Symptom burden, management and treatment goals of people with MS spasticity: Results from SEEN-MSS, a large-scale, self-reported survey.

BACKGROUND: Spasticity occurs frequently in people with multiple sclerosis (PwMS) and may affect non-physical aspects of life. However, there is a paucity of data assessing the full impact of spasticity in PwMS. OBJECTIVE: This survey of PwMS and spasticity (PwMSS) was undertaken to understand the impact of spasticity in physical, functional, emotional, and social domains. METHODS: SEEN-MSS (Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity), an online survey, was developed in collaboration with three US-based MS organizations (conducted February-April 2021). RESULTS: Survey was completed by 1,177 PwMSS, 78% female, mean age 56.8yrs, 16.8yrs from MS diagnosis, 11.5yrs with spasticity. Considering day-to-day goals of treatment, respondents reported that managing symptoms(46%) was nearly as important as slowing disease progression(54%). Most reported spasticity was a constant reminder of their MS. Participants reported that spasticity limited daily activities (92%), caused pain (92%), impaired sleep (89%) and negatively impacted emotional well-being (87%). Spasticity fostered a sense of dependence (61%), isolation (40%), decline in self-confidence (75%), self-image (70%), and social connection (62%). CONCLUSIONS: Spasticity has wide-reaching negative impacts on multiple aspects of life, causing substantial burden for PwMSS. Results emphasize the need to fully understand the burden of spasticity and addressing individual needs of PwMSS.

Hyaluronic acid-stimulating activity in the pathophysiology of Wilms' tumors.

Markedly elevated levels of hyaluronic acid occur in the serum and urine of some patients with Wilms' tumor. We have recently described a glycoprotein factor in fetal serum that stimulates deposition of hyaluronic acid. In a survey of bovine fetal tissue extracts, we have identified the fetal kidney as the source of this circulating activity. Wilms' tumors arise from transformed "rests" of fetal kidney. We demonstrate here that such tumors continue to produce this fetal factor and that the hyaluronic acid-stimulating activity is found in the urine of children with Wilms' tumors. In the three patients with Wilms' tumor who were followed, elevated levels of hyaluronic acid-stimulating activity were found in their urine before treatment. By 2 months after surgical removal of their tumors, these levels had returned to baseline. We propose that hyaluronic acid-stimulating activity is the mechanism for the elevated levels of hyaluronic acid in the sera and urine of these patients. The activity is an oncofetal protein and the first for which a function has been identified. It also is a marker for this common childhood solid tumor and has the potential for identifying children at increased risk.

Cerebellar degeneration with Hodgkin disease. An immunological study.

A 21-year-old woman with subacute cerebellar degeneration was found to have Hodgkin lymphoma. Radiation therapy for the lymphoma halted the progression of her neurological disease. Using an immunofluorescent technique, we found the patient's serum to have antibodies to cerebellar Purkinje cells.

Identification of spermatozoa and round spermatids in the ejaculates of men with spermatogenic failure.

OBJECTIVES: As many as 10% of infertile men have azoospermia caused by spermatogenic failure or ductal obstruction. The histologic diagnoses associated with spermatogenic failure--Sertoli cell-only syndrome, maturation arrest, and hypospermatogenesis--do not necessarily represent global changes in the affected testis, as occasional seminiferous tubules may still produce mature germ cells. Intracytoplasmic sperm injection (ICSI) allows individual sperm that have been isolated from testicular tissue to fertilize oocytes. This study assessed whether mature germ cells (either round spermatids or spermatozoa) were present in the ejaculates of patients with spermatogenic failure. METHODS: All semen analyses performed at our tertiary care institution from January 1993 through December 1995 were reviewed to identify azoospermic men with spermatogenic failure. During this period, our laboratory employed Nuclear-Fast Red and picroindigocarmine staining (NF-PICS) of cytospin slides to identify rare spermatozoa and spermatids in otherwise azoospermic ejaculates. RESULTS: Of 3005 analyses reviewed, 20 azoospermic men whose infertility was solely attributable to spermatogenic failure were identified. The histologic diagnoses were germinal cell aplasia (n = 7), complete maturation arrest (n = 6), incomplete maturation arrest (n = 3), and hypospermatogenesis (n = 4). Using the NF-PICS technique, mature germ cells were identified in the ejaculates of 15 men (75%), and 9 men (45%) had fully formed spermatozoa present. CONCLUSIONS: In the clinical management of azoospermic infertile men, the NF-PICS technique may be used to identify men who have some degree of testicular spermatogenesis. This might obviate the need for the purely diagnostic testis biopsy that is performed before therapeutic biopsy for testicular sperm extraction in conjunction with ICSI.

