Nephrogenic diabetes insipidus partially responsive to oral desmopressin in a subject with lithium-induced multiple endocrinopathy.

Lithium (Li) may cause multiple endocrinopathies, including hypercalcaemia, thyroid dysfunction and nephrogenic diabetes insipidus (NDI), but rarely in the same patient. The management of NDI remains a challenge. We report on a patient on long-term Li who had simultaneous NDI (paired serum and urine samples had abnormal osmolalities, typical of NDI, and treatment with parenteral desmopressin failed to affect urinary volume and serum osmolality), 'destructive' thyroiditis (hyperthyroidism, absent radioiodine uptake and absent thyrotrophin receptor antibodies) and primary hyperparathyroidism (compatible biochemistry, urine calcium excluding 'set point' anomalies and hypocalciuric hypercalcaemia, and normal parathyroid imaging). The thyroiditis resolved spontaneously and hypercalcaemia responded to reduction of Li dose. The NDI was unresponsive to amiloride, thiazides and ibuprofen in combination. However, urine output was reduced by 50% when a high dose of oral desmopressin was given. We conclude that Li-induced multiple endocrinopathy remains rare and, although NDI is difficult to manage, high dose oral desmopressin should be tried when other medications fail.

A combined spectroscopic and functional MRI investigation of the dorsal anterior cingulate region in opiate addiction.

Converging neuropsychological and functional neuroimaging evidence indicates that the dorsal anterior cingulate cortex (dACC) is dysfunctional in drug-addicted populations. Few studies, however, have investigated the biochemical and physiological properties of the dACC in such populations. We used proton magnetic resonance spectroscopy ((1)H-MRS) together with functional magnetic resonance imaging (fMRI) to probe dACC biochemistry and physiological activity during performance of a behavioural control task in 24 opiate-dependent individuals (maintained on a stable dose of methadone or buprenorphine at the time of study) and 24 age, gender, intelligence and performance-matched healthy subjects. While both groups activated the dACC to comparable levels, the opiate-using group displayed relatively increased task-related activation of frontal, parietal and cerebellar regions, as well as reduced concentrations of dACC N-acetylaspartate and glutamate/glutamine. In addition, the opiate-using group failed to show the expected correlations between dACC activation and behavioural measures of cognitive control. These findings suggest that the dACC is biochemically and physiologically abnormal in long-term opiate-dependent individuals. Furthermore, opiate addicts required increased, perhaps compensatory, involvement of the fronto-parietal and cerebellar behavioural regulation network to achieve normal levels of task performance/behavioural control. These neurobiological findings may partly underpin key addiction-related phenomena, such as poor inhibitory control of drug-related behaviour in the face of adverse consequences, and may be of relevance to the design of future treatment studies.

Inhibition of fibril formation in beta-amyloid peptide by a novel series of benzofurans.

A series of benzofuran derivatives have been identified as inhibitors of fibril formation in the beta-amyloid peptide. The activity of these compounds has been assessed by a novel fibril-formation-specific immunoassay and for their effects on the production of a biologically active fibril product. The inhibition afforded by the compounds seems to be associated with their binding to beta-amyloid, as identified by scintillation proximity binding assay. Binding assays and NMR studies also indicate that the inhibition is associated with self-aggregation of the compounds. There is a close correlation between the activity of the benzofurans as inhibitors of fibril formation and their ability to bind to beta-amyloid. Non-benzofuran inhibitors of the fibril formation process do not seem to bind to the same site on the beta-amyloid molecule as the benzofurans. Thus a specific recognition site might exist for benzofurans on beta-amyloid, binding to which seems to interfere with the ability of the peptide to form fibrils.

The effect of intermittent local heating on fracture healing in the distal tibia of the rabbit.

Two series of controlled experiments were carried out to investigate the effect of intermittent local heating on fracture healing in the distal tibia of the rabbit. In the first series, the distal tibia was fractured in a reproducible manner and then treated by compression plate fixation. Nine animals received intermittent local heating around the fracture site for 6 weeks postoperatively in comparison with 5 control animals. The mechanical strength of the healed tibia was then measured in a standardized 3-point bend test. Intermittent local heating produced stronger bones than the untreated controls in 6 of the 9 cases, a result which was marginally significant (P = 0.055). In the second series of experiments, a reproducible bone defect was created by drilling a 2 mm diameter hole through the distal tibia; compression plate stabilization was not required. Fourteen animals received intermittent local heating around the fracture site for 3 weeks postoperatively in comparison with 7 control animals. Intermittent local heating produced stronger bones than the untreated controls in 8 of the 14 cases, a result which was not significant (P greater than 0.1). It is concluded that intermittent local heating of the type studied has too small an effect on accelerating the rate of fracture repair to be clinically useful.

Disk diffusion susceptibility tests with norfloxacin: confirmation of proposed interpretive criteria.

One hundred and eighty three clinical isolates of aerobic bacteria were tested against norfloxacin by both agar dilution (WHO-ICS) and disk diffusion test procedures (standardized FDA single disk test). Two experimental 10 microgram norfloxacin disks were studied. Results were analyzed in terms of recently recommended breakpoints for clinical susceptibility (MIC less than or equal to 16 micrograms/ml, zone diameter greater than or equal to 17 mm) and resistance (MIC greater than or equal to 32 micrograms/ml, zone diameter less than or equal to 12 mm). Excellent correlation was demonstrated by statistical analysis between paired MIC and zone size values (average value for each MIC; r = -0.9782). An MIC of 16 micrograms/ml was found to correlate with a zone of 10.4 mm. Application of the recommended zone size breakpoints resulted in prediction of 177 isolates as being susceptible while six (3.3%) were predicted to be either intermediate or resistant. The findings of this study validate the earlier recommendations stated above.