[Sepsis: case numbers increasing worldwide but new strategies too]. / Sepsis - weltweit steigende Fallzahlen, aber auch neue Strategien.

With the numbers of cases rising worldwide and consistently high mortality, sepsis is one of the world's most significant health issues. The Jena Symposium was dedicated to the challenges in research and development, new approaches to treatment, internationally successful strategies, and a potentially successful new initiative for improving the quality of prophylaxis, early diagnosis, and therapy. The importance of intensifying efforts in the fight against sepsis is becoming increasingly recognized by health care policy. Knowledge of lay people/the public about sepsis is lacking and the standards of quality are in need of improvement.

[Validation of an advance directive]. / Validierung einer Patientenverfügung.

BACKGROUND: German Legislation has defined the legal significance of advance directives (AD). Nevertheless, many precast ADs are of limited help in clinical decision making. Empirical results are rare and controversial. The SUPPORT study showed that precast ADs had a tendency to being ignored. Value-based AD proved to be of help in the interpretation of patients' wills by physicians. We therefore investigated whether a value-based AD that can be individualized with the help of a check-box-system is a valid instrument of communicating the patient's preferences. This is the first validation of an AD. MATERIAL AND METHODS: In our study we evaluated the acceptance and practicability of an AD. Questionnaires and the AD itself were handed out to patients, relatives, and members of the nursing and medical staff. All were asked to fill out the AD, mark all unclear passages, make amendments to the AD if wanted and finally were asked to answer a questionnaire regarding the AD. The level of significance was defined at 5%, meaning that every "unwanted" answer exceeding 5% or passages with more than 5% of the total remarks were analyzed and it was checked whether changes to the AD should be made. RESULTS: The return rate was 64.8% (201 of 310). The results were highly positive for the items "understandable" (81,6%), "clarifying" (65,7%), "helpful" (76,1%), and "sensible" (75,1%). 70% of patients and relatives stated that they were able to express personal wishes and values with this AD, as well as a majority of the medical staff (44% vs. 30%). The discrepancy between the groups was significant (ChiSq=13.11, p<.001). All paragraphs of the check-box-system were validated as understandable and clear in intention. Major concerns were the inability of expressing own wishes and values (by 16,4% of all participants) and the fear of later alterations (15,4%). According to the findings and the evaluations the AD was modified. DISCUSSION: The value-based AD which is routinely used in a university hospital and which can be individualized by a check-box-system was broadly accepted by the test subjects and showed highly positive results with respect to the analyzed items. Only minor changes were derived from our study to hopefully raise its acceptance even more. The discrepancy between patients, relatives and the medical staff concerning the possibility to express one's wishes and values was surprising and in contradiction to former findings. However, our study cannot answer whether the higher level of distrust among medical staff can be explained by negative professional experiences. CONCLUSION: The investigated AD with a check box system seems to be an adequate instrument to communicate patient's wishes and directives.

[Rehabilitation outcomes of a psychosomatic clinic integrating fully inpatient and partial hospitalization rehabilitation approaches: a comparison]. / Vergleich von Rehabilitationsergebnissen aus einer psychosomatischen Fachklinik mit integriertem vollstationären und teilstationären Rehabilitationskonzept.

As publications from the domain of psychosomatic rehabilitation pertaining to the conceptual approaches and effects of partial-hospitalization rehabilitation have so far relied on very small case numbers, the effectiveness of partial-hospitalization rehabilitation was analysed in 318 patients in comparison to a large sample of rehabilitants who had participated in fully inpatient rehabilitation. No relevant differences were found among the groups studied in sociodemographic respects or range of diagnoses. The same was true concerning the level of complaints present at the onset of rehabilitation. Good rehabilitation outcomes were achieved in both groups, however, the effect sizes found for changes in depressiveness and indulgence to complaining ("Klagsamkeit") (GSI from the SCL-90) were lower in the partial-hospitalization group than in the patients in fully inpatient rehabilitation. Also, the relatively high share of partial-hospitalization patients discharged unable to return to work might be clinically significant. While our findings confirm the good results reported from other disciplines, they nevertheless are a reminder of the need for very careful selection of patients for partial-hospitalization rehabilitation, in order not to withhold "better" rehabilitation than could be provided on a partial-hospitalization basis from patients with special sociomedical problems. The best rehabilitation outcomes seem to be achieved by those patients who, towards the end of fully inpatient rehabilitation, were granted transition to the partial-hospitalization programme.

