Previous tubal ectopic pregnancy raises the incidence of repeated ectopic pregnancies in in vitro fertilization-embryo transfer patients.

PURPOSE: To investigate the incidence of Tubal Ectopic Pregnancies (TEP) in IVF-ET patients with respect to the status of the fallopian tubes after a previous TEP. MATERIAL AND METHODS: This retrospective study compares patients undergoing 481 IVF-ET cycles after conservatively or surgically treated TEP(s) with a Control Group (idiopathic or male factor for IVF-ET indication). Medical reports of surgery and/or hysterosalpingograms prior to the IVF cycles classified the status of the fallopian tubes. RESULTS: 12 TEPs (8.95%/Pregnancies (PR)) occurred in the Study Group. In the Control Group one TEP (0.75%/PR; p < 0.001) was found. Smoking increased the probability of TEPs (p = 0.0028) and of pathological pregnancies (abortion, biochemical and ectopic PR; (p = 0.0411)). For statistic evolution logistic regression (PROC GENMOD) and a repeated measure model were applied. CONCLUSION: Women with a previous TEP should be informed about the significantly increased risk for a further TEP in IVF-ET treatment, especially if they are smoking.

Mortality in opioid-maintained patients after release from an addiction clinic.

AIM: To investigate the mortality rate in a cohort of 269 opioid-dependent patients and the outcome of survivors meeting DSM-IV criteria for opioid dependence. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients enrolled in synthetic opioid maintenance therapy during a time frame from 1998 to 1999 originally at the Addiction Clinic and then discharged to general practitioners. METHODS: Structured interviews (Europ-ASI), urinalysis at time of interview as well as autopsy findings from deceased patients. RESULTS: After six mailings, information from 147 (54.6%) patients was gained. 85 patients (31.6%) were interviewed. From these 76.5% (n = 65) were still enrolled in maintenance therapy, 18.8% (n = 16) were drug-free and 4.7% (n = 4) relapsed. From 29 fatalities, 37.9% died of intoxication with illicit substances, 34.5% related to AIDS and 27.6% of somatic complications. The Standardized Mortality Ratio (SMR) was 29.13 (95% CI = 19.27-44.04). A higher lifetime frequency of hospitalization, less working days and a lack of social relationships were factors associated with high mortality. CONCLUSIONS: The study confirms the high mortality rate in this patient group and supports the importance of maintenance therapy. Although great efforts were undertaken in locating patients, about 45% of the target group could not be located.

Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation.

BACKGROUND: Because mammalian target of rapamycin (mTOR) inhibitors combine anticancer and immunosuppressive properties we investigated: 1) the activation status and prognostic significance of the mTOR pathway in hepatocellular carcinoma (HCC) tissues of patients undergoing orthotopic liver transplantation (OLT) for HCC, and 2) the single and combinatorial efficacy of RAD001 in HCC cells. METHODS: PTEN, p-AKT, p-mTOR, p-p70S6K, and p-4EBP-1 were analyzed by immunohistochemistry in explanted HCCs of 166 patients undergoing OLT. Efficacy of RAD001 as mono- and combination therapy with doxorubicin was tested in Hep3B and SNU398 cells. RESULTS: The mTOR pathway is activated in about 40% of patients undergoing OLT for HCC but no direct correlation between up- and downstream proteins was observed. We found no influence of mTOR pathway protein expression on disease free survival (DFS) or overall survival (OS). There was a marked single agent and chemo-sensitizing effect of RAD001 against HCC cells in vitro. CONCLUSION: The mTOR pathway is active in 40% of patients with HCC undergoing OLT, but has no influence of DFS or OS. No direct correlation was observed between up- and downstream proteins limiting the use of upstream proteins to predict mTOR activity. Prospective clinical trials are needed to test whether the activation status of the mTOR pathway in HCCs predicts the antitumor effect of rapamycin derivative in the posttransplantation course.

