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PubMed2005

Markers of lacunar stroke in patients with moderate internal carotid artery stenosis.

The benefits of surgical correction of moderate internal carotid artery stenosis have been demonstrated only in symptomatic subjects. It is debatable whether patients with lacunar infarct ipsilateral to a moderate carotid stenosis may be considered symptomatic like those with large-artery stroke. The aim of the study was to seek markers capable of differentiating patients with lacunar or non-lacunar stroke ipsilateral to a moderate internal carotid artery stenosis. We enrolled 95 patients with a first stroke ipsilateral to a moderate (50-69 %) stenosis of the internal carotid artery and divided them into lacunar and non-lacunar stroke based on clinical presentation and neuroradiological findings; 34 subjects with asymptomatic moderate carotid stenosis and 31 normal individuals were also studied. Baseline characteristics; risk factors, cerebrovascular reactivity to hypercapnia evaluated by means of the breath-holding index (BHI), the presence and severity of carotid stenosis and intimamedia thickness (IMT) of the common carotid arteries were determined. There were 36 patients with lacunar and 59 with non-lacunar stroke. Degree of stenosis, and IMT and BHI ipsilateral to symptomatic stenosis were found to be significant independent predictors as each 10 % increase of stenosis carried a 4.3 higher probability of non-lacunar stroke (95 % CI: 1.91-9.51); each decimillimeter increment in IMT increased this probability by 1.45 (95 % CI: 1.10-1.92); and the risk odds ratio associated with each 0.1 increase in BHI was 1.88 (95 % CI: 1.33-2.66). A decrease in BHI of 0.1 thus carried a 90% greater probability of having a lacunar stroke. The results show that patients with moderate internal carotid artery stenosis and lacunar stroke can be differentiated from those with non-lacunar stroke on the basis of distinctive ultrasonographic findings. Further studies are needed to clarify whether our findings have pathogenetic implications and may be of help for the planning of different therapeutic strategies in patients with moderate internal carotid stenosis and lacunar or non-lacunar ipsilateral stroke.

Aged↗

PubMed1995

Mapping of the consequences of bilirubin exposure in the immature rat: local cerebral metabolic rates for glucose during moderate and severe hyperbilirubinemia.

The regional cerebral metabolic consequences of bilirubin intoxication are not well known. With the quantitative autoradiographic [14C]2-deoxyglucose (2DG), we studied the effect of moderate or severe bilirubin infusion on local cerebral metabolic rates for glucose utilization (LCMRglcs) in 10 (P10) and 21 day-old (P21) rats. After an 80 or 160 mg/kg loading dose of bilirubin administered over 15 min, the speed of bilirubin infusion was reduced to 32 or 64 mg/kg/h for the following 105 min, for moderate or severe intoxication, respectively. This infusion protocol led to plasma bilirubin concentrations of 100-200 nmol/ml (moderate intoxication) or 200-300 nmol/ml (severe intoxication). Cerebral bilirubin concentration was 10 nmol/g at P10 and undetectable at P21 in moderate hyperbilirubinemia while it reached 22-34 nmol/g at both ages during severe hyperbilirubinemia. At P10, bilirubin infusion, moderate or severe, induced significant decreases in LCMRglcs in 17 and 15 brain regions of the 24 studied, respectively. At P21, moderate hyperbilirubinemia induced a decrease in LCMRglcs in only 2 regions, auditory cortex and auditory nerve. Conversely, at that age, severe bilirubin intoxication led to significant decreases in LCMRglcs in all regions studied. These results demonstrate that metabolic changes induced by bilirubin are directly correlated to its entry into the brain which occurs without any alteration in the blood-brain barrier. Indeed, the effects of the dye are quite discrete during moderate hyperbilirubinemia at P21 when no bilirubin is detectable in the brain while they are massive during severe hyperbilirubinemia at P21 and at both levels of intoxication at P10 when bilirubin has entered the brain in measurable amounts.

Animals↗

PubMed2005

Importance of moderate ischemic mitral regurgitation.

