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Biomedical subjects

L M Nelson

Publications and source records attributed to L M Nelson.

At least 91 records · Page 5Linked to original sources

Evaluation of treatment protocols on minimal to moderate spasticity in multiple sclerosis.

Thirty men and women diagnosed with definite multiple sclerosis (MS) were treated for ten weeks in a blinded, cross-over study. Patients with minimal to moderate spasticity were randomized to one of three sequences to evaluate the effects on MS-related spasticity of baclofen alone, stretching regimen with placebo, placebo alone, and stretching regimen with baclofen. The Cybex II isokinetic unit, timed gait, Ashworth scale, and subject's assessment of function were objective and subjective measures used to evaluate changes in hypertonicity. There was significant correlation between the Cybex and Ashworth as methods of measuring spasticity. Overall, treatment with baclofen alone significantly improved moderate quadriceps spasticity as measured by Cybex flexion scores. A trend, indicative of enhancing the beneficial effects of baclofen, was noted when stretching exercises were added to the treatment.

Adult↗

Failure of clonal deletion in neonatally thymectomized mice: tolerance is preserved through clonal anergy.

Self-tolerance is achieved in part through intrathymic deletion of self-reactive T cells. The necessity of the thymus for this process is suggested by the development of autoimmune diseases in neonatally thymectomized (neoTx) mice and by the failure of clonal deletion in nude mice. Indeed, the present study demonstrates that neonatal thymectomy on day 3 after birth results in the failure of clonal deletion of V beta 11+ T cells in BALB/c mice and V beta 5+ and V beta 6+ T cells in DBA/2 mice. However, these potentially autoreactive cells are nonfunctional as measured by proliferation and lymphokine production after stimulation with appropriate anti-V beta mAbs or stimulator cells. It appears that this induction of nonresponsiveness may have occurred extrathymically: the early neonatal thymus (presumably the source of the peripheral T cells observed in neoTx mice) also contains T cells with self-reactive receptors, but these cells are fully functional. Therefore, neonatal thymectomy aborts deletion of self-reactive T cells, but self-tolerance is maintained through functional inactivation of potentially self-reactive clones.

Animals↗

Fluorescent detection of rabbit endometrial implants resulting from monodispersed viable cell suspensions.

A model for early stage endometriosis was prepared in rabbits by intraperitoneal injection of monodispersed viable endometrial cells. With this model, we have found that DHE fluorescence increases the sensitivity of detection of endometrial tissue. The potential experimental and clinical significance of ectopic endometrial detection by porphyrin fluorescence is enhanced by the recent report of endometrial transplant destruction by PDT. Although caution must be exercised for extrapolation from animal experiments to human conditions, these results encourage further evaluation of photosensitization for the study and potential treatment of disorders involving endometrial tissue.

Animals↗

Multiple sclerosis sibling pairs: clustered onset and familial predisposition.

We evaluated 48 relapsing-remitting multiple sclerosis (R/R MS) sibling pairs derived from 44 families for age and date of onset of MS symptoms, clinical course, and family history of MS. Age- and sex-matched R/R MS clinic patients provided a statistical comparison group. The age of onset tended to cluster within multiplex families. The initial symptom of MS occurred within 5 years of age in 30/48 sibling pairs compared with 16/48 controls. A positive family history of MS (other than siblings) was present in 43% of the multiplex families compared with 20% among simplex controls. In 1st-, 2nd-, and 3rd-degree relatives who had lived into the age at risk, 22/1,134 family members of multiplex sibling pairs had probable or definite MS compared with 10/1,215 control family members. Age of onset clustering in siblings concordant for R/R MS and an increased risk of MS in other family members suggest that factors influencing disease onset may be in part inherited in these kindreds.

Adult↗

Efficacy of assisted reproductive technology during diagnostic and operative infertility laparoscopy.

Women being evaluated for infertility were offered assisted reproductive technology at the time of diagnostic laparoscopy. Oocyte retrieval was performed after ovulation induction in 33 women, of whom 19 had concurrent operative laparoscopy. Gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF) and embryo transfer were performed subsequently depending on laparoscopic assessment of pelvic architecture, oocyte maturity, and semen parameters. The clinical pregnancy rate was 24% per cycle and 28% per gamete or embryo transfer (four pregnancies after GIFT and four after IVF/embryo transfer). The clinical pregnancy rate per transfer did not differ significantly between the 19 women who had therapeutic operations in conjunction with laparoscopy (lysis of adhesions and/or fulguration of endometriosis) and the 13 who did not (25 versus 30%; P greater than .05). Assisted reproductive technology can be performed successfully during diagnostic infertility laparoscopy. Operative endoscopic manipulation did not adversely influence pregnancy outcome.

