Final ART success rates: a 10 years survey.

BACKGROUND: Cumulative pregnancy rates (CPRs) and live birth rates (CLBRs) are much better indicators of success in IVF programmes than cross-sectional figures per cycle or embryo transfer. They allow a better estimation of patient's chances of having a child and enable comparisons between centres and treatment strategies. METHODS: A 10 year cohort study of patients undergoing their first assisted reproductive technique cycle was conducted. Patients were followed until live birth or discontinuation of treatment. All IVF and ICSI cycles and cryo-cycles with embryos derived from frozen pronuclear stage oocytes were included. The CPR and CLBR were estimated using the Kaplan-Meier method for both the number of treatment cycles and transferred embryos. The analysis assumed that couples who did not return for subsequent treatment cycles would have had the same chance of success as those who had continued treatment. RESULTS: A total of 3011 women treated between 1998 and 2007 were included, and 2068 children were born; women already with a live birth re-entered the analysis as a 'new patient'. For 3394 'patients under observation' with 8048 cycles, the CLBR was 52% after 3 cycles (the median number of cycles per patient), 72% after 6 cycles and 85% after 12 cycles. A CLBR of ∼ 50% was achieved for patients aged under 40 years, after the cumulative transfer of six embryos. The mean live birth rate from one fresh cycle and its subsequent cryo-cycle(s) was 33%. Our analysis also shows that ART can reach natural fertility rates but not exceed them. CONCLUSIONS: Most couples with infertility problems can be treated successfully if they continue treatment. Thereby ART can reach natural fertility rates. Even with the restrictions in place as a result of the German Embryo Protection Law, CLBR reach internationally comparable levels.

Non-enhanced 3D MR angiography of the lower extremity using ECG-gated TSE imaging with non-selective refocusing pulses--initial experience.

PURPOSE: To evaluate non-enhanced 3D MR angiography using turbo spin echo (TSE) imaging with non-selective refocusing pulses (NATIVE SPACE MRA) for the visualization of the arteries of the lower extremity. MATERIALS AND METHODS: Three-station imaging (iliac arteries, femoral arteries, arteries of the lower leg) was performed in 8 healthy volunteers and 3 patients with peripheral artery disease (PAD) using a 1.5 T MR scanner. In 8 healthy volunteers, 4 different acquisition schemes were performed with the following imaging parameters: S 1: acquisition with every heartbeat (RR = 1), spoiler gradient of 25 % (SG = 25 %); S 2: RR = 1, SG = 0 %; S 3: RR = 2, SG = 25 %; S 4: RR = 2, SG = 0 %. The subjective image quality on a 4-point-scale (4 = excellent to 1 = not diagnostic) and relative SNR were assessed. In 3 patients with peripheral artery disease (PAD), SPACE MRA was performed for assessment of stenosis. RESULTS: The mean subjective image quality was significantly lower for the iliac arteries compared to the femoral arteries and arteries of the lower leg (p < 0.0001). The subjective image quality for acquisition scheme S 1 was significantly lower than the image quality for S 3 and S 4 for the iliac arteries (p < 0.01), while the subjective image quality for acquisition scheme S 2 was significantly lower than S 3 and S 4 for the femoral arteries and the arteries of the lower leg (p < 0.01). The relative SNR was significantly higher for acquisition schemes S 3 and S 4 as compared to S 1 and S 2 (p < 0.0001) for all regions. SPACE MRA disclosed 7 significant stenoses in 3 PAD patients. CONCLUSION: ECG-gated SPACE MRA is a promising imaging technique for non-enhanced assessment of the arteries of the lower extremity.

[Dose reduction and image quality in MDCT of the upper abdomen: potential of an adaptive post-processing filter]. / Dosisreduktion und Bildqualität in der MDCT des Oberbauchs: Potenzial eines adaptiven Nachverarbeitungsfilters.

