Sparing the hippocampus and the hypothalamic- pituitary region during whole brain radiotherapy: a volumetric modulated arc therapy planning study.

BACKGROUND: Feasibility testing of a simultaneous sparing approach of hippocampus, hypothalamus and pituitary gland in patients undergoing whole-brain radiotherapy (WBRT) with and without a concomitant boost to metastatic sites. INTRODUCTION: Cognitive impairment and hormonal dysfunction are common side effects of cranial radiotherapy. A reduced dose application to the patho-physiologically involved functional brain areas, i.e. hippocampus, hypothalamus and pituitary gland, could reduce these common side effects. While hippocampal sparing is already a common practice to improve cognitive outcome, technical experience of additional combined sparing of the hypothalamus/pituitary gland (HT-P) is insufficient. METHODS: Twenty patients were included in the planning study. In 11 patients, a total dose of 36 Gy of WBRT (2 Gy per fraction) plus a simultaneous integrated boost (SIB) of 9 Gy (0.5 Gy per fraction, total dose: 45 Gy) to the brain metastases was applied. In 9 patients, prophylactic cranial irradiation (PCI) was simulated with a total dose of 30 Gy (2 Gy per fraction). In both patient cohorts, a sparing approach of the hippocampus and the HT-P area was simulated during WBRT. For all treatment plans, volumetric modulated arc therapy (VMAT) was used. Quality assurance included assessment of homogeneity, conformality and target coverage. RESULTS: The mean dose to the hippocampus and HT-P region was limited to less than 50% of the prescribed dose to the planning target volume (PTV) in all treatment plans. Dose homogeneity (HI) of the target volume was satisfying (median HI = 0.16 for WBRT+SIB and 0.1 for PCI) and target coverage (conformation number, CN) was not compromised (median CN = 0.82 for SIB and 0.86 for PCI). CONCLUSION: Simultaneous dose reduction to the hippocampus and the HT-P area did not compromise the PTV coverage in patients undergoing WBRT+SIB or PCI using VMAT. While the feasibility of the presented approach is promising, prospective neurologic, endocrine outcome and safety studies are required.

Are hypothalamic- pituitary (HP) axis deficiencies after whole brain radiotherapy (WBRT) of relevance for adult cancer patients? - a systematic review of the literature.

BACKGROUND: Cranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound endocrinological follow-up data from survivors of childhood cancer treated with cRT, little knowledge exists for adult cancer patients. METHODS: A systematic search of the literature was conducted using the PubMed database and the Cochrane library offering the basis for our debate of the relevance of HP axis impairment after cRT in adult cancer patients. Against the background of potential relevance for patients receiving whole brain radiotherapy (WBRT), a particular focus was set on the temporal onset of hypopituitarism and the radiation dose to the HP axis. RESULTS: Twenty-eight original papers with a total of 1728 patients met the inclusion criteria. Radiation doses to the HP area ranged from 4 to 97 Gray (Gy). Hypopituitarism incidences ranged from 20 to 93% for adult patients with nasopharyngeal cancer or non-pituitary brain tumors. No study focused particularly on hypopituitarism after WBRT. The onset of hypopituitarism occurred as early as within the first year following cRT (range: 3 months to 25.6 years). However, since most studies started follow-up evaluation only several years after cRT, early onset of hypopituitarism might have gone unnoticed. CONCLUSION: Hypopituitarism occurs frequently after cRT in adult cancer patients. Despite the general conception that it develops only after several years, onset of endocrine sequelae can occur within the first year after cRT without a clear threshold. This finding is worth debating particularly in respect of treatment options for patients with brain metastases and favorable survival prognoses.

Phenotypic and antibiogram pattern of V. cholerae isolates from a tertiary care hospital in Mumbai during 2004-2013: a retrospective cross-sectional study.