[What are the physical complaints without pathological clinical signs in patients with diabetes mellitus?]. / Wie lassen sich Körperbeschwerden bei Patienten mit Diabetes mellitus ohne pathologische klinische Befunde verstehen?

UNLABELLED: In previous research it was found that patients with diabetes mellitus suffer from multiple physical symptoms even early in their disease course. Such complaints may relate to blood glucose levels or can be understood as a sign of distress in respect to the diagnosis of a chronic disease. PURPOSE: This study was performed to evaluate in a cross-sectional analysis all the symptoms that patients may complain of and to relate these symptoms to a possible dysfunction of the autonomic nervous system. METHOD: We assessed the complaints of 66 patients with diabetes mellitus and compared these variables with those of patients with psychological disturbances (n = 794) or somatic disease (n = 162). The symptoms were recorded by means of several questionnaires such as the "Giessener Beschwerdebogen" (GBB), "the Freiburger Persönlichkeitsinventar" (FPI), the German version of the State Trait Anxiety Inventory (STAI) and the German version of the State Trait Anger Expression Inventory (STAXI). The autonomic nervous system was assessed using resting and mental stress conditions in a subset of patients with diabetes mellitus (n = 29) and psychological disturbances (n = 44). RESULTS: Patients suffering from diabetes mellitus and psychological disturbances showed a tendency to higher scores in GBB, STAI and STAXI. As far as psychological disturbances are concerned, the complaints experienced by patients with diabetes mellitus were found to be similar to those with somatic diseases. Both groups, however, rate clearly below those with psychological disturbances. The results of autonomic testing showed a significant disturbance in patients with diabetes mellitus with reduced sensitivity of the baroreceptor indicating autonomic neuropathy. CONCLUSION: Some of the physical complaints of patients with diabetes mellitus can be understood in connection with autonomic dysfunction. Moreover, an explicitly psychological view of these complaints may not be correct.

Autonomic cardiovascular regulation in obesity.

Obese persons suffer from an increased mortality risk supposedly due to cardiovascular disorders related to either continuously lowered parasympathetic or altered sympathetic activation. Our cross-sectional correlation study establishes the relationship between obesity and autonomic regulation as well as salivary cortisol levels. Three patient cohorts were sampled, covering ranges of body mass index (BMI) of 27-32 (n=17), 33-39 (n=13) and above 40 kg/m(2)(n=12), and stratified for age, sex and menopausal status. Autonomic cardiovascular regulation was assessed by use of heart rate variability and continuous blood pressure recordings. Spectral analytical calculation (discrete Fourier transformation) yields indices of sympathetic and parasympathetic activation and baroreflex sensitivity. Morning salivary cortisol was concurrently collected. Contrary to expectation, BMI and waist/hip ratio (WHR) were inversely correlated with sympathetic activity. This was true for resting conditions (r=-0.48, P<0.001; r=-0.33, P<0.05 for BMI and WHR respectively) and for mental challenge (r=-0.42, P<0.01 for BMI). Resting baroreflex sensitivity was strongly related to the degree of obesity at rest (BMI: r=-0.35, P<0.05) and for mental challenge (r=-0.53, P<0.001). Salivary cortisol correlated significantly with waist circumference (r=-0.34, P=0.05). With increasing weight, no overstimulation was found but a depression in sympathetic and parasympathetic activity together with a significant reduction in baroreflex functioning and in salivary cortisol levels.

[1-Year follow-up of inpatient treatment in a psychosomatic rehabilitation clinic with either a psychoanalytic or behavior therapy oriented treatment]. / 1-Jahres-Katamnese stationärer psychosomatischer Rehabilitation nach differentieller Zuweisung zu psychoanalytisch oder verhaltenstherapeutisch orientierter Behandlung.

