Which elderly patients with severe aortic stenosis benefit from surgical treatment? An aid to clinical decision making.

BACKGROUND AND AIM OF THE STUDY: Clinical decision-making in an individual elderly patient with severe aortic stenosis (AS) is difficult. The prognosis is influenced by increased age and various cardiac morbidity and comorbidity, and the benefit of surgery is uncertain because the prognosis with conservative treatment has rarely been described. The study aim was to identify those patients who would gain from surgical therapy. METHODS: The long-term survival of a cohort of elderly patients after an initial diagnosis of severe aortic stenosis was analyzed. Multivariate analysis was used to develop patient profiles on the basis of four main variables of age, severity of AS, cardiac morbidity, and comorbidity, to illustrate the benefit of surgical treatment over conservative treatment. RESULTS: A total of 280 consecutive patients aged > or = 70 years (median age 78 years) with a first-time diagnosis of isolated AS made between 1991 and 1993 was included. Of these patients, 120 underwent surgery. The seven-year predicted survival ranged from 6.9% to 83% in surgically treated patient, and from 0.6% to 48% in conservatively treated patients. The benefit of surgical treatment over conservative treatment was greatest in patients aged < 80 years, with a more critical AS, cardiac morbidity, and without (7-year survival 78% versus 14%) or with (7-year survival 56% versus 1%) comorbidity. Minimal benefit was seen in patients aged > 80 years with a less critical AS and without cardiac morbidity. CONCLUSION: This model illustrated the benefit of surgical treatment over conservative treatment in 16 different profiles of elderly patients with severe AS. These findings may provide support for clinical decision making in individuals within this patient group.

A cardiac-specific health-related quality of life module for young adults with congenital heart disease: development and validation.

This study represents the development and validation of a cardiac-specific module of the generic health-related quality of life (HRQoL) instrument, the TAAQOL (TNO/AZL Adult Quality Of Life), for young adults with congenital heart disease (CHD). Items were selected based on literature, an explorative previous study in CHD patients, interviews with patients, and the advice of experts. The newly developed Congenital Heart Disease-TNO/AZL Adult Quality of Life (CHD-TAAQOL) was tested in 156 patients with mild or complex CHD and consisted of three hypothesised subject scales: 'Symptoms' (9 items), 'Impact Cardiac Surveillance' (7 items), and 'Worries' (10 items). Cronbach's alpha for the three scales were 0.77, 0.78, and 0.82, respectively. Scale structure was confirmed by Principal Component Analysis, corrected item-scale and interscale correlations. Overall, 55% of reported health status problems were associated with negative emotions, which is an argument for assessing HRQoL as a concept distinct from health status. Convergent validity with validated generic instruments (TAAQOL and Short Form-36, SF-36) showed satisfactory coefficients. Discriminant validity was proven by significantly higher scores for mild CHD patients compared with those with complex CHD. In conclusion, the CHD-TAAQOL module together with the generic TAAQOL can be used to assess group differences for cardiac-specific HRQoL in young adults with CHD. Testing psychometric properties of the CHD-TAAQOL shows satisfactory results. However, to detect changes in HRQoL over time, further research is needed.

Chemokine blockade and chronic inflammatory disease: proof of concept in patients with rheumatoid arthritis.

BACKGROUND: Chemokines and their receptors are considered important contributors in cell migration and inflammation in chronic inflammatory disorders. Chemokines affecting monocytes/macrophages are considered potential therapeutic targets, but no studies of the effects of blocking the chemokine repertoire in humans with a chronic inflammatory disease have been reported. OBJECTIVE: To carry out a double blind, placebo controlled, phase Ib clinical trial with a specific, oral CCR1 antagonist. METHODS: 16 patients with active rheumatoid arthritis (RA) were randomised 3:1 to active:placebo treatment for 14 days. Synovial biopsy specimens were obtained on days 1 and 15. Immunohistochemistry was used to detect the presence of various cell types before and after treatment and the results measured by digital image analysis. Results before and after treatment were compared by paired t test, and a two sample t test was used to compare the changes from baseline in the two groups. RESULTS: All patients completed the study. A significant reduction in the number of macrophages (p=0.016), intimal macrophages (p=0.026), and CCR1+cells (p=0.049) in patients treated with the chemokine antagonist compared with the placebo group occurred in the synovium. Significant decreases in overall cellularity, intimal lining layer cellularity, CD4+ T cells, and CD8+ T cells also occurred in treated patients. Cells lacking CCR1 were not affected. Trends towards clinical improvement were seen in the treated patients but not in the placebo group. Severe side effects were not reported. CONCLUSION: Specific chemokine receptor blockade can result in relevant biological effects in patients with active RA.

