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Biomedical subjects

J Wacker

Publications and source records attributed to J Wacker.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alteration of the activity of the 11beta-hydroxysteroid dehydrogenase in pregnancy: relevance for the development of pregnancy-induced hypertension?

In this study we evaluated the activity of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in patients with pregnancy-induced hypertension (PIH). A reduction of the activity of 11beta-HSD2 leads to pseudohyperaldosteronism due to insufficient interconversion of cortisol to its inactive 11-oxo-metabolite cortisone in the renal tubulus cell. We measured urinary free cortisol and cortisone in patients with and without PIH and calculated the urinary free cortisol to free cortisone ratio, which is well accepted as a correlate of the activity of renal 11beta-HSD2. One hundred twenty-six pregnant women were included. Fifty-nine patients had PIH (mean age 31.5 +/- 4.4 yr, blood pressure 158.7 +/- 16.0/100.8 +/- 9.5 mm Hg), and 67 were normotensive (mean age 29.4 +/- 4.6, blood pressure 112.6 +/- 8.9/68.8 +/- 8.6 mm Hg). The excretion rate of cortisol was increased in the PIH group (138.8 +/- 93.0 vs. 106.5 +/- 65.4 nmol/d, P = 0.027), whereas excretion rate of cortisone was similar (362.9 +/- 254.1 vs. 366.5 +/- 221.7 nmol/d, P = 0.933). The free cortisol to free cortisone ratio was significantly higher in the PIH group (0.47 +/- 0.25 vs. 0.31 +/- 0.12, P < 0.00002). Within this group, the patients with blood pressure in the uppermost quartile had a significantly higher free cortisol to free cortisone ratio than those in the lowest quartile [0.61 +/- 0.31 vs. 0.38 +/- 0.15 (P = 0.019) for diastolic, 0.60 +/- 0.29 vs. 0.35 +/- 0.13 (P = 0.012) for systolic, and 0.62 +/- 0.32 vs. 0.39 +/- 0.16 (P = 0.023) for mean blood pressure, respectively]. We conclude that a reduction of the activity of the 11beta-HSD2 is a relevant factor for the development of PIH. Whether the ratio of urinary free cortisol to free cortisone is a useful risk factor for the development of PIH must be investigated in further prospective studies.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Down-regulation of insulin-like growth factor-I receptor and insulin receptor substrate-1 expression in advanced human breast cancer.

The ligands, receptors and related signaling proteins of the insulin-like growth factor family are involved in the regulation of breast-cancer cell growth. We investigated the expression pattern of insulin-like growth factor-I receptor (IGF-IR), insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), a core downstream signaling protein, in 69 primary breast-cancer specimens of different grades and in 21 control tissues by immunohistochemistry. In addition, cell proliferation (percentage of Ki67(+) nuclei) and estrogen receptor (ER) expression were determined. IGF-IR, IRS-1 and IR were expressed mainly in epithelial cells. IRS-1 and IGF-IR were expressed at high levels in control tissues and in well and moderately differentiated carcinomas but at low levels in poorly differentiated breast cancers. IR expression did not show a significant correlation with the differentiation grade of the tissues investigated. Statistical analysis (ROC analysis for tumor grade) demonstrated that down-regulation of IGF-IR and IRS-1 correlated better with tumor progression than reduction of ER expression or increase in cell proliferation, IGF-IR showing the best correlation, followed by IRS-1 and, less significant, ER and Ki67. Our findings clearly show that progression of breast cancer is accompanied by a reduction of IGF-IR/IRS-1 expression and that IGF-IR/IRS-1 expression inversely correlates with high proliferation rate in dedifferentiated breast cancers. The strong correlation of IGF-IR and IRS-1 down-regulation with tumor progression suggests the use of IGF-IR and IRS-1 as a novel set of marker proteins for tumor grading.

Adult↗
PubMed2000

Riboflavin deficiency and preeclampsia.

