A randomized double-blind controlled study on the efficacy of laser zona pellucida thinning on live birth rates in cases of advanced female age.

BACKGROUND: It is conceivable that defective embryo hatching plays a part in the mechanisms involved in the decrease of embryo implantation rates with advancing age. In an effort to test this hypothesis, we tested the effectiveness of assisted hatching (AH) in women > or =37 years of age. METHODS: We prospectively studied 103 IVF-embryo transfer patients undergoing 103 embryo transfers. All of them were > or =37 years of age and had <3 previous IVF-embryo transfer attempts. Laser-AH of transferred embryos was either performed (AH group, n = 49) or not (control group, n = 54) according to randomized and double-blind methodology. Primary outcome was live birth rate. RESULTS: Population characteristics were comparable in AH and control groups as well as the mean number of embryos transferred (2.7 +/- 0.6 versus 2.7 +/- 0.6) and the prevalence of top quality embryos transferred (65 versus 59%, respectively). We failed to find any statistically significant difference between AH and control groups with regard to implantation (16.1 versus 16.7%, respectively) and live birth rates (22.4 versus 29.6%, respectively). CONCLUSION: The present study indicates that AH does not improve IVF-embryo transfer outcome in women aged > or =37 years.

Myocardial blood flow and flow reserve in response to hormone therapy in postmenopausal women with risk factors for coronary disease.

Estrogen has beneficial effects on markers of coronary heart disease (CHD) risk, but may increase overall CHD events. The effects of hormone therapy on vascular endothelial function have been mixed, and require further assessment. We studied the myocardial blood flow (MBF) response to postmenopausal combination hormone therapy (CHT) in postmenopausal women with risk factors for CHD. We performed dynamic [13N]ammonia positron emission tomography in 15 postmenopausal women in a 7-month placebo-controlled crossover trial of continuous conjugated equine estrogen/cyclical micronized progesterone. MBF was measured at rest, after sympathetic stimulation with the cold pressor test (CPT), and after i.v. adenosine infusion, to determine baseline, endothelium-dependent, and maximal flows, respectively. Response to CPT was neutral in all women at baseline (-0.51 +/- 27%). Adenosine induced a marked increase in MBF (161 +/- 111%). Treatment with 3 months of combined estrogen/progestin CHT did not change CPT or adenosine MBF responses. Myocardial flow reserve was unchanged as well. In this group of postmenopausal women at higher cardiovascular risk, no association was found between CHT assignment and change in MBF. Further study is needed to clarify the effects of CHT on the endothelium of women with presumably diseased vasculature.

Myocardial blood flow and flow reserve in response to short-term cyclical hormone replacement therapy in postmenopausal women.

OBJECTIVES: To measure the effects of combined cyclical hormone replacement therapy (HRT) on myocardial blood flow (MBF) in postmenopausal women at high risk for coronary heart disease (CHD) and in women with documented CHD. BACKGROUND: Estrogen restores endothelium-dependent vasodilation in response to acetylcholine in postmenopausal women, and it has a direct, endothelium-independent vasodilatory effect on coronary arteries. METHODS: To determine whether coronary microcirculation can be affected by short-term, combined HRT, we performed positron emission tomography (PET) in two groups of women without previous HRT. Group I (n = 10) had one or more risk factors for CHD; group II (n = 8) had documented CHD and previous myocardial infarction. Group II was older (54 +/- 4 vs 59 +/- 5 y, P = .03) and had lower total cholesterol levels at baseline because of lipid-lowering therapy (244 +/- 31 vs 203 +/- 40 mg/dL, P = .03). Patients underwent baseline dynamic PET with N-13 ammonia at rest and during maximal adenosine-induced hyperemia to assess MBF. Each then began taking HRT (conjugated equine estrogen alone or with medroxyprogesterone acetate (MPA), administered in cyclical fashion), and returned for follow-up PET 46 +/- 12 days later. RESULTS: There was no difference in resting MBF between groups I and II prior to starting therapy or at follow-up. Stress MBF and flow reserve (FR) tended to be higher in group I patients at baseline. MBF values remained unchanged at follow-up and resulted in similar FR values at baseline and during HRT for both groups. Women using only estrogen (n = 6) tended to show higher FR values after estrogen therapy, however. CONCLUSIONS: Short-term HRT in postmenopausal women did not lead to improvements in MBF or FR. Combined cyclical HRT may not exert measurable effects on coronary microcirculation. MPA may attenuate estrogen effects on the coronaries, which may be largely endothelium-dependent.