Immune restoration disease in HIV-infected individuals receiving highly active antiretroviral therapy: clinical and immunological characteristics.

BACKGROUND: HIV-infected patients responding to HAART can show a diverse spectrum of symptoms caused by inflammatory reaction. The pathogenesis of this phenomenon, called immune restoration disease (IRD), is unclear. This study describes the spectrum of IRD and analyses the immunological and clinical parameters that could be related to its development. METHODS: In a retrospective, matched case-control study, 17 HIV-infected individuals who developed inflammatory symptoms < 12 months after initiation of HAART were included. HIV-infected controls were matched for age, gender and CDC classification. Factors included in the analysis were: CD4+ and CD8+ cell counts, deltaCD4+ and deltaCD8+, CD4/CD8 ratios, HIV-1-RNA load (VL), AVL and the number of CDC events prior to HAART. RESULTS: The median time after initiation of HAART and developing IRD (n = 17) was 72 days (range 2-319). In nine cases (53%) a mycobacterial infection was identified as the underlying cause. HAART was started at a mean CD4+ count (+/- SD) of 55 x 10(6) /l (+/- 59) and 85 x 10(6) /l (+/- 78.0) for cases and controls, respectively (p = 0.13). After initiation of HAART, the CD4+ count showed a 10.6 fold increase at the onset of IRD in the cases and a 2.7 fold increase in the controls in an equal period of time (p = 0.020). The other parameters analysed did not differ significantly between cases and controls. CONCLUSION: We conclude that the risk of developing IRD is associated with a high-fold increase in CD4+ lymphocytes. In this study, mycobacteria are the pathogens most frequently associated with IRD.

The Donati stitch revisited: favorable cosmetic results in a randomized clinical trial.

BACKGROUND: Literature on the cosmetic results of various surgical methods to close the skin is scarce. We sought to compare the cosmetic results of two different surgical techniques of skin closure after lower midline laparotomy. MATERIALS AND METHODS: A randomized clinical trial compared a running nylon skin suture to interrupted Donati stitches in 58 patients undergoing gynecological surgery. Scar hypertrophy, scar width, scar color, the presence of cross-hatching marks, and a total scar score were assessed in all patients at 2 weeks, 6 months, and 12 months postoperatively. RESULTS: On average closing the wounds with Donati stitches took 5 min longer than using a running suture (P > 0.001). The Donati sutures caused significantly less cross-hatching at 2 weeks and 6 months postoperatively. At 1 year, the scar color following Donati closure was also significantly less pronounced than in the running suture arm. The total scar score was significantly better in the Donati arm at each of the three time periods of assessment. The difference at 6 months was equal to the difference at 1 year. CONCLUSIONS: Closing the skin of lower midline laparotomy wounds with Donati stitches resulted in a cosmetically better scar. Scar cosmetics of lower midline laparotomies could be improved by using interrupted Donati stitches instead of a running suture. The difference was significant at 2 weeks, 6 months, and 12 months postoperatively, but the magnitude of the difference was the same at 6 and at 12 months.

Health related quality of life and health status in adult survivors with previously operated complex congenital heart disease.

