The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis

OBJECTIVE: To determine whether sulfasalazine is better than placebo in slowing disability progression in MS. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 199 patients with active relapsing-remitting (n = 151) or progressive (n = 48) MS were evaluated at 3-month intervals for a minimum of 3 years (94% completed 3 years of follow-up; mean follow-up, 3.7 years). MRI studies were performed at 6-month intervals on a subset of 89 patients. RESULTS: Sulfasalazine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability Status Scale [EDSS] score by at least 1.0 point on two consecutive 3-month visits). Sulfasalazine influenced favorably a number of secondary outcomes during the first 18 months of the trial (e.g., annualized relapse rate, proportion of relapse-free patients; progressive subgroup only: rate of EDSS progression at 1 and 2 years, median time to EDSS progression) but these positive findings were not sustained into the second half of the trial. CONCLUSIONS: Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, at least temporarily, without providing sustained slowing of EDSS progression. Phase III MS trials should be of sufficient length to determine a meaningful impact on disease course.     

Clinical characterization of patients with multiple sclerosis defined in Cuba

INTRODUCTION: Since 1975 no studies have been done in Cuba defining the clinical characteristics of patients with multiple sclerosis (MS). OBJECTIVE: To describe the characteristics of a group of Cuban patients with definite clinical MS. MATERIAL AND METHODS: Fifty eight patients with definite clinical MS were studied (Poser et al) with normal motor (VCM) and sensory (VCS) conduction velocities. Tests were done on them: clinical scale (Scripps), incapacity (EDSS) and quality of life (Steps), together with various complementary tests. Each patient was classified according to the way in which the disease evolved. Also the two commonest clinical types were compared and we applied the difference test between percentages of non-paired samples with an alfa level of 0.05. RESULTS: Onset of the illness in most cases was before the age of 40 (86.1%), 75.9% were women and 82.8% were white. In 15.3% there was a family history of MS. In 25.9% there were psychiatric disorders and trigger factors (43.1%. The most frequent initial symptoms were pyramidal (48.3%) sensorial (41.4%) and cerebellar (39.7%). Scripps scale scores were < 80 in 60.2%, in EDSS < 5 (61.9%) and in the Clinical Steps < 3 in 65.4%). Motor potentials (81.9%) somatosensory potential (PESS) (72.3%) and magnetic resonance imaging (MR) (76.4%) were the most abnormal results. Exacerbation-remission (ER) was the most frequent type of evolution (53.4%) generally affecting patients aged under 40 years old (p = 0.02), EDSS < 5 (64.4%), Scripps > 80 (61.2%), Steps < 3 (95.6%), pyramidal system involvement (58.5%), cerebellar (29.2%) and MRI abnormality (80%). The progressive primary form (PP) was the second most frequent (29.3%); 29.4% were under 40 years of age, had more marked changes in all functional system (100%), degree of incapacity and quality of life (100%). PESS (92.5%); the urodynamic tests 58.85%) were less positive on MRI (54.5%) as compared with the ER form. CONCLUSIONS: The differences found between the clinical forms ER and II indicate that there is greater deterioration in the PP form, probably due to age and more cerebellar and spinal cord involvement.     

In vitro and in vivo antibacterial activities of AM-1155 in the fields of obstetrics and gynecology