PURPOSE: To evaluate the effects of a 2D non-linear adaptive post-processing filter (2D-NLAF) on image quality in dose-reduced multi-detector CT (MDCT) of the upper abdomen. MATERIALS AND METHODS: MDCT of the upper abdomen was simulated on a 64-slice scanner using a multi-modal anthropomorphic phantom (CIRS, Norfolk, USA). While keeping the collimation (64 x 0.6 mm) and pitch (p = 1) unchanged, the tube current (100 - 500 mAs) and tube potential (80 - 140 kVp) were varied to perform MDCT as high dose (CTDI > 20), middle dose (CTDI 10 - 20) and low dose (CTDI < 10) level protocols. Four independent blinded radiologists evaluated axial images with a thickness of 7 and 3 mm with respect to the presentation of "mesenteric low contrast lesions", "liver veins", "liver cysts", "renal cysts" and "big vessels". The subjective image quality of original data and post-processed images using a 2D-NLAF (SharpViewCT, Linköping, Sweden) was graded on a 5-point scale (from "1" not visible to "5" excellent) and statistically analyzed. The effective dose (E) was estimated using commercial software (CT-EXPO). RESULTS: For all protocol groups, 2D-NLAF led to a significant improvement in subjective image quality for all examined lesions (p < 0.01), particularly at the protocols of middle dose (E: 5 - 8 mSv) and low dose level (E: 1 - 5 mSv). A maximum effect was seen in middle dose protocols for "low contrast lesions" (score "3.3" with filter versus "2.5" without) and "liver veins" ("4.5" versus "3.9"). CONCLUSION: The phantom study indicates a potential dose reduction of up to 50 % in MDCT of the upper abdomen by use of a 2D-NLAF, which should be further examined in clinical trails.

Relevance of anti-Mullerian hormone measurement in a routine IVF program.

BACKGROUND: Diminished ovarian reserve has become a major cause of infertility. Anti-Mullerian hormone (AMH) seems to be a promising candidate to assess ovarian reserve and predict the response to controlled ovarian hyperstimulation (COH). This prospective study was conducted to evaluate the relevance of AMH in a routine IVF program. METHODS: Three hundred and sixteen patients were prospectively enrolled to enter their first IVF/ICSI-cycle. Age, FSH-, inhibin B- and AMH-levels and their predictive values for ovarian response and clinical pregnancy rate were compared by discriminant analyses. RESULTS: A total of 132 oocyte retrievals were performed. A calculated cut-off level < or =1.26 ng/ml AMH alone detected poor responders (< or =4 oocytes) with a sensitivity of 97%, and there was a 98% correct prediction of normal response in COH if levels were above this threshold. With levels <0.5 ng/ml, a correct prediction of very poor response (< or =2 oocytes) was possible in 88% of cases. Levels of AMH > or =0.5 ng/ml were not significantly correlated with clinical pregnancy rates. CONCLUSIONS: AMH is a predictor of ovarian response and suitable for screening. Levels < or =1.26 ng/ml are highly predictive of reduced ovarian reserve and should be confirmed by a second line antral follicle count. Measurement of AMH supports clinical decisions, but alone it is not a suitable predictor of IVF success.

Chlamydia pneumoniae, herpes simplex virus and cytomegalovirus in symptomatic and asymptomatic high-grade internal carotid artery stenosis. Does infection influence plaque stability?

