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Biomedical subjects

M Moser

Publications and source records attributed to M Moser.

At least 307 records · Page 17Linked to original sources
PubMed1987

Implications of the clinical trials on the management of hypertension.

All of the major clinical trials that employed diuretics as initial monotherapy or as one of several first-step drugs have demonstrated a marked reduction in overall cardiovascular events and stroke deaths in treated patients. Benefit has been demonstrated in all trials in patients with initial diastolic pressures of 95 mm Hg or above and in the Hypertension Detection and Follow-up Program, the only study to test the hypothesis, benefit of treatment was noted in patients with pretreatment diastolic pressures of 90 to 95 mm Hg. Although several of the trials failed to show a significant decrease in coronary events in treated patients, the two studies (Hypertension Detection and Follow-up Program and European Working Party on Hypertension in the Elderly) that treated either elderly patients or patients with pretreatment target-organ involvement, reported a reduction in deaths from ischemic heart disease following effective lowering of blood pressure. The long-term benefits of effective treatment of hypertension appear to justify the use of pharmacological intervention if nondrug treatment proves ineffective.

Adult↗
PubMed1987

Diuretics in the management of hypertension.

Thiazide diuretics have been in use for over 30 years in the treatment of hypertension. Their action results in a reduction in peripheral resistance without a significant decrease in cardiac output or a major shift in plasma volume. They are as or more effective than any of the other antihypertensive agents when used as monotherapy and can serve as baseline therapy in combination with any of the available adrenergic, converting enzyme-inhibiting agents, or calcium-entry blockers. There is a high degree of patient acceptance; titration to an effective dosage is relatively easy; and cost, relatively low. Although certain undesirable metabolic changes may occur following the use of these agents, most of them are controllable, and there is no evidence to date that they offset the benefits achieved by blood pressure lowering. Asymptomatic elevated uric acids have not been shown to be of great significance. If gout occurs, it can be managed. Alterations in glucose metabolism may occur, and in some patients, it appears that blood glucose levels are elevated over time. This is not a desirable metabolic change, but is one of doubtful prognostic significance. Changes in lipids are generally short-term, and in the major clinical trials, lipid levels have not remained elevated with a continuation of diuretic therapy. Although diuretics produce hypokalemia in a fairly high percentage of patients, this is not generally severe (less than 3.3 mEq per liter) and usually does not produce symptoms. There is no firm evidence that the hypokalemia produced by diuretics predisposes the patient to severe arrhythmias or sudden death, although this point has been emphasized repeatedly in recent publications. Diuretics can usually be given without potassium-maintenance therapy. However, hypokalemia should be prevented in the elderly, in patients with ischemic heart disease, left ventricular hypertrophy and those on digitalis, or with diabetes. We prefer potassium-sparing agents along with a diuretic over supplements to prevent hypokalemia; the number of pills is kept at a reasonable level, and cost is minimized. Physicians should continue to prescribe diuretics as first-step therapy in the majority of patients to maximize therapeutic outcome.

Blood Pressure↗
PubMed1987

Diuretics and alternative drugs in geriatric hypertension.

Thiazide diuretics are the preferred initial therapy in the majority of elderly hypertensive patients--based upon efficacy and long-term safety data. Alternative therapies may be used in subjects with persistent gout, impotence, fatigue, or electrolyte disturbances. In patients with ischemic heart disease and/or angina, beta adrenergic inhibitors or calcium entry blockers are acceptable initial therapy. Converting enzyme inhibitors may be especially useful in hypertensives with congestive heart failure. The combination of small dose diuretic therapy and one of the above alternative drugs has an important place in the treatment of the elderly hypertensive.

Age Factors↗
PubMed1986

Treating hypertension. A review of clinical trials.

Extensive clinical trials have been carried out to test the effectiveness of antihypertensive therapy in controlling high blood pressure and in reducing the morbidity and mortality associated with hypertension and related cardiovascular and cerebrovascular disease. These trials have studied more than 40,000 individuals in programs worldwide. Although they answered many important questions, some of these trials have failed to produce conclusive results concerning certain issues, such as the results of treatment on coronary artery disease. The medical community has come to rely on clinical trials in evaluating the treatment of many different chronic diseases, and this methodology has become the accepted means of evaluating therapy. Analyses of the clinical trials on hypertension and their implications should review factors other than fatal and non-fatal end points if their results are to be useful for the practicing physician in making treatment decisions.

