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Biomedical subjects

S Jacobson

Publications and source records attributed to S Jacobson.

At least 19 recordsLinked to original sources

Longitudinal studies of the duplication form of Charcot-Marie-Tooth polyneuropathy.

This study presents a longitudinal comparison of motor nerve conduction velocities (MCVs) in patients with Charcot-Marie-Tooth type 1A with proven duplication of a segment of chromosome 17p11.2p12. Results were compared for 8 CMT1A duplication patients from one family whose MCV measurements were taken 22 years apart (1967 and 1989). Measurements from a total of seven median motor and five peroneal motor MCVs were compared. Median MCVs showed a slight reduction that averaged 2.2 m/s, and peroneal MCVs showed an average decrease of 3.0 m/s. In addition, mild objective increase in limb weakness was seen in only 1 of 8 patients and subjective symptoms of gradual worsening of leg strength were noted in half the patients over the same period. In this study of a small group of CMT1A patients with proven segmental duplication of chromosome 17p11.2p12, the motor conduction velocities and clinical motor exam did not change significantly over 22 years.

Adolescent

Detection of human T-lymphotropic virus type I (HTLV-I) tax RNA in the central nervous system of HTLV-I-associated myelopathy/tropical spastic paraparesis patients by in situ hybridization.

Autopsy specimens from 3 patients with human T-lymphotropic virus (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were examined for the presence of HTLV-I in the central nervous system (CNS). In situ hybridization using an HTLV-I tax RNA probe detected cells containing HTLV-I RNA in spinal cord and cerebellar sections. HTLV-I infected cells were located within the white matter and, in particular, within the anterior and lateral funiculi of the spinal cord. Consistent with previously described HAM/TSP pathology, there were perivascular infiltrates in these CNS specimens. Significantly, HTLV-I RNA was not localized to these infiltrates but was detected deeper within the neural tissue. Furthermore, phenotypic analysis demonstrated that at least some of the infected cells were astrocytes. While previous polymerase chain reaction studies have demonstrated the presence of proviral HTLV-I in CNS specimens, here we provide evidence for the in situ expression of HTLV-I RNA in the CNS of HAM/TSP patients.

Aged

Human T lymphotropic virus, type-I myelopathy: an immunopathologically mediated chronic progressive disease of the central nervous system.

The human T lymphotropic virus, type-I is associated with a slowly progressive neurologic disorder termed human T lymphotropic virus, type-I associated myelopathy/tropical spastic paraparesis. Considerable information on the pathology, epidemiology, virology, and immunology is known about this disorder and will serve as a framework to define the role that a human retrovirus can play in human disease. In particular, this review will discuss the role of cellular immune responses to the virus in patients with human T lymphotropic virus, type-I associated myelopathy/tropical spastic paraparesis and how these responses may be associated with the pathogenesis of this disorder. By defining virus-specific functional cellular host responses we hope to improve our understanding of the underlying mechanisms that may be involved in the neuropathology of human T lymphotropic virus, type-I associated neurologic disease.

Adult

Culture sensitivity in assessing urban Native American parenting.

Assessing urban Native American (NA) parenting remains a challenge for public health nurses. This study explored the effectiveness of using the NCATS and HOME instruments with urban NA mothers and their children. Scores for 63 sets of mothers and their children age 3 months to 3 years on the home observation for measurement of the environment (HOME) and nursing child assessment teaching scale (NCATS) instruments were compared with norms for those instruments. Scores were lower than the norms on the play and involvement subscales of the HOME, and higher than the norms on the total parent, clarity of cues, response to parent, and total child subscales of the NCATS. Analysis of responses to specific items indicated that these mothers were unlikely to structure and intervene in children's activities and likely to use nonverbal parenting techniques. Findings supported the usefulness of these instruments with NA parents when accompanied by discussion of findings with them, and nurse awareness of common family structures and traditional values.

Child, Preschool

Screening for pregnancy risk-drinking.

The efficacy of alcohol screening questionnaires, the TWEAK, T-ACE, NET, MAST, and CAGE, in detecting periconceptional risk-drinking, > or = 1 oz absolute alcohol/day, was investigated in 4743 African-American women attending an inner-city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow-up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cut-points defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T-ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut-point 1 were TWEAK (87/72) and T-ACE (83/75). At cut-point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T-ACE (70/85; p = 0.002). At cut-point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; risk-drinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy. This study confirms the utility, when screening for risk-drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T-ACE and provides preliminary data indicating that TWEAK may outperform T-ACE.

Adolescent

Induction of HLA class I and class II expression in human T-lymphotropic virus type I-infected neuroblastoma cells.

