Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation.

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. x 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10-21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.

A new Coenzyme Q10 tablet-grade formulation (all-Q) is bioequivalent to Q-Gel and both have better bioavailability properties than Q-SorB.

Commercial Coenzyme Q10 (CoQ10, ubiquinone) formulations are often of poor intestinal absorption. We investigated the bioavailability of DSM Nutritional Products Ltd. (Kaiseraugst, Switzerland) CoQ10 10% TG/P (all-Q), a new tablet-grade formulation, with CoQ10 Q-Gel Softsules based on the Bio-Solv technology (Tishcon Corp., Salisbury, MD; marketed by Epic4Health, Smithtown, NY) and Q-SorB (Nature's Bounty, Bohemia, NY). Twelve healthy male subjects participated in a randomized, three-period crossover bioequivalence study. Plasma CoQ10 was determined from pre-dose until +36 hours. To compare bioavailability, corrected maximum concentration (Cmax) and area under the curve from 0 to +14 hours [AUC(0-14 h)] were assessed and tested for bioequivalence. The bioequivalence ranges of 0.8-1.25 hour x microg/mL for AUC(0-14 h) and 0.75-1.33 microg/mL for Cmax were applied. In summary, the kinetic profiles of all CoQ10 preparations revealed a one-peak plasma concentration-time course. Highest Cmax values were seen after Q-Gel application, whereas time to Cmax was nearly identical across all treatments. The AUC(0-14 h) values were highest for Q-Gel, narrowly followed by all-Q. The tests for bioequivalence showed a bioequivalence between Q-Gel and all-Q, and both preparations were found to have better bioavailability properties than Q-SorB. Although all-Q and Q-Gel have equivalent bioavailability properties, all-Q can be directly used in tablets, while this is not the case for Q-Gel or other similar forms.

The effects of local anaesthetic solution in the navicular bursa of horses with lameness caused by distal interphalangeal joint pain.

REASONS FOR PERFORMING STUDY: Analgesia of the palmar digital (PD) nerves has been demonstrated to cause analgesia of the distal interphalangeal (DIP) joint as well as the sole. Because the PD nerves lie in close proximity to the navicular bursa, we suspected that that analgesia of the navicular bursa would anaesthetise the PD nerves, which would result in analgesia of the DIP joint. OBJECTIVES: To determine the response of horses with pain in the DIP joint to instillation of local anaesthetic solution into the navicular bursa. METHODS: Lameness was induced in 6 horses by creating painful synovitis in the DIP joint of one forefoot by administering endotoxin into the joint. Horses were videorecorded while trotting, before and after induction of lameness, at three 10 min intervals after instilling 3.5 ml local anaesthetic solution into the navicular bursa and, finally, after instilling 6 ml solution into the DIP joint. Lameness scores were assigned by grading the videorecorded gaits subjectively. RESULTS: At the 10 and -20 min observations, median lameness scores were not significantly different from those before administration of local anaesthetic solution into the navicular bursa (P > or = 0.05), although lameness scores of 3 of 6 horses improved during this period, and the 20 min observation scores tended toward significance (P = 0.07). At the 30 min observation, and after analgesia of the DIP joint, median lameness scores were significantly improved (P < or = 0.05). CONCLUSIONS: These results indicate that pain arising from the DIP joint can probably be excluded as a cause of lameness, when lameness is attenuated within 10 mins by analgesia of the navicular bursa. POTENTIAL RELEVANCE: Pain arising from the DIP joint cannot be excluded as a cause of lameness when lameness is attenuated after 20 mins after analgesia of the navicular bursa.

Oxidative stress in humans during work at moderate altitude.

Increased oxidative stress has been associated with work at high altitude; however, it is not known whether oxidative stress is a significant problem at moderate altitudes. The oxidative stress indicators, breath pentane (BP), 8-hydroxydeoxyguanosine (8-OHdG), oxygen radical absorption capacity (ORAC), 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and lipid peroxides (LPO) were measured in breath, blood and urine samples of U.S. Marines engaged in moderate altitude ( approximately 3000 m) cold weather field training. The test subjects were divided into a placebo and four antioxidant supplement groups (n = 15/group) and received the following supplements for 28 d: 1) vitamin E, 440 alpha-tocopherol equivalents (alpha-TE); 2) vitamin A, 2000 retinol equivalents (RE) of beta-carotene; 3) vitamin C, 500 mg ascorbic acid; 4) a mixture of 440 alpha-TE, 2000 RE of beta-carotene, 500 mg ascorbic acid, 100 microg selenium and 30 mg zinc daily. Strenuous work ( approximately 23 MJ/d) in cold weather at moderate altitude was accompanied by increases in several indicators of oxidative stress that were not effectively controlled by conventional antioxidant supplements. The group receiving the antioxidant mixture exhibited lower BP (P < 0. 05) compared with those receiving single antioxidant supplements; however, not all markers of oxidative stress responded like BP. Because these markers did not respond in the same manner, it is important to include markers from more than one source to assess the effect of supplemental dietary antioxidants.

Identification and management of pregnancy-related low back pain.

Back pain is a common complaint of women during pregnancy. It is frequently dismissed as trivial and inevitable. This article gives an overview of recent research on pregnancy-related back pain that documents the impact of this pain on women's lives, during and beyond the childbearing year. It argues for a more active approach to the prevention and management of back pain during pregnancy. Two common back pain types, lumbar pain and posterior pelvic pain, are described and basic management techniques for the woman and her primary caregiver are suggested. Red flag findings that necessitate specialist referral are also highlighted, as are suggestions for further research.

Nephrotoxicity of high-dose ifosfamide/carboplatin/etoposide in adults undergoing autologous stem cell transplantation.