BACKGROUND: Current debates are focused on inflammatory processes in atherosclerotic lesions as a possible pathomechanism for destabilization and thrombembolism. In this prospective study the role of systemic and local infection in patients with high-grade internal carotid artery stenosis (ICA) was evaluated. PATIENTS AND METHODS: Serum antibody titers of 109 consecutive patients, who underwent surgery for ICA stenosis (asymptomatic n = 40, symptomatic n = 69) were prospectively measured for Chlamydia pneumoniae (Cpn) (IgA and IgG), Herpes simplex virus (HSV) (IgG, IgM) and Cytomegalovirus (CMV) (IgG, IgM) respectively. 53 carotis plaques of this group (asymptomatic n = 17, symptomatic n = 36) could be analyzed by polymerase chain reaction (PCR) for Cpn-, HSV- and CMV-DNA presence. RESULTS: Seropositivity was found in 61,5% for Cpn, 91,7% for HSV and 72,5% CMV respectively. No significant relation was found between symptomatic and asymptomatic patients as well as no difference was seen for presence of IgA antibodies against Cpn comparing both groups. Plaque-PCR revealed Cpn in 7 cases (13,2%), HSV in 2 cases (3,8%) and no CMV had been detected. Again, no significant relationship was found concerning symptomatic and asymptomatic patients. All 9 PCR-positive plaques displayed lesions of "complicated atherosclerosis" as central fibrous necrosis and calcification or plaque bleeding and surface thrombosis. CONCLUSIONS: Our results do not support the hypothesis that systemic Cpn, HSV or CMV- infection or evidence of Cpn-, HSV- or CMV-DNA in carotid plaques causes plaque destabilization and cerebral thromboembolism. Plaque infection could only be observed in cases with advanced atherosclerosis.

Definition and prevalence of subfertility and infertility.

A common definition of sub- and infertility is very important for the appropriate management of infertility. Subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. Infertility may be used synonymously with sterility with only sporadically occurring spontaneous pregnancies. The major factor affecting the individual spontaneous pregnancy prospect is the time of unwanted non-conception which determines the grading of subfertility. Most of the pregnancies occur in the first six cycles with intercourse in the fertile phase (80%). After that, serious subfertility must be assumed in every second couple (10%) although--after 12 unsuccessful cycles--untreated live birth rates among them will reach nearly 55% in the next 36 months. Thereafter (48 months), approximately 5% of the couples are definitive infertile with a nearly zero chance of becoming spontaneously pregnant in the future. With age, cumulative probabilities of conception decline because heterogeneity in fecundity increases due to a higher proportion of infertile couples. In truly fertile couples cumulative probabilities of conception are probably age independent. Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age: Couples with a reasonably good prognosis (e.g. unexplained infertility) may be encouraged to wait because even with treatment they do not have a better chance of conceiving. The others may benefit from an early resort to assisted reproduction treatment.

[Ranking of systemic steroids after normal-risk keratoplasty. Results of a randomized prospective study]. / Stellenwert der systemischen Steroidtherapie nach Normalrisikokeratoplastik. Eine randomisierte prospektive Pilotstudie.

BACKGROUND: The aim of this study was to evaluate the efficacy of sole application of topical steroids after normal-risk keratoplasty. PATIENTS AND METHODS: This randomized prospective clinical study assessed 40 patients who had undergone penetrating normal-risk keratoplasty. Twenty patients were treated exclusively with prednisolone acetate 1% eye drops 5x/day for 6 months postoperatively. Another 20 patients additionally received systemic fluocortolone 1 mg/kg body weight per day tapered within 3 weeks postoperatively. The main outcome measures included clear graft survival, ratio of graft rejection, and side effects. RESULTS: The mean postoperative follow-up was 18+/-9 months. Three graft rejections were observed in the group receiving only topical steroids. Two graft rejections were observed in the group administered combined systemic and topical steroid therapy. None of the patients has developed irreversible graft failure so far. CONCLUSION: Sole topical steroid application seems to be an effective immune prophylaxis in patients undergoing penetrating normal-risk keratoplasty.

Exclusion of brain lesions: is MR contrast medium required after a negative fluid-attenuated inversion recovery sequence?