OBJECTIVES: Until relatively recently southern Europe was regarded as having a medium to low multiple sclerosis prevalence, of about 20 or less per 100,000. However, recent studies in Sardinia, Sicily, continental Italy, Cyprus and Spain have yielded higher MS prevalence rates, between 32 and 102.6 per 100,000. We present the results of a prevalence study of MS in the municipality of M6stoles, central Spain. MATERIAL AND METHODS: To ascertain the prevalence of multiple sclerosis in M6stoles (195,979 inhabitants), an intensive study was undertaken using several sources of information. We used the Poser criteria in diagnosis. RESULTS: There were 85 patients (53 women and 32 men) classified as definite or probable, prevalence 43.4/100,000 (95% CI, 34.7 to 53.7). The incidence rate was 3.8/100,000/year (95% CI, 2.7 to 5.3) in the last 5 years. Mean age on prevalence day was 38.8+/-10.9 years. Mean age at onset was 31.7+/-9.3 years. Mean interval between initial symptoms and diagnosis was 1.7 years. Mean duration of disease was 7.6+/-6.1 years. Overall, 70.6% had a relapsing-remitting course, 18.8% had a primary progressive and 10.5% had a secondary progressive. Mean EDSS score was 2.7+/-1.9. CONCLUSION: The M6stoles study confirms the conclusions of previous smaller population studies that Spain is a moderately high or medium MS risk zone.     

Endocrine orbitopathy: comparison of the long-term result and classification after radiotherapy

BACKGROUND: This study compares 4 classifications in patients with progressive refractory Graves orbitopathy (GO) and examines their prognostic value in long-term follow-up. PATIENTS AND METHODS: From 1984 to 1994, 60 consecutive patients (49 female, 11 male) received 20 Gy (10 x 2 Gy) radiotherapy with 6 MV Linac photons. Ocular symptoms and functional impairment was evaluated according to 4 GO-classification systems: Werner-, modified ATA- and Stanford-Score and Ophthalmopathy-Index (OI) according to Grussendorf. In addition, all patients noted their subjective response on a linear scale (0 to 100%). RESULTS: Improvement was achieved within 1 year after radiotherapy according to the Werner-Score in 28 (47%) patients in > or = 1 symptom category, according to the modified ATA-score in 48 (80%), the Stanford-score in 47 (78%) and the OI-Score in 55 (92%) patients (reduction of > 2 points). The Werner-Score correlated less to the other scores (coefficient r < 0.5) than the other scores among themselves (r approximately 0.9). The ATA-Score improved in the different symptom categories between 47% (stage VI) and 87% (stage V). The OI-Score was reduced by a mean of 6 points. The patients reached a mean subjective improvement of +70 +/- 25%. Acute or chronic side effects were not observed. In multivariate analysis the "male gender" (p = 0.08), a "symptom duration prior to radiotherapy > 1 year" (p = 0.14) and a "high symptom category" (p = 0.11) indicated a negative prognostic trend. CONCLUSIONS: External radiotherapy is effective for severe, progressive GO after pretreatment. A minimum follow-up of at least 12 months and standardized classification and success criteria are required.     

High levels of cerebrospinal fluid IgM binding to myelin basic protein are associated with early benign course in multiple sclerosis

We assessed human myelin basic protein (MBP) binding IgM levels in CSF. MBP is the most studied putative antigen in multiple sclerosis (MS) and immune responses against it may be involved in the demyelination process. We also correlated these levels with EDSS score and other parameters of disease progression and prognosis, both at the time of CSF analysis and during follow-up. CSF IgM anti-MBP levels were assayed by measuring total IgM levels with solid-phase ELISA in CSF samples from 66 patients with relapsing-remitting MS, 11 subjects without neurological diseases, 20 patients with non-inflammatory neurological diseases and 7 patients with lymphocytic meningitis, before and after immunoabsorption with human MBP. Confirmation of IgM binding specificity was performed by immunoblotting of positive CSF samples onto MBP coated-nitrocellulose sheets. Clinical evaluation (disability score, number and time of attacks) was performed during a mean follow-up of 2.7 +/- 1.1 years. 23 of the 66 relapsing-remitting MS patients (33.8%) had elevated IgM anti-MBP levels. In this patient subgroup, IgM anti-MBP levels correlated with the IgM index (r = 0.71; P = 0.0001), but not with CSF/serum albumin (r = 0.08; P = 0.72). In the first year of follow-up, patients with low IgM anti-MBP suffered from more numerous attacks than those with elevated levels (0.86 +/- 0.63 versus 0.43 +/- 0.58; P = 0.017). Patients with high IgM binding to MBP had a first attack during follow-up in a significantly higher time than those with low binding (28.87 +/- 4.7 versus 17 +/- 2.6 months, respectively; P = 0.005) and reached a decrease of 0.5 EDSS point significantly faster than those with low IgM (16.17 +/- 1.2 versus 29.7 +/- 2.6 months, respectively; P = 0.0002). A similar significant finding was observed when the time to reach low disability score (EDSS < or = 2.0) was analyzed (10.7 +/- 2.57 +/- 3.3 months, respectively; P = 0.014). These findings demonstrate that in a subgroup of MS patients, elevated CSF levels of IgM anti-MBP are associated with early favorable course and therefore suggest that IgM binding to MBP could be a possible prognostic marker in relapsing-remitting MS to select early MS patients for future trials.     

