Biomedical subjects
Publications and source records attributed to Ralf Dittrich.
This study evaluated the effect of gonadotropin stimulation on the primordial follicle reserve of cryopreserved human ovarian tissue after transplantation in severe combined immunodeficient mice. We found that prolonged gonadotropin stimulation significantly reduces primordial follicles.
BACKGROUND: Measured endocrinological parameters (total testosterone [TT], free testosterone [FT], dihydrotestosterone [DHT], dehydroepiandrosterone sulfate [DHEAS], and sex hormone binding globulin [SHBG]) and calculated parameters (calculated FT (cFT), calculated bioavailable testosterone (cBT), and the free androgen index [FAI]) in women with hirsutism were compared to the values of a control group. The question remains if cFT or cBT are more appropriate markers for assessment of hyperandrogenemia in clinical situations such as hirsutism in women. METHODS: Sixty-six women showed an modified Ferriman-Gallwey (mF-G) score of >or=6 and were classified as hirsutism group and 58 women showed mF-G scores of <or=5 and were classified as control group. TT, FT, DHT, DHEAS, and SHBG were measured with enzyme immunoassays in one serum sample. Albumin was measured in the same sample. Afterwards, cFT, cBT, and the FAI were calculated. RESULTS: The hirsutism group revealed significantly increased cFT, cBT, and FAI, while SHBG was significantly decreased compared to the controls. All values of the hirsutism group showed significant, but poor correlation with the mF-G score. SHBG correlated negatively with the mF-G score and BMI. CONCLUSION: Despite the limited correlation of all endocrinological parameters to severity of hirsutism described by the mF-G score, cFT, cBT, and FAI may be more appropriate markers for assessment of hyperandrogenemia in women with hirsutism in comparison with measured values of simple enzyme immunoassays.
OBJECTIVE: Aggressive chemotherapy and radiotherapy or radical oncological surgery in young women with cancer has greatly enhanced these patients' life expectancy, but these treatments often cause infertility or premature ovarian failure due to a massive destruction of the ovarian reserve. The objective of this review is to discuss the effect of the various cancer treatments on fertility and present the various fertility sparing operations and fertility preservation strategies. METHOD: An extensive survey of the most up-to-date literature was performed. RESULTS: This review discusses the impact of current cancer treatment on fertility potential and the various surgical and assisted-reproduction innovations available today for the most common cancers in young women. Although the ability to retain reproductive potential is becoming a major quality-of-life factor in an increasing number of young female cancer survivors, they are still being poorly counseled with regard to the negative impact of the treatment on their fertility and on their options for fertility preservation. CONCLUSION: As the emerging discipline of fertility preservation is steadily attracting increasing interest, developments in the near future promise to be very exciting. However, in everyday routine work, better interdisciplinary cooperation between gynecological and pediatric oncologists, surgeons, immunologists, and endocrinologists is necessary so that individualized options for fertility preservation can be offered in advance of surgical procedures or cancer treatments.
Aggressive chemotherapy and radiotherapy in young patients with cancer has greatly enhanced the life expectancy of these patients, but these treatments often cause infertility because of the massive destruction of the ovarian reserve resulting in premature ovarian failure (POF). This review focuses on the effect of cancer treatments on fertility and on the various surgical and assisted-reproduction innovations that are available to provide the patient with the option of future pregnancies. As the emerging discipline of fertility preservation is steadily attracting increasing interest, developments in the near future promise to be very exciting. However, in everyday routine work, better interdisciplinary cooperation between gynecological and pediatric oncologists, surgeons, immunologists and endocrinologists is necessary so that individualized options for fertility preservation can be offered in advance of surgical procedures or cancer treatments. GnRH analog treatment can preserve fertility in some patients, but not in all. At present, cryopreservation of ovarian tissue appears as a very promising method of providing the cancer patient with a realistic chance of preserving fertility-a prospect that is also extremely important to patients for psychological reasons.
Maillard products, such as Nepsilon-carboxymethyllysine (CML), are readily formed during the manufacturing of infant formulas. Little has been known, however, about the presence of CML in human breast milk and about the uptake of CML by infants. In this study, CML was measured in the serum and breast milk of 32 healthy mothers by ELISA. CML concentrations in breast milk (137 +/- 82.7 ng/mL) were significantly lower than in the serum (399 +/- 67.8 ng/mL, p < 0.001) and on average 35-fold lower than in infant formulas (4754 +/- 4299.5 ng/mL). CML was also measured in the urine of 21 infants, which were fed with breast milk or formulas. Although there was a tendency toward higher urinary CML excretion in infants fed with hypoallergenic formulas compared to breast-fed ones, the differences were not significant. Neonates that were delivered by vaginal birth had significantly higher concentrations of CML compared to those delivered by caesarean section (1306 +/- 653 vs 601 +/- 220 ng/mL, p = 0.012). It is concluded that CML passes from the serum into the breast milk, but the levels are by far lower than in infant formulas. In very young neonates (< or =3 days), the mode of delivery has a greater influence on urinary CML excretion than the nutrition.