We hypothesized that in patients with negative fluid-attenuated inversion recovery (FLAIR) images T(2) weighted fast spin-echo (FSE) images and T(1) weighted spin-echo (SE) images before and after intravenous administration of gadolinium-based contrast medium display no pathology either. Thus, we assessed the negative predictive value of FLAIR images to rule out MR-detectable brain lesions. 1026 consecutive cranial MR examinations were reviewed. Routine MRI of the brain included T(1) weighted coronal imaging before and after administration of gadopentetate dimeglumine, axial T(2) weighted FSE and fast-FLAIR imaging. The FLAIR images were rated by two radiologists into categories of 0 (without pathologic changes) and 1 (with pathologic changes). Two other radiologists analysed the complete examination. In 284 MR examinations of the brain no abnormalities were found (28%). FLAIR-ratings were false-negative in four cases and false-positive in 30 cases. Sensitivity and specificity of the FLAIR sequence for MR-detectable brain lesions were 99.5% and 89.4%. The unselective application of gadolinium avoided one false-negative MR-reading and improved the sensitivity of the MR-examination from 99.5% to 99.6%. Positive and negative predictive values were 96.1% and 98.4%, respectively. The interobserver reliability was kappa=0.93 for the FLAIR-readers and 0.89 for the readers who rated the complete examination. In conclusion, negative FLAIR images provide a high negative predictive value for MR-detectable brain lesions. Thus, in patients with negative FLAIR images the unselective application of gadolinium seems to be unnecessary.

Management of the persistent ductus arteriosus in infants of very low birth weight: early and long-term results.

The hemodynamically relevant persistent ductus arteriosus (PDA) impairs pulmonary and cardiac function. Frequently, PDA can be closed only via surgery. In this retrospective study, early and long-term results in very low birth weight newborns are evaluated. Eighty-seven of 634 very low weight newborns presented with PDA All patients (pts; age: +/-14 days; weight: +/-1064 g) were ventilator-dependent. Surgical closure (after 29+/-5 days) was indicated if echocardiography and prolonged ventilation (>20+/-2 days) evidenced a hemodynamically relevant PDA. Sixteen pts, in which indomethacin therapy failed preoperatively are included in the 36 surgically treated pts; no pt died intra- or early postoperatively (<3 day). Overall mortality 30 days after delivery was n=9. Early plus late mortality was n=19. Long-term follow-up (3-12 years) in 46 (68%) pts: 15 were solely physically, 11 were mentally and neurologically, and 4 were physically, mentally and neurologically retarded. From these 30 pts, 15 were severely (e.g. tetraspasm; severe cerebral paresis) and 15 were slightly (e.g. psychosomatic and language development prolongation) retarded. Sixteen pts exhibited no disability; no long-term complications owing to surgery. The relatively large number of neurological injuries was not owing to chromosomal syndromes or pre-existing abnormalities but can be explained by severe and frequent prematurity, hypoxia, and intracerebral bleeding. Indomethacin was successful only in a few patients. Early surgery (after frustran early indomethacin therapy) of a hemodynamically relevant PDA is recommended. In the long-term, severe disabilities develop.

[The efficacy of a combination herbal medicine in the treatment of functional dyspepsia. Meta-analysis of randomized double-blind studies on the basis of a valid gastrointestinal symptom profile]. / Wirksamkeit eines pflanzlichen Kombinationspräparats bei funktioneller Dyspepsie. Metaanalyse randomisierter Doppelblindstudien auf Basis eines validen gastrointestinalen Symptomprofils.

BACKGROUND AND AIM: Functional dyspepsia is a heterogeneous clinical entity of incompletely known etiology. Overall, four randomized double-blind studies from the nineteen-nineties investigating acute treatment of this condition with the combination herbal medicine Iberogast, are available. A meta-analysis of the studieswas carried out to evaluate the overall therapeutic effect. PATIENTS AND METHODS: In all four, triple-arm, controlled multicentre studies, the efficacy of 4 weeks of treatment with 3 x 20 drops daily, applied after a washout phase, was investigated, the primary efficacy parameter being a specific gastrointestinal symptom score. Of the 592 participants in the studies, 196 were treated with Iberogast, 131 with placebo, and 61 with cisapride as positive control. The remaining 204 patients, who were treated with an experimental herbal preparation of similar composition, were not admitted to the final analysis. RESULTS: While overall appreciable improvement of the clinically relevant symptoms of moderate severity was seen under treatment with the combination herbal preparation, the individual studies differed in terms of the statistical significance of the results obtained. The meta-analysis of studies revealed a clear therapeutic effect for the herbal medicine (p < 0.0001). CONCLUSION: The clinical experience with the combination preparation for the treatment of functional dyspepsia was confirmed by the meta-analysis of the modern double-blind studies.

