Medial posteroventral pallidotomy for the treatment of Parkinson's disease]

Stereotactic medial posteroventral pallidotomy for treatment of Parkinson's disease attracts increasing attention. We report on the preliminary results of 12 patients at 1 year after microelectrode-guided unilateral pallidotomy. The primary indications were severe bradykinesia and levodopa-induced dyskinesias. After radiofrequency lesioning all patients had immediate improvement of contralateral parkinsonian signs. Postoperative magnetic resonance imaging confirmed the localization of the lesions. At the 1-year follow-up, all patients had sustained benefit. The global improvement was rated as moderate in six cases, and as marked in six other cases. The mean values of various subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) showed highly significant changes in the "off" state (pre/postoperatively): UPDRS Motor score (60.3/31). UPDRS Activities of Daily Living (ADL) score (33.2/18.3), gait/postural stability score (13.8/7.0), and subscores for contralateral rigidity (4.9/2.1), tremor (7.1/1.4) and bradykinesia (11.6/5.3). There was also significant improvement of ipsilateral bradykinesia and rigidity. Furthermore, we found significant changes of the mean values of the UPDRS ADL and motor "on" scores, an increase of the percentage of "on" time with reduced on-off fluctuations, and a decrease of the percentage of levodopa-induced dyskinesias, with marked improvement or complete abolition of contralateral dyskinesias in particular. The preoperative levodopa regimen was maintained, in general, or only slightly modified, if necessary. Two patients had transient complications: one patient suffered postoperative pneumonia and altered mental status; another patient displayed mild Broca's aphasia secondary to a small stroke involving the dorsal thalamus and the adjacent white matter. There were no persistent side effects at the 1-year follow-up. Contemporary unilateral pallidotomy is an effective and promising therapeutical option for surgical treatment of advanced Parkinson's disease.     

Outcomes after stereotactically guided pallidotomy for advanced Parkinson's disease

OBJECT: Parkinson's disease (PD) is a prevalent neurodegenerative disorder that becomes refractory to medication as the disease progresses. Although in the past 5 years increasing numbers of patients have undergone stereotactically guided posteroventral pallidotomy for advanced PD, the safety and efficacy of surgery remains to be documented. The goal in this study was to determine the potential operative morbidity and types of functional outcomes by using validated PD rating scales and a patient survey. METHODS: In a prospective analysis of a consecutive surgical series the authors evaluated 58 patients with advanced PD who ranged in age from 40 to 79 years (mean 67 years) and who had undergone surgery between 1994 and 1997. They used a patient survey and the Unified Parkinson's Disease Rating Scale (UPDRS) to study patients during periods of medication administration ("on") and withdrawal ("off"; mean off score before surgery = 96). Temporary surgical morbidity was found in four patients (6.9%), three of whom developed transient dysarthria and one of whom exhibited transient confusion (1.7%). One patient had persistent dysarthria (1.7%). No patient developed a visual field deficit or sustained a brain hemorrhage. All patients were discharged from the hospital within 24 hours. Significant postsurgical improvements were noted in the UPDRS off-period total and motor scores, as well as in tremor, rigidity, bradykinesia, and contralateral dyskinesia (p < 0.005). Improvements persisted in dyskinesia and tremor for the 21 patients who were evaluated past 1 year. The authors found no improvement in any on-period symptoms except dyskinesia. Thirty-one (61 %) of 51 patients surveyed reported functional gains and/or dramatic improvement in symptoms, 17 (33%) reported symptomatic improvement without functional gains, and three (6%) had minimal or no change in symptoms. No change in the mini mental state examination score was noted during follow up. There were no significant postoperative changes in the use of medication. CONCLUSIONS: In advanced PD associated with either a medically refractory state with significant off periods or levodopa-induced dyskinesias, magnetic resonance imaging-guided pallidotomy with macrostimulation was associated with minimal morbidity and yet significantly reduced dyskinesia and off-period disability. These improvements were of value to the patient and persisted beyond the 1st year.     