OBJECTIVE: To examine the impact of previously operated complex congenital heart disease on health related quality of life and subjective health status and to determine the relation between these parameters and physical status. DESIGN: Cross sectional; information on medical follow up was sought retrospectively. SETTING: Patients were randomly selected from the archives of the paediatric cardiology department, Leiden University Medical Centre, Leiden, The Netherlands, and approached irrespective of current cardiac care or hospital of follow up. PATIENTS: Seventy eight patients with previously operated complex congenital heart disease (now aged 18-32 years) were compared with the general population. MAIN OUTCOME MEASURES: Health related quality of life was determined with a specifically developed questionnaire (Netherlands Organisation for Applied Scientific Research Academic Medical Centre (TNO-AZL) adult quality of life (TAAQOL)) and subjective health status was assessed with the 36 item short form health survey (SF-36). Physical status was determined with the objective physical index, Somerville index, and New York Heart Association functional class. RESULTS: Health related quality of life of the patients was significantly worse than that of the general population in the dimensions gross motor functioning and vitality (p < 0.01). Correlations between health related quality of life and physical status were poor. Patients had significantly worse subjective health status than the general population in the dimensions physical functioning, role functioning physical, vitality, and general health perceptions (p < 0.01). Correlations between subjective health status and physical indices were weak. CONCLUSION: Adult survivors with previously operated complex congenital heart disease experienced limitations only in the physical dimensions of health related quality of life and subjective health status. Objectively measured medical variables were only weakly related to health related quality of life. These results indicate that, when evaluating health related quality of life, dedicated questionnaires such as the TAAQOL should be used.

Expression of co-stimulatory and adhesion molecules and chemokine or apoptosis receptors on acute myeloid leukaemia: high CD40 and CD11a expression correlates with poor prognosis.

The expression of adhesion and co-stimulatory molecules, and chemokine and death receptors such as tumour necrosis factor (TNF) and FAS on acute myeloid leukaemia (AML) may influence the biology of the disease and response to chemotherapy and immunotherapy. In this study, we analysed the expression of these molecules in 99 AML patients using monoclonal antibodies and flow cytometry, and correlated the expression with French-American-British (FAB) classification and survival. The following molecules were studied: the co-stimulatory molecules CD80, CD86 and CD40; the adhesion molecules CD11a-c, CD31, CD43, CD50, CD54, CD102, CD58 and CD62L; the chemokine receptor CXCR4; and the death receptors TNFR1 and TNFR2 and FAS. The expression of all molecules was significantly higher in the M4/M5 FAB subgroups except for CD80, CD43, CD54 and CD62L. The AML M3 subgroup had a significant lower expression of CD11a (P = 0.02) and CD11c (P = 0.03). Five-year survival was significantly shorter in cases of high CD40 expression [> 20% positive cells, relative risk (RR) 2.56, P = 0.02] or high CD11a expression (> 80% positive cells, RR 2.6, P = 0.03). This effect was most prominently present in the AML M4/M5 FAB subgroups. We conclude that the expression levels of adhesion and co-stimulatory molecules, CXCR4 and apoptosis-receptors are predominantly FAB subtype-related with high CD40 and CD11a expression as poor prognostic factors.

Similar myeloid recovery despite superior overall engraftment in NOD/SCID mice after transplantation of human CD34(+) cells from umbilical cord blood as compared to adult sources.

Umbilical cord blood (UCB), bone marrow (BM) and mobilized peripheral blood (mPB) are used as sources of hematopoietic stem cells for transplantation. The NOD/SCID mouse model was used to compare the lineage-specific repopulating potential of CD34(+) cells derived from these sources. Six to 8 weeks after transplantation, blood, BM, spleen, liver and thymus, were harvested, and analyzed by flow cytometry using CD34, CD45, myeloid, and lymphoid lineage-specific antibodies. Fifty percent engraftment of human cells in bone marrow of mice was estimated to be reached with 0.55 x 10(6) CD34(+) UCB cells or with 7.9 x 10(6) CD34(+) cells from adult sources, illustrating a 10-fold superiority of UCB CD34(+) cells to engraft NOD/SCID mice. Lineage-specific characterization of engrafted human cells showed that the high engraftment potential of CD34(+) cells from UCB was due to a preferential B cell development (2-81%). In contrast, comparable percentages of myeloid cells were found following transplantation of CD34(+) cells from UCB, BM and mPB (1-38%), and occurred at significant levels only at relatively high doses. Since the CD34 content of UCB transplants is usually at least one log lower than of transplant from adult sources, these results correspond to the clinical findings with UCB transplantation showing a relatively high overall engraftment, but delayed myeloid recovery.