Estimated maximum failure rates of cycle monitors using daily conception probabilities in the menstrual cycle.

BACKGROUND: A number of menstrual cycle monitors have been developed to detect the fertile window of the menstrual cycle, mainly for contraceptive purposes. Reliable data on most of these systems are still missing but are urgently needed because many women use them and the tested systems differ enormously in price and effectiveness. We suggest a new efficacy estimating method to evaluate cycle monitors prior to full prospective clinical trials. METHODS: Sixty-two women prospectively tested seven cycle monitors and the symptothermal method (STM) of natural family planning (NFP) but not more than two different systems at the same time. The clinical fertile window was determined by detecting the day of ovulation using daily urinary LH measurements and daily ultrasonic folliculometry. This was compared to the fertile phase predicted by the systems. Maximum failure rates were estimated for each cycle monitor and the STM, using the daily conception probability rates taken from the European Fecundability Study. Intercourse was assumed to occur on each of all falsely predicted days of infertility. RESULTS: Sixty-two women with a mean age of 31 years (range: 21-42 years) contributed a total of 122 cycles to this study. Monitors based on the microscopic evaluation of saliva or mucus had many more false infertile days than the other methods based on temperature or hormonal measurements (225 versus 42 days). The maximum unintended pregnancy rates per cycle for temperature computers were estimated to be 0.0134-0.0336, for the hormonal computer 0.1155 and for mini-microscopes 0.2313-0.2369. For the STM of NFP, there were no false infertile days. CONCLUSIONS: The STM of NFP proved to be the most effective contraceptive method to detect the fertile window among all the methods tested. The estimated efficacy of the other cycle monitors range from the temperature computers (upper level) to the hormonal computer (medium level) and the mini-microscopes with very low estimated contraceptive efficacy.

Time to pregnancy: results of the German prospective study and impact on the management of infertility.

BACKGROUND: The likelihood of spontaneous conception in subsequent cycles is important for a balanced management of infertility. Previous studies on time to pregnancy are mostly retrospective and biased because of exclusion of truly infertile couples. The study aim was to present a non-parametric estimation of cumulative probabilities of conception (CPC) in natural family planning (NFP) users illustrating an ideal of human fertility potential. METHODS: A total of 346 women was observed who used NFP methods to conceive from their first cycle onwards. The couples practising NFP make optimal use of their fertility potential by timed intercourse. The CPC were estimated for the total group and for couples who finally conceived by calculating Kaplan-Meier survival rates. RESULTS: A total of 310 pregnancies occurred among the 346 women; the remaining 36 women (10.4%) did not conceive. Estimated CPC for the total group (n = 340 women) at one, three, six and 12 cycle(s) were 38, 68, 81 and 92% respectively. For those who finally conceived (truly fertile couples, n = 304 women), the respective pregnancy rates were 42, 75, 88 and 98% respectively. Although the numbers of couples in both groups were similar, the impact of age on time to conception, as judged by the Wilcoxon test, was less in the truly fertile than in the total group. CONCLUSIONS: Most couples conceive within six cycles with timed intercourse. Thereafter, every second couple is probably either subfertile or infertile. CPC decline with age because heterogeneity in fecundity increases. In the subgroup of truly fertile couples, an age-dependent decline in CPC is statistically less obvious because of high homogeneity, even with advancing age.