OBJECTIVES: Cholera is a major gastroenteric disease with reports on fluctuation and resistance. Hence, the objective is to determine the trend in seasonality, resistance pattern, prevalent biotypes, serotypes and phage types between 2004 and 2013 among Vibrio cholerae isolates. DESIGN: A retrospective cross-sectional study. SETTINGS: A single-centre study was carried out at a tertiary care hospital in a metropolitan city (Mumbai) of a developing country (India). METHODS: Records of stool specimen cultures of patients with suspected cholera from January 2004 to December 2013 were analysed. The organisms were identified as per standard protocol. Antimicrobial susceptibility testing was performed as per Clinical Laboratory Standard Institute. Biotyping, serotyping and phage typing were carried out. From the confirmed cases of cholera, demographic and laboratory details were noted. Descriptive analysis was used and the data were presented in the form of percentages. RESULTS: Vibrio cholerae was predominant in males and was isolated from 9.41% (439/4664) of stool specimens. Variability was found in terms of the gross appearance of stool specimens, seasonal trend and antibiotic resistance pattern. The antimicrobial susceptibility showed a waxing and waning pattern for most of the antibiotics (ampicillin, cefuroxime, chloramphenicol, tetracycline) tested, while for a few others the strains were either uniformly sensitive (gentamicin, norfloxacin) or resistant (trimethoprim-sulfamethoxazole, nalidixic acid). All isolates belonged to subgroup O1 and biotype El Tor. The most common serotype was Ogawa. The predominant phage type was T2 (old scheme) and T27 (new scheme). CONCLUSIONS: The predominant biotype, serotype and phage type were El Tor, Ogawa and T27 phage, respectively. The changing trends in antimicrobial resistance pattern over the years necessitate continued epidemiological and microbiological surveillance of the disease.

Is methicillin-resistant Staphylococcus aureus involved in community acquired skin and soft tissue infections? Experience from a tertiary care centre in Mumbai.

BACKGROUND: To improve the empiric antimicrobial therapy of community-acquired (CA) skin and soft tissue infections (SSTIs), it is necessary to generate data on the current spectrum and susceptibility profile of associated bacteria. CA methicillin-resistant Staphylococcus aureus (CA MRSA) is increasingly being reported in SSTIs in India and globally. AIMS: The present study was undertaken to determine the bacterial profile of CA-SSTIs, to know the contribution of MRSA in these infections, to determine inducible clindamycin resistance in S. aureus and to compare the resistance patterns of isolates from hospital-acquired (HA) SSTIs. MATERIALS AND METHODS: Eight hundred and twenty patients with CA SSTIs were prospectively studied. Pus samples were cultured and antimicrobial susceptibility pattern determined. Inducible clindamycin resistance was detected by D-test. Laboratory records were analyzed retrospectively to generate data on HA SSTIs. RESULTS: 619 isolates were recovered in CA-SSTIs, of which S. aureus (73%) and Streptococci (12%) were the most common. Pseudomonas aeruginosa (28%) and Acinetobacter spp (18%) were the predominant HA-SSTI pathogens. Susceptibility of CA S. aureus to antibiotics tested was, penicillin (6%), co-trimoxazole (20%), ciprofloxacin (37%), cefazolin (100%), erythromycin (84%), clindamycin (97%), gentamicin (94%) and fusidic acid (95%). No MRSA was found in CA SSTIs whereas 45% of HA S. aureus strains were methicillin-resistant. HA strains demonstrated significantly higher resistance as compared to their CA counterparts (P<0.001). D test was positive in 22% of CA S. aureus tested. CONCLUSIONS: In CA SSTIs, methicillin-susceptible S. aureus is the predominant pathogen. Penicillinase-resistant penicillins, clindamycin and erythromycin in that order can be used as suitable antimicrobials for empiric therapy. D test should be carried out routinely. No CA MRSA was detected in the present series.

Early clinical indicators of transplant-associated thrombotic microangiopathy in pediatric neuroblastoma patients undergoing auto-SCT.

Patients undergoing auto-SCT for neuroblastoma present a unique population to study transplant-associated thrombotic microangiopathy (TA-TMA), due to standardized chemotherapy and later exposure to radiation and cis-retinoic acid (cis-RA). We retrospectively analyzed 20 patients after auto-SCT to evaluate early clinical indicators of TA-TMA. A total of 6 patients developing TA-TMA (30% prevalence) were compared with 14 controls. Four of six patients were diagnosed with TA-TMA by 25 days after auto-SCT. Compared with controls, TA-TMA patients had higher average systolic and diastolic blood pressure levels during high-dose chemotherapy and developed hypertension by day 13 after auto-SCT. Proteinuria was a significant marker for TA-TMA, whereas blood and platelet transfusion requirements were not. Serum creatinine did not differ between groups post transplant. However, patients with TA-TMA had a 60% decrease in renal function from baseline by nuclear glomerular filtration rate, compared with a 25% decrease in those without TA-TMA (P=0.001). There was no TA-TMA-related mortality. Significant complications included end-stage renal disease (n=1) and polyserositis (n=3). Patients with TA-TMA were unable to complete cis-RA therapy after auto-SCT. We suggest that careful attention to blood pressure and urinalysis will assist in the early diagnosis of TA-TMA, whereas serum creatinine seems to be an insensitive marker for this condition.