Quality of life in preschool children born preterm.

The relationship of preterm birth to health-related quality of life (HRQoL) was examined for children aged 1 to 4 years. Three gestational age groups with a NICU history were selected, <32 weeks (n=65), 32 to 36 weeks (n=41), 237 weeks (n=54), and a reference group from the open population (n=50). The main instrument was the TNO-AZL Preschool Quality Of Life (TAPQOL) questionnaire, which was completed by the parents. In addition, other outcome measures obtained from parents or neonatologists were investigated. Children born <32 weeks had significantly lower HRQoL than the reference group in the scales for lungs, stomach, eating disorders, motor functioning, communication, and anxiety. Parental feelings towards the child were related to the child's HRQoL. We found differences between the neonatologists' and parents' perceptions of the children's situation, which can have clinical consequences (e.g. different opinions about what needed treatment). Neonatal intensive care after birth has HRQoL implications for all children, particularly in children born at <32 weeks of gestation.

Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression.

Earlier work has shown that plasma vasopressin levels of depressed patients were higher than those of healthy controls. The aim of the present study was to determine whether plasma vasopressin levels were correlated to parameters of the circadian rhythm. Forty-one patients with major depression and twenty-five controls participated in a case-control design under natural circumstances in a field study to investigate plasma vasopressin levels three times daily, circadian motor activity, and the 24-h periodicity of body temperature for five consecutive 24-h periods. Temperature measurements consisted of at least five, but mostly six or more measurements every 24 h. Twenty-two percent of the patients, but none of the controls lacked 24-h periodicity of body temperature. In melancholic patients increased vasopressin levels in plasma correlated with a weak 24-h periodicity of body temperature. The role of vasopressin is discussed in the light of the present findings.

On the pathogenesis of brain tumour cysts: a volumetric study of tumour, oedema and cyst.

Chemical analysis of brain tumour cyst contents has invalidated the concept of cyst formation being the result of tumour necrosis, and a common mechanism of vasogenic brain oedema and cyst formation, namely blood-brain barrier (BBB) disruption, has been suggested. To analyse a possible relationship between the occurrence of vasogenic oedema and the presence of cysts, we performed a volumetric analysis on the MRI and CT studies of 60 patients with primary or metastatic brain tumours. We compared four groups of tumours: 30 gliomas, of which 15 were cystic and 15 not and 30 metastatic brain tumours of which 15 were cystic and 15 not. Although the mean volume of oedema was similar for cystic and noncystic tumours, the ratio of oedema to tumour volume was approximately four times as high in cystic supratentorial tumours. This would support the view that cyst formation may be related to relatively greater production of oedema, possibly due to fusion of microcysts containing oedema fluid. The ratio of oedema to tumour volume is not greater in cystic cerebellar and intraventricular tumours. This may be due to the different anatomical organization of the cerebellar white matter, and the fact that the intraventricular tumours are bordered by subcortical grey matter. In these cases, spread of oedema is impeded. Formation of a large amount of brain oedema is therefore not an essential prerequisite for cyst formation.

Increased cellularity and expression of adhesion molecules in muscle biopsy specimens from patients with rheumatoid arthritis with clinical suspicion of vasculitis, but negative routine histology.

