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PubMed1986

Evaluation of possible interactions between ethanol and trazodone or amitriptyline.

The pharmacodynamic effects of single doses of trazodone (100 mg), amitriptyline (50 mg) or placebo either alone or with ethanol (0.5 ml/kg) were investigated in 6 healthy volunteers in a double-blind crossover study. Plasma concentrations of the drugs and ethanol were also measured. Pharmacodynamic tests were critical flicker fusion frequency threshold (CFF), choice reaction time (CRT), manual dexterity, a digit span test and visual analogue scales. Blood ethanol concentrations were not influenced by the co-administration of either antidepressant. tmax for trazodone was prolonged by ethanol but the other pharmacokinetic parameters for trazodone and amitriptyline were not influenced by ethanol. Trazodone and amitriptyline caused the expected profound depressant effects on CFF, CRT, manual dexterity and on the rating scales for drowsiness, 'clearheadedness', aggression and disinhibition. Ethanol alone impaired manual dexterity, increased drowsiness, reduced 'clearheadedness' and also tended to reduce feelings of aggression. In combination with either trazodone or amitriptyline, ethanol caused little additional effect except in the case of manual dexterity, which was further impaired. This result may reflect the profound effects of the antidepressants alone and does not suggest that it is safe for patients receiving antidepressant medication to take ethanolic drinks.

Adult↗
PubMed1986

Abrupt change from propranolol to verapamil. Safety and feasibility in stable angina pectoris.

To study the safety and feasibility of abruptly changing antianginal therapy from propranolol hydrochloride to verapamil, we gave propranolol to ten patients with stable angina and coronary artery disease for 14 days, then, on day 15, we began verapamil therapy, which continued for 14 more days. Anginal frequency and nitroglycerin use were similar throughout the study. No patient had symptomatic bradycardia or atrioventricular block. Such crossover therapy is effective when propranolol is replaced by verapamil abruptly.

Angina Pectoris↗
PubMed1981

Double-blind, placebo-controlled, crossover trial of propranolol as treatment for menopausal vasomotor symptoms.

A trial of propranolol for the treatment of vasomotor symptoms was conducted among 37 menopausal women in a double-blind, placebo-controlled, crossover fashion. When compared with placebo, propranolol had a statistically significant effect on the reduction of both the frequency and severity of vasomotor symptoms (P less than 0.01). In selected patients, propranolol may be an alternative to the treatment of vasomotor symptoms with exogenous estrogens.

Adult↗
PubMed2001

A randomized, crossover comparison of standard-dose versus low-dose lenograstim in the prophylaxis of post-chemotherapy neutropenia.

The aim of this trial was to compare the severity of neutropenia, the frequency of hospital admission for fever or infection, and the use of antibiotics among patients treated with a standard dose of lenograstim (263 microg/day of Euprotin) and others treated with half of this dose (131.5 microg/day) and the cost-effectiveness of each of the two doses. In this single-center study, 44 patients with solid tumors, who were all receiving standard-dose chemotherapy regimens following previous neutropenia or were at high risk of neutropenia, were randomized to receive lenograstim at a dose of 263 microg or 131.5 microg daily in the first cycle and then crossed over to the alternate dose for the following cycle. Crossover to the alternate dose was repeated for patients who received more than two cycles. Lenograstim was administered from day +5 to day +14. The absolute neutrophil count (ANC) was assessed on days +5, +8, +12 and +15 of each cycle. Statistical analysis was performed using a general lineal model for repeated samples. In all, 120 cycles were administered, with a median of 3 cycles (range 1-6). Only 4 patients received only 1 cycle. No statistically significant difference (P=0.324) in ANC was observed between standard-dose (mean 5.3, 10.7, 8.3, 11.4 x 10(9)/l) and low-dose (5.0, 8.6, 5.4, 7.5 x 10(9)/l) treatment at days +5, +8, +12 and + 15. Neutropenia grade III-IV was more common in patients receiving the low than in those receiving the standard dose of lenograstim (20% vs 12%, respectively), but the difference did not reach statistical significance (P=0.1). The incidence of fever and frequency of hospital admission were not affected by the dose of lenograstim: 3 patients presented with fever with the standard dose (all of those were admitted to hospital) and 2 patients with the low dose (1 was admitted). ANC in both groups (standard and low doses) was independent of chemotherapy line (first versus second or more). Lenograstim at a dose of 131.5 microg/day is as effective as the standard dose in limiting the severity of neutropenia and in preventing episodes of fever and hospital admissions after chemotherapy for solid tumors. The lower dose of lenograstim is cost-effective in neutropenia prophylaxis. Starting its administration on day +5 reduces costs while maintaining efficacy.

