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The urea cycle disorders (UCDs) are important models for developing gene replacement therapy for liver diseases. Long-term correction of the most common UCD, ornithine transcarbamylase (OTC) deficiency, has yet to be achieved in clinical or preclinical settings. The single human clinical trial using early-generation adenovirus (Ad) failed to show any biochemical correction. In adult OTC-deficient mice, an E1/E2-deleted Ad vector expressing the mouse OTC gene, but not the human, was only transiently therapeutic. By using post-transcriptional overexpression in the context of the less immunogenic helper-dependent adenoviral vector, we achieved metabolic correction of adult OTC-deficient mice for >6 months. Demonstrating this result were normalized orotic aciduria, normal hepatic enzyme activity, and elevated OTC RNA and protein levels in the absence of chronic hepatotoxicity. Overexpressing the human protein may have overcome two potential mechanisms accounting for poor cross-species complementation: a kinetic block at the level of mitochondrial import or a dominant negative effect by the mutant polypeptide. These data represent an important approach for treating human inborn errors of hepatocyte metabolism like the UCDs that require high-level transduction and gene expression for clinical correction. [Copyright &y& Elsevier]

Reports on the examination of nutrient dynamics and soil disturbances since 1979 on paired control and intensively managed watersheds in central Maine. Harvest of mature spruce-fir stand and application of triclopyr to watershed; Application of nitrogen fertilizer to a subset of thinned plots; Increase in soil solution nitrate and cation concentrations by nitrogen fertilization.

An experiment was conducted so examine the impact of simultaneous threats to social- and self-esteem on evaluation apprehension. Subjects were told they would take a potentially ego-threatening test and that only they, only another individual, both they and the other individual, or no one would see their test scores. Prior to the test, evaluation apprehension was assessed. Results showed that potential threats to self- and social-esteem both increased apprehension, but only in the absence of the other type of ego threat. Further, the presence of both sources of threat did not produce greater apprehension titan either threat alone. Also, subjects who scored low versus high on a measure of self-esteem differed in their reactions to social- and self-esteem threats. Results suggest that the effects of conjoint threats to social- and self-esteem are no: cumulative. [ABSTRACT FROM AUTHOR]

Background: Eccentric exercise is commonly used in the management of Achilles tendinopathy (AT) but its effectiveness for insertional AT has been questioned. Soft tissue treatment (Astym) combined with eccentric exercise could result in better outcomes than eccentric exercise alone., Hypothesis: Soft tissue treatment (Astym) plus eccentric exercise will be more effective than eccentric exercise alone for subjects with insertional AT., Study Design: Prospective randomized controlled trial., Level of Evidence: Level 2., Methods: Sixteen subjects were randomly assigned to either a soft tissue treatment (Astym) and eccentric exercise group or an eccentric exercise-only group. Intervention was completed over a 12-week period, with outcomes assessed at baseline, 4, 8, 12, 26, and 52 weeks. Outcomes included the Victorian Institute of Sport Assessment Achilles-Specific Questionnaire (VISA-A), the numeric pain rating scale (NPRS), and the global rating of change (GROC)., Results: Significantly greater improvements on the VISA-A were noted in the soft tissue treatment (Astym) group over the 12-week intervention period, and these differences were maintained at the 26- and 52-week follow-ups. Both groups experienced a similar statistically significant improvement in pain over the short and long term. A significantly greater number of subjects in the soft tissue treatment (Astym) group achieved a successful outcome at 12 weeks., Conclusion: Soft tissue treatment (Astym) plus eccentric exercise was more effective than eccentric exercise only at improving function during both short- and long-term follow-up periods., Clinical Relevance: Soft tissue treatment (Astym) plus eccentric exercise appears to be a beneficial treatment program that clinicians should consider incorporating into the management of their patients with insertional AT.

We report the incidental discovery of a flexor carpi radialis brevis tendon, a rare anatomical variant identified during a surgical procedure. Magnetic resonance imaging of the contralateral side helped to delineate the anatomy of the flexor carpi radialis tendon and to differentiate the flexor carpi radialis brevis tendon from it. We describe the use of this rare tendon in ligament reconstruction of the basal joint of the thumb.