OBJECTIVE: Histological analysis of random quadriceps muscle biopsy specimens can be used to detect vasculitis in patients with rheumatoid arthritis (RA). This study aimed at determining the immunohistological features in patients with clinical suspicion of rheumatoid vasculitis, but without a transmural infiltrate or fibrinoid necrosis of the vessel wall on routine histology. METHODS: Three groups of patients with RA were studied: (a) without clinical signs of vasculitis (n=6); (b) with recent onset of extra-articular features and a clinical suspicion of vasculitis but normal routine histology (n=11); and (c) with recent onset of extra-articular features and vasculitis, histologically proved either in muscle or other biopsy specimens (n=14). A control group of patients with osteoarthritis was also included (n=5). Frozen sections from quadriceps muscle biopsy specimens were analysed with monoclonal antibodies to detect CD3, CD4, CD8, CD68, ICAM-1, VCAM-1, and HLA-DR. The slides were evaluated using a semiquantitative scoring system (0-4). RESULTS: The mean scores gradually increased from group 1 to 3, leading to significant differences between groups 1 and 2, but not between groups 2 and 3 for most markers (p< 0.05). Thus the pathological changes were similar for the two groups with clinical signs of vasculitis, even when the conventional histological evaluation was negative. Higher immunohistological scores were associated with perivascular infiltrates on routine histology. CONCLUSION: The pathophysiological events leading to vasculitis are reflected by the changes in the quadriceps muscle biopsy specimens. The data indicate that the sensitivity of examination of muscle biopsy specimens for the diagnosis of rheumatoid vasculitis can be increased by the use of new criteria.

Antibody response after influenza vaccination in HIV-infected individuals: a consecutive 3-year study.

In a consecutive 3-year study the antibody response after immunization with influenza vaccine of a cohort of HIV-infected adults was studied. The haemagglutination-inhibiting (HAI) antibody titres after vaccination correlated with the number of CD4(+) T lymphocytes (p<0.001), the prevaccination antibody titres (p<0.001), and the proliferative response to anti-CD3 (p<0.001). Severely impaired antibody responses were observed in HIV-infected individuals with CD4(+) T-lymphocyte counts < or =100x10(6)/l. Significantly higher prevaccination antibody titres were observed in healthy controls in the 2nd or 3rd year of vaccination, but not in HIV-infected individuals. Annually repeated vaccination of HIV-infected individuals did not lead to higher postvaccination antibody titres. Annual vaccination of HIV-infected individuals with CD4(+) T-lymphocyte counts exceeding 100x10(6)/l seems to be worthwhile, although it may not be expected to render the same level of protection against influenza as in non-infected individuals.

Expression and induction of costimulatory and adhesion molecules on acute myeloid leukemic cells: implications for adoptive immunotherapy.

OBJECTIVE: Previously, we observed an increased recognition of malignant cells by cytotoxic T lymphocytes (CTL) when the target cells were cultured in vitro for 24 hours. In this study, we analyzed the expression of costimulatory and adhesion molecules on acute myeloid leukemia (AML) cells and determined whether 24-hour culture of the cells was associated with upregulation of these molecules. We analyzed whether this incubation period improved recognition of AML cells by CTL. MATERIALS AND METHODS: Expression of costimulatory and adhesion molecules on leukemic blasts of 34 patients comprising each AML FAB subclassification were analyzed directly and after 24 hours of culture, and the recognition of these AML cells by an HLA-A2 restricted CTL clone was determined. Blocking studies were performed with antibodies against CD54, CD58, and CD11a. RESULTS: Immunophenotyping showed a low expression of CD80 and CD40 and a variable CD86 expression on most AML cells. CD54 expression was generally low, CD58 expression was high, and CD11a expression was variable, with a higher expression in AML M0, M1, M4, and M5. Twenty-four hours of culture resulted in a significant upregulation of CD40, CD54, and CD58. Impaired recognition of AML cells by the HLA-A2 restricted CTL clone was enhanced 100-200% by 24 hours of preincubation of the leukemic cells. Blocking studies showed the importance of multiple adhesion molecules on the AML cells. CONCLUSION: Low expression of multiple costimulatory and adhesion molecules on AML could be upregulated by 24 hours of culture, which was associated with increased recognition of the AML blasts by CTL. Blocking multiple adhesion molecules completely abolished CTL recognition, showing the importance of the combination of these molecules for T-cell interaction with AML.