BACKGROUND: The importance of moderate ischemic mitral regurgitation in patients presenting for coronary artery bypass grafting (CABG) is controversial. Therefore, we tracked the course of unrepaired moderate ischemic mitral regurgitation after CABG surgery alone, identified factors associated with worsening postoperative ischemic mitral regurgitation, and assessed the impact of unrepaired moderate ischemic mitral regurgitation on survival. METHODS: From 1980 to 2000, 467 patients with moderate ischemic mitral regurgitation underwent CABG alone. The course of unrepaired mitral regurgitation was estimated by a longitudinal analysis of 267 follow-up echocardiograms from 156 patients. The survival impact of moderate ischemic mitral regurgitation was determined among propensity-matched patients with and without ischemic mitral regurgitation. RESULTS: Mitral regurgitation was dynamic early postoperatively. Immediately postoperatively, it was absent or mild in 73% and severe in 6%; by 6 weeks, these figures were 40% and 22%, respectively. The course of postoperative mitral regurgitation was not associated with the preoperative extent of coronary artery disease or left ventricular dysfunction. Five-year survival of matched bypass patients without ischemic mitral regurgitation was 85% compared with 73% for patients with moderate ischemic mitral regurgitation (p = 0.003). CONCLUSIONS: Moderate ischemic mitral regurgitation does not reliably resolve with CABG surgery alone and is associated with reduced survival. Therefore, a mitral valve procedure may be warranted for such patients presenting for CABG. A randomized trial comparing strategies of revascularization with mitral valve repair and revascularization alone is required to determine optimal treatment.

Adult↗

PubMed1998

Recurrent abortion and moderate or strong antiphospholipid antibody production.

OBJECTIVE: To investigate the treatment outcome for women suffering recurrent miscarriages associated with strong or moderate antiphospholipid antibody (aPL) production. METHODS: Sixty-seven pregnancies in 61 women demonstrating at least one kind of aPL with a history of recurrent miscarriages were treated with: (1) aspirin (ASA) alone; (2) prednisolone (PSL) and ASA; and (3) PSL, ASA, heparin and/or immunoglobulin (IgG). For comparison purposes the aPL-positive patients were divided into two groups, strongly and moderately-positive. IgG and IgM antibodies against PE and five negatively-charged phospholipids were measured by ELISA between 1987 and 1993. Beta2-glycoprotein I (beta2GPI) dependent anticardiolipin antibodies were measured by ELISA since 1993. Lupus anticoagulant was measured by a diluted aPTT method since 1993. RESULTS: Out of a total of 16 (50%) patients strongly-positive for aPL and 47 out of 51 (92.2%) moderately-positive demonstrated a successful outcome. The live birth rate moderate group was significantly higher than in the strongly-positive cases (P < 0.0005). In the cases exhibiting moderate aPL production, 28 out of 30 (93.3%) receiving PSL and ASA and 14 out of 15 (93.3%) treated with ASA alone successfully gave birth. None of the 14 given ASA alone suffered preterm delivery or IUGR. In contrast 12 (36.4%) and 6 (18.2%) of the 33 patients treated with the PSL combination therapy suffered from preterm delivery and IUGR, respectively. CONCLUSIONS: The live birth rate in patients strongly positive for aPL is lower than that in patients with moderate aPL production even if treatment is performed during pregnancy. However, ASA is useful to treat cases with moderate aPL so that distinction of the two groups is warranted.

Abortion, Habitual↗

PubMed1982

Moderate potassium supplementation in essential hypertension.

23 unselected patients with mild to moderate essential hypertension, whose average supine blood pressure after two months' observation on no treatment was 154/99 mm Hg, were entered into an eight week double blind randomised crossover study of one month's treatment with slow release potassium tablets (60 mmol/day) versus placebo without alteration of dietary sodium or potassium intake. By the fourth week mean supine blood pressure had fallen by 4% on potassium supplementation compared with placebo. Urinary potassium excretion increased from 62 +/- 4.7 mmol/24 h on placebo to 118 +/- 7.4 mmol/24 h on potassium. The fall in blood pressure was not related to urinary sodium excretion before entry to the trial or while on placebo. Moderate potassium supplementation caused a small but significant fall in blood pressure in patients with mild to moderate essential hypertension and could be additive to the effects of moderate sodium restriction. This increase in potassium intake could be achieved with a potassium-based salt substitute and a moderate increase in vegetable and fruit consumption. Moderate dietary sodium restriction with dietary potassium supplementation may obviate or reduce the need for drug treatment in some patients with mild to moderate hypertension.

Adult↗

PubMed1996

One-year follow-up results of photorefractive keratectomy for low, moderate, and high primary astigmatism.