OBJECTIVE: To examine in a prospective study riboflavin deficiency as a predisposing factor for preeclampsia in a high-risk collective of pregnant women in Zimbabwe. METHODS: At an antenatal clinic in Bulawayo, Zimbabwe, 154 women at increased risk for preeclampsia were observed prospectively until delivery. Riboflavin status was determined using the erythrocyte glutathione reductase activation coefficient test on the day of antenatal booking. Riboflavin deficiency was expressed by erythrocyte glutathione reductase activation coefficient of 1.4 or greater. RESULTS: Riboflavin deficiency was frequently found among the study population (33.8%). Incidence rose toward the end of pregnancy (27.3% at 29-36 weeks' gestation compared with 53.3% at over 36 weeks). In the riboflavin-deficient group, mothers were more likely to develop preeclampsia (28.8%) than in the riboflavin-adequate group (7.8%; P <.001, odds ratio [OR] 4.7, 95% confidence interval [CI] 1.8-12.2). The calculated concentrations of intracellular free flavin adenine dinucleotide were significantly lower in patients who developed preeclampsia than in normal pregnancies (P <.05). CONCLUSION: Riboflavin deficiency should be considered a possible risk factor for preeclampsia. Insufficient concentrations of the riboflavin-derived cofactors flavin adenine dinucleotide and flavin adenine mononucleotide could contribute to the established pathophysiologic changes including mitochondrial dysfunction, enhanced oxidative stress, and disturbances in nitric oxide release.

Adult↗
PubMed2000

No correlation of tyrosinase mRNA in bone marrow with prognosis of metastatic melanoma.

BACKGROUND: Recent publications suggest that tyrosinase mRNA in blood as well as in bone marrow is detectable only in a subgroup of patients with metastatic melanoma. OBJECTIVE: We addressed the question, whether patients with metastatic melanoma and with RT-PCR-detectable tyrosinase mRNA in blood or bone marrow have a different prognosis compared to tyrosinase mRNA-negative patients. METHODS: 20 melanoma patients with widespread clinical metastases were enrolled and the survival time after first diagnosis of visceral metastases was correlated to tyrosinase mRNA presence in blood and bone marrow samples. RESULTS: The time of survival of 8 patients with metastatic melanoma and detectable tyrosinase mRNA in either blood or bone marrow was not different from the prognosis of 12 patients without detectable tyrosinase mRNA in either blood or bone marrow. CONCLUSION: Although based on a limited number of patients our results suggest that detection of tyrosinase mRNA in blood or bone marrow samples of melanoma patients with advanced disease seems to have no substantial relevance for survival time and outcome of disease. For this purpose, detection of tyrosinase mRNA by RT-PCR is not a valid tumor marker. Nevertheless, tyrosinase positivity in bone marrow in earlier tumor stages might indicate increased risk for the development of distant metastases. This should be addressed in further studies.

Bone Marrow↗
PubMed1999

Delayed sequential ruptures of the index and thumb flexor tendons due to an occult scaphoid nonunion.

A case of sequential spontaneous loss of flexion in the thumb and index finger over a 10 year period is reported. Previously unrecognized carpal collapse as a consequence of a longstanding scaphoid nonunion was identified as the cause. Fusion of the interphalangeal joint of the thumb and suture of the index profundus tendon to the middle profundus tendon resulted in a good outcome.

Aged↗
PubMed1999

[Significance of the renin-angiotensin-aldosterone system for pathogenesis and early diagnosis of pregnancy-induced hypertension with special reference to mineralocorticoid receptors].

OBJECTIVE: In women with pregnancy-induced hypertension (PIH) the density of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) is reduced compared with healthy pregnant women. The same applies to plasma levels of aldosterone and 18-hydroxycorticosterone. In this study, we investigated whether alterations of these parameters preceded the development of clinical symptoms and, therefore, might be potential predictors of PIH involved in the pathogenesis. PATIENTS AND METHODS: In eighty-four women belonging to the risk-group for PIH but not showing any symptoms neither of PIH nor preeclampsia (PE) we characterized prospectively before the onset of disease in the second trimester of pregnancy mineralocorticoid receptor status in HML and steroid plasma levels of aldosterone and its precursors as well as cortisol through radioimmunoassay. RESULTS: 15 women developed PIH, three of which developed PE. Neither in the density of MR nor in the affinity the women that developed PIH showed any difference from healthy women. Steroid plasma levels were identical as well. CONCLUSION: We conclude that a reduction of mineralocorticoid receptors does not precede PIH within the peripheral blood. But still one can assume that the RAAS may be involved in the pathogenesis of PIH, possibly on a local level within the placenta or as a secondary change, initiated by still unknown factors.