Adult↗
PubMed1986

Implications of recent clinical trials in systemic hypertension. Results of a multicenter trial of nitrendipine, for mild to moderately severe systemic hypertension.

Results of the European Working Party group study and the Medical Research Council clinical trial in mild hypertension have important implications for the practicing physician. They appear to confirm 2 previous impressions. The first is that therapy for elderly patients with both systolic and diastolic hypertension is beneficial; cardiovascular mortality can be reduced by lowering blood pressure. These data are consistent with the findings in the 60- to 69-year-old cohort in the Hypertension Detection and Follow-up Program study in the US. The second is that specific treatment with antihypertensive agents in patients with mild hypertension will decrease overall cardiovascular mortality compared with placebo treatment. The approach to treatment in both of these studies was relatively simple, using a diuretic as step 1 therapy in the European study, and either a diuretic or a beta-adrenergic inhibiting agent in the Medical Research Council study. These data provide further evidence for the benefits of treatment of hypertension.

Aged↗
PubMed1986

Historical perspective on the management of hypertension.

Remarkable progress has been made during the past 30 years in the management of hypertension, a disease that affects approximately one out of every four adults in the United States. In the 1960s, at least half of the individuals with hypertension were unaware of their disease, and the blood pressures of fewer than 20 percent were controlled at normotensive levels. In contrast, in the 1980s, only a small percentage, perhaps as few as 10 or 15 percent of hypertensive patients, are unaware of their disease and, in many parts of the country, more than 60 percent are being treated to goal blood pressure levels. More effective treatment of hypertension is probably a major reason for the 45 percent decrease in stroke mortality rates in the last 12 years alone and for the dramatic decrease in the number of hypertensive patients in whom renal failure or congestive heart failure develops. In addition, at least a portion of the 25 to 30 percent decrease in coronary mortality rates can probably be attributed to better management of patients with hypertension. The availability of antihypertensive drugs in the 1950s (rauwolfia preparations, veratrum derivatives, thiocyanates, hydralazine, and the ganglion blockers) and the discovery of more effective agents in the period from the 1960s to the present have dramatically improved the prognosis of hypertensive patients. Thiazide diuretics, centrally acting sympatholytic agents, beta-adrenergic inhibitors, and, more recently, selective alpha-adrenergic inhibitors, converting-enzyme inhibitors, and calcium entry blockers are examples of these medications. All of these agents have some side effects, with varying patient acceptability. The search continues for newer drugs that are well tolerated, that lower blood pressure by reducing peripheral resistance, and that produce few metabolic changes. A detailed review of the physiologic effects of antihypertensive medications, as well as a critique of the clinical trials and some of the problems noted in the pharmacologic management of hypertension, is presented.

Adrenergic alpha-Antagonists↗
PubMed1986

Molecular mapping of idiotopes of anti-arsonate antibodies.

As part of understanding molecular function in structural terms, we have been attempting to map the idiotypic topography of specific anti-arsonate (Ars) antibodies. A panel of anti-Ars hybridomas of which the complete primary sequences are known were used. These molecules show a varied reactivity profile with a panel of monoclonal anti-idiotypic antibodies. By judicious chain recombination experiments and chemical modifications that altered this reactivity profile, we were able to identify particular amino acid residues or discreet regions of anti-Ars antibodies as having crucial roles in the expression of idiotypic determinants. Idiotopes were mapped to the heavy chain second hypervariable region and D segment, and to the light chain first and third hypervariable regions.

Amino Acid Sequence↗
PubMed1986

Study of idiotopic suppression induced by anti-cross-reactive idiotype monoclonal antibody in the anti-p-azophenylarsonate antibody response.

