments for the fifth set of recommendations issued by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC). METHODS: The published studies are reviewed, and the various opinions are discussed. RESULTS: The 1993 recommendation from the JNC that diuretics or beta-adrenergic blockers be preferred for therapy in most patients with hypertension has proved controversial. This recommendation derived primarily from recent long-term studies showing convincing reductions in cardiovascular morbidity and mortality when these agents are used to control hypertension. Comparable data have not yet been obtained for newer agents, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Nonetheless, some critics of the JNC recommendation still favor the newer agents because of their putatively superior side-effect profile, from both a metabolic and a compliance standpoint. CONCLUSION: The issue of optimal antihypertensive drug therapy will not be definitively resolved until long-term studies directly comparing the various classes of agents are completed in future years.

Hypothyroidism: a comprehensive review.

Hypothyroidism is a common clinical entity encountered frequently in most adult primary care settings. The reported prevalence in the general population is approximately 3% in men, but as high as 10% in women (Sawin, Geller, Hershman, Castelli, & Bacharach, 1989). The disease process affects every major organ system, contributing to a broad range of symptoms. Clinicians need to be familiar with the signs, the symptoms, and the appropriate laboratory studies, so that timely and accurate diagnoses can be made. This article reviews normal thyroid physiology and thyroid pathophysiology, as well as the diagnosis and treatment of several important clinical entities resulting in hypothyroidism. Research findings are included insofar as they relate to current clinical practice.

A dose-response trial of once-daily diltiazem.

This trial was performed to determine the safe and effective dosage range of once daily diltiazem (diltiazem CD) capsules for treatment of essential hypertension. Patients with essential hypertension having supine diastolic blood pressure values greater than or equal to 95 mm Hg and less than or equal to 110 mm Hg were randomly assigned to receive placebo or one of four doses of diltiazem CD: 90, 180, 360, or 540 mg. Blood pressure was measured at trough, 24 hours after the dose, and at the time of peak effect, 10 hours after the dose. Diltiazem CD lowered both supine diastolic and systolic blood pressure. A linear dose response was seen with changes in diastolic and systolic blood pressure and heart rate for trough and peak measurements. Trough/peak ratios for the 180, 360, and 540 mg doses were all greater than 0.50. Adverse effects were dose related; those most commonly reported were headache (8.6%), bradycardia (8.1%), and edema (7%), with bradycardia and edema possibly dose related. It is therefore concluded that diltiazem CD is a safe and effective antihypertensive agent.

Hyperthyroidism: a comprehensive review.

Hyperthyroidism is an endocrine disorder encountered in adult primary care clinics. This article reviews normal thyroid physiology as well as the pathophysiology, diagnosis, clinical signs and symptoms, and diagnostic tests and treatment for the most common clinical hyperthyroid entities. Current research is also discussed as it relates to clinical practice.

Evaluating arthritic complaints.

Adults with arthritic conditions are seen frequently in primary care clinics. However, more than 100 different entities can produce joint and muscle symptoms, which makes it challenging to correctly diagnose musculoskeletal complaints. There are several logical steps to follow in assessing joint disorders. The first is to differentiate between what is and what is not arthritis. Additional steps necessary for an appropriate diagnosis include analysis of a thorough history, physical examination, and laboratory and X-ray results. It is of critical importance to identify the most common forms of arthritis, as well as the specific conditions that require immediate referral. The onset, incidence, findings and pathophysiology of the following entities in the adult population are discussed: septic arthritis, osteoarthritis, rheumatoid arthritis, the crystal-induced diseases, human immunodeficiency virus (HIV) and arthritis, the seronegative spondyloarthropathies and systemic lupus erythematosus.

Treating diabetes in the elderly. What are the special considerations?

Management of diabetes in elderly patients generally follows the same lines as in younger patients; that is, improvement of blood glucose status with diet, oral hypoglycemic, and insulin therapy as required. Older patients are more fragile, however, and more caution must be used with therapeutic interventions.

When to worry about hypoglycemia.

The important causes of hypoglycemia unrelated to known diabetes are relatively few. Postprandial hypoglycemia is a relatively benign disorder. Fasting hypoglycemia is more serious and may be caused by metabolic disturbances or tumors. Several hereditary disorders cause hypoglycemia in infants and must be diagnosed and treated before serious damage occurs. A systematic clinical approach increases the likelihood of making the correct diagnosis in a timely fashion.

Fibromyalgia syndrome.