OBJECTIVE: To study the efficacy of excimer laser photorefractive keratectomy (PRK) for high, moderate, and low degrees of primary myopic astigmatism. PATIENTS AND METHODS: Ninety-two eyes of 54 patients with different degrees of compound myopic astigmatism underwent PRK. The eyes were divided by degree of refractive astigmatism into three groups-high (-2.75 to -5.0 diopters [D]), moderate (-1.25 to -2.50 D), and low (< or = 1.0 D). Refraction, corneal topography, slit-lamp findings, and visual acuity with and without correction were assessed. RESULTS: At 12 months, the mean reduction from the preoperative refractive cylinder was 80.7% in the high astigmatism group, 68.4% in the moderate astigmatism group, and 47.6% in the low astigmatism group. The post-treatment residual cylinder axis remained stable in 23 (38.3%) of 60 eyes and deviated in 37 (61.7%) of 60 eyes. The maximal deviation of the residual cylinder axis was 15 degrees. Of the 89.2% of eyes with low cylinder, 81.8% had moderate cylinder, and 85% of the eyes with high cylinder achieved a final uncorrected visual acuity between 20/20 and 20/35 at 12 months. CONCLUSIONS: A statistically significant reduction in the refractive cylinder was found in the high, moderate, and low astigmatism groups. The difference between the mean reduction of the high and moderate cylinders compared with the mean reduction of the low cylinders also was found to be statistically significant. The laser used in this study is an efficient tool for correcting high and moderate astigmatism. However, regarding low astigmatism, it was found to be less effective.

Adult↗

PubMed2001

Moderate hypothermia during cardiopulmonary bypass reduces myocardial cell damage and myocardial cell death related to cardiac surgery.

OBJECTIVES: The goal of this study was to test the hypothesis that moderate hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance. BACKGROUND: Moderate hypothermia during experimental CPB stimulates production of interleukin-10 (IL10) and blunts release of tumor necrosis factor-alpha (TNFalpha). METHODS: Twelve young pigs were assigned to a temperature (T degrees ) regimen during CPB: moderate hypothermia (T degrees : 28 degrees C; n = 6) and normothermia (T degrees : 37 degrees C; n = 6). Intra-myocardial TNFalpha- and IL10-messenger RNA were detected by competitive reverse transcriptase polymerase chain reaction and quantification of cytokine synthesis by Western blot. Levels of cardiac troponin I (cTnI) in cardiac lymph and in arterial and coronary venous blood were examined during and after CPB. Myocardial cell damage was assessed by histologic and ultrastructural anomalies of tissue probes taken 6 h after CPB. RESULTS: Synthesis of IL10 was significantly higher, while that of TNFalpha was significantly lower, in pigs that were in moderate hypothermia during surgery than in the others. In contrast with normothermia, moderate hypothermia was also associated with significantly lower cumulative cardiac lymphatic flow during and after CPB, significantly lower lymphatic cTnI concentrations after CPB, significantly lower percentages of myocardial cell necrosis and a significantly lower score of ultrastructural anomalies of myocardial cells. While the percentage of apoptotic cells was not different between groups, the apoptosis/necrosis ratio tended to be higher in animals that were in moderate hypothermia during surgery. In all animals, TNFalpha synthesis correlated positively while IL10 production correlated negatively with necrosis and total cell death, respectively. CONCLUSIONS: Our results suggest that moderate hypothermia during CPB provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance.

Animals↗

PubMed1996

The effects of overfeeding and moderate dietary restriction on Sprague-Dawley rat survival, pathology, carcinogenicity, and the toxicity of pharmaceutical agents.