In a naturalistic setting, we studied the long-term effects of an inpatient treatment program at a psychosomatic rehabilitation clinic, where patients were assigned to a department with either a psychoanalytic or behavior therapeutic orientated treatment after one week of comprehensive diagnosis. The study is based on a self-developed questionnaire which gathers retrospective information in a broad spectrum of problem areas at the point of admittance and release (t0 and t1) as well as current assessments one year following treatment (t2). Additionally, a symptom checklist (Giessener Beschwerdebogen) and a questionnaire assessing depression (Allgemeine Depressionsskala) were prospectively employed at t0 and t2. We asked a consecutive sample of 376 patients to participate, of which 56% answered at t2. Despite limitations of the internal and external validity of the study, we were able to show that substantial improvements are maintained following treatment for both therapies at one-year follow-up, whereas only small difference are found between the outcomes of the two different schools implemented in the clinic.

Early autonomic dysfunction in patients with diabetes mellitus assessed by spectral analysis of heart rate and blood pressure variability.

Patients with diabetes mellitus (DM) often have alterations of the autonomic nervous system (ANS), even early in their disease course. Previous research has not evaluated whether these changes may have consequences on adaptation mechanisms in DM, e.g. to mental stress. We therefore evaluated whether patients with DM who already had early alterations of the ANS reacted with an abnormal regulatory pattern to mental stress. We used the spectral analysis technique, known to be valuable and reliable in the investigation of disturbances of the ANS. We investigated 34 patients with DM without clinical evidence of ANS dysfunction (e.g. orthostatic hypotension) and 44 normal control subjects (NC group). No patients on medication known to alter ANS responses were accepted. The investigation consisted of a resting state evaluation and a mental stress task (BonnDet). In basal values, only the 21 patients with type 2 DM were different in respect to body mass index and systolic blood pressure. In the study parameters we found significantly lower values in resting and mental stress spectral power of mid-frequency band (known to represent predominantly sympathetic influences) and of high-frequency and respiration bands (known to represent parasympathetic influences) in patients with DM (types 1 and 2) compared with NC group (5.3 +/- 1.2 ms2 vs. 6.1 +/- 1.3 ms2, and 5.5 +/- 1.6 ms2 vs. 6.2 +/- 1.5 ms2, and 4.6 +/- 1.7 ms2 vs. 6.2 +/- 1.5 ms2, for resting values respectively; 4.7 +/- 1.4 ms2 vs. 5.9 +/- 1.2 ms2, and 4.6 +/- 1.9 ms2 vs. 5.6 +/- 1.7 ms2, and 3.7 +/- 2.1 ms2 vs. 5.6 +/- 1.7 ms2, for stress values respectively; M/F ratio 6/26 vs. 30/14). These differences remained significant even when controlled for age, sex, and body weight. However, patients with DM type 2 (and significantly higher body weight) showed only significant values in mental stress modulus values. There were no specific group effects in the patients with DM in adaptation mechanisms to mental stress compared with the NC group. These findings demonstrate that power spectral examinations at rest are sufficiently reliable to diagnose early alterations in ANS in patients with DM. The spectral analysis technique is sensitive and reliable in investigation of ANS in patients with DM without clinically symptomatic autonomic dysfunction.

[Quality assurance in inpatient psychosomatic treatment and rehabilitation]. / Qualitätssicherung in der stationären psychosomatischen Behandlung und Rehabilitation.

In addition to the requirements of quality management imposed by legislative and in consideration of research projects on the evaluation of psychotherapy the German pension funds introduced a systematic program for quality control in 1994. By the end of this year all the German rehabilitation centers will regularly have to provide information concerning the structure and concepts of the hospital and details of the rehabilitation programs. All therapeutic interventions are listed for every patient. In a subsample of patients detailed information regarding diagnosis and outcome (goal attainment) is required in addition to the final report. A subsample of the final reports is peer-reviewed. Patient's satisfaction and estimation of outcome variables are regularly assessed 3 months after discharge. Within and between institutions quality circles meet regularly. Advantages and limits of these programs are discussed and additional approaches towards total quality management in Bad Kreuznach are described.

Discontinuation of antihypertensive therapy: prevalence of relapses and predictors of successful withdrawal in a hypertensive community.

