A high resolution deletion map of human chromosome Xp22.

We have developed a 32-interval deletion panel for human chromosome Xp22 spanning about 30 megabases of genomic DNA. DNA samples from 50 patients with chromosomal rearrangements involving Xp22 were tested with 60 markers using a polymerase chain reaction strategy. The ensuing deletion map allowed us to confirm and refine the order of previously isolated and newly developed markers. Our mapping panel will provide the framework for mapping new sequences, for orienting chromosome walks in the region and for projects aimed at isolating genes responsible for diseases mapping to Xp22.

Identification and characterization of the gene causing type 1 spinocerebellar ataxia.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat. In this study, we describe the identification and characterization of the gene harbouring this repeat. The SCA1 transcript is 10,660 bases and is transcribed from both the wild type and SCA1 alleles. The CAG repeat, coding for a polyglutamine tract, lies within the coding region. The gene spans 450 kb of genomic DNA and is organized in nine exons. The first seven fall in the 5' untranslated region and the last two contain the coding region, and a 7,277 basepairs 3' untranslated region. The first four non-coding exons undergo alternative splicing in several tissues. These features suggest that the transcriptional and translational regulation of ataxin-1, the SCA1 encoded protein, may be complex.

An experimental design for the control and assembly of magnetic microwheels.

Superparamagnetic colloidal particles can be reversibly assembled into wheel-like structures called microwheels (µwheels), which roll on surfaces due to friction and can be driven at user-controlled speeds and directions using rotating magnetic fields. Here, we describe the hardware and software to create and control the magnetic fields that assemble and direct µwheel motion and the optics to visualize them. Motivated by portability, adaptability, and low-cost, an extruded aluminum heat-dissipating frame incorporating open optics and audio speaker coils outfitted with high magnetic permeability cores was constructed. Open-source software was developed to define the magnitude, frequency, and orientation of the magnetic field, allowing for real-time joystick control of µwheels through two-dimensional (2D) and three-dimensional (3D) fluidic environments. With this combination of hardware and software, µwheels translate at speeds up to 50 µm/s through sample sizes up to 5 × 5 × 5 cm3 using 0.75 mT-2.5 mT magnetic fields with rotation frequencies of 5 Hz-40 Hz. Heat dissipation by aluminum coil clamps maintained sample temperatures within 3 °C of ambient temperature, a range conducive for biological applications. With this design, µwheels can be manipulated and imaged in 2D and 3D networks at length scales of micrometers to centimeters.

Genetic variation in an inbred plant: variation in tissue cultures of soybean [Glycine max (L.) Merrill].

Although soybean [Glycine max (L.) Merrill] grows as an inbreeding, generally homozygous, plant, the germplasm of the species contains large amounts of genetic variation. Analysis of soybean DNA has indicated that variation of RFLP (restriction fragment length polymorphism) markers within the species usually entails only two alleles at any one locus and that mixtures of such dimorphic loci account for virtually all of the restriction fragment variation seen in soybean (G. max), and in its ancestors, G. soja and G. gracilis. We report here that tissue cultures prepared from root tissue of individual soybean plants develop RFLP allelic differences at various loci. However, these newly generated alleles are almost always the same as ones previously found and characterized in other varieties of cultivated soybean (cultivars). This repeated generation of particular alleles suggests that much of the genetic variation seen in soybean could be the consequence of specific, relatively frequently employed, recombinational events. Such a mechanism would allow inbred cultivars to generate genetic variation (in the form of alternative alleles) in a controlled manner, perhaps in response to stress.

Incidence of and risk factors for medical complications during stroke rehabilitation.