Surgical interventions in the treatment of Parkinson's disease (PD) and essential tremor (ET): medial pallidotomy in PD and chronic deep brain stimulation (DBS) in PD and ET

Surgical treatments for PD and ET are promising. Medial Pallidotomy, the surgical lesioning of the pallidum, often improves symptoms of long-standing PD. We enrolled twenty-seven late stage PD patients for unilateral medial pallidotomy who were then assessed by the Core Assessment Program for Intracranial Transplantation (CAPIT) protocol. One year after surgery persistent improvement was seen contralateral to the lesion in the following features: drug-induced dyskinesias (92%), akinesia (38%), rigidity (51%), and tremor (42%). Complications included transient dysarthria (7 patients), facial weakness (9 patients), limb weakness (1 patient), swallowing problems (4 patients) and intracerebral haemorrhage (1 patient). Thalamic DBS may improve tremor in PD and ET patients. Therefore, we enrolled fifteen patients (9 PD and 6 ET patients) with disabling tremor, unresponsive to medication. They were assessed by the United Parkinson's Disease Rating Scale (UPDRS) and the Tremor Rating Scale (for PD and ET patients, respectively). Three months after surgery, limb tremor contralateral to stimulation improved by 71% in PD patients and 76% in ET patients. Complications included transient paresthesias (all), confusional state (1 patient) and intracerebral bleed (1 patient). Unilateral medial pallidotomy safely improves some Parkinsonian symptoms contralateral to the lesion. Thalamic DBS may effectively and safely improve contralateral limb tremor in PD and ET.     

Posteroventral medial pallidotomy in advanced Parkinson's disease

BACKGROUND: Posteroventral medial pallidotomy sometimes produces striking improvement in patients with advanced Parkinson's disease, but the studies to date have involved small numbers of patients and short-term follow-up. METHODS: Forty patients with Parkinson's disease underwent serial, detailed assessments both after drug withdrawal ("off" period) and while taking their optimal medical regimens ("on" period). All patients were examined preoperatively and 39 were examined at six months; 27 of the patients were also examined at one year, and 11 at two years. RESULTS: The percent improvements at six months were as follows: off-period score for overall motor function, 28 percent (95 percent confidence interval, 19 to 38 percent), with most of the improvement in the contralateral limbs; off-period score for activities of daily living, 29 percent (95 percent confidence interval, 19 to 39 percent); on-period score for contralateral dyskinesias, 82 percent (95 percent confidence interval, 72 to 91 percent); and on-period score for ipsilateral dyskinesias, 44 percent (95 percent confidence interval, 29 to 59 percent). The improvements in dyskinesias and the total scores for off-period parkinsonism, contralateral bradykinesia, and rigidity were sustained in the 11 patients examined at two years. The improvement in ipsilateral dyskinesias was lost after one year, and the improvements in postural stability and gait lasted only three to six months. Approximately half the patients who had been dependent on assistance in activities of daily living in the off period before surgery became independent after surgery. The complications of surgery were generally well tolerated, and there were no significant changes in the use of medication. CONCLUSIONS: In late-stage Parkinson's disease, pallidotomy significantly reduces levodopa-induced dyskinesias and off-period disability. Much of the benefit is sustained at two years, although some improvements, such as those on the ipsilateral side and in axial symptoms, wane within the first year. The on-period symptoms that are resistant to dopaminergic therapy do not respond to pallidotomy.     

Kallikrein gene therapy: a new strategy for hypertensive diseases

The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p = 0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p = 0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p = 0.0001) and the Cmax (maximum concentration) was also decreased by 80%d after the administration (p = 0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.     

NMDA but not AMPA receptor antagonists impair the delay-interposed radial maze performance of rats

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.     

Stereotactic pallidotomy and thalamotomy using individual variations of anatomic landmarks for localization