Adjuvants, Immunologic↗
PubMed1998

The nature of human immunodeficiency virus type 1 strand transfers.

The diploid nature of human immunodeficiency virus type 1 (HIV-1) suggests that recombination serves a central function in virus replication and evolution. A system was developed to examine HIV-1 strand transfers, including the obligatory DNA primer strand transfers as well as recombinational crossovers during reverse transcription. Sequence heterogeneity between different strains of HIV-1 was exploited for examining primer transfer events. Both intra- and intermolecular primer transfers were observed at similar frequencies during minus-strand DNA synthesis, whereas primer transfers during plus-strand DNA synthesis were primarily intramolecular. Sequence analysis of long terminal repeats from progeny proviruses also revealed a high rate of homologous recombination during minus-strand synthesis, corresponding to an overall rate of approximately three crossovers per HIV-1 genome per cycle of replication. These results imply that both viral genomic RNAs serve as templates during HIV-1 reverse transcription and that primer strand transfers and recombination may contribute substantially to the rapid genetic variation of HIV-1.

Base Sequence↗
PubMed2001

High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral cortex: EEG topography during waking and subsequent sleep.

Repetitive transcranial magnetic stimulation (rTMS) is a novel research tool in neurology and psychiatry. It is currently being evaluated as a conceivable alternative to electroconvulsive therapy for the treatment of mood disorders. Eight healthy young (age range 21-25 years) right-handed men without sleep complaints participated in the study. Two sessions at a 1-week interval, each consisting of an adaptation night (sham stimulation) and an experimental night (rTMS in the left dorsolateral prefrontal cortex or sham stimulation; crossover design), were scheduled. In each subject, 40 trains of 2-s duration of rTMS (inter-train interval 28 s) were applied at a frequency of 20 Hz (i.e. 1600 pulses per session) and at an intensity of 90% of the motor threshold. Stimulations were scheduled 80 min before lights off. The waking EEG was recorded for 10-min intervals approximately 30 min prior to and after the 20-min stimulations, and polysomnographic recordings were obtained during the subsequent sleep episode (23.00-07.00 h). The power spectra of two referential derivations, as well as of bipolar derivations along the antero-posterior axis over the left and right hemispheres, were analyzed. rTMS induced a small reduction of sleep stage 1 (in min and percentage of total sleep time) over the whole night and a small enhancement of sleep stage 4 during the first non-REM sleep episode. Other sleep variables were not affected. rTMS of the left dorsolateral cortex did not alter the topography of EEG power spectra in waking following stimulation, in the all-night sleep EEG, or during the first non-REM sleep episode. Our results indicate that a single session of rTMS using parameters like those used in depression treatment protocols has no detectable side effects with respect to sleep in young healthy males.

Adult↗
PubMed2004

A role for the MutL homologue MLH2 in controlling heteroduplex formation and in regulating between two different crossover pathways in budding yeast.

BACKGROUND AND AIMS: Mismatch repair proteins play important roles during meiotic recombination in the budding yeast Saccharomyces cerevisiae and most eukaryotic organisms studied to date. To study the functions of the mismatch repair protein Mlh2p in meiosis, we constructed mlh2Delta strains and measured rates of crossing over, gene conversion, post-meiotic segregation and spore viability. We also analysed mlh1Delta, mlh3Delta, msh4Delta, msh5Delta, exo1Delta and mus81Delta mutant strains singularly and in various combinations. RESULTS: Loss of MLH2 resulted in a small but significant decrease in spore viability and a significant increase in gene conversion frequencies but had no apparent effect on crossing over. Deletion of MLH2 in mlh3Delta, msh4Delta or msh5Delta strains resulted in significant proportion of the "lost" crossovers found in single deletion strains being regained in some genetic intervals. We and others propose that there are at least two pathways to generate crossovers in yeast (Ross-Macdonald and Roeder, 1994; Zalevsky et al., 1999; Khazanehdari and Borts, 2000; Novak et al., 2001; de los Santos et al., 2003). Most recombination intermediates are processed by the "major", Msh4-dependent pathway, which requires the activity of Mlh1p/Mlh3p/Msh4p/Msh5p as well as a number of other proteins. The minor pathway(s) utilizes Mms4p/Mus81p. We suggest that the absence of Mlh2p allows some crossovers from the MSH4 pathway to traverse the MUS81-dependent pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1983