Adequate uterine contractility and periovulatory peristalsis, interpreted as "rapid sperm transport" to the side bearing the dominant follicle, may be a precondition for successful reproduction in humans. Estrogen and progesterone fluctuate characteristically during the menstrual cycle, and their source is the dominant follicle and corpus luteum. The question is, how is the direction to the left or right side of transport mechanisms influenced? An extracorporeal perfusion model of the swine uterus was used that maintained the uterus in a functional condition and that was suitable for the study of physiological questions. The effects of side-dependent estrogen, progesterone, and estrogen plus progesterone perfusion on oxytocin-induced uterine peristalsis were assessed using two intrauterine microcatheters placed in each horn of the swine uterus. Estrogen perfusion was associated with an increase in intrauterine pressure (IUP) in a dose-dependent manner only in the estrogen-perfused horn of the swine uterus. There was a significant difference between the IUP increase measured in the estrogen-perfused horn and that in the non estrogen-perfused horn of the swine uterus. Progesterone perfusion showed no effect in general. Furthermore, progesterone antagonized the estrogen effects. This study demonstrates that side-dependent estrogen perfusion resulted in side-dependent contractility in the swine uterus perfusion system used. These observations show that estrogen stimulates uterine contractility in the estrogen-perfused uterine horn and that estrogens may be the "trigger" for the transport mechanisms to the side bearing the dominant follicle during the periovulatory phase through their locally increased concentration and distribution via the utero-ovarian counter-current system in humans.
This study examines the possible predictive value of the LIVE/DEAD fluorescence viability assay for evaluation of survival of cryopreserved human ovarian tissue. Ovarian tissue from ten patients was examined by LIVE/DEAD viability staining before and after cryopreservation and after freezing in a -20 C freezer (negative control). After cryopreservation with a slow freezing protocol and cryoprotectant the LIVE/DEAD assay showed 86% viable follicles (an intact oocyte and at least more than 50% of the granulosa cells alive), whereas after freezing at -20 C the survival rate was 67%. The healthy follicular loss after cryopreservation was 4%, whereas with freezing at -20 C, it was 25%. Although this assay overestimates the survival rate of cryopreserved primordial follicles, if the LIVE/DEAD assay yields greater than approximately 85% viable follicles, it can be assumed that the follicles in the cryopreserved tissue have maintained their developmental potential and that the tissue is suitable for retransplantation.
BACKGROUND: Prostaglandins (PGs) are important stimulators of uterine contractility. Limited data are available at present on the effects of different PGs on uterine contractility, measured using intraluminal pressure changes in the complete uterus. The goal of this study was to assess dynamic changes in uterine contractility and peristalsis in response to PGs in comparison with the effects of oxytocin administration. METHODS: An extracorporeal perfusion model of swine uteri was used, which keeps the uterus in a functional condition, and is appropriate for the study of physiological questions. Oxytocin- and PG-induced uterine contractility and peristalsis were assessed using an intrauterine double-chip microcatheter. RESULTS: A dose-dependent increase in intrauterine pressure (IUP) in the isthmus uteri (P < 0.001) and the corpus uteri (P < 0.001) was observed after the administration of PGF(2alpha) and oxytocin, which reached a plateau after further stimulation. A dose-dependent increase in IUP in the isthmus uteri (P < 0.001) and the corpus uteri (P < 0.001) was also observed after the administration of PGE(1) and PGE(2), with a plateau in IUP in the middle-concentration range and a decrease in the course of further stimulation. PGE(2) caused significantly more contractions starting in the corpus uteri and moving to the isthmus uteri (P = 0.008). The direction of most contractions caused by PGE(1), PGE(2) and oxytocin differed from that of PGF(2alpha). CONCLUSIONS: This study demonstrates that the PGs tested modulate contractility in non-pregnant swine uteri in a characteristic way, resulting in different contractility patterns.
BACKGROUND AND PURPOSE: The CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts. METHODS: As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (ps+/-values). For all DATs included in CARESS (n=300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator). RESULTS: For the reference tape, the cumulative ps+/-value was 0.894 based on 12 of 14 observers. Two observers with very different results improved after a training procedure. Agreement between post-trial validator and central reader was ps+=0.805, indicating very good agreement. Correlation between online evaluation and off-line evaluation of DATs was very good overall (cumulative rho=0.84; P<0.001). CONCLUSIONS: Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.