Antihypertensive therapy has been thought to be a life-long treatment. Nevertheless, antihypertensive medication may be discontinued in a substantial proportion of hypertensive patients at least for some time. The current study focused on predictors for the development of elevated blood pressure levels after discontinuation of antihypertensive drug therapy. In an open, prospective study, 88 white male patients with newly discovered essential hypertension (age 42 +/- 7 years) were tested at baseline. Blood pressure was measured in various situations (at work, at rest, before and during treatment, and at follow-up), and the hemodynamic profile at rest and cardiovascular response patterns during stress tests were evaluated. Left ventricular mass and other cardiovascular risk factors were also carefully determined. After 6 months of strict blood pressure control (< 140/90 mm Hg), they were treated by their primary care physician (mean duration of antihypertensive therapy 1.3 +/- 1.7 years). After 6 years, 37 patients were still on antihypertensive therapy, but 19 of the 37 had blood pressure values > or = 160/95 mm Hg. In 51 patients, therapy was discontinued: 29 were hypertensive, 15 were borderline hypertensive and 7 were normotensive. Relapse of hypertensive blood pressure in these 51 patients off therapy was predicted by resting blood pressure values before therapy (138 +/- 11/91 +/- 5 vs. 131 +/- 11/85 +/- 7 mm Hg, p < 0.05/0.01), cardiac output at rest (7.5 +/- 1.9 vs. 6.2 +/- 2.1 l/min, p < 0.05), total peripheral resistance (20 +/- 9 vs. 14 +/- 4 U, p < 0.05), increased heart rate during ergometry (50 +/- 8 vs. 44 +/- 6 b.p.m., p < 0.05) and left ventricular mass determined by echocardiography (212 +/- 60 vs. 189 +/- 44 g, p < 0.01). There was no difference in age, blood pressure levels before and during treatment, the number of consultations with the primary care physician or cardiovascular risk factor profiles. In conclusion, intermittent rather than life-long antihypertensive treatment may be possible in hypertensive patients with low resting blood pressure, high cardiac output, low total peripheral resistance and low left ventricular mass.

Predictors for hypertensive nephropathy: results of a 6-year follow-up study in essential hypertension.

OBJECTIVE AND DESIGN: To identify predictors for the development of early hypertensive nephropathy, 88 previously untreated patients with mild-to-moderate essential hypertension (World Health Organization stage I or II) were re-examined after 6 years of follow-up. According to previous results, protein excretion, urinary excretion of N-acetyl-beta-glucosaminidase (NAG), serum NAG concentration and glomerular filtration rate (creatinine clearance) may predict the change in renal function. RESULTS: Serum creatinine level increased significantly, but none of the patients developed serum creatinine of > 1.3 mg/dl. An elevated protein excretion between 200 and 500 mg/day at baseline (microproteinuria), urinary NAG excretion, serum NAG concentration and blood pressure control during treatment were not related to serum creatinine level at follow-up or change in serum creatinine level throughout the 6 years of follow-up. In contrast, a high creatinine clearance at baseline was related to a marked rise in serum creatinine level after 6 years. The patients with a clear-cut increase in serum creatinine level of > 0.2 mg/dl (n = 23) were characterized by a significantly higher pretreatment blood pressure at the worksite and a significantly greater initial creatinine clearance than the patients with no significant change in serum creatinine level. In the two groups age, blood pressure level during therapy, and the intensity and duration of blood pressure control were not different. CONCLUSION: In patients with uncomplicated essential hypertension, microproteinuria, NAG parameters and treatment blood pressure level did not predict the change in serum creatinine level in the first 6 years of follow-up. A high creatinine clearance (suggesting glomerular hyperfiltration) emerged as a clinical diagnostic marker of early hypertensive nephropathy.

Reduced parasympathetic cardiac control in patients with hypertension at rest and under mental stress.

