Dimensional measures of psychopathology. The probability of being classified with a psychiatric disorder using empirically derived symptom scales

Objectives: We sought to develop a ranking scheme that assigns a probability of having one of four psychiatric disorders to children based on their scores on a symptom scale. We then estimated the impact of each scale symptom on the prevalence of the disorder in the population. Method: Logistic regressions were specified for ADHD, ODD, depressive, and conduct disorders using all the individual symptoms in the pertinent scale as predictors. Individual fitted values from the regression function then served as a probability scale measure. We combined the prevalence and influence of each scale symptom to calculate its overall impact on the prevalence of the disorder. Results: Probability distributions had a wide range of values and discriminated between cases and non-cases. Those having a disorder were consistently associated with higher probabilities in the scale. The estimated probability corresponds to the empiric prevalence of the diagnosis in a group of persons sharing the same estimated probabilities. Symptoms varied on their impact on the prevalence of the disorder. Conclusions: We recommend the estimated probability of the disorder based on the empirically defined scales as dimensional measures that complement prevalence of the disorder. Different symptoms are identified as targets for screening when selection is based on their impact on the prevalence of the disorder than when selection is based on the strength of the association with the disorder. We recommend using a common nosology with different classification schemes; the categorical definition of the disorder, the probability of having the disorder, and the impact of each symptom in the prevalence. Different measures serve different purposes. Accepted: 5 April 2002 Correspondence to Maritza Rubio-Stipec     

The Marchetti-Vincenzi humeral nail--a useful device in fresh fractures

Whilst most humeral fractures may be treated by closed methods, humeral nailing has gained popularity where a surgical option is indicated. Concern has been expressed regarding placement of proximal and distal locking screws whilst the efficiency of the ingenious intra-medullary locking device of the Seidel nail has also been questioned. The Marchetti-Vincenzi nail, which "locks" proximally with the spreading of intra-medullary pins and distally with a single screw inserted via the surgical wound, apparently avoids potential neurovascular and tendon injury.Prospectively recorded data was analysed in 19 "fresh" fractures, i.e. within 3 weeks of injury, and in 13 "late" fractures (total of 32 humeral fractures) treated with the Marchetti nail. All fresh fractures thus treated progressed to union, whilst in the late fracture group there were three non-unions all of whom were in osteoprotic females.Whilst we commend the use of the Marchetti humeral nail in fresh fractures, we have reservations about its use in "late" fractures particularly where the patient is female and osteoporotic.     

Conversion of a fused hip to total hip arthroplasty

BACKGROUND: Arthrodesis of the hip remains a viable treatment for severe unilateral arthritis after traumatic injury or infection in a young but otherwise healthy individual. The goal of the present study was to review the long-term clinical and radiographic results after conversion of a fused hip to a total hip arthroplasty and to identify the risk factors that would lead to a higher rate of failure. METHODS: We performed a retrospective review of the charts and radiographs of 187 patients (208 hips) who had conversion of a fused hip to a total hip arthroplasty. The mean duration of follow-up after the conversion to total hip arthroplasty was 9.2 years (range, two to twenty-six years). RESULTS: The mean age at time of the arthroplasty was fifty-one years. The mean time-interval between the arthrodesis and the conversion to a total hip arthroplasty was twenty-seven years. According to the information in the charts, at a mean duration of follow-up of 9.2 years after the total hip arthroplasty, 79% of hips were either pain-free or had minimal pain, 83% had good-to-excellent function, and 79% had good-to-excellent range of motion. Complications, which included fifteen nerve palsies, occurred in twenty-four hips. Twenty-eight hips had heterotopic ossification, but it was not associated with a recurrence of ankylosis or a marked reduction of motion. Revision arthroplasty was performed in twelve hips. The probability of survival of the implant was 96.1% (95% confidence interval, 91.5% to 98.2%) at ten years, 89.9% (95% confidence interval, 85.3% to 96.1%) at fifteen years, and 72.8% (95% confidence interval, 36% to 90.6%) at twenty-six years. CONCLUSIONS: Conversion of a fused hip to a total hip arthroplasty has a favorable outcome. However, the technically demanding nature of the procedure should not be underestimated. Patients should be cautioned with regard to the possibility of a higher rate of complications than that seen with primary total hip arthroplasty.     