Immunosuppressive therapy does not prevent the occurrence of immunoglobulin E-mediated allergies in children and adolescents with organ transplants.

BACKGROUND: Allogeneic organ transplantation has become a common procedure in acute and chronic organ failure. The major limitation, rejection of the allograft by the host's immune system, can be limited by various immunosuppressive drugs that target the adaptive T-cell response. Most of these drugs are used in the treatment of allergic diseases as well, suggesting that transplant recipients under long-term immunosuppressive therapy should not develop any sensitizations or at least not show any clinical signs of allergy. Surprisingly, organ-transplanted children and adults do report symptoms of type 1 allergies, such as allergic rhinoconjunctivitis, bronchial asthma, and food allergies. Thus far, mainly case reports and series on the occurrence of allergy after orthotopic liver transplantation exist. OBJECTIVE: Our purpose with this study was to evaluate in a cross-sectional design the prevalence of immunoglobulin E-mediated sensitizations and type 1 allergies in solid organ-transplanted children and adolescents and to identify risk factors. METHODS: Seventy-eight organ-transplanted subjects (50 kidney, 9 lung, 19 liver; mean age: 14.06 +/- 5.94 years; range 1.42 to 24.25 years) were studied by standardized interviews (modified International Study of Asthma and Allergies in Childhood [ISAAC] criteria), skin-prick tests, and measurement of specific and total serum immunoglobulin E. RESULTS: Nineteen patients (24.4%) were found to be sensitized to > or = 1 common inhalant or food allergens, as reflected by elevated specific immunoglobulin E levels and/or positive skin-prick test results, and 8 subjects (10.3%) additionally reported a corresponding present history of atopic diseases. No severe anaphylactic reactions were reported. No statistically significant associations with gender, kind of transplanted organ, distinct immunosuppressive therapies, and age at time of transplantation or age at investigation were found (chi2 test, Fisher's exact test, and Wilcoxon rank-sum test, respectively). Multiple logistic-regression analysis did not identify any independent risk factor either. CONCLUSION: This study demonstrates that therapeutic immunosuppression does not control sensitizations and clinical manifestation of type 1 allergies in organ-transplanted children and adolescents.

Prevalence of aneurysmal and solitary bone cysts in young patients.

Aneurysmal and solitary bone cysts develop most commonly during skeletal growth. The objective of our epidemiologic study was to evaluate the prevalence, recurrence rate, and probability of recurrence-free survival for aneurysmal and solitary bone cysts in young patients. We did a population-based analysis of 141 histologically confirmed cases. Seventy-three patients with aneurysmal bone cysts and 68 patients with solitary bone cysts were registered. The annual prevalence was 0.32 per 100,000 individuals (range, 0-1.238) for aneurysmal cysts, with a 1.8:1 male to female ratio and a median age of the patients of 11.1 years (range, 1-19.7 years). For solitary bone cysts, the calculated annual prevalence was 0.30 (range, 0-0.963) with a median age of the patients of 1.1 years (range, 0.5-19.9) and a 1.96:1 male to female ratio. Recurrent lesions occurred frequently in young males. Secondary aneurysmal bone cysts were observed only in females. During skeletal growth, aneurysmal and juvenile bone cysts more often occur in males with a peak prevalence at approximately 11 years of age. A greater prevalence of aneurysmal bone cysts in young individuals is associated with skeletal growth and immaturity. Young age and male gender are associated with an increased risk of local recurrence.

Vitrectomy for persistent diffuse diabetic macular edema.