The role of prognostic factors in treatment selection for early-stage Hodgkin's disease

PURPOSE: To identify poor prognostic factors in early-stage Hodgkin's disease that predict a high rate of relapse after radiotherapy alone. MATERIALS AND METHODS: A total of 153 patients with stages I and II supradiaphragmatic Hodgkin's disease, treated between 1964 and 1986 with either radiotherapy alone (120 patients) or combined modality therapy (33 patients), were studied retrospectively to determine factors affecting freedom from relapse and absolute survival. Median follow-up was 13 years. Clinical factors were assessed by the stepwise use of a stratified log-rank test and included maximum tumor dimension in any site (< or = 6 cm or > 6 cm), age (< or = 40 or > 40), presence or absence of B symptoms, pathologic and clinical stages (I or II), number of sites involved (< or = 4 or > 4), gender, histologic subtype, and large mediastinal mass (none, small [< or = 6 cm], large [> 6 cm]). RESULTS: The only factors independently predicting a high rate of relapse were tumor dimension (> 6 cm) and number of sites (> 4 sites). At 10 years, in patients with and without the two poor prognostic factors treated with radiotherapy alone, the freedom from relapse rates were 53% and 84% (p < .0001) and the absolute survival rates were 72% and 85% (p = .004), respectively. Combined modality therapy significantly improved freedom from relapse, but not absolute survival, in patients with one or both poor prognostic factors. CONCLUSIONS: Two poor prognostic factors were identified that were highly significant in predicting a high risk of relapse after radiotherapy alone. The addition of three cycles of chemotherapy to standard radiotherapy significantly reduced the relapse rate in high-risk patients.     

High oxygen delivery and extraction by perfluorocarbon-primed extracorporeal membrane oxygenation do not prevent anaerobic metabolism in rabbits

BACKGROUND: The development of endocrine tumours of the duodenopancreatic area (ETDP) is thought to be slow, but their natural history is not well known. The aim of this study was to determine the factors that influence survival of patients with ETDP. PATIENTS/METHODS: Eighty two patients with ETDP (44 non-functioning tumours, 23 gastrinomas, seven calcitonin-secreting tumours, four glucagonomas, three insulinomas, one somatostatinoma) followed from October 1991 to June 1997 were included in the study. The following factors were investigated: primary tumour size, hormonal clinical syndrome, liver metastases, lymph node metastases, extranodular/extrahepatic metastases, progression of liver metastases, local invasion, complete resection of the primary tumour, and degree of tumoral differentiation. The prognostic significance of these factors was investigated by uni- and multi-variate analysis. RESULTS: Twenty eight patients (34%) died within a median of 17 months (range 1-110) from diagnosis. Liver metastases (p = 0.001), lymph node metastases (p = 0.001), progression of liver metastases (p < 0.00001), lack of complete resection of the primary tumour (p = 0.001), extranodular/extrahepatic metastases (p = 0.001), local invasion (p = 0.001), primary tumour size > or = 3 cm (p = 0.001), non-functioning tumours (p = 0.02), and poor tumoral differentiation (p = 0.006) were associated with an unfavourable outcome by univariate analysis. Multivariate analysis identified only liver metastases (risk ratio (RR) = 8.3; p < 0.0001), poor tumoral cell differentiation (RR = 8.1; p = 0.0001), and lack of complete resection of the primary tumour (RR = 4.8; p = 0.0007) as independent risk factors. Five year survival rates were 40 and 100% in patients with and without liver metastases, 85 and 42% in patients with and without complete resection of primary tumour, and 17 and 71% in patients with poor and good tumour cell differentiation respectively. CONCLUSION: Liver metastases are a major prognostic factor in patients with ETDP. Progression of liver metastases is also an important factor which must be taken into account when deciding on the therapeutic approach. The only other independent prognostic factors are tumoral cell differentiation and complete resection of the primary tumour.     