Specific mismatch correction in bacteriophage lambda crosses by very short patch repair.

In crosses under rec+, red+, gam+ conditions, mutation am6 in the cI (repressor) gene of bacteriophage lambda recombines with other cI mutations much more frequently than predicted by the physical distances involved. In four-factor crosses of am6 with mutations located 22-60 base pairs to the left, cI+ recombinants that are expected to require three crossovers (triple recombinants) are more frequent than recombinants that require only one crossover. However, when am6 is crossed with large insertions in cI, which may be expected to interfere with the formation of heteroduplexes by branch migration, the frequency of cI+ triple recombinants is very low. In addition, cI+ recombinants in crosses between am6 and adjacent mutations have a high probability of retaining the flanking markers of the am6 parent. These findings suggest that am6 is particularly susceptible to mismatch repair in heteroduplexes spanning cI. A large fraction of such heteroduplexes are presumed to be the result of branch migration from crossovers occurring at some distance from am6. The absence of co-repair when am6 is crossed with adjacent cI mutations indicates that most repair tracts extend no farther than about 20 bp to either side of the mismatch. The am6 mutation arose in the glutamine codon in a CCAGG sequence, in which the central cytosines are methylated in K12 strains. Their location in methylated sequences may make certain amber mutations susceptible to a specific very short patch (VSP) repair.

Bacteriophage lambda↗
PubMed2003

High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking.

BACKGROUND: The mesolimbic dopaminergic reward system seems to play a crucial role in reinforcing effects of nicotine. Recently, acute high-frequency repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions has been shown to efficiently modulate the mesostriatal and mesolimbic dopaminergic system in both animals and humans. For this reason, we investigated whether high-frequency rTMS would be able to influence nicotine-related behavior by studying rTMS effects on craving and cigarette smoking. METHOD: Fourteen treatment-seeking smokers were included in a double-blind crossover trial, conducted in 2002, comparing single days of active versus sham stimulation. Outcome measures were rTMS effects on number of cigarettes smoked during an ad libitum smoking period and effects on craving after a period of acute abstinence. RESULTS: High-frequency (20-Hz) rTMS of left dorsolateral prefrontal cortex reduced cigarette smoking significantly (p <.01) in an active stimulation compared with sham stimulation. Levels of craving did not change significantly. CONCLUSION: High-frequency rTMS may be useful for treatment in smoking cessation.

Adult↗
PubMed2006

Effect of scraping frequency in a freestall barn on volatile nitrogen loss from dairy manure.

The objective of this investigation was to evaluate the effect of scraping frequency (2x vs. 6x daily) on N volatilization from manure on the floor of a dairy free-stall barn. Three trials (crossover design) were conducted in the summers of 2001 and 2002, and in the winter of 2003. Nitrogen volatilization was estimated from the change in the N:P ratio in excreta at the time of excretion to the time when manure was scraped from the barn. Total N loss was considered a maximum estimate of NH3-N loss, because small amounts of nonammonia N may be volatilized. Nitrogen was determined after manure subsamples were lyophilized; P content was measured by direct current emission spectroscopy of ashed subsamples of manure. Lactating dairy cows were fed high-protein (18.5 to 19.3% crude protein), alfalfa-based diets. Average milk yield was 31.9 (SD = 7.4) kg/d. Scraping frequency had no effect on N loss in summer 2001. An average of 41% of excreted N, or 238 +/- 19.0 g of N/d per cow, was volatilized. For the trial in summer 2002, nitrogen volatilization was reduced from 50% of the excreted N with 2x to 46.7% with 6x, equivalent to 265 and 248 g of N lost/d per cow, respectively. Scraping had no effect on N volatilization during the winter trial. An average of 17.7% of excreted N was volatilized during the winter, equivalent to 109 +/- 11.0 g of N lost/d per cow. Scraping frequency of manure had little or no effect on N loss from manure in a freestall barn. Nitrogen loss during the winter was less than half of the loss during the summer.

