Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.     

The treatment of associated intracranial aneurysms and arteriovenous malformations.

Cerebral arterial aneurysm associated with arteriovenous malformation (AVM) has been described with a variable incidence, averaging 10% of AVM cases. The present series includes 39 patients with this association, derived from a total of 400 patients with AVM's evaluated and treated since 1970. The aneurysms are classified into four major groups, each carrying particular therapeutic implications. Optimum treatment of these lesions is based in part on a knowledge of the hemodynamic alterations associated with the AVM's. In most of these cases, the symptomatic lesion was treated first; occasionally, when feasible, both lesions were treated during the same operation. All patients had some form of treatment, either surgical or endovascular, directed to at least one of the two types of lesions. All symptomatic lesions were treated and all ruptured aneurysms were obliterated. There were no deaths in this series.     

Factors influencing results of femoropopliteal bypass operations for lower limb ischemia

An ideal way to assess the effectiveness of femoropopliteal bypass procedures is to standardize patient- and surgeon-related variables by randomization. Through statistical analysis of multiple factors influencing patency, limb loss, death rate and hospital stay, the authors reviewed retrospectively 136 bypass procedures performed over 5 years. Variables that contributed significantly to the results were: preoperative symptoms (p = 0.037), graft material used (p = 0.016), age of the patient (p = 0.007), adequacy of runoff (p = 0.041) and smoking postoperatively (p = 0.013). Autogenous vein grafts were superior to prosthetic grafts, the cumulative patency at 5 years being 67.5% and 38.2% respectively. The authors emphasize that all patients needing vascular surgery should be advised to stop smoking, since in this study postoperative smoking increased the probability of limb loss and adversely affected the cumulative patency rate by interaction with other variables such as preoperative symptoms, graft material and age.     

A prospective investigation of pulmonary embolism in women and men.

OBJECTIVE. The aim of this study was to compare, in women and men suspected of pulmonary embolism, the frequency, risk factors, diagnosis, and presentation of pulmonary embolism as well as the accuracy of the ventilation/perfusion scan (V/Q scan) as a diagnostic tool. DESIGN. Data were collected during a prospective study (the Prospective Investigation of Pulmonary Embolism Diagnosis) to establish the accuracy of the V/Q scan compared with pulmonary angiograms. SETTING. Six tertiary medical centers in Massachusetts, Michigan, Connecticut, Pennsylvania, and North Carolina. PARTICIPANTS. Patients suspected of pulmonary embolism for whom a request was made for a V/Q scan or pulmonary angiogram (496 women and 406 men). RESULTS. Women 50 years old and under had a decreased frequency of pulmonary embolism compared with men of that age (16% vs 32%), but there was no difference in patients over 50 years old (Breslow-Day test, P less than .01). Risk factors for pulmonary embolism, the usefulness of the V/Q scan, and 1-year mortality were not different for women and men. Estrogen use in women was not associated with an increased frequency of pulmonary embolism, except in women using oral contraceptives who had undergone surgery within 3 months; four of five (80%) had emboli compared with four of 28 (14%) age-matched surgical patients not using estrogens (P less than .01). CONCLUSION. Women 50 years old and under (even young women using oral contraceptives) who were suspected of having pulmonary emboli and were enrolled in the Prospective Investigation of Pulmonary Embolism Diagnosis study had a smaller frequency of pulmonary embolism than men of that age, The risk factors for pulmonary embolism were the same for women and men, except that women using oral contraceptives had an increased risk of pulmonary embolism following surgery. Although the V/Q scan was a useful tool in the preliminary evaluation for pulmonary embolism in these women, a pulmonary angiogram was often needed for accurate diagnosis.     

Similar co-stimulation requirements of CD4+ and CD8+ primary T helper cells: role of IL-1 and IL-6 in inducing IL-2 secretion and subsequent proliferation.

Primary murine CD4+ and CD8+ T helper (Th) cells provide help for various immune responses by secreting lymphokines which activate effector cells. The purpose of the present study was to investigate the co-stimulatory signals that, together with T cell receptor (TCR) cross-linking, induce phenotypically distinct primary Th cells to secrete IL-2 and proliferate. We isolated highly purified populations of primary CD4+ or CD8+ T cells and stimulated them in vitro with platebound anti-CD3 mAb. TCR cross-linking by anti-CD3 mAb induced both IL-2 receptor expression and responsiveness to exogenous IL-2, but was not sufficient to induce either IL-2 secretion or T cell proliferation. Rather, for both CD4+ and CD8+ primary Th cells, IL-2 secretion and proliferation required both TCR cross-linking and antigen presenting cell (APC)-derived co-stimulatory signals. Based on G-10 adherence and sensitivity to gamma-irradiation, the APC populations able to induce primary CD4+ Th cells and primary CD8+ Th cells to secrete IL-2 were indistinguishable. In addition, we found that either IL-1 or IL-6 could replace the requirement for APC-derived co-stimulatory signals for IL-2 secretion and proliferation by both primary CD4+ Th cells and primary CD8+ Th cells. Thus, the present study has examined and compared the co-stimulatory requirements of rigorously purified subsets of IL-2-secreting primary CD4+ and primary CD8+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical considerations in bypassing coronary arteries with 100% proximal occlusion.

