Detection of expiratory flow limitation by manual compression of the abdominal wall.

We have assessed a new method, manual compression of the abdominal wall (MCA) during expiration, in the detection of expiratory flow limitation. Twelve stable patients with chronic obstructive pulmonary disease (COPD) and five normal subjects were studied during spontaneous breathing in the supine and seated posture. MCA was performed during expiration with one hand at the umbilical level and we measured flow, volume, pleural (Ppl) and gastric (Pga) pressures and abdominal anteroposterior (AP) diameter at the umbilical level with magnetometers. No increase in expiratory flow during MCA relative to the preceding breath despite associated increases in pressures was considered as indicating expiratory flow limitation. In seven additional patients with increased upper airway collapsibility (obstructive sleep apnea syndrome [OSAS]), MCA was compared with negative expiratory pressure (NEP). In normal seated subjects, MCA was associated with a decrease in abdominal AP dimension (mean +/- SD: -27 +/- 6%), an increase in Pga (14.7 +/- 7.4 cm H(2)O) and Ppl (6.2 +/- 2.2 cm H(2)O), and an increase in expiratory flow. MCA caused similar changes in abdominal AP dimension and pressures in seated patients with COPD but six of them (50%), including four patients with FEV(1) less than 1 L, had no increase in expiratory flow. In the supine posture, MCA always increased expiratory flow in normal subjects but four additional patients with COPD showed evidence of flow limitation. MCA invariably increased expiratory flow in patients with OSAS whereas the NEP method suggested flow limitation in some cases. We conclude that MCA is a very simple method that allows detection of flow limitation in different positions.

Severe hyperthermia during tetrabenazine therapy for tardive dyskinesia.

We recently observed a 45-year-old patient with a history of psychiatric illness who presented with severe hyperthermia (rectal temperature above 41 degrees C) with intense rhabdomyolysis and liver cytolysis during tetrabenazine therapy for neuroleptic tardive dyskinesia. In addition to tetrabenazine, this patient took lorazepam and two antidepressant drugs: clomipramine, a potent serotonin-reuptake inhibitor, and mianserin. Hyperthermia responded to parenteral sodium dantrolene and oral bromocriptine administration. The significant role of tetrabenazine (a central nervous system dopamine-depleting drug) and the contribution of antidepressants to the mechanism of this neuroleptic malignant syndrome - like hyperthermia are discussed.

Magnetic transcranial stimulation: clinical interest of the silent period in acute and chronic stages of stroke.

There is little information on the silent period during facilitation of the target muscle at the acute stage of stroke and the ultimate clinical status. We studied 69 subjects with transcranial magnetic stimulation: 20 matched controls and 49 hemiparetic patients investigated 7 and 90 days after the stroke (D7, D90). We measured the silent period duration (SPD) in the first dorsal interosseous muscle at 10 and 100% of maximal voluntary isometric contraction (VIC). The SPD index (the ratio of SPD at VIC 100% by SPD at VIC 10%) at D7 was matched with the clinical outcome at D90. Two patterns of responses could be determined at D7. In the normal subjects and in 27 out of 32 patients who eventually recovered satisfactory function at D90, the SPDs were stable during facilitation (SPD index 100%). On the contrary, in 10 out of the 17 patients with a poor functional outcome, the mean SPD decreased when VIC was increased (SPD index 80%); besides, their muscle tone was significantly increased at D90. Similar patterns were still present in the patients at D90: the mean SPD indexes were not significantly different from D7. We conclude that in the early stage of stroke, a low SPD index appears to be correlated with the eventual occurrence of spasticity.

Magnetic transcranial stimulation: dissociation of excitatory and inhibitory mechanisms in acute strokes.

