Second Week Of Treatment Research Articles

The role of benzodiazepines in the treatment of insomnia: meta-analysis of benzodiazepine use in the treatment of insomnia.

The role of benzodiazepines in the treatment of insomnia: meta-analysis of benzodiazepine use in the treatment of insomnia.

G‐CSF induces elevation of circulating CA 15‐3 in breast carcinoma patients treated in an adjuvant setting

BACKGROUND Cancer antigen 15-3 (CA 15-3), a circulating marker that determines secreted products of the polymorphic MUC1 gene, has been established as a convenient tool for monitoring breast carcinoma patients. METHODS The authors investigated alterations of soluble CA 15-3 in 57 postoperative breast carcinoma patients while they were receiving intensified adjuvant chemotherapy with granulocyte colony stimulating factor (G-CSF) support; 26 patients had American Joint Committee on Cancer (AJCC) Stage II, and 31 patients had AJCC Stage III breast carcinoma. Serial CA 15-3 values recorded thoughout the treatment were compared with baseline values, analyzed for correlation with hematologic and biochemical parameters, and compared with clinicopathologic characteristics and patient outcome. At a median follow-up time of 32 months, 47 of these patients remained relapse-free. RESULTS A twofold increase of CA 15-3 was detected at the end of the second week of treatment, remained significantly elevated in most patients at above the cutoff level of 30 U/mL throughout the treatment period (P < 0.0001), and subsided to pretreatment values 1–2 months after treatment cessation. CA 15-3 values were found to be associated strongly with absolute neutrophil count, serum lactate dehydrogenase, and alkaline phosphatase. The median values and the kinetics of tumor markers did not differ over time in regard to hormonal receptor status and disease recurrence. CONCLUSIONS These data provide strong evidence that G-CSF administration can induce elevation of CA 15-3 and indicate that false-positive results should be considered when evaluating CA 15-3 in patients who are receiving G-CSF. It is speculated that this phenomenon occurs through the induction of MUC1 antigen of unknown origin by G-CSF. Experimental investigation of this clinical observation is warranted. Cancer 2001;91:909–17. © 2001 American Cancer Society.

G-CSF induces elevation of circulating CA 15-3 in breast carcinoma patients treated in an adjuvant setting

Cancer antigen 15-3 (CA 15-3), a circulating marker that determines secreted products of the polymorphic MUC1 gene, has been established as a convenient tool for monitoring breast carcinoma patients. The authors investigated alterations of soluble CA 15-3 in 57 postoperative breast carcinoma patients while they were receiving intensified adjuvant chemotherapy with granulocyte colony stimulating factor (G-CSF) support; 26 patients had American Joint Committee on Cancer (AJCC) Stage II, and 31 patients had AJCC Stage III breast carcinoma. Serial CA 15-3 values recorded thoughout the treatment were compared with baseline values, analyzed for correlation with hematologic and biochemical parameters, and compared with clinicopathologic characteristics and patient outcome. At a median follow-up time of 32 months, 47 of these patients remained relapse-free. A twofold increase of CA 15-3 was detected at the end of the second week of treatment, remained significantly elevated in most patients at above the cutoff level of 30 U/mL throughout the treatment period (P < 0.0001), and subsided to pretreatment values 1-2 months after treatment cessation. CA 15-3 values were found to be associated strongly with absolute neutrophil count, serum lactate dehydrogenase, and alkaline phosphatase. The median values and the kinetics of tumor markers did not differ over time in regard to hormonal receptor status and disease recurrence. These data provide strong evidence that G-CSF administration can induce elevation of CA 15-3 and indicate that false-positive results should be considered when evaluating CA 15-3 in patients who are receiving G-CSF. It is speculated that this phenomenon occurs through the induction of MUC1 antigen of unknown origin by G-CSF. Experimental investigation of this clinical observation is warranted.

