A high performance liquid chromatography method for the detection of brodifacoum in serum

A procedure for the detection of brodifacoum (BDF) in serum was developed. Extraction of BDF was achieved by acidification of 2 ml of serum with 1 ml of 1.5% acetic acid followed by dual extractions with 10 ml diethyl ether and ether: acetonitrile [1:1]. In spiking experiments, 68 +/- 3, 61 +/- 4 and 65 +/- 5% of added BDF was recovered from serum containing 1000, 100 and 25 ng BDF/ml, respectively. Two high performance liquid chromatography solvent systems were used for chromatographic separation (A: 1.5% acetic acid, pH 4.5: acetonitrile [1:2] with 1% dibutylamine; and B:O.2 M tris(hydroxymethyl)aminomethane, pH 7.5:acetonitrile [1:3]). Detection limits were 75 and 3 ng BDF/ml of serum using ultraviolet absorption (254 nm) and fluorescence measurement (313 nm excitation, 375 nm emission), respectively. This method has been used successfully to monitor serum concentrations of BDF in experimental and field cases of exposure.     

Differential effects of substance P on serotonin-modulated spinal nociceptive reflexes

Recent immunohistochemical studies indicate the presence of a bulbospinal substance P (SP) system, as well as a bulbospinal serotonin (5-HT) system, involved in spinal pain transmission. Although electrophysiological studies indicate that SP may modulate the effects of 5-HT on post-synaptic spinal nociceptive neurons, the functional relationship between SP and 5-HT on “pain behavior” remains obscure. To bridge this gap between mechanism and behavior, the purpose of the present study was to determine specific postsynaptic behavioral effects of SP and 5-HT on local spinal nociceptive reflexes in spinally transected animals. Administration of the 5-HT agonists 5-methoxydi-methyltryptamine (5-MeODMT) (0, 0.5, 1.5, 2.0 mg/kg) and quipazine (0, 5, 10, 20 mg/kg) 2 days after transection significantly expanded the receptive field (RF) areas of three spinal reflexes, as previously reported. Intrathecal administration of SP alone (0, 0.25, 2.5, 7.5 ng) also resulted in hyperalgesia, indicated by a significant expansion of the RF areas of all three nociceptive reflexes. However, administration of SP, in animals pretreated with 5-HT agonists, decreased the 5-HT-induced expansion of RF size. Therefore, SP had opposite effects on spinal nociceptive reflexes depending on whether or not the animal was pretreated with 5-HT agonists, i.e., hyperalgesia in the absence of 5-HT agonists, and analgesia in the presence of 5-HT agonists. The two effects of SP on local spinal reflexes may be related to the anatomical organization of the two spinal SP systems: 1) SP released from primary afferents facilitates nociceptive reflexes, and 2) SP associated with the descending bulbospinal system interacts with the descending bulbospinal 5-HT system and inhibits nociceptive reflexes. The present results help explain contradictory literature regarding the effect of SP on spinal nociceptive reflexes.     

Further evidence supporting a cause and effect relationship between blood transfusion and earlier cancer recurrence.

Studies of associations between perioperative blood transfusions and later recurrence of solid tumors have yielded conflicting results. A previous analysis of transfused patients suggested that recurrence was associated with transfusion of whole blood as opposed to red blood cell concentrates. Additional analyses were performed on patients with cancers of the colon, rectum, cervix, and prostate to determine if patients receiving whole blood, red blood cells only, or no transfusions had differing outcomes. Patients receiving 1 unit or more of whole blood had uniformly poor outcomes compared with nontransfused patients (p less than 0.001). In contrast, patients receiving only red blood cells had progressively worse recurrence and death rates with increasing numbers of transfusion, suggesting the presence of a dose-effect relationship. Employing multivariate techniques, blood transfusion of less than or equal to 3 units that included any whole blood were independently and significantly associated with earlier recurrence (p = 0.003) and death due to cancer (p = 0.02). Transfusions of less than or equal to 3 units of blood comprised solely of red blood cell concentrates were associated with no greater risk of recurrence than that seen in patients receiving no transfusion (p = 0.50). These results provide a potential explanation for the disparate results reported in studies of blood transfusion and cancer outcome. The marked difference in outcome seen between patients receiving a few units of red blood cells and comparable patients receiving even one unit of whole blood are consistent with the hypothesis that transfusion of stored blood plasma causes earlier tumor recurrence in some instances. Strategies for reducing these risks might include avoidance of whole blood transfusions when only 1-3 units are required, more conservative transfusion practice, use of autologous blood transfusions, and perhaps, use of red blood cells washed free of plasma and white cell debris. Clinical trials to test these hypotheses are urgently needed.     