A/J mice immunized with p-azophenylarsonate coupled to keyhole limpet hemocyanin produce antibodies expressing a cross-reactive idiotype (CRIA). The pretreatment of A/J mice with anti-idiotypic polyclonal or monoclonal antibody directed against the major cross-reactive idiotype (CRIA) borne by p-azophenylarsonate-specific antibody can lead to idiotypic suppression. In this study, we investigate this idiotypic suppression by using four mAb2 (E4, H8, E3, 2D3) recognizing distinct idiotopes whose expression is related to the presence of particular gene segments of the heavy chain V region. 2D3 expression has been related to the presence of some amino acid in the CDR2 region of the VH gene segment derived from the germ line VH IdCR11. So far, the latter is the only germ-line gene coding for CRIA+ antibody that has been identified in the A/J genome. E4 and H8 expression has been related to the use of a particular D segment, whereas E3 expression has been attributed to certain combinations of D and JH segments. Therefore, we might expect independent regulation of the expression of those various idiotopes in relation to the mechanism of gene recombination. Indeed, we observed that 2D3-suppressed A/J mice still produce the three other idiotopes, suggesting the recombination of those particular D and J segments with a different VH gene. Such a gene has been identified in the genome of BALB/c mice. A/J mice pretreated with one of the other three mAb2 are generally cosuppressed for the expression of E4, H8, and E3, but they still produce 2D3+ antibody. In this case, the IdCR11 VH germ-line gene is most probably recombined with different D and J segments. Molecular evidence for the existence of such molecules has also been presented in the literature. So our serologic data on idiotopic suppression in the arsonate system can be compared with recent data provided by molecular genetics.

Amino Acid Sequence↗
PubMed1986

Analysis of coronary-sinus-occlusion pressure by iterating the convolution integral.

Intermittent coronary sinus occlusion (ICSO) has been shown to reduce infarct size and to improve regional myocardial function. Since the efficiency of the procedure is closely related to proper intervals of occlusion and release of the coronary sinus, the reactions of coronary haemodynamics to this intervention have to be investigated. Coronary sinus pressure measurements obtained from anaesthetized dogs are analysed for three different conditions: normal coronary perfusion, experimentally induced infarction of the LAD performed according to a specific time pattern. The mathematical modelling of the coronary sinus pressure (CSP) reaction upon ICSO is accomplished by a convolution integral, incorporating a memory function g(x). With the aid of a numerical technique this function is evaluated to reproduce the measured data as closely as possible. Since g(x) describes the CSP response in a universal manner it can serve subsequently to predict reactions to different occlusion and release patterns not actually measured. This use of a mathematical model may provide economical paths for future investigations by avoiding prohibitively large numbers of animal studies. For different physiological states; normal perfusion, infarction and reperfusion; we obtained different memory functions. These differences in g(x) are then shown to be precisely related to known characteristics of the normal and diseased state of the myocardium. Understanding the link between cardiovascular physiology and its mathematical representation is seen as an important aid in the selection of therapeutic interventions.

Animals↗
PubMed1986

Randomized clinical trials: alternatives to conventional randomization.

The randomized allocation format remains an exceedingly powerful tool for clinical research. Because humans are the subjects in clinical research, this area of scientific study must operate within the limits dictated by such basic principles as individual autonomy, justice, and beneficence. As randomized studies have become more common in clinical research, it has become apparent that there is often need for modification of the basic randomized format or for alternatives. The most widespread modification is the use of sequential analyses to monitor the progress of a trial and ensure early identification of either unanticipated adverse effects or more pronounced differences than expected. Although this modification does not affect the basic randomized allocation format, it does provide a protection that is lacking in the conventional trial and should be utilized whenever feasible. Modifications that do affect the basic structure of the randomized trial include adaptive allocation and pre-randomization. The former is attractive and useful but limited to studies in which results from early enrollees are known before late enrollees are allocated. The greater the linkage between preceding subject results and subsequent assignments, the greater is the protection afforded by such a format. Pre-randomization, more universally applicable than adaptive allocation, suffers from pronounced cross-over potential and has been criticized on ethical grounds, a combination of weaknesses that raises questions of whether pre-randomization truly offers advantages to conventional randomized formats. True alternatives to the randomized format include the self-controlled study and the historical control design. Both possess significant ethical advantages over the simple randomized study. Unfortunately, both are at some methodological disadvantage when the same comparison is made. The self-controlled study is limited to the study of conditions sufficiently stable or recurrent that they permit two or more treatment courses in a single patient. In emergency medicine and critical care, this description fits only a small proportion of the illness spectrum. This design is underutilized in clinical research focused on less severe problems of the type seen in ambulatory and primary-care settings. Such problems can be suitable topics for research by emergency medicine specialists. Historical control studies are eminently applicable in the emergency and critical-care setting.(ABSTRACT TRUNCATED AT 400 WORDS)

Antihypertensive Agents↗
PubMed1986

Randomized clinical trials: problems and values.

Problems with randomization can be grouped as ethical or methodological. Those who consider randomization unethical believe it deprives patients of their best chance for a good result or actually does them harm. Methodological criticisms are based on the selectivity of randomized studies in terms of time and money. Finally, although no one suggests that randomization produces any statistical disadvantage, some critics think that its statistical advantages have been exaggerated.