Adult↗

Clomiphene citrate directly impairs endometrial receptivity in the mouse.

Clomiphene citrate (CC) has known antifecundity effects in animal models. To help define the site of action of this effect, we studied the direct effect of CC on endometrial receptivity by transferring embryos to hormonally prepared prepubertal mice. Prepubertal mice were begun on one of four blinded hormonal preparations consisting of two consecutive 3-day periods of daily injections: oil vehicle, oil-progesterone (P), estradiol (E2)-P, or CC-P. Blastocysts, which had not been exposed to CC, were then surgically transferred to these prepubertal recipients. Fourteen days after embryo transfer, implantations and term pregnancies were counted at necropsy. In this model, CC demonstrated no estrogen agonist effect, and had a significant adverse effect on endometrial receptivity. CC appeared to lower fecundity by a direct endometrial effect.

Animals↗

A comparison of dementia in Alzheimer's disease and multiple sclerosis.

We compared results of comprehensive neuropsychological testing in 42 patients with clinically diagnosed Alzheimer's disease (AD) and in an equal number of patients with clinically definite chronic-progressive multiple sclerosis. Age, sex, and education were controlled using demographically corrected T scores based on a large normal sample. Both groups showed significant impairment on the test battery, but the degree of dementia was more severe in the patients with AD. A deviation score analysis, controlling for overall level of cognitive impairment, revealed significant differences between the groups. Alzheimer's disease was associated with relatively greater impairment of learning, memory, and verbal skills, whereas the MS group showed greater relative impairment of attention, incidental memory, and psychomotor functions. These data suggest that both the degree and pattern of mental impairement differ in patients with AD and patients with multiple sclerosis. Our results support a distinction between "gray matter" and "white matter" dementia, and may help clarify the issue of "cortical" vs "subcortical" dementia by demonstrating neuropsychological differences based on secure neuropathologic distinctions.

Aged↗

Cognitive loss in multiple sclerosis. Case reports and review of the literature.

Neuropsychological and neuroradiologic evidence of cerebral lesions is described for 12 patients with multiple sclerosis in whom cognitive disability was far greater than any other neurologic disability. Cognitive dysfunction resulted in significant functional impairment at work or home in three fourths (9 of 12) of the patients described here, despite mild physical disability (mean Kurtzke Expanded Disability Status Scale score, 3.2). A unique feature of the neurologic examination in these patients was the presence of prominent frontal release signs (gait apraxia and placing response) in the lower extremities. Two new scales, a Cognitive Function Scale and a Frontal Release Scale, were adapted for the investigation of these patients. The extensive literature relating to cognitive dysfunction in multiple sclerosis is reviewed and discussed with regard to its clinical relevance.

Adult↗

Photodynamic therapy of rabbit endometrial transplants: a model for treatment of endometriosis.

The potential of photodynamic therapy for endometriosis was evaluated by autotransplantation of endometrial tissue in 15 female virgin New Zealand white rabbits. After maturation, 14 animals were injected intravenously with 10 mg/kg of dihematoporphyrin ether (DHE) and, 24 hours later, transplants were exposed to 630 nm light at 100 to 210 mW/cm2. Sixteen transplants received 100 J/cm2, 10 transplants received 50 J/cm2; 13 untreated transplants served as controls. In the remaining animal that did not receive DHE, 3 transplants were irradiated with 100 J/cm2. Six days after treatment, transplants were harvested with the underlying musculature, and multiple sections were examined histopathologically. Complete endometrial epithelial destruction was seen in 13 of 16 transplants (81%) in the 100 J/cm2 group and in 6 of 10 transplants (60%) in the 50-J/cm2 group. Nearly complete endometrial epithelial destruction was seen in 2 other transplants in each group. No damage occurred in either the 3 transplants that received 100 J/cm2 without prior DHE or in the 13 transplants with DHE and no irradiation. The sensitivity of ectopic rabbit endometrial tissue encourages further evaluation of photodynamic therapy for the treatment of human endometrial disorders.

Animals↗

Counseling employees at risk for HIV.

The human immunodeficiency virus (HIV) infection is a preventable, bloodborne, and sexually transmitted disease which represents the major public health crisis of the century. Because treatments are costly and in their infancy, education in disease prevention is a major tool in battling this epidemic. One technique is to target individuals whose behavior places them at risk for infection and then providing individualized counseling and HIV antibody testing. The HIV antibody test is an important complement to diagnosis and care, and a mechanism to educate and foster behavior change through counseling in those who believe they are at risk. The occupational health nurse's role is to assess employees' risk and provide or refer those employees with a risk factor for individualized counseling and voluntary HIV antibody testing. Counseling and testing should be provided by a knowledgeable health care provider in a climate that protects individuals from discrimination and provides confidentiality.