Background and Purpose: Mid-portion Achilles tendinopathy (AT) is a common injury among runners and recreational athletes. The conservative management of mid-portion AT typically includes eccentric exercise as recommended in multiple systematic reviews and practice guidelines. However, an eccentric program typically requires 12 weeks for satisfactory results and problems with compliance have been reported. Astym® is a non-invasive instrument assisted soft tissue treatment that can be used in the management of tendinopathies but there is limited published research on this treatment approach. The purpose of this case report is to present the management and outcomes of a patient with AT who was treated with eccentric exercise and Astym®., Case Description: The patient was a 56-year-old recreational tennis player referred to physical therapy with mid-portion AT of 6 weeks duration. Her primary complaints were pain with walking and an inability to play tennis. She was treated in physical therapy 2 times per week for 10 visits with treatment focused on Astym® and eccentric exercise., Outcomes: By her 6(th) visit she subjectively reported being 75% functionally normal and was able to play a doubles tennis match. After 10 visits she reported that she was pain-free and able to play singles and doubles tennis without limitation., Discussion: The patient in this case report was able to return to her normal activities after 5 weeks of treatment with Astym® and eccentric exercise. These results were achieved in less than half of the time commonly reported with eccentric exercise alone., Conclusion: This case suggests that Astym® combined with eccentric exercise may be a beneficial treatment approach for patients with AT.

High hamstring tendinopathy (HHT) is an overuse injury that occurs most commonly in runners. The management of HHT is often challenging and the research supporting many interventions is limited. Eccentric exercise has been proven effective in the treatment of various tendinopathies but has not been thoroughly studied with HHT. Soft tissue mobilization, including ASTYM, is often utilized in the treatment of tendinopathies, though there is limited evidence supporting this approach. The purpose of this paper is to present the case of a patient referred to physical therapy with bilateral HHT. The patient was a 41-year-old recreational runner that had an insidious onset of right buttock pain 12 months prior to initiating therapy and left buttock pain 9 months prior. Her primary complaints included an inability to run, pain with prolonged or brisk walking, and pain with sitting on hard surfaces. The patient was treated in physical therapy two times per week for 16 visits with treatment focused on eccentric hamstring strengthening and ASTYM. By her eighth visit, the patient was able to walk 2·5 miles without pain and by her 12 visit, she was able to jog 1 mile before the onset of pain. After 16 visits, the patient reported that she was approximately 95% improved, was able to run 2·5 miles without pain, and had no pain with sitting on hard surfaces. This case suggests that eccentric exercise combined with ASTYM may be an effective treatment for HHT.

Adhesive capsulitis (AC) is a common and disabling shoulder condition seen in physical therapy, and there is no clear consensus as to the best treatment approach. Recently there has been emerging evidence that manual therapy directed at the thoracic spine may be beneficial for patients with shoulder pain; however, this has not been examined specifically in patients with AC. The purpose of this paper is to present the case of 59-year-old female referred to physical therapy with a diagnosis of AC. The patient presented with complaints of left shoulder pain and significant limitations in range of motion (ROM) and upper extremity function. The initial treatment included exercises and manual therapy directed at the glenohumeral and scapulothoracic joints, and after 10 visits only minimal progress had been made. Further examination revealed mobility and ROM deficits in the thoracic spine, and manual therapy directed at this region was incorporated into her treatment. After the first session of thoracic spine manual therapy (TSMT) a 25 degree improvement was noted in active shoulder flexion. After four total visits of TSMT substantial improvements in pain, ROM, and function were noted compared to those made during the first 10 visits. This case adds to the emerging evidence that manual therapy directed at the thoracic spine should be considered for patients with shoulder pain.

We retrospectively review the cases of 5 men with closed, impacted intra-articular fractures of the middle phalanx at the proximal interphalangeal joint and describe a new technique-involving percutaneous reduction and Kirschner-wire fixation-that minimizes surgical trauma, allows fixation for early range of motion, and provides results as good as, if not superior to, those obtained with existing techniques.

Two patients with partial deletions of the long arm of chromosome 13, del(13)(13q21-q34) and del(13)(13q22-q33), respectively, multiple congenital anomalies including holoprosencephaly (HPE) and the Dandy-Walker malformation (DWM) are described. The occurrence of HPE and the DWM in both of these patients suggests that, in addition to ZIC2, which is important for normal development of the forebrain, there is at least one other dosage-sensitive gene in 13q22-q33 that plays an important role in brain development. The DWM is anatomically and developmentally distinct from HPE. The presence of a DWM in each of these two patients with partial deletions of the long arm of chromosome 13 suggests that haploinsufficiency at a locus in 13q22-q33 may cause this anomaly. These findings suggest that microdeletions in 13q22-q33 may be found in a proportion of patients with an apparently isolated DWM. Therefore, careful high-resolution cytogenetic analysis (550 band level or greater) of 13q22-q33 may be considered in these patients. Furthermore, future molecular studies of this region may reveal candidate gene loci for the DWM.