PURPOSE: To evaluate the potential benefit of vitrectomy in eyes with persistent diffuse macular edema. DESIGN: Prospective randomized comparative clinical trial. METHODS: Eyes with diffuse diabetic macular edema for 6 to 18 months, an attached posterior hyaloid, and grid laser photocoagulation performed at least 4 months before were included. Patients were randomized either to a vitrectomy group or to a control group. MAIN OUTCOME MEASURES: Evaluations of Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, reading vision, and retinal thickness were carried out at baseline and 1, 3, and 6 months after enrollment. RESULTS: Fifty-six eyes (100%) were enrolled in this study. Twenty-five eyes (44.6%) were randomized into Gr I (vitrectomy group) and 31 eyes (55.4%) into Gr II (controls). Both groups were comparable in mean age (62.7 years and 63.9 years) and distribution of gender (one third male, two thirds female). ETDRS visual acuity showed a statistical significance in favor of Gr I at all time points (P = .035 to .005 Fisher's exact test). With Jaeger charts a significance for Gr I was found only at the 6-month examination (P = .01). With optical coherence tomography, the different behavior of retinal thickness changes in both groups during follow-up was statistically significant; P values were <.0001 for month 1, 3, and 6, preferring Gr I. CONCLUSIONS: We provide evidence that vitrectomy with internal limiting membrane peeling is superior to observation alone in eyes with persistent diffuse diabetic macular edema for 6 to 18 months. Longer follow-up periods and larger series might be needed to confirm these results and gain additional information.

Citrate for long-term hemodialysis: prospective study of 1,009 consecutive high-flux treatments in 59 patients.

BACKGROUND: Regional citrate anticoagulation during hemodialysis is performed in selected patients at highly specialized units. We postulated that routine use of citrate at a long-term dialysis ward is safe and efficient. METHODS: During a 2-year period, we studied 1,009 consecutive citrate-anticoagulated high-flux hemodialysis treatments performed in 59 patients at our long-term dialysis ward. We used a simple citrate infusion protocol, calcium-free dialysate, and intravenous calcium substitution. Simple and clear algorithms allowed adjustments of the calcium substitution rate and dialysate settings by the attending nurse. Adverse events; indications for citrate anticoagulation; clotting; technical data; blood ionized calcium, sodium, and potassium levels; and acid-base homeostasis were analyzed prospectively. RESULTS: Of the treatments, 99.6% were accomplished successfully. Two adverse events were attributed to citrate use. Overall, ionized calcium levels were stable during the procedures and electrolyte and acid-base balances were well controlled. The use of central venous catheters for dialysis was associated with paradoxical behavior of ionized calcium levels (increasing blood ionized calcium levels despite decreased calcium infusion). Anticoagulation was excellent. CONCLUSION: Routine use of citrate anticoagulation in the setting of a long-term hemodialysis ward is safe and efficient. Measured ionized calcium levels should be interpreted with care if central venous catheters are used for vascular access because they could be biased by recirculation.

Parathyroid hormone secretion during citrate anticoagulated hemodialysis in acutely ill maintenance hemodialysis patients.

Regional citrate anticoagulation during extracorporeal treatment is used in patients at risk for hemorrhage. We conducted a prospective clinical trial on the effect of large- versus small-dose calcium supplementation during citrate anticoagulated hemodialysis on ionized calcium and intact parathyroid hormone (iPTH). Twenty-five treatments were studied in 25 patients with active bleeding or at risk for hemorrhage. Sixteen patients received large-dose calcium (15 mmol/h), and 9 received small-dose calcium (5 mmol/h) substitution during treatment. Ionized calcium increased in 13 of 16 patients in the large-dose calcium group and decreased in 8 of 9 patients in the small-dose calcium group. Intact PTH decreased by 25% in the large-dose group and increased by 121% in the small-dose group (P = 0.0007 for Delta; P = 0.007 for Delta%). In the 14 patients in whom ionized calcium increased, iPTH decreased. In 10 of 11 patients in whom ionized calcium decreased, iPTH increased. The increase or decrease of ionized calcium was more predictive for changes in iPTH than was the calcium-substitution rate (R(2) = 0.5526 versus 0.3962, respectively). We conclude that the behavior of iPTH can be influenced in a predictive manner by adjusting the calcium-substitution rate during treatment.