Adult↗
PubMed1999

[Doppler ultrasound findings in therapy with urapidil].

OBJECTIVE: In a prospective study we investigated, whether changes in fetal or maternal circulation can be found by Doppler sonography under therapy with urapidil. PATIENTS AND METHODS: We investigated in 11 patients with severe pregnancy-induced hypertension (PIH) or superimposed preeclampsia in the third trimester. Doppler flow results of maternal and fetal vessels before and during therapy with urapidil. Hemodynamic parameters, like maternal blood pressure, and heart rate as well as other clinical parameters were assessed. RESULTS: Whereas the antihypertensive effects in the systolic and diastolic blood pressure were significant, we couldn't find changes in the resistance indices of fetal circulation. In contrast we found a decrease in the resistance indices in maternal vessels after an average of six days of urapidil therapy. These changes were significant in the uterine artery on the side of placental insertion. CONCLUSIONS: Because of only few side effects and a safe lowering of blood pressure, therapy with urapidil seems preferable to other well known drugs. Although Doppler flow velocimetry of uteroplacental vessels has no diagnostic benefit in monitoring PIH, the findings with this method under prolonged antihypertensive therapy are a chance for a better understanding of hemodynamic changes. The decrease in the resistance indices is another argument for the use of urapidil.

Adult↗
PubMed1999

[Pre-eclampsia and anesthesia].

The management of anaesthesia in patients suffering preeclampsia has to be selected individually. There is a high rate of caesarean sections in patients with preeclampsia. Intubation anaesthesia or regional anaesthesia are commonly used methods and can be considered comparable and equally useful. In our opinion, the application of regional anaesthesia should be preferred, if the initial criteria, such as normal neurologic status and blood coagulation, are fulfilled. We believe in a considerable reduction of vital risks when using regional anaesthesia. Our aim was to figure out the risk-factors of preeclampsia and preterm maturity regarding anaesthesia management. Preeclampsia is a severe illness in pregnancy with a frequency of 5-10%. In 1997, we experienced 73 patients with praeeclampsia according to the definition of ISSPH. Mode of delivery was conventional in 10 patients, 2 patients had a vacuum extraction and 61 patients needed a caesarean section. The rate of epidural anesthesia for delivery was 51%. We used epidural anaesthesia in 6 spontaneous deliveries, in 2 vacuum extractions and in 30 caesarean sections. There were no problems with epidural anaesthesia and the outcome of mother and child was also considered to be excellent. We suggest to use regional anesthesia techniques whenever possible.

Anesthesia, Conduction↗
PubMed1999

[Current aspects of antihypertensive therapy in pregnant patients with pre-eclampsia].

Preeclampsia is a disease which occurs in Europe in about 6-8%, in the USA in about 7-10% and in Africa in about 18% of all pregnancies. A causal treatment of preeclampsia is, with the exception of delivery, not possible up to now. Since a prematurely delivery of the newborn has to be avoided because of the risks caused by immaturity of lungs, treatment and care of pregnant women having preeclampsia or any other kind of hypertensive diseases is restricted to the following approaches: antihypertensive treatment, volume expansion, and eclampsia prophylaxis with magnesium sulfate. Object of this treatment is to avoid complications on the mother's side caused by the disease and to postpone delivery, as far as possible from the child's side, in order to reduce the consequences of premature birth. During antihypertensive treatment of patients with serious hypertension, i.e. with diastolic blood pressure of 110 x mm Hg and higher, dihydralazine is in clinical use since 40 years, although many patients suffer from side-effects of dihydralazine such as distinctive tachycardia, headaches, fluid retention and nausea. With urapidil a well controllable antihypertensive is available, which prevents the effect of catecholamines at the vascular wall by a postsynaptic alpha-1 receptor blockade. Previous studies related to the application of urapidil in the treatment of hypertension during pregnancy certify the good controllability of urapidil following intravenous application as well as minor side-effects after start of treatment.

Antihypertensive Agents↗
PubMed1998

Treatment of hypertension in patients with pre-eclampsia: a prospective parallel-group study comparing dihydralazine with urapidil.