The use of image registration in the analysis of bone scans for the assessment of temporomandibular joint uptake

OBJECTIVE: To examine risk factors for chronic airway disease (CAD) in elderly nonsmokers, as determined by pulmonary function tests (PFTs), and to correlate reported respiratory symptoms with PFT measures. DESIGN: An observational survey. SETTING: Several communities in California. MEASUREMENTS: Exposures and respiratory history were assessed by standardized questionnaire. PFTs were performed and prediction equations derived. RESULTS: Significant risk factors for obstruction on PFTs in multiple logistic regression included reported environmental tobacco smoke (ETS) exposure (relative risk [RR]=1.44), parental CAD or hay fever (RR=1.47), history of childhood respiratory illness (RR=2.15), increasing age, and male sex. The number of years of past smoking was of borderline significance (RR=1.29 for 10 years of smoking; p=0.06). The prevalence of obstruction on PFTs was 24.9% in those with definite symptomatic CAD, compared with 7.5% in those with no symptoms of CAD. The prevalence of obstruction was 36.0% among those with asthma and 70.6% among those with emphysema. Also, symptomatic CAD correlated with reduction in lung function by analysis of covariance. The mean percent predicted FEV1 adjusted for covariates was 90.6% in persons with definite symptoms of CAD, compared with 97.8% in those without it (p < 0.001). CONCLUSIONS: Age, sex, parental history, childhood respiratory illness, and reported ETS exposures were significant risk factors for obstruction on PFTs. Self-reported respiratory symptoms also correlated significantly with PFTs.     

Health status of persons with acute radiation sickness caused by Chernobyl AES accident

Chemical prophylaxis is known to reduce the venographic prevalence of deep-vein thrombosis (DVT) after total knee replacement (TKR), but it is uncertain whether this affects the incidence of symptoms. Further analysis depends on the basic epidemiology of thromboembolic symptoms. We therefore studied the pattern of such symptoms in a consecutive series of 1000 patients with primary TKR, with particular reference to risk factors and prophylaxis. We reviewed all the clinical records and contacted all the patients individually, noting risk factors, prophylaxis, symptomatic pulmonary embolus (PE) or DVT and its timing, death and its causes, and all complications. All the patients wore antiembolism stockings, 83% had regional anaesthesia and 33.9% had chemical prophylaxis. One patient died from PE on the day of surgery, having had no prophylaxis giving a rate of 0.1% (95% CI 0.003% to 0.56%). Symptomatic, radiologically confirmed thromboembolism (VTE) was common with a rate of 10.6% (95% CI 8.7% to 12.5%). There was a similar incidence of VTE in those with and without chemical prophylaxis (10.1% v 10.5%, RR 0.96, NS). VTE was more common in patients with risk factors (15.1% v 9.5%, RR 1.59, p = 0.02) and tended to occur earlier in this group (median day of onset 5 v 7, p = 0.01). Chemical prophylaxis did not reduce the frequency of symptomatic thromboembolism in either those with risk factors (RR 0.81, p = 0.5) or those without them (RR 0.94, p = 0.8). Haematoma or wound dehiscence was more common in those having chemical prophylaxis (11.9% v 6.9%; RR 1.73 95% CI 1.16 to 2.60). Readmission for symptomatic, radio-logically confirmed thromboembolism involved 1.1% of patients (95% CI 0.55% to 2.1%). Four patients were readmitted with proven non-fatal PE and six with proven DVT (the latest on day 40). Our results show that the main risk factor for thromboembolism was TKR itself; chemical prophylaxis did not reduce the incidence of symptomatic thromboembolism but gave an increased perception of side-effects. New prophylactic methods or combinations of methods are needed, with their efficacy compared by randomised controlled studies of both the clinical and the radiological effect.     