Arterial remodeling and hemodynamics in carotid stents: a prospective duplex ultrasound study over 2 years.

OBJECTIVE: This study was undertaken to study negative and positive arterial remodeling processes within self-expanding carotid stents, their interaction, and the resulting changes in hemodynamics over 2 years, with duplex ultrasound scanning. SUBJECTS AND METHODS: One hundred twelve consecutive patients with 121 successfully stented carotid arteries were examined with color-coded duplex ultrasound scanning the day after the stent procedure and at 3, 6, 12, and 24 months of follow-up. The stent diameters at the proximal, middle, and distal regions, and the maximal neointimal thickness (B-mode) and hemodynamic parameters were recorded. Pre-interventional plaques were assigned to three types: soft, fibrous, and largely calcified. RESULTS: The diameters of the self-expanding stents steadily increased over 2 years (positive arterial remodeling), from (mean +/- SD) 5.80 +/- 0.89 mm to 6.77 +/- 0.98 mm in the proximal stent area, from 3.51 +/- 0.76 mm to 4.92 +/- 0.89 mm in the middle stent area, and from 3.7 +/- 0.5 mm to 4.68 +/- 0.61 mm in the distal stent area (P<.001). Stent expansion was most marked in the middle stent area, depending on the type of pre-interventional plaque. The extent in stent expansion was more in soft than in fibrous and calcified plaques (P<.001). Neointimal thickness increased up to 12 months, and stabilized thereafter. The mean (+/- SD) neointimal thickness at 3, 6, 12, and 24 months was 0.61 +/- 0.28 mm, 0.97 +/- 0.39 mm, 1.06 +/- 0.36 mm, and 1.12 +/- 0.38 mm, respectively. These complex interactions resulted in the dominance of negative remodeling secondary to neointimal proliferation, with an increased flow ratio during the first year, from 1.16 +/- 0.37 at day 1 to 1.23 +/- 0.46 at 3 months, 1.67 +/- 1.37 at 6 months, and 1.57 +/- 0.70 at 12 months (P<.001), followed by a tendency to decrease as a result of stent expansion thereafter (flow ratio at 24 months, 1.49 +/- 0.70). Two of 121 stents (1.6%) had recurrent stenosis that required a secondary procedure. CONCLUSIONS: Neointimal proliferation or negative arterial remodeling prevails up to 12 months, and may give rise to rare stent recurrent stenosis. Stent expansion reduces this effect in the first year, and dominates in the second year. This might contribute to the good mid-term outcome of carotid stenting. Poor stent expansion in heavily calcified plaques calls for primary surgical management.

Acetylsalicylic acid, diclofenac, and lornoxicam, but not rofecoxib, affect platelet CD 62 expression.

UNLABELLED: Nonsteroidal antiinflammatory drugs are routinely administered in the perioperative period. Because of the absence of cyclooxygenase-2 in platelets, cyclooxygenase-2-selective drugs are thought not to cause platelet inhibition. Because platelets play an important role in the coagulation process, the absence of platelet function inhibition may lead to fewer bleeding complications after surgery. We studied the influence of aspirin, diclofenac, lornoxicam, and rofecoxib on arachidonic acid and collagen-induced CD 62 P (P selectin) expression by using flow cytometry. Blood from 68 volunteers was obtained before and 1, 3, and 12 h after the oral ingestion of 1 of the randomly assigned study medications. Aspirin, diclofenac, and lornoxicam had a significant effect on arachidonic acid and collagen-induced CD 62 P expression in platelets, whereas rofecoxib did not show this effect. We conclude that rofecoxib is safe to use perioperatively with respect to inhibition of platelet function. IMPLICATIONS: We compared the effect of rofecoxib and three nonselective nonsteroidal antiinflammatory drugs on platelet function, measured by CD 62 P expression. Platelet function was not altered by rofecoxib, but it was inhibited by aspirin, diclofenac, and lornoxicam. Rofecoxib may be safer than classic NSAIDs with respect to platelet function during the perioperative period.