Ad libitum (AL) overfeeding is the most significant uncontrolled variable effecting the rodent bioassay. There is a highly significant correlation between food consumption, the resultant body weight, and two-year survival in laboratory rats. We have studied the effects of AL overfeeding, moderate dietary restriction (DR) and several modified diets on Sprague-Dawley (SD) rat longevity, spontaneous disease, carcinogenesis and the toxicity of pharmaceuticals. AL feeding of diets varying in protein, fiber and metabolizable energy content did not significantly alter two-year rat survival. Moderate DR (within the range of reported AL food intake) of all diets tested significantly improved survival and delayed the onset of spontaneous degenerative disease and diet-related tumors compared to AL-fed rats. Moderate DR resulted in a similar incidence of spontaneous tumors by 2 years, however, the tumors were more likely to be incidental and not result in early mortality. There was a decreased, age-adjusted incidence of pituitary and mammary gland tumors, but tumor volume and growth time was similar between AL and DR groups indicating similar tumor progression with a delay in tumor onset. Moderate DR did not change Phase I and Phase II drug metabolizing enzyme levels and did not significantly alter the toxicological response to 5 pharmaceuticals tested at maximum tolerated doses (MTDs). Additional studies with 4 pharmaceutical candidates did demonstrate that moderate DR allowed higher doses of compounds to be given before classical MTDs were observed. However, toxicokinetic studies of two of these compounds demonstrated steady state systemic exposures that were either equal of higher in the moderate DR fed rats. These and other data indicate that the moderate DR fed SD rat is a more appropriately controlled rodent model for toxicity and carcinogenicity studies to assess human safety of candidate pharmaceuticals.

Animals↗

PubMed2002

Prevalence of moderate penicillin resistant invasive Neisseria meningitidis infection in Scotland, 1994-9.

We examined the serological characteristics of 774 invasive meningococcal isolates collected through an active laboratory-based surveillance system in Scotland from 1994 to 1999. Of these, 72-73% of isolates were tested for susceptibility to several antimicrobial agents. Meningococci with high-level resistance to sulphadiazine had a prevalence of 10% and incidence of 0.22 per 100,000 population. High-level resistance to penicillin and other antibiotics was not detected. The prevalence of moderate penicillin resistant meningococci was 8.3%. There was no increase in moderate penicillin resistant meningococcal isolates during the study period, but there were temporal and geographic variations. The estimated incidence of moderate penicillin resistant meningococci was 0.15 per 100,000 population. High and low incidence of moderate penicillin resistant meningococci appeared to correlate with the number of doses of penicillin prescribed in some geographic locations. The majority of moderate penicillin resistant isolates belonged to serogroups B (52.2%) and C (39.2%). However, the prevalence of moderate penicillin resistance in serogroup W135 was substantially higher (51.7%) than serogroups B (7.8%) and C (7.6%). Serogroup W135 accounted for a higher proportion of moderate penicillin resistance (8.7%) than disease (1%). There was no predominant penicillin resistant serotype/subtype within any serogroup. Constant surveillance is necessary to monitor the emergence and spread of resistance and to guide appropriate public health interventions in preventing drug resistant meningococci.

Humans↗

PubMed2002

Preoperative predictors of moderate to intense acute postoperative pain in patients undergoing abdominal surgery.

BACKGROUND: Pain is a sensory and emotional experience that is influenced by physiologic, sensory, affective, cognitive, socio-cultural, and behavioral factors. Consistent with the perspective to improve the postoperative pain control, the present study has the purpose of assessing the effect of presurgical clinical factors, psychological and demographic characteristics as predictors for reporting moderate to intense acute postoperative pain. METHODS: A prospective cohort study was performed with 346 inpatients undergoing abdominal elective surgery (ASA physical status I-III, age range 18-60 years). The measuring instruments were Pain Visual Analog Scale, the State-Trait Anxiety Inventory, and the Montgomery-Asberg Depression Rating Scale. Multivariate conditional regression modeling was used to determine independent predictors for moderate to intense acute postoperative pain. RESULTS: Moderate to intense acute postoperative pain was associated with status ASA III (odds ratio (OR) = 1.99), age (OR = 4.72), preoperative moderate to intense pain (OR = 2.96), chronic pain (OR = 1.75), high trait-anxiety and depressive mood moderate to intense (OR = 1.74 and OR = 2.00, respectively). Patients undergoing surgery to treat cancer presented lower risk for reporting moderate to intense pain OR = 0.39, as well as those that received the epidural analgesia and multimodal analgesia with systemic opioid (OR = 0.09 and OR = 0.16, respectively). CONCLUSIONS: The identification of predictive factors for intense acute postoperative pain may be useful for designing specific preventive interventions to relieve patient suffering. Especially because few of these variables are accessible for medical intervention, which would improve the clinical outcomes and quality of life of patients at risk of moderate to intense acute postoperative pain.

Abdomen↗

PubMed1990

Conjunctive moderator variables in vulnerability and resiliency research: life stress, social support and coping skills, and adolescent sport injuries.

