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S Niesert

Publications and source records attributed to S Niesert.

At least 19 recordsLinked to original sources

Evaluation of different protocols for gene transfer into non-obese diabetes/severe combined immunodeficiency disease mouse repopulating cells.

PURPOSE: Although gene transfer with retroviral vectors has shown distinct clinical success in defined settings, efficient genetic manipulation of hematopoietic progenitor cells remains a challenge. To address this issue we have evaluated different transduction protocols and retroviral constructs in the non-obese diabetes (NOD)/severe combined immunodeficiency disease (SCID) xenograft model. METHODS: An extended transduction protocol requiring 144 h of in vitro manipulation was compared to a more conventional protocol requiring 96 h only. RESULT: While pretransplantation analysis of cells transduced with a retroviral vector, expressing the enhanced green fluorescent protein (EGFP) marker gene, demonstrated significantly higher overall transduction rates for the extended protocol (33.6 +/- 2.3 vs. 22.1 +/- 3.8%), EGFP expression in CD34+ cells before transplantation (4.0 +/- 0.9 vs. 11.6 +/- 2.5%), engraftment of human cells in NOD/SCID bone marrow 4 weeks after transplantation (4.5 +/- 1.7 vs. 36.5 +/- 9.4%) and EGFP expression in these cells (0 +/- 0 vs. 11.3 +/- 2.8%) were significantly impaired. When the 96 h protocol was used in combination with the spleen focus forming virus (SFFV)/murine embryonic stem cell (MESV) hybrid vector SFbeta11-EGFP, high transduction rates for CD45+ (41.0 +/- 5.3%) and CD34+ (38.5 +/- 3.7%) cells prior to transplantation, as well as efficient human cell engraftment in NOD/SCID mice 4 weeks after transplantation (32.4 +/- 3.5%), was detected. Transgene expression was observed in B-lymphoid (15.9 +/- 2.0%), myeloid (36.5 +/- 3.5%) and CD34+ cells (10.1 +/- 1.5%). CONCLUSION: Our data show that CD34+ cells maintained in cytokines for multiple days may differentiate and loose their capacity to contribute to the haematological reconstitution of NOD/SCID mice. In addition, the SFFV/MESV hybrid vector SFbeta11-EGFP allows efficient transduction of and gene expression in haematopoietic progenitor cells.

Animals↗

Pregnancy in congenital cardiac disease: an increasing challenge for cardiologists and obstetricians -- a prospective multicenter study.

OBJECTIVES: Aim of this study was to assess the occurrence of pregnancy-related complications of mother and child during pregnancy, delivery and puerperium in women with CCD prospectively. STUDY DESIGN, POPULATION: This prospective multicenter study included 122 pregnancies in 106 women with CCD (72 with, 34 without previous cardiac surgery). Patient age was 17-44, median 26 years. Cardiac and non-cardiac complications, mode of delivery, abortion, and CCD of the newborn were assessed. RESULTS: Initially all women were in Functional Class I or II. Worsening during pregnancy occurred in 25.5% (n=27), mainly during the second and third trimester. Significant problems due to bleeding, hypertension, rhythm disturbances, endocarditis, liver congestion, increasing cyanosis or death, occurred in 11.3%. Twelve per cent of deliveries were premature. Five women had therapeutic abortion, nine spontaneous abortions, nine preterm births, and one intrauterine death. Seventy-nine per cent (n=85) delivered spontaneously; 21.3% (n=23) had caesarean section. Of the 111 live born children, 5.4% (n=6) had a CCD. CONCLUSIONS: Most women with CCD and a good functional class before pregnancy tolerate pregnancy without major problems. However, pregnancy may induce serious cardiac and obstetric complications. The specific risks require an individualized multidisciplinary patient-management by experienced physicians.

Adolescent↗

[The course of hypertension in pregnancy].

Pregnancy-included hypertension (PIH) and chronic hypertension are the most common medical disorders during pregnancy. They are a major cause of maternal and neonatal morbidity and mortality. Therefore a correct diagnosis and the knowledge of the classification of hypertension are necessary to choose the best treatment for the mother and the child. This review presents the guidelines for the diagnosis and management of the different forms of PIH.

Antihypertensive Agents↗

Outcome of 22 successful pregnancies after liver transplantation.