OBJECTIVE: The optimal choice of imaging and localization for stereotactic surgery for movement disorders remains uncertain, with controversy surrounding the use of microelectrode recording and the role of distortion of magnetic resonance imaging (MRI) scans in reducing the accuracy of lesion placement. We review our experience with 67 pallidotomies and 35 thalamotomies performed without microelectrode recording, using instead individual variations in anatomic landmarks. METHODS: Computed tomography is used as the primary modality, with comparison with carefully angled MRI scans and the use of neural structures, such as the mamillary bodies and the vascular anatomy. Pallidal target sites are chosen immediately lateral and superior to the optic tract on a line bisecting the axis of the peduncle, with macrostimulation guiding the final adjustment of target position. Forty-seven patients undergoing unilateral pallidotomies were studied in the "off" state and the "on" state using a modified Unified Rating Scale for Parkinson's disease (URSP) score and a dyskinesia scale, preoperatively and postoperatively at 2 weeks, 2 months, 6 months, and 12 months. In the 31 patients undergoing thalamotomy, tremor was rated preoperatively and postoperatively as near-complete resolution, partial resolution, and failure. RESULTS: The "off" state Unified Rating Scale for Parkinson's disease motor score declined from 42.0 to 32.2 at 2 weeks after surgery (P < 0.0001, n = 42). The Unified Rating Scale for Parkinson's disease motor score was 34.2 at 2 months (P < 0.0001, n = 35), 29.4 at 6 months (P < 0.0001, n = 27), and 24.9 at 12 months (P = 0.005, n = 12), representing an overall improvement in "off" state motor function of approximately 25 to 40%. The "on" state dyskinesia score fell from 5.5 to 2.0 at 2 weeks (P < 0.0001) and persisted in the later visits. The dyskinesia score for the contralateral side fell from 2.5 preoperatively to 0.26 at 2 weeks, 0.28 at 2 months, 0.22 at 6 months, and 0.0 at 12 months. Of the patients undergoing thalamotomies, 65% experienced near-complete or complete tremor resolution, 23% experienced partial tremor relief, and 13% were considered treatment failures. CONCLUSION: Stereotactic procedures for movement disorders requiring high precision can be safely and successfully performed without the use of microelectrode recording techniques. Meticulous alignment of MRI and computed tomographic scans based on visualized anatomy allows precise lesion placement and avoids the distortion inherent in MRI scans.     

Endoscopic treatment of reflux by subureteric collagen injection: critical review of 5 years'' experience

This retrospective study analyses the benefit of surgery to patients with pelvic metastases. Forty-three patients were operated on between 1980 and 1992, 37 having intralesional and 6 extralesional resections. Thirty-nine had perioperative adjuvant therapy. Survival time was calculated by the Kaplan-Meier method. Clinical evaluation used the Karnofsky performance status which showed improvement from 55% before operation to 74% at 3 months (p = 0.0001) and 77% after 6 months (p = 0.0001). Those having an intralesional resection had a median survival time of 13 months, a complication rate of 24% and a local recurrence rate of 19%. The comparable figures for those with extralesional resection were 16 months survival, complications in 3 out of 6, and no local recurrences. The quality of life was improved by operation and intralesional resection is preferable in most of these patients.     

A trial of dextromethorphan in parkinsonian patients with motor response complications

The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications.     

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.     

Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer

PURPOSE: To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients, at high predicted risk for lymph node involvement, receiving definitive radiotherapy. MATERIALS AND METHODS: Between October 1987 and December 1995, 506 patients with clinically localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions. Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up was 35 months and 30 months, respectively). PSA failure was defined as: 1. a PSA value > or = 1 ng/ml; or 2. a PSA value that rose > or = 0.5 ng/ml in < or = 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as 2/3(iPSA) + 10(GS-6), and high risk was defined as %rLN+ > or = 15%. Univariate and multivariate analyses were performed. RESULTS: A total of 201 high-risk patients were identified. High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment (median PFS = 34.3 months vs. 21.0 months; p = 0.0001). Potential confounding variables, including initial PSA, Gleason score, T stage, radiation dose, year of treatment, use of three-dimensional (3D) conformal techniques, and use of hormone therapy, did not account for the observed difference in time to PSA failure. Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome. CONCLUSION: Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity.     

Serum N-terminal osteocalcin is a good indicator for estimating responders to hormone replacement therapy in postmenopausal women

To estimate the response to hormone replacement therapy (HRT) by bone metabolic markers, 36 patients with postmenopausal osteoporosis or osteopenia were studied to assess the correlation between percent baseline changes in lumbar bone mineral density (BMD) after 12 months and those in various bone metabolic markers after 3, 6, and 12 months of HRT. All the patients were treated with 0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone per day and continued for 12 months. BMD was significantly increased up to 4.19 +/- 0.87% after 6 months and 4.93 +/- 1.27% after 12 months of HRT (p = 0.0001 by analysis of variance). In accordance with this, changes in the levels of osteocalcin (p = 0.041), alkaline phosphatase (p = 0.0001), N-terminal osteocalcin (p = 0.0001), urinary excretion of pyridinoline/Cr (p = 0.0001), and deoxypyridinoline/Cr (p = 0.0001) were significantly decreased, respectively. Among these bone metabolic markers, only the change in the serum N-terminal osteocalcin at 3 months (r = 0.557, p = 0.0022), at 6 months (r = 0.470, p = 0.0184), and at 12 months (r = 0.545, p = 0.0061) significantly correlated with the change in BMD 12 months after HRT. The elution profiles of immunoreactive osteocalcin-related molecules in serum fractionated by reverse-phase high performance liquid chromatography revealed that the N-terminal fragment as well as the intact osteocalcin molecule decreased after 3 months of HRT. These results demonstrate that N-terminal osteocalcin is a suitable predictor for estimating good responders to HRT in postmenopausal women.     

