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Fine needle aspiration cytology of metastatic olfactory neuroblastoma.

OBJECTIVE: Olfactory neuroblastoma (ONB) is an uncommon malignant neoplasm that originates in the upper nasal cavity. Cytomorphologic descriptions of ONB have been limited to isolated case reports. The features of a series of metastatic ONB diagnosed by fine needle aspiration (FNA) are described. STUDY DESIGN: Cytologic findings in four patients with ONB metastatic to cervical lymph nodes who underwent FNA were reviewed, and the cytomorphologic findings were summarized. Immunocytochemical findings and ultrastructural features with selected immunoelectron microscopy from three cases are described. RESULTS: Aspiration cytology revealed a predominance of single cells with intermixed small, loosely cohesive, three-dimensional cell groups. Cell size was small to intermediate, with round nuclei. There was an overall monomorphic appearance, with minimal nuclear pleomorphism. Chromatin was finely granular and stippled, with multiple, small chromocenters. Cytoplasm in the cell groups had a fibrillary quality and was moderate in amount. Single nuclei were frequently stripped of cytoplasm. Occasional pseudorosettes were noted. Immunocytochemical stains were positive for both neuronspecific enolase and synaptophysin. Ultrastructural examination showed neuritic cell processes with neurosecretory granules and microtubules. Immunoelectron microscopy showed positive labeling of neurosecretory granules by chromogranin A. CONCLUSION: FNA cytomorphology, in combination with ancillary studies, can provide an accurate diagnosis of metastatic ONB.

Adult↗

Echocardiographic predictors of nonrheumatic atrial fibrillation. The Framingham Heart Study.

BACKGROUND: Although structural heart disease is often present in patients with nonrheumatic atrial fibrillation, the echocardiographic precursors of atrial fibrillation have not been reported previously. In this elderly, population-based cohort, our objective was to examine prospectively the echocardiographic predictors of nonrheumatic atrial fibrillation. METHODS AND RESULTS: Subjects in the Framingham Heart Study were routinely evaluated with M-mode echocardiography; 1924 subjects, ranging in age from 59 to 90 years, comprised the population at risk. Cox proportional hazards modeling was used to analyze the association of selected echocardiographic features with atrial fibrillation risk after adjustment for age, sex, hypertension, coronary heart disease, congestive heart failure, diabetes, and valvular heart disease. During a mean follow-up interval of 7.2 years, 154 subjects (8.0%) developed atrial fibrillation. Multivariable stepwise analysis identified left atrial size (hazard ratio [HR] per 5-mm increment, 1.39; 95% confidence interval [CI], 1.14 to 1.68), left ventricular fractional shortening (HR per 5% decrement, 1.34; 95% CI, 1.08 to 1.66), and sum of septal and left ventricular posterior wall thickness (HR per 4-mm increment, 1.28; 95% CI, 1.03 to 1.60) as independent echocardiographic predictors of atrial fibrillation. For each of the echocardiographic predictors, risk increased progressively over successive quartiles. Moreover, risk increased markedly when highest-risk-quartile measurements for these features were present in combination; the cumulative 8-year age-adjusted atrial fibrillation rates were 7.3% and 17.0%, respectively, when one and two or more highest-risk-quartile features were present, compared with 3.7% when none was present. CONCLUSIONS: In this elderly, population-based sample, left atrial enlargement, increased left ventricular wall thickness, and reduced left ventricular fractional shortening were predictive of risk for nonrheumatic atrial fibrillation. These echocardiographic precursors offer prognostic information beyond that provided by traditional clinical atrial fibrillation risk factors.

Adult↗

[The revised homology].