In life event research relating to vulnerability and resilience factors, single moderator variables have typically been the focus of study. Little is known about the ways in which moderator variables may interact with one another to increase vulnerability or resilience. We propose a distinction between conjunctive moderation, in which multiple moderators must co-occur in a specific combination or pattern to maximize a relation between a predictor and an outcome variable, and disjunctive moderation, in which any one of a number of moderators maximizes the predictor-criterion relation. Our results indicate that social support and psychological coping skills are statistically independent psychosocial resources and that they operate in a conjunctive manner to influence the relation between life stress and subsequent athletic injury in adolescents. Only athletes low in both coping skills and social support exhibited a significant stress-injury relation, and in that vulnerable subgroup, negative major life events accounted for up to 30% of the injury variance. Methodological considerations in the assessment of conjunctive moderator effects are discussed.

Adaptation, Psychological↗

PubMed1998

The retinoblastoma protein-associated cell cycle arrest in S-phase under moderate hypoxia is disrupted in cells expressing HPV18 E7 oncoprotein.

We have studied the role of the oxygen-dependent pyrimidine metabolism in the regulation of cell cycle progression under moderate hypoxia in human cell lines containing functional (T-47D) or non-functional (NHIK 3025, SAOS-2) retinoblastoma gene product (pRB). Under aerobic conditions, pRB exerts its growth-regulatory effects during early G1 phase of the cell cycle, when all pRB present has been assumed to be in the underphosphorylated form and bound in the nucleus. We demonstrate that pRB is dephosphorylated and re-bound in the nucleus in approximately 90% of T-47D cells located in S and G2 phases under moderately hypoxic conditions. Under these conditions, no T-47D cells entered S-phase, and no progression through S-phase was observed. Progression of cells through G2 and mitosis seems independent of their functional pRB status. The p21WAF1/CIP1 protein level was significantly reduced by moderate hypoxia in p53-deficient T-47D cells, whereas p16(INK4a) was not expressed in these cells, suggesting that the hypoxia-induced cell cycle arrest is independent of these cyclin-dependent kinase inhibitors. The addition of pyrimidine deoxynucleosides did not release T-47D cells, containing mainly underphosphorylated pRB, from the cell cycle arrest induced by moderate hypoxia. However, NHIK 3025 cells, in which pRB is abrogated by expression of the HPV18 E7 oncoprotein, and SAOS-2 cells, which lack pRB expression, continued cell cycle progression under moderate hypoxia provided that excess pyrimidine deoxynucleosides were present. NHIK 3025 cells express high levels of p16INK4a under both aerobic and moderately hypoxic conditions, suggesting that the inhibitory function of p16(INK4a) would not be manifested in such pRB-deficient cells. Thus, pRB, a key member of the cell cycle checkpoint network, seems to play a major role by inducing growth arrest under moderate hypoxia, and it gradually overrides hypoxia-induced suppression of pyrimidine metabolism in the regulation of progression through S-phase under such conditions.

Aerobiosis↗

PubMed2001

A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.

CONTEXT: Long-term success in weight loss with dietary treatment has been elusive. OBJECTIVE: To evaluate a diet moderate in fat based on the Mediterranean diet compared to a standard low-fat diet for weight loss when both were controlled for energy. DESIGN: A randomized, prospective 18 month trial in a free-living population. PATIENTS: A total of 101 overweight men and women (26.5-46 kg/m(2)). INTERVENTION: (1) Moderate-fat diet (35% of energy); (2) low-fat diet (20% of energy). MAIN OUTCOME MEASUREMENTS: Change in body weight. RESULTS: After 18 months, 31/50 subjects in the moderate-fat group, and 30/51 in the low fat group were available for measurements. In the moderate-fat group, there were mean decreases in body weight of 4.1 kg, body mass index of 1.6 kg/m(2), and waist circumference of 6.9 cm, compared to increases in the low-fat group of 2.9 kg, 1.4 kg/m(2) and 2.6 cm, respectively; P < or = 0.001 between the groups. The difference in weight change between the groups was 7.0 kg. (95% CI 5.3, 8.7). Only 20% (10/51) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54% (27/50) in the moderate-fat group, (P<0.002). The moderate-fat diet group was continued for an additional year. The mean weight loss after 30 months compared to baseline was 3.5 kg (n = 19, P = 0.03). CONCLUSIONS: A moderate-fat, Mediterranean-style diet, controlled in energy, offers an alternative to a low-fat diet with superior long-term participation and adherence, with consequent improvements in weight loss.