Identifying patients with a high risk of relapse in quiescent Crohn's disease. The GETAID Group. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives

No reliable identification of quiescent Crohn's disease (CD) patients with a high risk of relapse is available. The aim of this study was to develop a prognostic index to identify those patients. Untreated adult patients with quiescent disease (not induced by surgery) included in three phase III clinical trials were analysed retrospectively with respect to time to relapse. Nineteen factors related to biology, disease history, and topography were investigated. A relapse was defined as either a CD Activity Index (CDAI) > or = 200, a CDAI > or = 150 but over the baseline value by more than 100, or acute complications requiring surgery. The inclusion criteria were fulfilled by 178 patients. The median follow up was 23 months. The Cox model retained the following bad prognostic factors: age < or = 25 years, interval since first symptoms > 5 years, interval since previous relapse < or = 6 months, and colonic involvement (p < 0.001). Bootstrapping confirmed the variable selection. Patients were classified into three groups with an increasing risk of relapse (p < 0.001). The worst risk group was composed of patients presenting at least three of the four bad prognostic factors. These results make possible the design of clinical trials in quiescent CD patients with a high risk of relapse.     

Patients' awareness of stroke signs, symptoms, and risk factors

BACKGROUND AND PURPOSE: We sought to determine knowledge at the time of symptom onset regarding the signs, symptoms, and risk factors of stroke in patients presenting to the emergency department with potential stroke. METHODS: Patients admitted from the emergency department with possible stroke were identified prospectively. A standardized, structured interview with open-ended questions was performed within 48 hours of symptom onset to assess patients' knowledge base concerning stroke signs, symptoms, and risk factors. RESULTS: Of the 174 eligible patients, 163 patients were able to respond to the interview questions. Of these 163 patients, 39% (63) did not know a single sign or symptom of stroke. Unilateral weakness (26%) and numbness (22%) were the most frequently noted symptoms. Patients aged > or = 65 years were less likely to know a sign or symptom of stroke than those aged < 65 years (percentage not knowing a single sign or symptom, 47% versus 28%, P = .016). Similarly, 43% of patients did not know a single risk factor for stroke. The elderly were less likely to know a risk factor than their younger counterparts. CONCLUSIONS: Almost 40% of patients admitted with a possible stroke did not know the signs, symptoms, or risk factor of a stroke. Further public education is needed to increase awareness of the warning signs and risk factors of stroke.     

Anal and urinary incontinence after obstetric anal sphincter rupture]

The aim of the study was to assess the long term impact of obstetric anal sphincter rupture on the frequency of anal and urinary incontinence, and identify factors to predict patients at risk. In 94 consecutive women who had sustained an obstetric anal sphincter rupture, anal manometry, anal sphincter electromyography and pudendal nerve terminal motor latency at three months post partum was performed. A questionnaire regarding incontinence was sent between two to four years post partum. Forty-two percent of responders had anal incontinence, 32% had urinary and anal incontinence. Overall, 56% of the women had incontinence symptoms. The occurrence of anal incontinence was associated with pudendal nerve terminal motor latencies > 2.0 milliseconds and the occurrence of urinary incontinence was associated with the degree of rupture, the use of vacuum extraction and previous presence of urinary incontinence. Thirty-eight percent of the women with incontinence wanted treatment, but only a few had sought medical advice.     

Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord

The course of pulmonary Langerhans' cell granulomatosis (pulmonary LCG) is variable, difficult to predict and ranges from spontaneous remission to progressive respiratory insufficiency and death. To identify the determinants of survival, we performed a survival analysis on 45 patients with pulmonary LCG. The patients were aged 28 +/- 10 yrs (mean +/- SD) (range 12-62 yrs), 32 males and 13 females, almost exclusively current smokers (96%), and 78% presented symptoms at the time of diagnosis. Diagnosis was made by lung biopsy in 25 patients (56%) and by bronchoalveolar lavage (BAL) analysis in 20 patients (44%). The patients were followed for a median period of 6 yrs (range 1-29 yrs) after the diagnosis. During the period of observation, 33 (73%) patients survived (median follow-up period = 5.8 yrs; range, 1-29 yrs) and 12 (27%) died or underwent lung transplantation (median follow-up period = 8.4 yrs; range 1.4 - 16.1 yrs). The median survival was approximately 13 years. A univariate analysis demonstrated that diminished survival was significantly associated with: an older age at diagnosis (p = 0.0001); a lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio at diagnosis (p = 0.005); a higher residual volume/total lung volume (RV/TLC) ratio at diagnosis (p = 0.02); and steroid therapy during follow-up (p = 0.03). Additional predictive information on mortality was: age > 26 yrs (sensitivity 83%, specificity 64%); FEV1/FVC ratio < 0.66 (sensitivity 75%, specificity 86%); and a RV/TLC ratio > 0.33 (sensitivity 75%, specificity 63%). In multivariate Cox analysis, the combination of factors which gave the best prognostic value was FEV1/FVC ratio and age (p < 0.01). The present findings suggest that adverse prognosis factors at diagnosis in pulmonary Langerhans' cell granulomatosis include older age, lower FEV1/FVC ratio and higher RV/TLC ratio, with additional predictive information on mortality if aged > 26 yrs, FEV1/FVC ratio < 0.66, and RV/TLC ratio > 0.33.     

Epidemiological features of Adamantiades-Beh?et's disease in Germany and in Europe

The German Registry of Adamantiades-Beh?et's disease was founded in 1990 in Berlin and it provides current data on the epidemiology, the clinical manifestations and the course of the disease in Germany on a continuous basis. A total of 218 patients, including 89 German and 100 Turkish patients, had been reported to the German Registry until October 1997. One hundred and ninety-six patients fulfilled the criteria of the Beh?et's disease classification tree. The prevalence of the disease evaluated in Berlin-West was 1.68/100,000 in 1989 and had risen to 2.26/100,000 by 1994. The median age of onset was 25 years (range 5 to 66 years; German-Turks, ns). Juvenile disease was recorded in 6.9% of patients. The complete clinical picture according to the criteria of the International Study Group of Beh?et's Disease developed in 15.5 months. The interval between onset of the disease and diagnosis was 35 months, which was significantly longer than the duration of the development of the complete clinical picture (p < 0.0001). The disease was diagnosed later in German (48.5 months) than in Turkish patients (25.5 months, p = 0.003). While German patients presented an equal male-to-female ratio, a male predominance was shown in Turkish patients (M:F 2.1:1, p = 0.022). Familial occurrence was detected in 2.0% of German and 15.9% of Turkish patients (p = 0.013). The frequencies of major clinical manifestations were: oral ulcers 99%, skin lesions 76%, genital ulcers 75%, ocular manifestations 59%, arthritis 59%, and positive pathergy test 52%. Clinical differences between German and Turkish patients were only found in the frequency of ocular lesions (48% vs. 66%, p = 0.025). Oral ulcers were with 72% the most common onset symptom of the disease followed by erythema nodosum (9%), uveitis (7%), arthritis (7%), genital ulcers (3%), superficial thrombophlebitis (2%) and papules/sterile pustules (2%). Uveitis and erythema nodosum as onset symptoms shortened the median interval to diagnosis to 1.5 and 15 months, respectively, while arthritis delayed diagnosis (43.5 months; p = 0.029). A severe course developed in 25% of the patients; irreversible retinal vasculitis to blindness in 15%, sterile meningoencephalitis in 8%, severe arthritis in 5%, hemoptysis in 2%, lethal outcome in 2% and bowel perforation in 1%. The relative risk of HLA-B5 positive German natives developing the disease. HLA-B5 was confirmed as a marker of severe prognosis. Cardiolipin autoantibodies were associated with cutaneous vasculitis and superficial thrombophlebitis was correlated with systemic vessel involvement.     

