Severe hypoglycemia in an elderly patient treated with metformin.

UNLABELLED: The following case of severe hypoglycemia was reported during a systematic evaluation of hospital admissions caused by adverse drug reactions (supported by BfArM). HISTORY AND FINDINGS ON ADMISSION: A 79-year-old diabetic woman was admitted to hospital in a stuporous and unresponsive state. The initial physical examination revealed no other abnormal findings. Serum blood glucose was found to be 2.0 mmol/l and HbA1c was 4.6%. The patient had been started on antidiabetic therapy with metformin 2 months earlier. Treatment with other drugs being taken at that time, an ACE inhibitor, an NSAID and nitrofurantoin, remained unchanged. DIAGNOSIS, TREATMENT AND FOLLOW-UP: Laboratory tests excluded lactic acidosis and renal insufficiency. Cerebral computed tomography findings were normal. The patient improved dramatically following administration of glucose. Other laboratory findings confirmed the diagnosis of hypoglycemia. Blood glucose concentrations ranged between 4.0 and 10.0 mmol/l in the subsequent days and the patient could be discharged in full health. CONCLUSIONS: Drug-induced hypoglycemia is possible even in diabetics not receiving insulin or oral antidiabetic agents increasing insulin secretion. The risk of drug-induced hypoglycemia should be particularly considered when drugs containing blood glucose-lowering components are combined. Metformin does not usually cause hypoglycemia when administered as monotherapy. We suspected that hypoglycemia in this patient was caused by additional blood glucose-lowering effects of the ACE inhibitor and the NSAID possibly combined with a suboptimal nutrition. The indications for metformin administration undergo critical scrutiny.

Veratridine-mediated Ca2+ dynamics and exocytosis in paramecium cells.

We analyzed [Ca2+]i transients in Paramecium cells in response to veratridine for which we had previously established an agonist effect for trichocyst exocytosis (Erxleben & Plattner, 1994. J. Cell Biol. 127:935-945; Plattner et al., 1994. J. Membrane Biol. 158:197-208). Wild-type cells (7S), nondischarge strain nd9-28 degrees C and trichocyst-free strain "trichless" (tl), respectively, displayed similar, though somewhat diverging time course and plateau values of [Ca2+]i transients with moderate [Ca2+]o in the culture/assay fluid (50 microM or 1 mm). In 7S cells which are representative for a normal reaction, at [Ca2+]o = 30 nm (c.f. [Ca2+]resti = approximately 50 to 100 nm), veratridine produced only a small cortical [Ca2+]i transient. This increased in size and spatial distribution at [Ca2+]o = 50 microM of 1 mm. Interestingly with unusually high yet nontoxic [Ca2+]o = 10 mm, [Ca2+]i transients were much delayed and also reduced, as is trichocyst exocytosis. We interpret our results as follows. (i) With [Ca2+]o = 30 nm, the restricted residual response observed is due to Ca2+ mobilization from subplasmalemmal stores. (ii) With moderate [Ca2+]o = 50 microM to 1 mm, the established membrane labilizing effect of veratridine may activate not only subplasmalemmal stores but also Ca2+o influx from the medium via so far unidentified (anteriorly enriched) channels. Visibility of these phenomena is best in tl cells, where free docking sites allow for rapid Ca2+ spread, and least in 7S cells, whose perfectly assembled docking sites may "consume" a large part of the [Ca2+]i increase. (iii) With unusually high [Ca2+]o, mobilization of cortical stores and/or Ca2+o influx may be impeded by the known membrane stabilizing effect of Ca2+o counteracting the labilizing/channel activating effect of veratridine. (iv) We show these effects to be reversible, and, hence, not to be toxic side-effects, as confirmed by retention of injected calcein. (v) Finally, Mn2+ entry during veratridine stimulation, documented by Fura-2 fluorescence quenching, may indicate activation of unspecific Me2+ channels by veratridine. Our data have some bearing on analysis of other cells, notably neurons, whose response to veratridine is of particular and continuous interest.

Utilization management of workers' compensation: outpatient physical therapy.

Workers' compensation insurance carriers are becoming aware of the potentially high cost of physical therapy. Utilization management of outpatient physical therapy by means of a precertification process is a relatively new development in workers' compensation. Physical therapy treatment plans are reviewed by peers to ensure that proposed care is appropriate and cost-effective and that past care has resulted in measurable, objective, functional progress. Treatment plans are thus either certified or noncertified, or changes are negotiated. Ongoing care is monitored to facilitate the patient's progress through appropriate phases of physical therapy toward "maximum medical improvement."