Factors related to genetic testing in adults at risk for Huntington disease: the prospective Huntington at-risk observational study (PHAROS).

Huntington disease (HD) is a late onset ultimately fatal neurodegenerative disorder caused by a cytosine-adenine-guanine ( CAG) triplet repeat expansion in the Huntingtin gene which was discovered in 1993. The PHAROS study is a unique observational study of 1001 individuals at risk for HD who had not been previously tested for HD and who had no plans to do so. In this cohort, 104 (10%) individuals changed their minds and chose to be tested during the course of the study but outside of the study protocol. Baseline behavioral scores, especially apathy, were more strongly associated with later genetic testing than motor and chorea scores, particularly among subjects with expanded CAG repeat length. In the CAG expanded group, those choosing to be tested were older and had more chorea and higher scores on the behavioral section of the unified Huntington's disease rating scale at baseline than those not choosing to be tested. Following genetic testing, 56% of subjects with CAG < 37 had less depression when compared to prior to testing, but depression generally stayed the same or increased for 64% of subjects in the expanded group. This finding suggests that approaches to testing must continue to be cautious, with appropriate medical, psychological and social support.

The product of the Saccharomyces cerevisiae cell cycle gene DBF2 has homology with protein kinases and is periodically expressed in the cell cycle.

Several Saccharomyces cerevisiae dbf mutants defective in DNA synthesis have been described previously. In this paper, one of them, dbf2, is characterized in detail. The DBF2 gene has been cloned and mapped, and its nucleotide sequence has been determined. This process has identified an open reading frame capable of encoding a protein of molecular weight 64,883 (561 amino acids). The deduced amino acid sequence contains all 11 conserved domains found in various protein kinases. DBF2 was periodically expressed in the cell cycle at a time that clearly differed from the time of expression of either the histone H2A or DNA polymerase I gene. Its first function was completed very near to initiation of DNA synthesis. However, DNA synthesis in the mutant was only delayed at 37 degrees C, and the cells blocked in nuclear division. Consistent with this finding, the execution point occurred about 1 h after DNA synthesis, and the nuclear morphology of the mutant at the restrictive temperature was that of cells blocked in late nuclear division. DBF2 is therefore likely to encode a protein kinase that may function in initiation of DNA synthesis and also in late nuclear division.

Rasagiline-associated motor improvement in PD occurs without worsening of cognitive and behavioral symptoms.

BACKGROUND: Cognitive and behavioral adverse events (AEs) such as hallucinations, confusion, depression, somnolence and other sleep disorders commonly limit effective management of motor symptoms in PD. Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a novel, second-generation, selective, irreversible monoamine oxidase type B inhibitor, demonstrated in monotherapy and adjunctive trials to be effective for PD with excellent tolerability. METHODS: The occurrence of cognitive and behavioral AEs and the change from baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) part I mental subscores were reviewed in two multicenter, randomized, placebo-controlled, 26-week trials of rasagiline for early and moderate-to-advanced patients with PD. The UPDRS is a multi-item rating scale specific to PD; part I rates the patient's intellectual impairment, thought disorders, depression and motivation/initiative. RESULTS: The TEMPO study evaluated rasagiline monotherapy in early PD patients (n=404). The PRESTO study evaluated rasagiline as adjunctive therapy in moderate-to-advanced PD patients with motor complications who were receiving optimized levodopa/carbidopa (n=472). In the analysis of adverse event reporting for both studies, no cognitive and behavioral AE in either the rasagiline 1 mg or placebo groups exceeded 10% of the study population and the frequency differences between rasagiline 1 mg and placebo never exceeded 3%. There was no adverse effect on the UPDRS mental subscore relative to placebo in either of the two studies. CONCLUSION: Rasagiline 1 mg once daily improves PD symptoms and motor fluctuations in early and moderate-to-advanced PD patients without causing significant cognitive and behavioral AE or adverse changes in mentation, behavior and mood.

One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome.

