Dry storage of mammalian spermatozoa and cells: state-of-the-art and possible future directions.

This review provides a snapshot of the current state-of-the-art of drying cells and spermatozoa. The major successes and pitfalls of the most relevant literature are described separately for spermatozoa and cells. Overall, the data published so far indicate that we are closer to success in spermatozoa, whereas the situation is far more complex with cells. Critical for success is the presence of xeroprotectants inside the spermatozoa and, even more so, inside cells to protect subcellular compartments, primarily DNA. We highlight workable strategies to endow gametes and cells with the right combination of xeroprotectants, mostly sugars, and late embryogenesis abundant (LEA) or similar 'intrinsically disordered' proteins to help them withstand reversible desiccation. We focus on the biological aspects of water stress, and in particular cellular and DNA damage, but also touch on other still unexplored issues, such as the choice of both dehydration and rehydration methods or approaches, because, in our view, they play a primary role in reducing desiccation damage. We conclude by highlighting the need to exhaustively explore desiccation strategies other than lyophilisation, such as air drying, spin drying or spray drying, ideally with new prototypes, other than the food and pharmaceutical drying strategies currently used, tailored for the unique needs of cells and spermatozoa.

Familial factors in the antihypertensive response to lisinopril.

BACKGROUND: Although it is widely recognized that there are familial elements in the pathogenesis of hypertension, remarkably little is known about the influence of family history on response to specific antihypertensive agents. METHODS: This study was designed to address that issue by comparing the depressor response to lisinopril in a dose range of 10 to 40 mg in 74 patients enrolled as sibling pairs. Because all patients were treated with lisinopril, ambulatory blood pressure monitoring (ABPM), an objective measure not influenced by the investigators, was used to assess the primary blood pressure (BP) outcome variable. RESULTS: Diastolic BP was highly correlated between sibling pairs at baseline (r = 0.476; P < .03) and on treatment (r = 0.524; P = .0021). Ethnicity/race had a striking influence on lisinopril dose and response rate. Among African American patients, 23 of 28 reached the top dose of 40 mg/day, whereas only 14 of 36 Caucasian patients reached that dose level. Among Caucasians, 92% responded, and only 48% of African Americans. Responders were characterized by being younger and heavier, having significantly lower microalbuminuria at baseline, higher baseline renal plasma flow (RPF), and higher urinary kallikrein. CONCLUSION: Among Caucasians, the presence of a hypertensive sibling predicts a striking therapeutic response to angiotensin converting enzyme inhibition.

Noninvasive outcome measures of urinary incontinence and lower urinary tract symptoms: a multicenter study of micturition diary and pad tests.

PURPOSE: We assessed the test-retest reliability of a 24, 48 and 72-hour micturition diary and pad test in patients referred for the evaluation of urinary incontinence and lower urinary tract symptoms. MATERIALS AND METHODS: We prospectively enrolled 109 patients referred for the evaluation of lower urinary tract symptoms in our multicenter study. Patients were requested to complete a 72-hour micturition diary and pad test, and repeat each test during a 1-week interval. The test-retest reliability of various parameters of the 72-hour micturition diary and pad test was analyzed and compared. Further analysis was done to compare the test-retest reliability of 24, 48 and 72-hour studies performed on the same days after a 1-week interval. Reliability was assessed by Lin's concordance correlation coefficient (CCC) with a cutoff value of 0.7 indicating test-retest reliability. RESULTS: Of the 109 patients 106 (97%) with a median age of 64 years completed the study. The number of pads and total weight gain appeared to be reliable measures of the 24, 48 and 72-hour pad tests. For the 24-hour diary the total number of incontinence episodes was a reliable measure, while the total number of voiding episodes was marginally reliable (mean CCC 0.785 and 0. 689, respectively). For the 48-hour diary the number of incontinence episodes and total number of voiding episodes were reliable measures (mean CCC 0.78 and 0.83, respectively), while for the 72-hour diary each parameter was highly reliable (CCC 0.86 and 0.826, respectively). However, an increased test period was associated with decreased patient compliance. CONCLUSIONS: The 24-hour pad test and micturition diary are reliable instruments for assessing the degree of urinary loss and number of incontinent episodes, respectively. Increasing test duration to 48 and 72 hours increases reliability but is associated with decreased patient compliance.

