Frizzled-7 and limb mesenchymal chondrogenesis: effect of misexpression and involvement of N-cadherin.

Products of the Frizzled family of tissue polarity genes have been identified as putative receptors for the Wnt family of signaling molecules. Wnt-signaling is implicated in the regulation of limb mesenchymal chondrogenesis, and our recent study indicates that N-cadherin and related activities are functionally involved in Wnt-7a-mediated inhibition of chondrogenesis. By using an in vitro high-density micromass culture system of chick limb mesenchymal cells, we have analyzed the spatiotemporal expression patterns and the effects on chondrogenesis of RCAS retroviral-mediated misexpression of Chfz-1 and Chfz-7, two Frizzled genes implicated in chondrogenic regulation. Chfz-1 expression was localized at areas surrounding the cartilaginous nodules at all time points examined, whereas Chfz-7 expression was limited to cellular aggregates during initial mesenchymal condensation, and subsequently was down-regulated from the centers toward the periphery of cartilage nodules at the time of chondrogenic differentiation, resembling the pattern of N-cadherin expression. Chondrogenesis in vitro was inhibited and limited to a smaller area of the culture upon misexpression of Chfz-7, but not affected by Chfz-1 misexpression. Analyses of cellular condensation and chondrogenic differentiation showed that the inhibitory action of Chfz-7 is unlikely to be at the chondrogenic differentiation step, but instead affects the earlier precartilage aggregate formation event. At 24 hr, expression of N-cadherin, a key component of the cellular condensation phase of chondrogenesis, was delayed/suppressed in Chfz-7 misexpressing cultures, and was limited to a significantly smaller cellular condensation area within the entire culture at 48 hr, when compared with control cultures. Chfz-1 misexpressing cultures appeared similar to control cultures at all time points. However, neither Chfz-1 nor Chfz-7 misexpression affected mesenchymal cell proliferation in vitro. These results suggest that Chfz-7 is active in regulating N-cadherin expression during the process of limb mesenchymal chondrogenesis and that Chfz-1 and Chfz-7 are involved in different Wnt-signaling pathways.     

Responsiveness and calibration of the general well-being adjustment scale in patients with hypertension

We examined the discriminant ability and responsiveness of the General Well-Being Adjustment Scale in patients enrolled in a randomized clinical trial of antihypertensive therapy. We also tried to translate the effects of physical symptoms on general well-being. This secondary analysis used demographic, clinical, physical symptom, and general well-being data for 545 white, male hypertensive patients. General well-being was measured by the General Well-Being Adjustment Scale (GWB) collected on 2 occasions over 8 weeks of treatment. Patients with any one of 14 physical symptoms or problems, compared to those without symptoms, had lower GWB scores (p < 0.003 to p < 0.0001). Decreases of 2.83–8.76 points in GWB scores were observed in patients developing physical symptoms over the 8 week study period (p < 0.05 to p < 0.0001). These effects were demonstrated in patients developing cold sensitivity, sexual problems, chest pain, shortness of breath, loss of taste, nausea, hot or cold spells, numbness and tingling, dry mouth, blurred vision, and dizziness. We conclude that the GWB is responsive to clinically meaningful changes in symptoms and may provide a more complete evaluation of the effects of medical treatment. The GWB is a valid and responsive measure of health status outcomes in the evaluation of antihypertensive treatment.     

Disseminated strongyloidiasis in AIDS: uncommon but important

Disseminated Strongyloides stercoralis infection is a rare and severe but treatable complication of AIDS. We present a case where this infection was successfully treated and review the available literature. Cases may present many years after they have left an area endemic for Strongyloides infection, emphasizing the need for a full travel history. Symptoms are typically gastrointestinal and pulmonary, with infiltrates often seen on chest radiography. Diagnosis requires stool examination and biopsy of affected sites. Treatment with repeated courses of thiabendazole (25 mg/kg twice daily for 5 days) was successful in our case, but maintenance regimens have not yet been defined. The relative rarity of this complication of AIDS suggests that, where both infections are present, disseminated strongyloidiasis only arises either when HIV-induced immunodeficiency is profound or, possibly, when it is accompanied by impaired granulopoiesis.     

Down's syndrome

We discuss the ethical, psychosocial, economic, and medical dimensions of the treatment and management of a child with Down's syndrome and a congenital heart defect.     