PURPOSE: One hundred autotransplants for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) were examined prospectively to identify variables with prognostic significance. PATIENTS AND METHODS: Ninety-six patients with relapsed or refractory HD or NHL underwent 100 autotransplants. Patients received high-dose carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem-cell rescue. RESULTS: The 3-year actuarial event-free survival (EFS) rate for the 47 HD patients is 49%, with a median followup duration of 2 years. For the 53 NHL patients, the 3-year actuarial EFS rate is 40%, with a median follow-up duration of 19 months. By multivariate analysis, minimal disease on admission (all areas < or = 2 cm) is associated with improved EFS (HD, P = .003, NHL, P = .03). The projected EFS rate for HD patients entering with minimal disease is 70% versus 15% for patients with bulky disease (P = .0001). The projected EFS rate for NHL patients with minimal disease is 48% versus 25% for patients with bulky disease (P = .04). Posttransplant involved-field radiotherapy, administered to 26 of the last 61 patients, was associated with an improved EFS rate for NHL patients (P = .015). The BEAC regimen was well tolerated by patients who entered the study with minimal disease (mortality rate, < 5%), but caused significant toxicity in patients with bulky disease (mortality rate, 25%). CONCLUSION: Disease burden before autotransplantation is an important predictor of regimen-related toxicity and EFS. Posttransplant involved-field radiotherapy may improve outcomes in select patients with NHL. The BEAC regimen is safe and effective, particularly for patients with minimal disease.

Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants.

PURPOSE: To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy. PATIENTS AND METHODS: Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea. Potential covariates included patient age, sex, diagnosis, treatment protocol, transplantation type, stem-cell source, and rate of neutrophil recovery. The three selected end points were also examined for correlation with blood infections and transplant-related mortality. RESULTS: A diagnosis of leukemia, use of total body irradiation, allogeneic transplantation, and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support. No factors were associated with diarrhea. Also, moderate to severe oral mucositis (MUCPEAK > or = 18 on a scale of 8 to 24) was correlated with blood infections and transplant-related mortality: 60% of patients with MUCPEAK > or = 18 had positive blood cultures versus 30% of patients with MUCPEAK less than 18 (P =.001); 24% of patients with MUCPEAK > or = 8 died during the transplantation procedure versus 4% of patients with MUCPEAK less than 18 (P =.001). CONCLUSION: Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality, emphasizing the need for corrective strategies. The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinically significant events, including blood infections and treatment-related mortality.

[123I]beta-CIT SPECT imaging assessment of the rate of Parkinson's disease progression.

BACKGROUND: [123I]beta-CIT and SPECT imaging of the dopamine transporter is a sensitive biomarker of PD onset and severity. OBJECTIVE: In this study, the authors examine the change in [123I]beta-CIT uptake in sequential SPECT scans to assess the rate of progression of the dopaminergic terminal loss in patients with PD. METHODS: Patients with PD (n = 32) and healthy controls (n = 24) recruited from the Yale Movement Disorders Center underwent repeat [123I]beta-CIT SPECT imaging during a 1- to 4-year period. The primary imaging outcome was the ratio of specific to nondisplaceable striatal activity. Disease severity was assessed by Hoehn and Yahr staging, and Unified Parkinson Disease Rating Scale after 12 hours off drug. RESULTS: Sequential SPECT scans in PD subjects demonstrated a decline in [123I]beta-CIT striatal uptake of approximately 11.2%/year from the baseline scan, compared with 0.8%/year in the healthy controls (p < 0.001). Although [123I]beta-CIT striatal uptake in the PD subjects was correlated with clinical severity, the annual percentage loss of [123I]beta-CIT striatal uptake did not correlate with the annual loss in measures of clinical function. CONCLUSIONS: - The rate of dopaminergic loss in PD is significantly greater than that of healthy controls, and [123I]beta-CIT SPECT imaging provides a quantitative biomarker for the progressive nigrostriatal dopaminergic degeneration in PD. As new protective and restorative therapies for PD are developed, dopamine transporter imaging offers the potential to provide an objective endpoint for these therapeutic trials.

A randomized trial of the effect of dust control on children's blood lead levels.