Study of HIV-1 subtypes in serodiscordant couples attending an integrated counselling and testing centre in Mumbai using heteroduplex mobility analysis and DNA sequencing.

AIMS: To determine the prevalent subtypes of HIV-1 in serodiscordant couples. SETTING: Integrated Counselling and Testing Centre (ICTC), Department of Microbiology. STUDY DESIGN: Prospective pilot study. PARTICIPANTS: Thirty HIV-1 serodiscordant couples. INCLUSION CRITERIA: a) Documentation of HIV-1 infection in one partner and seronegative status in the other, current history of continued unprotected sexual activity within the partnership, demonstration that they have been in a partnership for at least 1 year and are not currently on highly active antiretroviral therapy HAART; b) willingness of both partners to provide written informed consent including consent to continued couple counselling for 3 months. MATERIALS AND METHODS: HIV-1 subtyping was carried out by heteroduplex mobility analysis (HMA) by amplifying env region; and DNA sequencing by amplifying gag region. RESULTS: HIV-1 env gene was amplified successfully in 10/30 samples; gag gene, in 25/30 samples; and both env and gag gene were amplified successfully in 5/30 samples. HIV-1 subtype C was detected from 21 samples; subtype B, from 7; and subtype A, from 2. Sample from 1 positive partner was detected as subtype C by env HMA and subtype B by gag sequencing. CONCLUSION: HIV-1 subtype C was found to be the predominant subtype of HIV-1 in serodiscordant couples attending our ICTC, followed by HIV-1 subtype B and HIV-1 subtype A, respectively. DNA sequencing was found to be the most reliable method for determining the subtypes of HIV-1.

Early results for treatment of unilateral vocal fold palsy with injection medialisation under local anaesthetic.

BACKGROUND: The diagnosis and treatment of unilateral vocal fold palsy is a common part of otolaryngology practice. In those patients in whom resolution of symptoms is slow, the resulting dysphonia can have a dramatic effect on the patient's quality of voice and life. We have previously described the procedure of direct phonoplasty under local anaesthesia using the transnasal laryngoesophagoscope. OBJECTIVE: To examine the subjective and objective data for the first five patients to undergo this procedure, in the form of laryngographic speech analysis, perceptual assessment and therapy outcome measures. RESULTS: Analysis showed a statistically significant improvement in voice quality, in all the above assessment categories, following local anaesthetic direct phonoplasty using the transnasal laryngoesophagoscope. CONCLUSION: Collagen injection via transnasal flexible laryngoesophagoscopy is a particularly useful technique for treating vocal fold medialisation, especially in palliative care patients and those with shortened life expectancy.

Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder.

N,N-dimethylglycine, a dietary supplement, has been reported to be beneficial in children with autism and pervasive developmental disorder. We examined the effectiveness of dimethylglycine in children with autism and pervasive developmental disorder in a double-blind, placebo-controlled study. Thirty-seven children between 3 and 11 years of age with a diagnosis of autism and/or pervasive developmental disorder were gender and age matched and randomly assigned to receive either placebo or dimethylglycine for 4 weeks. All children were assessed before and after treatment on two behavioral measures, the Vineland Maladaptive Behavior Domain and the Aberrant Behavior Checklist. Standardized neurologic examinations before and after treatment on 33 children showed no change. An overall improvement on all behavioral measures was observed for both the placebo and the dimethylglycine groups. However, the improvement among the children who received dimethylglycine was not statistically different from the improvement observed among the children who received the placebo. The children who participated in this study were a heterogeneous group, and their apparent responses to the dimethylglycine varied. Some children appeared to respond positively to the dimethylglycine, and there was a smaller proportion of negative changes in the dimethylglycine group, but the quantitative changes in the dimethylglycine behavioral assessments were not significantly different from what was observed among children who received placebo.