EuroSCORE as a predictor for complications and outcome.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of EuroSCORE in terms of prediction of the outcome as a result of preoperative information in a cohort of patients. METHODS: We analyzed the data from 751 patients treated between Jan 1 and Dec 31, 1998. We used contingency tables and applied methods of discriminant analysis for the evaluation. RESULTS: Compared to the 14.799 patients from whose data the EuroSCORE system had originally been derived [1,2], we had a smaller portion of patients in the low-risk group (24.5% vs. 30.6%), a comparable portion of patients in the medium-risk group (42.2% vs. 40.5%) and a higher proportion of patients in the high-risk group (33.2% vs. 29.0%). This difference in the risk distributions was highly significant (p < 0.001). The application of the EuroSCORE system showed that deaths only occurred in the high-risk group in our hospital. We had 36 deaths amongst the patients, which gives an overall mortality rate of 4.9% and a mortality rate of 1.6% in the medium-risk group and of 12.4% in the high-risk group. The discriminant analysis showed that with the EuroSCORE as single predicting variable - virtually all survivors were classified correctly (giving a specificity of 99.0%). The sensitivity was rather low at only 25%; however, this means that many of the high-risk patients in our clinic survived. The total misclassification rate, however, was 12.7%. Additionally, we found that a higher score value predicts a significantly higher probability for perioperative complications and also results in significantly increased average times for the bypass and total time for surgery. CONCLUSION: The EuroSCORE is a valuable score system for the prediction of the overall outcome of patients following open heart surgery, and is easy to use. As far as perioperative complications are concerned, however, some specifications seem desirable.

Cycle characteristics after discontinuation of oral contraceptives.

Nearly 60% of the women between 20 and 40 years of age who do not want to conceive choose oral contraceptives (OCs) for contraception in Germany. In an ongoing prospective study on the use of natural family planning in Germany, 175 women have been observed for 3,048 cycles immediately after having discontinued OCs (post-pill group). They were compared to a control group of 284 women observed for 6,251 cycles, who had never taken OCs. Both groups were comparable in age and sociodemographic characteristics. After discontinuing OCs, 57.9% of all first cycles were ovulatory with sufficient luteal phases. However, for the total post-pill group the cycle length was significantly prolonged up to the ninth cycle. A significantly higher number of luteal phases were insufficient in the post-pill group. Major cycle disturbances (cycle length > 35 days or luteal phase of < 10 days of elevated basal body temperature or anovulatory cycles) were significantly more frequent in the post-pill group up to the seventh cycle. Cycle disturbances after discontinuing OCs were reversible but the time of regeneration took up to 9 months (significant) or even longer (not significant). These results will help to counsel couples who wish to conceive after discontinuing OCs or who want to continue contraception with alternative methods.

Differential diagnosis of hyperthyroidism: Doppler sonographic quantification of thyroid blood flow distinguishes between Graves' disease and diffuse toxic goiter.

The aim of our study was to evaluate the usefulness of color duplex sonography to distinguish Graves' disease from diffuse toxic goiter. 24 patients with Graves' disease and 13 patients with diffuse toxic goiter underwent B-mode- and color duplex sonography of the thyroid gland. All patients had hyperthyroidism and elevated (99m)Tc-uptake. Spectral Doppler recordings were obtained at all thyroid arteries. Representative color flow maps of the thyroid gland were analyzed, calculating the percentage area of the thyroid gland, occupied by color pixels (color pixel density). The B-mode ultrasound pattern was subjectively assessed on a 4-point rating scale. In patients with Graves' disease the mean peak systolic velocity (PSV) (SD) was 110 (+/- 49) cm/s, the mean volume flow rate (VFR) was 123 ( +/- 67) ml/min and the mean color pixel density (CPD) was 33 (+/- 12) %. For patients with diffuse toxic goiter mean PSV (SD) was 43 ( +/- 9) cm/s (p < 0.001), mean VFR was 23 (+/- 10) ml/min (p < 0.001) and mean CPD was 9 (+/- 6) % (p = 0.007). CPD and spectral duplex recordings were positively correlated (CPD/PSV: rs = 0.77, CPD/VFR: rs = 0.75; p < 0.0001). No significant differences were observed concerning RI values. Sensitivity was 87% and specificity 92% for CPD and VFR and 87% and 100% for PSV. We conclude, that color duplex sonography can reliably distinguish diffuse toxic goiter from Graves' disease and therefore contributes significantly to the differential diagnosis of hyperthyroidism in diffuse thyroid disease.

