Quantitative studies on the urinary metabolic fate of 2-chloro-4-trifluoromethylaniline in the rat using 19F-NMR spectroscopy and directly coupled HPLC-NMR-MS

1. The metabolism and urinary excretion of 2-chloro-4-trifluoromethylaniline has been studied in the rat using 19F-NMR spectroscopy and directly coupled HPLC-NMR-MS methods. The compound was dosed to three male Sprague-Dawley rats (50 mg kg(-1) i.p.) and urine collected over 0-8, 8-24 and 24-48 h post-dosing. 2. A total urinary recovery of 56.3+/-2.2% of the dose was achieved up to 48 h after dosing. The major metabolite in the urine was identified as 2-amino-3-chloro-5-trifluoromethylphenylsulphate accounting for a total of 33.5+/-2.2% of the dose. 3. Further metabolites detected and characterized included 2-chloro-4-trifluoromethylphenylhydroxylamine glucuronide (13.2+/-0.5% of the dose), 2-amino-3-chloro-5-trifluoromethylphenylglucuronide (3.8+/-0.4% of the dose) and 2-chloro-4-trifluoromethylaniline-N-glucuronide (3.6+/-0.1% of the dose). Several minor metabolites were also found and identified, including 2-chloro-4-trifluoromethylphenylsulphamate, which together accounted for 2.1+/-0.4% of the dose. 4. Directly coupled HPLC-NMR-MS and 19F-NMR spectroscopy is shown to provide an efficient approach for the unequivocal and rapid determination of the quantitative urinary metabolic fate and excretion balance of a fluorinated xenobiotic without the necessity for specific radiolabelling.     

Functional hallux rigidus in the rheumatoid foot

Hallux rigidus results from arthritic involvement of the first metatarsophalangeal joint. The authors have observed loss of motion at this joint in patients with rheumatoid arthritis in the absence of hallux valgus or joint destruction. A hyperextension deformity of the interphalangeal joint has also been observed, with a painful callus beneath it. The first metatarsophalangeal joint appears normal on roentgenograms, and passive motion of the joint is normal when it is examined clinically. The loss of first metatarsophalangeal motion is functional, and stems from muscle spasm of the great toe intrinsic muscles in an effort to relieve pressure on the lesser metatarsal heads. The interphalangeal hyperextension may develop secondary to "functional hallux rigidus."     

Adult height in patients with childhood onset atopic dermatitis

Cross sectional studies have reported impaired growth in children with atopic dermatitis. If this growth impairment is irreversible, it would be expected to adversely influence final height attainment. The standing heights and other anthropometric parameters were assessed in 35 adults with onset of atopic dermatitis before 5 years of age and a control group of 35 adults with adult onset contact dermatitis or psoriasis. There was no significant difference in the standing height SD score, mid-parental height SD score, sitting height SD score, subischial leg length SD score, nor body mass index between the atopic dermatitis and control groups. The standing height SD score was not significantly different among: (a) patients with atopic dermatitis affecting less than 50% of their body surface area and those with greater than 50% affected; (b) patients using the four different potency topical corticosteroids; and (c) patients with atopic dermatitis without asthma and those with coexisting asthma. It is concluded that short stature is not a feature of our group of adult patients with onset of atopic dermatitis before 5 years of age, continuing into adulthood, and severe enough to require specialist care. This suggests that if growth impairment occurs in childhood, it is likely to be temporary and reversible.     

Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry

OBJECTIVE: To establish criteria for the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency in the UK population using a method in which carnitine species eluted from blood spots are butylated and analysed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). DESIGN: Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A985G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes. RESULTS: All patients with MCAD deficiency had an octanoylcarnitine concentration ([C8-Cn]) > 0.38 microM and no accumulation of carnitine species > C10 or < C6. Among the patients with MCAD deficiency, the [C8-Cn] was significantly lower in children > 10 weeks old and in children with carnitine depletion (free carnitine < 20 microM). Neonatal blood spots from patients with MCAD deficiency had a [C8-Cn] > 1.5 microM, whereas in heterozygotes and other normal neonates the [C8-Cn] was < 1.0 microM. In contrast, the blood spot [C8-Cn] in eight of 27 patients with MCAD deficiency > 10 weeks old fell within the same range as five of 15 MCAD heterozygotes (0.38-1.0 microM). However, the free carnitine concentrations were reduced (< 20 microM) in the patients with MCAD deficiency but normal in the heterozygotes. CONCLUSIONS: Criteria for the diagnosis of MCAD deficiency using ESI-MS/MS must take account of age and carnitine depletion. If screening is undertaken at 7-10 days, the number of false positive and negative results should be negligible. Because there have been no instances of death or neurological damage following diagnosis of MCAD deficiency in our patient group, a strong case can be made for neonatal screening for MCAD deficiency in the UK.     