Acquiescence to adjunctive experimental therapies may relate to psychological distress: pilot data from a bone marrow transplant center.

Use of alternative therapy for breast cancer outside of the hospital setting has been identified as a marker of psychological distress. Whether acquiescence to experimental therapies within the medical setting might also be a sign of psychological distress is not well known. We therefore evaluated patients with breast cancer undergoing bone marrow transplantation (BMT), an experimental method for treatment, to determine if acquiescence to further adjunctive experimental therapy related to psychological distress. In order to do this, we studied psychological test results of 42 breast cancer patients undergoing BMT at the University of Florida between January and December 1997. These tests included the Medical Outcomes Short Form Health Survey, the Beck Depression Inventory, the State-Trait Anxiety Inventory and the Medical Coping Modes Questionnaire. Women who accepted adjunctive experimental therapy had significantly higher trait anxiety and poorer role functioning compared to women who did not (both P < 0.001). These findings suggest that psychological distress may be a factor in medical decision-making even within the medical setting and that prospective research in this area is warranted.

Use of alternative therapies for children with cancer.

OBJECTIVE: To compare the use of alternative therapy (AT) in families of children with cancer with its use in those with routine pediatric conditions. BACKGROUND AND RATIONALE: AT refers to healing practices such as therapeutic massage, acupuncture, and use of medicinal herbs that have become increasingly popular with the general public, but are not widely accepted by the medical profession. Although studies have investigated the use of AT in the families of both healthy children and children with cancer, no comparison of the incidence of its use between these two populations has been published. We hypothesized that AT was used more frequently among the families of children with cancer. METHODS: Using a prevalence survey design, we interviewed 81 parents of children with cancer attending a pediatric hematology/oncology clinic and 80 parents of children attending a continuity care clinic for routine check-ups and acute care. We explored the types of AT being used, the reasons for its use, and the frequency with which it was discussed with the patient's physician. RESULTS: 1) Overall, 65% of the cancer group were using AT, compared with 51% of the control group. This was not statistically significant. 2) Prayer, exercise, and spiritual healing were three AT practices most often used by the cancer group, and prayer, massage, and spiritual healing by the control group. 3) Discussion of AT with the physician varied according to group, with 53% of the cancer patients discussing its use; income level, with 59% of parents in the higher income group discussing its use; and ethnicity, with 47% of whites discussing its use. CONCLUSION: Use of AT is not limited to the families of children with life-challenging illnesses, but is commonly used by those of children with routine pediatric problems. Pediatricians need to be aware that their patients may not tell them about AT practices they are using in addition to prescribed treatment.

Platelet inhibitory effect of nitroglycerin in platelet-rich plasma: relevance of glutathione-s-transferases in plasma.

BACKGROUND: Nitroglycerin (NTG) is believed to exert its platelet inhibitory effect via its biotransformation to nitric oxide (NO). We examined the relevance of glutathione-s-transferases (GST) in plasma in the conversion of NTG to NO and the platelet inhibitory effect of NTG. METHODS AND RESULTS: Nitroglycerin (1-100 micrograms/mL) was incubated with human platelet-rich plasma (PRP) for 10-60 minutes. Nitroglycerin caused a concentration-dependent inhibition of platelet aggregation in PRP with IC50 approximately 50 micrograms/mL. NTG also enhanced nitrite levels in PRP and stimulated cyclic GMP accumulation in platelets. In contrast, when NTG was incubated with washed platelets (WP) in concentrations as high as 100 micrograms/mL, there was no inhibition of platelet aggregation, formation of nitrite, or accumulation of cGMP. However, treatment of WP suspension with authentic NO exhibited diminished platelet aggregation, suggesting that NTG delivers NO in plasma that subsequently inhibits platelet aggregation. In keeping with this concept, the aggregation inhibitory effect of NTG in PRP was blocked by oxyhemoglobin. The platelet aggregation inhibition by NTG was potentiated by propylthiouracil (600 micrograms/mL), a GST inducer, and antagonized by ketoprofen (100 micrograms/mL), a GST inhibitor. Direct measurement indeed showed significant GST activity in plasma (24 +/- 3 mU/mL). CONCLUSIONS: We suggest that NTG inhibits platelet aggregation in PRP by its biotransformation to NO in plasma. The presence of GST, and perhaps other cofactors, in plasma is relevant in the platelet inhibitory effects of NTG in PRP.

