Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients’ FGF-21 results were assessed by the use of age-adjusted z-scores based on normalised FGF-21 values from a healthy population. One hundred and fifty five patients were investigated. One hundred and four of these patients had molecular evidence for MD, 27 were deemed to have disorders other than MD (non-MD), and 24 had possible MD. Patients with defects in mitochondrial DNA (mtDNA) maintenance (n = 32) and mtDNA rearrangements (n = 17) had the highest median FGF-21 among the MD group. Other MD patients harbouring mtDNA point mutations (n = 40) or mutations in other autosomal genes (n = 7) and those with partially characterised MD had lower FGF-21 levels. The area under the receiver operating characteristic curve for distinguishing MD from non-MD patients was 0.69. No correlation between FGF-21 and creatinine, creatine kinase, or cardio-skeletal myopathy score was found. FGF-21 was significantly associated with plasma lactate and ocular myopathy. Although FGF-21 was found to have a low sensitivity for detecting MD, at a z-score of 2.8, its specificity was above 90%. We suggest that a high serum concentration of FGF-21 would be clinically useful in MD, especially in adult patients with chronic progressive external ophthalmoplegia, and may enable bypassing muscle biopsy and directly opting for genetic analysis. Availability of its assay has thus modified our diagnostic pathway.

Obesity, short stature, hypotonia and excessive daytime sleepiness are characteristic features of the Prader-Willi syndrome. Excessive daytime sleepiness has been attributed to obstructive sleep apnoea (OSA). To investigate the role of anatomical factors in OSA in the Prader-Willi syndrome, clinical and ENT assessment, radiology of the upper airway and polysomnography including sleep oximetry were done in 14 subjects. Excessive daytime sleepiness was present in eight of 14 subjects as determined by a mean sleep latency to non-rapid eye movement stage I-II of < 5 min and/or self-rating sleepiness score > 9 (Epworth Sleepiness scale). Seven subjects were snorers or mouth breathers and dental abnormalities were present in 11. Sleep apnoea, as determined by a combined apnoea-hypopnoea index of more than 10 respiratory events per hour was present in 12 of 14 subjects. On clinical assessment, the nasopharynx, oropharynx and hypopharynx were small in one subject. No subject had redundant pharyngeal mucosa or an enlarged tongue. However, radiological studies performed in the awake supine posture showed a slight reduction in the cross-sectional area in nine subjects at the oropharyngeal level and in four subjects at the nasopharyngeal level as compared with normal control subjects. Sleep apnoea and minor radiological evidence of narrowing of the upper airway are common in the Prader-Willi syndrome, although clinical otolaryngological examination is often unremarkable. Excessive daytime sleepiness occurs in approximately 50% of all patients with Prader-Willi syndrome. Although obstructive sleep apnoea is one important factor related to sleepiness, an additional central disturbance of sleep mechanisms is present.

We performed a randomised prospective double blind trial to study the effect of the calcium antagonist nimodipine on the outcome of head injured patients. The subjects were not obeying commands at the time of entry to the study, within 24 hours of injury. One hundred and seventy-five patients received nimodipine IV, 2 mg per hour for up to 7 days and 176 received placebo. The two groups were well matched for important prognostic features. Six months after injury 93 (53%) of the nimodipine group and 86 (49%) of the control group had a favourable outcome (moderate/good recovery). The relative increase in favourable outcomes (8%) was not significant but is compatible (95% C.I.) with an increase in favourable outcomes in treated patients by 33% or a decrease by 12%. Nimodipine was well tolerated and there were few adverse reactions; means of systolic and diastolic blood pressures and the intracranial pressure did not differ between the groups. It is unlikely that nimodipine has a marked effect on outcome (ie an increase in favourable outcome of greater than 15%) after head injury of this severity but the study does not exclude a modest but clinically useful benefit.

Thirty-one patients with serious or complicated urinary tract infections were treated with oral enoxacin for between four and eight days. Twenty-five patients with microbiologically confirmed infections completed treatment with 400 mg enoxacin twice daily and at the end of treatment all urine cultures were negative. At short term follow-up, five to nine days after therapy, 21 of the 25 patients were still infection free. In total, reinfection or relapse occurred in 12 patients during the four to six weeks follow up period after termination of treatment. Significant side-effects (nausea and vomiting) occurred in only one patient.