Improved detection of left main coronary artery disease with attenuation-corrected SPECT.

BACKGROUND: Myocardial perfusion imaging has demonstrated a limited sensitivity as a means of accurately identifying left main (LM) coronary disease. Because regional quantitative perfusion biases are eliminated with attenuation corrected (AC) single photon emission computed tomography (SPECT), as compared with uncorrected (NC) SPECT, we hypothesized that AC SPECT would demonstrate increased diagnostic accuracy for the detection of significant LM coronary stenosis. METHODS AND RESULTS: We studied 28 patients (23 men, 5 women; mean age, 66+/-9 years) with significant LM stenoses (> or =50%) and 34 control patients (27 men, 7 women; mean age, 65+/-11 years) with 2-vessel coronary disease. Rest thallium-201 and stress technetium 99m sestamibi SPECT imaging with and without AC were performed, as described earlier. Both AC and NC images were analyzed visually and quantitatively in comparison with corresponding normal databases. A greater sensitivity for detection of an LM defect pattern (64% vs. 7%, P = .0009) with equivalent specificity (94% vs. 100%, P = not significant) was demonstrated by means of visual analysis of AC SPECT images. More disease was demonstrated in a greater number of territories with AC SPECT images than with NC images (2.14+/-0.97 for AC images vs. 1.43+/-0.84 for NC images, P = .0001). Similar improvement in the detection of LM disease was shown by means of automated quantitative analysis (57% for AC SPECT vs 14% for NC SPECT, P = .0005), again with no loss in specificity. CONCLUSIONS: AC SPECT with the University of Michigan method in consecutive patients with LM stenoses and a select control population with severity matched multivessel coronary disease significantly improved the diagnostic accuracy of myocardial perfusion imaging for the identification of LM coronary disease, compared with uncorrected SPECT.

Gender differences in myocardial blood flow dynamics: lipid profile and hemodynamic effects.

OBJECTIVES: The purpose of the study was to compare myocardial blood flow (MBF) in hyperlipidemic postmenopausal women and age-matched hyperlipidemic men, and to analyze the relationship between cholesterol subfractions and myocardial blood flow in men and women. BACKGROUND: Women are protected from coronary artery disease (CAD) events until well after menopause, in part due to gender-specific differences in lipid profiles. METHODS: To examine the effect of these influences on coronary microcirculation, MBF was quantitated with N-13 ammonia/PET (positron emission tomography) at rest and during adenosine hyperemia in 15 women and 15 men, all nondiabetic, who were matched for age and total cholesterol levels (53+/-4 vs. 50+/-8 years, p = NS, 6.44+/-1.1 vs. 6.31+/-0.85 mmol/liter, or 249+/-41 vs. 244+/-33 mg/dl, p = NS). RESULTS: Women had significantly higher high density lipoprotein (HDL) and lower triglyceride (Tg) levels than did men, and they showed significantly higher resting MBF and stress MBF levels. Significant correlations were found between resting and hyperemic MBF and HDL and Tg levels (r = 0.44, p < 0.02 for stress MBF vs. HDL; r = 0.48, p < 0.007 for stress MBF vs. Tg). Gender was the strongest predictor of hyperemic MBF in multivariate analysis. Women responded to adenosine hyperemia with a significantly higher heart rate than did men, and hemodynamic factors correlated significantly with blood flow both at rest and during stress. CONCLUSIONS: These data suggest that the favorable lipid profile seen in women may be associated with preserved maximal blood flow in the myocardium.

Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries.

OBJECTIVES: Myocardial blood flow (MBF) in children late after arterial switch operation (ASO) was investigated quantitatively by positron emission tomography (PET). BACKGROUND: In children with transposition of the great arteries (TGA), ASO is widely accepted as the management of choice. The long-term patency of coronary arteries after surgical transfer to the neo-aorta, however, remains a concern. METHODS: Twenty-two normally developed, symptom-free children were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilation 10+/-1 years after ASO. A subgroup of 15 children (9+/-1 years; group A) had simple TGA and underwent ASO within 20 days after birth while 7 (13+/-3 years; group B) had complex TGA and underwent ASO and correction of associated anomalies later after birth. Ten young, healthy adults (26+/-6 years) served as the control group. RESULTS: Resting MBF was not different between groups. After correction for the rate-pressure product as an index of cardiac work, younger children of group A had significantly higher MBF at rest compared to healthy adults (102+/-29 vs. 77+/-6 ml/100 g/min; p = 0.012) while flow in group B was not different from the other groups (85+/-22 ml/100 g/min; p = NS). Hyperemic blood flows were significantly lower in both groups after ASO compared to normals (290+/-42 ml/100 g/min for group A, 240+/-28 for group B, 340+/-57 for normals; p < 0.01); thus, coronary flow reserve was significantly lower in both groups after ASO compared to healthy adults (3.0+/-0.6 for group A, 2.9+/-0.6 for group B, 4.6+/-0.9 for normals; p < 0.01). CONCLUSIONS: Blood flow measurements suggest decreased coronary reserve in the absence of ischemic symptoms in children late after arterial switch repair of TGA. The global impairment of stress flow dynamics may indicate altered vasoreactivity; however, the prognostic significance of these findings needs to be determined.

Acute myocardial infarction in two adolescent males.

Acute myocardial infarction in previously healthy children is rare in the absence of congenital anomalies. We describe two cases of acute anterior myocardial infarction in adolescent males with no congenital heart disease, without prior history of or risk factors for coronary heart disease, and with no history of drug abuse. These cases illustrate that myocardial infarction in the absence of systemic illness or coronary anomalies can occur in an adolescent population.

Assessment of diagnostic performance of quantitative flow measurements in normal subjects and patients with angiographically documented coronary artery disease by means of nitrogen-13 ammonia and positron emission tomography.

OBJECTIVES: Regional myocardial blood flow (MBF) and flow reserve measurements using nitrogen-13 (N-13) ammonia positron emission tomography (PET) were compared with quantitative coronary angiography to determine their utility in the detection of significant coronary artery disease (CAD). BACKGROUND: Dynamic PET protocols using N-13 ammonia allow regional quantification of MBF and flow reserve. To establish the diagnostic performance of this method, the sensitivity and specificity must be known for varying decision thresholds. METHODS: MBF and flow reserve for three coronary territories were determined in 20 normal subjects and 31 patients with angiographically documented CAD by means of dynamic PET and a three-compartment model for N-13 ammonia kinetics. Ten normal subjects defined the normal mean and SD of MBF and flow reserve, and 10 normal subjects were compared with patients. PET flow obtained in the territory with the most severe stenosis in each patient was correlated with the angiographic assessment of the stenosis (severity > or = 50%, > or = 70%, > or = 90%). Receiver operating characteristic (ROC) curve analysis was performed for 1.5, 2.0, 2.5, 3.0 and 4.0 SD of flow abnormalities. RESULTS: MBF and flow reserve values from the normal subjects and from territories with documented stenoses > or = 50% were significantly different (p < 0.05). A significant difference was found between normal subjects and angiographically normal territories of patients with CAD. High diagnostic accuracy and sensitivity, with moderately high specificity, were demonstrated for detection of all stenoses. CONCLUSIONS: Quantification of myocardial perfusion using dynamic PET and N-13 ammonia provides a high performance level for the detection and localization of CAD. The specificity of dynamic PET was excellent in patients with a low likelihood of CAD, whereas an abnormal flow reserve in angiographically normal territories was postulated to represent early functional abnormalities of vascular reactivity.