To evaluate course and outcome of pregnancies in liver transplanted patients and to provide a brief summary on the development of these children, 22 pregnancies and 23 children (1 month-99 months old) of 16 patients who had been liver transplanted at our institution (mean interval from transplantation to pregnancy 43.1 months) were reviewed. Standard immunosuppressive regimen during pregnancy consisted of cyclosporine A (CyA), tacrolimus (FK), azathioprine (Aza) and/or a low-dose steroid therapy. CyA and FK whole blood trough levels were monitored on a routinely basis to keep therapeutic range (CyA 80-150 ng/mL; FK 4-8 ng/mL). No patient had a graft loss and there were no lethal complications. Beside de novo hypertension (n = 3) and preeclampsia (n = 3) problems during pregnancy included one steroid-sensitive rejection at 36 wk gestation, one case of tacrolimus toxicity at 24 wk with complete reconstitution, and one case of de novo choledocholithiasis with recurrent cholangitis. Three cases of infections occurred. In total, 23 children, including one set of twins, were born. Terms of gestation (mean = 38.1 wk, +/- 2.2 SD), deliveries (spontaneous n = 13, cesarean section n = 7, forceps n = 1, vacuum extraction (VE) n = 1) and birth weights (2876 g, +/- 589.3 SD) were typical. Three pregnancies were preterm, one being a twin pregnancy. Neither congenital malformations nor unusual infections were seen in the children. Postnatal follow-up revealed appropriate physical growth to date. Psychological development seems to be adequate. Our data indicate that successful pregnancies after liver transplantation (LTX) under careful management by transplant specialists, obstetricians and perinatalogists have a good outcome. So far, neither pre- nor postnatal child development appear to be influenced by maternal immunosuppressive therapy during pregnancy.

Adult↗

Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women.

A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.

Case-Control Studies↗

-Obstetric prognosis after pre-eclampsia, eclampsia or HELLP syndrome-.

Preeclampsia, eclampsia and the HELLP syndrome are serious pregnancy complications associated with increased maternal and perinatal mortality and morbidity. The question of subsequent pregnancy outcome in these patients is of great importance for the patient and the obstetrician. The risk of recurrence of hypertensive complications during subsequent pregnancy is related to the time of the onset and the clinical signs of hypertension during the first pregnancy. Patients having hypertensive pregnancies should be examined for chronic hypertension, kidney disease and other internal diseases. The recurrence risk is for preeclampsia between 19.5% and 25.9% and for eclampsia between 21.9% and 46.8%. Patients developing the disease early in pregnancy and with chronic hypertension are at higher risk. For the HELLP syndrome the risk of recurrence is between 3% and 5%. These patients should be considered to be at increased risk for obstetric complications in subsequent pregnancies and close perinatal care is indicated in subsequent pregnancies.

Eclampsia↗

[Prevalence of hepatitis B in pregnancy and selective screening].

Infants of mothers positive for HBsAg are at risk for peripartal transmission of hepatitis B infection. Active and passive immunisation administered immediately after birth can prevent neonatal hepatitis B. In a prospective study the prevalence of hepatitis B in pregnant women and the efficiency of selective antepartal screening of women with identifiable risk factors for hepatitis B were analysed. From November 1992 to May 1994, 912 women presenting at the department of obstetrics and gynaecology of the Medizinischen Hochschule Hannover were tested for HBsAg, HBeAg, anti HBs, anti Hbc, and HBV-DNA. Venous blood samples were taken during the third trimester of pregnancy or immediately post partum. 13 (1.4%) patients were found to be HBsAg positive. The prevalence of HBsAg in German females and women from countries with low endemia for hepatitis B was 0.38% versus 5.7% for women from endemic areas. HBeAg was detected in two patients. 10 patients with a positive serological result belonged to groups considered to be of increased risk for hepatitis B infection. Nevertheless, 6 of these women had not undergone antepartal screening. These findings support a need for routine screening of all pregnant women for HBsAg, as it has been recently introduced in Germany.

Cross-Sectional Studies↗

-Glucose, insulin and C-peptide kinetics during tocolysis with oral fenoterol-.

OBJECTIVE: The effect of oral fenoterol therapy (40 mg/day) on the kinetics of glucose, insulin and C-peptide during an oral glucose tolerance test (oGTT; 100 g glucose) was investigated in the third trimester. METHODS: 54 patients without tocolytic therapy (25 with a pathologic oGTT) were compared with 36 patients who received tocolytic therapy (18 patients with a pathologic oGTT). RESULTS: The patients with a normal or pathologic oGTT and with or without tocolytic therapy showed no significant differences in respect of the concentrations of glucose, insulin and C-peptide. During tocolytic therapy, an early increase in insulin was observed as well as slightly elevated C-peptide concentrations and a decreased C-peptide/insulin quotient.

