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Biomedical subjects

A Himmelmann

Publications and source records attributed to A Himmelmann.

At least 37 records · Page 2Linked to original sources

Ambulatory blood pressure 16-26 years after the first urinary tract infection in childhood.

OBJECTIVE: To evaluate blood pressure in a population-based cohort with urographic renal scarring after childhood urinary tract infection. DESIGN: Follow-up investigation 16-26 years after the first recognized urinary tract infection. SETTING: University out-patient clinic for children with urinary infections serving the local area. PATIENTS: From the original cohort of 1221 consecutive children with first urinary tract infection diagnosed during 1970-1979, 57 of 68 with non-obstructive renal scarring participated as well as 51 matched subjects without scarring. MAIN OUTCOME MEASURE: 24 h ambulatory blood pressure. RESULTS: Acceptable blood pressure monitorings were obtained from 53 individuals with and 47 without scarring. There were no significant differences between the two groups even when only patients with the most extensive scarring (individual kidney clearance < 30 ml/min per 1.73 m2) or patients with bilateral scarring were compared with the non-scarring group. Mean systolic or diastolic blood pressure above +2 SD were found in 5/53 (9%) and 3/47 (6%) in the scarring and non-scarring group, respectively. Plasma renin activity, angiotensin II and aldosterone concentrations were not significantly different, but atrial natriuretic protein was significantly higher in the scarring group (P = 0.004). CONCLUSION: This study demonstrates a low risk of hypertension two decades after childhood urinary tract infection. It should be stressed that the patients with renal scarring were under close supervision throughout childhood. Those with scarring had higher concentrations of atrial natriuretic protein which might indicate a counter-regulation mechanism.

Adolescent↗

[A 100-year perspective on renal function and hypertension. Anti-renin therapy has made hypertensive renal failure a rarity].

One hundred years ago, in 1898, Professor Robert Tigerstedt, Karolinska institutet, Sweden, discovered renin. The subsequent elaboration in 1960 of the renin-angiotensin-aldosterone system signalled the start of modern hypertension research. The kidney takes part in blood pressure regulation in a number of ways. Indications are that increased renovascular resistance due to increased renin-angiotensin activity is of importance for the barostatic function of the kidneys and for the pathogenesis of human hypertension. Several commonly used, efficacious and well tolerated antihypertensive agents act by blocking the renin-angiotensin system, thus normalising kidney function. A number of current large-scale trials--utilising ACE inhibitors and angiotensin receptor antagonists--will, it is hoped, elucidate the proper role of 'anti-renin therapy' in the treatment of hypertension. Thanks to effective modern management of hypertension, renal failure due to hypertensive kidney disease is rare in Sweden today.

Acute Kidney Injury↗

Cloning of the hereditary hemochromatosis gene: implications for pathogenesis, diagnosis, and screening.

Hereditary hemochromatosis (HH) is one of the most common genetic disorders affecting populations of European ancestry. It is characterized by an inappropriately high iron absorption that leads to iron overload preferentially in the parenchymal organs. Although the severity of the phenotype can be modified by a number of factors, it is clear that most homozygotes will eventually become symptomatic. Clinical manifestations are often nonspecific and easily overlooked. Untreated HH can be associated with substantial morbidity and mortality. Diagnosis in the pre-cirrhotic stage, however, results in normal life expectancy. Early diagnosis and the initiation of phlebotomy therapy are therefore keys to preventing complications related to iron overload. The recent isolation of a strong candidate gene for hemochromatosis has the potential to allow for genetic diagnosis and screening in the near future. This exciting finding is likely not only to change clinical practice but also to yield new insights into the poorly understood pathophysiology of the disease.

Cloning, Molecular↗

New information on the role of beta-blockers in cardiac therapy.