Repair of critical aortic coarctation in neonatal age.

BACKGROUND: The data of 111 (male: 64; female: 47) in the period of 1967 until 12/93 consecutive operated neonatals (<1 month) were studied retrospectively (mean weight 3270 g, mean age at operation 14 days). METHODS: Preductal anatomy was present in 96 patients. The coarctation was isolated in 30 patients (group I), 34 patients had additional large ventricular septal defects (group II) and 47 had complex heart disease (group III). The preoperative heart catheterization revealed a gradient of <20 mmHg in 35%, >20 mmHg in 51.4% and >50 mmHg in 12.9%. The indication for repair was conservatively untreatable heart insufficiency. In the vast majority (n=97) of patients resection and end-to-end anastomosis were performed, in 31 cases using an absorbable suture, in 18 of these using a continuous suture line. In 4 patients a subclavian flap angioplasty (SFA) was done, in 4 a patch enlargement, 4 times a repair was described as not possible and in 2 patients there was no gradient after division of the ductus. RESULTS: Early lethality was 3.3% (n=1) in group I, 24.2% (n=8) died in group II and 39.1% (n=18) in group III; after introducing Prostaglandin E1 0% in group I, 15% in II and 25% in III. Relevant recoarctation (Gradient >20 mmHg) developed in 9 (among them 4 with hypoplastic arch, 2 after SFA) of the 77 long-term survivors; 6 of these were reoperated on, 5 without residual gradient, 1 with a gradient of 25 mmHg without clinical symptoms (after 4 years). In the last 3 patients a balloon dilation was carried out without residual gradient. Mean follow-up time was 6 (0-24) years. No patient needs antihypertensive treatment. The cumulative survival rate is 96.7% (+6.6%) for group I, 77.4% (+15.0%) for II and 51.9% (+16.6%) for III. CONCLUSIONS: Resection and end-to-end anastomosis using a continuous absorbable suture is the method of choice at theoretical considerations and in our experiences. The number of recoarctations in neonatal age is relatively high; reinterventions (operation respectively dilation) can be done safely and successfully.

Changes in coronary vessel resistance during postischemic reperfusion and effectiveness of nitroglycerin.

OBJECTIVE: Microvascular incompetence after ischemia and reperfusion may compromise the normal postischemic coronary perfusion and additionally jeopardize the recovery of the myocytes. We investigated whether such a form of acute endothelial dysfunction occurs in the routine operative setting despite the use of protective measures. For this purpose, we measured pressure-flow relations in the coronary vasculature during heart operations before and after ischemia and after reperfusion and their reaction to the nitric oxide donor nitroglycerin. METHODS: Forty-eight patients with a low risk profile scheduled for routine coronary artery bypass surgery were included. During normothermic extracorporeal circulation, the fibrillating heart was completely excluded from bypass by clamping of the ascending aorta and snaring of the caval veins. It was relieved of blood by opening the right atrium and venting the left atrium and ventricle to avoid distention. The coronary vessels were perfused under controlled flow, and the perfusion pressures were monitored. This protocol was performed in 24 patients before and immediately after ischemia and after a reperfusion period. RESULTS: Compared with the preischemic control, vascular resistance was decreased by 17% (P <.003) immediately after ischemia but increased again by 46% (P <.0001) during an average of 25 minutes of reperfusion and, even more important, by 23% (P <.028) in comparison with the preischemic values. In two groups of 12 patients, nitroglycerin was added to the perfusate either in a dosage of 3 microg. kg. min(-1) or as a bolus injection of 2 mg. Low-dose nitroglycerin did not reduce the elevated postreperfusion resistances significantly, but bolus injection did (P <.0002). Coronary vessel resistance increased during reperfusion in particular in patients with a history of hypertension. CONCLUSION: Coronary vasoconstriction during postischemic reperfusion is regularly present in the routine operative setting in cardiac surgery, despite myocardial protection measures. The amount of vasoconstriction varies considerably and is particularly increased in patients with hypertension. The nitric oxide donor nitroglycerin can normalize the elevated resistances, but only in high dosages. This demonstrates a preserved ability of vascular smooth muscle to relax. The phenomenon had no sequelae in our low-risk patients having elective operations. However, it may gain significance in the case of severe left heart hypertrophy and in patients at risk with both a postoperative low-output syndrome and reduced mean arterial pressures during reperfusion.