BACKGROUND AND PURPOSE: The aims of this study were to examine the frequency, types, and clinical factors associated with medical complications that occur during inpatient rehabilitation and to identify risk factors for complications that require a transfer to an acute care facility. METHODS: A cohort of 1029 patients consecutively admitted for inpatient stroke rehabilitation was studied. Demographic and stroke information, impairment, preexisting medical conditions, and admission laboratory abnormalities were recorded. Medical complications, defined as new or exacerbated medical problems, were documented for each patient. Complications that required transfer off rehabilitation were noted. Univariate and multiple logistic regression analyses were used to determine factors that were associated with risk of medical complications and risk of transfer off rehabilitation. RESULTS: Seventy-five percent of patients experienced >/=1 medical complication during rehabilitation. Significant factors for the development of any medical complication included greater neurological deficit (odds ratio [OR], 4.10; confidence interval [CI], 1.88 to 8.91), hypoalbuminemia (OR, 1.71; 95% CI, 1.15 to 2.52), and history of hypertension (OR, 1.81; 95% CI, 1.27 to 2.59). Nineteen percent of patients had a medical complication that required transfer to an acute care facility. Significant factors for transfers were elevated admission white blood cell counts (OR, 1.92; 95% CI, 1.32 to 2.79), low admission hemoglobin levels (OR, 1.89; 95% CI, 1.32 to 2.68), greater neurological deficit (OR, 2.46; 95% CI, 1.37 to 4.39), and a history of cardiac arrhythmia (OR, 1.79; 95% CI, 1.18 to 2.67). CONCLUSIONS: Medical complications are common among patients undergoing stroke rehabilitation. A significant number of these medical complications may require a transfer to an acute facility.

Multivariate analysis of improvement and outcome following stroke rehabilitation.

This study documented the status of 432 patients and characteristics of functional improvements and outcomes achieved by 163 patients who participated in comprehensive stroke rehabilitation. Scores on the 100-point Activities of Daily Living Index improved from hospital admission to discharge and declined slightly at follow-up. An average Activities of Daily Living Index point gain of 0.6 per day was found that was unrelated to age, sex, side of hemiparesis, or admission functional status. Seventy-nine percent of the patients were discharged home; 85% were home at follow-up. Eleven percent of the patients were working at follow-up. Patients traveled outside their homes an average of 24.6 days during the three months immediately following discharge. A significant number of patients achieved favorable functional housing, employment, and social outcomes. This study supported referral for rehabilitation services regardless of age, side of hemiparesis, or degree of impairment.

Benefits of rehabilitation for traumatic spinal cord injury. Multivariate analysis in 711 patients.

The functional outcomes of 711 patients with traumatic spinal cord injuries who were admitted to a rehabilitation hospital during an eight-year period were studied. The modified Barthel index, a 100-point scale, was used to assess ability to perform self-care and mobility skills at rehabilitation admission and discharge. There were statistically significant improvements in self-care and mobility subscores of the modified Barthel index. Mean total modified Barthel index scores increased from 13.8 at admission to 46.1 at discharge for patients with quadriplegia, and from 37.7 to 74.4 for patients with paraplegia. Functional gains made by patients with incomplete spinal lesions were greater than those made by patients with complete lesions. This study documents improvement in ability to perform self-care and mobility skills among patients with spinal cord injuries who participate in comprehensive rehabilitation.

Functional outcome following spinal cord injury. A comparison of specialized spinal cord injury center vs general hospital short-term care.

The functional outcomes of 185 patients with spinal cord injuries undergoing rehabilitation who were initially treated in a specialized short-term care unit (center patients) were compared with those of 153 patients initially treated in general hospitals (noncenter patients). After stabilization, all patients were admitted to the Rehabilitation Institute of Chicago (Ill) and received the same rehabilitation program. The groups were comparable in terms of demographic, injury, and medical characteristics at the time of rehabilitation center admission, but the duration from injury to rehabilitation was more than twice as long for noncenter patients. While center patients were discharged from the rehabilitation center at equivalent functional skill levels, their daily rate of functional gains during the rehabilitation center stay was significantly greater than that of noncenter patients although the length of stay at the rehabilitation center was comparable for the two groups. These results support the practice of specialized short-term spinal cord injury care as a means of enhancing rehabilitation outcome.

Isolation of a yeast artificial chromosome contig spanning the X chromosomal translocation breakpoint in a patient with Rett syndrome.