Hypertension and ischemic heart disease are important precursors of heart failure. The prevention of progression to heart failure is a prime objective when treating patients with hypertension or ischemic heart disease. In patients with hypertension, treatment with either diuretics or beta-blockers reduces the risk of chronic heart failure. In patients with ischemic heart disease, beta-blocker therapy reduces the risk of recurrent myocardial infarction and ensuing cardiac dysfunction. The beneficial effects of beta-blocker therapy may be greater in post-infarction patients who have impaired left ventricular function than in those patients without such impairment. When considering heart failure itself, the efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in patients with mild-to-severe left ventricular dysfunction and their use is indicated for all stages of heart failure to reduce symptoms and retard further impairment of left ventricular function. Diuretics and digitalis offer relief from the symptoms of the disease, while positive inotropes are reserved for parenteral administration in end-stage heart failure, as a bridge to transplantation, or in acute exacerbations of the disease. Added to standard therapy, beta-blockade is of value in the treatment of heart failure, preventing further deterioration and improving hemodynamics, exercise tolerance, quality of life, and longterm prognosis.

Adrenergic beta-Antagonists↗

Hypertension: an important precursor of heart failure.

Hypertension is an important risk factor for cardiovascular morbidity and mortality. Hypertension is associated with the development of congestive heart failure by way of left ventricular hypertrophy, with left ventricular dilatation and through myocardial ischemia and left ventricular damage. Reports on the natural history of untreated hypertension indicate that at least 50% of affected subjects develop congestive heart failure. Hypertension is an important precursor of heart failure, and still the most common risk factor for congestive heart failure in the population. In clinical trials, particularly in elderly patients, a reduction in the incidence of congestive heart failure has been observed. Despite increments in the use of antihypertensive drugs, mortality from congestive heart failure among the elderly is increasing. Moreover, several patients with hypertension are unaware, untreated and uncontrolled for the most important risk factor for congestive heart failure. For the primary prevention of heart failure, improvements in blood pressure control are of vast importance.

Aged↗

The efficacy and tolerance of one or two daily doses of eprosartan in essential hypertension. The Eprosartan Multinational Study Group.

OBJECTIVE: The primary objective of this double-blind, parallel-group, placebo-controlled, multicentre study was to compare the antihypertensive efficacy of one versus two daily doses of eprosartan, a novel nonbiphenyl, nontetrazole angiotensin II receptor antagonist, in 243 patients with mild to moderate hypertension (sitting diastolic blood pressure > or = 95 to < or = 114 mmHg). PATIENTS AND METHODS: The patients were randomized to titrated doses of eprosartan at 400-800 mg once a day, eprosartan at 200-400 mg twice a day, or placebo, with the incremental dose titrated over a 9-week period. Patients reaching target blood pressure (sitting diastolic blood pressure of < or = 90 mmHg) continued the fixed-dose treatment for 4 weeks. The primary efficacy measure was the mean change in trough sitting diastolic blood pressure from baseline to the study endpoint, determined on an intent-to-treat basis. RESULTS: By the end of the study, eprosartan had significantly reduced mean trough sitting systolic and diastolic blood pressure relative to baseline and to placebo. The mean +/- SD change from baseline in diastolic pressure was -9 +/- 8.4 mmHg for the single daily dose, -9 +/- 8.5 mmHg for two doses a day and -4 +/- 8.1 mmHg for placebo (P < 0.0001 versus placebo for both eprosartan regimens). Similarly, both eprosartan regimens significantly reduced mean trough standing systolic and diastolic blood pressure. At the end of the study, the response rate in the single daily dose group (46.8%) was significantly higher than in the placebo group (25.6%). There were no significant differences between the treatment groups in the number of patients whose blood pressure responded to treatment; 41.7% of those taking eprosartan once a day and 44.4% of those taking eprosartan twice a day, and who responded to treatment, were maintained on their original starting doses. The total daily dose required to achieve target blood pressure was comparable, whether eprosartan was administered once or twice a day. Both eprosartan regimens were well tolerated and the incidence of adverse events with eprosartan was similar to that of placebo. CONCLUSIONS: These results demonstrate that there was no significant difference in antihypertensive efficacy or tolerance between eprosartan taken in one or in two daily doses. Both dosing regimens provided significant and clinically meaningful reductions in blood pressure that were superior to placebo. Eprosartan in a single daily dose was shown to be an effective antihypertensive agent. Because of the good adverse-effect profile and the simplicity of a single daily dose, eprosartan has the potential to improve patient compliance.