An off-line strategy for constructing a patient-specific planning target volume in adaptive treatment process for prostate cancer

Purpose: To improve the efficacy of dose delivery and dose escalation for external beam radiotherapy of prostate cancer, an off-line strategy for constructing a patient-specific planning target volume is developed in the adaptive radiotherapy process using image feedback of target location and patient setup position. Materials and Methods: We hypothesize that a patient-specific confidence-limited planning target volume (cl-PTV), constructed using an initial sequence of daily measurements of internal target motion and patient setup error, exists and ensures that the clinical target volume (CTV) in the prostate cancer patient receives the prescribed dose within a predefined dose tolerance. A patient-specific bounding volume to correct for target location and compensate for target random motion was first constructed using the convex hull of the first k days of CT measurements. The bounding volume and the initial days of CT measurements were minimized based on a predefined dosimetric criterion. The hypothesis was tested using multiple daily CT images by mimicking the actual treatment of both conventional 4-field-box and intensity-modulated radiotherapy (IMRT) on each of 30 patients with prostate cancer. For each patient, a patient-specific setup margin was also applied to the bounding volume to form the final cl-PTV. This margin was determined using the random setup error predicted from the initial days of portal imaging measurements and the residuals after correcting for the systematic setup error. Results: The bounding volume constructed using daily CT measurements in the first week of treatment are adequate for the conventional beam delivery to achieve maximum dose reduction in the CTV of 2% or less of the prescription dose, for at least 80% of patients ( p = 0.08), and 4.5% or less for 95% of patients ( p = 0.1). However, for IMRT delivery, 2 weeks of daily CT measurements are required to achieve a similar level of the dosimetric criterion, otherwise the maximum dose reduction of 7%, on average, in the CTV is expected. Furthermore, the patient-specific setup margin required for the IMRT treatment is at least twice larger than that for the conventional treatment, to maintain the same dosimetric criterion. As compared to the conventional PTV, the volume of cl-PTV is significantly reduced, while maintaining the same dosimetric criterion. Conclusion: The cl-PTV for prostate treatment can be constructed within the first week of treatment using the feedback of imaging measurements. The cl-PTV has the capability to exclude the systematic variation and compensate for the patient-specific random variation on target location and patient setup position. This implies that in the current off-line image feedback adaptive treatment process, a single plan modification can be performed within the second week of treatment to improve the efficacy of dose delivery and dose escalation for external beam therapy of prostate cancer.

Clinical prediction of endoscopic healing in reflux esophagitis the second week of treatment

Clinical prediction of endoscopic healing in reflux esophagitis the second week of treatment

Positive Treatment Effect of Estradiol in Postpartum Psychosis

Postpartum illnesses with psychiatric symptoms and serious adverse sequelae are highly prevalent during the childbearing years. Despite multiple medical contacts, these illnesses often remain unidentified and untreated. To study the association between estradiol and puerperal psychosis, we measured serum concentration of estradiol and performed an open-label trial of physiologic 17beta-estradiol in women with this disorder. Ten women with ICD-10 psychosis with postpartum onset consecutively recruited from a psychiatric duty unit were studied. Serum estradiol concentration was measured at baseline and weekly during sublingual 17beta-estradiol treatment for 6 weeks. The treatment effect was evaluated by a clinician-rated psychiatric symptom scale (the Brief Psychiatric Rating Scale [BPRS]). The baseline serum estradiol levels (mean = 49.5 pmol/L; range, 13-90 pmol/L) were even lower than the threshold value of gonadal failure, and the patients exhibited high scores on the psychiatric symptom scale (mean BPRS total score = 78.3; range, 65-87). During the first week of 17beta-estradiol treatment, psychiatric symptoms diminished significantly (BPRS score decreased to a mean of 18.8, p < .001). Until the end of the second week of treatment, serum estradiol concentrations rose to near the values normally found during the follicular phase, and the patients became almost free of psychiatric symptoms. The reversal of psychiatric symptoms in all patients by treating documented estradiol deficiency suggests that estradiol plays a role in the pathophysiology and may have a role in the treatment of this condition. There was a rebound of psychotic symptoms in the 1 patient who discontinued estradiol treatment. Given the small number of patients, this area deserves further study.

