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.     

Timed intercourse after intrauterine insemination for treatment of infertility

Objective: To compare the pregnancy rates, between intrauterine insemination (IUI) followed by timed intercourse and IUI only for treatment of the infertile couples. Study design: A prospective study of two different protocols of intrauterine insemination in two hundred and one infertile couples with a normal spermiogram was carried out. Of these, 101 couples were treated with IUI alone and 100 couples had both IUI and timed intercourse within a 12-18 h period. The pregnancy rates were compared between groups. Results: The characteristics of the two groups were similar in terms of the mean age, as well as the duration and causes of infertility. The cycle characteristics following follicular stimulation were also similar between two groups. The pregnancy rate per cycle increased with increasing numbers of total motile sperm per insemination in the IUI alone group (P=0.045). Timed intercourse increased pregnancy rate in patients with lower motile sperm number (<40×10⁶) (27.7% versus 10.5%, P=0.023), but not in patients with higher sperm number (≥40×10⁶) (25.7% versus 22.7%, P=0.671). Conclusions: In IUI with low number of motile sperm inseminated, timed intercourse significantly increases the pregnancy rates over IUI alone in infertile couples with a normal sperminogram. This alternative treatment appears to be a practical, simple, and inexpensive addition that improves the pregnancy rate in patients receiving ovulation induction and intrauterine insemination program.     

Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment

Involvement of the dopaminergic system has been suggested in patients suffering from attention deficit hyperactivity disorder (ADHD) since the symptoms can be successfully treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). This study reports the findings on the status of the DAT in adults with ADHD before and after commencement of treatment with methylphenidate, as measured using [99mTc]TRODAT-1. Seventeen patients (seven males, ten females, aged 21-64 years, mean 38 years) were examined before and after the initiation of methylphenidate treatment (3x5 mg/day). All subjects were injected with 800 MBq [99mTc]TRODAT-1 and imaged 3 h p.i. Single-photon emission tomography (SPET) scans were acquired using a triple-headed gamma camera. For semiquantitative evaluation of the DAT, transverse slices corrected for attenuation were used to calculate specific binding in the striatum, with the cerebellum used as background [(STR-BKG)/BKG]. Data were compared with an age-matched control group. It was found that untreated patients presented with a significantly increased specific binding of [99mTc]TRODAT-1 to the DAT as compared with normal controls [(STR-BKG)/BKG: 1.43+/-0.18 vs 1.22+/-0.06, P<0.001]. Under treatment with methylphenidate, specific binding decreased significantly in all patients [(STR-BKG)/BKG: 1.00+/-0.14, P<0.001]. Our findings suggest that the number of DAT binding sites is higher in drug-naive patients suffering from ADHD than in normal controls. The decrease in available DAT binding sites under treatment with methylphenidate correlates well with the improvement in clinical symptoms. The data of this study help to elucidate the complex dysregulation of the dopaminergic neurotransmitter system in patients suffering from ADHD and the effect of treatment with psychoactive drugs.     

Factors Associated With Health Care Personnel Influenza Vaccination Behavior

Influenza vaccination is recommended for all health care personnel (HCP), but immunization rates for this group continue to be suboptimal. This study explores relationships between individual characteristics, beliefs, knowledge, attitudes, and vaccination behavior through 2 surveys conducted at a university health center. The findings suggest that HCP who were vaccinated the year before, intended to be vaccinated next year, believed influenza vaccination was important, and were more knowledgeable are more likely to receive a vaccine.     

