Low-speed rotational angioplasty in chronic peripheral artery occlusions: experience in 83 patients. Work in progress

Between December 1986 and October 1988, 83 patients with chronic peripheral artery occlusions were treated with a new technique. In 56 patients, the superficial femoral artery was completely occluded; in 21 patients, the popliteal artery; and in six patients, the iliac artery. The length of occlusion ranged from 5 to 35 cm (mean, 12.5 cm). The duration, estimated by history, was 5-48 months (mean, 16.5 months). In seven patients, durations of 6-36 months were documented angiographically. A flexible, blunt, motor-driven rotating catheter was introduced through an 8-F sheath, and rotational angioplasty was performed at low speed (up to 200 rpm). In 49 of 60 (82%) patients in whom this new technique was used as the primary intervention, the occlusions were successfully reopened. In 23 patients in whom conventional methods had failed more than 4 weeks earlier, the success rate for rotational angioplasty was 67% (12 of 18 patients); when the time interval was less than 4 weeks, only one of five patients was treated successfully. In none of the 83 patients did a perforation occur. This new technique can reopen chronic artery occlusions with a high degree of success and without the danger of vessel-wall perforation, even after failure of conventional techniques.     

Liver metastases: detection by phase-contrast MR imaging

Forty patients with biopsy-proved metastatic liver cancers were studied by magnetic resonance (MR) imaging using one or more conventional (in-phase) pulse sequences and a corresponding phase-contrast (opposed-phase) pulse sequence. Pulse-sequence performance was quantitated by measuring signal-difference-to-noise (SD/N) ratios between cancerous tissue and liver. The SD/N performance of T2-weighted spin-echo (SE) pulse sequences improved when used with the phase-contrast technique. SE 2,000/30 opposed-phase images showed improved (P less than .001) SD/N in 72% of patients over in-phase images. The SD/N of T1-weighted SE or inversion recovery pulse sequences deteriorated when used with the phase-contrast technique. Changes in measured SD/N correlated well with image appearance and actual lesion detectability in individual cases. Phase-contrast imaging should be employed routinely when T2-weighted SE pulse sequences are relied on to detect liver cancer.     

The significance of cone biopsy resection margins.

This 12-year retrospective study examines the significance of margin involvement with dysplasia at cone biopsy in relation to follow-up. Of 300 cone biopsies, 123 (41%) had margin involvement. These cases of margin involvement were associated with more severe dysplasia (P less than 0.0001) and a higher chance of subsequent abnormal cytological follow-up (P less than 0.0001) and residual dysplasia at subsequent surgery (P less than 0.0001). Involvement of the endocervical margin at the initial cone biopsy was a sensitive predictor of future abnormality, with an incidence of subsequent abnormal cytology of 29% and residual disease of 82% in those undergoing further surgery. In those cases where the margins had been clear, the incidence of abnormal cytological follow-up was 8%, with 12% residual disease in those undergoing subsequent surgery. Margin involvement was a better predictor of residual disease at repeat surgery than abnormal follow-up cytology (positive predictive value, 79% vs 60%, respectively).     

Methotrexate Pharmacology and Resistance in Childhood Acute Lymphoblastic Leukemia

Impressive gains have been made in the therapy of childhood acute lymphoblastic leukemia (ALL) in recent years such that remissions today are commonly achieved in up to 95% of patients and long term disease-free survival rates approach 70%. Methotrexate is a key component in ALL consolidation and maintenance therapies and is administered intrathecally in the prophylaxis and treatment of central nervous system leukemia. Critical determinants of methotrexate sensitivity and resistance (di-hydrofolate reductase levels, methotrexate membrane transport, methotrexate polyglutamylation) previously described in cultured cells have recently been identified in lymphoblasts from children with ALL. Heterogenous expressions of increased dihydrofolate reductase or impaired methotrexate transport can be detected in both diagnostic and relapsed ALL specimens by flow cytometry with fluorescent methotrexate analogues. Lymphoblasts from children with ALL synthesize long chain polyglutamates and correlations have been established between the accumulation of methotrexate polyglutamates in ALL blasts and characteristic patient prognostic features. Variations in methotrexate polyglutamate accumulation may reflect changes in polyglutamate synthetic or degradative enzymes, or may be secondary to changes in methotrexate influx or dihydrofolate reductase levels. Other critical elements in treatment response to methotrexate include the dose and route of methotrexate administration, its catabolism to 7-hydroxymethotrexate, and the rate of methotrexate plasma clearance. A unique relationship exists between chromosome 21 and ALL leukemogenesis, and response to treatment including methotrexate. A better understanding of the molecular bases of methotrexate response and the development of methotrexate resistance in childhood ALL should facilitate further improvements in the effectiveness of methotrexate-based chemotherapy for this disease.     

Chronic thalamic stimulation for treatment of dystonic paroxysmal nonkinesigenic dyskinesia

The authors report the effect of chronic stimulation of the ventrointermediate (Vim) thalamus for treatment of dystonic paroxysmal nonkinesigenic dyskinesias (PNKD). A 37-year-old patient had a 4-year history of severe and painful PNKD of the right arm. Chronic stimulation through a stereotactically implanted monopolar electrode in the left Vim resulted in a decrease of the frequency, duration, and intensity of the dystonic paroxysmal movement disorder. The benefit of stimulation has been maintained over 4 years of follow-up.     

A processive versus a distributive mechanism of action correlates with differences in ability of normal and xeroderma pigmentosum group A endonucleases to incise damaged nucleosomal DNA

A DNA endonuclease, isolated from the nuclei of normal human and xeroderma pigmentosum complementation group A (XPA) cells, which recognizes predominately pyrimidine dimers, was examined for the mechanism by which it locates sites of damage on UVC-irradiated DNA. In reaction mixtures with low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease locate sites of UV damage on both naked and reconstituted nucleosomal DNA by different mechanisms. On both of these substrates, the normal endonuclease acts by a processive mechanism, meaning that it binds non-specifically to DNA and scans the DNA for sites of damage, whereas the XPA endonuclease acts by a distributive one, meaning that it randomly locates sites of damage on DNA. However, while both the normal and XPA endonucleases can incise UVC irradiated naked DNA, they differ in ability to incise damaged nucleosomal DNA. The normal endonuclease showed increased activity on UVC treated nucleosomal DNA compared with naked DNA, whereas the XPA endonuclease showed decreased activity on the damaged nucleosomal substrate. Since a processive mechanism of action is sensitive to the ionic strength of the micro-environment, the KCl concentration of the reaction was increased. At 70 mM KCI, the normal endonuclease switched to a distributive mechanism of action and its ability to incise damaged nucleosomal DNA also decreased. These studies show that there is a correlation between the ability of these endonucleases to act by a processive mechanism and their ability to incise damaged nucleosomal DNA; the normal endonuclease, which acts processively, can incise damaged nucleosomal DNA, whereas the XPA endonuclease, which acts distributively, is defective in ability to incise this substrate.      

A new amino acid mixture permits new approaches to the treatment of phenylketonuria

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.