Transcultural understanding of a hereditary disorder. Mucopolysaccharidosis VI in a Vietnamese family

A case study of a family referred for clarification of cultural issues illustrates how a transcultural psychiatric service developed in the pediatric hospital setting can be used to advantage. A Vietnamese family with an inherited disorder. Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI), resisted genetic counseling and contraception. Three out of their six children were affected, one with a fatal outcome. The transcultural consultation offered an understanding of their behavior and facilitated subsequent management.     

A short-term follow-up comparison of two trans-obturator tape procedures

The objective of the study was to compare the clinical outcomes at the short-term follow-ups of two novel transobturator mid-urethral sling procedures – the transobturator tape (TOT) procedure and the tension-free vaginal tape (TVT)-obturator procedure. The study cohort consisted two groups of 40 women with urodynamically proven stress urinary incontinence (SUI). The patients in one group underwent the TOT procedure, performed according to Delorme (Prog Urol 11:1306–1313, 2001); those in the second group underwent the TVT-obturator operation, performed according to de Leval (Eur Urol 44:724–730, 2003). Intra-operative diagnostic cystoscopy was not performed with either the TVT-obturator or the TOT procedures. The average follow-up was 12 months. The two patient groups were similar in terms of demographic and therapeutic criteria, except for patient age, which was significantly younger in the TVT-obturator group. Previously reported TVT-related operative complications, such as bladder penetration, intra-operative bleeding, field infection and post-operative pelvic floor relaxation, were not observed in patients of either group. Bowel and urethral injuries were also not recorded. The therapeutic failure rates were 10% for the TOT procedure and 5% for the TVT-obturator procedure. Urinary frequency and urgency post-operatively were reported in 25% of the TOT patients and 19% of the TVT-obturator patients, pelvic or vaginal pain affected 10% of the TOT and 5% of the TVT-obturator patients, while post-operative voiding difficulty was experienced by 12.5% of the TOT and 7.5% of the TVT-obturator patients. None of the above-mentioned differences between the two patient groups were of statistical significance. The TVT-obturator and TOT procedures, both minimally invasive, novel, mid-urethral sling procedures, seem to be safe, easy-to-perform and effective in treating female SUI. The patients of both study groups suffered less intra- and post-operative surgical complications than previously been reported in connection with the TVT operation. The TVT-obturator patients had fewer therapeutic failures, less post-operative urinary frequency and urgency, less pelvic pain and less voiding difficulty. All of these findings, however, had no statistical significance; consequently, long-term comparative data collection will be required before solid conclusions can be drawn on the superiority of either of these two operative techniques.     

Familial fixed subaortic stenosis

In this report, we give details of two families in which fixed subaortic stenosis was found in more than one member. It is rare for this entity to show familial incidence.     

123I-FP-CIT SPECT imaging of dopamine transporters in patients with cerebrovascular disease and clinical diagnosis of vascular parkinsonism.

The purpose of our study was to prospectively evaluate the striatal uptake of 123I-labeled N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane (FP-CIT) and the response to l-dopa therapy in patients with cerebrovascular disease (CVD) who develop clinical symptoms of vascular parkinsonism (VP). METHODS: Twenty consecutive patients who developed VP in the course of CVD were prospectively enrolled in the study. All patients had CT evidence of CVD (17 patients had lacunar infarcts, 3 patients had territorial strokes). The clinical stage of the patients was assessed using the Hoehn and Yahr scale, and the severity of the symptoms was measured using the Unified Parkinson's Disease Rating Scale score. Ten age-matched subjects were used as controls. SPECT was performed 180 min after injection of 185 MBq 123I-FP-CIT using a dual-head gamma-camera. The ratio of the mean specific-to-nonspecific striatal binding for the entire striatum, caudate, and putamen was calculated in all patients and compared with that of controls. Putamen-to-caudate binding ratios were compared as well. The response to therapy was compared between patients with normal and abnormal 123I-FP-CIT binding. RESULTS: No correlation was found between any of the clinical variables and response to therapy in patients with VP. Nine patients had normal striatal 123I-FP-CIT binding with no significant differences in striatal or subregional binding ratios compared with those of the controls. In contrast, 11 patients had significantly diminished striatal binding compared with that of controls (P < 0.001). Subanalyses showed significantly decreased binding in the caudate (P < 0.04 and P < 0.01 for the right and left caudate, respectively), diminished binding in the putamen (P < 0.04 and P < 0.01 for the right and left putamen, respectively), and a decreased putamen-to-caudate ratio on the right side (P < 0.001). The latter ratio was not significant on the left. Two of the 3 patients with territorial strokes had significantly diminished striatal 123I-FP-CIT binding in the hemisphere contralateral to the CT lesion. All 9 patients with normal scan findings had a poor response to L-dopa. Six of 11 patients with abnormal studies had no response to L-dopa, whereas 5 patients had a good response (P < 0.03). CONCLUSION: The diagnosis of VP cannot be accurately confirmed on the basis of clinical features alone because CVD may alter the typical presentation of PD. Functional imaging with 123I-FP-CIT is highly recommended in patients with CVD who develop symptoms of VP to confirm or exclude the existence of nigrostriatal dopaminergic degeneration. Identifying a subset of patients with reduced 123I-FP-CIT binding in the striatum is important for better treatment selection.     

Cardiac conduction abnormalities and rhythm changes after neonatal anatomical correction of transposition of the great arteries.