Identification and evaluation of existing nursing homes quality indicators

We summarize work done to identify and evaluate existing quality indicators (QIs) for long-term care (LTC) settings. Indicators operationally defined using routinely collected and computerized patient assessments were identified and then aggregated to characterize the performance of the nursing facility over a specific period of time. Of 143 indicators reviewed, only 22 were recommended for use in comparing performance across facilities. Conceptual and technical issues influence the appropriateness of QIs for different audiences.     

Induction of HLA-A2-restricted CTL responses by a tubular structure carrying human melanoma epitopes

Epitope-based vaccination strategies designed to induce strong tumor-specific CD8(+) T cell responses are being widely considered for cancer immunotherapy. Here, two recombinant tubular structures, NS1-Mela 1 and NS1-Mela 2, carrying, respectively two HLA-A2 epitopes derived from human melanoma antigens were constructed and their capability to induce CTL responses in vivo were studied in HLA-A2 transgenic mice. Strong CTL responses specific for GnT-V/NA 17-A and gp100 (154-162) epitopes were generated in HLA-A2 transgenic mice immunized by the construct NS1-Mela l carrying these two epitopes. The second construct NS1-Mela 2 carrying both Tyrosinase (369-377Da) and Melan-A/Mart-1 (27-35) epitopes induced a weak Tyrosinase-specific CTL response in mice but failed to induce specific CTL responses against the Melan-A/Mart-1 (27-35) epitope in the tested mice. Thus, recombinant tubular structures containing multiple tumoral epitopes may lead to new strategies for the induction of strong tumor-specific CTL responses in cancer patients.     

The recombinant chimeric human parainfluenza virus type 1 vaccine candidate, rHPIV3-1cp45, is attenuated, immunogenic, and protective in African green monkeys

A recombinant live-attenuated chimeric human parainfluenza virus type 1 (HPIV1) candidate vaccine was previously generated by replacing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein open reading frames (ORFs) of the HPIV3 candidate vaccine, rHPIV3cp45, with those of wild-type HPIV1. Previously, this recombinant chimeric virus, designated rHPIV3-1cp45, exhibited a greater level of the temperature sensitivity of replication in vitro and a greater level of attenuation of replication in the respiratory tract of immunized hamsters when compared to its HPIV3cp45 parent virus. In the present study, rHPIV3-1cp45 was evaluated for its level of attenuation and efficacy in African green monkeys (Cercopithecus aethiops), a primate in which both HPIV1 and HPIV3 wild-type viruses replicate efficiently. The rHPIV3-1cp45 candidate vaccine was as restricted in replication in the upper and lower respiratory tract as its thoroughly characterized rHPIV3cp45 parent indicating that the attenuating mutations present in the rHPIV3cp45 backbone specified an appropriate level of attenuation of rHPIV3-1cp45 for primates. The level to which rHPIV3-1cp45 replicated in the respiratory tract of African green monkeys was also sufficient to induce a strong immune response to HPIV1 and provided protection against challenge with wild-type HPIV1. These results provide a basis for further evaluation of this HPIV1 candidate vaccine in humans.     