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PURPOSE: Magnetic Resonance Imaging (MRI) has become the method of choice in the evaluation of patients with suspected cervical artery dissection (CAD). However, reliable identification of acute CAD might be impaired by the limited spatial resolution of standard 1.5 T MRI. In this preliminary study, we implemented a multicontrast high-resolution noninvasive vessel wall imaging approach at 3.0 T in patients with spontaneous CAD. METHODS AND MATERIALS: Ten patients with CAD of the internal carotid artery (ICA) were included in the study. 3.0 T MRI (Gyroscan Intera, Philips) was acquired using a dedicated phased-array coil. MRI-protocol consisted of: (1) bright blood 3D inflow MRA (TR/TE/FA = 25 milliseconds/3.1 millisecond/16 degrees , 120 slices, reconstructed voxel size 0.3 x 0.3 x 0.8 mm); (2) black blood cardiac-gated water-selective T1w 3D spoiled GE (TR/TE/FA = 31 milliseconds/7.7 milliseconds/15 degrees , 36 slices, 0.3 x 0.3 x 1.0 mm); and (3) black blood cardiac triggered fat suppressed T2w TSE (TR/TE/ETL = 3 heart beats/44 milliseconds/7, 18 slices, 0.3 x 0.3 x 2 mm). Three observers in consensus performed image analysis. Special attention was paid to the integrity of the luminal and adventitial vessel boundary and the presence of a communicating intimal tear or flap. RESULTS: 3.0 T MRI provided excellent delineation of vessel lumen and vessel wall as a result of the nearly complete suppression of arterial blood signal. An intramural hematoma could be identified in all patients, confined between the luminal and adventitial vessel boundary. In no patient a communicating intimal tear could be identified. Clear distinction between intramural hematoma and thrombus was possible. CONCLUSION: High-resolution vessel wall imaging in patients with acute CAD is feasible. The increased signal-to-noise ratio at 3.0 T can be invested to obtain a higher spatial resolution, permitting depiction of intimal and adventitial vessel wall boundary and the intramural hematoma in the diseased vessel segment. The morphologic information that is gained is helpful in the understanding of the underlying pathomechanismen of CAD.
AIM: To compare two freezing protocols in an automatic open-vessel freezing system for cryopreservation of rat ovarian tissue. METHODS: Ovarian tissue was transplanted heterotopically into the neck muscle, either without cryopreservation (group 1, n = 6) or with cryopreservation after equilibration with 1.5 mol/L dimethyl sulfoxide and propanediol (protocol A, group 2, n = 6) or 1.5 mol/L ethyl glycol (protocol B, group 3, n = 6). The ovarian tissue was examined with LIVE/DEAD fluorescent viability staining and histologically after isotransplantation. RESULTS: The healthy follicular loss (intact oocyte and >50% granulosa cells alive) due to cryopreservation was 15.5% with protocol A and 12.2% with protocol B. Histological examination showed follicles in all developmental phases in all groups: group 1, 35.5 +/- 5.7/mm(2) (mean +/- SD); group 2, 16.0 +/- 5.0/mm(2); group 3, 17.3 +/- 5.7/mm(2). The differences between groups 1 and 2 and between groups 1 and 3 were significant (P < 0.001). The difference between groups 2 and 3 was not significant (P = 0.33). CONCLUSIONS: These results demonstrate that the use of an open freezing system with both freezing protocols allows cryopreservation of rat ovarian tissue with equally good survival rates.
It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization (IVF) after cancer treatment are also presented.
Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted reproduction techniques using in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI). Its etiology has still not yet been fully resolved. Human chorionic gonadotrophin, administered exogenously as well as produced endogenously during pregnancy, is responsible for the onset of OHSS, and high levels of estradiol appear to worsen the condition. In this case series, the course of mild to severe OHSS was evaluated in 19 intact twin pregnancies after IVF/ICSI. Another serious complication associated with OHSS is thromboembolic events. In these cases, the pregnancy can be protected through anticoagulation treatment, but there may be exceptions to this. This series includes a case of bilateral thrombosis of the internal and external jugular veins in the 7th gestational week in a twin pregnancy after OHSS and ICSI, with termination of the pregnancy in the 9th gestational week due to progressive thrombosis during anticoagulation therapy.