Seventy three infants who underwent neonatal anatomical correction for transposition of the great arteries with or without a ventricular septal defect were reviewed for evidence of conduction and rhythm abnormalities on preoperative and postoperative 12 lead electrocardiograms and during 24 hour Holter monitoring. There was a partial right bundle branch block pattern in 47% (29/62) of all patients and in 60% (24/40) of those with simple transposition. Complete right bundle branch block was noted in 21% including 5% with simple transposition. Holter monitoring showed sinus rhythm in all patients except three: one had episodes of supraventricular tachycardia, another an intermittent second degree heart block, and a third a complete heart block. Atrial extrasystoles were noted in 47% (29/62) of patients but were frequent in only three patients. Occasional unifocal ventricular extrasystoles were encountered in 37% (23/62) of patients and were frequent in a further 3% (2/62). Only one patient (2%) developed multifocal ventricular extrasystoles. The frequency of important cardiac arrhythmias after neonatal anatomical correction of transposition of the great arteries was 5%, significantly less than that reported after atrial inflow diversion for the same malformation.     

The Role and Limitations of 18-Fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose Positron Emission Tomography (FDG-PET) Scan and Computerized Tomography (CT) in Restaging Patients with Hepatic Colorectal Metastases Following Neoadjuvant Chemotherapy: Comparison with Operative and Pathological Findings

Background Recent data confirmed the importance of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the selection of patients with colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before hepatic resection in selected cases may improve outcome. The influence of chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases is not known. Methods Patients were assigned to either neoadjuvant treatment or immediate hepatic resection according to resectability, risk of recurrence, extrahepatic disease, and patient preference. Two-thirds of them underwent FDG-PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and FDG-PET/CT. Those without extensive extrahepatic disease underwent open exploration and resection of all the metastases according to original imaging findings. Operative and pathological findings were compared to imaging results. Results Twenty-seven patients (33 lesions) underwent immediate hepatic resection (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET: 93.3 vs 49%, P < 0.0001; CT: 87.5 vs 65.3, P = 0.038). CT had a higher sensitivity than FDG-PET in detecting CR metastases following neoadjuvant therapy (65.3 vs 49%, P < 0.0001). Sensitivity of FDG-PET, but not of CT, was lower in group 2 patients whose chemotherapy included bevacizumab compared to patients who did not receive bevacizumab (39 vs 59%, P = 0.068). Conclusions FDG-PET/CT sensitivity is lowered by neoadjuvant chemotherapy. CT is more sensitive than FDG-PET in detecting CR metastases following neoadjuvant therapy. Surgical decision-making requires information from multiple imaging modalities and pretreatment findings. Baseline FDG-PET and CT before neoadjuvant therapy are mandatory. The abstract was presented before the 58th Cancer Symposium of the Society of Surgical Oncology, Atlanta, GA, USA, 2005, and before the 2005 Congress of the American Hepato-Pancreato-Biliary Association, Fort-Lauderdale, FL, USA.     

Beneficial autoimmunity to proinflammatory mediators restrains the consequences of self-destructive immunity

Therapies that neutralize the function of TNF-alpha suppress rheumatoid arthritis (RA) but not osteoarthritis (OA). We show that patients suffering from RA but not OA have significant levels of autoantibodies directed to TNF-alpha. Thus, the immune system can selectively generate autoimmunity to proinflammatory mediators when such a response is beneficial for the host. A well-defined model of RA was used to elaborate the contribution of beneficial autoimmunity to the regulation of disease. We show that during the disease autoantibody production is elicited against few inflammatory, but not regulatory, mediators. Selective amplification of these beneficial antibodies by targeted DNA vaccines provided protective immunity. Epitope mapping revealed that anti-TNF-alpha immunity is highly restricted and excretes no crossreactivity to other known gene products. Its selective exclusion substantially exacerbated the disease. Administration of anti-TNF-alpha antibodies could then override this aggravation. This substantiates the significance of beneficial autoimmunity in restraining self-destructive immunity.     

Differential effects of growth factors on tissue-engineered cartilage

The effects of four regulatory factors on tissue-engineered cartilage were examined with specific focus on the ability to increase construct growth rate and concentrations of glycosaminoglycans (GAG) and collagen, the major extracellular matrix (ECM) components. Bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid (PGA) scaffolds and cultured in medium with or without supplemental insulin-like growth factor (IGF-I), interleukin-4 (IL-4), transforming growth factor-beta1 (TGF-beta1) or platelet-derived growth factor (PDGF). IGF-I, IL-4, and TGF-beta1 increased construct wet weights by 1.5-2.9-fold over 4 weeks of culture and increased amounts of cartilaginous ECM components. IGF-I (10-300 ng/mL) maintained wet weight fractions of GAG in constructs seeded at high cell density and increased by up to fivefold GAG fractions in constructs seeded at lower cell density. TGF-beta1 (30 ng/mL) increased wet weight fractions of total collagen by up to 1.4-fold while maintaining a high fraction of type II collagen (79 plus minus 11% of the total collagen). IL-4 (1-100 ng/mL) minimized the thickness of the GAG-depleted region at the construct surfaces. PDGF (1-100 ng/mL) decreased construct growth rate and ECM fractions. Different regulatory factors thus elicit significantly different chondrogenic responses and can be used to selectively control the growth rate and improve the composition of engineered cartilage.