Fibromyalgia is a chronic rheumatologic disorder. The primary symptoms include musculoskeletal pain and aching, disturbed sleep, fatigue, morning stiffness, and local tenderness. It is frequently misdiagnosed, despite being a fairly common, chronic disorder in most primary care clinics. Failure to make this diagnosis often leads to unnecessary medical and surgical treatment. The treatment of fibromyalgia syndrome is multifaceted. Goals include reassurance, education about pain management and modification, and symptom reduction. Exercise may be beneficial. Amitriptyline is effective in reducing certain symptoms of fibromyalgia, such as pain and lack of restful sleep. Narcotics, steroids, and nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided.

Cushing's syndrome. How to pinpoint and treat the underlying cause.

In addition to prolonged glucocorticoid therapy (not discussed here), at least five other conditions cause Cushing's syndrome. They are excessive corticotropin secretion by the pituitary gland (which results in Cushing's disease), ectopic production of corticotropin by malignant nonpituitary tumors, benign adrenal adenoma, adrenal carcinoma, and primary adrenocortical nodular dysplasia. Each can be distinguished by a specific pathophysiologic process that triggers the adrenal glands to overproduce glucocorticoids. At present, diagnosis of Cushing's syndrome or disease relies heavily on the dexamethasone (Decadron, Hexadrol) suppression test. After diagnosis, other studies, including computed tomography, magnetic resonance imaging, and corticotropin radioimmunoassay, can be used to localize the site of the lesion. Treatment, of course, depends on the underlying cause.

Painful, painless, and postpartum thyroiditis. Distinct entities or merely variants?

Subacute thyroiditis is a common disease that often goes undetected. Indeed, both painful and painless thyroiditis are easily overlooked or misdiagnosed and perhaps mistreated unless careful attention is paid to the patient's history and physical examination. Treating the hyperthyroidism of subacute thyroiditis as if it were Graves' disease, for example, would be inappropriate, since therapy for the two entities is completely different. A form of painless thyroiditis, for reasons that remain unclear, can occur in the postpartum period and may be related to postpartum psychosis or depression.

Atrial natriuretic peptide attenuates the reflex sympathetic responses to lower body negative pressure.

The authors studied the effect of intravenous infusion of atrial natriuretic peptide (ANP) on the plasma catecholamine and forearm vasoconstrictor responses to cardiopulmonary baroreflex deactivation in six normal, male volunteers in order to determine whether ANP influences reflex forearm vasoconstriction in humans. Unloading of low-pressure cardiopulmonary baroreceptors (CPBR) was accomplished by application of low levels (-10 and -20 mm Hg) of lower body negative pressure (LBNP). The authors measured the plasma norepinephrine (NE) and epinephrine, the mean arterial pressure (MAP), and the forearm vascular resistance (FVR) responses to reflex sympathetic activation by LBNP. ANP infusion (0.1 microgram.kg-1.min-1) decreased (p less than 0.01) basal MAP, as well as plasma renin activity and plasma aldosterone levels (p less than 0.05). ANP infusion also reduced (p less than 0.01) plasma NE responses to both levels of LBNP and tended to decrease both epinephrine and FVR during ANP infusion at -20 mm Hg LBNP (p = 0.8). These data suggest that exogenous ANP inhibits the reflex sympathetic responses that occur with CPBR unloading. The blunted plasma NE responses to CPBR unloading parallel the attenuation of FVR response to LBNP during ANP infusion, despite significant LBNP-induced hypotension.

Effects of illness on thyroid function tests.

Severe illness of any type predictably leads to abnormal results on thyroid function tests. The first apparent changes are a decrease in total triiodothyronine (T3) and an increase in reverse T3. As disease progresses, a marked decline in thyroxine and an increase in T3 resin uptake are observed. Thyrotropin levels remain normal, confirming that the patient is euthyroid despite marked alterations in thyroid function tests. Supplemental thyroid hormone has never been shown to be of any value, and may indeed be harmful, in euthyroid patients with abnormal thyroid function. Recognition of the euthyroid sick syndrome is vital to avoid needless therapy.

Age-related changes in calcium metabolism. Why they occur and what can be done.

Aging has myriad effects on calcium homeostasis and metabolism. Levels of parathyroid hormone rise, making the diagnosis of primary hyperparathyroidism more difficult. Vitamin D levels decline, affecting the rate of calcium absorption from the intestine. As more and more physicians attempt to combat osteoporosis with calcium supplements, an increasing number of cases of hyperparathyroidism will likely be diagnosed. The use of supplemental calcium is probably appropriate for most elderly patients, particularly white women, but experimental evidence supporting this recommendation is surprisingly scanty. The patient's age is a major consideration when assessing laboratory results, disease risk, and optimal therapeutic strategies.