Air Pollutants↗
PubMed1994

Effect of acute magnesium administration on the frequency of ventricular arrhythmia in patients with heart failure.

BACKGROUND: There is a high incidence of ventricular arrhythmia and sudden death in patients with heart failure. Unfortunately, currently available antiarrhythmic agents have only limited efficacy and may result in proarrhythmia and hemodynamic deterioration in these patients. METHODS AND RESULTS: We studied the acute effect of intravenous magnesium chloride on the frequency and severity of ventricular arrhythmia in 30 patients with symptomatic heart failure using a double-blind, placebo-controlled crossover design. The left ventricular ejection fraction was 23.0 +/- 8.0% (mean +/- SD). No patient had a history of symptomatic ventricular arrhythmia or was receiving antiarrhythmic agents, calcium channel antagonists, or beta-blockers. Patients were randomized to receive placebo (5% dextrose [D5W] in water alone) or magnesium chloride in D5W given as a bolus of 0.3 mEq/kg over 10 minutes followed by a maintenance infusion of 0.08 mEq/kg per hour for 24 hours. The magnesium concentrations 30 minutes and 24 hours after the bolus were 3.6 +/- 0.1 and 4.2 +/- 0.1 mg/dL, respectively. There was no significant change in serum potassium concentration during magnesium administration. Blinded analysis revealed that administration of intravenous magnesium chloride, compared with placebo, significantly decreased total ventricular ectopy per hour (mean +/- SEM, 70 +/- 26 versus 149 +/- 64, P < .001), couplets per day (23 +/- 11 versus 94 +/- 59, P = .007), and episodes of ventricular tachycardia per day (0.8 +/- 0.2 versus 2.6 +/- 1.0, P = .051). CONCLUSIONS: Intravenous magnesium chloride administration reduces the frequency of ventricular arrhythmia in patients with symptomatic heart failure.

Adult↗
PubMed1999

Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism.

BACKGROUND: Recent studies suggest that both high frequency (10-20 Hz) and low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) have an antidepressant effect in some individuals. Electrophysiologic data indicate that high frequency rTMS enhances neuronal firing efficacy and that low frequency rTMS has the opposite effect. METHODS: We investigated the antidepressant effects of 10 daily left prefrontal 1 Hz versus 20 Hz rTMS with the hypothesis that within a given subject, antidepressant response would differ by frequency and vary as a function of baseline cerebral glucose metabolism. After baseline PET scans utilizing [18F]-Fluorodeoxyglucose, thirteen subjects participated in a randomized crossover trial of 2 weeks of 20 Hz paired with 2 weeks 1 Hz or placebo rTMS. RESULTS: We found a negative correlation between degree of antidepressant response after 1 Hz compared to 20 Hz rTMS (r = -0.797, p < .004). Additionally, better response to 20 Hz was associated with the degree of baseline hypometabolism, whereas response to 1 Hz rTMS tended to be associated with baseline hypermetabolism. CONCLUSIONS: These preliminary results suggest that antidepressant response to rTMS might vary as a function of stimulation frequency and may depend on pretreatment cerebral metabolism. Further studies combining rTMS and functional neuroimaging are needed.

Adult↗
PubMed2004

Decreased thermic effect of food after an irregular compared with a regular meal pattern in healthy lean women.