BACKGROUND: The primary objective of treatment in women with severe hypertension and pre-eclampsia is to prevent complications such as encephalopathy and haemorrhage. In many countries dihydralazine is considered the drug of choice for treating hypertension in pregnancy, because it now has been used safely for about 30 years, and the introduction of a new drug in pregnancy is a difficult task with partially unknown hazards. In some other countries combined alpha- and beta-blockers are also used. Taking into account that some patients with pre-eclampsia do not respond to dihydralazine and the drug has serious side-effects like headache and reflex tachycardia, there is some need for developing alternative treatment strategies using drugs that are more adequate for pregnancy than dihydralazine. METHODS: Urapidil is a post-synaptic alpha 1 adrenoceptor antagonist, which is widely used to control hypertensive crises unrelated to pregnancy. Since it is known that pre-eclampsia is associated with increased sympathetic activity, administration of an alpha 1 adrenoceptor antagonist provides a reasonable therapeutic basis. So far there is only one report describing the i.v. use of urapidil in the treatment of hypertension in pregnancy unresponsive to dihydralazine and one report which describes the oral use of urapidil. In an earlier pilot study we examined the dose range for i.v. application of urapidil necessary for adequate blood pressure control in patients with pre-eclampsia. In the present randomized controlled study 26 white women with pre-eclampsia and hypertension in pregnancy were included. Treatment was not blinded. During the initial period of intensive intravenous treatment all subjects were under constant surveillance by a physician and a nurse. RESULTS: Effective prolonged control of blood pressure (values below 150/100 mmHg) was achieved in all patients of the two groups. In one patient of the dihydralazine group signs of lightheadedness and near syncope were noted. After this side-effect of dihydralazine the patient was treated with urapidil. At the end of the observation period the maternal heart rate in the dihydralazine group was higher than in the urapidil group. CONCLUSIONS: Since urapidil decreased the high blood pressure in patients with pre-eclampsia without serious side-effects urapidil appears preferable superior to dihydralazine. The haemodynamic effects of urapidil were more predictable than those of dihydralazine. The reduction of intracerebral pressure could be an additional advantage of urapidil in the treatment of patients with pre-eclampsia.

Adult↗
PubMed1998

Introduction of a simplified round partogram in rural maternity units: Seno province, Burkina Faso, West-Africa.

After a 3-day seminar on the utilization of a rectangular World Health Organization (WHO) version of the partogram and the round partogram, both versions were used under supervision in the maternity rooms of the Seno province, Burkina Faso, West-Africa, for 3 months. After this period a semi-standardized questionnaire was distributed among the partogram users. Using the round partogram with a plastic dial (dilatation indicator for the assessment of labour--DIAL), the two most common errors in the utilization of the rectangular partogram, incorrect recording at the initial examination and at the transition from latent to active phase, were largely avoided. Although the partogram was used in only 46.6% of all deliveries at the health unit level, 86% of the maternity staff using the partograms preferred the round partogram because of its time-saving and user-friendly qualities. Eighty-six per cent of its users felt that by starting the alert- and action-lines at a point later than that in the WHO partogram they would be able to avoid transferring patients unnecessarily. The wide acceptance of the simplified round partogram among the peripheral health units surveyed shows that the partogram would be an attractive tool for its users when it is made easy to use and a useful indicator for determining whether a patient transfer is necessary.

Adult↗
PubMed1998

Seasonal change in the incidence of preeclampsia in Zimbabwe.

BACKGROUND: The aim of our study was to evaluate the number of women with hypertensive complications during pregnancy in a southern province in Zimbabwe and to examine the annual change in the incidence of preeclampsia. METHODS: In three different hospitals the preeclamptic women who were treated between January 1992 and August 1995 were counted. This data was compared with the amount of rainfall obtained from the local meteorological stations. RESULTS: A distinctive change in the incidence of preeclampsia during the year could be observed. These changes go along with the seasonal variation in precipitation: at the end of the dry season and in the first months of the rainy season there is an increase in the incidence. CONCLUSIONS: The relationship between climate and occurrence of preeclampsia raises new questions in the pathophysiology of preeclampsia. Possible explanations could be the impact of humidity and temperature on vessels or the production of vasoactive substances. Dry and rainy seasons influence the agricultural yields and therefore the nutritional status could also play a role in the pathophysiology.

Adult↗
PubMed1998

[Pregnancy in corrected transposition of great arteries and therapy with ACE inhibitors].

