Unusual mechanism of Chance fracture in an adolescent

Transverse fractures of the vertebral arch or Chance fractures are rare in children. The few cases described have been associated with lap-type seat belt use. The adolescent female reported sustained a transverse fracture of L2 from a fall. This is an unusual mechanism of injury producing a Chance-type fracture in an adolescent.     

Statins, neuromuscular degenerative disease and an amyotrophic lateral sclerosis-like syndrome: an analysis of individual case safety reports from vigibase.

BACKGROUND: The WHO Foundation Collaborating Centre for International Drug Monitoring (Uppsala Monitoring Centre [UMC]) has received many individual case safety reports (ICSRs) associating HMG-CoA reductase inhibitor drug (statin) use with the occurrence of muscle damage, including rhabdomyolysis, and also peripheral neuropathy. A new signal has now appeared of disproportionally high reporting of upper motor neurone lesions. AIM AND SCOPE: The aim of this paper is to present the upper motor neurone lesion cases, with other evidence, as a signal of a relationship between statins and an amyotrophic lateral sclerosis (ALS)-like syndrome. The paper also presents some arguments for considering that a spectrum of severe neuromuscular damage may be associated with statin use, albeit rarely. The paper does not do more than raise the signal for further work and analysis of what must be regarded as a potentially very serious and perhaps avoidable or reversible adverse reaction, though it also suggests action to be taken if an ALS-like syndrome should occur in a patient using statins. METHODS: The 43 reports accounting for the disproportional reports in Vigibase (the database of the WHO Programme for International Drug Monitoring) are summarised and analysed for the diagnosis of an ALS-like syndrome. The issues of data quality and potential reporting bias are considered. RESULTS: 'Upper motor neurone lesion' is a rare adverse event reported in relationship to drugs in Vigibase (a database containing nearly 4 million ICSRs). Of the total of 172 ICSRs on this reported term, 43 were related to statins, of which 40 were considered further: all but one case was reported as ALS. In 34/40 reports a statin was the sole reported suspected drug. The diagnostic criteria were variable, and seven of the statin cases also had features of peripheral neuropathy. Of a total of 5534 ICSRs of peripheral neuropathy related to any drug in Vigibase, 547 were on statins. The disproportional reporting of statins and upper motor neurone lesion persisted after age stratification, and such disproportionality was not seen for statins and Parkinson's disease, Alzheimer's disease, extrapyramidal disorders, or multiple sclerosis-like syndromes. DISCUSSION: Because the cases were sometimes atypical we propose the use of the term 'ALS-like syndrome' and speculate whether this is part of a spectrum of rare neuromuscular damage. The diagnosis of ALS is often problematic, and the insidiousness and chronicity of the disease make causality with a drug difficult to assess. The disproportionally high reporting makes this an important signal nevertheless, since ALS is serious clinically and statins are so widely used. Wide use of the statins also makes a chance finding more probable, but is unlikely to cause disproportional reporting when there are no obvious biases identified. CONCLUSION: We emphasise the rarity of this possible association, and also the need for further study to establish whether a causal relationship exists. We do advocate that trial discontinuation of a statin should be considered in patients with serious neuromuscular disease such as the ALS-like syndrome, given the poor prognosis and a possibility that progression of the disease may be halted or even reversed.     

Genetic polymorphism in the 3' ntranslated region of human phosphoglucomutase-1

A 317-bp segment of DNA from the 3' region of the human phosphoglucomutase-1 (PGMl) gene has been examined by a non-radioactive technique for the occurrence of single-strand conformation polymorphism (SSCP), Eight phenotypes were detected and attributed to the presence of four alleles. Genetic analysis of 75 unrelated individuals and six CEPH families whose PGMl protein phenotypes were known revealed strong association between the PGMl '+' and '−' isozyme phenotypes and the variation detected in this region, but no association with the PGMl 1 and PGMl 2 isozyme phenotypes. DNA sequence analysis demonstrated the presence of three nucleotide substitutions underlying the alleles, which were located in the untranslated region of the PGMl gene. There was complete correlation between the nucleotide sequence and the phenotype detected by SSCP analysis. This study provides support for the model that the PGMl isozyme polymorphism is determined at two distinct sites in the coding sequence, one coding for the '1' and '2' alleles and the other coding for the '+' and '−' alleles, separated by a region where intragenic recombination occurs.     