OBJECTIVE: Dust control is recommended as one of the cornerstones of controlling childhood lead exposure; however, the effectiveness of dust control has not been demonstrated for children who have low to mild elevations in blood lead (ie, less than 25 micrograms/dL). The objective of this study was to determine whether dust control, as performed by families, had an effect on children's blood lead levels and dust lead levels in children's homes. DESIGN: Randomized, controlled trial. SETTING: Community-based trial in Rochester, NY. PARTICIPANTS: One hundred four children, 12 to 31 months of age at baseline. INTERVENTION: Families and children were randomized to one of two groups. Families of children in the intervention group received cleaning supplies, information about cleaning areas that are often contaminated with lead, and a cleaning demonstration. Families in the control group received only a brochure about lead poisoning prevention. OUTCOME MEASURES: Baseline measurements of lead in blood, house dust, soil, water, and paint were taken from both groups. Seven months after enrollment, a second blood lead assay was obtained, and lead levels in household dust were measured. The main outcome measures were change in blood lead levels and dust lead levels by treatment group. RESULTS: The median blood lead level of children enrolled in the study was 6.7 micrograms/dL (range, 1.7 to 30.6 micrograms/dL). There was no significant difference in the change of children's blood lead levels or dust lead levels by treatment group. The median change in blood lead levels among children in the intervention group was -0.05 micrograms/dL compared with -0.60 micrograms/dL among those in the control group. There also was no significant difference in the change of dust lead by group assignment, although there was a trend toward a significant difference in the percentage of change in dust lead levels on noncarpeted floors, which was greater among houses in the intervention group. CONCLUSIONS: These data suggest that an intervention that consists only of providing cleaning supplies and a brief description of dust control is not effective at reducing blood lead levels among urban children with low to mild elevations in blood lead levels at a 7-month follow-up.

Primary prevention of childhood lead exposure: A randomized trial of dust control.

BACKGROUND: Dust control is recommended as one of the primary strategies to prevent or control children's exposure to residential lead hazards, but the effect of dust control on children's blood lead levels is poorly understood. OBJECTIVE: To determine the effectiveness of dust control in preventing children's exposure to lead, as measured by blood lead levels, during their peak age of susceptibility. DESIGN: A randomized, controlled trial. SETTING: Rochester, NY. PARTICIPANTS: A total of 275 urban children were randomized at 6 months of age, of whom 246 (90%) were available for the 24-month-old follow-up visit. INTERVENTIONS: Children and their families were randomly assigned to an intervention group (n = 140), which received cleaning equipment and up to eight visits by a dust control advisor, or a control group (n = 135). OUTCOME MEASURES: Geometric mean blood lead levels and prevalence of elevated blood lead levels (ie, >10 microg/dL, 15 microg/dL, and 20 microg/dL). RESULTS: At baseline, children's geometric mean blood lead levels were 2.9 microg/dL (95% confidence interval [CI] = 2.7, 3.1); there were no significant differences in characteristics or lead exposure by group assignment, with the exception of water lead levels. For children in the intervention group, the mean number of visits by a dust control advisor during the 18-month study period was 6.2; 51 (36%) had 4 to 7 visits, and 69 (49%) had 8 visits. At 24 months of age, the geometric mean blood lead was 7.3 microg/dL (95% CI = 6.6, 8.2) for the intervention group and 7.8 microg/dL (95% CI = 6.9, 8. 7) for the control group. The percentage of children with a 24-month blood lead >/=10 microg/dL, >/=15 microg/dL, and >/=20 microg/dL was 31% versus 36%, 12% versus 14%, and 5% versus 7% in the intervention and control groups, respectively. CONCLUSIONS: We conclude that dust control, as performed by families and in the absence of lead hazard controls to reduce ongoing contamination from lead-based paint, is not effective in the primary prevention of childhood lead exposure.

Instantaneous cardiac death in the posthospital period after acute myocardial infarction.