Acrylates↗

Prospectively detected cancer in familial breast/ovarian cancer screening.

BACKGROUND: Early diagnosis and treatment are shown to improve survival of breast and ovarian cancer. Identification and medical follow-up of high-risk groups may be important for early diagnosis. METHODS: A prospective study of 845 women from breast/ovarian- and ovarian cancer kindreds who were classified according to pre-set inclusion criteria (Table I), were offered genetic counseling and annual medical examinations of breasts and ovaries. The material consisted of three series: 1) 754 unaffected women, 2) 49 women with breast cancer, and 3) 42 women with ovarian cancer. RESULTS: In series 1) nine ovarian cancers and 20 breast cancers, in series 2) seven ovarian cancers, and in series 3) three breast cancers were found. All but one of the ovarian cancers were 40 years or older, and 4/16 (25%) were Borderline cancer. All breast cancers were 30 years or older, and 89% were detected before spread. CONCLUSIONS: This is to our knowledge the first prospective report of the combined breast/ovarian cancer findings in breast/ovarian cancer kindreds. A woman with both breast and ovarian cancer is the hallmark of inherited breast/ovarian cancer, and 50% of the ovarian cancers were detected in these families. Borderline ovarian cancer may represent a manifestation of this syndrome. If prophylactic oophorectomy prevents ovarian cancer, oophorectomy at age 45 would have prevented 75% of such cancers. Based on these results we revised our protocol for annual follow-up in these kindreds: 1) clinical breast examination and mammography (ultrasound/cytology if indicated) from 30 years of age, 2) gynecologic examination (including vaginal ultrasound, serum-CA125) from 35 years of age, and 3) discuss oophorectomy at 45 years of age.

Adolescent↗

Long-term results from a phase II study of single agent paclitaxel (Taxol) in previously platinum treated patients with advanced ovarian cancer: the Nordic experience.

BACKGROUND: Owing to the wide spread perception of a possible benefit from paclitaxel in the second-line situation the Nordic Gynecologic Oncology Group (NGOG) conducted two prospective phase II studies of paclitaxel single agent treatment (175 mg/m2, three-hour i.v. infusion with standard pre-medication every third week) in patients with relapsing or progressing epithelial ovarian cancer following platinum. PATIENTS AND METHODS: Between 1992-1994 138 patients in total were enrolled of whom 136 received paclitaxel and were included in the toxicity and survival analysis, while 112 were evaluable for response. RESULTS: The overall response rate (CR + PR) was 28% with 16 patients achieving a CR (14%). The estimated median (range) time to progression was 4.1 (0.7-60.7) months. The projected four-year overall survival was 7%, with a median (range) of 9.6 (0.3-60.7) months. A multivariate logistic regression analysis showed that platinum resistance, and WHO performance status at baseline, independently correlated with survival at all three time points (median survival time 9.6, 18, and 24 months). Patients with platinum sensitive tumors and WHO performance status 0 had a median survival of 25.6 months compared to 7.0 months for the rest of the patients (P < or = 0.0001). No serious toxicity was registered. CONCLUSION: Paclitaxel could safely be administered in an outpatient setting using this schedule. Patients with platinum sensitive tumors and a good performance status were most likely to survive. However, these patients are also most likely to respond to re-treatment with a platinum compound. With reference to the reasonably good tumor control and limited toxicity observed in this study, we conclude that paclitaxel single agent therapy is a viable option in the salvage situation, which in some patients can give long-lasting responses. However, although responses can be induced in a significant number of patients, the survival figures remain poor.

Adult↗