Effects of 2 weeks of treatment with fluticasone propionate 100 mcg b.d. by comparison with zafirlukast 20 mg b.d. on bronchial hyper-responsiveness in patients with mild to moderate asthma

This study was designed to compare the effects of low-dose inhaled fluticasone propionate (100 mcg twice daily) with those of the leukotriene antagonist, zafirlukast (20 mg twice daily), on bronchial hyper-responsiveness. The study recruited 30 patients (nine men, 21 women; mean age 45 years) with forced expiratory volume in 1 sec (FEV1) >50% and airway reversibility to salbutamol ≥15%. This was a single centre, double-blind, double-dummy cross-over study, composed of two successive 2-week treatment periods, each preceded by a 2–4 week single-blind placebo period. Following 2 weeks of treatment with fluticasone propionate and zafirlukast, the mean provocational concentration causing a 20% fall in FEV1(PC20) histamine was 1·61 mg ml−1(SD 2·34) and 0·99 mg ml−1(SD 1·74) respectively. Taking baseline differences into account, the difference between treatments was equivalent to 0·77 doubling doses of histamine (95% CI, 0·05–1·50;P=0·037). Morning peak flow values were significantly higher (17 l min−1;P=0·049) after treatment with fluticasone propionate during the second week of treatment. Both treatments were well tolerated. The results of this short-term study show that compared with zafirlukast, a low dose of fluticasone propionate offers greater clinical benefit and is more cost effective.

Broad Spectrum Herbal Therapy against Superficial Fungal Infections

Skin disease associated with keratinized tissues in animal and human beings has been investigated. The essential oil of Eucalyptus pauciflora in vitro showed strong antifungal activity at 1.0 μl/ml against human pathogenic fungi, viz. Epidermophyton floccosum, Microsporum audouinii, M. canis, M. gypseum, M. nanum, Trichophyton mentagrophytes, T. rubrum, T. tonsurans and T. violaceum. The oil has heavy doses of inoculum potential at 1.0 μl/ml. Moreover, it did not exhibit any adverse effects on mammalian skin up to 5% concentrations. Further, we formulated the oil in the form of ointment ‘BSHT’ (broad spectrum herbal therapy) (1% v/v) and subjected it to topical testing on patients attending the outpatient department of M.L.N. Medical College, Allahabad. Fifty patients were selected on the basis of KOH-positive results and diagnosed as either tinea pedis, tinea corporis or tinea cruris. After the second week of treatment, all patients were KOH-negative. At the end of medication, 60% of patients recovered completely and 40% showed significant improvement from the disease. No KOH-negative cases of relapse were observed when patients were re-examined after 2 months following the end of treatment. Thus, the ointment can be exploited commercially after undergoing successful multicenter clinical trials, which are in progress.

Effect of drought on sorbitol and sucrose metabolism in sinks and sources of peach