Sudden arrhythmic cardiac death is a major unresolved health problem, yet there is no agreement on the chronologic definition of sudden death. This retrospective study investigates the frequency distribution of the chronology of the terminal cardiac event in a large postinfarction population and identifies factors associated with instantaneous (< 1 minute) cardiac death. This study involved 229 patients enrolled in the Multicenter Diltiazem Post-infarction Trial who died during 2-year follow-up and had quantitative information on the chronology of the terminal event. Thirty-two percent of the cardiac deaths occurred instantaneously. Patients who died instantaneously were more likely (p < 0.05) to be men, to have a baseline ejection fraction < 0.40, and to have frequent (> or = 10/hour) and repetitive (> or = 3 in a row) ventricular ectopic complexes (VECs) on an ambulatory electrocardiogram than those who did not die instantaneously. Patients who died instantaneously received more digitalis and class IA antiarrhythmic agents and less beta blockers in the week before death than those dying noninstantaneously. Logistic regression analysis identified 3 independent factors that differentiated instantaneous from noninstantaneous death (relative risk; 95% confidence interval): frequent VECs (2.15; 1.11 to 4.17); digitalis (2.57; 1.31 to 5.06); and no beta blocker medication (2.90; 1.09 to 7.75). Instantaneous death (within 1 minute) was responsible for almost one third of the cardiac deaths that occurred in this postinfarction population. Frequent VECs, digitalis, and absence of beta-blocker therapy distinguished patients who died instantaneously from those who died noninstantaneously.

Interrelation of left ventricular ejection fraction, pulmonary congestion and outcome in acute myocardial infarction.

The interrelation of different grades of pulmonary congestion evaluated by chest roentgenogram in the coronary care unit, predischarge left ventricular (LV) ejection fraction (EF) and long-term prognosis was studied in 1,850 surviving patients of acute myocardial infarction (AMI). Pulmonary congestion was categorized as: none, mild or moderate, or severe; LVEF was classified as: greater than or equal to 40%, 25 to 39%, or less than 25%. The majority of patients (1,060; 57%) had an LVEF greater than or equal to 40% and no signs of pulmonary congestion. Severe pulmonary congestion was noted in 63 patients (3.4%), 17 with LVEF less than 25% and 16 with LVEF greater than or equal to 40%. One hundred twenty-five patients (6.8%) had an LVEF less than 25%, 49 of whom had no signs of pulmonary congestion. During a mean 2-year follow-up, cardiac mortality occurred in 212 patients (11.5%). The cardiac mortality rate was related to both predischarge LVEF impairment and severity of pulmonary congestion. Cardiac mortality hazard ratios (95% confidence intervals [CI]) for LVEF less than 25%, and 25 to 39% were 5.32 (CI 3.49, 8.13; p less than 0.0001) and 2.91 (CI 2.10, 4.02; p less than 0.0001), respectively, where a referent hazard ratio of 1 was assigned to patients with LVEF greater than or equal to 40% and to those with no pulmonary congestion. Development of pulmonary congestion during AMI significantly increased the cardiac mortality risk derived from LVEF, with a marked mortality effect in patients with severe pulmonary congestion; (hazard ratio 4.20; 95% CI 2.67, 6.62; p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of diltiazem on long-term outcome after acute myocardial infarction in patients with and without a history of systemic hypertension. The Multicenter Diltiazem Postinfarction Trial Research Group.

The effect of diltiazem on long-term outcome in patients with acute myocardial infarction with and without a history of systemic hypertension was investigated in 2,466 patients using the Multicenter Diltiazem Postinfarction Trial data-base. The baseline variables were comparable in the diltiazem and placebo-treated patients within the groups with and without hypertension. The initial 60-mg dose of diltiazem was associated with a significant (p less than 0.001) but modest (3%) reduction in blood pressure and heart rate in both groups with and without hypertension. Univariate and multivariate analyses revealed a meaningful overall reduction in first recurrent cardiac events (cardiac death or nonfatal reinfarction, whichever occurred first) and cardiac death in patients with hypertension treated with diltiazem compared with results in those treated with placebo. Similar effects were not observed in patients without a history of hypertension. When first recurrent cardiac events were used as the end point, the diltiazem:placebo hazard ratio (95% confidence limits) was 0.77 (0.58, 1.01) for the total hypertension group, and 0.67 (0.47, 0.96) and 1.32 (0.83, 2.10) for patients with hypertension with and without pulmonary congestion during the acute infarction, respectively. Similar results were observed using cardiac death as the end point. Beta blockers had a negligible effect on the hypertension-diltiazem relation. These findings suggest that diltiazem may exert a long-term beneficial effect in most patients with hypertension who do not have pulmonary congestion during an acute infarction, and a detrimental effect in the minority who have pulmonary congestion.

