The efficacy and efficiency of an in-vitro fertilization programme including embryo cryopreservation: a cohort study

A cohort of 485 couples starting their first in-vitro fertilization(IVF) attempt between January, 1989 and February, 1991 inclusive,were followed until June 1, 1992. A total of 1086 treatmentcycles were initiated (mean 2.2, range 1–6). Of these,235 (21.8%) cycles were cancelled, giving a total of 851 embryoreplacements (mean 1.7, range 1–5). After IVF treatment,189 women have either delivered or have an ongoing pregnancyin the second or third trimester. This gives a baby take-homerate of 17.4% per started cycle and 22.2% per embryo replacement.For 91 (18.6%) of the couples, the treatment was abandoned priorto completion of the three scheduled IVF attempts and 57 (11.7%)of these had no completed IVF cycles. In the group of coupleswith reduced sperm quality, the delivery rate was significantlylower than that of the other groups. A total of 193 women hadembryos cryopreserved in at least one IVF cycle; 124 of thesewomen started a frozen embryo replacement cycle and 88 had atleast one cycle with replacement of frozen/thawed embryos, resultingin 25 deliveries/ongoing pregnancies. Due to the Norwegian lawon assisted procreation 65 (33.7%) of the women have had theirfrozen embryos thawed and discarded after 12 months of storage.The cryopreservation programme, with the limitations of theNorwegian law, gives a 5.2% increase in the baby take-home ratefor women entering the IVF programme, an increase of 13.2% inthe number of ongoing pregnancies/deliveries and an 11.6% increasein number of children/viable fetuses. A total of 214 women havedelivered or have ongoing pregnancies in the second or thirdtrimester. This represents 44.1% of the 485 women accepted forIVF treatment, irrespective of whether they were treated ornot, and 50.0% of those couples who completed at least one IVFcycle.     

Subsets of Glioblastoma Multiforme Defined by Molecular Genetic Analysis

Glioblastoma multiforme is a clinically and histologically heterogeneous lesion; however, to date, it has not been possible to subdivide glioblastomas on a clinical, histopathological or biological basis. Previous studies have demonstrated that loss of portions of chromosomes 10 and 17 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequent genetic alterations in glioblastoma. We therefore examined 74 glioblastomas from 67 patients for loss of heterozygosity on chromosomes 10 and 17, and for amplification of the epidermal growth factor receptor gene, to determine whether glioblastomas can be subtyped on a genetic basis. Using Southern blot analysis we were able to detect different patterns of genomic alterations. Eighteen of 67 informative patients were characterized by a loss of heterozygosity on the short arm of chromosome 17 in the tumor tissue. Forty-five of 64 informative patients showed a loss of heterozygosity on chromosome 10. Amplification of the epidermal growth factor receptor gene was noted in 25 of 67 patients and was restricted to those glioblastomas that had lost portions of chromosome 10. Epidermal growth factor receptor gene amplification occurred significantly more often in patients without chromosome 17p loss than in patients with chromosome 17p loss (p = 0.01). In addition, those glioblastomas with a loss of chromosome 17p occurred in patients significantly younger than those with glioblastomas characterized by EGFR gene amplification (p = 0.001). These data emphasize the genetic heterogeneity of glioblastoma and suggest the division of glioblastoma into genetic subsets.     

Apolipoprotein B gene DNA polymorphisms are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus

Ukkola O, Savolainen MJ, Salmela PI, von Dickhoff K, Kesäniemi YA. Apolipoprotein B gene DNA polymorphisms are associated with macro-and microangiopathy in non-insulin-dependent diabetes mellitus. Clin Genet 1993: 44: 177–184. © Munksgaard, 1993 The relationship between diabetic macroangiopathy or microangiopathy and apolipoprotein B (apoB) polymorphism was studied in 139 male and 129 female patients with non-insulin-dependent diabetes (NIDDM) mellitus, comprising consecutive patients with poor diabetic control (HBA1 13.2%\pm2.7 (SD)) referred to our hospital. Plasma cholesterol and triglyceride concentrations were higher in the patients who were homozygous for the X2 allele (presence of Xba I cleavage site). Patients with the X1 allele (absence of Xba I cleavage site) tended to have a higher frequency of macroangiopathy, although the differences were not statistically significant. There was no difference in the prevalence of microangiopathy between the groups. In subjects with only an R1 allele (= R +; homozygous for the presence of EcoR I cleavage site) the prevalence of coronary heart disease (CHD) was observed to be high (61.9%) as compared to the subjects possessing an R2 allele (= R —; homozygous or heterozygous for the absence of the EcoR I cleavage site) (46.7%; p<0.02). When the polymorphisms Xba I (subjects homozygous for the absence of the cutting site = X +; subjects homozygous or heterozygous for the presence of the cutting site = X —) and EcoR I were combined, the prevalence of macroangiopathy was observed to be high in X + R + (80.0%) as compared with X + R- (44.2%), X-R+ (56.8%) and X-R- (50.0%) (p<0.03). The prevalence of macroangiopathy tended to be particularly high in patients with the apoprotein E4 allele (phenotype E4\4 or E4/3), combined with either X+ or R +. Our findings suggest that variation at the apoB locus is one of the factors involved in predisposing diabetic patients to the development of arterial disease. As in previous studies the effect of the variation at the apoB gene on circulating lipid levels was observed. The data also support a role for the e4 allele of the apolipoprotein E gene as an important determinant of macroangiopathy in NIDDM.     

Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease

Invasive Doppler catheter-derived coronary flow reserve, echocardiographic measurements of left ventricular hypertrophy and intravenous dipyridamole-limited stress thallium-201 scintigraphy were compared in 48 patients (40 were hypertensive or diabetic) with clinical ischemic heart disease and no or minor coronary artery disease. Abnormal vasodilator reserve (ratio less than 3:1) occurred in 50% of the study group and markedly abnormal reserve (less than or equal to 2:1) occurred in 27%. Coronary vasodilator reserve was significantly lower (2.2 +/- 0.8 versus 3.5 +/- 1.3, p = 0.003) and indexed left ventricular mass significantly higher (152.6 +/- 42.2 versus 113.6 +/- 24.0 g, p = 0.0007) in patients with a positive (n = 11) versus a negative (n = 32) thallium perfusion scan. Coronary flow reserve was linearly related in coronary basal flow velocity as follows: y = -0.17x + 4.59; r = -0.57; p = 0.00002. The decrement in flow reserve was not linearly related to the degree of left ventricular hypertrophy. Abnormal vasodilator reserve subsets found in hypertensive patients were defined on the basis of basal flow velocity, indexed left ventricular mass and clinical factors. In this series, diabetes did not cause a detectable additional decrement in flow reserve above that found with hypertension alone. These findings demonstrate that thallium perfusion defects are associated with depressed coronary vasodilator reserve in hypertensive patients without obstructive coronary artery disease. Left ventricular hypertrophy by indexed mass criteria is predictive of which hypertensive patients are likely to have thallium defects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibroblast-mediated acceleration of human epithelial tumor growth in vivo.

Transformed fibroblasts coinoculated with epithelial cells accelerated the growth and shortened the latency period of human epithelial tumors in athymic mice. Addition of NbF-1 fibroblasts caused epithelial tumors to grow from five marginally tumorigenic or "nontumorigenic" (nontumor-forming) human tumor cell lines or strains: PC-3 (prostate), WH (bladder), MDA-436 (breast), and cells derived from the ascites fluids of patients with metastatic renal pelvic or prostate cancers. Evidence for the human and epithelial nature of these experimental tumors was provided by histologic, immunohistochemical, Southern and dot-blot hybridization, and cytogenetic analyses. Transformed fibroblasts induced predominantly carcinosarcomas, whereas nontumorigenic fibroblasts (NIH 3T3) and lethally irradiated transformed fibroblasts induced exclusively carcinomas. The fibroblast-epithelial interaction appears to occur bidirectionally and does not result from cell fusion. Because coculture experiments in vitro did not demonstrate an increased cell proliferation, it appears that undefined host factors can influence tumor growth. This tumor model may be useful in drug-screening programs and in mechanistic studies of factors regulating human tumor growth and progression.     

Diagnostic Impact of Bone-Subtraction CT Angiography for Patients with Acute Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE:Detection and evaluation of ruptured aneurysms is critical for choosing an appropriate endovascular or neurosurgical intervention. Our aim was to assess whether bone-subtraction CTA is capable of guiding treatment for cerebral aneurysms in patients with acute SAH and could replace DSA.MATERIALS AND METHODS:We prospectively studied 116 consecutive patients with SAH with 16–detector row bone-subtraction CTA and DSA before intracranial aneurysm treatment. Two independent neuroradiologists reviewed the bone-subtraction CTA blinded to DSA (reference standard). We determined the accuracy of bone-subtraction CTA for aneurysm detection and the measurement of aneurysm dimensions and compared the radiation doses of the 2 imaging modalities.RESULTS:Seventy-one patients (61%) had 74 aneurysms on DSA. Bone-subtraction CTA detected 73 of these aneurysms, but it detected 1 additional aneurysm. On a per-aneurysm basis, sensitivity, specificity, and positive and negative predictive values for bone-subtraction CTA were 99%, 98%, and 99% and 98%, respectively. For aneurysms of ≤3 mm, sensitivity was 94% (95% CI, 73%–99%). Bone-subtraction CTA slightly overestimated neck and dome diameters by <0.2 mm and overestimated the dome-to-neck ratios by 2% on average. Dose-length product was 565 ± 201 mGy × cm for bone-subtraction CTA and 1609 ± 1300 mGy × cm for DSA.CONCLUSIONS:Bone-subtraction CTA is as accurate as DSA in detecting cerebral aneurysms after SAH, provides similar information about aneurysm configuration and measures, and reduces the average effective radiation dose for vascular diagnostics by 65%. Diagnostic equivalence in association with dose reduction suggests replacing DSA with bone-subtraction CTA in the diagnostic work-up of spontaneous SAH.

