Can saliva replace plasma for the monitoring of methadone?

The aims of this study were to determine the relationship between saliva and plasma methadone concentrations and the influence of variability in saliva pH. Saliva and plasma samples were taken before the daily dose of methadone in 60 patients undergoing methadone maintenance treatment (MMT). Saliva pH was measured immediately after sampling, and concentrations of (RS)-, (R)-, and (S)-methadone in saliva and plasma were assayed by LC/MS. In addition, unbound (R)- and (S)-methadone concentrations were measured in plasma samples by ultrafiltration. Plasma binding and pH differences between plasma and saliva were then used to estimate methadone saliva/plasma ratios and to compare them with observed values. Saliva pH ranged from 5.1 to 7.6 (mean +/- SD, 6.7 +/- 0.5). Plasma and saliva concentrations correlated weakly [(RS)-, r = 0.14, P = 0.007, n = 44; (R)-, r = 0.10, P = 0.04, n = 43; (S)-, r = 0.22, P = 0.002, n = 43], and the mean saliva-to-plasma methadone concentration ratios were 1.1 (+/-1.3 SD), 1.5 (+/-1.5), and 0.8 (+/-0.8), for (RS)-, (R)-, and (S)-methadone, respectively. Corresponding values based on unbound concentrations of methadone in plasma were 21 (+/-20.6, n = 31), 21 (+/-19, n = 34), and 17 (+/-15, n = 36). The salivary concentration-to-dose ratios showed statistically significant but weak inverse correlations with saliva pH [(RS)-, r = 0.27, P < 0.001; (R)-, r = 0.25, P < 0.001; (S)-, r = 0.29, P < 0.001, respectively]. There were significant correlations between predicted and observed saliva/plasma ratios [(RS)-, r = 0.44, P < 0.001, n = 31; (R)-, r = 0.58, P < 0.001, n = 32; (S)-, r = 0.10, P = 0.04, n = 34], but the mean predicted saliva concentrations were about 5 times lower than the mean observed values. The poor correlations between salivary and plasma methadone concentrations observed in this study are partly related to the effect of variable saliva pH. However, saliva pH explained only 10%-36% of the total variation. As a conclusion, monitoring methadone concentrations in saliva may not be a useful alternative to plasma concentration measurements. Correction for saliva pH measured immediately after collection improves the relationship between saliva and plasma methadone concentration, but most of the variation remains unexplained.     

Choice of oximeter affects apnea-hypopnea index

STUDY OBJECTIVES: Current Medicare guidelines include an apnea-hypopnea index (AHI) > or = 15 events per hour, in which all hypopneas must be associated with 4% desaturation, to qualify for reimbursement for therapy with continuous positive airway pressure (CPAP). The present data demonstrate the effect of pulse oximeter differences on AHI. DESIGN: Prospective study, blinded analysis. SETTING: Academic sleep disorder center. PATIENTS: One hundred thirteen consecutive patients (84 men and 29 women) undergoing diagnostic sleep studies and being evaluated for CPAP based on the Medicare indications for reimbursement. INTERVENTIONS: Patients had two of four commonly used oximeters with signal averaging times of 4 to 6 s placed on different digits of the same hand during nocturnal polysomnography. MEASUREMENTS AND RESULTS: Apneas and candidate hypopneas (amplitude reduction, > 30%) were scored from the nasal cannula airflow signal without reference to oximetry. Candidate hypopneas then were reclassified as hypopneas by each oximeter if they were associated with a 4% desaturation. Although the use of three oximeters resulted in a similar AHI (bias, < 1 event per hour), the fourth oximeter showed an overall increase in AHI of 3.7 events per hour. This caused 7 of 113 patients to have an AHI of > or = 15 events per hour (meeting the Medicare criteria for treatment) by one oximeter but not when a different oximeter was used. More importantly, when our analysis was limited to those patients whose number of candidate hypopneas made them susceptible to the threshold value of 15 events per hour, 7 of 35 patients who did not meet the Medicare AHI standard for treatment by one oximeter were reclassified when a different oximeter was used. CONCLUSION: In the present study, oximeter choice affected whether the AHI reached the critical cutoff of 15 events per hour, particularly in those with disease severity that was neither very mild nor very severe. As oximetry is not a technique that produces a generic result, there are significant limitations to basing the definition of hypopnea on a fixed percentage of desaturation in determining the eligibility for CPAP therapy.     