RAD, a new immunosuppressive macrolide in murine corneal transplantation.

BACKGROUND: RAD is a novel macrolide immunosuppressant with effects on growth factor signalling. We investigated the potency of RAD in inhibiting allograft rejection in the rat model of orthotopic allogeneic penetrating keratoplasty. METHODS: Fifty-four allogeneic orthotopic penetrating keratoplasties were performed using Fisher rats as donors and Lewis rats as recipients. The animals were divided into five groups: syngeneic control, allogeneic control, RAD 1.5 mg/kg bw per day, RAD 2.5 mg/kg bw per day, cyclosporin A (CSA) 10 mg/kg bw per day. Medication started on the day of operation and continued daily for the duration of 18 days. Each animal was examined by slit-lamp microscopy every 3rd day. For immunohistological evaluation rats were killed on day 14. Immunohistology was performed using monoclonal mouse anti-rat antibodies against CD4, CD8, CD25, CD45 and CD54. RESULTS: The average transplant survival time in the allogeneic combination was 12.3 days (+/- 0.3). Therapy with RAD 1.5 mg/kg and 2.5 mg/kg led to a statistically significant prolongation of transplant survival to 32.3 days (+/- 11.3, P<0.05) and 37.7 days (+/- 12.5), respectively. This efficacy was similar to that of CSA 10 mg/kg (39.7 +/- 12.5 days). There was a statistically significant reduction in the number of CD4+, CD8+ as well as CD45+ cells in both the RAD- and the CSA-treated animals compared with the allogeneic control. CONCLUSIONS: The results show that oral immunosuppression with RAD significantly prolongs corneal allograft survival. Further investigation of RAD in preclinical and clinical high-risk keratoplasty is warranted.

Topical treatment of acute adenoviral keratoconjunctivitis with 0.2% cidofovir and 1% cyclosporine: a controlled clinical pilot study.

OBJECTIVE: To evaluate the efficacy of 0.2% cidofovir eyedrops and 1% cyclosporine eyedrops administered 4 times daily (qid) to treat acute adenoviral keratoconjunctivitis. METHODS: A randomized, controlled, double-masked study was conducted on 39 patients with acute adenoviral keratoconjunctivitis of recent onset. Patients were divided into 4 treatment groups: (1) cidofovir qid, (2) cyclosporine qid, (3) cidofovir + cyclosporine qid, and (4) sodium chloride qid (control). The diagnosis was confirmed using adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days. MAIN OUTCOME MEASURES: Severity of conjunctival hyperemia, conjunctival chemosis, superficial punctate keratitis during treatment, and presence and severity of corneal subepithelial infiltrates were evaluated using a clinical score. Duration until subjective improvement of symptoms was recorded. RESULTS: Subjective improvement of local symptoms was accelerated in the cyclosporine group. All other clinically relevant variables showed no statistically significant difference among the 4 treatment groups. Particularly, we did not find a difference in the frequency of corneal subepithelial infiltrates at the end of treatment. CONCLUSIONS: Use of cidofovir, cyclosporine, or both did not accelerate the improvement of clinical symptoms of acute adenoviral keratoconjunctivitis compared with the natural course of the infection as demonstrated by this pilot study. This might be because of the wide spectrum of the clinical course of the infection, low sensitivity to cidofovir, too low of a concentration of cidofovir, or early cessation of viral replication in the course of the infection. The effect of a higher concentration of topical cidofovir with and without cyclosporine requires investigation in a larger group of patients.