In peach (Prunus persica[L.] Batsch.), sorbitol and sucrose are the two main forms of photosynthetic and translocated carbon and may have different functions depending on the organ of utilization and its developmental stage. The role and interaction of sorbitol and sucrose metabolism was studied in mature leaves (source) and shoot tips (sinks) of ‘Nemaguard’ peach under drought stress. Plants were irrigated daily at rates of 100, 67, and 33% of evapotranspiration (ET). The relative elongation rate (RER) of growing shoots was measured daily. In mature leaves, water potential (Ψw), osmotic potential (Ψs), sorbitol‐6‐phosphate dehydrogenase (S6PDH, EC 1.1.1.200), and sucrose‐phosphate synthase (SPS, EC 2.4.1.14) activities were measured weekly. Measurements of Ψs, sorbitol dehydrogenase (SDH, 1.1.1.14), sucrose synthase (SS, EC 2.4.1.13), acid invertase (AI, EC 3.2.1.26), and neutral invertase (NI, EC 3.2.1.27) activities were taken weekly in shoot tips. Drought stress reduced RER and Ψwof plants in proportion to water supply. Osmotic adjustment was detected by the second week of treatment in mature leaves and by the third week in shoot tips. Both SDH and S6PDH activities were reduced by drought stress within 4 days of treatment and positively correlated with overall Ψwlevels. However, only SDH activity was correlated with Ψs. Among the sucrose enzymes, only SS was affected by drought, being reduced after 3 weeks. Sorbitol accumulation in both mature leaves and shoot tips of stressed plants was observed starting from the second week of treatment and reached up to 80% of total solutes involved in osmotic adjustment. Sucrose content was up to 8‐fold lower than sorbitol content and accumulated only occasionally. We conclude that a loss of SDH activity in sinks leads to osmotic adjustment via sorbitol accumulation in peach. We propose an adaptive role of sorbitol metabolism versus a maintenance role of sucrose metabolism in peach under drought stress.

Intravascular infusions of soluble β-amyloid compromise the blood–brain barrier, activate CNS glial cells and induce peripheral hemorrhage

Vascular wall levels of soluble β-amyloid 1–40 (Aβ 1–40) are elevated in Alzheimer's disease (AD). Moreover, plasma Aβ levels are increased in familial AD, as well as in some cases of sporadic AD. To determine the histopathologic and behavioral consequences of elevated vascular Aβ levels, Aβ 1–40 (50 μg in distilled water) or vehicle was intravenously infused twice daily into 3-month old male Sprague–Dawley rats for 2 weeks. Intravenous Aβ infusions impaired blood–brain barrier integrity, as indicated by substantial perivascular and parenchyma IgG immunostaining within the brain. Also evident in Aβ-infused animals was an increase in GFAP immunostaining around cerebral blood vessels, and an enhancement of OX-42 microglial immunostaining in brain white matter. Gross pulmonary hemorrhage was noted in most Aβ-infused animals. All the observed changes occurred in the absence of Congo red birefringence. No significant cognitive deficits were present in Aβ-infused animals during water maze acquisition and retention testing, which was conducted during the second week of treatment. These results indicate that circulating Aβ can: (1) induce vessel dysfunction/damage in both the brain and the periphery without complex Aβ fibril formation/deposition, and (2) induce an activation of brain astrocytes and microglia. Taken together, our results suggest that if circulating Aβ is elevated in AD, it is likely to have a pathophysiologic role.

Spongiform neuropathy induced in dogs by prolonged, low-level administration of 6-aminonicotinamide (6-ANA)

The objective of this study was to demonstrate the effects of prolonged exposure to 6-ANA at low dose-levels in dogs. A male and a female Beagle dog received daily oral repetitive doses of 1 mg/kg or less for 20 weeks. Both dogs showed lacrimation, conjunctivitis, reduced motility and anemia since the second week of treatment. The female dog was more affected than the male and at the end of treatment period it had tremor, hanging lower jaw, stepping gait of the hind limbs, hunched posture, and general debilitation. Post-mortem examination of the female dog revealed prominent brain edema with pressure atrophy of the dorsal cranial bones. Microscopic examination of the nervous system revealed spongiform neuropathy in both animals mainly affecting the telencephalic cortex and hippocampal fascia dentata, the substantia gelatinosa in the spinal cord and the dorsal root and autonomic ganglia. The changes were produced by vacuolation of astrocytes in the central nervous system and perineuronal satellite cells in the ganglia. Examination of the other organs revealed thymic atrophy and high hematopoietic activity of the bone marrow in both dogs. The male had severe interstitial edema and vacuolar degeneration of the testicular seminiferous tubules and the female had marked chronic pyelonephritis. This chemically induced spongiform neuropathy in dogs obviously represents a subchronic form of the "energy deprivation syndrome" induced by impaired glucose utilization. Vacuolar degeneration of the testicular seminiferous epithelium may have the same pathogenesis.