Magnetic transcranial stimulation was applied to 12 normal subjects and 30 patients (24 acute and 6 chronic) with hemiparesis contralateral to an ischaemic stroke. In the 24 acute patients, the recordings were made at the 7th day on the contralateral first dorsal interosseous (FDI) muscle. We studied the amplitudes of the motor evoked potential (MEP) responses and the post-MEP silent period durations (SPD) at different levels of stimulation intensity (SI) and voluntary isometric contraction (VIC). The evolution of these parameters was matched to the clinical status of the 24 acute patients evaluated 7, 30 and 90 days after the stroke (D7, D30 and D90). Our results may be summarised as follows: (1) in all cases, the MEP-amplitudes increased with facilitation and SI; (2) in the normal subjects and in patients who did recover, the SPD augmented with stronger SI but was found to be independent on the strength of voluntary contraction; (3) in the acute patients with poor recovery, as well as in the chronic patients with spasticity, the SPD decreased with stronger VIC. It may be concluded that MEP-amplitudes and SPD patterns point out excitatory and inhibitory mechanisms which may be differently affected in cerebral injuries. The association between shortening of the SPD with increasing VIC of the target muscle and poor recovery of the stroke after 3 months could be a useful clinical test to predict eventual recovery early after a stroke.

Magnetic transcranial stimulation in acute stroke: early excitation threshold and functional prognosis.

Magnetic transcranial stimulation was used in 90 subjects (60 acute ischaemic sylvian strokes and 30 healthy controls) in order to evaluate the clinical value of the excitation threshold (ET) in the estimation of functional prognosis. ET mean values recorded 7, 30 and 90 days after stroke (at D7, D30 and D90) in two distal muscles of the upper limbs of the patients were compared with results obtained in 30 healthy control subjects. The data from the patients who ultimately achieved a satisfactory functional recovery at D90 were compared with those from patients who had not recovered in that time. Our results suggest that ET evolution differs according to functional outcome: (1) ET mean values were increased in the stroke patients at D7, but ET was constantly lower at D30 and D90 in patients who recovered than in those who did not. (2) ET temporal evolution showed a gradual decrease of the mean values from D7 to D90 in both stroke groups. This ET decrease was more marked in the patients who recovered from D30 to D90, but with only minor change after D30. (3) The localisation of the lesion had no significant effect on ET mean values at D7, D30 or D90. We conclude that the predictive value of ET estimation might be utilised at D30 in patients with ischaemic sylvian strokes.

Magnetic transcranial stimulation in non-haemorrhagic sylvian strokes: interest of facilitation for early functional prognosis.

Magnetic transcranial stimulation was applied to 40 patients in the early stage of a non-haemorrhagic sylvian stroke. Results were evaluated with regards to the clinical outcomes at days 7, 30 and 90. The presence or absence of an early response had a critical prognostic significance. Response latency and amplitude parameters and the excitation threshold were of little value. Facilitation in patients unresponsive at rest was another determinant parameter since 9 out of 10 such cases ultimately recovered.

Phase I clinical trial with carbetimer.

Carbetimer, a low molecular weight polymer derived from ethylene and maleic anhydride, belongs to a class of chemical compounds different from previously available anticancer agents. It has shown moderate antitumor activity against the Madison 109, Lewis lung, colon 26 and M5076 ovarian carcinomas. In the human tumor stem cell assay, antitumor activity was seen against carcinomas of the breast, ovary, lung, colon and kidney. A total of 26 patients with solid tumors were entered into this trial; carbetimer was given on 5 consecutive days as a 1-2-h intravenous infusion. The dose was escalated from 1.08 to 11 g/m2/day. The drug did not induce the usual side-effects of chemotherapy: leukopenia, thrombocytopenia, alopecia and mucositis were minimal or totally absent. Gastrointestinal toxicity was limited to mild to moderate nausea and vomiting; these were observed at all dose levels and required antimetics in only two patients. The major side-effects of carbetimer consisted of hypercalcemia and neurotoxicity. Hypercalcemia was dose- and treatment duration-dependent. The precise mechanism of hypercalcemia is presently under investigation, but remains unclear. Neurotoxicity was observed only after prolonged therapy; two patients, who received cumulative doses higher than 250 g/m2, developed a peripheral neuropathy with paresthesia, decrease in sensory perception and motor weakness. One patient recovered completely; the other patient improved slightly before developing fatal brain metastases. Two patients with malignant melanoma exhibited major antitumor response; both were previously treated; after excellent partial responses to carbetimer, both were operated on and one is presently disease-free 2 1/2 years after completion of therapy with carbetimer. In conclusion, carbetimer is a new compound with an unusual pattern of side-effects and interesting antitumor activity against malignant melanoma. Its antitumor activity is presently being investigated in phase II trials.