Microsurgical repair of iatrogenic injury to the vas deferens.

PURPOSE: We determined the incidence of iatrogenic injuries to the vas deferens at a tertiary care university infertility center and the results of surgical repair. MATERIALS AND METHODS: Records of 472 patients surgically explored for obstructive azoospermia between 1984 to 1996 were reviewed. Enrollment criteria included history of inguinal, pelvic and scrotal (other than vasectomy) surgery. Conventional ipsilateral and crossover vasovasostomies and vasoepididymostomies were performed. Patency rate was defined as presence of complete sperm with tails in a postoperative semen analysis. Followup included a minimum of 2 semen analyses. Only naturally conceived pregnancies were included. RESULTS: Of 472 patients 34 (7.2%) had an iatrogenic injury to the vas deferens with a mean obstruction interval of 20.5 +/- 1.9 years. Mean patient age was 36.7 +/- 1.8 years. Iatrogenic injury to the vas deferens was secondary to bilateral inguinal hernia repair in 19 patients, unilateral hernia repair in 11, renal transplantation in 2, appendectomy in 1 and spermatocelectomy in 1. Pediatric inguinal hernia repair was the most common etiology of the vasal injury (20 patients), followed by adult inguinal hernia repair (10). A total of 36 microsurgical reconstructive procedures were performed, including 20 ipsilateral and 16 crossed vasovasostomies and vasoepididymostomies. There were 26 patients (29 procedures) available for followup (mean 21.0 +/- 3.7 months). Total patency rate per procedure was 65% and pregnancy rate was 39%. Patency and pregnancy rates per conventional ipsilateral procedures were 62.5 and 35.7% and per crossover procedures 64.2 and 42.8%, respectively. CONCLUSIONS: Pediatric inguinal hernia repair is the most common cause of iatrogenic injury to the vas deferens. Results of treatment of iatrogenic injury to the vas deferens are somewhat lower than for patients with obstructive azoospermia due to vasectomy. Iatrogenic injuries are associated with longer vasal defects, impaired blood supply and longer obstructive intervals frequently resulting in secondary epididymal obstruction. Crossover reconstruction is particularly useful when contralateral testicular atrophy is present. Intraoperatively aspirated sperm should be cryopreserved for later use in case the reconstruction fails.

Hyaluronic acid in a cardiac myxoma: a biochemical and histological analysis.

Cardiac myxoma is the most common primary tumor of the heart. This tumor has a gelatinous stroma that is thought to be composed of glycosaminoglycans, the classical acid mucopolysaccharide ground substance. We examined both biochemically and histologically the hyaluronic acid in a case of cardiac myxoma using a newly developed hyaluronic acid-binding protein probe. We observed that hyaluronic acid was localized in the amorphous stroma and occurred at levels 30 times that found in normal atrial septum.

Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity.

