Disposition and placental transfer of etidocaine in pregnancy

Summary Following epidural administration of etidocaine hydrochloride to non-pregnant and pregnant patients, a similar rate of absorption was observed and there was no significant difference in total systemic blood clearance (Cl_sb) of etidocaine in the two groups. There were no major differences in the urinary excretion of etidocaine and metabolites in 48 h urine in both groups. The ability of pregnant women to form the N-glucuronide of the metabolite ABX (2-amino-2-butyroxylidide) was similar to that of non-pregnant individuals. In vitro experiments showed that the blood/plasma concentration ratio () of etidocaine was significantly higher in pregnant females than in males, presumably due to the lower haematocrit in females. The fraction unbound in plasma (f_p) of etidocaine was low in control subjects (mean 0.057) and was not significantly different in pregnant women of 35 to 37 weeks gestation. A marked increase in f_p was observed in pregnant women during delivery (mean 0.264). This finding has potentially serious clinical implications because it is the unbound drug in blood which is pharmacologically important. Placental transfer of etidocaine was rapid and the cord/maternal venous blood concentration ratio at delivery (CM_b) was, with one exception, always less than unity (mean 0.342). Following epidural administration of etidocaine to pregnant women in labour, measurable concentrations of mono-dealkylated metabolites of etidocaine, PABX (2-N-propylamino-2-butyroxylidide) and EABX (2-N-ethylamino-2-butyroxylidide) were detectable in maternal blood within 5 min and cord blood within 30 min. The CM_b for PABX and EABX was 0.401 and 0.658 respectively.List of Abbreviations Used ABX 2-Amino-2-butyroxylidide - EABX 2-N-Ethylamino-2-butyroxylidide - PABX 2-N-Propylamino-2-butyroxylidide - Cl_sb Total systemic blood clearance - Cl_sp Total systemic plasma clearance - Blood/plasma concentration ratio - f_p Fraction of unbound drug in plasma - f_pw Fraction of free drug in plasma water in blood - C_mb Cord/maternal venous blood concentration ratio at delivery - C_mp Cord/maternal venous plasma concentration ratio at delivery - t_1/2 Terminal phase half-life - t_p Time of attainment of peak plasma concentration - E Mean hepatic extraction ratio - Q Liver blood flow     

The Pars Tuberalis: The Missing Link in the Photoperiodic Regulation of Prolactin Secretion?

The endocrine function of the pars tuberalis of the pituitary gland has been an enigma for many years. Recent work suggests that one of its primary functions in seasonal mammals is to mediate photoperiodically regulated changes in prolactin secretion via an unidentified factor called tuberalin.     

Metastatic testicular cancer presenting as spinal cord compression: report of two cases

BACKGROUND: Testicular cancers are heterogenous neoplasms often found in young adults. They tend to metastasize to the chest, retroperitoneum, or neck, but rarely to the long bones or skeleton. However, they can cause neurologic compromise and should be considered in young male patients who present with symptoms of a spine lesion and no known primary cancer. METHODS: Two patients presented with back pain and a rapid progression of lower extremity weakness. Both underwent radiographic workup and emergency surgery. Metastatic workup revealed testicular cancer and widespread metastases. RESULTS: Both patients improved neurologically after surgery, but neither regained the ability to ambulate independently. They both underwent chemotherapy. One patient is alive at 1 year follow-up; the other died 9 months after surgery of widespread metastases. CONCLUSIONS: Vertebral metastases from testicular tumors, although rare, should be considered in young men presenting with spinal cord compression. Work-up should include magnetic resonance imaging (MRI) of the spine and computed tomography (CT) of the chest, abdomen, and pelvis. Urgent intervention may be required, as these two cases show that loss of neurologic function can be rapid and permanent.     

The impact of simulated distal interphalangeal joint fusion on grip strength

This study assessed the impact of distal interphalangeal (DIP) joint fusion on grip strength and how this may be related to a profundus quadriga. Nineteen adults (12 men and 7 women) with an average age of 32.6 years (range: 24-61 years) underwent a series of grip strength measurements with simulation of DIP arthrodesis to the index, long, and index and long (index-long) fingers. The nondominant hand served as a control for the testing. All participants were tested in the same manner: baseline dominant and nondominant hands without DIP block followed by blocking of DIP flexion on the dominant hand only for index, index-long, and long finger alone. Nondominant hands also were tested each time, but without blocking to serve as a control for normal changes in grip strength with repeated testing. Grip strength values were compared to baseline for each trial using the Student's t test. Significant decreases in grip strength were seen for all DIP blocking compared with baseline, but no significant differences were noted in the equivalent trial in the nondominant, nonblocked hand. These findings may have clinical relevance when performing DIP arthrodesis.     

Tuberculous encephalopathy. A rare complication of pulmonary tuberculosis

A case of tuberculous encephalopathy, a rare form of neuro-tuberculosis, is reported in a 16-year-old girl who had pulmonary tuberculosis and extensive cerebral demyelination. The clinical, laboratory and pathological features of this entity are highlighted and the pathogenesis discussed.     

Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids

Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP ( n = 20) and standard Aptamil ( n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group ( n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg⁻¹) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil ( p < 0:01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.     

Effects of nonimmobilizers and halothane on Caenorhabditis elegans

We studied the effects of two nonimmobilizers, a transitional compound, and halothane on the nematode, Caenorhabditis elegans, by using reversible immobility as an end point. By themselves, the nonimmobilizers did not immobilize any of the four strains of animals tested. Toluene appears to be a transitional compound for all strains tested. The additive effects of the nonimmobilizers with halothane were also studied. Similar to results seen in studies of mice, the nonimmobilizers were antagonistic to halothane in the wild type nematode. However, the nonimmobilizers did not affect the 50% effective concentrations of halothane for two other mutant strains. For halothane, the slopes of the dose response curves were smaller in more sensitive strains compared with the wild type. As in mammals, nonimmobilizers antagonize the effects of halothane on the nematode, C. elegans. The variation in slopes in the response to halothane in different strains is consistent with multiple sites of action. These results support the use of C. elegans as a model for the study of anesthetics.     

Using routinely recorded ethnicity: analysis of waiting times for elective admissions by ethnic group.

OBJECTIVE: To assess whether patients from non-white ethnic groups wait longer than white patients for elective in-patient admissions at St Mary's Hospital in London. METHODS: Patients who came off the waiting list for an elective inpatient admission between 1 April 2000 and 31 March 2001 were selected. A multivariable log linear model was developed to assess geometric mean waiting times for Black, Asian, Other and Missing ethnic groups compared to the White group, adjusted for age, sex, urgency and distance. RESULTS: Caution is needed in interpreting results, as a large number of patients had no usable ethnic code. There was no strong evidence that waiting times for ethnic groups were systematically different than for the White group. However, there was some evidence that white patients waited longer for a coronary arteriography than patients in other ethnic groups. This was partially explained by age, sex, clinical urgency and residential distance from St Mary's. CONCLUSIONS: The large proportion of patients with no usable ethnic code, lack of robust methods for case-mix adjustment and multiple ethnic categories makes analysis methodologically difficult. Regular and informative analysis of ethnic coded data is a necessary step in improving the accuracy and completeness of coding.