The case for completing the lymphadenectomy when positive lymph nodes are found during radical hysterectomy for cervical carcinoma.

BACKGROUND: In the present study we report on the results of a retrospective study on the effect on survival of the pelvic lymphadenectomy in a group of 294 patients with stage Ia2-IIa cervical carcinoma treated by radical hysterectomy from 1984 through 1996 at the Leiden University Medical Center. METHODS: Lymphadenectomy was called 'complete' when lymph node bearing tissue had been removed from 5 or 6 lymph node stations and 'not-complete' when this was the case in 1-4 stations. RESULTS: A radical hysterectomy was carried out in 294 patients. In 63 patients positive lymph nodes were found. Patients with positive nodes showed poorer 5 year survival: 64.5% compared to 90% in patients with negative nodes. In the univariate analysis the following factors were found to affect the presence of node metastases in a statistically significant way: age, tumor size, depth of infiltration, vaso-invasion, surgical margins, parametrial infiltration, stage and place of referral. In 63 patients with positive nodes, a complete lymphadenectomy was carried out in 23 patients, and in 40 patients the procedure was incomplete. All 63 patients were treated by adjuvant radiation therapy; those with complete lymphadenectomy had significantly less recurrences (25%) compared to those with incomplete lymphadenectomy (56%): the relative risk (RR) was 2.9 (95% ci: 1.3-6.7), p=0.012. After adjustment for other prognostic factors including tumor size, depth of infiltration and parametrial involvement, the complete lymphadenectomy showed an independent effect on disease free survival: RR= 3.2 (95% ci: 1.3-7.7), p=0.011. Prognostic factors were not significantly different for patients with complete or incomplete lymphadenectomy. CONCLUSIONS: From the results of this study, although retrospective and non randomized, it can be concluded that to complete removal of lymph nodes in combination with radical hysterectomy seems to have a beneficial effect on prognosis in case of positive nodes. The policy of aborting the procedure when lymph node metastases are found in frozen section should be questioned.

The long learning curve of gynaecological cancer surgery: an argument for centralisation.

OBJECTIVE: To study the development of surgical performance of an unchanging surgical team over 13 years. DESIGN: Prospective, observational study. SETTING: A university hospital, The Netherlands. PARTICIPANTS: Three hundred and eight women who underwent surgical treatment for early cervical cancer. INTERVENTIONS: Radical hysterectomy and pelvic lymphadenectomy between 1 January 1984 and 31 December 1996. RESULTS: The surgical procedure and indication for treatment remained unchanged during the study period. This applied also to the surgical team. The women's age increased significantly during the study years, as was the case with the number of nodes removed. The depth of infiltration by the tumour increased steadily throughout the study, but this failed to reach statistical significance. The distribution of FIGO stages, percentage of positive lymph nodes, radicality of the surgical margins and post-operative morbidity remained the same. Overall, the five year survival rate was 83%; for women with negative nodes 91%, and for women with positive nodes 53%. Survival tended to improve during the course of the study, but this was not statistically significant. Blood loss during surgery decreased consistently during the whole study period, from a mean of 1,515 mL at the beginning of the study to a mean of 1,071 mL at the end (P < 0.0001). The operating time also diminished significantly by 8 minutes per year (P < 0.0001). In 1985 the average operating time was 270 minutes, compared with 187 minutes in 1996. CONCLUSIONS: These findings indicate that it takes a long time to acquire skill in the surgical treatment of early cervical cancer. Centralisation of relatively infrequent operations for cancer should be encouraged.

Phase III efficacy study of interleukin-3 after autologous bone marrow transplantation in patients with malignant lymphoma.