Long-term palliation with the classic Blalock-Taussig shunt.

Eighty-five patients received a classic Blalock-Taussig shunt between 1973 and 1986. Their age range was 1 day to 9.3 years and their median age was 4 months. Forty-one percent (35/85) were less than 1 month of age. The basic operative technique was unchanged throughout the time period. The subclavian artery opposite the side of the arch was used in 89% (79/88) of the patients. All anastomoses were done with monofilament suture and there was a tendency toward smaller suture material (7-0) in the latter years. All anastomoses except one were done with an interrupted suture technique. The operative mortality rate was 4.7% (4/85) and was not statistically related to age, diagnosis, or year of operation. Palliation was considered to be satisfactory until either a second shunt or a premature corrective operation were necessary. Seven patients required a second shunt and three, a premature corrective operation. The mean time between the initial shunt and the second procedure, either a second shunt or a corrective operation, was 2.9 years and 2.4 years, respectively. Twenty-five patients have had an elective corrective operation and the mean interval to that procedure was 3.9 years. Two years after the operation, 97% of patients older than 1 month of age at operation remain in well-palliated condition, as do 87% of those less than 1 month of age. At 4 years, 87% of those older than 1 month and 54% of those less than 1 month of age continue to be in well-palliated condition. The classic Blalock-Taussig shunt provides excellent palliation at a low operative mortality for virtually all patients for a minimum of 2 years. It will provide adequate pulmonary blood flow for most patients for an extended period of time beyond 2 years.

A dilemma in analysis: issues in the serial measurement of quality of life in patients with advanced lung cancer.

Despite the availability of several instruments to evaluate quality of life (QL) over time in patients with lung cancer, barriers in measurement remain. This methodological study used LCSS data (Lung Cancer Symptom Scale, a disease- and site-specific QL measure) to examine analysis methods to quantify QL where data needed for serial evaluation may be missing. Data from two large randomized trials, conducted at 30 centers, of a new combination chemotherapy regimen incorporating a new agent for patients (n = 673) with Stage III and IV non-small cell lung cancer were obtained for this study. QL had been prospectively measured at baseline, day 29, and every six weeks thereafter using the LCSS. For the slope analysis (SA) and area under the curve (AUC) analyses, an adjustment score of zero was used to indicate QL on the day of death (mortality adjustment) and each subsequent day until the end of the assessment period. Significant differences in QL, symptom scores and known prognostic factors at baseline were found in the attrition group. SA and AUC analysis allowed inclusion of 581 patients, giving an adequacy rate of 86%. By using a mortality adjustment, an additional 45 patients were included, increasing the inclusion rate to 93%. With the use of the mortality adjustment, QL was shown to decline over the interval, as opposed to rise if the adjustment had not been performed. The conclusions of the study were: (1) analysis for serial data using SA and AUC provides useful, but differing information; (2) when attrition (caused by death) is a factor, a mortality adjustment presented a more accurate assessment of QL as an endpoint; (3) more frequent evaluations of QL will capture rapid changes in patient status and reduce the attrition bias; (4) all patients should be followed until they die; and (5) QL should be given full consideration as a primary endpoint separate from survival.

Patients > or = age 40 years undergoing autologous or allogeneic BMT have regimen-related mortality rates and event-free survivals comparable to patients < age 40 years.