The Irbesartan type II diabetic nephropathy trial: study design and baseline patient characteristics. For the Collaborative Study Group.

BACKGROUND: Diabetic nephropathy is the most common cause of end-stage renal disease in the developed world. Angiotensin-converting enzyme inhibitors have been demonstrated to be renoprotective in type I diabetes and are now the standard of care for both hypertensive and non-hypertensive type I diabetic patients with any level of proteinuria. The role of blockade of the renin-angiotensin system in type II diabetic patients is not defined. The Collaborative Study Group has initiated the Irbesartan Type II Diabetic Nephropathy Trial (IDNT), studying the effect of the angiotensin II receptor antagonist irbesartan on progression of renal disease and mortality in type II diabetic patients with overt nephropathy and hypertension. Here we report the study design and baseline patient characteristics. METHODS: To qualify, hypertensive type II patients, age 30-70 years, must have a 24 h urinary protein excretion of >900 mg and a serum creatinine 90-265 micromol/l (1.0-3. 0 mg/dl) in women and 110-265 micromol/l (1.2-3.0 mg/dl) in men. Three treatment arms include irbesartan, placebo and amlodipine, with every attempt made to achieve similar blood pressure levels in all treatment arms. A total of 1650 patients will be enrolled utilizing approximately 225 clinics worldwide. The primary outcome measure is time to event to the composite end-point of doubling of serum creatinine, end-stage renal disease or death. The secondary outcome measure is time to composite end-point of fatal or non-fatal cardiovascular events. The average length of patient follow-up is expected to be approximately 36 months. RESULTS: The baseline characteristics of the study subjects are: age 59+/-8 years, duration of diabetes 15+/-9 years, height 168+/-11 cm (5 ft 6 in), weight 87+/-19 kg (192 lb), body mass index 31+/-7 kg/m(2), blood pressure 156+/-18 mmHg/85+/-11 mmHg, serum creatinine 150+/-53 micromol/l (1.7+/-0.6 mg/dl), creatinine clearance 66+/-34 ml/min and 24 h urine protein 4.0+/-3.5 g/day.

Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group.

Because obesity-associated hypertension has unique hemodynamic and hormonal profiles, certain classes of antihypertensive agents may be more effective than others as monotherapy. Thus, we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week, multicenter, double-blind trial in 232 obese patients with hypertension. Patients with an office diastolic pressure between 90 and 109 mm Hg were randomized to treatment with daily doses of lisinopril (10, 20, or 40 mg), hydrochlorothiazide (12.5, 25, or 50 mg), or placebo. Mean body mass indexes were similar for all patients. At week 12, lisinopril and hydrochlorothiazide effectively lowered office diastolic (-8.3 and -7.7 versus -3.3 mm Hg, respectively; P<.005) and systolic (-9.2 and -10.0 versus -4.6 mm Hg, respectively; P<.05) pressures compared with placebo. Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo (P<.001). Significant dose-response differences were observed between treatments. Sixty percent of patients treated with lisinopril had an office diastolic pressure <90 mm Hg compared with 43% of patients treated with hydrochlorothiazide (P<.05). Responses to therapies differed with both race and age. Neither treatment significantly affected insulin or lipid profiles; however, plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril (+0.31 versus -0.21 mmol/L; P<.001). Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline. In conclusion, lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension. Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics, may have a more rapid rate of response, and may offer advantages in patients at high risk of metabolic disorders.

An intervention for preventing alcohol use among inner-city middle school students.