Many different and even contrasting notions of homology have been proposed over two centuries of comparative biology, beginning beginning with the initial reference to idealised archetypes, down to the current concepts based on derivation from a common ancestor, or on shared developmental pathways or genetic (more extensively, informational) background. Select anatomical features such as the patterns of innervation, or the expression patterns of genes putatively involved in key developmental events, e.g. the Hox genes, have been repeatedly suggested as the most reliable cues to homology. This confidence, however, rests on shaky ground and results are never certain. Recent work in comparative morphology and evolutionary developmental biology increasingly suggests the need to abandon the traditional all-or-nothing notion of homology, in favour of a more flexible, factorial or combinatorial approach. In this way it will be possible to accommodate within one broad comparative view, respectful of phylogeny and developmental biology alike, many disparate notions such as positional and special homology, serial homology and temporal serial homology. All statements of homology, however, will thus require inadequate qualification of the context specifically taken in consideration and the criteria used to address the comparison. It remains to be seen, in the near future, how far the old concept of homology, now under the burden of so many and so different notions, will still be of use to comparative biology.

Biology↗

Finite element modeling of optic nerve head biomechanics.

PURPOSE: Biomechanical factors have been implicated in the development of glaucomatous optic neuropathy, particularly at the level of the lamina cribrosa. The goal of this study was to characterize the biomechanics of the optic nerve head using computer modeling techniques. METHODS: Several models of the optic nerve head tissues (pre- and postlaminar neural tissue, lamina cribrosa, central retinal vessel, sclera, and pia mater) were constructed. Stresses, deformations, and strains were computed using finite element modeling for a range of normal and elevated intraocular pressures. Computed retinal surface deformations were compared with measured deformation patterns in enucleated human eyes. A sensitivity analysis was performed in which tissue properties and selected geometric features were varied. RESULTS: Acute IOP-induced deformation of the vitreoretinal interface was highly dependent on optic cup shape but showed a characteristic "W-shaped" profile that did not match the deformation of the anterior surface of the lamina cribrosa. The central retinal vasculature had surprisingly little effect on optic nerve head biomechanics. At an IOP of 50 mm Hg, strains (fractional elongation) in the lamina cribrosa averaged 4% to 5.5%, dependent on model geometry, with maximum strains up to 7.7%. Strains in the lamina cribrosa were more dependent on scleral stiffness, scleral thickness, and scleral canal diameter than on lamina cribrosa stiffness and optic cup shape. CONCLUSIONS: Computed levels of strain in the lamina cribrosa are biologically significant and capable of contributing to the development of glaucomatous optic neuropathy, even without considering the probable accentuating effect of the lamina cribrosa's microarchitecture. Depending on optic cup shape, IOP-induced deformation of the vitreoretinal interface may not match lamina cribrosa deformation. This finding implies that scanning laser tomography has limited ability to estimate lamina cribrosa deformation when imaging the anterior topography of the optic nerve head. Biomechanical effects in the lamina cribrosa depend strongly on scleral properties.

Elasticity↗

Breast tissue classification using diagnostic ultrasound and pattern recognition techniques: II. Experimental results.

The methods of statistical pattern recognition have been applied to the problem of in vivo ultrasonic characterization of breast disease in humans. Backscattered A-mode signals obtained from a commercial pulse imaging system were used to generate a large set of potentially useful features. Using statistical tests, a small subset of discriminatory features was selected to design a Bayes decision rule for each of two tissue classification schemes: malignant disease vs. benign disease, and malignant disease vs. (benign disease + normal tissue). Classification results obtained by the rotation method included sensitivities of 88 percent and 76 percent for the two schemes, based on data obtained from 32 women. These results are encouraging, though a definitive statement concerning the extrapolation of these numbers to the general population should only be made after obtaining results with a large data base.

Breast Diseases↗

A trial of benorylate tablets in the symptomatic relief of osteoarthritis.

A two-week assessment of Benoral tablets was carried out in general practice in 171 patients with degenerative joint disease to see how symptomatic response related to selected presenting features of the disease. A short history, less severe initial state and multiple joint involvement were each associated with a better response. Overall 84-4% of patients reported Benoral tablets to have helped relieve their symptoms and a high proportion preferred Benoral to their previous anti-arthritic medication.

Adolescent↗

DSM-III in residency training: results of a Canadian survey.