PURPOSE: Because varicocele is seen often in infertile men and oxidative stress has been implicated in sperm dysfunction, we assessed spermatozoal reactive oxygen species and seminal total antioxidant capacity in men with and without varicocele. MATERIALS AND METHODS: Levels of reactive oxygen species and total antioxidant capacity were measured in the semen of 21 infertile men with varicocele, 15 men with incidential varicocele and 17 normal donors without varicocele (controls). Men with leukocytospermia (more than 1 x 10(6) white blood cells per ml.) were excluded from study. Reactive oxygen species were measured in washed spermatozoa with a luminol dependent chemiluminescence assay. Total seminal antioxidant capacity was measured with an enhanced chemiluminescence assay, and the results were expressed as trolox equivalents. Sperm characteristics were assessed with a computer assisted semen analyzer, and sperm morphology was assessed using World Health Organization and Kruger's strict criteria. RESULTS: Patients with varicocele had significantly higher reactive oxygen species levels than controls (p = 0.02). Reactive oxygen species levels did not differ significantly between infertile and men with incidental varicocele. Total antioxidant levels were significantly lower among men with varicocele (p = 0.02) and those with incidental varicocele compared to controls (p = 0.05). Reactive oxygen species and total antioxidant capacity levels did not correlate in any group. CONCLUSIONS: Our results suggest that elevated reactive oxygen species and depressed total antioxidant capacity levels are associated with varicocele. These changes may be related to functional sperm abnormalities and infertility seen commonly in these patients. These findings support a possible rationale for controlled clinical trials of antioxidant supplementation in infertile men with varicocele.

Investigation of fertilizing capacity of cryopreserved spermatozoa from patients with cancer.

PURPOSE: There are few published reports concerning fertilization and pregnancy outcomes achieved with cryopreserved spermatozoa from cancer patients. Controversy exists regarding the value of sperm banking for these patients before therapy, whether the spermatozoa are viable after long-term storage and whether they can fertilize the ovum. We assess fertilization and pregnancy outcomes achieved with cryopreserved spermatozoa from cancer patients using assisted reproductive techniques. MATERIALS AND METHODS: We studied 10 cancer patients who transferred cryopreserved semen specimens from our sperm bank to outside in vitro fertilization programs for assisted reproductive technique. Of these patients 5 had Hodgkin's disease, 2 testicular cancer, 1 leukemia and 2 prostate cancer. The length of specimen storage ranged from 14 to 135 months (median 49, interquartile range 24 and 82). RESULTS: The median pre-freeze motility was 44% (interquartile range 36 and 55%) and the median total sperm count was 31.1 x 10(6) (interquartile range 6.3 and 53.9 x 10(6)). At 24 hours after banking the median post-thaw motility was 11% (interquartile range 6 and 35%) and the median total sperm count was 6.6 x 10(6) (1.2 and 17.1 x 10(6)). A total of 18 cycles of assisted reproductive technique were performed among 10 couples with an overall pregnancy rate of 50% per couple, with 2 deliveries, 1 ongoing pregnancy and 2 miscarriages. The pregnancy rate per cycle of in vitro fertilization and intracytoplasmic sperm injection was 36.4% with an implantation rate of 13%. CONCLUSIONS: These results indicate that poor quality cryopreserved spermatozoa from cancer patients, irrespective of the length of storage, may provide successful results with the latest micromanipulative techniques such as intracytoplasmic sperm injection.

Hyaluronic acid deposition in cardiac myxomas: localization using a hyaluronate-specific binding protein.

Myxomas are the most common primary tumors of the heart. These lesions contain a gelatinous, ground-substancelike material which has been described as glycosaminoglycan in nature. Using a newly developed, cartilage-derived hyaluronic acid-binding protein and a modification of the avidin-biotin immunostaining procedure, we demonstrate that hyaluronic acid is contained in the jellylike material of cardiac myxomas.

Effect of clinical and semen characteristics on efficacy of ovulatory stimulation in patients undergoing intrauterine insemination.

PURPOSE: We measured the effect of ovulatory stimulation (OS) upon intrauterine insemination (IUI) success rates, particularly among patients with risk factors for IUI failure. METHODS: Retrospective review of medical and laboratory results from 512 patients who underwent 1576 cycles of IUI with partner's sperm over a 3 year period. Data were collected on 3 risk factors for IUI failure (advanced female age > 37.7 years, prior corrective pelvic surgery, and poor post-wash sperm motility), and on method of OS (none, clomiphene citrate, or gonadotropin). RESULTS: Patients who underwent OS had significantly higher pregnancy rates (7.6%) than those who did not (4.7%, p = 0.02). However, when patients were stratified by their risk factors, OS made a significant difference only for patients without risk factors. These patients had a 15.5% per cycle pregnancy rate with OS, compared to 7.9% in unstimulated IUI cycles (p = 0.04). CONCLUSIONS: Ovulatory stimulation doubles IUI pregnancy rates among young patients without a prior pelvic surgery and with good post-wash semen quality. The benefit of OS for patients with risk factors for IUI failure is unclear. These patients should be counseled that their chances for success with IUI are limited, with or without OS.