Two patients with partial deletions of the long arm of chromosome 13, del(13)(13q21-q34) and del(13)(13q22-q33), respectively, multiple congenital anomalies including holoprosencephaly (HPE) and the Dandy-Walker malformation (DWM) are described. The occurrence of HPE and the DWM in both of these patients suggests that, in addition to ZIC2, which is important for normal development of the forebrain, there is at least one other dosage-sensitive gene in 13q22-q33 that plays an important role in brain development. The DWM is anatomically and developmentally distinct from HPE. The presence of a DWM in each of these two patients with partial deletions of the long arm of chromosome 13 suggests that haploinsufficiency at a locus in 13q22-q33 may cause this anomaly. These findings suggest that microdeletions in 13q22-q33 may be found in a proportion of patients with an apparently isolated DWM. Therefore, careful high-resolution cytogenetic analysis (550 band level or greater) of 13q22-q33 may be considered in these patients. Furthermore, future molecular studies of this region may reveal candidate gene loci for the DWM., (Copyright 2002 Wiley-Liss, Inc.)

A wire interlock technique useful for harvesting a partial-width tendon graft with an intact insertion for local reconstructive procedures is described. This technique is rapid and reliable for procuring attached tendon grafts with minimal exposure. The technique was used to harvest a flexor carpi radialis tendon graft for basal joint interposition arthroplasty in 12 patients. This method also may be readily applicable for other procedures requiring local ligament reconstruction with a partial-width tendon graft. (J Hand Surg 2000; 25A:176-182., (Copyright 2000 by the American Society for Surgery of the Hand.).)

We performed a prospective study in order to assess the utility of high-resolution magnetic resonance imaging in the detection and specific localization of tears of the triangular fibrocartilage complex. Seventy-seven patients who had pain in the wrist were studied with use of a dedicated surface coil and three-dimensional gradient-recalled techniques with a field of view of eight centimeters and a slice thickness of one millimeter. The patients had pain on the ulnar side of the wrist, ligamentous instability, occult ganglia, or a combination of these. Magnetic resonance images were assessed for radial or ulnar avulsion, or both; central defects; degenerative intrasubstance changes; and complex tears of the triangular fibrocartilage complex. Partial tears were differentiated from complete tears. The findings on the magnetic resonance images were then compared with the arthroscopic findings. Fifty-seven of the fifty-nine tears that were suspected on magnetic resonance images were confirmed with arthroscopy; the two suspected tears that were not confirmed had been interpreted as small partial tears on the magnetic resonance images. With use of arthroscopy as the standard, magnetic resonance imaging had a sensitivity of 100 per cent (fifty-seven of fifty-seven), a specificity of 90 per cent (eighteen of twenty), and an accuracy of 97 per cent (seventy-five of seventy-seven) for the detection of a tear (kappa = 0.93, p < 0.00001). Fifty-three of the fifty-seven tears were localized correctly with use of magnetic resonance imaging. With regard to the location of the tear, magnetic resonance imaging had a sensitivity of 100 per cent (fifty-three of fifty-three), a specificity of 75 per cent (eighteen of twenty-four), and an accuracy of 92 per cent (seventy-one of seventy-seven) (kappa = 0.9, p < 0.0001). We concluded that high-resolution magnetic resonance imaging permits accurate depiction and localization of tears of the triangular fibrocartilage complex. When the appropriate pulse sequence is used, magnetic resonance imaging is an accurate and effective method for the non-invasive evaluation of pain in the wrist.

Thirty-six consecutive patients with 37 complete tears of the ulnar collateral ligament of the thumb metacarpophalangeal (MP) joint were treated with primary repair using a miniature intraosseous suture anchor. Thirty patients were evaluated by clinical examination or by questionnaire at an average of 11 months after repair. Loss of interphalangeal joint motion averaged 15 degrees on the involved side versus the other side, while loss of MP joint motion averaged 10 degrees. There was no significant difference on stress testing measurements between repaired and nonrepaired thumbs. There were no instances of nerve injury, infection, device failure, or reoperation. The authors concluded that this is a safe and effective method for repair of complete tears of the ulnar collateral ligament of the thumb MP joint.

Forty-six patients with histologically confirmed osteoid osteoma of the upper extremity seen from 1947 to 1990 were retrospectively reviewed. The patients' age at presentation averaged 20 years. Twenty-four of the lesions were located in the wrist and hand and 22 in the arm and forearm. The average duration of symptoms before diagnosis was 15 months. Pain was the presenting symptom in 44 of 46 patients. Of the 28 patients who took aspirin for pain, 24 obtained at least partial relief. A mass or swelling was more commonly noted in lesions of the hand and wrist as compared to the arm and forearm. The diagnosis of osteoid osteoma was made by plain x-ray films alone in 35 cases. Bone scans were performed on 13 patients; all were positive at the site of the lesion. Tomography was performed in 13 cases to identify the intraosseous location of the lesion. All lesions were treated by excision and curettage. Thirty-four of the 46 patients were followed at our institution for more than 6 months, with an average follow-up period of 27 months. Six of the patients had persistent lesions. Of the six persistent osteoid osteomas, five occurred in the wrist or hand (p = .0012). A total of 15 procedures were required to excise these lesions.