The neurogenic component in the pathogenesis of essential hypertension has predominantly been analyzed with regard to the sympathetic part of the autonomous nervous system; the parasympathetic branch has largely been neglected. We investigated whether 54 normotensive (mean causal blood pressure [cBP]: 125 +/- 6/82 +/- 4 mm Hg), 41 borderline hypertensive (cBP: 134 +/- 8/90 +/- 5 mm Hg), and 34 hypertensive men (cBP: 152 +/- 13/101 +/- 5 mm Hg) without secondary target organ damage differed in parasympathetic cardiac control. Parasympathetic cardiac control was assessed via the amount of fast fluctuations (0.15 to 0.40 Hz; vagus band) and by the amount of respiratory-linked fluctuations (mean respiratory frequency +/- 0.03 Hz) in the power spectra of continuously registered interbeat intervals under the following conditions: mean of three rest phases with 10, 5, and 5 minutes' duration (REST); mean of two modes of a reaction time task with 10 and 5 minutes' duration (RTT); mean of 5 minutes' mental arithmetic plus noise (MA). Analysis of variance (ANOVA) shows that spectral energy in the so-called vagus band reveals the most prominent differences between blood pressure groups under all conditions: REST = normotensive, 2.70 +/- 0.31; borderline hypertensive, 2.55 +/- 0.33; and hypertensive, 2.43 +/- 0.43 (F[2.126] = 6.19; p < 0.01). RTT = normotensive, 2.41 +/- 0.35; borderline hypertensive, 2.19 +/- 0.33; and hypertensive, 2.17 +/- 0.46 (F[2.126] = 6.04; p < 0.01); MA = normotensive, 2.69 +/- 0.34; borderline hypertensive, 2.52 +/- 0.33; and hypertensive, 2.38 +/- 0.46 (F[2.126] = 7.04; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Obesity as a determinant for response to antihypertensive treatment.

OBJECTIVE: To test the hypothesis that beta blockers lower blood pressure more effectively than calcium entry blockers in obese hypertensive patients and that calcium entry blockers are more effective in lean patients. DESIGN: Double blind, randomised controlled trial of treatment over six weeks. SETTING: Tertiary referral centre. SUBJECTS: 42 white men with uncomplicated mild to moderate essential hypertension (World Health Organisation stage I or II); 36 completed the study. INTERVENTION: Patients were randomised to metoprolol 50-100 mg twice daily or isradipine 2.5-5.0 mg twice daily for six weeks after a two week run in phase. MAIN OUTCOME MEASURE: Blood pressure after six weeks of treatment. RESULTS: When stratified according to treatment and presence of obesity (body mass index < or = 27 kg/m2), the mean (SD) fall in blood pressure in the beta blocker group was 24 (13)/18 (10) mm Hg in obese patients and 18 (19)/12 (13) mm Hg in lean patients. In the calcium entry blocker group, the fall in blood pressure was 21 (15)/17 (6) mm Hg in lean patients and 18 (11)/8 (10) mm Hg in obese patients. After taking age and blood pressure before treatment into account there was a significant interaction between obesity and drug therapy (p = 0.019) with a better diastolic blood pressure response to calcium entry blockers in lean patients and to beta blockers in obese hypertensive patients. CONCLUSION: Obesity affects the efficacy of metoprolol and isradipine in reducing blood pressure.

Renal hemodynamics and cardiovascular reactivity in the prehypertensive stage.

To examine whether sympathetic nervous activation has an impact on renal circulation in subjects at risk for high blood pressure, we assessed renal hemodynamics and cardiovascular response to mental stress in 40 healthy young white males, 12 normotensive subjects without and 14 with familial hypertension, and 14 with borderline hypertension. The response of systolic and diastolic blood pressure to mental stress was assessed while each patient performed a mental arithmetic task; this was taken as the parameter for the activation of the sympathetic nervous system. Renal plasma flow was measured by para-aminohippuric acid clearance under steady-state conditions. In parallel, glomerular filtration rate as a parameter for functional impairment of the kidneys was determined by creatinine clearance, and filtration fraction was also calculated. Patients with borderline hypertension were characterized by a reduced renal blood flow and increased filtration fraction in comparison with both normotensive groups. The increase in systolic blood pressure during mental stress was more pronounced in borderline hypertensives. We observed no significant difference in renal hemodynamics and cardiovascular response to mental stress between normotensives with and without a family history of hypertension. In the total population, cardiovascular response to mental stress was correlated with renal hemodynamics: The greater the increase in systolic blood pressure during mental stress, the lower was the renal plasma flow and the greater the filtration fraction. Thus, renal plasma flow was found to be already reduced and filtration fraction increased before sustained hypertension developed. Because this pattern in renal hemodynamics was related to cardiovascular response to mental stress, our data suggest that sympathetic activation already appeared to affect renal hemodynamics at the onset of essential hypertension.