Albumin gene expression in adenocarcinomas with hepatoid differentiation

Multiple sclerosis (MS) is a disease of the central nervous system characterized by immune-mediated destruction of myelin. In patients with progressive deterioration, we have intensified immunosuppression to the point of myeloablation. Subsequently, a new hematopoietic and immune system is generated by infusion of CD34-positive hematopoietic stem cells (HSC). Three patients with clinical MS and a decline of their Kurtzke extended disability status scale (EDSS) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS of 8.0 at the time of enrollment were treated with hematopoietic stem cell (HSC) transplantation using a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg), methylprednisolone (4 g) and total body irradiation (1200 cGy). Reconstitution of hematopoiesis was achieved with CD34-enriched stem cells. The average time of follow-up is 8 months (range 6-10 months). Despite withdrawal of all immunosuppressive medications, functional improvements have occurred in all three patients. We conclude that T cell-depleted hematopoietic stem cell transplantation can be performed safely in patients with severe and debilitating multiple sclerosis. Stem cell transplantation has resulted in modest neurologic improvements for the first time since onset of progressive disease although no significant changes in EDSS or NRS scales are evident at this time.     

Relation of systemic arterial pulse pressure to coronary atherosclerosis in patients with mitral stenosis

The relation of a wide systemic arterial pulse pressure to coronary atherosclerosis has not been fully defined. One hundred fifty-nine patients > 40 years old with symptomatic mitral stenosis (MS) who received routine coronary angiography were classified into 2 groups according to the presence of > or = 50% diameter narrowing of > or = 1 coronary artery (n = 48) or no significant disease (n = 111). Pulse pressure was determined both by noninvasive sphygmomanometer and invasive catheterization methods. There were no significant differences in risk factors of coronary artery disease (CAD) or the severity of MS between the 2 groups. From multivariate logistic regression analysis, independent predictors of development of CAD in MS were age (standardized coefficient beta = 1.3437, p = 0.0025), gender (beta = 0.0107, p = 0.0105), mean blood pressure (beta = 1.1839, p = 0.0105), and pulse pressure (beta = 1.3157, p = 0.0008). A wide pulse pressure (> or = 60 mm Hg) correlated with the presence of angiographically significant CAD with a sensitivity and specificity of 88% and 77%. The negative predictive value was 93%. Pulse pressure assessed by sphygmomanometry provided important clinical information. A wide pulse pressure in patients with MS was associated with a high incidence of CAD.     

Midterm results of balloon dilation of congenital aortic stenosis: predictors of success