OBJECTIVE: To examine the effectiveness of a brief, school-based intervention for preventing alcohol use. DESIGN AND SETTING: Randomized, control trial assigning inner-city public school students to an intervention program or a comparison program. PARTICIPANTS: Sixth, seventh, and eighth grade students in Jacksonville, Fla (N=104). INTERVENTIONS: Students assigned to the intervention program were given a self-instructional module and corresponding audiotape, a health consultation with a physician or nurse, and a follow-up consultation with a trained peer health model. MAIN OUTCOME MEASURES: Alcohol consumption during the month after the intervention and students' assessments of the interventions were measured. RESULTS: Students' t tests showed participants were more satisfied with physician or nurse consultations than with peer consultations or the self-instructional module and audiotapes (P=.05). Analysis of covariance tests showed significant main effects for 30-day quantity of alcohol use (F=5.15, P=.02), with intervention students reporting less alcohol consumption at follow-up than comparison students, and for 30-day frequency of alcohol use (F=5.92,P=.01) with intervention students again showing less frequent use at follow-up. CONCLUSIONS: A multicomponent, school-based intervention using print and audiotape media, brief physician or nurse consultations, and follow-up peer contacts holds promise in altering short-term alcohol use and selected behavioral factors among inner-city youth.

Factors associated with the stages of alcohol use among inner city school youth.

This study explored stages of alcohol acquisition and risk-factors associated with stages based on the Multi-Component Motivational Stages model. Two hundred fifty-four sixth-eighth grade students from an urban school completed a confidential questionnaire. Most students were in a precontemplation stage (86%), preparation stage (6%), or action stage (5%) for alcohol use. Significant differences were found across stage status on 11 of 22 risk factors. Discriminant analysis results indicated alcohol use, perceived prevalence of alcohol consumption, and intentions to drink in the future successfully discriminated youth in action and preparation from those in precontemplation and contemplation stages. Meanwhile, tobacco use discriminated students in preparation and action stages. Multiple regression analysis showed alcohol use was the most powerful predictor of acquisition stage status, followed by intentions, influenceability, and perceived severity of alcohol use. Implications for school-aged youth alcohol use prevention are discussed.

High-density lipoprotein-cholesterol: determining hygienic factors for intervention.

Current guidelines of the Adult Treatment Panel on High-Density Lipoprotein-Cholesterol (HDL-C) emphasize the protective effect of HDL-C in reducing one's risk for coronary heart disease and recommend that individuals with serum HDL-C levels below 35 mg/dL utilize hygienic means to raise them. A cross-sectional study was performed to examine the relationship of the hygienic factors obesity (measured by percent body fat and body mass index), smoking, and aerobic exercise to HDL-C. The sample, consisting of 1701 male employees of a large aerospace hardware assembly plant, were evaluated by health risk appraisal and anthropometric measurement. Regression analysis revealed a significant negative relationship between body mass index, percent body fat, age, smoking and the level of HDL-C in the blood. Alcohol consumption was directly related to HDL-C, and Whites had a lower HDL-C than all other races combined. Aerobic exercise was not found to be significantly related to HDL-C. A model (multiple R2 = .1136) consisting of age, race, alcohol consumption, smoking, and body mass index fit the data well. These findings justify weight management and smoking cessation interventions for raising HDL-C. However, the role of aerobic exercise was not supported in this study as a means of raising HDL-C. Future studies should use maximum oxygen consumption as a measure of aerobic capacity, which may be a better indicator of aerobic exercise level. The role of medication and genetic and dietary factors in HDL-C management should also be explored. Although findings from this study support smoking cessation and weight management interventions, longitudinal research is needed to determine the most effective strategy for HDL-C management.

Effect of angiotensin converting enzyme inhibitor (lisinopril) on insulin sensitivity and sodium transport in mild hypertension.

