Clinical Review Recent advances

General medicine

BMJ 1998; 317 doi: (Published 19 September 1998) Cite this as: BMJ 1998;317:792
  1. Laura A Petersen, assistant professor of medicine
  1. Health Services Research and Development, Department of Veteran's Affairs Medical Centre, Houston, TX 77030, USA
  • Accepted 22 January 1998

One review could not encompass all the noteworthy recent advances in general medicine, but research findings relevant to the treatment of HIV, congestive heart failure, prostatic hypertrophy, hypertension, hypercholesterolaemia, oestrogen replacement, osteoporosis, cancer screening, and symptoms of the common cold have generated particular interest.


For this review, I defined advances in general medicine as research that might change the management of chronic disease or the strategies to prevent disease. Given the breadth of the subject, I asked colleagues to nominate the three to five articles published in the previous 18 months that they believed had been most important to the practice of general medicine.

HIV infection

Advances in understanding of the pathogenesis and treatment of HIV related illness have resulted in new recommendations for antiretroviral treatment and disease monitoring. Plasma HIV RNA concentrations are now thought to be the most important predictor of outcome,13 and reductions in the viral load are associated with a reduced risk of disease progression.4 Concerns that treatment with only one agent is associated with rapid selection of resistant virus variants have led to the current recommendation of a regimen incorporating three drugs—two nucleoside analogue reverse transcriptase inhibitors and a protease inhibitor. All patients with plasma HIV RNA concentrations >5000 to 10 000 copies/ml should be given triple therapy, regardless of their CD4+ cell count. Triple therapy is also recommended for patients with symptomatic HIV disease or with CD4+ cell counts below 0.50 × 109/l.5 Unfortunately, these regimens are costly, complicated, and require great commitment on the part of both patients and health care providers. Lack of diligence in adhering to the complex drug regimen may result in emergence of drug resistant strains.

Recent advances

  • New recommendations for antiretroviral therapy and disease monitoring in HIV related illness have been drawn up

  • Blockade may be effective in selected patients with congestive heart failure but should not replace angiotensin converting enzyme inhibitors

  • Systolic and diastolic blood pressures were reduced by a diet rich in fruits, vegetables, and low fat dairy foods and low in saturated and total fats

  • Reducing low density lipoprotein cholesterol concentrations after myocardial infarction was effective even in patients whose cholesterol concentrations were average

  • Oestrogen replacement therapy prolongs life on average, and its protective effect in coronary artery disease is not lost when progestins are added

  • Vaginal smears after hysterectomy for benign disease have very low positive predictive value

Prostatic hyperplasia

A comparison of two treatments for symptomatic benign prostatic hyperplasia may change practice. When the α-adrenergic blocker terazosin (10 mg daily) was compared to a 5-α-reductase inhibitor, finasteride (5 mg daily), and placebo in 1200 men, symptoms in the terazosin group promptly improved, and the improvement persisted at one year. The finasteride and placebo groups did not differ in the American Urological Association's symptom score or in peak urinary flow rates at baseline and one year.6

Congestive heart failure

Carvedilol, a β-adrenergic blocker, is one new treatment for congestive heart failure. In 415 selected patients, fewer in the treatment group died or were admitted to hospital (P=0.02), but the two groups did not differ for mortality alone, exercise performance, or symptoms of congestive heart failure.7 The study of left ventricular dysfunction (SOLVD) showed that angiotensin converting enzyme inhibitors improve symptoms and reduce mortality in congestive heart failure,8 and now new data show that angiotensin converting enzyme inhibitors reduce long term mortality in patients with congestive heart failure who have an acute myocardial infarction. In a study of 603 patients with confirmed myocardial infarction complicated by congestive heart failure, mortality was lower at three years in the group randomised to receive angiotensin converting enzyme inhibitors 2-9 days after infarction than in the placebo group (83 (28%) v 117 (39%) deaths, P=0.002).9 Given the expanding indications for angiotensin converting enzyme inhibitors, losartan, an angiotensin receptor blocker, may prove useful for patients with “captopril cough” or other side effects. A randomised trial comparing losartan to captopril in older patients with congestive heart failure (ejection fraction 40%) found that all cause mortality and hospital admissions were lower with losartan than with captopril, but there were relative few hard end points in comparison with large studies of angiotensin enzyme inhibitors.10 Until results of larger trials are available, new agents should not generally be used to treat congestive heart failure and should not be substituted for angiotensin converting enzyme inhibitors.