Clinical Trials as Topic↗
PubMed1986

Idiotypic games within the immune network.

In this paper, we have considered the problem of selection of available repertoires. With Ab2 as immunogens, we have used the idiotypic cascade to explore potential repertoires. Our results suggest that potential idiotypic repertoires are more or less the same within a species or between different species. A given idiotype "à la Oudin" can become a recurrent one within the same outbred species or within different species. Similarly, an intrastrain crossreactive idiotype can be induced in other strains, even though there is a genetic disparity between these strains. The structural basis of this phenomenon has been explored. We next examined results showing the loss and gain of recurrent idiotypes without any intentional idiotypic manipulation. A recurrent idiotype can be lost in a syngeneic transfer and a private one can become recurrent by changing the genetic background. The change of available idiotypic repertoires at the B cell level has profound influences on the idiotypic repertoires of suppressor T cells. All these results imply that idiotypic games are played by the immune system itself, a strong suggestion that the immune system is a functional idiotypic network.

Animals↗
PubMed1986

Fluid and protein shifts after postural changes in humans.

With the use of a new mass density detection method, blood density (BD), plasma density (PD), and erythrocyte density (ED) were measured during different postures in euhydrated humans. ED remained stable under various head-up tilt (HUT) procedures. Changes of PD and BD mirrored the time course of hemodilution and hemoconcentration. The mass density of the shifted fluid (FD) was virtually identical for the outward filtrated fluid when upright and for the inward movement of fluid when supine; it averaged 1,008.3 g/l (37 degrees C), which is equivalent to a protein concentration of 30 g/l. PD and BD increased almost linearly with increasing angles of tilt. A stepwise increase from supine position to 90 degrees HUT within 2 h resulted in a mean plasma volume (PV) loss of 18%. Repeated sudden HUT to 70 degrees for 45 min, separated by 45-min supine (0 degree) periods, resulted in slightly reduced PV shifts which averaged -14% during 45 min of quiet HUT. The results indicate that erythrocyte volume remains constant after assuming different HUT positions in euhydrated subjects; a net loss of intravascular protein occurs during postural hemoconcentration, and protein gain occurs with postural hemodilution; the protein concentration of the shifted fluid resembles that of whole-body lymph; and microsample densitometry on blood and plasma is an accurate technique for measuring dynamic responses of rapid blood-volume changes in humans.

Adult↗
PubMed1986

The diuretic dilemma and the management of mild hypertension.

Diuretics are used in first-step antihypertensive monotherapy or in combination with adrenergic-inhibiting agents in the majority of hypertensive patients in the United States. A 30-year experience has demonstrated that blood pressure is lowered to as great or greater a degree with diuretics than when many of the presently available antihypertensive drugs, including converting enzyme inhibitors, calcium entry blockers, beta- or alpha-adrenergic inhibitors, or centrally acting sympatholytic agents, are used. Diuretics appear to be especially effective in the elderly and in black patients. All of the major hypertension clinical trials upon which we base our decisions for treatment have employed diuretics as step-1 therapy--with a reduction in morbidity and mortality. In addition, data suggest that more effective treatment of hypertension has contributed to the decrease of over 45% in deaths from cerebrovascular disease and the overall reduction of cardiovascular deaths over the past 15 to 20 years in the United States. The debate concerning the long term safety of diuretic therapy has focused on the USA Multiple Risk Factor Intervention Trial (MRFIT) results and several papers, suggesting that the lipid-raising or potassium-lowering properties of diuretics may produce adverse effects. Suggestions have been made that the use of other drugs without metabolic side effects may result in greater benefit with less risk, especially in the management of mild hypertension where the risk of the disease is not immediate or great. A review of the MRFIT and lipid data from long term studies has failed to establish the 'toxicity' of diuretic agents. In addition, recent studies have not confirmed previous observations that diuretic-induced hypokalaemia increases ventricular ectopy or contributes to sudden death. Although hypokalaemia should be avoided and corrected if it occurs, especially in patients with ischaemic heart disease, in the elderly, in patients with pretreatment ectopy or in patients on low potassium diets, the fear of this metabolic side effect of diuretics should not deter the physician from continuing the use of these agents both as monotherapy in most patients and as second-step therapy with an adrenergic-inhibiting drug.

Arrhythmias, Cardiac↗