The authors surveyed directors of residency training as well as residents across Canada to determine the extent to which DSM-III has been incorporated into the Canadian psychiatric residency training programs, how this has been accomplished, and the respondents' assessment of certain effects of DSM-III on residency training. This study is a replication of an earlier study done by another team in the United States. Our study indicates that, in most cases, the attitude towards DSM-III was positive: 100% of respondents described the system as useful or somewhat useful in the training settings. The most frequently selected positive features were its value as a common language, an aid in differential diagnosis, its empirical approach and specificity or clarity of the criteria. The criticisms frequently centred on the DSM-III's potential to induce a false impression of all encompassing theoretical knowledge, to be misused in a mechanistic manner as a "cookbook", and on the DSM-III's inadequacy with some patients (for example, children, neurotic disorders, and personality disorders).

Attitude of Health Personnel↗

The role of qualitative methods for investigating barriers to adult immunization.

In 1999, the Agency for Healthcare Research and Quality funded a study of barriers to immunization, which included a short-term qualitative data collection to assess the organizational and cultural features of selected primary care practices and to explore their impact on adult immunization rates. The authors describe the short-term qualitative data collection system and the contributions made by the qualitative study to the parent project. They address previously held concerns about qualitative research and provide a system that can be replicated or modified for use for projects designed to assess complex attitudes and behaviors that affect health outcomes.

Adult↗

Chernoff faces: an orthodontic application.

This retrospective study examined 21 children (12 males and nine females) with Class III malocclusions, who had been successfully treated by a non-extraction technique and for whom follow-up records were available at least 2 years after all treatment and retention had ceased. On the basis of their post-retention records, children were divided into two groups: those who remained stable (n = 10) and those whose treatment relapsed (n = 11). A graphical technique of data description, Chernoff faces, in which variables for each individual may be portrayed by appropriate scaling of selected facial features, was used to construct cartoon faces for each child. Seven variables, overjet, overbite, upper and lower incisor inclination, the numbers of anterior and posterior teeth in lingual occlusion and the angle ANB were chosen and diagrammatic faces drawn using data from both the start of treatment and post-retention stages. These were arranged according to relapse status and scrutinized to determine whether the groups possessed any common features which were related to the outcome of treatment. The faces showed a wide range of variation, especially at the pretreatment stage. Whilst the cartoons were easy to read, no typical features could be identified at the start of treatment which might indicate that therapy would later relapse.

Adolescent↗

Novel therapeutic approaches in sickle cell disease.

In this update, selected clinical features of sickle cell disease and their management are reviewed. In addition, the current status of interventions that have curative potential for sickle cell disease is discussed, with particular attention focused on indications, methodology, recent results, and challenges to wider clinical application. In Section I, Dr. Nienhuis describes recent improvements in vector technology, safety, and replacement gene expression that are creating the potential for clinical application of this technology. In Section II, Dr. Vichinsky reviews our current understanding of the pathophysiology and treatment of pulmonary injury in sickle cell disease. The acute and chronic pulmonary complications of sickle cell disease, modulators and predictors of severity, and conventional and novel treatment of these complications are discussed. In Section III, Dr. Walters reviews the current status of hematopoietic cell transplantation for sickle cell disease. Newer efforts to expand its availability by identifying alternate sources of stem cells and by reducing the toxicity of transplantation are discussed.

Anemia, Sickle Cell↗

Patients' perspectives on high-tech home care: a qualitative inquiry into the user-friendliness of four technologies.

