The straight cervical spine: does it indicate muscle spasm?

The loss of cervical lordosis in radiographs of patients presenting with neck pain is sometimes ascribed to muscle spasm. We performed a cross-sectional study of the prevalence of 'straight' cervical spines in three populations: 83 patients presenting to an accident department with acute neck pain, 83 referred to a radiology department with chronic neck problems, and 80 radiographs from a normal population survey carried out in 1958. Curvature was assessed on lateral radiographs both subjectively and by measurement. The prevalence of 'straight' cervical spines was 19% in the acute cases and 26% in the chronic cases. The 95% confidence interval for the difference was -6.4% to +19.3%. In the normal population 42% showed a straight spine, but a further third of these films had been taken in a position of cervical kyphosis; this probably reflects a difference in positioning technique. Women were more likely than men to have a straight cervical spine, with an odds ratio of 2.81 (95% CI 1.23 to 6.44). Our results fail to support the hypothesis that loss of cervical lordosis reflects muscle spasm caused by pain in the neck.

Updated toxicology test methods for new industrial chemicals: Implications for regulatory acceptance of in vitro alternatives now and in the future.

Toxicology studies submitted under the Notification of New Substances Regulations are conducted according to standard ('Annex V') methods first published in 1984. In December 1992, updated methods became available that indicate where progress has been made in developing in vitro alternatives to animal testing which are acceptable to the regulatory authority (Health and Safety Executive). Although some changes reflect concern for animal welfare (e.g. the introduction of the fixed-dose method), for most toxicological endpoints an animal test remains obligatory. The major advance in the potential use of in vitro methods is as part of a tiered approach to irritancy testing. The updated method for eye irritation, for example, allows positive results in 'well-validated alternative studies' to override the need for an animal test. The substance is then classified as irritant and labelled with R41. The challenge facing such methods is to achieve full validation, so that negative data will be acceptable to the regulatory authorities. There are other challenges: a validated in vitro screen for developmental toxicity is needed for new substances, as are methods for detecting respiratory sensitizers and for replacing guinea pig skin sensitization tests.

Spontaneous pyelo-jejunal fistula.

This case report describes a patient with a spontaneous jejunal fistula. This is a rare type of nephro-intestinal fistula with only two previously recorded similar cases. Our patient presented with such a fistula diagnosed by antegrade pyelography, associated with a staghorn calculus and proven at surgery. The value of antegrade pyelography is discussed along with the treatment options and the outcome to be expected in such patients.

Effects of glutathione depletion, chelation and diuresis on iron nitrilotriacetate-induced lipid peroxidation in rats and mice.

1. Rats and mice dosed with iron nitrilotriacetate (FeNTA) i.p. (2-12 mg Fe/kg) showed evidence of lipid peroxidation as indicated by increased exhalation of ethane and increased malondialdehyde formation in liver and kidney. 2. Buthionine sulphoximine (BSO) administered i.p. to rats and mice decreased the total glutathione (GSH) content of liver and kidney. When the rodents were pretreated i.p. with BSO prior to injection of FeNTA the increases in ethane exhalation, and in liver and kidney malondialdehyde production, were greater than with FeNTA alone, and the total GSH of liver and kidney were decreased. 3. Diuresis produced by i.p. administration of furosemide to mice substantially decreased the ethane exhalation resulting from FeNTA administration, had a lowering effect on kidney MDA, but had no significant effect on liver MDA production. 4. Similarly, desferrioxamine beta-mesylate administered i.p. to mice markedly decreased the ethane exhalation and kidney MDA production resulting from FeNTA administration.

Radiological assessment of post laryngectomy speech.