Zinc deficiency and its repletion following liver transplantation in humans.

Zinc deficiency is common in patients with end-stage liver disease but its prevalence and resolution in liver transplant recipients has not been reported. We hypothesized that with normalization of liver function after transplant, zinc levels should rapidly return to normal, obviating the need for oral supplementation. Serum zinc levels were obtained as part of routine laboratory studies just prior to liver transplantation in 34 patients. Of these, 22 had at least one additional zinc level obtained post-transplant. The charts of these 34 patients were retrospectively reviewed for pre- and post-transplant zinc, albumin, protein, and cholesterol levels, prothrombin times, use of oral zinc supplementation, and patient demographics including age, gender, cause of liver failure, UNOS status at the time of transplant, and the use of a pre-transplant trans-jugular intrahepatic portosystemic shunt (TIPS). Post-transplant, the patients received standard enteral formula for nutrition. The overall zinc level for the group was 37.4 +/- 9.0 micrograms/dl (mean +/- s.d., normal = 60-150 micrograms/dl). Thirty-two of the 34 patients (94%) had a zinc level in the subnormal range. There were no differences in zinc levels between patients with alcoholic and non-alcoholic liver failure, males versus females, UNOS status (low = status 1 and 2, high = 3 and 4), pre-transplant use of TIPS nor correlation between age and zinc level. All 22 patients who had a post-transplant zinc level demonstrated an increase from 40.1 +/- 9.7 micrograms/dl to 68.5 +/- 14.1 micrograms/dl (p < and = 0.0001, paired t-test). Our findings indicate that zinc deficiency, generally profound, should be assumed to be present in every patient with end-stage liver disease awaiting transplant. During the waiting period oral supplementation with zinc should be provided. The degree of deficiency is not effected by cause of liver failure, UNOS status, or the presence of TIPS. Following transplantation, zinc levels rapidly recover, obviating the need for checking levels and oral supplementation.

Antibiotic inhibition of pectolytic and cellulolytic enzyme activity in two Fusarium species.

Among all antibiotics tested, amoxycillin (500 ppm) completely inhibited the polygalacturonase and pectinmethylgalacturonase enzyme activity in F. oxysporum; none of the antibiotics did so in F. moniliforme. No antibiotic completely inhibited the cellulase activity in both test organisms, however, amoxycillin was better than other antibiotics in inhibiting the cellulase activity in both the organisms.

Omega-3 polyunsaturated fatty acids augment endothelium-dependent vasorelaxation by enhanced release of EDRF and vasodilator prostaglandins.

Dietary supplementation with fish oil results in augmentation of endothelium-dependent vasorelaxation in experimental animals. The present study was designed to evaluate the direct in vitro effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on vascular reactivity in isolated rat aortic rings. Aortic rings were incubated with the omega-6PUFA arachidonic acid (AA, 10(-7) M) or the omega-3 PUFAs eicosapentaenoic acid (EPA, 10(-7) M) and docosahexaenoic acid (DHA, 10(-7) M) in an organ bath at 37 degrees C. Following contraction with norepinephrine, changes in isometric force were measured in response to the endothelium-dependent vasodilators acetylcholine (ACh, 10(-10) to 10(-5) M) or the calcium ionophore A23187 (10(-10) to 10(-5) M). Parallel sets of vascular rings were pretreated with the cyclooxygenase inhibitor indomethacin (10(-5) M) or the inhibitor of nitric oxide synthesis NG-monomethyl L-arginine (L-NMMA 5 x 10(-5) M) prior to treatment with AA or EPA. Treatment of rings with EPA resulted in an increase (P less than 0.05) in ACh-mediated vasorelaxation compared both to AA-treated and buffer-treated rings (maximum relaxation 83 +/- 5% vs 46 +/- 5% and 63 +/- 4%, respectively). A similar augmentation was observed in DHA-treated rings. Pretreatment of rings with indomethacin or I-NMMA decreased (P less than 0.05) the ACh-mediated vasorelaxation, although EPA-treated rings showed less (P less than 0.05) attenuation of ACh response compared to AA-treated or untreated control rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic consequences of taurine deficiency in cats.