Life-sustaining therapy. A model for appropriate use

New strategies are needed to curb the proliferation of life-sustaining therapies that rarely benefit patients. We propose a model for appropriate use of such therapies that incorporates effectiveness, utility, and marginal costs. If a therapy is rarely effective and rarely desirable, it is considered medically inappropriate. If the marginal cost-effectiveness ratio is inordinately high, it is considered economically inappropriate. If a therapy is either medically or economically inappropriate, it should not be automatically offered. The model provides an operational definition of futility and is illustrated with an analysis of out-of-hospital cardiopulmonary resuscitation for chronically ill older people. Advance directives, explicit health care rationing, and defining futile therapy based on survival predictions are alternatives to the appropriate care model, but are insufficient strategies to solve the problem of inappropriate life-sustaining care.     

Facilitating access to glucometer reagents increases blood glucose self-monitoring frequency and improves glycaemic control: a prospective study in insulin-treated diabetic patients.

AIMS: To investigate whether availability of glucometer reagents increases the frequency of self-blood glucose monitoring (SBGM) and improves glycaemic control in diabetic patients. METHODS: Sixty-two insulin-treated diabetic patients were randomized to two groups, matched for age, gender, education, income, type and duration of diabetes, years of insulin treatment, number of daily insulin injections, and haemoglobin (Hb)A1c. All patients were given a glucometer, but one group (no cost, NC) was provided glucometer test strips free of charge. The other group (control, C) had to purchase strips as they found it necessary. Both groups of patients were followed longitudinally at 2-monthly intervals for 12 months with measurement of blood glucose and HbA1c, and the frequency of SBGM was determined by downloading the glucometer memory. RESULTS: The SBGM frequency was significantly higher in the NC group vs. the C group during the first 4 months (2.0 +/- 0.2 tests/day vs. 1.4 +/- 0.1 tests/day, P<0.025). Mean HbA1c remained stable over the 12 months in the NC group, whereas an increase with time was observed in the C group. The difference in HbA1c between the two groups was significant (P<0.002) after 6 months. Random blood glucose measured at each visit and average glucose recorded by the glucometer were also lower in the NC group vs. the C group (P<0.005). There was a negative correlation between HbA1c and SBGM frequency, and HbA1c in patients testing at least twice a day was lower than in those testing less than twice a day (8.8 +/- 0.2% vs. 9.6 +/- 0.2%, P<0.001). CONCLUSIONS: In this prospective study, having easy access to glucometer strips provided free of charge to patients increased SBGM frequency. The relationship between HbA1c and SBGM frequency supports the view that SBGM is an essential tool in diabetes management.     

Healthy choices: motivational enhancement therapy for health risk behaviors in HIV-positive youth.

This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16-25. Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention. Youth were randomized to receive a four-session motivational enhancement intervention (N = 25) or to a wait-list control (N = 26). Of the eligible youth approached, 88% agreed to participate, and 80% percent of participants completed at least three of four sessions. The treatment group showed significantly greater reductions in unprotected sex acts and in viral load compared with controls. Although change scores for substance use were not significantly different between the two groups, paired t tests demonstrated that reductions in alcohol use and marijuana use were significant for the treatment group at the trend level. There were no significant differences in substance use from baseline to posttest for the control group. Findings demonstrate the potential of a brief motivational enhancement intervention to improve health risk behaviors in HIV-positive youth. Larger randomized clinical trials are warranted. Resources required for retention should not be underestimated.     

Shunt nephritis

Six children with shunt nephritis are reported of whom two did not show complete recovery of renal function. Follow up and outcome in relation to the delay in diagnosis and renal biopsy appearances are discussed.