Anhedonia and relapse in alcoholism

The aim of this study was to determine the role of anhedonia among other psychopathological dimensions in the relapse of alcoholics 6 months after withdrawal. Psychometric assessments included: the Social and Physical Anhedonia Scales, the Sensation Seeking Scale, the Pleasure–Displeasure Scale (including Fawcett–Clark's Pleasure Scale), the Depressive Mood Scale, the Thymasthenic Syndrome Rating Scale and the Comprehensive Psychopathological Rating Scale. Forty-four alcoholics participated in the study. The baseline values recorded during the second week of treatment showed that the more anhedonic the alcoholics were, the less they sought sensations. Type 2 alcoholics (Cloninger's classification) scored higher on the Thrill and Adventure Seeking Subscale. Relapsed alcoholics had higher baseline values on the Thrill and Adventure Seeking Subscale. This was in agreement with the step-wise discriminant analysis which showed that this subscale was the main variable that differentiated abstinent alcoholics from those who relapsed. Our results indicate that anhedonia does not predict relapse.

High-dose rate interstitial with external beam irradiation for localized prostate cancer – results of a prospective trial

Purpose: A prospective phase II trial was carried out to test the feasibility and effectiveness of a combined interstitial with external beam radiotherapy approach for localized prostate cancer. Materials and methods: Between October 1992 and December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according to the AJCC classification system of 1992, were found in 21 and 61 cases, respectively. The median follow-up was 24 months; three patients were lost during follow-up. All of the patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a week was prescribed during the first and second weeks of treatment (10 Gy each week from October 1992 to December 1993) interstitially with high-dose rate Iridium-192 brachytherapy to the prostate and tumour extension beyond the capsule. External beam four-field box irradiation was then given to the prostate to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December 1993). Results: Before starting treatment, a PSA value of ≥10 ng/ml was found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70 ng/ml, respectively. The PSA value was <1.0 ng/ml in 52.9% of patients at 2 years. Negative punch biopsies 12 and 24 months after therapy were observed in 69.8% (44/63) and 73.1% (38/52) of patients, respectively. A positive biopsy combined with a PSA value of >1.0 ng/ml was considered as local failure. The local tumour control rate was 79.5% at 2 years. Acute side-effects were not increased relative to external beam irradiation alone. Severe side-effects were observed in three patients (two of the three patients had additional risk factors (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae requiring colostomy after biopsies from the anterior rectal wall. Conclusion: The described method is feasible and well tolerable. The three complications observed were not caused by irradiation alone. Biopsies from the anterior rectal wall after definitive high-dose radiotherapy for prostate cancer have to be seen as obsolete. The rate of negative prostate biopsies of 73.1% after 24 months represents an encouraging result.

PULMONARY TUBERCULOSIS AND ITS THERAPY DO NOT SIGNIFICANTLY AFFECT THYROID FUNCTION TESTS

SUMMARYBasal thyrotropin, total thyroxine, total tri‐iodothyronine and free tri‐iodothyronine were measured in 30 HIV‐negative patients with focal pulmonary tuberculosis upon starting and after one and two weeks of isoniazid, rifampicin and pyrazinamide therapy. Rapid and statistically significant elevations in free tri‐iodothyronine and total tri‐iodothyronine were noted after the first and second week of treatment respectively. For most patients, however, hormone levels remained within normal limits throughout the study. Overall, the effects of pulmonary tuberculosis and of its therapy on the thyroid function parameters examined, in otherwise healthy individuals, appear to be minimal.

Hepatitis C viral RNA status at two weeks of therapy predicts the eventual response.