The role of nitrogen 13 ammonia positron emission tomography in predicting functional outcome after coronary revascularization.

BACKGROUND: We sought to evaluate the predictive value of positron emission tomography (PET) by using blood flow imaging with semiquantitative data analysis techniques for predicting recovery of regional function after revascularization. Positron emission tomography in combination with fluorodeoxyglucose (FDG) has been shown to predict tissue recovery after revascularization. Previous studies have suggested a quantitative threshold for perfusion as evaluated by PET that separates scar from viable tissue. METHODS AND RESULTS: In a group of 25 patients with impaired regional wall motion at baseline as measured by radionuclide ventriculography, we examined the relationship between myocardial blood flow and functional outcome of myocardial segments in patients who underwent coronary revascularization within 2 months after PET. Regional wall motion was graded on a 5-point scale, from normal to dyskinetic. Regional nitrogen 13 (N-13) ammonia uptake values were expressed as a percentage of maximal myocardial N-13 ammonia uptake and compared with values obtained from healthy volunteers. Results were displayed as polar maps, on which regions of interest were placed corresponding to revascularized vascular territories. We were able to show a statistically significant relationship between regional wall motion abnormalities and decreasing blood flow by N-13 ammonia uptake. An N-13 ammonia uptake of greater than 80% for any given segment was highly accurate in predicting normal or nearly normal postoperative regional wall motion, whereas severely decreased ammonia uptake less than 40% showed normalization of regional wall motion in only 13% of segments. CONCLUSIONS: Relative ammonia uptake of greater than 80% and less than 40% preoperatively had excellent predictive value for functional outcome, but intermediate quantitative ammonia uptake (between 40% to 80%) necessitates additional information to accurately predict functional recovery.

Detection and partial characterization of a developmentally regulated nuclear antigen in neural cells in vitro and in vivo.

We report that a monoclonal antibody directed against phosphorylated neurofilaments (SMI 31) recognizes nuclear antigens present in embryonic but not in adult neural cells. On Western blots, the antibody reacts with four proteins of apparent MW 35, 37, 52/54, and 250 KD which are found exclusively in developing brain tissue. These nuclear antigens are expressed by glial and neuronal cells. Both nuclear staining and immunoreactive proteins decrease with ongoing in vitro differentiation. A computer search for proteins that share the epitope recognized by antibody SMI 31 did not yield any proteins of known nuclear localization that exhibit the same molecular weights and solubility characteristics as the above immunoreactive proteins. We conclude that antibody SMI 31 recognizes hitherto unknown nuclear proteins which, in neural cells, are developmentally regulated.

Surgical approach to lung cancer with solitary cerebral metastasis: twenty-five years' experience.

From 1960 to 1985, 41 patients underwent resection of a lung cancer and one or more brain metastases. There were 24 men and 17 women ranging in age from 40 to 71 years (average, 56 years). Cell type was adenocarcinoma in 19 patients, squamous in 16, small cell in 4, and large cell in 2. Wedge resection was performed in 4 patients, lobectomy in 20, pneumonectomy in 14, and bilobectomy in 3. Brain irradiation was used for 25 patients (61%). To date, the longest survival is 18.3 years after craniotomy; mean survival is 2.3 years +/- 3.8 (+/- standard deviation). Survival was 55 +/- 7.9% (+/- standard error) at 1 year, 31 +/- 7.4% at 2 years, 21 +/- 6.5% at 5 years, and 15 +/- 6.0% at 10 years. Using multivariate analysis, we evaluated possible significant predictors of improved survival. Only wedge resection was a significant predictor (p less than .01), which suggests better results with a small peripheral lung tumor. Results of our 25 years' experience using an aggressive approach to lung cancer with solitary cerebral metastasis indicate significantly improved patient survival that justifies its widespread use.