THalidomide sensory neurotoxicity: results of a collaborative clinical and neurophysiolgical study

We investigated the possible use of individual Total Neuropathy Scale (TNS) items to predict the neurological outcome in patients undergoing cisplatin and paclitaxel combination chemotherapy in a series of thirty‐four women divided, according to the worst TNS score reached during the period of observation, into three groups, i.e. with a score <5 (n = 14), >5 but <10 (n = 5) or >10 (n = 15). At the visit performed before the onset of the worst neuropathy signs, 14 out of the 15 patients with the worst TNS had a change of 2 or more points in the sum of the semiquantitative vibration score (tuning fork) plus the DTR examination. In 12 of them the change was due to both vibration perception and DTR impairment. A change in the combined score was observed also in 7 out of the 14 patients with the better neurological outcome, but none of them had any change in the vibration perception. Early disappearance of DTR in the lower limbs (i.e. both ankle and patellar reflexes bilaterally) was observed in 7 out of the 15 patients with a worst outcome, while only 1 patient in the better outcome group had this clinical sign. The results of the VDT score obtained with a vibrameter did not improve the accuracy of the neurological assessment. Our study indicates that the accurate clinical evaluation of the patients treated with platinum and taxane combination polychemotherapy can be used to predict the final neurological outcome of the treatment.     

Diagnosis of the Prader-Willi syndrome by proving the absence of the unmethylated PW71 DNA fragment

The Prader-Willi syndrome (PWS) is a genetic disorder which is difficult to diagnose from clinical symptoms in newborns and young children. However, it is known that in PWS a fragment within the q11-13 region of the paternally derived chromosome 15 is deleted. Recently it has been observed that the D15S63 (PW71) locus in chromosome 15q11-13 is methylated on the maternally derived chromosome, but unmethylated on the paternally derived chromosome. Based on this observation a rapid diagnostic test (the PW71 methylation test) using methylation-sensitive restriction enzymes has been developed for patients presumed to have PWS. We have studied 56 patients; 30 patients with classical features of PWS and 26 patients with only psychomotor retardation and obesity, referred to us from different parts of Sweden. Twenty-nine of the 30 classical PWS patients were found to have an absence of the unmethylated paternally derived PW71(D15S63) locus in chromosome 15q11-13. None of the patients with only obesity and psychomotor retardation had this "absence" pattern on chromosome 15q11-13. Using the PW71 methylation test on patients with PWS, a concordance of 96% was found. The PW71 methylation test is presently the method of choice for rapid diagnostic testing of patients suspected of having PWS.     

Gastrointestinal perforation by chicken bones

Four cases of gastrointestinal perforation by chicken bones are presented. Variability in the clinical manifestations generally precludes a correct preoperative diagnosis of intraabdominal chicken bone abscess. However, in 2 patients, a diagnosis was possible with plain abdominal radiographs. Although the abnormalities seen were nonspecific, the identification of a chicken bone with an associated mass or extraluminal gas collection in a patient with signs of peritonitis, mechanical bowel obstruction, or pneumoperitoneum strongly suggests the diagnosis. A history of alcoholism or wearing dentures strengthens it.     

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations

The kinetics and dynamics (inhibition of exercise tachycardia) of two controlled-release preparations of propranolol (Elanolol and Inderal LA) were examined in six normal volunteers. Conventional propranolol (Inderal) was also studied for comparison purposes. As compared to conventional propranolol (120 mg), single doses of Elanol (120 mg) and Inderal LA (160 mg) produced a smoother serum level profile, with lower and delayed peak times. Dose-corrected AUC0-24 values were greater after Elanol than after Inderal LA (651 +/- 147 vs 402 +/- 159 ng ml-1 h, means +/- s.e. mean, P greater than 0.05). The profile of inhibition of exercise tachycardia mirrored closely that of the serum levels. At steady state, all regimens studied (Inderal 40 mg three times daily; Elanol 120 mg once daily; Inderal LA 160 mg once daily) ensured relatively sustained serum levels and a stable degree of pharmacological effect. Dose-corrected AUC0-24 values were 797 +/- 148 ng ml-1 h after Inderal, 908 +/- 113 ng ml-1 h after Elanol and 602 +/- 122 ng ml-1 after Inderal LA. The bioavailability of Inderal LA was significantly lower than that of the other preparations. These results demonstrate that long-acting formulations of propranolol can be developed which are not necessarily associated with reduced bioavailability secondary to enhanced first-pass metabolism.     

Spontaneous periodic hypothermia with lipoma of the corpus callosum

A patient with spontaneous periodic hypothermia who had both a lipoma and agenesis of the corpus callosum is described. Spontaneous periodic hypothermia associated with corpus callosum abnormalities is a distinct entity and although the mechanism underlying the hypothermic episodes is unexplained, the term “diencephalic autonomic epilepsy” does not seem appropriate.     

Modification of phenytoin clearance by valproic acid in normal subjects.

1 The effect of valproic acid on the distribution and elimination kinetics of intravenously administered phenytoin has been investigated in eight normal volunteers. 2 In each of the subjects studied the volume of distribution of phenytoin increased significantly during treatment with sodium valproate (1200 mg daily for 7 days). 3 Phenytoin clearance was markedly increased in presence of valproic acid as compared to control values (0.52 +/- 0.17 v 0.38 +/- 0.11 ml min-1 kg-1 respectively, P less than 0.02). 4 It is suggested that the increase of the volume of distribution and of the serum clearance are secondary to displacement of phenytoin from plasma protein binding sites by valproic acid.     

Pharmacological studies of the rabbit and human renal pelvis

Summary The responses of the isolated rabbit and human renal pelvis to drugs and to electrical stimulation have been investigated. Regular spontaneous changes in tension occur in the circular smooth muscle, which in the rabbit are synchronous with electrical waves. The responses to electrical stimulation seem to be due to the release of catecholamines from adrenergic nerves. Such nerves have been observed by means of a fluorescence technique. The cholinergic system appears functionally unimportant. The adrenergic responses in human and rabbit seem to be mediated exclusively by -adrenoceptors.The denervated rabbit organ shows hypersensitivity, mainly to low concentrations of adrenaline. The failure of uptake inhibitors to potentiate the responses to noradrenaline seems in favour of postsynaptic hypersensitivity.