Improvement in quality of life in patients with heart failure who undergo transplantation

BACKGROUND: Very few studies have examined quality of life longitudinally in heart failure patients from before or after heart transplantation. The purpose of this study was to compare quality of life of patients with heart failure at the time of listing for a heart transplant with that 1 year after the operation. Major dimensions of quality of life measured in this study were health, physical and emotional functioning, and psychosocial functioning. METHODS: A convenience sample of 148 patients (80% male and mean age 52 years) was recruited from a midwestern and southern medical center. Data were collected from chart review and six patient-completed instruments: the Heart Transplant Symptom Checklist, Sickness Impact Profile, Heart Transplant Stressor Scale, Jalowiec Coping Scale, Quality of Life Index, and Rating Question Form. Informed consent was obtained, and patients who agreed to participate in the study completed the booklet of self-administered instruments. Statistical analyses included frequencies, measures of central tendency, paired t-tests, and Wilcoxon signed-ranks tests. RESULTS: Total symptom distress decreased significantly overall from before to after heart transplantation (before = 0.19 versus after = 0.15, p < 0.0001). Patients rated themselves as having significantly poorer health while listed as a heart transplant candidate than at 1 year after surgery (before = 4.5 versus after = 7.5, p < 0.0001). Although the overall level of functional disability was fairly low before and 1 year after transplantation, patients still reported significant improvement after surgery (before = 0.21 versus 1 year after = 0.13, p < 0.0001). No significant differences were found in total stress, which was low to moderate (before = .026 versus 1 year after = 0.26, p = not significant), coping use (before = 0.48 versus 1 year after = 0.48, p = not significant), or coping effectiveness (before = 0.40) versus 1 year after = 0.42, p = not significant), from before to 1 year after heart transplantation. However, changes in types of symptoms, functional disability, stressors, and coping were noted over time. Overall satisfaction with life, which was fairly high at both time periods, increased significantly from the time of listing for a transplant to 1 year after surgery (before = 0.72 versus 1 year after = 0.82, p <0.0001), and overall quality of life improved significantly from before to after heart transplantation (before = 5.5 versus after = 7.8, p < 0.0001). CONCLUSIONS: End-stage heart failure patients had improved quality of life from before to 1 year after heart transplant due to less total symptom distress, better health perception, better overall functional status, more overall satisfaction with life, and improved overall quality of life. However, post-transplant patients still experienced some symptom distress, functional disability, and stress, but were coping well.     

A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome

To compare the efficacy (induction of remission) and safety of cyclosporine (CsA) with those of supportive therapy in patients with steroid-resistant idiopathic nephrotic syndrome (INS), we organized an open, prospective, randomized, multicentric, controlled study for parallel groups, stratified for adults and children. Forty-five patients with steroid-resistant INS were randomly assigned to supportive therapy or CsA (5 mg/kg/day for adults, 6 mg/kg/day for children) for six months, then tapered off by 25% every two months until complete discontinuation. Four patients were lost to follow-up. During the first year 13/22 CsA-treated patients versus three of 19 controls attained remission of the nephrotic syndrome (P < 0.001). A symptom score was assessed at time 0 and at six months. The mean score significantly decreased in the CsA group (P < 0.001), but remained unchanged in the controls. At month 6 the mean urinary protein excretion, the mean serum proteins and plasma cholesterol had significantly improved in the CsA group but were not changed in the controls. There were no significant differences in serum creatinine and creatinine clearance between treatments (interaction time* treatments, P = 0.089 and P = 0.935, respectively) at month 6 versus basal. The CsA-related side-effects were mild; no significant difference in blood pressure between the two groups was seen at any time. This study shows that CsA can bring about remission in some 60% of patients with steroid-resistant INS. In patients with normal renal function and without severe hypertension, CsA at the therapeutic scheme adopted did not produce severe renal or extrarenal toxicity.     