Prompt detection and evaluation of ruptured intracranial aneurysms is critical for choosing an appropriate endovascular or neurosurgical intervention.¹ Invasive digital subtraction angiography carries an overall risk of neurologic complications, resulting in permanent deficits in 0.5%.^2,3 Providing false-negative results in 5%–10% of patients,⁴ it also may increase the risk of rebleeding.^5,6Multidetector CT angiography with high spatial resolution and bone-subtraction CTA (BSCTA) approaches the diagnostic accuracy of DSA in the detection of intracranial aneurysms.^7–12 Thus, BSCTA can be considered an alternative to DSA in treatment planning.^13,14 Some authors already recommend BSCTA as the primary imaging in acute SAH.^7,15,16 However, it still seems unclear whether BSCTA can provide sufficient information for therapy decisions, making diagnostic DSA redundant.^17,18We therefore tested the hypothesis that BSCTA is as accurate as DSA for the identification and characterization of cerebral aneurysms in patients with SAH, even for small aneurysms and for those at the level of the skull base. We additionally studied the reliability of BSCTA and radiation-exposure reduction by avoiding diagnostic DSA.     

Anteroposterior stability after posterior cruciate-retaining total knee arthroplasty

Purpose  

A functional posterior cruciate ligament (PCL) is important for the knee stability after PCL-retaining total knee arthroplasty (TKA). The objectives of this study were to determine the anteroposterior (AP) displacement of the knee after a mobile- or fixed-bearing PCL-retaining TKA operated with a ligament-balancing technique and the correlation of AP stability with the clinical outcome.     

ECG-Triggered Non-Contrast-Enhanced MR Angiography (TRANCE) versus Digital Subtraction Angiography (DSA) in patients with peripheral arterial occlusive disease of the lower extremities

Objective

To prospectively determine the diagnostic value of electrocardiography-triggered non-contrast-enhanced magnetic resonance angiography (TRANCE) of the lower extremities including the feet versus DSA.

Methods

All 43 patients with symptomatic peripheral arterial occlusive disease (PAOD) underwent TRANCE before DSA. Quality of MRA vessel depiction was rated by two independent radiologists on a 3-point scale. Arterial segments were graded for stenoses using a 4-point scale (grade 1: no stenosis; grade 2: moderate stenosis; grade 3: severe stenosis; grade 4: occlusion). Findings were compared with those of DSA.

Results

In the 731 vessel segments analysed, intra-arterial DSA revealed 283 stenoses: 33.6% moderate, 16.6% severe and 49.8% occlusions. TRANCE yielded a mean sensitivity, specificity, positive and negative predictive value and diagnostic accuracy to detect severe stenoses or occlusions of 95.6%, 97.4%, 87.2%, 99.2%, 97.1% for the thigh segments and 95.2%, 87.5%, 83.2%, 96.6%, 90.5% for the calf segments. Excellent overall image quality was observed for TRANCE in 91.4% versus 95.7% (DSA) for the thigh and in 60.7% versus 91.0% for the calves, while diagnostic quality of the pedal arteries was rated as insufficient.

Conclusion

TRANCE achieves high diagnostic accuracy in the thigh and calf regions, whereas the pedal arteries showed limited quality.     

Exercise and osteoporosis-related fractures: perspectives and recommendations of the sports and exercise scientist

Osteoporosis-related fractures represent a major health concern, particularly in elderly populations. Direct and indirect costs (amounting to nearly $17 billion in 2005), increased morbidity, and loss of independence place substantial burden on the health care system. Observational studies have shown that a physically active lifestyle is associated with a 30% to 50% decrease in vertebral or hip fractures, and a recent meta-analysis that determined the effects of exercise on fracture incidence further confirmed these results. However, because no randomized controlled exercise trials have selected fractures as a primary endpoint, causality between a sedentary lifestyle and fractures may be potentially confounded by participants' poor health status. With regard to fall reduction and bone strength as the main surrogates for fracture risk, many randomized controlled trials and corresponding meta-analyses have reported significant positive outcomes. Interestingly, no study that has assessed fall-related injuries has focused specifically on interventions that aimed to reduce fall impact. There is ongoing debate as to which factor, osteoporosis or falls, is more important for fracture prevention. This may be dependent on the region prone to fracture and the subjects' health status. In randomized controlled trials on exercise, the type, mode, and composition of exercise parameters are predictors of study outcome. Unfortunately, many exercise trials on fall prevention have not adequately described the exercise protocol used, which makes it difficult to determine which fall prevention protocol was most effective. A recent meta-analysis recommended Tai Chi and/or a mix of balance and resistance exercises for fall prevention. More sophisticated protocols are required to impact bone strength. Corresponding state-of-the-art protocols have focused on periodized high-impact/high-intensity resistance protocols performed at least twice per week. In the frail elderly, high-frequency/high-cycle number exercise programs with low-to-moderate strain intensity may also positively affect bone strength.