The objective of this study was to evaluate nephrotoxicity in adult patients treated with high-dose ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation. We conducted a retrospective analysis of clinical and laboratory data from 131 patients with various malignancies who received treatment with escalating doses of ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation as part of a phase I/II therapeutic trial. Abnormalities in glomerular filtration were evaluated by measuring peak creatinine levels and tubular dysfunction by the lowest recorded serum levels of potassium, magnesium, and bicarbonate, at different time periods after administration of ifosfamide, carboplatin, and etoposide, and after autologous stem cell transplantation. For the entire group of 131 patients, peak creatinine levels were > 1.5 mg/dL but < 3.0 mg/dL in 37% and levels were > 3.0 mg/dL in 11% at some time during their hospital stay. At the time of discharge, creatinine levels were 1.6 mg/dL to 3.0 mg/dL in 25% of patients and were > 3 mg/dL in 5%. Immediately after high-dose therapy, peak creatinine levels were significantly higher in patients receiving higher doses of ifosfamide compared to those receiving lower doses (P < 0.00001) and those receiving intermediate doses (P < 0.005). There was a dramatic decrease in serum bicarbonate, potassium, and magnesium levels immediately after chemotherapy, and they remained significantly decreased throughout the patient's hospital stay, despite massive replacement efforts (P ranging between < 0.008 and < 0.001). This is the largest adult population study documenting the incidence and severity of ifosfamide/carboplatin/etoposide-associated acute nephrotoxicity. Renal dysfunction was dose related and reversible in the majority of patients.

The haemostatic effectiveness of autologous platelet rich plasma sequestered after heparin administration and institution of cardiopulmonary bypass.

Preoperative harvesting and postoperative reinfusion of autologous platelet rich plasma (PRP) has been reported to decrease blood loss as well as the requirement for homologous blood transfusion following cardiopulmonary bypass (CPB). We have developed a technique of intraoperative PRP sequestration which occurs during the initial period of CPB after the patient's circulation is supported and heparin has been given (PRP+). This process does not require any additional hardware, personnel or expense and it is performed without difficulty or complication. To evaluate the effect of PRP+ sequestration and reinfusion on blood loss and homologous blood requirement after CPB, we randomly assigned 126 consecutive patients undergoing elective open heart surgery into the experimental group 1 (PRP+) (n = 64) or the control (no platelet pheresis) group 2 (n = 52). A third group (n = 10) were not included in the randomization. Patients in group 3 had PRP prepared by conventional techniques (PRPc) prior to heparin administration and given to the patient after protamine infusion. Aggregation and activation studies were performed on the PRP+, PRPc, and blood bank platelets (BBP). Per cent aggregation of PRP in response to ADP was superior to that of BBP. There were no significant differences in ADP induced aggregation between PRP+ and PEPc. There was no significant difference in platelet activation (CD62) or number between the three groups. Patients infused with PRP+ showed significantly increased aggregation to ADP when compared with untreated patients 120 minutes after return to the ICW. Furthermore, more homologous haemostatic components (platelets/fresh frozen plasma) were required in the control group. We have demonstrated that collection of autologous PRP+ after administration of heparin does not interfere with its haemostatic effectiveness compared with PRPc prepared before the initiation of bypass. Moreover, this can be performed universally in haemodynamically unstable patients without any additional costs.

Treating hypertension in non-insulin-dependent diabetes: a comparison of atenolol, nifedipine, and captopril combined with bendrofluazide.

Twenty-five of thirty NIDDS who remained hypertensive (diastolic greater than 95 mmHg supine) after 4 weeks on bendrofluazide 2.5 mg daily (B), completed a single-blind, observer-blind randomized crossover study, in which the additional use of atenolol (50 mg daily) (A), slow-release nifedipine (20 mg twice daily) (N), and captopril (25 mg twice daily) (C) was compared. Patients took each drug for 8 weeks with dose doubling at 4 weeks if supine diastolic remained greater than 90 mmHg. All three combinations were more effective than bendrofluazide alone (p less than 0.01). In nine patients studied 2 h after tablets at the end of each treatment period nifedipine was more effective than the other two drugs (B:174/104 mmHg, A:162/95 mmHg, -8%, N:141/88 mmHg, -17%, C:157/94 mmHg, -10%, supine), whereas in 16 patients studied 15 h after their evening dose there was no significant difference. Fasting insulin and HbA1 levels were not significantly different between groups. No drug had a significant adverse effect on creatinine, glomerular filtration rate, overnight urinary albumin excretion or foot transcutaneous oxygen levels (43 degrees C). All three drugs studied were effective without deleterious effects on renal function or peripheral blood flow.

Infant blood pressure and heart rate: relation to ethnic group (black or white), nutrition and electrolyte intake.

Blood pressure (BP) and heart rate were measured during non-rapid-eye-movement sleep in 392 full-term newborns and in 318 of these infants at age six months. Two-day records of food intake were collected at age six months for 150 infants. Black babies did not differ substantially in BP from white babies either at birth or at six months. The earliest BP tracking was from age six to 15 months (systolic (SBP): r = .29, p less than .001; diastolic:r = .45, p less than .001). No relationship was found between BP at six months and breast- or bottle-feeding, infant weight or weight change, or nutrient intake. The relationship between parental BP, on the one hand, and infant electrolyte intake and BP on the other, suggested that electrolyte intake was related to BP in the six-month-old infant, and that the relationship was different in white babies than in black babies. Among 56 white infants whose mother's mean BP was above the median for this population, infant sodium intake correlated with infant SBP (r = .31, p less than .009). Among 32 black infants, regardless of parents' BP, sodium intake was negatively correlated with SBP (r = -.36, p less than .021).