Laryngectomy for carcinoma of the larynx has a five year survival rate of approximately 80% but the operation has a high morbidity as most patients do not develop effective alaryngeal speech. The published literature states that poor speech is occasionally due to anatomical or physiological problems in the reconstructed pharynx but is usually due to psychological, sociological or educational difficulties. We devised a radiological technique using a combination of video-fluoroscopy and static or spot films to assess the anatomy and function of the reconstructed pharynx of post-laryngectomy patients, and investigated 24 good and 134 poor or failed speakers. We examined the pharynx during the acts of swallowing, attempted phonation and attempted phonation with air insufflation. A single vibrating segment (P-E segment) in an otherwise dilated pharynx was present in all good speakers, but was absent in poor or failed speakers whom we classified as hypotonic (19), hypertonic (40), spastic (62) and strictured (13) according to the radiological appearances. This classification has been used to plan subsequent clinical management and 46 of the 55 patients treated to date (84%) have developed effective alaryngeal speech.

Effect of dilatation of peptic esophageal strictures on gastroesophageal reflux, dysphagia, and stricture diameter.

In 10 patients with peptic esophageal stricture the effect of esophageal dilatation on intraesophageal pH, stricture diameter, and dysphagia has been studied. Percentage of time during which intraesophageal pH was less than 4 and the number of reflux episodes per hour did not change significantly. Stricture diameter increased slightly, but consistently, from 7.0 +/- 0.5 mm to 9.1 +/- 0.5 mm (P less than 0.01) four days after dilatation, but was not significantly different from predilatation values after 12 weeks. Improvement in symptoms of dysphagia was striking (P less than 0.01) four days and six weeks after dilatation, but worsened again at 12 weeks (P = NS). It is unlikely that esophageal dilatation adversely affects the intraesophageal environment.

The induction of autoxidative tissue damage by iron nitrilotriacetate in rats and mice.

Iron nitrilotriacetate (FeNTA) is a potent initiator of lipid peroxidation, and, when injected intraperitoneally into mice, it greatly increased ethane and pentane exhalation within 30 min. The time course and dose-response of the exhalation of ethane were studied and compared with the increase in tissue malondialdehyde (MDA) production. Production of MDA was greater in mouse kidney than liver and correlated better with the exhalation of ethane. In rats FeNTA also increased ethane exhalation and MDA, but the rat was less susceptible than the mouse to FeNTA toxicity. MDA production was greater in rat liver than kidney and both correlated well with ethane exhalation (r = 0.97 and 0.98, respectively). Renal proximal tubular damage was observed histologically 35 min after mice were given FeNTA, but in rats the lesion appeared 24 hr after dosage. Histopathological assessment of kidney damage at these times showed fair correlation with ethane exhalation in mice (r = 0.73) and rats (r = 0.62), respectively. Activities of kidney brush-border marker enzymes were decreased in mice, 35 min after FeNTA administration, and showed a similar trend in rats. Some rats also showed periportal necrosis of the liver, 24 hr after FeNTA administration. The very rapid onset of autoxidative damage suggests that FeNTA itself is the causative agent rather than subsequently formed, less reactive complexes, such as transferrin. The site of damage in the kidney tubule is consistent with the region of concentration of filtered FeNTA. It is suggested that FeNTA supports the formation of superoxide ion from dissolved oxygen and may be responsible for the subsequent formation of hydroxyl radical which initiates lipid peroxidation. The species difference between rat and mouse may be due to the greater resistance of the rat kidney to FeNTA-induced autoxidative damage.

The mechanism of action of phenformin in starved rats.

The ability of phenformin to lower the blood glucose concentration after an intraperitoneal glucose load, with a concomitant increase in blood lactate concentration, indicated that the drug was increasing the rate of anaerobic glycolysis. The results of experiments in which glucose and gluconeogenic precursors were given to starved rats were explained by a hypothesis for the mechanism of action of phenformin involving inhibition of certain NAD+-dependent dehydrogenases. Substrates with NAD+-linked oxidations could be discriminated from those, like succinate, with FAD-linked oxidations, and succinate may be of use in the treatment of clinical lacticacidosis caused by biguanide drugs.