Elevated hypothalamic neuropeptide Y levels in rats with dorsomedial hindbrain lesions

Lesions centered on the area postrema (AP) and adjacent nucleus of the solitary tract (AP/mNTS-lesions) are reported to result in increased consumption of highly palatable diets. Recent studies suggest that neuropeptide Y (NPY) may cause a preference for carbohydrate-rich diets. Thus, it is possible that NPY may play a role in the enhanced intake of highly palatable diets by AP/mNTS-lesioned rats. In the studies reported here, we found that lesions centered on the AP result in increased levels of NPY-immunoreactivity in the paraventricular nucleus of the hypothalamus. Additionally, steady-state NPY mRNA in the basomedial hypothalamus including the arcuate nucleus was elevated. Enhanced NPY was not found throughout the hypothalamus however, as NPY-immunoreactivity was not elevated in the lateral hypothalamus or the tissue bordering the anteroventral third ventricle. These data suggest the possibility that elevated hypothalamic NPY, particularly in the arcuate and paraventricular nuclei, may contribute to the altered food intake and energy balance observed in rats with lesions centered on the AP.     

Economic impact of reducing hospitalization for mastectomy patients.

In 1985, two policies designed to reduce hospitalization charges for mastectomy patients were instituted at the M.D. Anderson Cancer Center at Houston. The first was a policy of "same-day" admissions for elective surgery patients, and the second was early postoperative discharge for mastectomy patients with suction catheter drains in place. The economic savings resulting from these policies was analyzed by comparing demographics, operation, stage of disease, hospital stay, hospital charges, and complications for two groups of patients. Fifty-nine consecutive mastectomy patients treated between 1983 and 1984, before these policy changes, had "standard management" consisting of hospital admission 24 hours before surgery and discharge only after the surgical drains were removed. Sixty-one consecutive mastectomy patients treated between 1986 and 1987, after these policy changes went into effect, were admitted from the recovery room after surgery and were discharged with drainage catheters in place, usually within 72 hours. All operations were performed by the same faculty surgeon as a representative experience of the General Surgery faculty. The average hospital stay was reduced from 10.5 to 4.3 days. A mean 39% reduction in hospital charges (from $4867.00 to $2981.00) was achieved by instituting the policies of "same-day" admission and early postoperative discharge with drainage catheters in place. Complication rates were not changed. Implementation of this policy resulted in an estimated savings of $750,000.00 in the hospital care of approximately 400 patients treated at the M.D. Anderson Cancer Center at Houston each year. Adjustments in patient care delivery systems from a predominantly inpatient to an outpatient setting required changes in outpatient nursing responsibilities (although not in new personnel). Patient education and written instructions for home care of surgical wounds and drainage catheters were essential for implementing an early discharge policy. With these facts in mind, hospital admission on the day of operation and early postoperative discharge with drainage catheters in place should be the goal for most mastectomy patients.     

The pharmacokinetics of doxifluridine and 5-fluorouracil after single intravenous infusions of doxifluridine to patients with colorectal cancer

Summary The disposition kinetics of a new 5-fluorouracil prodrug, 5-deoxy-5-fluorouridine (5dFUR, doxifluridine), were investigated in six patients with colorectal carcinoma. Each patient randomly received two single intravenous doses of 5dFUR (2 and 4 g · m^–2) on separate days.Plasma concentrations of 5dFUR fell rapidly with terminal half-lives ranging from 16.1 to 27.7 min. A disproportionate increase in the area under the curve with increasing dose was seen in most patients. Doubling the dose resulted in a 40% decrease in nonrenal clearance (0.60 to 0.37 l · min^–1) but no apparent change in renal clearance (0.32 to 0.29 l · min^–1) or steady-state apparent volume of distribution (19.8 to 20.4 l).The mechanism for dose-dependence of 5dFUR appears to be primarily due to nonlinear elimination associated with nonrenal processes rather than nonlinear plasma protein or tissue binding.