Living kidney donor follow-up in a dedicated clinic

BACKGROUND: Long-term effects of uninephrectomy for kidney donation are of particular interest in the currently increasing practice of living-donor transplantation. We have retrospectively analyzed the general health status and renal and cardiovascular consequences of living-related kidney donation. METHODS: Data of living-related kidney donors who were regularly followed up in a dedicated clinic at the Sindh Institute of Urology and Transplantation between July 2000 and January 2004 was retrieved. They had donated their kidneys from 1986 onward. Data on weight, blood pressure, creatinine clearance, level of proteinuria, and new onset diabetes mellitus were analyzed. RESULTS: Seven hundred and thirty-six donors with a mean age of 36+/-10.9 years (M:F 1.1:1) were evaluated. With a mean postnephrectomy duration of 3+/-3.2 years (range 6 months-18 years), the creatinine clearance fell to 87% of prenephrectomy values, and 49 (6.7%) had a creatinine clearance of less than 60 mL/ min. Hypertension developed in 76 (10.3%) donors, and 179 (24.3%) had proteinuria exceeding 150 mg/24 hr. Overweight (27.8%) and obese subjects (11.5%) had a higher prevalence of hypertension and new onset diabetes mellitus. One donor developed end-stage renal failure. CONCLUSION: Donor nephrectomy has minimal adverse effects on overall health status. Regular donor follow-up identifies at-risk populations and potentially modifiable factors.     

Switchability of neoral and equoral according to Food and Drug Administration rules and regulations

According to the US Food and Drug Administration (FDA), if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product, then it is equivalent and can be substituted (switchable) for that drug product. Methods used to define bioequivalence as stated by the FDA rules (FDA 21 CFR 320, 24) are (1) pharmacokinetic (PK) studies in healthy volunteers, (2) comparative clinical trials, and (3) pharmacodynamic (PD) studies (bioactivity). We evaluated the switchability of Equoral (IVAX-USA) with Neoral (Novartis Switzerland using all FDA rules. In a single oral dose, we undertook a comparative bioavailability study of Equoral (IVAX, USA) Neoral (Novartis, USA), and Neoral (Novartis UK). The pharmacokinetics of Equoral and Neoral were determined with blood levels at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 42, and 48 hours. The area under curve (AUC), AUC extrapolated to infinity (AUC0-inf), rate of absorption (Tmax), extent of absorption (Cmax), half time (t1/2) of Equoral and Neoral were all within the 90% confidence interval of 80% to 125% boundaries. A comparative multinational multicenter clinical trial in stable renal transplant patients included 70 patients (22 women and 48 men) of mean age of 33 years (range, 26 to 43) was performed in Turkey, Lebanon, and Pakistan. In this study the ratios of LSM and the 90% confidence intervals for the Nontransformed/Parameters (AUC0-t, AUCinf, Tmax, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, which are within the 80% to 125% FDA acceptance range. For immunosuppressive drugs, the site of action is the lymphocyte and the measurable response is the decrease in lymphocyte count caused by the relative concentration of the drug in the lymphocyte. In a controlled switch, fixed-dose study, both Equoral and Neoral achieved the same concentration in the lymphocytes and caused the same degree of lymphocyte count reduction. The results of the testing (bioavailability-bioequivalence, clinical studies, and pharmacodynamic-bioactivity) required by FDA for interchangeability ("switchability") of immunosuppressive agents suggests that Neoral and Equoral are switchable.     