PURPOSE: This study examined the effect of insulin on sex cord stromal tumors in the rat. METHODS: Sex cord stromal tumors were induced by transplantation of ovaries under the splenic capsule of ovariectomized rats (Lewis-inbred). These tumors were then transplanted into new inbred rats. Hyperglycemic conditions were induced by treatment with streptozotocin (STZ, which selectively destroyed pancreatic islet cells) and hypoglycemic conditions by treatment with a subcutaneously implanted insulin pump (Alzet). The animals were killed 28, 56, and 84 days later. Tumor growth, animal weight, food and water consumption, and serum concentrations of glucose, FSH, LH, and estradiol were measured. RESULTS: Treatment with STZ and insulin with osmotic Alzet pumps induced continuous hypoglycemic and hyperglycemic conditions, respectively. No significant influence of the hypoglycemic or hyperglycemic status on tumor growth was measured during the first 28 and 56 days. Eighty-four days after transplantation and substitution of 1 or 2 IU/100 g body weight/d insulin, there was a significant stimulation of tumor growth (2.2-fold and 2.7-fold, respectively). In hyperglycemic animals (treated with STZ), no influence on tumor growth was found in comparison with the controls. CONCLUSION: This study confirms that hyperinsulinemic conditions contribute to the progression of tumors.
OBJECTIVE: Comparison of the effect of tocolytic drugs on isolated swine uterus preparations. STUDY DESIGN: Forty swine uteri were perfused with the aim to preserve a viable organ, which should be responsive to oxytocic hormones and tocolytic pharmaca. An intrauterine catheter recorded the pressure changes. After initiation of rhythmical uterine contractions we administered known tocolytic drugs (fenoterol, ritodrine, terbutaline, propofol, acetylsalicylic acid, alcohol, atosiban, verapamil, and glyceryl trinitrate) in various concentrations. RESULTS: Perfusate pH and lactate, partial oxygen and carbon dioxide tensions, and oxygen saturation in the perfusate showed good preservation of the organ for up to 8h. All substances showed a tocolytic effect on the swine uterus. The effect varied substantially with regard to the length of the contraction free intervals, which was our main effect parameter. Fenoterol, acetylsalicylic acid, and alcohol showed the most and glyceryl trinitrate the least powerful effect. CONCLUSIONS: A direct comparison of various tocolytic substances in the same experimental model showed the best effect for fenoterol. Furthermore, we could demonstrate that the swine uterus perfusion system is a suitable model to study the influence of various conditions like the administration of drugs or the induction of oxidative stress on the uterus function.
OBJECTIVES: Proper assessment of the intracranial arteries by transcranial color-coded duplex sonography (TCCD) is occasionally made difficult by an insufficient temporal bone window, an unfavorable insonation angle, or low flow velocity or volume. In these cases, echocontrast could be helpful to increase the diagnostic confidence or to make the diagnosis at all. MATERIAL AND METHODS: We investigated 67 temporal windows of 47 patients with insufficient native transtemporal insonation conditions before and after the application of the second-generation (gas-filled) microbubble contrast agent Sonovue (in 20 patients out of these 47, both temporal windows were insufficient, in the remaining 27 only one side). RESULTS: As compared to the precontrast scans, echocontrast allowed for more segments to be evaluated by pulsed Doppler sonography (p < 0.0001) and for longer lumen segments to be displayed on color mode (p < 0.0001). With the help of contrast medium, flow velocity in the middle cerebral artery could be measured through 65 windows as compared to only 26 windows before contrast was applied (p < 0.0001). CONCLUSIONS: In patients with poor precontrast visualization of intracranial arteries, echocontrast-enhanced TCCD is very helpful.
Since sleep apnea (SA) and stroke have many shared risk factors an independent contribution of SA to the overall risk of stroke is not easily proven and has been questioned recently. To contribute to this controversy, we analysed the frequency of SA in groups of patients with first and recurring ischemic stroke. We prospectively studied 102 patients admitted to our stroke unit. The prevalence of vascular risk factors and a history of previous stroke were recorded. All patients received cardio-respiratory polygraphy during the first 72 hours after admission. CT and MRI scans were evaluated for the location of the acute stroke and the presence of older vascular lesions. Thirty-four women and 68 men with a mean age of 64.5 +/- 13.7 years were included in the study. Cerebral lesions attributable to a previous stroke were identified in 25 patients, of whom 19 reported to have suffered a stroke before. Patients with stroke recurrence had a higher mean apnea-hypopnea index (AHI) (26.6/h vs. 15.1/h, p<0.05) and more often presented with a sleep apnea syndrome (SA) defined by an AHI >or=10/h (80 vs. 52%, p < 0.05) than patients with first ever stroke. Logistic regression analysis including the variables "age", "gender", "cumulative risk factors", "AHI >or=10/h", and "diabetes" identified diabetes (Odd's ratio [OR]=4.5) and AHI >or=10/h (OR=3.5) as independent risk-factors for stroke recurrence. According to our results SA is an independent risk factor for stroke recurrence. We therefore advocate routine sleep-apnea screening in all patients having suffered an ischemic stroke.