The impact of Helicobacter pylori eradication on peptic ulcer healing

OBJECTIVE: Current literature was reviewed analyzing the outcome of peptic ulcer healing in relation to the results of the posttherapeutic Helicobacter pylori (HP) status. METHODS: Literature was reviewed along with an analysis of 60 studies, comprising a total of 4329 patients. RESULTS: Successful Helicobacter pylori eradication was found to induce a better response in peptic ulcer healing, regardless of diagnosis: gastric ulcer 88% vs 73% (odds ratio [OR] 2.7, p < 0.01), duodenal ulcer 95% vs 76% (OR 5.6, p < 0.0001), and peptic ulcer 95% vs 76% (OR 6.6, p < 0.0001), for patients having their HP infection successfully cured versus those remaining HP-positive, respectively (Fisher's exact test). For all evaluated time points (< or = 6, 7-8, and 10-12 wk after beginning treatment), HP-negative patients had higher healing rates than HP-positive patients (95% vs 82%, 94% vs 69%, and 96% vs 78% with corresponding OR of 4.2, 6.5, and 7.4, all p < 0.0001, Fisher's exact test). The use of concomitant acid suppression therapy during initial HP eradication provided a benefit on peptic ulcer healing only for patients with persistent HP infection (improved healing rates of 78% vs 67%; otherwise rates were 94-96%). Likewise, prolonged acid inhibition in HP treatment failures after the initial HP treatment phase resulted in 7-20% improved healing rates, whereas patients becoming HP-negative did not profit. CONCLUSION: Successful HP eradication therapy accelerates peptic ulcer healing even without concomitant acid suppression.     

Dermal application of lisuride on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset and on cases with Parkinson''s disease

BACKGROUND: Follow-up study of patients with surgical repair of aneurysmal subarachnoidal hemorrhage (SAH), looking for clinical outcome predictors. PATIENTS AND METHODS: Sixty two patients consecutively admitted to a teaching hospital, from January 1992 to December 1995 were included in the study. We studied preoperative, intraoperative and postoperative features looking for their relationship with the outcome. The ultimate outcome was evaluated by means of Glasgow Outcome Scale on discharge and 6 months later. RESULTS: Smoking (p = 0.0001) and arterial hypertension (AHT) (p = 0.0186) were more frequent in these patients than in general population, but without relationship to the outcome as with the age of the clinical status on admission. The greatest statistical relationship was found between the level of consciousness on postoperative awakening (measured by the Hunt and Hess scale), and the outcome (p = 2.53 x 10(-8). From our results we made an algorithm that correctly assigned 92% of studied patients to their outcome. CONCLUSIONS: All patients admitted on with aneurysm SAH deserve intensive care treatment besides their clinical grade. The level of consciousness on postoperative awakening was a good outcome predictor.     

Evidence that the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in human serum may not be secreted by the pituitary gland

A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.     

Imaging of delta- and mu-opioid receptors in temporal lobe epilepsy by positron emission tomography

The authors report the postoperative magnetic resonance (MR) imaging findings in 36 patients with advanced Parkinson's disease who underwent unilateral microelectrode-guided posteroventral pallidotomy. The lesions were placed within 1 mm of the ventral border of the globus pallidus internus (GPi) to include pallidothalamic outflow pathways. Sequential MR studies were obtained within 1 to 3 days postoperatively and at 6-month follow-up examination. Thirty-four (94%) of the 36 patients enjoyed sustained moderate or marked improvement of their parkinsonian symptoms 6 months postoperatively. Transient side effects occurred in five patients (14%), but there were no persistent complications. The pallidal radiofrequency lesions were prolate spheroid shaped and were composed of three concentric zones in the early postoperative studies. The mean volume of the middle zone, corresponding to the area of hemorrhagic coagulation necrosis, was 44.4 +/- 17.6 mm3; the mean lesion volume as defined by the outer zone, corresponding to perilesional edema, was 262.2 +/- 111.6 mm3. Additional edema spreading to the internal capsule was noted in 32 of 34 cases and to the optic tract in 11 of 34 cases. In two patients small ischemic infarctions involving the corona radiata were found, and in one a venous infarction was detected. Ischemic infarction resulted in mild transient Broca's aphasia in one patient, but there was no detectable neurological deficit in the other two. The mean volume of late-phase (6 months) lesions was 22 +/- 28.8 mm3. In three patients no lesion was identified despite sustained clinical improvement. The lesion was located in the posteroventral GPi in all cases except in one patient in whom it was confined to the GP externus (GPe). This 49-year-old woman did not experience sustained benefit. The authors found no consistent correlations between lesion size and location and clinical outcome as measured by a global outcome score, the Unified Parkinson's Disease Rating Scale motor, activities of daily living, and bradykinesia "off" scores or rating of dyskinesias. Lesioning of pallidal and subpallidal pathways may contribute to the sustained clinical benefit in this series. Magnetic resonance imaging analysis showed that intraoperative microelectrode recording facilitated accurate placement of the lesion in this critical area.     