OBJECTIVES: To investigate the impact of irregular meal frequency on body weight, energy intake, appetite and resting energy expenditure in healthy lean women. DESIGN: Nine healthy lean women aged 18-42 y participated in a randomised crossover trial consisting of three phases over a total of 43 days. Subjects attended the laboratory at the start and end of phases 1 and 3. In Phase 1 (14 days), subjects were asked to consume similar things as normal, but either on 6 occasions per day (regular meal pattern) or follow a variable predetermined meal frequency (between 3 and 9 meals/day) with the same total number of meals over the week. In Phase 2 (14 days), subjects continued their normal diet as a wash-out period. In Phase 3 (14 days), subjects followed the alternative meal pattern to that followed in Phase 1. Subjects recorded their food intake for three predetermined days during the irregular period when they were eating 9, 3 and 6 meals/day. They also recorded their food intake on the corresponding days during the regular meal pattern period. Subjects fasted overnight prior to each laboratory visit, at which fasting resting metabolic rate (RMR) was measured by open-circuit indirect calorimetry. Postprandial metabolic rate was then measured for 3 h after the consumption of a milkshake test meal (50% CHO, 15% protein and 35% fat of energy content). Subjects rated appetite before and after the test meal. RESULTS: There were no significant differences in body weight and 3-day mean energy intake between the regular and irregular meal pattern. In the irregular period, the mean energy intake on the day when 9 meals were eaten was significantly greater than when 6 or 3 meals were consumed (P=0.0001). There was no significant difference between the 3 days of the regular meal pattern. Subjective appetite measurement showed no significant differences before and after the test meal in all visits. Fasting RMR showed no significant differences over the experiment. The overall thermic effect of food (TEF) over the 3 h after the test meal was significantly lower after the irregular meal pattern (P=0.003). CONCLUSION: Irregular meal frequency led to a lower postprandial energy expenditure compared with the regular meal frequency, while the mean energy intake was not significantly different between the two. The reduced TEF with the irregular meal frequency may lead to weight gain in the long term.

Adolescent↗
PubMed1995

Gene-centromere mapping of bovine DYA, DRB3, and PRL using secondary oocytes and first polar bodies: evidence for four-strand double crossovers between DYA and DRB3.

A genetic map consisting of three loci anchored at the centromere of bovine chromosome 23 was constructed by genotyping secondary oocytes (SO) and first polar bodies (PB1) using a polymerase chain reaction (PCR)-based approach. Primary oocytes arrested in prophase of meiosis I were stimulated in vitro to resume division and extrude PB1. Sixty SO and their matched PB1 were collected from 14 cows by micro-manipulation, subjected to amplification of the whole genome by primer extension preamplification, and genotyped independently for the linked genes PRL, DRB3, and DYA by PCR-RFLP analysis. Single-locus analysis of gene-centromere recombination rates were theta cen-DYA = 0.042, theta cen-DRB3 = 0.113, and theta cen-PRL = 0.166. The most likely order is cen-DYA-DRB3-PRL. Analysis of typing data from 3 cows revealed three meiotic divisions consistent with "linkage phase exchange" between DYA and DRB3 or PRL. One of the three linkage phase exchanges was confirmed by complementary genotypes in a matched secondary oocyte-first polar body pair. Such linkage phase exchanges could result from four-strand double crossovers between homologous chromosomes. Because all four gametes produced by four-strand double crossovers will be recombinant, more frequent occurrence of such events in females may explain the sexual dimorphism in genetic maps. Alternatively, four-strand crossovers could represent a type of recombination hotspot between DYA and DRB3, suggesting a mechanism for the high recombination frequency (15%) between these two class II genes of the bovine major histocompatibility complex.

Animals↗
PubMed1982

Synaptonemal complex analysis of mouse chromosomal rearrangements. IV. Synapsis and synaptic adjustment in two paracentric inversions.

Two paracentric inversions in the mouse, In (1) 1 Rk and In (2) 5 Rk, have been studied in surface microspreads of spermatocytes from heterozygotes. At zytogene, synaptic initiation occurs independently in three regions: within the inversion, and without, on either side. Synaptonemal complex (SC) formation is restricted to homologous regions, resulting in inversion loops in all early pachytene spermatocytes. An adjusting phase then occurs during pachytene in which the inversion loop is reduced by desynapsis of homologously synapsed SC, followed immediately by non-homologous synapsis with the alternate pairing partner, progressing from the ends toward the middle. Adjustment occurs during the first half of pachytene, but is not closely synchronized with sub-stage. It is complete by late pachytene, the loop having been eliminated in all cases and replaced by "straight" SCs in which the inverted region is heterosynapsis. Synapsis in the adjustment phase is evidently permitted only after the homosynaptic phase, and is indifferent to homology. It may lead to hetersynapsis, as in the inversion region, or to synapsis of homologous regions not synapsed at zytogene. The anaphase bridge frequency, a measure of crossing over within the inversion, is about 34% for both inversions studied, indicating that such crossovers do not block adjustment, that crossing over probably occurs before or during the adjustment period, and that there is some crossover suppression. The last could be the consequence of blocking by desynapsis/heterosynapsis. Synaptic adjustment appears to be a general phenomenon that occurs to varying extents in different forms. A hypothetical scheme for two phases of synapsis is proposed: at zytogene, a basic propensity for indifferent SC formation is limited by a restricting condition to synapsis between homologous regions, Subsequently, the restriction is lifted, whereupon synaptic instability is resolved by desynapsis, followed by resynapsis that is indifferent to homology, but that results in a topologically more stable structure.