A pregnancy after Mustard repair for transposition of the great arteries and ventricular septal defect with pulmonary stenosis is reported. The 23-year-old gravida 1 was treated with ACE inhibitors up to 26 weeks of gestation until cardiac medication was changed to dihydralazine. At 28 weeks of gestation the patient developed cardiac decompensation leading to caesarean section for maternal indication at 29 weeks of gestation. The neonate did not show any congenital malformation nor anuria. The patient was moved to a normal ward six days after delivery. A cardiac follow-up examination showed no difference to the condition before pregnancy.

Adult↗
PubMed1997

A rationale for positive selection of peripheral blood stem cells in multiple myeloma: highly purified CD34+ cell fractions of leukapheresis products do not contain malignant cells.

In multiple myeloma (MM), the presence of tumor cells in leukapheresis products (LP) has been demonstrated with highly sensitive molecular biological tools in up to 100% of cases. Therefore methods to reduce the tumor load of LP by CD34+ selection are envisaged. However, there is controversy as to whether the CD34+ cell is already involved in the malignant process. We have established a PCR assay with allele-specific oligonucleotide primers (ASO) complementary to the CDR3-hypervariable region of the immunoglobulin heavy chain gene of each patient's myeloma clone. Using this ASO-PCR, 43 LP of 10 patients with MM eligible for high-dose therapy were assessed for malignant cells. Furthermore, in an experimental setting we have examined 10 CD34+ and four CD19+ fractions obtained from PCR-positive LP by sequential preparative magnetic and fluorescence activated cell sorting (purity >96%) for the presence of the tumor-specific CDR3 region. The majority of LP harbored cells of the myeloma clone (93%), while all CD34+ fractions were PCR-negative. In all CD19+ fractions malignant cells were detected. These results confirm that CD34+ selection can be considered for LP in MM. The sensitivity of the ASO-PCR (up to 10[-5]) enables us further to monitor the efficacy of CD34+ enrichment protocols in the clinical setting.

Adult↗
PubMed1996

Maternal mortality in the main referral hospital in The Gambia, west Africa.

A retrospective analysis of 78 maternal deaths was performed during 1991-1992 to estimate maternal mortality at the maternity unit of the main tertiary level hospital in The Gambia. The non-abortion maternal mortality ratio (MMR) was 736 per 100 000 live births. Among the direct causes, haemorrhage caused most deaths (24%), followed by hypertensive disorders in pregnancy (HDP) (21%). Sepsis was the main cause of death in 15%. Anaemia led among the indirect causes of death (8%) and was a co-factor in 41% of all deaths. Substandard care factors other than medical causes were determined involving health care facilities, staff, drugs and equipment, and patient-related factors. Well known risk factors of low age (< or = 19 years) and nulliparity were highly represented in the maternal death group, and delivery by Caesarean section occurred more than threefold compared to the overall Caesarean section rate. Taking haemorrhage as an example, it is demonstrated that the way diagnoses are grouped significantly affects the statistical elaboration of maternal deaths.

Adolescent↗
PubMed1995

Training birth attendants in the Sahel.

A small-scale training programme for birth attendants in a remote area of Burkina Faso was evaluated two years after it had been started. The evaluation methods included interviews with trained birth attendants and the analysis of health service statistics and survey data. The findings showed that the programme had been moderately successful in imparting knowledge and overcoming cultural inhibitions about assisted deliveries. However, the effectiveness of the programme was severely curtailed by structural deficits in the health system, especially lack of skilled staff, supervision and transport. In deprived areas such as the Sahel, it is probably the health centre, the hospital and the referral system that should be the first priority for improvement, rather than grass-roots practices.

Adult↗
PubMed1994

[Anti-hypertensive therapy in pregnancy-induced hypertension with urapidil].

Urapidil is an antagonist of postsynaptic alpha 1 receptors, which leads to a diminution of the increased blood pressure by reducing the peripheral vascular resistance. With this pilot study we examined, whether it is possible to reduce the pregnancy-induced-hypertension with urapidil postpartum. The postpartum dosage of dihydralazine was diminished step by step and finally discontinued. We started i.v. treatment with urapidil at a diastolic blood pressure of more than 100 mm Hg. We observed a declining blood pressure in all cases without any tachycardia or serious side effects. Further studies will have to classify the rank of urapidil in the treatment of hypertension in preeclampsia.

Antihypertensive Agents↗