Botulinum toxin in spastic infantile cerebral palsy: results in 27 cases during one year

INTRODUCTION AND OBJECTIVES: Positive outcome of patients with spastic cerebral palsy treated with botulinum toxin reported in the last three years has led us to perform this study with the aim to show our experience in the management of spastic cerebral palsy with the toxin, determine its indications, analyze the results and propose new possible indications in the future. MATERIAL AND METHODS: We include 10 hemiplegic and 17 diplegic patients with an average age of 6 years and 7 months, followed up between 5 and 17 months. Clinical improvement was monitored using the PRS and EVFEL scales and articular motion range was measured 6 months before and after the injection while continuing physiotherapy. The injected muscles were adductor, hamstrings, triceps and posterior tibialis, and the doses were 1-2 U/muscle/kg body weight. RESULTS: The values on PRS improved an average of 24%, adductor angle 66% (p < 0.01), knee angle 40% (p = 0.05) and ankle angle 52% (p < 0.01); 96% of patients could get more physiological static or walking patterns because of the decrease of spasticity and those persisted after the effect of the toxin had worn off. It was maximum at 2 months, stabilized 4 to 6 months later and decreased during further 2 months. CONCLUSIONS: This experience leads us to propose higher starting dosage and to take into account the stability of postural pattern of each patient to choice the muscle to be injected. Other therapeutic possibilities are also proposed in children with fixed shortening e.g. combining the toxin with stretching casts.     

Percutaneous transluminal coronary angioplasty versus medical therapy for stable angina pectoris: outcomes for patients with double-vessel versus single-vessel coronary artery disease in a Veterans Affairs Cooperative randomized trial. Veterans Affairs ACME InvestigatorS

OBJECTIVES: This study sought to assess outcomes of men with double-vessel coronary artery disease randomly assigned to treatment by percutaneous transluminal coronary angioplasty (PTCA) or medical therapy, compared with previously reported outcomes for men with single-vessel disease. BACKGROUND: We previously reported that PTCA provides better symptom relief and treadmill performance than medical therapy for men with stable angina pectoris due to single-vessel disease. Whether this advantage applies to patients with double-vessel disease is unknown. METHODS: Male patients (n = 328) with stable angina pectoris and ischemia on treadmill testing were randomly assigned to PTCA or medical therapy; 101 patients had double-vessel disease, and 227 had single-vessel disease. Symptoms, treadmill performance, quality of life score, coronary stenosis and myocardial perfusion were compared at baseline and at 6 months. Patients were followed up for up to 6 years and underwent additional treadmill testing 2 to 3 years after randomization. RESULTS: PTCA-treated and medically treated patients with double-vessel disease experienced comparable improvement in exercise duration (+1.2 vs. +1.3 min, respectively, p = 0.89), freedom from angina (53% and 36%, respectively, p = 0.09) and improvement of overall quality of life score (+1.3 vs. +4.4, respectively, p = 0.32) at 6 months compared with baseline. This contrasts with greater advantages favoring PTCA by these criteria in patients with single-vessel disease (p = 0.0001 to 0.02). Trends present at 6 months persisted at late follow-up. Patients undergoing double-vessel dilation had less complete initial revascularization (45% vs. 83%) and greater average stenosis of worst lesions at 6 months (74% vs. 56%). Likewise, patients with double-vessel disease showed less improved myocardial perfusion imaging (59% vs. 75%). CONCLUSIONS: PTCA is beneficial in male patients with double-vessel disease; however, we cannot demonstrate the same advantage over medical therapy seen in similar patients with single-vessel disease. Less complete revascularization and greater restenosis for patients having multiple dilations would account for these findings. Alternatively, a type 2 error might be operative. Technical advances since completion of this trial might improve these outcomes. These findings warrant further investigation in a larger trial.