OBJECTIVES: We evaluated patient and procedural characteristics that influence the midterm success of balloon dilation of congenital aortic stenosis. BACKGROUND: Balloon dilation is a new treatment for congenital aortic stenosis. Factors that influence midterm success are unknown. METHODS: We performed a retrospective review of 148 children >1 month old who underwent balloon dilation for aortic stenosis. RESULTS: Balloon dilation was successful in 87% of patients, with a procedural mortality rate of 0.7%. The average immediate peak to peak gradient reduction was 56.4 +/- 19.9% (mean +/- SD). Prior valvotomy was the only factor that significantly reduced the immediate gradient reduction after dilation (47.1 +/- 21.8% vs. 57.8 +/- 19.6%, p < 0.01). Survival after dilation was 95% at 8 years. Seventy-five percent of patients were free of repeat intervention 4 years after dilation, whereas 50% remained free of repeat intervention at 8 years. Asymmetrically thick valve leaflets (risk ratio [RR] 0.17, p < 0.01) and prior aortic valvotomy (RR 0.35, p = 0.02) decreased the risk of repeat intervention. Aortic regurgitation grade > or = 3 (RR 4.27, p = 0.04) and residual gradient after dilation (RR 1.63 for 10 mm Hg, p < 0.01) increased the risk. CONCLUSIONS: The 8-year survival rate after dilation was 95% with 50% of patients free of repeat intervention. Factors that increased the risk for repeat intervention included symmetrically thin or thick aortic valve leaflets, regurgitation grade > or = 3 after dilation and a high residual gradient after dilation. The incidence of repeat intervention after dilation was high owing to its palliative nature.     

Clinical study of primary progressive multiple sclerosis in Northern Ireland, UK

OBJECTIVE: To investigate the clinical and demographic characteristics of primary progressive multiple sclerosis (PPMS) in Northern Ireland and to establish a database of such patients for genetic and immunological studies and future therapeutic trials. METHODS: Diagnosis and categorisation were performed by two neurologists, potential cases being identified from the following sources: neurology outpatient clinics; neurology inpatients; a review of hospital discharges; and an ongoing epidemiological study of multiple sclerosis in Northern Ireland. Only those with a progressive course from onset and a clear history of no prior relapses were accepted. Potential cases were invited for interview and assessment, the minimal record of disability (MRD) being established. RESULTS: One hundred and eleven cases of PPMS have been identified, 63 women and 48 men (ratio 1.3:1), with a mean age at onset of 39.5 (SD 11.0) (range 17-66)years, and mean disease duration of 13.6 (SD 9.3)years. The mean interval between onset and diagnosis was 4.7 (SD 4.2) years. Nineteen patients (17.1%) did not satisfy the requirements for any category in the Poser criteria. Motor disturbance was the commonest mode of onset (67.6%) with visual loss occurring only rarely at onset (3.6%). Kurtzke EDSS scores were concentrated at the upper end of the scale with a median of 6.0 and levels of unemployment and financial dependence were high. CONCLUSIONS: PPMS in Northern Ireland has a generally later age at onset, lower female preponderance, and predominantly motor onset compared with other subgroups of multiple sclerosis. The delay to diagnosis reflects the often insidious onset and the nature of the clinical course makes application of the Poser criteria difficult. Levels of neurological impairment, disability, and handicap as measured by the MRD are high.     

Risk factors for developing multiple sclerosis after childhood optic neuritis

We reviewed the records of all children (younger than 16 years of age) who presented with a diagnosis of optic neuritis (ON) identified through the comprehensive records-linkage system at the Mayo Clinic and identified 94 cases between 1950 and 1988 with a documented history of idiopathic ON. Detailed follow-up information was available on 79 patients, with a median length of follow-up of 19.4 years. Life-table analysis showed that 13% of the 79 patients with isolated ON had progressed to clinically or laboratory-supported definite multiple sclerosis (MS) by 10 years of follow-up, 19% by 20 years, 22% by 30 years, and 26% by 40 years. Gender, age, funduscopic findings, visual acuity, or family history of either ON or MS did not predict the development of MS. The presence of bilateral sequential or recurrent ON increased the risk of developing MS (p = 0.002; hazard ratio = 5.09), whereas the presence of infection within 2 weeks before the onset of ON decreased the risk of developing MS (p = 0.060; hazard ratio = 0.24). This study of childhood ON supports the lower risk of recurrence and progression to MS compared with adults.