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Biomedical subjects

R Wiedemann

Publications and source records attributed to R Wiedemann.

At least 19 recordsLinked to original sources

[Therapy of pulmonary arterial hypertension].

New drugs for pulmonary arterial hypertension have shown efficacy in randomized controlled trials. Endothelin receptor antagonists (ERA) and prostanoids are most important for clinical practice. Bosentan represents the first approved orally active therapy for PAH. Besides its hepatotoxicity it is mostly well tolerated. The first approved prostanoid, epoprostenol, is currently first choice only for decompensated right heart failure in PAH. It has to be delivered continuously intravenously and is prone to complications, side effects and very high costs. Alternatively, subcutaneous treprostinil can be applied. It is less risky and expensive but may cause local pain at the infusion site. Inhaled iloprost combines the features of a prostanoid with pulmonary and intrapulmonary selectivity. Alternatively, iloprost is being used as continuous intravenous infusion. The phosphodiesterase-5 inhibitor sildenafil was effective in two randomized controlled trials but has not been approved for PAH therapy.

Antihypertensive Agents↗

Lung cGMP release subsequent to NO inhalation in pulmonary hypertension: responders versus nonresponders.

Inhalation of nitric oxide (NO) is widely employed for the assessment of pulmonary vasoresponsiveness in pulmonary hypertension (PH). However, the reasons for the huge differences in vascular reactivity to NO between patients are unknown, and the role of NO-induced cyclic guanosine monophosphate (cGMP) is unclear. Twenty patients with severe precapillary PH were investigated. Thirty-six Swan-Ganz catheter investigations were performed and the study subjects were tested for responses to NO inhalation. This included an assessment of pulmonary and systemic arterial plasma cGMP and atrial natriuretic peptide (ANP) levels. A significant NO response (pulmonary vascular resistance (PVR) decrease >20%) was noted in nine of 20 patients (45%) during the first catheterization. A highly significant correlation between baseline plasma cGMP and ANP levels with PVR was observed (r=0.62 and r=0.66, respectively; p<0.0001). In response to NO, systemic and mixed venous cGMP levels increased from 13.9 +/- 1.28 nM and 12.75 +/- 0.99 nM to 79.23 +/- 4.99 nM and 55.25 +/- 4.41 nM (p<0.001), respectively, accompanied by the appearance of a marked transpulmonary cGMP gradient. Although in the responder group ANP levels were significantly reduced after NO inhalation, no significant correlation was observed to the extent of PVR reduction. The magnitude of the NO-elicited cGMP response did not discriminate between haemodynamic responders and nonresponders. This study concludes that plasma cyclic guanosine monophosphate levels are significantly correlated with the severity of disease in pulmonary arterial hypertension. Nitric oxide inhalation provokes a prompt increase in cyclic guanosine monophosphate secretion, but the magnitude of this release is not linked with a decrease in pulmonary vascular resistance.

Administration, Inhalation↗

An unprecedented type of migratory insertion reactions of unsaturated C3 units into Rh-O and Rh-C bonds.

A series of iodo- and hydroxorhodium(I) complexes of the general composition trans-[RhX(=C=C=CRR')(PiPr3)2] (X = I: 5-7; X = OH: 8-11) was prepared from the related chlororhodium(I) precursors. The hydroxo compounds behave as organometallic Brønsted bases and react with acids like MeCO2H, PhCO2H, PhOH, or TsOH by elimination of water to give the substitution products trans-[RhX'(=C=C=CRR')(PiPr3)2] (X' = MeCO2: 12, 13; X' = PhCO2: 14; X' = PhO: 15, 16; X' = TsO: 17, 18) in good to excellent yields. In contrast to the tosylates 17, 18, which react with CO by cleavage of the allenylidene-metal bond to give trans-[Rh(OTs)(CO)(PiPr3)2] (19), treatment of the acetato and phenolato derivatives 12, 13 and 15, 16 with CO affords by migratory insertion of the allenylidene unit into the Rh-O bond the alkynyl complexes trans-[Rh[C(triple bond)CCR(R')X'](CO)(PiPr3)2] (X' = MeCO2: 20, 21; X' = OPh: 22, 23). Similarly, the reactions of the hydroxo compounds 8, 10, and 11 with CH2(CN)2 and either CO or CNMe yield the carbonyl and the isocyanide complexes trans-[Rh[C(triple bond)CCR(R')CH(CN)2](L')(PiPr3)2] (L' = CO: 25-27; L' = CNMe: 28-30), respectively. By protolytic cleavage of the Rh-C sigma bond the gamma-functionalized alkynes HC(triple bond)CCR(R')CH(CN)2 (31, 32) are generated from 25, 26 and HCl in benzene. The molecular structure of 22 was determined by X-ray crystallography.