To evaluate the safety and efficacy of marrow transplantation for older adults, the regimen-related mortality and event-free survival for patients > or = 40 years were compared with those for patients < 40 years. Of 148 consecutive patients receiving autotransplants for lymphoma or Hodgkin's disease, 70 were < 40 years and 78 were > or = 40 years at the time of transplant, including 40 who were > or = 50 years and 12 who were > or = 60 years. Eleven patients (16%) in the younger age group died from transplant-related complications compared with 4 (5%) in the older age group. The 4-year actuarial event-free survivals (EFS) for the younger and older age groups were 43% and 48%, respectively. After adjustment for covariates with prognostic significance, older age was marginally associated with improved event-free survival (P = 0.08). Of 92 consecutive patients undergoing allogeneic BMT during the same period, 62 patients were < 40 years and 30 patients were > or = 40 years, including 8 patients > or = 50 years, and 1 patient > 60 years. Non-relapse mortality (including deaths from GVHD) occurred in 28 of the younger patients (45%) and 9 of the older patients (30%). The 3-year actuarial EFS for the younger patients was 26% vs. 56% for the patients > or = 40 years (P = 0.057). However, this difference was mainly due to the higher proportion of patients with CML and early-stage leukemia in the older age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Autotransplantation for relapsed or refractory Hodgkin's disease: long-term follow-up and analysis of prognostic factors.

Seventy consecutive patients with refractory or relapsed Hodgkin's disease who received high-dose chemotherapy followed by autologous stem cell rescue were analyzed to identify clinically relevant predictors of long-term event-free survival. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine and cyclophosphamide (BEAC). The 5-year Kaplan-Meier event-free survival (EFS) for the entire cohort was 32% (95% confidence interval; 18-45%) with a median follow-up of 3.6 years (range 7 months-7.6 years). The most significant predictor of improved survival was the presence of minimal disease (defined as all areas < or =2 cm) at the time of transplant: the 5 years EFS was 46 vs 10% for patients with bulky disease (P = 0.0002). Other independent predictors identified by step-wise regression analysis included the presence of non-refractory disease and the administration of post-transplant involved-field radiotherapy (XRT). Treatment-related mortality occurred in 13 of 70 patients: nine patients (13%) died within the first 100 days, mainly from cardiopulmonary toxicity. However, only one of 24 patients (4%) transplanted during the last 4.5 years died from early treatment-related complications. While high-dose therapy followed by autotransplantation led to long-term EFS of 50% for patients with favorable prognostic factors, a substantial proportion of patients relapsed, indicating that new therapeutic strategies are needed.

Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long-term follow-up and analysis of prognostic factors.

One hundred and thirty-six patients autografted for relapsed or refractory non-Hodgkin's lymphoma (NHL) were evaluated to assess long-term event-free survival and to identify important prognostic factors. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem cell rescue. The 5-year Kaplan-Meier event-free survival (EFS) for the entire cohort was 34% (95% confidence interval: 24-44%) with a median follow-up of approximately 3 years (range 0-7.5 years). For patients entering with minimal disease (defined as all areas < or = 2 cm), the 5-year EFS was 40 vs 26% for those entering with bulky disease (P = 0.0004). In the multivariate analysis, minimal disease on entry and administration of involved-field XRT post-transplant were significantly associated with improved EFS; the latter association was observed mainly in the cohort of patients with bulky disease. The overall 100-day treatment-related mortality rate was 4.4% (3% for the last 71 patients). New strategies are needed to reduce the high rate of relapse (50-60%) following auto-transplantation for relapsed or refractory NHL.

Seasonal variations and age-related changes in human sperm count, motility, motion parameters, morphology, and white blood cell concentration.

OBJECTIVE: To determine the presence of any seasonal variations and age-related changes in sperm parameters in andrology patients and fertile donors. DESIGN: Retrospective analysis. SETTING: University medical center andrology laboratory. PATIENT(S): The database of 2,065 semen analyses was retrospectively reviewed for the period of March 1, 1996, to October 31, 1998. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): The sperm count, motility, motile count, progressive straightline velocity, and percentage of rapid sperm were determined with the Hamilton-Thorne IVOS analyzer with standard setup parameters. RESULT(S): There were no significant seasonal differences in the patient's volume, sperm count, motility, motile count, whereas the percentage of rapid sperm and progressive straightline velocity were significantly lower in the spring. Correlation analysis of patient semen parameters versus age implied that as age increases there is a tendency for these semen parameters to decrease, whereas percent tail defects showed a significant positive correlation with age. CONCLUSION(S): Age-adjusted analyses of seasonal variations in andrology patient semen parameters showed significant seasonal variation in the percentage rapid motile sperm and straightline velocity, as well as the percent tail defects, percent immature sperm, and the percent tapered sperm. Such seasonal variations might prove to be clinically relevant and important when designing experimental protocols.