Rett syndrome is a neurodevelopmental disorder observed exclusively in females. A de novo X;3 translocation was detected in a patient (TH) with Rett syndrome. The X chromosomal breakpoint maps to Xp21.3 between the distal end of the Duchenne muscular dystrophy (DMD) gene and the DXS28 (C7) locus. To determine if this translocation caused the Rett syndrome in this patient, our efforts focused on mapping and cloning of the X chromosomal breakpoint in this patient. Toward these goals, we generated a set of radiation-reduced hybrid cell lines for the short arm of the X chromosome to use as a source for region-specific markers. Using Alu-PCR, 13 new DNA markers were isolated from a radiation-reduced hybrid, which retained both DMD and DXS28. These markers were localized within Xp21 using DNA from males with various interstitial deletions in this region. Two new markers, K23-2p and K23b-1, were found to be closer flanking markers to the X chromosomal breakpoint than DMD and DXS28. Long range restriction mapping using K23-2p and K23b-1 determined that the maximum distance between them was 800 kb. Several of the new markers were developed into sequence tagged-sites and were used to isolate yeast artificial chromosome (YAC) clones. A total of 22 YAC clones was isolated and characterized; these YACs were then developed into 3 large contigs in the Xp21.3 region. This effort resulted in the cloning of the region containing the X chromosomal translocation breakpoint of the Rett syndrome patient in a 170-kb YAC clone.

Microphthalmia with linear skin defects (MLS) syndrome: clinical, cytogenetic, and molecular characterization.

The microphthalmia with linear skin defects (MLS) syndrome (MIM 309801) is a severe developmental disorder observed in XX individuals with distal Xp segmental monosomy. The phenotype of this syndrome overlaps with that of both Aicardi (MIM 304050) and Goltz (MIM 305600) syndromes, two X-linked dominant, male-lethal disorders. Here we report the clinical, cytogenetic, and molecular characterization of 3 patients with this syndrome. Two of these patients are females with a terminal Xpter-p22.2 deletion. One of these 2 patients had an aborted fetus with anencephaly and the same chromosome abnormality. The third patient is an XX male with Xp/Yp exchange spanning the SRY gene which results in distal Xp monosomy. The extensive clinical variability observed in these patients and the results of the molecular analysis suggest that X-inactivation plays an important role in determining the phenotype of the MLS syndrome. We propose that the MLS, Aicardi, and Goltz syndromes are due to the involvement of the same gene(s), and that different patterns of X-inactivation are responsible for the phenotypic differences observed in these 3 disorders. However, we cannot rule out that each component of the MLS phenotype is caused by deletion of a different gene (a contiguous gene syndrome).

Spinal cord injury rehabilitation outcome: the impact of age.

The effect of age on self-care and mobility skill performance after spinal cord injury was studied using a 15-task modified Barthel Index (MBI) to score functional abilities for 708 patients aged 6 through 88 years. Analysis of covariance showed no relationship between age and discharge MBI score; however, patients with paraplegia, incomplete lesions, and greater admission functional ratings had greater discharge functional scores than did those with quadriplegia, complete lesions, and lower admission scores, respectively. Advancing age was associated with increased dependence in only seven functional skills (bathing, upper and lower body dressing, stair climbing, and transfers to chair, toilet and bath) and only for patients with complete paraplegia. Other MBI component tasks and patients with complete quadriplegia, incomplete paraplegia and incomplete quadriplegia demonstrated no relationship between age and skill performance. Results of this study support the practice of providing comprehensive rehabilitation services to all patients following spinal cord injury regardless of age.

Classification of pressure ulcers.

Several systems exist for classifying pressure ulcers, though none of them have been evaluated for interrater reliability. A new grading scale was compared with the commonly used Shea classification. This new scale was developed to provide a more complete description of pressure ulcer healing. The advantages of this scale include a classification of red areas as ulcers to help prevent further deterioration and classification of healed sores to note potential problems. The Yarkony-Kirk scale classifies a red area as a grade 1 ulcer, and involvement of the epidermis and dermis with no subcutaneous fat observed as a grade 2 ulcer. Grade 3 indicates exposed subcutaneous fat with no muscle observed. Exposed muscle without bone involvement is classified as a grade 4 ulcer, and grade 5 describes exposed bone with no joint space involvement. Grade 6 indicates joint space involvement. There is a classification of pressure sore healed to indicate a healed pressure ulcer. Interrater reliability was assessed by two nurses. In spite of an increased number of categories for the Yarkony-Kirk scale, there was no decline in reliability. Reliability was excellent with an interrater correlation of 0.90 for the Yarkony-Kirk scale and 0.86 for the Shea classification when measured for 72 patients. Eighty-five percent of the ratings for the Yarkony-Kirk scale were identical, whereas only 68% were identical for the Shea classification. Three percent of the ratings for the Shea classification were greater than +/- 1 category; 6% of the ratings for the Yarkony-Kirk scale were greater than +/- 1 category. This scale appears to possess good reliability and to describe pressure ulcers more completely. This scale may also be used to teach prevention activities as well as ulcer classification.