BACKGROUND: The delivery of technology-enhanced home care is growing in most industrialized countries. The objective of our study was to document, from the patient's perspective, how the level of user-friendliness of medical technology influences its integration into the private and social lives of patients. Understanding what makes a technology user-friendly should help improve the design of home care services. METHODS: Four home care interventions that are frequently used and vary in their technical and clinical features were selected: Antibiotic intravenous therapy, parenteral nutrition, peritoneal dialysis and oxygen therapy. Our qualitative study relied on the triangulation of three sources of data: 1) interviews with patients (n = 16); 2) interviews with carers (n = 6); and 3) direct observation of nursing visits of a different set of patients (n = 16). Participants of varying socioeconomic status were recruited through primary care organizations and hospitals that deliver home care within 100 km of Montreal, the largest urban area in the province of Quebec, Canada. RESULTS: The four interventions have both a negative and positive effect on patients' lives. These technologies were rarely perceived as user-friendly, and user-acceptance was closely linked to user-competence. Compared with acute I.V. patients, who tended to be passive, chronic patients seemed keener to master technical aspects. While some of the technical and human barriers were managed well in the home setting, engaging in the social world was more problematic. Most patients found it difficult to maintain a regular job because of the high frequency of treatment, while some carers found their autonomy and social lives restricted. Patients also tended to withdraw from social activities because of social stigmatization and technical barriers. CONCLUSIONS: While technology contributes to improving the patients' health, it also imposes significant constraints on their lives. Policies aimed at developing home care must clearly integrate principles and resources supporting the appropriate use of technology. Close monitoring of patients should be part of all technology-enhanced home care programs.

Adult↗

An active electrode for biopotential recording from small localized bio-sources.

BACKGROUND: Laser bio-stimulation is a well-established procedure in Medical Acupuncture. Nevertheless there is still a confusion as to whether it works or the effect is just placebo. Although a plethora of scientific papers published, showing positive clinical results, there is still a lack of objective scientific proofs about the bio-stimulation effect of lasers used in Acupuncture. The objective of this work was to design and build a body surface electrode and an amplifier for biopotential recording from acupuncture points, considered here as small localized bio-sources (SLB). The design is aimed for studying SLB potentials provoked by laser stimulus, in search for objective proofs of the bio-stimulation effect of lasers used in Medical Acupuncture. METHODS: The active electrode presented features a new adjustable anchoring system and fractionation of the biopotential amplifier between the electrode and the cabinet's location. The new adjustable electrode anchoring system is designed to reduce the electrode-skin contact impedance, its variation and motion artifacts. That is achieved by increasing the electrode-skin tension and decreasing its relative movement. Additionally the sensing element provides local constant skin stretching thus eliminating the contribution of the skin potential artifact. The electrode is attached to the skin by a double-sided adhesive pad, where the sensing element is a stainless steel, 4 mm in diameter. The fractionation of the biopotential amplifier is done by incorporating the amplifier's front-end op-amps at the electrodes, thus avoiding the use of extra buffers. The biopotential amplifier features two selectable modes of operation: semi-AC-mode with a -3 dB bandwidth of 0.32-1000 Hz and AC-mode with a bandwidth of 0.16-1000 Hz. RESULTS: The average measured DC electrode-skin contact impedance of the proposed electrode was 450 kOmega, with electrode tension of 0.3 kg/cm2 on an unprepared skin of the inner forearm. The peak-to-peak noise voltage measured at the amplifier output, with input terminals connected to common, was 10 mVp-p, or 2 microVp-p referred to the input. The common-mode rejection ratio of the amplifier was 96 dB at 50 Hz, measured with imbalanced electrodes' impedances. The prototype was also tested practically and sample records were obtained after a low intensity SLB laser stimulation. All measurements showed almost a complete absence of 50 Hz interference, although no electrolyte gel or skin preparation was applied. CONCLUSION: The results showed that the new active electrode presented significantly reduced the electrode-skin impedance, its variation and motion artifact influences. This allowed SLB signals with relatively high quality to be recorded without skin preparation. The design offers low noise and major reduction in parts, size and power consumption. The active electrode specifications were found to be better or at least comparable to those of other existing designs.

Acupuncture Points↗

HIV-1 compartmentalization in diverse leukocyte populations during antiretroviral therapy.