Orbital ganglioglioma arising from ectopic neural tissue.

PURPOSE: To report a case of neonatal orbital ganglioglioma originating from ectopic neural tissue. METHOD: Case report. RESULTS: An African-American male presented at birth with proptosis and expansion of the left orbit. A discrete soft-tissue mass was located inferolateral to the globe, which proved to be a ganglioglioma. CONCLUSION: The tumor is presumed to have originated from ectopic neural tissue in the orbit. Although infrequent, this tumor should be included in the differential diagnosis of neonatal orbital neoplasms.

Endovascular occlusion of a carotid pseudoaneurysm complicating deep neck space infection in a child. Case report.

Pseudoaneurysm formation of the cervical internal carotid artery (ICA) is a rare, potentially lethal complication of deep neck space infection. This entity typically occurs following otolaryngological or upper respiratory tract infection. The pseudoaneurysm is heralded by a pulsatile neck mass, Homer's syndrome, lower cranial neuropathies, and/or hemorrhage that may be massive. The recommended treatment includes prompt arterial ligation. The authors present a case of pseudoaneurysm of the cervical ICA complicating a deep neck space infection. A parapharyngeal Staphylococcus aureus abscess developed in a previously healthy 6-year-old girl after she experienced pharyngitis. The abscess was drained via an intraoral approach. On postoperative Day 3, the patient developed a pulsatile neck mass, lethargy, ipsilateral Horner's syndrome, and hemoptysis, which resulted in hemorrhagic shock. Treatment included emergency endovascular occlusion of the cervical ICA and postembolization antibiotic treatment for 6 weeks. The patient has made an uneventful recovery as of her 18-month follow-up evaluation. Conclusions drawn.from this experience and a review of the literature include the following: 1) mycotic pseudoaneurysms of the carotid arteries have a typical clinical presentation that should enable timely recognition; 2) these lesions occur more commonly in children than in adults; 3) angiography with a view to performing endovascular occlusion should be undertaken promptly; and 4) endovascular occlusion of the pseudoaneurysm is a viable treatment option.

Cigarette smoking and the age at onset of a first non-fatal myocardial infarction.

BACKGROUND: Smoking is a major risk factor for coronary heart disease. Discontinuance of smoking is associated with a reduction in the risk of coronary disease; this risk approaches the level among non-smokers after stopping smoking for periods ranging from 6 months to several years. We analyzed pertinent prospectively accumulated data from our multicenter postinfarction studies to gain further insight into the complex relationship between cigarette smoking and the premature occurrence of a first myocardial infarction. METHODS: Retrospective analysis of the relationship between the number of cigarettes smoked and the age at onset of patients experiencing their first non-fatal myocardial infarction was investigated in 2445 patients. The intensity of smoking was quantitated in terms of the average number of packs per day smoked during adult years, subcategorized in increments of a half-pack per day up to more than two packs per day. Ex-smokers were identified if they had stopped smoking 1 month before their index infarction. Analysis of variance was used to adjust for the effects of relevant confounding risk factors. RESULTS: The adjusted age for first non-fatal infarction progressively declined with increasing smoking exposure, with an average age reduction of 8.7 years (95% confidence interval; 7.2, 10.2) in those smoking more than two packs per day compared with non-smokers. The graded effect was somewhat more marked in women than in men. The number of cigarettes smoked before infarction had no effect on the severity of the acute infarction or on mortality from cardiac causes during more than 2-year post-hospital follow-up. Those who stopped smoking 1 month or longer before the infarction were significantly older at the time of first infarction than active smokers in all smoking categories. CONCLUSION: This study provides strong evidence that active smoking is associated with an earlier age at onset of first infarctions, with a striking inverse dose-response effect. Stopping smoking appears to reduce the premature occurrence of coronary events.