The purpose of this study was to determine whether antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril would alter cell Na+ transport kinetics, metabolic parameters associated with insulin resistance, or both in young adults with mild hypertension. Sixteen young adults (mean age 29 +/- 4 years) were treated with placebo for 8 weeks, then with lisinopril for 12 weeks. Metabolic risk factors examined included plasma lipid levels, plasma insulin concentration during an oral glucose tolerance test, and insulin sensitivity determined by an euglycemic hyperinsulinemic clamp procedure. Red blood cells were assayed for Na+/H+ exchange, Na+/Li+ exchange, Na(+)-K+ pump activity, and Na(+)-K(+)-Cl- cotransport before and during treatment. Blood pressure decreased from 142 +/- 4/98 +/- 2 mm Hg before treatment to 131 +/- 3/85 +/- 1 mm Hg during lisinopril treatment (P < .001). During lisinopril treatment, there was a significant reduction in total cholesterol (from 177 +/- 8 to 161 +/- 8 mg/dL, P < .008), in low density lipoprotein-cholesterol (from 107 +/- 7 to 91 +/- 7 mg/dL, P < .002), and in insulin at 60 min into the oral glucose tolerance test (from 132 +/- 18 to 99 +/- 15 microU/mL, P < .05). There was a marginally significant increase in insulin sensitivity during lisinopril treatment (P < .08). The assays of cell Na+ transport showed a significant reduction in maximal activity (Vmax) for Na+/H+ exchange (from 33.7 +/- 3.8 to 19.7 +/- 2.6 mmol/L cell/h, P < .003).(ABSTRACT TRUNCATED AT 250 WORDS)

Stage theory and research on tobacco, alcohol, and other drug use.

The purpose of this article was to examine the conceptual and empirical foundations of individual drug use stage development and progression related to tobacco, alcohol, and drugs. This review indicated that while greater acceptance of the idea that drug use is a complex process, the majority of stage conceptualizations suffer from significant limitations. Although limited, research conducted to date is supportive of the existence of intra-drug use stages of acquisition for cigarettes and other drugs. Research examining inter-drug use progression among youth supports the idea of a generally invariant sequence at a macro-sequential level, involving nonuse to legal drug use, marijuana use, and finally other illegal drug use.

Comparison of the efficacy and tolerability of an angiotensin converting enzyme inhibitor (lisinopril) versus a calcium channel antagonist (diltiazem SR) in the treatment of moderate to severe hypertension.

One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension (DBP between 105 and 116 mmHg) were randomised to eight weeks of double-blind treatment with lisinopril (n = 56) or diltiazem SR (n = 54). Fourteen patients withdrew from therapy; six patients withdrew because of adverse events (lisinopril, n = 3; diltiazem SR, n = 1) and lack of BP control (lisinopril, n = 1; diltiazem SR, n = 1). Both monotherapies were titrated upward (lisinopril 20-40 mg daily, diltiazem SR 120-180 mg twice daily) to achieve an office DBP < 90 mmHg. Hydrochlorothiazide (HCTZ; 25 mg daily) was added to monotherapy after week 4 if patients did not reach the BP goal (i.e. non-responders). After four weeks of therapy, 72% of patients (74 of 103) were nonresponders. At eight weeks of therapy, 66 patients (lisinopril, n = 32; diltiazem SR, n = 34) had received HCTZ. At week 8, 53% of lisinopril and 36% of diltiazem SR patients met the response criteria. Mean office DBP decreased from baseline -18.1 +/- 8.6 mmHg for lisinopril patients and -15.9 +/- 10.1 mmHg for diltiazem SR patients at week 8. Lisinopril was as effective as diltiazem in reducing systolic and diastolic office BP at week 4 (p > 0.1). Likewise, at weeks 4 and 8, no statistically significant differences were detected between treatments (p > 0.05) for systolic and diastolic ambulatory BP averaged over 24 hours. Both treatments were well tolerated and showed important antihypertensive efficacy in patients with moderate to severe BP elevation.