Our results show that a lack of taurine in the diet of cats results in a significant leukopenia, a shift in the percentage of polymorphonuclear and mononuclear leukocytes, an increase in the absolute count of mononuclear leukocytes, and a change in the sedimentation characteristics of white cells. Functional studies of polymorphonuclear cells isolated from cats fed taurine-free diets show a significant decrease in the respiratory burst as measured by chemiluminescence as well as a decrease in phagocytosis of Staphylococcus epidermis compared to cats fed the same diet containing taurine. In addition, serum gamma globulin in cats fed taurine-free diets was significantly increased compared to taurine-supplemented cats, indicating that other immune cells may be affected by taurine deficiency. Histological examination of lymph nodes and spleen revealed regression of follicular centers with depletion of reticular cells, mature and immature lymphocytes (B cell areas), as well as mild extravascular hemolysis. These results indicate that there are profound immunologic consequences in cats with prolonged taurine deficiency.

Distribution of IgG subclasses in human colostrum and milk.

Immunoglobulin G (IgG) subclasses in human colostrum and milk were quantitated using mouse monoclonal antibodies specific for human IgG subclasses and an enzyme-linked immunosorbent assay (ELISA). The percentage of IgG1 was significantly increased and that of IgG2 was decreased in both colostrum and milk relative to the percentage distribution reported in healthy adult and maternal sera. Percentages of IgG3 and IgG4 in colostrum, milk and sera were similar. All IgG subclass concentrations decreased by 90% during the first week of lactation and remained constant thereafter. The possible antiviral role of high levels of IgG1 in colostrum and milk is discussed.

Magnesium metabolism in essential hypertension.

Hypertension is a complex, heterogeneous disorder of which the exact etiology is unknown. The difficulty in ascribing an independent role to a single dietary constituent in blood pressure regulation may be due to interactions among nutrients which influence blood pressure. The effect of any one nutrient, particularly magnesium, on hypertension should be considered within the context of overall nutrition in each patient. Clinical, experimental and epidemiologic studies support the role of magnesium in hypertension, whereas a few studies negate this role. Magnesium ions are important in arterial smooth muscle contraction. Since magnesium is found mainly at the inner surface of the cell membranes, it could play a role in cell membrane permeability for sodium and calcium which is important in the etiopathogenesis of hypertension. Magnesium deficiency can predispose to increased contractility of the arteries and its excess can modulate smooth muscle contractility caused by bradykinin, angiotensin II, serotonin, prostaglandins and catecholamines. Magnesium therapy can prevent the development of resistant hypertension and arrhythmias in hypertensives with diuretic-induced hypomagnesemia. It might also reduce blood pressure at least up to 10/5 mm Hg provided adequate magnesium salts are given for an adequate period of time. In view of the still ill defined role of magnesium in hypertension, magnesium supplementation is advised only to those hypertensives who are receiving diuretics and develop resistant hypertension or who have frank magnesium deficiency. A diet rich in magnesium may be used for prevention of hypertension in predisposed communities because of the other advantages of such a diet in prevention.

Lack of efficacy of nafazatrom, a novel anti-thrombotic compound, in patients with coronary artery disease.

Nafazatrom (Bay G 6575) is a novel antithrombotic compound, which acts by stimulation of prostacyclin as well as by inhibition of lipoxygenase enzymes. To determine its effects on exercise performance in coronary artery disease patients, a double-blind study was conducted. Twenty patients with coronary artery disease underwent an exercise stress test before and 2 hours after administration of placebo or nafazatrom (1.2 gm). Before the drug administration, there was evidence of enhanced platelet activity, as reflected by elevated resting plasma beta thromboglobulin and thromboxane B2 concentrations. Plasma 6-keto-PGF1 alpha levels were undetectable in most patients. All coagulation tests were in the normal range. None of these parameters changed with exercise. Administration of placebo or nafazatrom before the exercise stress test did not significantly influence any of the coagulation or platelet function parameters or plasma concentrations of thromboxane B2 and 6-keto-PGF1 alpha. This lack of effect was evident both at rest and upon exercise. Compared to placebo, nafazatrom did not significantly increase exercise tolerance time or exercise-induced symptoms. In conclusion, nafazatrom did not influence exercise performance in patients with coronary disease.