Trends in stroke rehabilitation.

Certain shifts and trends in stroke rehabilitation practices are occurring in the US, deriving from scientific developments, regulatory requirements, and other sources. The prevalence of stroke is increasing in the US, duration of rehabilitation hospitalizations is decreasing, and the availability of alternative methods and locations of rehabilitation services is expanding. More awareness of measures to treat medical comorbidities and the associated disabilities of stroke can be expected to enhance outcomes. New and innovative techniques, including constraint induced movement therapy, pharmacological agents, complementary or alternative medicine techniques such as acupuncture, and community activities such as exercise classes, are more widespread practices now. Novel technological interventions such as robotics and cortical stimulation are being developed to facilitate improved outcomes. The essential focus of these practices on enhancing quality of life of stroke survivors remains unaltered.

Heart disease in patients with stroke: incidence, impact, and implications for rehabilitation. Part 1: Classification and prevalence.

Heart disease is found in about 75% of patients who have suffered a stroke. Cardiovascular diseases can be risk factors, etiologic mechanisms, associated conditions, or direct consequences of stroke. Cardiac comorbidity may delay initiation of rehabilitation, complicate the course and care of the patient with stroke, inhibit participation in a therapeutic exercise program, limit functional outcomes, and contribute to early mortality in the individual with cerebrovascular disease. Part 1 of this two-part article describes the various forms of heart disease that may be seen in stroke patients, and reviews the incidence figures for each type of associated cardiac condition.

Heart disease in patients with stroke. Part II: Impact and implications for rehabilitation.

Cardiac disease reduces the long-term survival of stroke patients and increases the likelihood of intercurrent medical illness during the rehabilitation phase. It remains controversial whether heart disease negatively affects functional capabilities after stroke, but most studies agree that associated cardiac disease, especially congestive heart failure, adversely affects functional outcomes after stroke rehabilitation. Reliable clinical assessment of the presence and severity of heart disease in stroke patients may be hampered by mobility limitations, communication deficits, and other problems. Therefore, specialized diagnostic methods may be needed. The development and application of effective and consistent medical and rehabilitation guidelines for proper comprehensive care may enhance the likelihood of achieving favorable outcomes and of avoiding complications in patients with stroke.

Fever, bacteriuria, and pyuria in spinal cord injured patients with indwelling urethral catheters.

Little is known about the significance of pyuria in spinal cord injury patients with indwelling urethral catheters (IUCs). The hospital courses of 32 such patients admitted to a rehabilitation hospital from January 1986 to December 1987 were reviewed to determine the incidence of unexplained febrile episodes, ie, no obvious nonurinary source of infection. All patients had positive admission urine cultures (greater than 100,000 colony-forming units/mL). Patients were divided into two groups based on the level of pyuria in admission urinalyses. Group A (the low pyuria group) was composed of 22 patients with less than or equal to 50 white blood cells per high-power field (WBC/HPF). Group B (the high pyuria group) was composed of ten patients with less than 50 WBC/HPF. None were admitted to the rehabilitation program taking antibiotics; none were prophylactically treated for urinary tract infection. The difference in incidence of fever between febrile episodes. Group B had an incidence of 6/10 (60%) febrile episodes. The difference in incidence of fever between the groups was statistically significant (chi2 = 7.31, p less than .01). These results suggest that SCI patients with IUCs and gross pyuria may be at risk for increased morbidity secondary untreated urinary tract infection.