Background: Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer's disease that does not cause significant patient sedation. Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens. The purpose of this study was to document the efficacy of selegiline in Alzheimer's patients with behavior problems., Method: Eight Alzheimer's patients (6 women and 2 men) ranging in age from 50 to 82 years (mean +/- SD = 74.0 +/- 10.5) were enrolled in this single-blind study. Patients received selegiline 10 mg each day for 8 weeks. Prior to drug administration and at the end of Weeks 1, 2, 4, 6, and 8, patients were evaluated for behavior (BEHAVEAD), cognitive function (Mini-Mental State Examination), and caregiver stress (Caregiver Burden Scale)., Results: Of eight enrolled patients, five were available for analysis. No statistically significant differences were found between mean baseline and mean 8-week scores for any of the three tests. However, clinical significance was noted by improvement in cognition (orientation and recall), caregiver stress, and behavior. Behavior was noted to improve in the areas of paranoid and delusional ideation, hallucinations, activity disturbances, anxiety, and phobias., Conclusion: These data suggest that some Alzheimer's patients with behavior problems may benefit from selegiline therapy.

A cross sectional survey of a randomly selected population of 2,261 textile workers form an overall population of 8,539 eligible workers was performed to evaluate the prevalence of tendinitis in related upper extremity disorders. Of the sample, 2,047 respondents (91.3%) participated in a nurse screening history and examination: 1,091 (53%) had no upper extremity symptoms or abnormalities on examination; 959 (47%) with positive findings were examined by trained physicians. Of these, 347 (36.5%) were found to have no abnormality, whereas, 548 (57.3%) workers were assigned a diagnosis. Of these 227 were considered to fall into the categories of tendinitis (n = 69) or related disorders (n = 158). The projected prevalence of tendinitis and related disorders for the overall group was 11.6% (carpal tunnel syndrome 1.1%, epicondylitis 2.0%, tendinitis 3.5%, shoulder condition 2.3%, ganglion 2.3%, neck conditions 4.0%). Tendinitis was less frequent in the older age group and those employed for a longer time. The prevalence of tendinitis was found to be statistically higher in physically demanding job categories. Ninety-four percent of ailments were of mild or moderate severity. Although our study provides prevalence data for these conditions in a large manufacturing workforce across several job categories.

The cell cytosol superoxide dismutase (SODase) content of 46 human tumors was investigated. The extraction procedure of McCord and Fridovich was used with the epinephrine assay of Misra and Fridovich (J. Biol. Chem., 247; 3170-3175, 1975). The purpose of the study was to determine whether SODase could be reliably assayed from small, biopsy-sized pieces of tumor (0.5 to 1.0 g). In most cases it was possible to examined larger masses of tumor, which served as a control of the methodology. In this preliminary study SODase values, calculated from a standard curve derived from purified bovine blood SODase with a specific activity of 2584 units/mg, ranged from as little as 0.23 to as much as 160.5 units/g of tumor. These findings suggested that the procedures used might be feasable on a routine basis to determine the SODase content of tumors and its possible relationship to the radiation sensitivity of the tumors.

A new, quantitative modification of the vasoconstrictor assay was used to measure bioavailability of generic topical corticosteroid products in two categories: betamethasone valerate 0.1% cream and triamcinolone 0.1% cream. Betamethasone valerate products could be separated into two distinct categories, and triamcinolone acetonide products could be grouped into three categories of activity. A survey of local pharmacies showed that generic substitution would be made for the prescribed brand of betamethasone valerate in 58% of cases and for the prescribed triamcinolone acetonide 75% of the time. Because of the prevalence of generic substitution of products that may not have equivalent bioavailability, some standardization of the bioavailability of topical products is needed.

The survival of patients with bone sarcomas has improved dramatically with the advent of modern chemotherapeutic regimens, fostering a present trend toward limb sparing procedures. In skeletally immature patients, prosthetic replacement of resected bones and joints is unrealistic because of continued expected growth in the limbs. A stump-lengthening procedure, the reduction-rotation-plasty, has become a valuable alternative to high above-knee amputation. A rhombus-shaped skin incision around the thigh and calf, originally described by Kotz and Salzer, led to a significant discrepancy of the circumference of the proximal and distal skin borders. A circumferential skin incision at the midthigh and a fishmouth-shaped incision at the upper calf was designed to decrease this disproportion. This incision has been used in five consecutive patients with osteosarcoma about the knee. The cosmetic results were excellent, prosthetic fittings were facilitated, and neither vascular nor wound healing problems were encountered.