Adult↗

PubMed2007

The impact of reclassifying moderate CKD as a coronary heart disease risk equivalent on the number of US adults recommended lipid-lowering treatment.

BACKGROUND: The Third National Cholesterol Education Program Adult Treatment Panel (ATP-III) guidelines recommend consideration of lipid-lowering therapy at lower low-density lipoprotein cholesterol levels (>or=100 mg/dL [>or=2.59 mmol/L]) for adults with coronary heart disease risk equivalents. Chronic kidney disease is associated with increased coronary heart disease risk but is not included as a risk equivalent in these guidelines. METHODS: The impact of including moderate chronic kidney disease (estimated glomerular filtration rate, 30 to 59 mL/min/1.73 m(2) [0.50 to 0.98 mL/s]) as a coronary heart disease risk equivalent on the percentage and number of US adults with chronic kidney disease recommended lipid-lowering therapy was estimated by using data from the Third National Health and Nutrition Examination Survey. RESULTS: Of adults with moderate chronic kidney disease, 53.0% had a history of coronary heart disease or a risk equivalent, 24.7% reported a history of myocardial infarction or stroke, 17.7% had diabetes, 9.6% had angina, and 26.9% had a 10-year coronary heart disease risk greater than 20%. Using current ATP-III guidelines, lipid-lowering therapy is recommended for 61.4% of adults with moderate chronic kidney disease. If moderate chronic kidney disease was reclassified as a coronary heart disease risk equivalent, this percentage would increase to 87.7%, representing an increase in number of adults with moderate chronic kidney disease recommended lipid-lowering treatment from 4.5 to 6.5 million adults. CONCLUSION: This analysis shows that a majority of adults with moderate chronic kidney disease have coronary heart disease or risk equivalents. Nonetheless, a substantially greater proportion of US adults with moderate chronic kidney disease would be recommended lipid-lowering therapy through its reclassification as a coronary heart disease risk equivalent.

Aged↗

PubMed2006

Effective dose of escitalopram in moderate versus severe DSM-IV major depression.

INTRODUCTION: Data from the three available placebo-controlled trials with fixed doses of escitalopram in the acute therapy of DSM-IV major depressive disorder (MDD) were pooled. The hypothesis tested was that escitalopram 10 mg/d might be an effective dose in moderate MDD, whereas escitalopram 20 mg/d might be needed in severe depression. METHODS: The Montgomery-Asberg Depression Scale with all 10 items was used at baseline to differentiate between moderate (score range 22 to 29) and severe (scores > or = 30) major depression. The MADRS (6) was selected as the primary efficacy parameter, using a standardised effect size of 0.40 as indicator of clinically significant response. RESULTS: After 8 weeks of therapy, escitalopram 10 mg was superior to placebo, with a standardised effect size above 0.40 for patients with moderate depression, but not for those with severe depression. In contrast, 20 mg escitalopram was superior to placebo, with a standardised effect size above 0.40 in severe depression, but not in moderate depression. The MADRS (6) showed response (standardised effect sizes above 0.40) for moderate depression after two weeks of treatment with 10 mg escitalopram and in severely depressed patients after 4 weeks with 20 mg escitalopram. CONCLUSION: Escitalopram 10 mg/d was the optimal dose for the treatment of moderate DSM-IV MDD, while escitalopram 20 mg/d was an effective dose in patients with moderate to severe depression.

Antidepressive Agents, Second-Generation↗

PubMed1984

[Medium-dose oral cyproterone acetate therapy in women with moderate androgenization. Results of a multicenter double-blind study].

