Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.     

Intergenerational studies of human birthweight from the 1958 birth cohort. II. Do parents who were twins have babies as heavy as those born to singletons?

OBJECTIVE: To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants. DESIGN AND SUBJECTS: The association between the birthweight of singleton parents and their offspring and that between twin parents and their offspring was compared using data from the 23-year-old sample of the 1958 British national birth cohort. The numbers available for full comparison were 1027 female and 611 male singleton cohort members, and 26 female and 17 male twin cohort members and their first singleton livebirths. RESULTS: Of the mothers who had been twins, half had been of low birthweight, and overall their mean weight was 700 g less than that of their singleton counterparts. Nevertheless, the mean birthweight of babies of twin mothers was 133 g, and of twin fathers 94 g, greater than of babies of corresponding singletons. For female, but not male, parents this difference persisted after adjustment for confounding variables. CONCLUSIONS: We suggest two possible reasons for the difference between the weight of babies of twin and singleton mothers. Firstly, the growth of twins becomes retarded late in pregnancy, possibly after a period critical in determining long-term reproductive effects. Secondly, the twin survivors were of higher birthweight than the original twin cohort, whilst the singleton survivors were more representative of all singleton births, thus introducing a possible bias.     

Post-herpetic neuralgia and topical capsaicin

Topical 0.025% capsaicin was used to treat 33 patients with post-herpetic neuralgia (PHN). Thirty-nine percent of those entering the trial achieved at least a good result and 55% were improved or better. Fifty-six percent of the 23 patients completing the study had good or excellent pain relief after 4 weeks. Seventy-eight percent of the 23 noted at least some improvement in pain. Post-capsaicin burning was a common, untoward effect in most patients and in about one-third was so unbearable that the trial was terminated prematurely. This treatment appears to be a useful modality in PHN, particularly in the elderly in whom oral medications are often poorly tolerated; however, it does require supervision. A double-blind, controlled trial is now necessary.     

Validation of a modified one-step rebreathing technique for measuring exercise cardiac output

A modification of the Farhi one-step rebreathing technique (1) is described for determining submaximal exercise cardiac output (Q). Factors critical in the estimation of Q are initial rebreathing bag volume and constant bag volume during the maneuver. By substituting a high flow rate analyzer (500 ml.min-1) for the recommended low flow rate mass spectrometer (60 ml.min-1), adding a recirculation circuit from the outlet of the analyzer to an inlet at the base of the rebreathing bag, and reducing the length of sample tubing to the analyzer, we were able to recirculate the subject's expired gas and achieve no loss of bag volume. No statistically significant differences in estimate of cardiac output were noted between the mass spectrometer and LB-2 analyzer with recirculation circuit during submaximal cycling. Heart rate and oxygen uptake were highly correlated with cardiac output and agreed well with the literature, irrespective of the CO2 analyzer system used. A unique feature of our method is that the subject's tidal volume is measured prior to the maneuver and then used as the initial rebreathing bag volume. Varying the bag volume by +/- 0.2 L from the tidal volume had no significant effect on the estimate of cardiac output during exercise. Now quick, reliable, and noninvasive measurements of cardiac output are feasible in subjects--not only in the laboratory but also in the field where a mass spectrometer is not readily portable.     

Service needs of youths released from a state psychiatric facility as perceived by service providers and families

The following article reports on the results of service needs assessments of a cohort of youths released from a state psychiatric facility as perceived by service providers and families/caregivers. Families as well as service providers consistently agreed on three service areas of high need—psychotherapy for the child, family therapy and parent skill training. However, families perceived a need for a number of other services that are not traditionally provided by the mental health system such as after school recreation activities and self-help and support groups for the child. The discrepancies between service providers and families' perceptions of assessed needs may lead to families dropping out of service due to the unresponsiveness of the services in meeting their perceived needs. Steps that service providers need to take to be more responsive to the needs of families are discussed.This study was funded by a grant from the Office of Program Evaluation and Research, Ohio Department of Mental Health.     

