Chondral metaplasia in calcific insertional tendinopathy of the Achilles tendon.

OBJECTIVE: To ascertain whether tendon samples harvested from patients with calcific insertional Achilles tendinopathy showed features of failed healing response, and whether abnormal quantities of type II collagen had been produced in that area by these tenocytes. DESIGN: Comparative laboratory study. DESIGN: University teaching hospitals. PATIENTS: Tendon samples were harvested from eight otherwise healthy male individuals (average age 47.5+/-8.4 years, range 38 to 60) who were operated for calcific insertional Achilles tendinopathy and from nine male patients who died of cardiovascular events (mean age 63.1+/-10.9 years) while in hospital. INTERVENTIONS: Open surgery for calcific insertional Achilles tendinopathy. MAIN OUTCOME MEASURE: Semi-quantitative histochemical, immunohistochemical, and immunocytochemical methods to ascertain whether tendinopathic tendons were morphologically different from control tendons, and whether abnormal types of collagen were produced. RESULTS: Tenocytes from tendons from patients with calcific insertional Achilles tendinopathy exhibit chondral metaplasia, and produce abnormally high quantities of collagen type II and III. CONCLUSIONS: The altered production of collagen may be one reason for the histopathological alterations described in the present study. Areas of calcific insertional Achilles tendinopathy have been subjected to abnormal loads. These tendons may be less resistant to tensile forces. Further studies should investigate why some tendons undergo these changes.     

Cord insulin and C-peptide--distribution in an unselected population.

OBJECTIVE: To assess the distribution of cord blood insulin in an unselected population, and examine its relation to birthweight centiles. SETTING: District General Hospital in Nottinghamshire. SUBJECTS: 209 unselected singleton births. MEAN OUTCOME MEASURE: Cord blood insulin; cord blood C-peptide; birthweight centiles. RESULTS: Hyperinsulinaemic babies (greater than 97th centile for cord insulin) were found at all birthweight centiles. 15% of high birthweight babies were hyperinsulinaemic. For low birthweight babies, the distribution of cord insulin/C-peptide was skewed indicating a high number of low values. Hypoinsulinaemic babies were present up to the 50th centile for birthweight. CONCLUSIONS: Abnormalities of fetal insulinisation may be found in babies of all birthweights.     

Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve.

The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.     

THE EMERGING ROLE FOR LAPAROSCOPIC GASTROSTOMY

A gastrostomy was fashioned laparoscopically in a 15 year old patient with a severe head injury. A preceding attempt at percutaneous endoscopic gastrostomy had failed. The gastrostomy tube was inserted into the stomach under vision and the stomach attached to the anterior abdominal wall by sutures.     

Brief dialectical behavior therapy (DBT-B) for suicidal behavior and non-suicidal self injury.

The purpose of this study is to evaluate the effectiveness of a shorter course of Dialectical Behavior Therapy (DBT) in enhancing treatment retention and reducing: urges to engage in non-suicidal self injury (NSSI), NSSI, suicide ideation, and subjective distress in borderline personality disorder (BPD). Twenty patients with BPD received a six-month course of Dialectical Behavior Therapy (DBT-B). DBT-B was delivered in the standard manner except for the shortened duration from one-year minimum to six months. All variables were measured at baseline, and at six months. Data were analyzed using paired t-tests. Treatment retention rate was 95%. Significant reductions were found in NSSI urges, NSSI, suicide ideation, subjective distress, depression, and hopelessness between baseline and six months. These results support the use of DBT-B in a six-month format when NSSI and suicidal behavior and ideation are the targeted behaviors. Target behaviors were reduced significantly and retention was extremely high in comparison to other interventions for this population. A large scale randomized controlled trial investigating its efficacy is warranted to determine if the results can be replicated and if improvement can be sustained.     

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.