Journal Article↗

Atrial natriuretic peptide in severe primary and nonprimary pulmonary hypertension: response to iloprost inhalation.

OBJECTIVES: The goal of this study was to assess atrial natriuretic peptide (ANP) levels during inhalation of iloprost in severe primary (PPH) and nonprimary pulmonary hypertension (NPPH). BACKGROUND: The ANP system is activated in pulmonary hypertension and may help protect from right ventricular (RV) decompensation. It is unknown if ANP regulation is the same in severe PPH and NPPH and if the dynamic regulation is intact in a highly activated ANP system. METHODS: In 11 patients with PPH and seven patients with NPPH, right heart catheter investigations were performed. Pulmonary and systemic artery ANP and cyclic guanosine monophosphate (cGMP) levels as well as hemodynamics were measured before and after iloprost inhalation. RESULTS: The baseline hemodynamics of patients with PPH and patients with NPPH were comparable (mean pulmonary artery pressure [mPAP]: 61 +/- 5 mm Hg vs. 52 +/- 5 mm Hg, pulmonary vascular resistance [PVR]: 1,504 +/- 153 dyne.s.cm(-5) vs. 1,219 +/- 270 dyne.s.cm(-5). Atrial natriuretic peptide and cGMP levels were increased about tenfold and fivefold compared with controls in both PPH and NPPH. Iloprost inhalation significantly decreased mPAP (-9.1 +/- 2.5 mm Hg vs. -7.9 +/- 1.5 mm Hg), PVR (-453 +/- 103 dyne.s.cm(-5) vs. -381 +/- 114 dyne.s.cm(-5)), ANP (-99 +/- 63 pg/ml vs. -108 +/- 47 pg/ml) and cGMP (-4.6 +/- 0.9 nM vs. -4.2 +/- 1.6 nM). Baseline ANP including all patients significantly correlated with PVR, right atrial pressure, cardiac index, RV ejection fraction, mixed venous oxygen saturation and cGMP. CONCLUSIONS: The ANP system is highly activated in patients with severe PPH and NPPH. Atrial natriuretic peptide levels are significantly correlated with parameters of RV function and pre- and afterload. Iloprost inhalation causes a rapid decrease in ANP and cGMP in parallel with pulmonary vasodilation and hemodynamic improvement.

Administration, Inhalation↗

[Biochemical stress monitoring during cataract surgery; phenylephrine 10% shows no changes in serum-catecholamines in comparison with phenylephrine 5%].

BACKGROUND: There is a controversy about the concentration of topical phenylephrine recommended for diagnostic or therapeutic mydriasis. Phenylephrine 10% leads to a faster and more pronounced mydriasis but cardio-vascular side-effects like hypertension and arrhythmia have been reported. A maximal pupillary dilatation is a prerequisite for successful cataract surgery. The aim of this study was to evaluate the risk-benefit ratio of phenylephrine 10% in comparison to 5% in the daily practice of the cataract-surgery unit in our clinic by clinical assessment and monitoring of biochemical stress parameters. PATIENTS AND METHODS: 30 informed and consenting patients were randomly allocated to 2 groups of equal size. After a single application of 2 drops of phenylephrine 5% in group 1 and 10% in group 2 respectively and 1 drops of cyclopentolate 1% with neutral pupil (time 0), an ECG was recorded and blood pressure, pulse, oxygen-saturation and pupil size were measured. Simultaneously a blood-sample was taken and the serum-catecholamines adrenaline and noradrenaline were determined by HPLC (High Pressure Liquid Chromatography). These measurements were repeated after 5, 10 and 30 minutes. RESULTS: The mean pupil area after 30 minutes in group 1 was 31.97 (+/- 0.43) mm2 compared to 45.72 (+/- 0.39) mm2 in group 2. Our data showed no other significant variation between the groups: neither clinical monitoring nor catecholamine measurements showed concentration-dependent patterns in blood pressure development or serum levels. No systemic cardiovascular effects were observed. CONCLUSION: These results demonstrate that a controlled application of phenylephrine 10%--under observation of contraindications--yields no increased risk for the occurrence of cardio-vascular side-effects in comparison with phenylephrine 5%. Therefore, we recommend the use of phenylephrine 10% in the described dosage as routine medication for cataract surgery.