Effects of Crede's method on urine voiding within the first 8 h after surgery among post‐haemorrhoidectomy patients: a comparison study

Urinary retention is a common complication among patients after haemorrhoidectomy. Although Crede's method is recommended for urinary retention in nursing practice textbooks, its effects require further examination. The purpose of this study was to investigate the rate of urine voiding within the first 8 h following haemorrhoidectomy and to examine the effects of Crede's method on this postoperative outcome. A two‐group comparison study was conducted. All participants were over 20 years of age, and each had undergone haemorrhoidectomy. Outcome measurements included patients' self‐reported urine voiding within 8 h of surgery, personal demographics and disease‐related data. Before the surgical procedure, participants were divided into Crede's group and non‐Crede's group, and written educational materials were given. Patients in the Crede's group were taught Crede's method for application in the event that they were unable to void urine after haemorrhoidectomy. The non‐Crede's group patients were taught traditional methods without Crede's method. We examined urine voiding within the first 8 h after haemorrhoidectomy. The mean rate of urine voiding within 8 h of surgery was 60·9% overall, with 91·3% (21/23) in the Crede's group and 30·4% (7/23) in the non‐Crede's group reporting successful voiding. After controlling for the two groups' personal characteristics and disease‐related variables, age, educational level and perioperative fluid administration were treated as covariates and included in the multinomial logistic regression model. The odds ratio of urine voiding within the first 8 h after surgery was 52·70‐fold higher in the Crede's group than in the non‐Crede's group (p < 0·01). This study shows that Crede's method is an effective strategy to aid in urine voiding within the first eight postsurgical hours among patients following haemorrhoidectomy. Clear and concise information about urinary retention and related management strategies should be given to patients before haemorrhoidectomy.     

Intraoperative intracranial pressure and cerebral perfusion pressure for predicting surgical outcome in severe traumatic brain injury

Intraoperative intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were evaluated for use as prognostic indicators after surgery for severe traumatic brain injury (TBI), and threshold ICP and CPP values were determined to provide guidelines for patient management. This retrospective study reviewed data for 66 patients (20 females and 46 males) aged 13–83 years (average age, 48 years) who had received decompressive craniectomy and hematoma evacuation for severe TBI. The analysis of clinical characteristics included Glascow Coma Scale score, trauma mechanism, trauma severity, cerebral hemorrhage type, hematoma thickness observed on computed tomography scan, Glasgow Outcome Scale score, and mortality. Patients whose treatment included ICP monitoring had significantly better prognosis (p < 0.001) and significantly lower mortality (p = 0.016) compared to those who did not receive ICP monitoring. At all three major steps of the procedure, i.e., creation of the burr hole, evacuation of the hematoma, and closing of the wound, intraoperative ICP and CPP values significantly differed. The ICP and CPP values were also significantly associated with surgical outcome in the severe TBI patients. Between hematoma evacuation and wound closure, ICP and CPP values differed by 6.8 ± 4.5 and 6.5 ± 4.6 mmHg, respectively (mean difference, 6 mmHg). Intraoperative thresholds were 14 mmHg for ICP and 56mmH for CPP. Monitoring ICP and CPP during surgery improves management of severe TBI patients and provides an early prognostic indicator. During surgery for severe TBI, early detection of increased ICP is also crucial for enabling sufficiently early treatment to improve surgical outcome. However, further study is needed to determine the optimal intraoperative ICP and CPP thresholds before their use as subjective guidelines for managing severe TBI patients.     

The use of yeast to understand TRP-channel mechanosensitivity

Mechanosensitive (MS) ion channels likely underlie myriad force-sensing processes, from basic osmotic regulation to specified sensations of animal hearing and touch. Albeit important, the molecular identities of many eukaryotic MS channels remain elusive, let alone their working mechanisms. This is in stark contrast to our advanced knowledge on voltage- or ligand-sensitive channels. Several members of transient receptor potential (TRP) ion channel family have been implicated to function in mechanosensation and are recognized as promising candidate MS channels. The yeast TRP homolog, TRPY1, is clearly a first-line force transducer. It can be activated by hypertonic shock in vivo and by membrane stretch force in excised patches under patch clamp, making it a useful model for understanding TRP channel mechanosensitivity in general. TRPY1 offers two additional research advantages: (1) It has a large (∼300 pS) unitary conductance and therefore a favorable S/N ratio. (2) Budding yeast allows convenient and efficient genetic and molecular manipulations. In this review, we focus on the current research of TRPY1 and discuss its prospect. We also describe the use of yeast as a system to express and characterize animal TRP channels.