Administration, Oral↗

[Atrial natriuretic peptide in normotensive pregnancy: concentrations in physical stress, pre- and postpartal and in the umbilical cord].

The concentrations of the atrial natriuretic peptide (ANP) during the 3rd trimester of pregnancy (n = 54), the 1st, 2nd, and 3rd day post partum and in 10 non pregnant females were measured and compared. Moreover ANP was determined in the umbilical cord (artery n = 10, vein n = 48) and the influence of exercise on the concentration of ANP in pregnant (n = 10) and non pregnant women (n = 10) was analyzed. There was no significant difference of the ANP-values measured in non pregnant patients and during the third trimester (100 +/- 57 vs. 97 +/- 27 pg/ml). On the 3rd day post partum a significant rise of ANP was noted (1st day post partum 78 +/- 43, 3rd day post partum 102 +/- 46, 5th day post partum 84 +/- 40 pg/ml). During physical exercise the concentration of ANP increases significantly in pregnant (103 +/- 45 vs. 120 +/- 57 pg/ml, p < 0.05) as well as in non pregnant females (97 +/- 27 vs. 111 +/- 39 pg/ml, p < 0.05). In arterial blood samples from the umbilical cord the concentration of ANP was higher than in venous cord blood (62 +/- 34 vs. 51 +/- 28 pg/ml, p > 0.05).

Adult↗

Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions.

Most cases of low-grade cervical intraepithelial neoplasia (CIN) associated with oncogenic human papillomavirus (HPV) types regress spontaneously within years. Unknown co-factors seem to be necessary for a progression to malignancy. To determine the possible role of cellular immunodeficiency as such a co-factor in the genesis of genital neoplasia, 48 HIV-infected women and 52 allograft recipients were examined periodically during a 3-year period. Colposcopy, cytology and HPV-DNA typing (ViraType) were performed at each visit. Each cervical lesion was matched prospectively with 2 lesions from immunocompetent controls. In all, 29/100 patients suffered from cervical neoplasms, including 2 advanced cervical cancers and 9 CIN3 lesions. Correlation between grade of lesion and HPV DNA 16/18 was significant. Low-grade lesions among patients progressed more often than among controls and recurrent lesions after destructive treatment were seen more frequently among patients than among controls. All patients with CD4-lymphocyte counts of < 400/microliters or immunosuppression for more than 3 years suffered from progressive lesions. We conclude that malfunction of the cellular immune response following either HIV-induced depletion or iatrogenic inhibition of CD4-lymphocyte activation, enhances the progression of HPV-induced cervical lesions to malignancy.

CD4-Positive T-Lymphocytes↗

[Pregnancy and congenital heart failure].

While in the past, rheumatic heart disease accounted for the largest number of pregnant women with heart disease, the incidence has declined over the years. On the other hand, because of advances in medical treatment and surgical management, the ratio of adolescent females with congenital heart disease increased significantly during the last decade. Pregnancy is associated with many physiologic adjustments such as changes in blood volume, stroke volume, and cardiac output, and may result in deleterious clinical effects in patients with congenital heart disease. Although a good outcome for these women can often be expected, congenital heart disease still presents a high-risk pregnancy involving both mother and infant. The actual risk depends on the type of malformation and functional impairment of the mother. To bring these women safely through pregnancy, a strong cooperation between pediatric and adult cardiologists, obstetrician, and other physicians is necessary.

Female↗

[Differential diagnosis of seizures in the peripartal period].

Seizures remain an important cause of maternal morbidity and mortality during pregnancy and the puerperium. Encouraged by some cases treated in our clinic (9 cases have been observed between 29. 12. 1989 and 22.5. 1991), the management of differential diagnosis in seizures are discussed in this article. Despite all possibilities of using technical apparatus for investigations, case history and clinical examination remain the basics of diagnosis with regard to paroxysm. EEG is an important, noninvasive method for judgement of cerebral function. It can be carried out continuously as a bedside-test and is extremely helpful in the differential diagnosis of eclampsia versus epilepsia. With a view to substantial defects as a possible convulsant factor, visualised examination procedures, e.g. cranial computed tomography (CCT) and magnetic resonance imaging (MRI) are available. Especially MRI has advantages in the diagnostic procedure. It could help to find the cause of cerebral structure defects and to clear the question of aetiology. Thus, a specific therapeutic procedure might become possible.