Response to sublethal heat treatment of prostatic tumor cells and of prostatic tumor infiltrating T-cells.

BACKGROUND: To investigate the possibilities offered by high intensity focused ultrasound (HIFU) in the field of tumor vaccination, we analyzed how prostatic cancer (CaP) cells react towards heat treatment and whether increased access to CaP cells by the immune system would be the result. METHODS: Heat/stress response of CaP cells in situ and of CaP cell lines was analyzed by immunohistochemistry, Western blotting, and Atlas array. A heat-induced change in immune recognition was analyzed functionally using human T-helper (Th)1 and Th2-cytokine release with tumor infiltrating T-lymphocytes (TIL) as responder and autologous CaP cells either heated or untreated as stimulator cells. RESULTS: Transcription of 68 out of 500 genes was upregulated by sublethal heat in LNCaP and PC3 cells. Significantly upregulated stress protein (SP) expression (HSP-72, -73, GRP-75, -78) was seen at the border zone of HIFU treatment. Remarkably, even untreated benign prostatic hyperplasia (BPH) specimens revealed relative overexpression of heat shock protein (HSP)-72, -73 and glucose regulated protein (GRP)-75, -78. Heated CaP cells increased Th1-cytokine (IL-2, IFN-gamma, TNF-alpha) release but decreased Th2-cytokine (IL-4, -5, -10) release of TIL. CONCLUSIONS: HIFU treatment may alter the presentation of prostate tissue and tumor antigens and this presentation is most likely stimulatory. HSP-72/73 overexpression in untreated BPH may suggest a mechanism by which BPH can incite inflammation.

Effect of carotid artery stenting on the external carotid artery.

OBJECTIVE: We studied the fate of the ipsilateral external carotid artery (ECA) after stenting of the internal carotid artery (ICA) compared with the contralateral ECA. SUBJECTS AND METHODS: One hundred twenty-one ipsilateral ECAs in 112 consecutive patients who underwent carotid artery Wallstent placement were prospectively studied with color-coded duplex sonographic scanning (CCDS) and compared with 83 contralateral ECAs over 2 years. CCDS was scheduled for the day before (day 0), the day after (day 1) and 3, 6, 12, and 24 months after stenting. Development of ECA occlusive disease was evaluated with ECA-common carotid artery flow ratio (peak systolic velocity). For estimation of ECA stenosis 70% or greater, flow ratio 4.1 was used as the cutoff point. RESULTS: Before and after stenting, two and three (one additional) ECA occlusions were seen. Median grade of ECA stenosis on day 1 did not significantly change at angiography (P = 1.0; tendency of increase) or CCDS (P =.27; tendency of decrease).At follow-up (day 1-24 months, CCDS only), frequency of stenosis 70% or greater in the ipsilateral ECA was 21 of 120 (17.5%) on day 1 and 41 of 107 (38.32%) at 24 months, and 3 of 107 (2.5%) and 5 of 107 (4.67%) ECA occlusions were registered at the two time points. Progression of disease, as demonstrated by increase in flow ratio over time, was much more pronounced in the ipsilateral ECAs compared with the contralateral ECAs (P =.0002). In stented ICA, 2 (1.85%) asymptomatic recurrent stenoses 70% or greater were found at CCDS. One of three patients with new ECA occlusions reported jaw claudication for 10 days. Perioperative stroke (one major, four minor) occurred in 5 of 121 patients (4.46%). Two minor strokes caused by embolization occurred during the first year. CONCLUSION: The more pronounced progression of arteriosclerotic disease at the orifice of the ipsilateral ECAs during the first year after carotid stenting might be due to local factors of the ICA stent. Its clinical significance in respect to the effect of the ECA as collateral supply to the brain might depend on the incidence of carotid stent rerecurrent stenosis, which was low in the present study.