First line treatment for hypertension?


While drugs have been the source of several interesting developments in treatment of various clinical conditions, a recent study found that a diet rich in fruits, vegetables, and low fat dairy foods, and with reduced saturated and total fat, reduced systolic and diastolic blood pressures respectively by 11.4 mm Hg and 5.5 mm Hg more than a control diet that was low in fruits, vegetables, and dairy products and had a fat content typical of the average American diet.11 The authors suggest that the adoption of this diet should complement rather than supplant current recommendations—weight control, reduced sodium chloride intake, and reduced alcohol consumption. Since the reduction in blood pressure was similar to that observed in trials of single drug treatments, such a diet might be recommended as first line treatment for hypertension. In fact, the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure advocates such a “stepped care” approach to treatment in its 1997 report.12

Alcohol intake and health

The relation between alcohol consumption and health has been a popular topic in the lay press. A review of case-control and cohort studies of alcohol consumption provides evidence that all types of alcoholic drinks are associated with lower risk for coronary heart disease.13 A study of alcohol intake and low density lipoprotein cholesterol in nearly 3000 men found a strong inverse association between alcohol intake and risk for coronary heart disease in subjects with low density lipoprotein cholesterol concentrations in the highest fifth. Compared with abstainers, men who drank 22 or more alcoholic beverages per week had a relative risk for coronary heart disease of 0.2 (95% confidence interval 0.1 to 0.8; P<0.01). In the lowest fifth (subjects with low density lipoprotein cholesterol 3.62 mmol/l), however, the inverse association between alcohol intake and coronary heart disease was not significant,14 implying that people with low concentrations of low density lipoprotein will not benefit from consuming alcohol.


A five year randomised trial of pravastatin treatment (40 mg/day) in patients whose cholesterol concentrations after myocardial infarction were average (less than 240 mg/dl (6.2 mmol/l)), showed that lowering low density lipoprotein concentrations reduced the incidence of a combined end point of fatal coronary events and non-fatal myocardial infarction. In addition, the need for revascularisation procedures was reduced in the treatment group. The fact that little or no effect occurred in patients with a baseline low density lipoprotein concentration <125 mg/dl (<3.2 mmol/l) is noteworthy.15 Taken with data from previous studies, it seems that most patients will benefit from aspirin, β blockade, and hydroxymethyl glutaryl coenzyme A reductase inhibition after a myocardial infarction.

Risk factors for atherosclerotic disease

Hypertension and hyperlipidaemia are well accepted risk factors for coronary heart disease, but new risk factors for atherosclerotic disease have been proposed. In survivors of myocardial infarction, titres of Chlamydia pneumoniae antibody were correlated with the likelihood of adverse cardiovascular outcomes.16 In another study, in which atherosclerosis was determined by direct immunofluorescence, C pneumoniae was present in 73% of patients with atherosclerosis who had atherectomy compared with 4% of those who did not have atherosclerosis.17

Plasma homocysteine values have been associated with overall mortality in patients with confirmed coronary heart disease,18 and risk of death from coronary heart disease during 15 years' follow up was associated with low serum folate concentrations.19 The effect is postulated to occur through the conversion of homocysteine to methionine, which requires folate.

Verifying risk factors

While many of the newly proposed risk factors for atherosclerosis are biologically plausible, atherogenesis is probably a product of several interacting determinants. The challenge of the next stage in research into risk factors for atherosclerosis will be to determine how these new risk factors interact with those identified in the past and how to show that interventions, such as eradication of C pneumoniae20 or folate supplements affect the incidence and outcome of coronary heart disease.