Acquired Immunodeficiency Syndrome↗

Risk of multiple sclerosis exacerbation during pregnancy and breast-feeding.

Studies in the past have reported an increased risk of exacerbations in multiple sclerosis during the postpartum period; it is not known whether breast-feeding alters this risk. We interviewed 435 women regarding pregnancy and breast-feeding history, providing for analysis 191 pregnancies that had occurred during a nonprogressive phase of the disease. The exacerbation rates during the nine-month postpartum period (34%) were more than three times the exacerbation rate during the nine months of pregnancy (10%). The exacerbation risk was highest in the three-month period following childbirth and appeared to stabilize after the sixth postpartum month. The exacerbation rates in breast-feeding and non-breast-feeding pregnancies were 38% and 31%, respectively. The average time to exacerbation was similar in breast-feeding (3.0 months) and non-breast-feeding (3.1 months) pregnancies. Although differential exacerbation rates during pregnancy and the postpartum period may be related to hormonal effects on the immune system, the hormonal effects of breast-feeding do not appear to similarly affect the risk of exacerbation.

Adolescent↗

Referral bias in multiple sclerosis research.

Referral bias is a significant problem affecting the generalizability of clinical studies conducted in a university setting. To examine referral bias in our university-based multiple sclerosis referral center, we analyzed the characteristics of referral center patients compared to the population-based group of multiple sclerosis patients from which the referral center patients originated. The referral center patient group differed from those that remained in the population-based group in the following important ways: (1) they were younger, (2) they had more mobility impairment for their age, (3) disabled females were overrepresented compared to disabled males, (4) they more often reported recent disease worsening, (5) they had a higher frequency of early diagnosis supported by laboratory tests, and (6) they more often relied on neurologists and therapists for routine care of their disease. The multiple sclerosis referral center setting would appear to be ideal for the conduct of intervention trials, but inadequate for collecting representative natural history data.

Activities of Daily Living↗

Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis.

Sixty patients with chronic/progressive MS received a newly assembled neuropsychological screening battery (NSB) and a brain MRI. A neuroradiologist blinded to NSB findings quantified cerebral lesions on MRI. We developed weighted brain area lesion scores according to number and size of cerebral lesions. Patients who were impaired on NSB testing had a significantly higher mean bihemispheric lesion score (X = 26.1) than those who were unimpaired (X = 17.4); this MRI lesion rating score correlated significantly with the cognitive summary score of the NSB (r = 0.35, p less than 0.01). However, we did not find a significant correlation between the Kurtzke Expanded Disability Status Scale and any MRI or NSB summary measures. Compared with the Mini-Mental State Exam (MMSE), the NSB cognitive summary score yielded a prevalence estimate for cognitive impairment that is more consistent with previous findings in chronic/progressive MS. The NSB is a useful screening test for cognitive dysfunction in chronic/progressive MS because of its relationship to cerebral lesions on MRI and its greater sensitivity than the frequently used MMSE.

Adult↗

Service use and costs for Medicare beneficiaries in risk-based HMOs and CMPs: some interim results from the National Medicare Competition Evaluation.

The Health Care Financing Administration (HCFA) initiated the Medicare Competition Demonstration in 1982 in anticipation of congressional intent to establish a national program. Interim results on the 1984 service use and cost experience of the health maintenance organizations (HMOs) and competitive medical plans (CMPs) participating in the demonstrations indicate that Medicare enrollees in the demonstration experienced a median of 1,951 hospital days per 1,000 person years, 57 per cent of the median of 3,432 days per 1,000 in the local markets from which the plans drew enrollment. Independent practice association (IPA) HMOs experienced higher hospital use rates than staff and group model HMOs. These comparisons are not adjusted for various risk factors, the absence of which were likely to favor the demonstration plans. Plans with lower hospital service use were federally qualified and had been operating for more than five years. The median total annual revenue per enrollee across all plans was $2,312, compared to median annual expenses per enrollee of $2,250. The distribution of median annual expenses per enrollee by major category of expense was: institutional expenses ($1,038/enrollee), medical expenses ($720/enrollee), supplemental services expenses ($154/enrollee), and administrative and other expenses ($295/enrollee). Future analysis, using beneficiary-level data, will examine the impact of the demonstration and the nature and extent of evident biased selection and will compare the quality of care in the demonstrations to that in the fee-for-service sector.

Aged↗