The low-dose oral standard antiandrogen treatment with cyproterone acetate (CPA), Diane, is frequently associated with unsatisfactory results regarding moderate to severe seborrhoea/acne/acne and/or mild to moderate hirsutism. This multicenter double-blind study (n = 164) was, therefore, initiated to analyze the effectiveness of a medium dose oral regimen, i.e. the addition of 10 mg of CPA during the first 15 days of the Diane-treatment cycle. Good or satisfactory results after 3, 6, 9 and 12 months were observed in 61, 81, 95 and 97% of patients with moderate to severe seborrhoea (n = 79); in 53, 95, 98 and 100% of patients with moderate to severe acne (n = 62); and in 10, 28, 45 and 55% of patients with mild to moderate hirsutism (n = 89), respectively. The regression of moderate facial hirsutism and severe facial acne occurred faster and was more complete under the medium-dose than with the low-dose regimen. Side effects corresponded to those of conventional oral contraceptives except for a higher frequency of mastodynia. Both regimens caused a significant suppression of plasma dehydroepiandrosterone sulfate, while testosterone, triiodothyronine and thyroxine were lowered insignificantly. In contrast, cortisol, prolactin and insulin increased significantly. The extent of these changes did not differ in both modes of treatment. The medium-dose regimen (total dosage per cycle: 192 mg of CPA) is more effective than the low-dose regimen (42 mg of CPA per cycle) in the treatment of patients with moderate hyperandrogenism who do not require the high-dose oral standard antiandrogen therapy (1000 mg of CP A per cycle).

Acne Vulgaris↗

PubMed1998

Effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia on cerebral blood flow and metabolism, lactate, and extracellular glutamate in experimental head injury.

The effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia were investigated to determine which temperature was more effective against compression-induced cerebral ischemia. Eighteen cats were anesthetized. The animals were divided into three groups according to deep-brain temperature (control, 37 degrees C; mild hypothermia, 33 degrees C; and moderate hypothermia, 29 degrees C). Intracranial pressure (ICP) and cerebral blood flow (CBF) were monitored, the latter by hydrogen clearance. Arteriovenous oxygen difference (AVDO2) and cerebral venous oxygen saturation (ScvO2) were measured in blood samples from the superior sagittal sinus. The cerebral metabolic rate of oxygen (CMRO2) and the cerebral metabolic rate of lactate (CMR lactate) were calculated. Extracellular glutamate was measured by microdialysis. ICP was increased by inflation of an epidural balloon until CBF became zero, and this ischemia was maintained for 5 min, after which the balloon was quickly deflated. All parameters were recorded over 6 h. Evans blue was injected to examine vascular permeability changes. CBF was decreased by 56% by mild hypothermia and by 77% by moderate hypothermia. Mild hypothermia had a coupled metabolic suppression whereas moderate hypothermia significantly increased AVDO2 and decreased ScvO2, producing a low CBF/CMRO2 (relative ischemia). After balloon deflation, all three groups showed reactive hyperemia, which was significantly reduced by mild and moderate hypothermia. CBF then decreased to 50% of pre-inflation values and ScvO2 decreased (post-ischemic hypoperfusion). CBF/CMRO2, ScvO2, and AVDO2 did not differ significantly between the three groups. After balloon deflation, all three groups showed increased CMR lactate, which was significantly reduced by mild and moderate hypothermia. Extracellular glutamate increased in control animals (3.8 +/- 1.72 microM), an effect most effectively suppressed in the mild hypothermia group (1.0 +/- 0.46 microM). Damaged tissue volumes as indicated by Evans blue dye extravasation were 729 +/- 89 mm3 in control, 247 +/- 56 mm3 in mild hypothermia, and 267 +/- 35 mm3 in moderate hypothermia animals. These data suggest that mild hypothermia (33 degrees C) might be the optimal brain temperature to treat compression-related cerebral ischemia.

Animals↗

PubMed2000

The health effects of moderate alcohol intake in humans: an epidemiologic review.

A large body of scientific evidence associates the moderate intake of alcohol with reduced mortality among middle-aged and older people in industrialized societies. This association is due largely to a reduced risk of death from coronary heart disease, which appears to outweigh any possible adverse effects of moderate drinking. The regular consumption of small amounts of alcohol is more healthful than the sporadic consumption of larger amounts. No beneficial effect of moderate drinking on mortality has been demonstrated in young adults (premenopausal women and men who have not reached their forties). It is theoretically possible that moderate drinking in young adulthood might reduce the risk of later heart disease; however, this has not been clearly demonstrated. For some individuals (e.g., those who cannot keep their drinking moderate, pregnant women, and those who are taking medications that may interact adversely with alcoholic beverages), the risks of alcohol consumption, even in moderation, outweigh any potential benefits. Because even small amounts of alcohol can impair judgment and coordination, no one should drink alcoholic beverages, even in moderation, before driving a motor vehicle or performing other activities that involve attention and skill.

Alcohol Drinking↗