Adult↗

[Pregnancy following organ transplantation].

Pregnancies following organ transplantation are high-risk pregnancies for mother and fetus. There are many reports concerning pregnancies following renal transplantation whereas only few reports are published about pregnancies in recipients of liver, heart and bone marrow transplants. During the pregnancy after kidney transplantation pregnancy-induced hypertension can develop or the renal function can decrease. Risks for the fetus are prematurity, growth retardation and prenatal infections. A higher incidence of complications for mother and fetus is observed in patients with renal insufficiency or severe hypertension prior to conception. The risks can be reduced by an intradisciplinary cooperation of gynecologist, transplant specialist and paediatrician. The paediatrician. The experiences with pregnancies in women after organ transplantations in the Medical School of Hannover are analyzed and compared with the reports in the literature. The management of these patients is described on current state of knowledge.

Female↗

[GnRH analogs in gynecology. Possibilities for therapeutic use].

Gonadotropin releasing hormone (GnRH) agonists are synthetic peptide analogues of the natural gonadotropin releasing hormone with a stronger and more prolonged effect than the natural GnRH. Repeated administration of GnRH agonists induces pituitary desensitization followed by a decrease in gonadotropin secretion and estradiol synthesis. Thus reversible hypogonadotropic hypogonadism is produced. Consequently, estrogen-dependent diseases can be treated successfully with GnRH analogues. The therapeutic results obtained in patients with endometriosis, leiomyoma, pubertas praecox, and metastatic breast cancer are discussed. Furthermore the contraceptive properties of GnRH analogues, and combination treatment with HMG to induce ovulation is reviewed.

Female↗

[Twin pregnancy after liver transplantation].

Orthotopic liver transplantation was performed in a 29-year-old woman because of increasing decompensation of HBs-antigen positive post-hepatitic cirrhosis. Postoperatively she developed a mild rejection reaction and diabetes mellitus. Thirteen months after the transplant she conceived twins. This high risk pregnancy was complicated by a febrile viral infection with purulent tracheobronchitis at 9 weeks and a threatened abortion at 11 weeks. At 33 weeks there was a sudden drop in haemoglobin due to a minor uterine rupture which necessitated cesarean section. The female infants--of development in keeping with the dates--showed no clinical or ultrasound evidence of any malformations. Apart from initial difficulties--asphyxia (second twin), fluctuating glucose and calcium levels, an episode of neonatal jaundice which required phototherapy, reluctance to suck and hypotonia--the further development of both twins proceeded normally. The maternal diabetes disappeared after delivery, HBs-antigen remained negative and the HBs-antibody titre rose. The patient has remained in good condition, both mentally and physically.

Abortion, Threatened↗

[Pregnancy following liver transplantation and during immunosuppression with cyclosporine].

Orthotopic liver transplantation had been performed in 1983 in a now 40-year-old woman in the terminal stage of posthepatitis liver cirrhosis with recurrent oesophageal bleedings and precoma from complete liver-cell failure. She became pregnant in 1988 while under immunosuppression with cyclosporin (2.1-2.7 mg/kg body-weight) and prednisolone (5 or 7.5 mg daily in rotation). Pregnancy proceeded without complication and there were no side effects from cyclosporin. After premature membrane rupture in the 39th week of pregnancy uterine inertia developed during oxytocin stimulation of contractions, and caesarean section was performed. The female infant was normally developed without any malformations. Liver, kidney and adrenal functions were normal, as was haemopoiesis. But possible late sequelae of cyclosporin treatment in the child cannot as yet be assessed because of the short follow-up.

Abnormalities, Drug-Induced↗

[Puerperal thyroid gland dysfunction in healthy patients].

Elevated thyroid antibodies (AB) have been described in clinically healthy women indicating a postpartum thyroid dysfunction. We evaluated the incidence of the postpartum thyroid dysfunction in Hannover, FRG. 121 women were examined 1-5 days pp and 2-4 months later; 76 were restudied 5-7 months pp. Every time T3, T4, TSH, TBG, microsomal AB and thyroglobulin AB were determined. Six patients showed increased TAB and 10 increased MAB titers. Severe clinical symptoms were not complained. In some patients these elevated titers turned to normal subsequently. Further studies must evaluate the prognosis of this disease.

Adolescent↗