Impact of Generalist Care Managers on Patients with Diabetes

Objective. To determine how the addition of generalist care managers and collaborative information technology to an ambulatory team affects the care of patients with diabetes.
Study Setting. Multiple ambulatory clinics within Intermountain Health Care (IHC), a large integrated delivery network.
Study Design. A retrospective cohort study comparing diabetic patients treated by generalist care managers with matched controls was completed. Exposure patients had one or more contacts with a care manager; controls were matched on utilization, demographics, testing, and baseline glucose control. Using role-specific information technology to support their efforts, care managers assessed patients' readiness for change, followed guidelines, and educated and motivated patients.
Data Collection. Patient data collected as part of an electronic patient record were combined with care manager-created databases to assess timely testing of glycosylated hemoglobin (HbA1c) and low-density lipoprotein (LDL) levels and changes in LDL and HbA1c levels.
Principal Findings. In a multivariable model, the odds of being overdue for testing for HbA1c decreased by 21 percent in the exposure group ( n =1,185) versus the control group ( n =4,740). The odds of being tested when overdue for HbA1c or LDL increased by 49 and 26 percent, respectively, and the odds of HbA1c <7.0 percent also increased by 19 percent in the exposure group. The average HbA1c levels decreased more in the exposure group than in the controls. The effect on LDL was not significant.
Conclusions. Generalist care managers using computer-supported diabetes management helped increase adherence to guidelines for testing and control of HbA1c levels, leading to improved health status of patients with diabetes.     

Violence in the Schools: Clinical Issues and Case Analysis for High-Risk Children

School violence in rural communities has gained considerable attention nationally. Examined are theoretical considerations involving escape theory, the risk and protective factors for school violence, case analyses of recent case studies, and discussion of recent school violence involving fatal injuries to others. Also discussed are diagnostic issues in understanding children who are at-risk for school violence and ways school violence maybe managed in the schools. Suggestions and recommendations including recommendations provided by the National School Safety Center for school personnel are offered, as are steps to be taken in creating a safe school environment. This information may be helpful to child psychiatry and clinical personnel who provide services to school aged children.     

The significance of a high plasma ammonia value.

At a tertiary referral centre, just over 50% of patients with plasma ammonia values over 200 micro mol/l had inborn errors of metabolism. To distinguish artefactual high values from those requiring treatment, the measurement should be repeated immediately if the result is above 200 micro mol/l and at lower concentrations if the patient is encephalopathic.     

A quality assessment tool to evaluate tocolytic studies

Over the past 15 years, the use of β-agonists has declined worldwide. Following the Royal College of Obstetricians and Gynaecologists guidelines in 2002, clinicians in the UK and beyond were faced with the dilemma of continuing to use β-agonists, desist from using tocolytic therapy completely or choosing to change to atosiban or calcium channel blockers (CCBs). While grade A level 1 evidence exists to show that atosiban is significantly more efficacious than placebo and significantly safer than β-agonists for the treatment of spontaneous preterm labour, the evidence for CCBs, such as nifedipine, is much less robust and no placebo-controlled trials have been performed. Published studies on nifedipine are largely investigator-led studies of small sample size, which lack sufficient power. As a result, most of the evidence has been based on meta-analyses of these studies, which look retrospectively at pooled data and are only as good as the quality of the studies included. In light of this, a tool was developed to produce a systematic review of studies on tocolytic effectiveness, which can and should be applied to all tocolytics and which considered both method- and topic-specific markers of quality. In the process of applying this tool to nifedipine, an extensive literature search identified 31 studies for a systematic review of the quality of nifedipine studies assessed by eight paired reviewers with wide experience in the subject of spontaneous preterm labour and preterm birth. Forty topic- and method-specific items of quality were assessed. The paucity of good quality studies of nifedipine used for the treatment of spontaneous preterm labour should be highlighted in meta-analyses or systematic reviews, which measure efficacy and should limit and influence the degree to which recommendations and guidelines are made on the basis of such studies.