What contribution to the observed declines in the incidence of and mortality from coronary heart disease is made by various types of interventions that alter the accepted risk factors for atherosclerosis? A group of investigators sought to determine the proportional contributions of changes in various risk factors by using a computer simulation model of people in the United States between the ages of 35 and 84 years. They estimated that only a quarter of the fall in coronary heart disease mortality in 1980-90 was a result of primary prevention (decrease in incidence). Most could be explained by improvements in the management of patients with diagnosed heart disease through risk factor reduction (secondary prevention) and better treatment. Of various lifestyle changes, lipid profile improvements explained one third of the fall in mortality.

Hormone replacement therapy

Reducing the risk for heart disease is certainly one reason for advising postmenopausal women to use oestrogen replacement therapy. An observational study documented that the protective effect of oestrogen for coronary disease is not lost when progestins are added. This protective effect was only present for the 0.625 mg dose of conjugated oestrogen and was no longer statistically significant three years after stopping treatment.22 The same group showed that hormone replacement therapy prolongs life on average, with less impressive prolongation for women who had been taking hormones for a decade or longer, for those who had not taken oestrogen for the previous five years, and for those with no cardiac risk factors.23 A predictive model using data derived from published reports showed that hormone therapy should increase life expectancy for most women, including an increase of up to 41 months for women at the greatest risk for coronary heart disease and the lowest risk for breast cancer.24 New, tissue specific oestrogens may provide the benefits of coronary disease and osteoporosis prevention without the risks for breast cancer.25

Another observational study added additional items to the “benefit” side of the counselling equation for women considering oestrogen replacement therapy. A community based cohort of 1124 elderly women was followed longitudinally. Medication use was determined and blinded neurophysiological testing at baseline and follow up were performed to assess the presence of Alzheimer's disease. Altogether 5.8% of the cohort who had ever used oestrogen replacement therapy developed Alzheimer's disease compared to 16.3% of those who had never used it (P<0.001). Importantly, the risk for Alzheimer's disease showed a dose-response effect. The risk fell as the duration of oestrogen replacement therapy increased.26


More data regarding the use of alendronate in osteoporosis are available. In a randomised trial of postmenopausal women with low bone mass density and at least one vertebral fracture at baseline, alendronate increased mean bone mass by up to 6.2% over placebo and reduced the number of new fractures. The groups did not differ in complications not related to fractures. These data are the first in women with established osteoporosis.27

Smear testing and hysterectomy

For women who have previously undergone a hysterectomy for benign disease, there are now data that inform recommendations for cytological screening. A large study of inner city women in the southern United States showed that vaginal cytological screening after hysterectomy for benign disease had a very low positive predictive value. This result is not surprising, given the very low prevalence of cancer of the vagina.28

Common cold

And finally, until a cure for the common cold is developed we must be satisfied with an advance in treating symptoms. In a randomised trial, zinc gluconate lozenges begun in the first 24 hours after cold symptoms developed reduced the median duration of symptoms (4.4 days in the zinc group compared with 7.6 days in the placebo group; P<0.001). More patients in the intervention group noted an unpleasant taste or reported nausea, but the groups did not differ in relation to other side effects.29

Questions that need answers

  • Long term outcome of antiretroviral regimens in AIDS

  • How postulated risk factors for atherosclerosis (such as Chlamydia pneumoniae infection or raised homocysteine concentrations) interact with identified risk factors

  • Whether interventions such as eradication of Chlamydia pneumoniae or increased intake of antioxidants or folate supplementation affect the incidence and outcome of coronary heart disease

  • Whether use of tissue specific oestrogens affects the risk of cancer, coronary heart disease, and tolerance of side effects

  • Comparison of βblockers and angiotensin converting enzyme inhibitors for quality of life and mortality in coronary heart disease

  • Long term outcome of the use of “lifestyle modification” to treat hypertension

  • Mechanism for utility of zinc gluconate in treating cold symptoms, and its effectiveness in decreasing absenteeism, transmission of viruses, complications, and utilisation of health care


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