Some observations on whiplash injuries.

Motor vehicle accidents with a whiplash mechanism of injury are one of the most common causes of neck injuries, with an incidence of perhaps 1 million per year in the United States. Proper adjustment of head restraints can reduce the incidence of neck pain in rear-end collisions by 24%. Persistent neck pain is more common in women by a ratio of 70:30. Whiplash injuries usually result in neck pain owing to myofascial trauma, which has been documented in both animal and human studies. Headaches, reported in 82% of patients acutely, are usually of the muscle contraction type, often associated with greater occipital neuralgia and less often temporomandibular joint syndrome. Occasionally migraine headaches can be precipitated. Dizziness often occurs and can result from vestibular, central, and cervical injury. More than one third of patients acutely complain of paresthesias, which frequently are caused by trigger points and thoracic outlet syndrome and less commonly by cervical radiculopathy. Some studies have indicated that a postconcussion syndrome can develop from a whiplash injury. Interscapular and low back pain are other frequent complaints. Although most patients recover within 3 months after the accident, persistent neck pain and headaches after 2 years are reported by more than 30% and 10% of patients. Risk factors for a less favorable recovery include older age, the presence of interscapular or upper back pain, occipital headache, multiple symptoms or paresthesias at presentation, reduced range of movement of the cervical spine, the presence of an objective neurologic deficit, preexisting degenerative osteoarthritic changes; and the upper middle occupational category. There is only a minimal association of a poor prognosis with the speed or severity of the collision and the extent of vehicle damage. Whiplash injuries result in long-term disability with upward of 6% of patients not returning to work after 1 year. Although litigation is very common and always raises questions of secondary gain in patients with persistent symptoms, most patients are not cured by a verdict. Acute treatment of neck pain consists of ice for 24 hours followed by heat applications, pain pills, NSAIDs, and muscle relaxants. Trigger point injections can be beneficial in both the acute and the persistent phases. Use of cervical collars should probably be kept to a minimum during the first 2 to 3 weeks after the injury and then avoided. Early passive mobilization and range of motion exercises may accelerate recovery. Physical therapy and transcutaneous nerve stimulators may be helpful in reducing pain and improving movement.(ABSTRACT TRUNCATED AT 400 WORDS)     

Perinatal toxicology screening.

Accurate identification of substance abusing mothers and their infants is critical for appropriate medical management as well as the collection of accurate information on the effects of illicit drug use on perinatal morbidity, mortality, and long-term neurobehavioral outcome in the infants. This study examines the differences found using two methods for urine toxicology screening at the time of obstetrical admission to the hospital. The institution of universal screening identified significantly more women than were previously identified through the use of a risk-directed protocol (P less than .0001). Women identified using either protocol were significantly more likely than toxicology-negative women to have had poor prenatal care and to have smoked and used alcohol during pregnancy (P less than .001). In the population studied, the multiple criteria needed to accurately identify mothers with positive-toxicology screens would also include screening over one half of the toxicology-negative mothers.     

Sulphanilic acid: divergent results in the guinea pig maximization test and the local lymph node assay

The guinea pig maximization test (GPMT) has proven to be a valuable tool for the identification of the skin sensitization potential of chemicals. The method identifies a hazard which can lead in the EC to compulsory labelling of that chemical. In the present study, data on sulphanilic acid derived from the GPMT has been compared with results from a second guinea pig assay (the cumulative contact enhancement test) and the murine local lymph node assay, both of which require only topical application of chemical. Except for the GPMT, no test identified any sensitizing activity associated with exposure to sulphanilic acid. These latter results are consistent with the experience gained from substantial human exposure in an occupational setting and from which no cases of allergic contact dermatitis to sulphanilic acid have arisen over a 20-year period. In consequence, it is questioned which test protocol in practice has given the more accurate identification of sensitization hazard relevant to man.