Aged↗

[Tyndallometry in patients with diabetic macular edema before and after central laser coagulation].

BACKGROUND: It is known that the breakdown of the blood-retina-barrier (BRB) as well as the blood-aqueous-barrier (BAB) is one of the earliest pathopysiological changes in the diabetic eye. Some previous studies confirmed a statistically significant increase of flare values of the aqueous humor in eyes with diabetic retinopathy which is lineary correlated with the protein concentration. This study investigated the effect of a central laser photocoagulation in eyes with clinically significant macular edema on the permeability of the blood-aqueous-barrier (BAB). PATIENTS AND METHODS: We included 22 eyes of 22 patients with diabetes mellitus suffering from clinically significant macular edema determined by fluorescence angiography giving an indication for central laser treatment. Two measurements of aqueous flare were taken, the first before laser photocoagulation (grid with about 100 coagulations) and the second 6 to 8 weeks after treatment. RESULTS: The flare values before treatment were 11.4 +/- 4.1 phc/ms (4.9-23.8) and after treatment 10.0 +/- 3.5 phc/ms (5.7-16.7). There was a significant difference between both measurements (p = 0.039). CONCLUSIONS: The protein concentration of the aqeoues humor is a parameter which allows to characterize the permeability of the BAB. The central laser photocoagulation seems to seal the vessels.

Aged↗

[Keratoconjunctivitis sicca in patients with lipoprotein (a) elevation].

BACKGROUND: Elevated Lp(a) levels are known as risk factor for premature coronary artery disease and apoplexy. To our knowledge ophthalmologic alterations have not been described in combination with elevated Lp(a) levels. We examined whether patients with LP (a) elevation had an increased incidence of keratoconjunctivitis sicca. PATIENTS AND METHODS: 27 patients, 16 women and 11 men were examined. The Lp(a) value was in all patients definitively pathological. The following examinations were performed: history, slitlamp examination, Schirmer-test, impressioncytology, fluorescein staining of the cornea, applanation tonometry and examination of the ocular fundus. RESULTS: The results show a pathologic Schirmer-test in 70.3% of the eyes, in 81.5% a pathologic impressioncytology, and in 48.1% a pathologic fluorescein staining. The Schirmer-test is not sufficiently sensitive and specific in diagnosing the dry eye, whereas impression cytology is highly sensitive and specific. CONCLUSIONS: We could show, that in more than 80% of the examined patients at least one sign of keratoconjunctivitis sicca was found; however we did not find a correlation between the height of the Lp(a) level and the degree of pathologic impression cytology. Further examinations are needed to investigate the causal connection between keratoconjunctivitis sicca and Lp(a) elevation.

Adolescent↗

Beyond recanalizing proximal tube occlusion: the argument for further diagnosis and classification.

