A polymorphism in the dopamine receptor DRD5 is associated with blepharospasm.

Abnormalities in dopamine neurotransmission are thought to underlie the generation of dystonic movements. The authors performed a case-control allelic association study in patients with the focal dystonia blepharospasm, using polymorphisms in the dopamine receptor and transporter genes. Allele 2 of a DRD5 dinucleotide repeat was significantly associated with blepharospasm. This may indicate a pathogenic role for this receptor.     

Double-crush nerve compression in thoracic-outlet syndrome

We studied 165 cases of thoracic-outlet syndrome in 142 patients in whom resection of the first rib had been performed. In seventy-three cases (44 per cent), there was compression of a nerve distally, as shown by electromyography and conduction studies. The most common secondary compression was carpal tunnel syndrome (forty-one cases). Thirteen patients needed an operation at three sites or more. Our results show that proximal compression of a nerve lessens its ability to withstand more distal compression. Once the diagnosis of thoracic-outlet syndrome has been made, the possibility of an additional distal compression neuropathy should be investigated.     

Metabolism of the anti-psoriatic agent 5-methoxypsoralen in humans: comparison with rat and dog.

1. Single oral doses of 14C-5-methoxypsoralen (5-MOP) to human subjects (50 mg), rats (1 mg/kg) and dogs (1 mg/kg) were fairly well absorbed but subjected to extensive first-pass metabolism, at least in rat and human. Means of 62, 51 and 40% dose in urine and 31, 38 and 48% dose in faeces, were excreted by humans (during 5 days), rats (3 days) and dogs (1 day), respectively. In dogs, faecal 14C was probably derived, in part, from biliary excreted material. 2. Total 14C in human plasma reached peak concentrations after 2 h (mean 235 ng 5-MOP equivalent/ml) and declined relatively slowly, to about 60% of this value within 24 h. Unchanged 5-MOP was not detected in plasma using h.p.l.c. (< 5 ng/ml). 3. Tissue concentrations of 14C were generally greater in dogs than rats and reached peak levels at 1 h in dogs but at 24 h in rats. Apart from liver and bile, dog tissue 14C concentrations were lower than those in the corresponding plasma, whereas in rat they were lower only until the time of peak concentrations, after which they were generally greater. 4. 5-MOP was extensively metabolized in all three species. The major 14C-components in human and dog urine were glucuronic acid conjugates, mainly of an arylacetic acid and arylalcohols, resulting from initial oxidative metabolism of the furan ring of 5-MOP. In rat, these metabolites were excreted mainly unconjugated. An unusual metabolite was formed by reduction of the lactone moiety of 5-MOP, probably by the gut flora, giving rise to an arylpropionic acid, excreted as a glucuronic acid conjugate in the urine of all three species. 5. Unchanged drug was a very minor component of human and rat plasma, but a major component of dog plasma. In all three species, circulating 14C-metabolites were similar to those in the urine but were present mainly unconjugated. On the basis of these data, the metabolic fate of 5-MOP in humans was more similar to that in dog than to that in rat, although humans appeared to metabolize 5-MOP more rapidly than did dog.     

The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents.     

Gd DTPA. Future applications with advanced imaging techniques

In this admittedly preliminary view of the future, the authors present a number of new concepts in MR imaging and consider their possible advantages and limitations.     

DQ Wa gives rise to a DQβ restriction fragment pattern indistinguishable from that of the DQw3.2 sub-type Of DQw3

DQ beta restriction fragment patterns have been obtained from five DRw8 cell lines homozygous for the null DQ allele, DQWa. The enzymes Bgl II, Bam HI and Pvu II generate DQ beta patterns which are indistinguishable from those obtained from cell lines homozygous for DQw3.2.     

Distribution of retroperitoneal metastases after chemotherapy in patients with nonseminomatous germ cell tumors.

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.