We investigated the timing of the disappearance and reappearance of serum hepatitis C viral (HCV) RNA in patients with chronic hepatitis C during interferon treatment and follow-up. Serum samples were tested for HCV RNA by polymerase chain reaction in 62 patients with chronic hepatitis C treated with interferon-alpha for 24 weeks. We found that 17 patients obtained complete response, with absence of serum HCV RNA for 6 months after the treatment. Twenty-nine patients had a partial response, with reappearance of serum HCV RNA within 6 months of follow-up, and 16 patients were nonresponders who were positive for serum HCV RNA throughout the observation period. HCV RNA disappeared within 2 weeks of treatment in 31 patients, including all 17 (100%) complete responders and 14 (48.3%) of the 29 partial responders. The patients remaining positive for HCV RNA at the second week were 15 (51.7%) of the 29 partial responders and the 16 nonresponders. In all of the 29 partial responders, viremia recurred within 1 month after the treatment. These results indicate that the status of HCV RNA at the second week of treatment is a useful predictor of effective treatment, whereas status at the first month after cessation of treatment is useful for assessing the effectiveness of interferon itself.

The efficacy and safety of salmeterol compared to theophylline: meta-analysis of nine controlled studies

The aim of this study was to compare the efficacy and safety of salmeterol vs theophylline in asthma management using meta-analysis of clinical trials. Nine clinical studies, containing a total of 1330 patients, met meta-analysis inclusion criteria: randomized, controlled study, minimum 2-week treatment duration with either salmeterol or theophylline. The main outcome measurements were morning and evening peak expiratory flow rate (PEFR), morning and evening symptom scores, use of salbutamol as rescue medication, and withdrawal from treatment for any cause. During the second week of treatment, salmeterol patients had a 101 min −1 greater increase in mean morning PEFR from baseline than theophylline patients ( P<0·001). Similarly, in the second week, the increase in mean evening PEFR from baseline observed with salmeterol was significantly greater ( P<0·01) than that observed with theophylline. Salmeterol also produced a significantly greater increase in mean morning and evening PEFR than theophylline at weeks 3 and 4. Patients receiving salmeterol were free from daytime symptoms for a mean of 51% of days in the second week compared to 39% for theophylline patients ( P<0·001). Salmeterol patients experienced a mean of 63% symptom-free nights compared to 52% for theophylline patients ( P<0·001). Rescue medication with salbutamol was not required on 49% of days for salmeterol patients and 34% of days for theophylline patients. All results were maintained in the third and fourth weeks of treatment. Withdrawal and incidence of adverse events leading to withdrawal were significantly less frequent in patients receiving salmeterol ( P<0·001). Thus, this meta-analysis suggests that salmeterol has a superior safety and efficacy profile to theophylline in the management of symptoms of chronic asthma.

A comparison of two programs (pyrantel tartrate administered daily and 3X pyrantel pamoate adminitered at 8-week intervals) for the reduction of tapeworm EPG in the horse

Summary A 26-week study was conducted with 24 horses to compare the effectiveness of two different treatment regimens in reducing the number of tapeworm eggs per gram (EPG) of feces. Ten horses were treated daily with 2.6 mg/kg of pyrantel tartrate (approved normal dosage for nematodes). Eleven horses received pyrantel pamoate at 8-week intervals at 19.8 mg/kg (3X the normal use for nematodes). Three horses served as controls and received ivermectin at 8-week intervals. Levels of tapeworm EPG were monitored at 2-week intervals for the duration of the 26-week period of study. Prior to administration of the first treatment, all 24 horses had positive EPG counts. Following the second week of treatment, no tapeworm eggs were detected in fecal samples of the 10 horses treated with pyrantel tartrate. Of the 11 horses treated with 3X pyrantel pamoate at 8-week intervals, one to two at each sample collection date had positive tapeworm EPG counts through the tenth week following the initial treatment, that is, through two weeks following the second 3X pyrantel pamoate treatment. Of the three control horses treated only with invermectin, at least one, and sometimes all three, had positive EPG counts at each collection date, indicating continuous tapeworm infection.