Impact of angiotensin converting enzyme inhibition on the haemodynamic profile during laboratory stress tests.

To determine the haemodynamic profile of angiotensin converting enzyme (ACE) inhibitors during stress, the cardiovascular response to various stress tests was examined in patients with essential hypertension before and after three months of therapy with lisinopril. Eighteen white patients were enrolled in the trial, of whom 12 completed the protocol. ACE inhibition with lisinopril effectively reduced systolic and diastolic pressure in the office (P less than 0.001), at rest (P less than 0.002), during mental stress (P less than 0.003), cold pressor test (P less than 0.003), and reaction time task (P less than 0.05). During physical exercise only diastolic pressure was significantly reduced (P less than 0.02). The fall in peak systolic pressure during cold pressor test and reaction time task was more pronounced than the fall in casual systolic pressure (P less than 0.05). At rest, cardiac output was unchanged, but total peripheral resistance was reduced after medication with lisinopril (P less than 0.05). During the cold pressor test, the increase in total peripheral resistance was attenuated by ACE inhibition (P less than 0.04). The haemodynamic response profile was not altered during the other tests. It is concluded that in middle-aged men ACE inhibitors reduce blood pressure during a variety of stressful events without altering the haemodynamic profile and even attenuating vasoconstriction during stress. This response pattern to ACE inhibition with lisinopril may reduce the impact of recurring stress-induced increases of blood pressure and of exaggerated vasoconstrictive stimuli on the cardiovascular system.

Impact of antihypertensive therapy with isradipine and metoprolol on early markers of hypertensive nephropathy.

In a double-blind, randomized trial with 26 male white patients with essential hypertension in World Health Organization Stages I and II, we examined the impact of calcium entry blockade (5 to 10 mg/day isradipine, N = 14) and beta-blockade (100 to 200 mg/day metoprolol, N = 12) on early markers of hypertensive nephropathy before and after 7 weeks' treatment. Excretion of total protein, albumin, alpha 1-microglobuline, and N-acetyl-beta-glucosaminidase (NAG) were measured in the 24-h urine by radial immunodiffusion and fluorimetric method, respectively. Before therapy, 8 of 26 patients had microproteinuria (31%), six had microalbuminuria (22%), six had elevated urinary NAG activity (22%), and three had elevated alpha 1-microglobulin excretion (11%). In these subjects anti-hypertensive therapy led to a fall in proteinuria (296 +/- 56 v 127 +/- 116 mg/day, P less than .01), albuminuria (44 +/- 24 v 25 +/- 12 mg/day, P less than .05), and NAG excretion (45 +/- 22 v 28 +/- 5, P less than .05). The higher the pretreatment value, the greater the fall was in proteinuria (r = +0.55, P less than .01), albuminuria (r = 0.80, P less than .001), and NAG excretion (r = 0.60, P less than .01). We did not observe any significant difference in clinical characteristics, blood pressure, or urinary excretion of protein, albumin, or NAG between the two treatment groups, either before or after therapy. Thus, antihypertensive therapy reduced excretion of total protein, albumin, and NAG activity in hypertensive patients with elevated pretreatment values, potentially indicating reversal of early hypertensive nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Long-term 24-hour blood pressure measurement in genuine gestosis and hypertensive pregnancy]. / 24-Stunden-Langzeitblutdruckmessung bei genuiner Gestose und Pfropfgestose.

The clinical implications of diminished circadian blood pressure variations during hypertensive pregnancies are not fully understood. We used the COS-INOR-method to quantify circadian blood pressure amplitudes of 32 patients with preeclampsia (GG) and 21 patients with superimposed pre-eclampsia (PG). The two groups did not significantly differ in body weight, age, and gestational date at admission. No differences could be detected in 24-h blood pressure values between the two groups (GG: 127 +/- 14/82 +/- 12 mmHg, PG: 128 +/- 16/86 +/- 9 mmHg). Circadian amplitudes of systolic blood pressure variations (GG: 5.9 +/- 5.5 mmHg, PG: 4.5 +/- 6.9 mmHg) and diastolic blood pressure variations (GG: 3.8 +/- 3.0 mmHg, PG: 5.3 +/- 4.1 mmHg) did not differ significantly. The slope between successive changes of mean arterial blood pressure and successive changes in heart rate was significantly higher in patients with superimposed pre-eclampsia (GG: 0.16 +/- 0.27 mmHg/bpm, PG: 0.36 +/- 0.24 mmHg/bpm, p less than 0.005). We conclude that patients with pre-eclampsia and superimposed pre-eclampsia do not differ in 24-h blood pressure and circadian blood pressure variability, however, if blood-pressure variability is related to heart-rate variability differences become apparent that might be due to altered blood-pressure regulation.