Proximal tube occlusion (PTO) accounts for 20% of tubal factor cases. The classification into nodular (salpingitis isthmica nodosa or endometriosis), non-nodular (true fibrotic occlusion) and so-called pseudo occlusion (detritus, polyps, hypoplastic tubes) is essential. Using falloposcopy, PTO that is already diagnosed by laparoscopy and hysterosalpingography (HSG) can be confirmed or bypassed (false PTO); patients with false PTO were placed on a temporary waiting period. Nodular and pseudo occlusion patients were pre-treated with gonadotrophin-releasing hormone analogue (GnRH-a) for at least 6 weeks to shrink the underlying pathology, after which tubal re-catheterization was performed. In a prospective study starting in July 1993, 53 patients prediagnosed as having PTO were examined by falloposcopy. Three of these patients had non-nodular occlusion and were directed to microsurgical repair (conservative treatment not possible). A total of 19 cases revealed patent tubes with healthy mucosa and no underlying pathology (false PTO). Of the remaining 31 patients, 18 were classified as nodular and 13 as pseudo occlusion. In all of these patients at least one tube was patent after GnRH-a treatment. After a 6 month period, 37% of the false PTO patients achieved a spontaneous pregnancy (6% per cycle). The spontaneous pregnancy rate in the true PTO group was significantly lower (10% per patient, 1.6% per month; P < 0.05). Using assisted reproduction techniques, in particular gamete intra-Fallopian transfer (GIFT), as a subsequent treatment for the true PTO group, a pregnancy rate of 50% per cycle was achieved. A retrospective analysis of our entire PTO population (n = 109) showed a spontaneous pregnancy rate after achieving tubal patency (using falloposcopy and GnRH-a) that was dramatically low (1.8%), with no difference between the nodular and pseudo groups. The chance for pregnancy can be enhanced significantly (P < 0.001) using assisted reproduction techniques (GIFT) following tubal re-catheterization and GnRH-a treatment.

Buserelin↗

[Pseudocystic metastases of carcinoma of the uterine cervix mimicking polycystic liver disease].

Pseudocystic liver metastases are rare and mainly described in neuroendocrine or ovarian tumors. We report the case of a 46-year-old woman who presented with multiple hepatic metastases mimicking polycystic liver disease. Carcinoma of the uterine cervix had been diagnosed 9 years earlier, and initially treated by radiumtherapy and surgery. Although histological post mortem examination of the pseudocystic liver metastases was not characteristic, they were related to the uterine cervix carcinoma for the following reasons: no other primary tumor was discovered, especially carcinoid or ovarian tumors: immunostains were positive for epithelial cells and negative for the neuroendocrine panel: the cystic cerebellum metastasis had a typical histologic aspect. Uterine cervical carcinoma must thus be included in the list of tumors which may form cystic hepatic metastases.

Carcinoma, Squamous Cell↗

Superfetation occurring in connection with gamete intrafallopian transfer: a case report.

This observation reports a case of susperfetation which occurred in connection with gamete intrafallopian transfer (GIFT). The macroscopic and histological examination of a spontaneous abortion from a 33-year-old woman (15th week of pregnancy) revealed the existence of two embryos with a monochorionic diamniotic placenta (developmental age approximately 41 days) and two fetuses and a fetal remnant with a trichorionic and triamniotic placenta (developmental age approximately 98 days). The large developmental age difference of embryos and fetuses cannot be explained by retardation, because the embryos showed adequate development with the development of their placenta. Moreover, the usual causes of intrauterine growth retardation could be excluded as could retention of the embryos since the tissues showed no autolytic changes. Consequently the large developmental age difference is explained by assuming that the embryos developed from successive ovulations. A second nidation of blastocysts had occurred after the GIFT concurrently with the clinically reported hyperstimulation syndrome.

Abortion, Spontaneous↗

[Trans-uterine fallopian tube catheterization--a noninvasive, ambulatory evaluation of fallopian tube patency].