Clinical outcome of active extravasation in splenic trauma

The purpose of this study was to determine the necessity for splenectomy in patients with active extravasation on contrast enhanced CT secondary to splenic trauma. We reviewed cases of splenic injury and classified these according to the American Association for the Surgery of Trauma (AAST) grading scale. The presence of active extravasation and associated injuries was assessed. Chart review was then performed to determine age, sex, mechanism of injury, indications for splenectomy, and clinical outcome. Of 82 cases evaluated, 12 grade I, 15 grade II, 30 grade III, 17 grade IV, and 8 grade V injuries were present. Eighteen patients were actively extravasating. Of extravasating patients, 13 eventually underwent open splenectomy or embolization and five (27.8%) were managed expectantly with success. Of grade IV injuries, 9/17 showed active extravasation, of which six underwent splenectomy. Of grade V injuries, 3/8 showed active extravasation, and all three underwent intervention. Splenectomy may not be necessary in appropriately chosen patients with active extravasation from the spleen in blunt abdominal trauma.     

Glass front of gas fire places: a clear and present danger

BACKGROUND: Glass fronted gas fires have become a popular addition to many homes as a source of heat energy. The flames, however, provide curiosity for young children attracting them towards the hot glass plate resulting in contact burns. Our study aimed to ascertain the features and pattern of morbidity of such injuries, and to address preventive measures. METHODS: Retrospective analysis of children with contact burns who were treated in our unit over an eight-year period. The cases were identified from the burns database, and their case-notes and follow-up records reviewed. RESULTS: Thirty-five children (M: 20; F: 15; Age range: 6 months to 10 years) were identified. The total body surface area of the burn was between <1 and 5%. Hand or fingers were the commonest sites involved. The depth was variable with 21 children sustaining superficial and seven deep dermal burns. All but one child were treated conservatively. Follow-up visits ranged from one to 24 (median: five); follow-up period was from 2 days to 1 year (median: 17 days). CONCLUSION: Although glass plate contact burns may be minor and superficial, they nevertheless affect a vital anatomical area. They also result in psychological distress for the child, and stress and time off work for parents. Awareness and measures to prevent such injuries should therefore be addressed by the responsible authorities.     

Impact of maternal depression on infant nutritional status and illness: a cohort study

BACKGROUND: The risk for emotional and behavioral problems is known to be high among children of depressed mothers, but little is known about the impact of prenatal and postnatal depression on the physical health of infants. OBJECTIVE: To determine whether maternal depression is a risk factor for malnutrition and illness in infants living in a low-income country. DESIGN: Prospective cohort study. SETTING: Rural community in Rawalpindi, Pakistan. PARTICIPANTS: Six hundred thirty-two physically healthy women were assessed in their third trimester of pregnancy to obtain at birth a cohort of 160 infants of depressed mothers and 160 infants of psychologically well mothers. MAIN OUTCOME MEASURES: All infants were weighed and measured at birth and at 2, 6, and 12 months of age, and they were monitored for episodes of diarrhea and acute respiratory infections. The mothers' mental states were reassessed at 2, 6, and 12 months. Data were collected on potential confounders of infant outcomes, such as birth weight and socioeconomic status. RESULTS: Infants of prenatally depressed mothers showed significantly more growth retardation than controls at all time points. The relative risks for being underweight (weight-for-age z score of less than -2) were 4.0 (95% confidence interval [CI], 2.1 to 7.7) at 6 months of age and 2.6 (95% CI, 1.7 to 4.1) at 12 months of age, and the relative risks for stunting (length-for-age z score of less than -2) were 4.4 (95% CI, 1.7 to 11.4) at 6 months of age and 2.5 (95% CI, 1.6 to 4.0) at 12 months of age. The relative risk for 5 or more diarrheal episodes per year was 2.4 (95% CI, 1.7 to 3.3). Chronic depression carried a greater risk for poor outcome than episodic depression. The associations remained significant after adjustment for confounders by multivariate analyses. CONCLUSIONS: Maternal depression in the prenatal and postnatal periods predicts poorer growth and higher risk of diarrhea in a community sample of infants. As depression can be identified relatively easily, it could be an important marker for a high-risk infant group. Early treatment of prenatal and postnatal depression could benefit not only the mother's mental health but also the infant's physical health and development.     

Mesenteric panniculitis

Mesenteric panniculitis is a rare condition of unknown etiology that causes inflammation of the adipose tissue in the mesentery. We describe a case in which mesenteric panniculitis was diagnosed on the basis of imaging and resolved spontaneously.