Acquired Loss of Red-Cell Wj Antigen in a Patient with Hodgkin''s Disease

A patient with Hodgkin's disease became temporarily Wj-negative with alloanti-Wj in his serum. Four human autoantibodies, and 1 of 2 murine monoclonal antibodies, with serological characteristics of anti-Wj were nonreactive with his red cells, confirming that they have anti-Wj specificity. Six siblings of the patient are all Wj-positive. The patient was also temporarily Anton-negative, and cross-testing between Wj and Anton red cells and antisera showed mutual compatibility, indicating that the antigens are the same. The patient and 3 of his 6 siblings are also of the rare Lu: - 13 phenotype, providing the first evidence that this is an inherited characteristic.     

Anaesthesia for diagnostic muscle biopsy in an infant with Pompe’s disease

The anaesthetic management of children with glycogen-storage disease type lia (Pompe’s disease) presents a variety of challenges. A modification of a femoral nerve block, the inguinal paravascular block, as described by Winnie, was used in conjunction with intravenous ketamine to provide anaesthesia for a diagnostic muscle biopsy in a 5.5-month-old infant with Pompe’s disease. A peripheral nerve stimulator was used to locate the femoral nerve in lieu of eliciting a paraesthesia.     

An interpersonal communication perspective on resistance in psychotherapy.

This article discusses resistance in psychotherapy using the contemporary interpersonal communication model of psychotherapy. This perspective defines resistance as moments during sessions when the patient and therapist are interacting with one another in such a way that the patient is kept from becoming aware of any covert experiences or transactional patterns that are conflictual and anxiety provoking. The ways in which resistance may be conceptualized and worked with are discussed and applied to three patient vignettes, with an emphasis on working with resistances as they are manifested in the patient-therapist relationship. Some of the potential reactions of the therapist to resistance are discussed, including some relatively beneficial and some problematic instances.     

Delayed Gastric Emptying after Laparoscopic Anterior Highly Selective and Posterior Truncal Vagotomy

We describe a case of gastroparesis after laparoscopic highly selective anterior and posterior truncal vagotomy in a 30-yr-old male with gastric ulcer disease. Motility studies confirmed the diagnosis, and a pancreatic polypeptide sham feeding study suggested that a complete vagotomy may have been inadvertently performed. The experience with this procedure in gastric ulcer disease is extremely limited; review of the literature of laparoscopic highly selective vagotomy describes only two cases with delayed gastric emptying as defined by radiological examination. In view of the paucity of reports, caution is warranted, and this procedure should be undertaken only in the setting of a controlled trial.     

Primary care referrals for lumbar spine radiography: diagnostic yield and clinical guidelines.

BACKGROUND: Primary care requests for radiographs of the lumbar spine have come under increasing scrutiny. Guidelines aiming to reduce unnecessary radiographs by limiting referrals to patients at high risk of serious disease have been widely distributed. Trial evidence suggests that guidelines can reduce radiography referrals. It is not clear whether this reduction has been achieved in routine practice. AIM: This study, using routine data, was conducted to measure trends in pnmary care referrals for lumbar spine radiography at two hospitals between 1994 and 1999. DESIGN OF STUDY: Analysis of primary care requests for lumbar spine radiography from computerised records. SETTING: Addenbrooke's Hospital, Cambridge (1 July 1994 to 30 June 1999), and Ipswich General Hospital (1 July 1995 to 30 June 1999), United Kingdom. METHOD: All primary care requests for lumbar radiography were identified electronically from computerised information systems. A random sample of 2100 radiography reports were classified according to clinical importance. These classifications were used to examine whether the proportion of radiographs demonstrating potentially more serious findings had increased between 1994 and 1999. RESULTS: There was no evidence that primary care referrals for radiography of the lumbar spine had decreased between 1994 and 1999 at either hospital. General practitioners did not progressively refer more high-risk patients for lumbar radiography. Only a small proportion of patients had important radiographic findings that might warrant specialist referral or specific therapy. CONCLUSION: The implementation of diagnostic guidelines offers much to the NHS. However in these two hospitals, the reduction in radiograph utilisation evident in trials was not achieved. Guideline development is a resource intensive process; distribution must be supported by more effective implementation strategies.