In a prospective clinical study (March 89-June 91), we examined 114 infertile women to evaluate the diagnostic value of trans-uterine tubal cannulation with the injection of sterile fluid and consecutive sonographical control in the assessment of tubal patency. The results of this technique were compared with the findings of laparoscopy and/or hysterosalpingography. With the Jansen-Anderson Catheter (J-A-C) it was possible to reach the isthmic part of the tube without any analgesia or anaesthesia. 10 to 15 ml of sterile culture medium were injected. In case of tubal patency the fluid was detectable in the pouch of Douglas by transvaginal ultrasound. In 108 out of 114 women (94.7%), the cannulation of at least one tube was possible. All 97 patients with patent tubes (laparoscopy) were diagnosed correctly via the J-A-C. The three cases of proximal tubal occlusion were also diagnosed correctly, 8 patients with one or two-sided hydrosalpinx were also recognized. All five patients with bilateral hydrosalpinx were detected. Three women showed a unilateral hydrosalpinx in the laparoscopy. In these cases the diagnosis obtained by the J-A-C was once bilaterally patent and twice bilaterally distally occluded. Trans-uterine cannulation of the tubes with injection of sterile fluid and consecutive transvaginal sonography is an easy and safe method to evaluate the tubal status. It becomes possible thereby to prove tubal patency in a very early stage of diagnostics. Loss of time and futile treatment cycles (stimulations or inseminations in cases of tubal occlusion) can thus be avoided.

Adult↗

[Treatment of endometriosis with the GnRH agonist leuprorelin acetate depot (Enatone-Gyn monthly depot): a multicenter study].

In an open, non-randomized prospective phase-III-study the clinical and endocrine efficacy as well as the safety of leuprorelin acetate depot (Enantone-Gyn Monats-Depot) were investigated. The therapeutic results of 198 patients, gathered from 5 university institutions and two city hospitals, are reported. Endometriosis was classified by the revised American Fertility Society score (r-AFS) before and at the end of treatment. Serum levels of LH, FSH, prolactin, estradiol, progesterone, androstenedione, testosterone and leuprorelin acetate were determined by radioimmunoassay. The mean total r-AFS score changed as follows: before surgical intervention during first-look laparoscopy 21 +/- 24 at the end of first-look laparoscopy 15 +/- 19 at the end of the GnRH-treatment 8 +/- 14 During leuprorelin acetate treatment the r-AFS stages changed as follows: [table; see text] Using the scoring system 85.2% of the patients improved. Relief of dysmenorrhoea could be achieved in 95.4%, relief of dyspareunia in 64% and of pelvic pain in 69.4% of patients. Baseline hormone levels dropped sharply during treatment. [table; see text] Androstenedione, testosterone, blood pressure, body weight, haematological parameters, liver enzymes, creatinine, electrolytes and HDL-/LDL-cholesterin remained more or less unchanged. Side effects being hot flushes, sweating, sleeplessness, headache, nausea, depression and vaginal dryness were due to estradiol deprivation. In 135 patients resumption of menstruation occurred in 95.6% within the first three months post-treatment. 23 patients of whom 21 were judged as infertile, became pregnant immediately after treatment was finished. The study results confirm the efficacy of leuprorelin acetate depot in the treatment of even advanced stages of endometriosis.

Adolescent↗

[Hormonal and ultrasound monitoring of early pregnancy--differential diagnosis of extrauterine pregnancy and multiple pregnancy].

In this study sonographical and hormonal findings in 63 patients with intrauterine singleton pregnancy were compared with 18 patients with multiple pregnancies and 28 patients with ectopic pregnancy. The earliest detection of the intrauterine gestational sac was obtained with a HCG level of 659 mlU/ml. The sonographical development correlated well with HCG values. There was no statistically significant correlation between gestational age and HCG. In multiple pregnancies with sonographical findings comparable to the development in singletons HCG values were remarkably elevated. A discrimination between multiple and ectopic pregnancies by sonographical and hormonal criteria cannot be performed sufficiently in a HCG zone of 1500 mlU/ml. Close sonographical and hormonal follow-up until diagnosis of the intrauterine pregnancy is necessary.

Chorionic Gonadotropin↗

[Pregnancy with an extremely rare P blood group with anti-PP1Pk].

The authors report on a successful pregnancy in a young Turkish patient with p and anti-PP1Pk-antibodies. Anti-PP1Pk is considered to cause haemolytic diseases in the newborn and habitual abortions. The patient was treated via plasma exchange and substitution with intravenous immunoglobulin. At 31 weeks of gestation the patient underwent Caesarean section due to growth retardation and pathological signs in the fetal CTG. The child has developed well up to two years after the delivery. Based on our data and a review of the literature, the effectiveness of therapy by plasmapheresis and/or immunoglobulin is discussed.

Abortion, Habitual↗