We evaluated the efficacy of recombinant human interleukin-3 (rhIL-3) in reducing the number of platelet transfusions and major infections after autologous bone marrow transplantation (ABMT) in patients with malignant lymphoma. 198 patients with non-Hodgkin's lymphoma (NHL, n = 111) and Hodgkin's disease (HD, n = 87) were randomized to receive rhIL-3 10 microgram/kg/d (n = 130) or placebo (n = 68) for a maximum of 28 d after ABMT. Several well-known conditioning regimens were used. From day 1 after ABMT patients were treated with placebo or rhIL-3 at a dose of 10 microgram/kg/d by continuous i.v. infusion for 7 d and then by s.c. administration for 21 d or until platelet (50 x 109/l) and neutrophil (0.5 x 109/l) recovery had occurred. Treatment was completed in 54% of the patients in the rhIL-3 group versus 75% in the placebo group (P < 0.004). Adverse events were the main reason for premature discontinuation in the IL-3 group (23% IL-3 v 5% placebo). The median number of platelet transfusions was not significantly different between the IL-3 group and the placebo group (8.0 IL-3 v 6.0 placebo, P = 0.09). Platelet engraftment (>/= 20 x 109/l) was not significantly faster in the IL-3 group (28 d in the IL-3 and 27 d in the placebo group, P = 0.06) and the incidence of haemorrhagic complications was similar in both groups. In patients receiving the full intended dose of rhIL-3, platelet engraftment to >/= 20 x 109/l was delayed (P = 0.007). The median time to neutrophil engraftment was 23 d in the IL-3 and 25 d for the placebo group (P = 0.39). There was no difference in the incidence of major infections. We conclude that treatment with IL-3 has no clinical benefit in patients receiving ABMT for malignant lymphoma.

Postsurgical course of patients with congenitally corrected transposition of the great arteries.

Because congenitally corrected transposition is a rare congenital anomaly, little is known about the prognosis of patients with this syndrome. The present study evaluated the functional status and clinical course of 73 patients (42 male and 31 female) aged 10 days to 73 years. Follow-up was 1 week to 37 years (mean 12.7 years). Particular attention was paid to the systemic right ventricle, considering the current controversies about long-term right ventricular function. Survival of patients with this condition in general was significantly below normal. The total mortality rate was 11% (8 patients) after a mean follow-up of 12.7 years (range 10 days to 37 years). Mean age at death was 18.5 years (range 6 days to 63 years). The mean age of the survivors at latest follow-up was 21.4 years (range 4 months to 73 years). In most patients, right ventricular function deteriorated and tricuspid valve regurgitation increased, which began at a very young age. Patients without associated lesions developed complications at a higher age compared with the total group. Right ventricular and tricuspid valvular function deteriorated more frequently in patients following intracardiac operation (28% and 52%, respectively) compared with patients undergoing palliative intervention (16%) or no surgery at all (28%). We conclude that survival of patients with this condition is substantially reduced compared with the natural history of an age- and gender-matched general population. This could be explained by the associated cardiac defects, but also by the anatomic condition itself.

Unified Huntington's disease rating scale: a follow up.

An objective assessment of the clinical findings in patients with Huntington's disease (HD) is necessary for an evaluation of the longitudinal progression of the disease features. The Unified Huntington's Disease Rating Scale (UHDRS) is a scale to assess clinical performance and functional capacity. The authors examined the 1-year change in UHDRS scores in 78 patients with HD examined either in Leiden, the Netherlands (24 men, 25 women), or in Rochester, New York, United States (12 men, 17 women). A significant decline was seen in motor function, measured with the total motor scale. The total dystonia score increased significantly; the total chorea score did not. The frequency of behavioral disorders tended to increase. The scores on independence scale, functional assessment, total functional capacity, and symbol digit decreased significantly. No relation was observed between the UHDRS items and the age at onset or duration of illness. Thirteen patients with 2-year follow up showed a clear increase in score on the total motor scale and a decline on the independence scale and in total functional capacity. The UHDRS may also be used as a tool for determining therapeutic intervention. Annual evaluation of the total motor scale in every patient gives a clear description of the motor progression of the disease. The authors suggest performing a total UHDRS evaluation every second year for every HD patient as part of the routine longitudinal evaluation.