Objective data on the ability of cineangiography to predict the size of reconstituted totally occluded coronary arteries, as well as the clinical outcome of such revascularization, are sparse. Accordingly, we reviewed 200 consecutive cases of coronary revascularization to determine the answers to these questions. Group I patients (n = 57, with 86 totally occluded coronary arteries) had at least one coronary artery with a 100% proximal occlusion that reconstituted distally. Group II patients (n = 143, with 205 subtotally occluded coronary arteries) had 50% to 99% proximal stenosis of at least one coronary artery. Cineangiograms were blindly reviewed to measure the size of the coronary arteries, which were compared with the actual vessel size at operation. In group I, the totally occluded coronary arteries had a cineangiographic size of 1.9 +/- 0.7 mm and an actual size of 1.6 +/- 0.4 mm (p = 0.00004). In group II, the subtotally occluded coronary arteries had a cineangiographic size of 1.8 +/- 0.4 mm compared with an actual size of 1.8 +/- 0.3 mm (p = not significant). The site of bypass grafting was significantly smaller in group I (1.6 +/- 0.4 mm versus 1.8 +/- 0.3 mm; p = 0.00008). The two groups were similar with respect to preoperative and intraoperative parameters. Operative mortalities were similar (group I, 1.8%; group II, 3.5%; p = 0.68). Creatine kinase isoenzyme profiles and electrocardiographic changes were similar, except for a significant late rise of creatine kinase-MB in group I (56.1 +/- 14.7 versus 30.7 +/- 33.7 MIU/mL; p < 0.001). In conclusion, cineangiography significantly overestimates the size of totally occluded coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)     

Native genomic blotting: high-resolution mapping of DNase I-hypersensitive sites and protein-DNA interactions.

DNase I-hypersensitive sites are observed in the promoter regions of actively expressed genes, potentially active genes, and genes that were once active. We have developed an approach that greatly increases the resolution for mapping these sites by electrophoresing genomic DNA on native polyacrylamide gels prior to electroblotting and hybridization. This improved method has been used to scan the promoter and coding region of a cell-cycle-dependent human histone H4 gene with an accuracy of +/-5-10 base pairs. Protein-DNA interactions can be seen in the autoradiograph as light areas and DNase I-hypersensitive sites as dark bands. Therefore, this method provides a rapid and relatively simple means to accurately localize protein-DNA interactions as well as DNase I-hypersensitive sites, thus directly displaying DNase I hypersensitivity and protein-DNA complexes on one autoradiograph. It also potentially allows the analysis of small changes in DNase I-hypersensitive sites under various biological conditions. With this technique rather large regions of DNA can be screened to determine areas that should be analyzed by more sophisticated methods, such as genomic sequencing or gel retardation assays.     

Bilateral malignant glaucoma.

Two cases of bilateral malignant glaucoma are presented. In one case the condition developed sequentially in the two eyes; pars plana vitrectomy was eventually needed in the operated eye, whereas the condition responded to medical treatment in the fellow eye. In the second case the two eyes were involved simultaneously nearly 1 year after surgery, and the glaucoma responded to medical treatment.     

Salvage radical prostatectomy after failure of curative radiotherapy for adenocarcinoma of prostate.

Radical prostatectomy with curative intent was performed in 13 patients with prostate cancer after local failure of radiotherapy. Of these patients, 2 underwent cystoprostatectomy for bladder neck involvement by the prostatic tumor. Local recurrence had been diagnosed twenty-one to one hundred sixty-eight months (mean 65.4 months) after completion of radiotherapy (6,000-7,000 cGy; mean 6,136 cGy). Three patients had radioactive implants. Rising prostate-specific antigen (PSA) was part of the indication for surgery in 5 patients. Complications included minor rectal injury (1 patient) and total incontinence (2/13 patients). Two patients had positive surgical margins and 6/13 patients had involvement of seminal vesicles, 2 of whom also had positive lymph nodes. The authors conclude that salvage prostatectomy is feasible after radiation failure. Transrectal ultrasound and careful monitoring of PSA after irradiation treatment may improve patient selection and minimize the risk of complications and incomplete excision.     

Salmon calcitonin prevents cyclosporin-A-induced high turnover bone loss

Cyclosporin-A (CsA) has greatly influenced the outcome of organ transplantation and has also been effective in the treatment of many autoimmune diseases. Unfortunately, it has deleterious effects on bone remodelling, causing a high turnover bone loss, with bone resorption exceeding bone formation. Salmon calcitonin (SCtn) has been shown to inhibit bone resorption in high turnover states such as Paget's disease and postmenopausal osteoporosis. In an attempt to attenuate the high turnover bone remodelling caused by CsA alone, we studied the bone mineral effects of CsA in combination with SCtn in male Sprague-Dawley rats. Group A (n = 20) received vehicle as control, group B (n = 20) received CsA (15 mg/kg BW) by daily gavage and SCtn vehicle sc, group C (n = 20) received SCtn (1.3 IU/kg BW) daily sc and CsA vehicle, and group D (n = 20) received a combination of CsA and Ctn daily, as described above. Rats were bled weekly for determination of circulating biochemical bone parameters. Eight rats from each group were killed on day 14 (short term), and the remaining rats were killed on day 28 (long term). Tibiae were removed for bone histomorphometry after death, which revealed a reduction of trabecular bone volume and an increase in osteoclast number induced by CsA alone. These changes were significantly attenuated by the combination of CsA and SCtn to resemble the histomorphometry of the control group. The inhibition of osteoclast number by SCtn is the most plausible mechanism by which the combination therapy attenuates the high turnover bone loss induced by CsA alone.