Impact of diagnostic ureteroscopy on long-term survival in patients with upper tract transitional cell carcinoma.

PURPOSE: We determine whether diagnostic retrograde ureteroscopy for evaluation of upper tract transitional cell carcinoma adversely affects survival outcomes in terms of urothelial and metastatic tumor recurrence, and tumor-free and overall survival. MATERIALS AND METHODS: A total of 96 patients underwent total nephroureterectomy or resection of the distal ureter with a bladder cuff for upper tract transitional cell carcinoma. Of the patients 48 (study group) had undergone preoperative diagnostic ureteroscopy while 48 (control group) had not. Grade and stage of disease were compared, and time to recurrence, and disease-free and overall survival were analyzed. RESULTS: Grade and stage of disease were equivalent in both groups. There were no significant differences in recurrence rates, time to recurrence or mortality between the groups. Metastases developed in 9 patients (18.8%) in the control group and 6 (12.5%) in the study group (p = 0.58), while 5 (10.4%) in each group died of metastases of upper tract carcinoma (p = 1.00). Kaplan-Meier estimates were 0.67 and 0.71 for metastasis-free survival at 5 years (p = 0.25, not significant) and 0.87 and 0.76 for overall 5-year survival (p = 0.75, not significant) for the study and control groups, respectively. CONCLUSIONS: Diagnostic ureteroscopy has no clinically apparent adverse effect on long-term or disease specific survival of patients with upper tract transitional cell carcinoma who subsequently undergo standard definitive surgical management.

The effect of patient and semen characteristics on live birth rates following intrauterine insemination: a retrospective study.

PURPOSE: To identify characteristics of female patients and of semen that were associated with live birth following intrauterine insemination (IUI). METHODS: Retrospective review of medical and laboratory results from 533 women who underwent IUI with partner's sperm from 1993 through 1995. RESULTS: Among 1728 cycles, 116 (6.7%) resulted in live deliveries. Among the 38 patient and semen variables analyzed, only 3 were associated with successful IUI outcome: female age < 37.7 years at the time of treatment (P = 0.02); the absence of any corrective pelvic surgery (P < 0.001); and postwash sperm motility (P = 0.006). Couples with none of these three risk factors achieved per-cycle pregnancy rates of 12.4%. Women with two risk factors (age and pelvic surgery) achieved per-cycle pregnancy rates of 4.6% when sperm had good postwash motility. No pregnancies were achieved when low postwash motility was combined with any other risk factor. CONCLUSIONS: Advanced female age, poor postwash sperm motility, and a history of corrective pelvic surgery are significant risk factors for poor IUI success rates. Poor postwash sperm motility in combination with either of these other two risk factors resulted in no successful pregnancies.

Varicocelectomy improves intrauterine insemination success rates in men with varicocele.

PURPOSE: We determined whether varicocele treatment before intrauterine insemination significantly affects intrauterine insemination success rates. MATERIALS AND METHODS: A total of 58 infertile couples, of whom the women had normal evaluations and men had abnormal semen analyses and a history of varicocele, were included in this study. They were identified after reviewing the charts of all women undergoing intrauterine insemination for male factor infertility at our center. Of the men 24 participated in 63 intrauterine insemination cycles without varicocele treatment, while in the remaining 34 varicocele was treated before a total of 101 intrauterine insemination cycles. Variables associated with pregnancy or live birth were analyzed using repeat measures logistic regression with generalized estimating equation techniques. An initial stepwise generalized estimating equation was performed without including varicocele treatment status. Subsequently varicocele treatment status and the significant associated factors were included in analysis. The semen characteristics of untreated and treated varicocele groups were compared with repeat measures analysis of variance. RESULTS: On pre-wash semen analysis patients with untreated varicocele had significantly higher mean motility plus or minus standard error than patients whose varicoceles were treated (48.6% +/- 2.3% versus 38.1% +/- 1.8%, p = 0.02). However, no statistically significant difference was noted in the mean post-wash total motile sperm count in the treated and untreated groups (7.2 +/- 1.0 versus 14.8 +/- 2.6, p = 0.1). Despite these findings the pregnancy and live birth rates per cycle were significantly higher in patients in whom varicocele was treated than in those without varicocele treatment (11.8% versus 6.3%, p = 0.04 and 11.8% versus 1.6%, p = 0.007, respectively). CONCLUSIONS: Varicocele treatment may not improve semen characteristics in all men but it appears to improve pregnancy and live birth rates among couples undergoing intrauterine insemination for male factor infertility. A functional factor not measured on routine semen analysis may affect pregnancy rates in this setting. Men should be screened for varicocele before intrauterine insemination is initiated for male factor infertility.