CD4+ T lymphocytes are the primary target of human immunodeficiency virus type 1 (HIV-1), but there is increasing evidence that other immune cells in the blood, including CD8+ T lymphocytes and monocytes, are also productively infected. The extent to which these additional cellular reservoirs contribute to ongoing immunodeficiency and viral persistence during therapy remains unclear. In this study, we conducted a detailed investigation of HIV-1 diversity and genetic structure in CD4+ T cells, CD8+ T cells, and monocytes of 13 patients receiving highly active antiretroviral therapy (HAART). Analysis of molecular variance and nonparametric tests performed on HIV-1 envelope sequences provided statistically significant evidence of viral compartmentalization in different leukocyte populations. Signature pattern analysis and predictions of coreceptor use provided no evidence that selection arising from viral tropism was responsible for the genetic structure observed. Analysis of viral genetic variation in different leukocyte populations demonstrated the action of founder effects as well as significant variation in the extent of genetic differentiation between subpopulations among patients. In the absence of evidence for leukocyte-specific selection, these features were supportive of a metapopulation model of HIV-1 replication as described previously among HIV-1 populations in the spleen. Compartmentalization of the virus in different leukocytes may have significant implications for current models of HIV-1 population genetics and contribute to the highly variable way in which drug resistance evolves in different individuals during HAART.

Anti-Retroviral Agents↗

Amnesia: organic and psychogenic.

This paper describes the clinical features of selected examples of organic and psychogenic amnesia, and it discusses the nature of the dysfunction that these amnesias entail. The anterograde component of organic amnesia involves a severe impairment in acquiring (or learning) new information, rather than accelerated forgetting, and this may reflect an underlying limbic or neurochemical dysfunction. Retrograde amnesia has a basis which is (at least partially) independent of anterograde amnesia--in some patients, it appears to involve a failure to reconstruct past experience from contextual cues, and this may reflect a super-imposed frontal dysfunction. Two types of confabulation are discussed, one of which ('provoked') is a normal response to poor memory, and the other ('spontaneous') appears to reflect incoherent, context-free retrieval, associated with more severe frontal pathology. It is argued that many cases of psychogenic amnesia may resemble organic amnesia, in that they result from an impaired acquisition of information at the time of initial input, perhaps thereby predisposing the subject to subsequent retrieval difficulties.

Amnesia↗

Expression of the insulin-like growth factor-I receptor and proapoptotic Bax and Bak proteins in human colorectal cancer.

Insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR), despite their well-known roles in cell survival and proliferation, can also weakly enhance apoptosis. To study the relationships between the IGF-IR and Bax as well as Bak, 144 cases of colorectal cancer were examined by immunohistochemistry, using the avidin-biotin-peroxidase method. The results were correlated with selected clinicopathological features of colorectal cancer and with the expression of IGF-IR, Bax, and Bak in normal colon mucosa. In Bax-, Bak-, or IGF-IR-positive cancers, the adjacent colorectal mucosa revealed positive immunostaining for these proteins. In the majority of Bax-, Bak-, or IGF-IR-negative tumors, we observed no staining for these proteins in adjacent mucosa. The strong immunostaining for IGF-IR, Bax, and Bak was noted in 50.8, 55.5, and 49.3% of tumors, respectively. We observed positive correlations between IGF-IR and Bax (P < 0.002, r = 0.302), between IGF-IR and Bak (P < 0.0001, r = 0.407), and between Bax and Bak (P < 0.0001, r = 0.474). No relationship was noted between IGF-IR expression and tumor grade, stage, or lymph node status. We found negative associations between Bax, Bak, and tumor grade (P < 0.01 and P < 0.003, respectively), but no relationships between Bax and Bak and tumor stage or between Bax and Bak and lymph node status. Our results demonstrate that, in addition to overexpressed IGF-IR, there are relationships between IGF-IR and proapoptotic proteins in colorectal carcinomas that could contribute to increased cell turnover and the progression of colorectal cancer.

Adult↗

Population-based molecular detection of hereditary nonpolyposis colorectal cancer.

PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of individuals with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, creating a need to identify HNPCC. We studied how HNPCC identification should be carried out on a large scale in a sensitive and efficient manner. PATIENTS AND METHODS: Colorectal cancer specimens from consecutive newly diagnosed patients were studied for microsatellite instability (MSI). Germline mutations in the MLH1 and MSH2 genes were searched for in MSI(+) individuals. RESULTS: Among 535 colorectal cancer patients, 66 (12%) were MSI(+). Among these, 18 (3.4% of the total) had disease-causing germline mutations in MLH1 or MSH2. Among these 18 patients, five were less than 50 years old, seven had a previous or synchronous colorectal or endometrial cancer, and 15 had at least one first-degree relative with colorectal or endometrial cancer. Notably, 17 (94%) of 18 patients had at least one of these three features, which were present in 22% of all 535 patients. Combining these data with a previous study of 509 patients, mutation-positive HNPCC accounts for 28 (2.7%) of 1,044 cases of colorectal cancer, predicting a greater than one in 740 incidence of mutation-positive individuals in this population. CONCLUSION: Large-scale molecular screening for HNPCC can be done by the described two-stage procedure of MSI determination followed by mutation analysis. Efficiency can be greatly improved by using three high-risk features to select 22% of all patients for MSI analysis, whereby only 6% need to have mutation analysis. Sensitivity is only slightly impaired by this procedure.

Adult↗

Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy.

PURPOSE: Several new prognostic factors predicting rapid disease progression in chronic lymphocytic leukemia (CLL) have been identified, including unmutated Ig V(H) mutational status, del(11)(q23), del(17)(p13.1), and p53 mutations. To date, the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy. METHODS: We examined the impact of these new prognostic factors on predicting treatment outcome in symptomatic, untreated CLL patients who received chemoimmunotherapy with fludarabine and rituximab as part of a completed, randomized phase II study, Cancer and Leukemia Group B (CALGB) 9712. RESULTS: Eighty-eight patients treated as part of CALGB 9712 had detailed prognostic factor assessment performed. Using Ig V(H) mutational status to classify risk, there was no association between complete response rate with either unmutated Ig V(H) mutational status or high-risk interphase cytogenetics. However, the median progression-free survival (PFS; P = .048) and overall survival (OS; P = .01) were shorter among the Ig V(H) unmutated patients as compared with the Ig V(H) mutated patients. Using the hierarchical classification of Döhner, PFS (P = .005) and OS (P = .004) were significantly longer as the classification moved from high risk [del (11)(q22.3) or del (17)(p13.1)] to low risk. CONCLUSION: These data demonstrate that high-risk CLL patients characterized by Ig V(H) unmutated (> or = 98%) or high-risk interphase cytogenetics, including either del(17p) or del(11q), appear to have a shorter PFS and OS with chemoimmunotherapy. Larger prospective studies will be required to determine the independent influence of Ig V(H) mutational status and interphase cytogenetics on treatment outcome.

Adult↗

A laparoscopy-based score to predict surgical outcome in patients with advanced ovarian carcinoma: a pilot study.

BACKGROUND: Our objective was to set up a more objective quantitative laparoscopy-based model in predicting the chances of optimal cytoreductive surgery in advanced ovarian cancer patients. METHODS: Sixty-four advanced ovarian cancer patients were submitted to both laparoscopy and standard longitudinal laparotomy sequentially, to define the chances of optimal debulking surgery (residual disease < or = 1 cm). Three patients could not be evaluated by laparoscopy because of the presence of multiple and tenacious adherences. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each laparoscopic parameter. On the basis of the statistical probability of each factor to predict surgical outcome, seven laparoscopic features were selected for inclusion in the final model. Each parameter was assigned a numerical score based on the strength of statistical association, and a total predictive index value was tabulated for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict surgical outcome. RESULTS: After debulking surgery, 41 (67.2%) of 61 patients were left with optimal residual disease. The presence of omental cake, peritoneal carcinosis, diaphragmatic carcinosis, mesenteric retraction, bowel and/or stomach infiltration, and liver metastases satisfied the basic inclusion criteria and were assigned a final predictive index value of 2. In the final model, a predictive index score > or = 8 identified patients undergoing suboptimal surgery with a specificity of 100%. The positive predictive value was 100%, and the negative predictive value was 70%. CONCLUSIONS: The reliability of laparoscopy in assessing the chance of optimal cytoreduction can be improved by using a simple scoring system.

Female↗