Pharmacological modulation of stress-induced cardiovascular hyperreactivity in essential hypertension.

The effects of the calcium antagonist isradipine and the beta-blocker metoprolol, which are based on different antihypertensive therapeutic principles, were evaluated in 52 men with mild-to-moderate hypertension in a 6-week, double-blind, randomized study. Mental stress-testing was performed before and after active treatment. With isradipine (n = 26), the stress-induced responses of cardiac output and total peripheral resistance were not significantly changed, but the blood pressure (BP) response, specifically the diastolic response, was decreased. With metoprolol (n = 26), there was a decreased response of cardiac output and an increased response of total peripheral resistance, and the BP response was even greater than it had been before treatment. Thus, these results indicate that beta-blockade is effective in reducing cardiac responsiveness but, because of vascular counterregulatory mechanisms, BP responsiveness is not decreased. In contrast, calcium antagonism preserves the physiological hemodynamic profile while reducing BP responsiveness to stress.

Elevated serum activity of N-acetyl-beta-glucosaminidase in essential hypertension: diagnostic value and reversal to normal values after antihypertensive therapy.

Previous studies have shown that urinary N-acetyl-beta-glucosaminidase (NAG) is elevated in patients with hypertension, even without renal disease. To elucidate the value of measuring NAG, both in urine and serum of hypertensive patients, we measured NAG activity in the serum, plasma, and 24-hour urine by the fluorimetric method in 84 patients with uncomplicated essential hypertension before and after 6 months of effective treatment. NAG activities of these hypertensive patients were compared with those of 102 healthy normotensive subjects and 97 patients with various renal diseases and controlled hypertension. Serum NAG activity was clearly greater in patients with essential hypertension (427 +/- 124 U/mL) than in normotensive subjects (380 +/- 109 U/mL) or patients with renal disorders (393 +/- 115 U/mL) (P less than or equal to 0.004). The greater was the diastolic pressure in the hypertensive group, the greater was serum NAG activity (r = +0.30, P = 0.004). Hypertensive patients with high serum NAG activity were further characterized by a more exaggerated increase in systolic pressure (34 +/- 16 v 25 +/- 15 mm Hg, P = 0.051) and total peripheral resistance (19% +/- 18% v 12% +/- 13%, P = 0.042) in response to the cold pressor test and by a greater increase in systolic pressure (56 +/- 15 v 45 +/- 13 mm Hg, P = 0.009) and diastolic pressure (11 +/- 7 v 6 +/- 9, P = 0.043) in response to bicycle exercise testing than the group with low serum NAG activity. In contrast, urinary NAG activity tended to be only slightly higher in patients with essential hypertension than in the normotensive control group (33 +/- 31 v 23 +/- 29 U/mg creatinine [cr], P = 0.062), whereas patients with renal diseases had clearly increased urinary NAG activity (87 +/- 105 U/mg cr) (P less than 0.001). Following effective antihypertensive therapy, serum NAG activity decreased in patients with essential hypertension to values of normotensive control subjects (from 427 +/- 124 U/mL to 386 +/- 106 U/mL, P less than 0.01). A significant decrease in serum NAG activity was observed in patients with both initially high as well as low pretreatment serum NAG activities (P less than 0.001 and P less than 0.02, respectively). Urinary NAG activity overall was unchanged by antihypertensive treatment. We conclude that in patients with mild essential hypertension, serum NAG activity was already elevated (whereas urinary NAG activity was not) and was normalized by effective antihypertensive treatment.(ABSTRACT TRUNCATED AT 400 WORDS)