The effect of glurenorm on blood pressure in patients with non-insulin-dependent diabetes mellitus with hypertension

Effects of long glurenorm therapy on daily arterial pressure (AP), central hemodynamics, and diastolic function of the left ventricle were assessed in patients with non-insulin-dependent diabetes with stages I and II essential hypertension. The patients were divided in 2 groups: group I (n=24) treated with manilil (5-20 mg/day) and nifedipin (20-50 mg/day) and group II (n=24) treated with glurenorm (60-150 mg/day). Control groups consisted of diabetics without arterial hypertension: group III, glurenorm, and group IV, manilil. AP decreased in 88% of patients in groups I and II during the second week of treatment, the maximal decrease was observed by the and of week 12. Decrease of AP in groups I and II was paralleled by a decrease of the total peripheral resistance, improvement of leftventricular diastolic function, and no effect of myocardial contractility. One probable mechanism of the hypotensive and vasodilating effect of glurenorm is decrease of basal insulin level, whose values were higher in groups I and II in comparison with the control and correlated with daily AP values.

Transdermal clonidine in the prophylaxis of episodic cluster headache: an open study.

Transdermal clonidine has recently been reported to be efficacious in the prophylaxis of cluster headache. A 2-week course of transdermal clonidine (5 mg the first week, 7.5 mg the second week) preceded by a 5-day run-in period, was administered to 16 patients with episodic cluster headache in an active cluster period. In 5 patients, the painful attacks disappeared after the seventh day of treatment. For the group as a whole, no significant variations in headache frequency, pain intensity, or attack duration were observed between the run-in period and the first and second weeks of treatment (ANOVA). Further studies are necessary to clarify the effectiveness of transdermal clonidine in the prophylaxis of episodic cluster headache.

Kinetics of reticulocyte maturity fractions and indices and iron status during therapy with epoetin beta (recombinant human erythropoietin) in cardiac surgery patients

We evaluated the changes in reticulocyte maturity fractions and indices, as measured by flow cytometry, during preoperative treatment with recombinant human erythropoietin (epoetin beta) in cardiac surgery patients. A total of 72 patients was enrolled in this double-blind, randomized, placebo-controlled clinical trial and assigned to the two treatment groups (5 x 500 U/kg bodyweight epoetin beta or placebo intravenously over 14 days preoperatively). Therapy with epoetin beta produced continuous increases in hematocrit/hemoglobin, in the most mature fraction of reticulocytes (LR), and in reticulocyte count. In the first treatment week there were parallel increases in the fraction of most immature reticulocytes (HR) and in the reticulocyte mean cell volume. During the second week of treatment the reticulocyte mean cell hemoglobin content (CHr) decreased, but CHr was independent of all iron parameters, affecting neither the reticulocyte fractions nor the hematocrit/hemoglobin increase. The total preoperative rise in hematocrit correlated with the rises in LR fraction (P = 0.0270) and reticulocyte count (P = 0.0486) during the first week of treatment. Whereas in the epoetin beta patients the preoperative change in HR fraction showed negative correlations with transferrin saturation at baseline (P = 0.0058) and with the preoperative change in iron (P = 0.0113), the preoperative change in the LR fraction correlated positively with transferrin at baseline (P = 0.0115). Postoperatively, the reticulocyte parameters revealed that the onset of increased stimulation of erythropoiesis did not occur in the placebo patients until the second postoperative day, whereas erythropoietic activity in the epoetin beta patients was much higher during the postoperative period as well, as a result of the preoperative stimulation of erythropoiesis. The reticulocyte parameters measured by flow cytometry permitted an objective analysis of erythropoietic activity during treatment with epoetin beta and in all patients postoperatively. Further studies in various types of epoetin beta therapy are needed in order to clarify the value of these reticulocyte parameters for identification of iron deficiency and optimization of epoetin beta treatment regimen.