Animals↗
PubMed2001

Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested cohort crossover study.

BACKGROUND: Immunosuppressive treatments have been associated with an increased risk of skin cancer, especially in patients who have had organ transplants. We aimed to assess the risk of skin cancer in patients taking the ciclosporin who had been exposed to psoralen and ultraviolet-A light (PUVA) and other treatments for severe psoriasis. METHODS: We did a nested cohort crossover study of 28 participants in the PUVA follow-up study who were on ciclosporin to compare the frequency of squamous-cell carcinoma before and after first use of ciclosporin. We also analysed the entire PUVA study cohort (1380) to assess the relation between use of this drug and frequency of squamous-cell carcinoma. FINDINGS: In the 5 years before first use, six of 28 (21%) ciclosporin users developed a total of 20 squamous cell cancers. After ciclosporin use (average follow-up 6 years), 13 (46%) developed a total of 169 squamous-cell carcinomas. In the nested cohort, after adjustment for amount of exposure to PUVA and methotrexate, incidence of tumours was seven times higher after first ciclosporin use than in the previous 5 years (incidence rate ratio 6.9 [95% CI 4.3-11]). Multivariate analysis of the entire cohort showed that risk of squamous-cell carcinoma after any use of ciclosporin is close to that recorded for at least 200 PUVA treatments (3.1 [2.6-3.7] and 2.8 [2.6-3.2], respectively). INTERPRETATION: The risk of squamous cell cancer of the skin is increased by ciclosporin in patients with psoriasis who have been exposed to PUVA. Such risks should be balanced against the effectiveness of the drug and possible newer immunosuppressive agents.

Carcinoma, Squamous Cell↗
PubMed2005

Scandium(III) catalysis of transimination reactions. Independent and constitutionally coupled reversible processes.

Sc(OTf)(3) efficiently catalyzes the self-sufficient transimination reaction between various types of C=N bonds in organic solvents, with turnover frequencies up to 3600 h(-)(1) and rate accelerations up to 6 x 10(5). The mechanism of the crossover reaction in mixtures of amines and imines is studied, comparing parallel individual reactions with coupled equilibria. The intrinsic kinetic parameters for isolated reactions cannot simply be added up when several components are mixed, and the behavior of the system agrees with the presence of a unique mediator that constitutes the core of a network of competing reactions. In mixed systems, every single amine or imine competes for the same central hub, in accordance with their binding affinity for the catalyst metal ion center. More generally, the study extends the basic principles of constitutional dynamic chemistry to interconnected chemical transformations and provides a step toward dynamic systems of increasing complexity.

Journal Article↗
PubMed2001

Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder.

The study was undertaken to determine the safety and efficacy of NIPRISAN, a phytomedicine, developed for the management of patients with Sickle Cell Disorder (SCD). The study design is a placebo-controlled double blind cross-over trial. Eighty-two (82) patients with SCD were recruited and randomised into two groups. An initial 4 month pre-trial study was undertaken to determine the similarity of the groups. The main study was conducted over a twelve-month period with crossover at six months. Safety of the drug was assessed clinically and biochemically. NIPRISAN significantly (P < 0.01) reduced the frequency of SCD crisis associated with severe pains. Acute toxicity to the liver assessed by the activities of liver enzymes, indicate that NIPRISAN is safe. Renal function assessed by the serum levels of creatinine and blood urea nitrogen remained normal. Both the clinical and laboratory results of the present phase IIB (pivot) clinical study suggest that NIPRISAN is a safe and efficacious phytomedicine for the management of patients with Sickle Cell Disorder.

Adolescent↗