Tumor volume as a prognostic factor for sarcomatosis

BACKGROUND: The appropriate therapeutic interventions for sarcomatosis, or sarcoma characterized by intraabdominal dissemination, remain unclear. The authors performed a retrospective analysis of their recent experience with patients diagnosed with sarcomatosis to determine the overall survival and the effects of clinicopathologic features on survival rates at two and four years. METHODS: A query of the authors' prospective soft tissue sarcoma database identified 51 patients with a diagnosis of sarcomatosis who were evaluated at the authors' institution between June 1996 and June 1999. Clinical and pathologic factors were evaluated, and survival was calculated using a Kaplan-Meier survival analysis. Disease was categorized as low or high volume based on findings at surgical exploration or computed tomography scan evaluation. Disease was classified as low/intermediate grade or high grade based upon histologic examination. RESULTS: Twenty five patients were male and 26 were female. The median time from the initial diagnosis of sarcoma to the development of sarcomatosis was 0.9 years (range, 0-26 years). Thirty nine patients were treated with surgery, whereas 32 received primarily nonsurgical treatment. Histology revealed gastrointestinal stromal tumor (GIST) in 33 patients and other histologies in 18 patients. The two year overall survival rate of patients with GIST was similar to that of patients with other types of sarcoma (38% versus 42%, respectively, P = 0.77). Patients with low volume disease had an overall two year survival rate of 82%, compared with only 24% for patients with high volume disease (P = 0.008). There was no difference in the overall survival rates of patients with low grade (n = 18) versus high grade tumors (n = 33, P = 0.29). With a median followup of 2.7 years (range, 0.5-26.4 years), the median time from sarcomatosis to death was 13 months (range, 4-42 months). CONCLUSIONS: Evaluating volume of disease at the time of diagnosis permits stratification of patients into prognosis based subsets. We found no significant difference in two or four year survival rates in patients with GIST and those with non-GIST sarcomatosis.     

Evaluation of candidate genes MAP2K4, MADH4, ACVR1B,and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%

It is estimated that familial aggregation and genetic susceptibility play a role in as many as 10% of pancreatic ductal adenocarcinomas. To investigate the role of germ-line mutations in the etiology of pancreatic cancer, we have analyzed samples from patients with pancreatic cancer enrolled in the NFPTR for mutations in four tumor suppressor candidate genes: (a) MAP2K4; (b) MADH4; (c) ACVR1B; and (d) BRCA2 by direct sequencing of constitutional DNA. These genes are mutated in clinically sporadic pancreatic cancer, but germ-line mutations are either not reported or anecdotal in familial pancreatic cancer. Pancreatic cancer patient samples were selected from kindreds in which three or more family members were affected with pancreatic cancer, at least two of which were first-degree relatives. No mutations were identified in mitogen-activated protein kinase kinase 4 (0 of 22), MADH4 (0 of 22), or ACVR1B (0 of 29), making it unlikely that germ-line mutations in these genes account for a significant number of inherited pancreatic cancers. BRCA2 gene sequencing identified five mutations (5 of 29, 17.2%) that are believed to be deleterious and one point mutation (M192T) unreported previously. Three patients harbored the common 6174delT frameshift mutation, one had the splice site mutation IVS 16-2A > G, and one had the splice site mutation IVS 15-1G > A. Two of the five BRCA2 mutation carriers reported a family history of breast cancer, and none reported a family history of ovarian cancer. These findings confirm the increased risk of pancreatic cancer in individuals with BRCA2 mutations and identify germ-line BRCA2 mutations as the most common inherited genetic alteration yet identified in familial pancreatic cancer.     

N-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and suppresses neuroblastoma tumor growth

Angiogenesis is an indispensable prerequisite for the progression and metastasis of solid malignancies. Tumor angiogenesis appears to be governed by alterations of tumor suppressor or oncogenes operant in a broad range of tumors. We have addressed this issue in neuroblastoma, a malignancy characterized by the near-exclusive amplification and overexpression of the N-Myc oncogene. Here, we report that N-Myc overexpression results in down-regulation of interleukin-6 (IL-6) and that IL-6 is an inhibitor of endothelial cell proliferation and VEGF-induced rabbit corneal angiogenesis. STAT3 is instrumental for IL-6 activity as infection with adenoviruses expressing a phosphorylation deficient STAT3 mutant renders endothelial cells insensitive to the antiproliferative action of IL-6. Finally, though IL-6 does not influence neuroblastoma cell growth, IL-6-expressing xenograft tumors in mice exhibit reduced neovascularization and suppressed growth. Our data shed new light on the mechanisms by which N-myc oncogene amplification enhances the malignant phenotype in neuroblastomas.