Relationship of total motile sperm count and percentage motile sperm to successful pregnancy rates following intrauterine insemination.

PURPOSE: This study sought (i) to investigate the relationship between postwash total motile sperm count and postwash percentage motile sperm in predicting successful intrauterine insemination and (ii) to determine the minimal postwash total motile sperm count required to achieve pregnancy with intrauterine insemination. METHODS: Five hundred four women, who underwent 1636 intrauterine insemination cycles with their partner's sperm for infertility treatment from 1993 through 1995, were included in this retrospective study. All patient charts were reviewed for age, infertility etiology, ovarian stimulation regimens, semen characteristics, and treatment outcome. To determine the relationship between total motile sperm count and intrauterine insemination outcome, patients were grouped as (1) less than 0.5 million, (2) 0.5 to 1 million, (3) 1 to 5 million, (4) greater than 5 million, and (5) greater than 20 million. RESULTS: Similar live birth rates (per cycle) were seen among the postwash total motile sperm count groups: group 1, 3.5%; group 2, 2.4%; group 3, 7.0%; group 4, 6.9%; and group 5, 7.0% (P = 0.37). However, regardless of the postwash total motile sperm count, the postwash motility predicted intrauterine insemination success at a cutoff value of 40%. CONCLUSIONS: The percentage of postwash sperm motility, and not the postwash total motile sperm count, can predict successful intrauterine insemination outcome. Such information can be useful in counseling patients regarding their chance of success with intrauterine insemination and in determining when alternate methods of assisted reproduction may be a better approach.

Randomized trial of Cervene, a kappa receptor-selective opioid antagonist, in acute ischemic stroke.

The purpose of this randomized trial was to confirm drug safety and to obtain preliminary efficacy data on Cervene (nalmefene), an opioid antagonist with relative kappa receptor selectivity, for the treatment of acute ischemic stroke. Patients were treated for 24 hours with either intravenous Cervene (0.05 mg/kg as an initial infusion over 15 minutes and 0.01 mg/kg/h maintenance) or placebo within 6 hours of an ischemic stroke. Efficacy was assessed by comparing the change from baseline to day 7 in the National Institutes of Health stroke scale score (NIHSSS) and the Glasgow Outcome Scale and Barthel Index at 3 months. Forty-four evaluable patients were randomized (3:1) to Cervene (n = 34; treated at 5.0 +/- 0.9 hours after onset) and placebo (n = 10; treated at 4.6 +/- 1.5 hours). No deaths or serious adverse events reasonably attributable to Cervene have been reported. A "major improvement" (NHSSS > 4) was seen at day 7: placebo, 33% (three of nine patients) and Cervene, 66% (19 of 29 patients). Only patients with initial NIHSSS >/= 4 were considered evaluable for this primary endpoint. "Good recovery" at 3 months (Glasgow = 5) was as follows: placebo, 50% (5 of 10 patients) and Cervene, 73% (24 of 33 patients). The death rate at 3 months was placebo, 20% (2 of 10 patients) and Cervene, 9.1% (3 of 33 patients). One patient was lost to follow-up. In conclusion, results from this randomized trial suggest that Cervene is safe, tolerable, and may be beneficial in the treatment of acute stroke patients.