Human T-lymphotropic virus type I (HTLV-I) is associated with a neurologic disease, HTLV-I-associated myelopathy-tropical spastic paraparesis, in which both pathological and immunological changes are observed within the central nervous system. The pathogenesis of infection in HTLV-I-associated myopathy-tropical spastic paraparesis is not well understood with respect to the cell tropism of HTLV-I and its relationship to the destruction of neural elements. In this study, neuroblastoma cells were infected with HTLV-I by coculturing with HUT-102 cells to demonstrate that cells of neuronal origin are susceptible to this retroviral infection. HTLV-I infection of the neuroblastoma cells was confirmed by verifying the presence of HTLV-I gp46 surface antigens by flow cytometry and by verifying the presence of HTLV-I pX RNA by Northern (RNA) blotting and in situ hybridization techniques. To determine whether HTLV-I infection could potentially lead to changes in cell surface recognition by the immune system, the infected neuroblastoma cells were analyzed for altered HLA expression. The HTLV-I-infected, cocultured neuroblastoma cells were shown, through cell surface antigen expression and RNA transcripts, to express HLA classes I and II. In contrast, cocultured neuroblastoma cells that did not become infected with HTLV-I expressed only HLA class I. HLA class I expression was enhanced by the cytokines tumor necrosis factor alpha and gamma interferon and in the presence of HUT-102 supernatant. In this system, expression of HLA class I and II molecules appeared to be regulated by different mechanisms. HLA class I expression was probably induced by cytokines present in the HUT-102 supernatant and was not dependent on HTLV-I infection. HLA class II expression required HTLV-I infection of the cells. The observation of HTLV-I infection leading to HLA induction in these neuroblastoma cells provides a possible mechanism for immunologic recognition of infected neuronal cells.

Cell Communication

Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities.

PURPOSE: To determine whether hydrogen-1 magnetic resonance (MR) spectroscopy of the brain allows detection of subclinical hepatic encephalopathy (SCHE). MATERIALS AND METHODS: In a double-blind study, overt hepatic encephalopathy (HE) and SCHE (defined with clinical and neuropsychiatric tests) were compared by means of H-1 MR spectroscopic criteria--reduction in cerebral myo-inositol (< 2 standard deviations [SDs] from normal) and choline (< 2 SDs from normal) with or without increased cerebral glutamine (> 1 SD from normal)--in 20 patients with cirrhosis. RESULTS: Concordance between MR spectroscopic and neuropsychiatric test results was 94% (kappa = 0.84). MR spectroscopy allowed diagnosis of SCHE in nine of nine patients (100%) and of HE in seven of eight (88%). Myo-inositol depletion alone had 80%-85% sensitivity for detection of HE and SCHE. CONCLUSION: H-1 MR spectroscopy allows accurate diagnosis of SCHE, and the results suggest an important role for myo-inositol in psychomotor and visuopractic functions.

Adult

Reorganization: premises, processes, and pitfalls.

As the technological environment changes and libraries assume new and more active roles in their institutions, the traditional library hierarchy ceases to be an effective organizational structure. Guided by theories that emphasize teamwork, quality, and employee empowerment and participation, libraries are developing flatter, more networked organizations. The Health Sciences Library at Columbia University in New York, New York, recently underwent a reorganization in an effort to become a more resilient, more flexible organization. The process was beneficial overall. While some errors and confusion occurred, these are seen as opportunities for learning and evidence of the library's new atmosphere of creativity and experimentation.

Hospital Restructuring

Prompt diagnosis of ectopic pregnancy in an emergency department setting.

OBJECTIVE: To evaluate quantitative hCG measurements and transvaginal ultrasound in the diagnosis of ectopic pregnancy in patients presenting to the emergency department. METHODS: A discriminatory zone for detecting the presence or absence of an intrauterine pregnancy by transvaginal ultrasound was established prospectively. Women presenting to the emergency department were evaluated prospectively using a diagnostic algorithm consisting of clinical examination, quantitative serum hCG, and transvaginal ultrasound. Finally, ectopic pregnancies diagnosed over a 22-month period were evaluated prospectively. RESULTS: All viable intrauterine pregnancies were identified in those subjects with hCG levels of 1500 mIU/mL (First International Reference) or greater. One thousand two hundred sixty-three subjects were evaluated prospectively; 59.8% were diagnosed with intrauterine pregnancy, 26.8% with spontaneous abortion, and 7.8% with ectopic pregnancy. At presentation, 13.2% of intrauterine pregnancies were diagnosed by clinical examination, whereas 82.9% were diagnosed by transvaginal ultrasound. Only 4% of normal intrauterine pregnancies were not confirmed on initial visit. Of 205 ectopic pregnancies diagnosed, 81.5% were hemodynamically stable; of these, 49.1% were diagnosed on initial presentation. Of all ectopics, 59% never reached an hCG level of 1500 mIU/mL and 35.8% had an hCG lower than the level at presentation. This protocol diagnosed ectopic pregnancies with a sensitivity of 100% and a specificity of 99.9%. CONCLUSION: A protocol of quantitative hCG levels (available within hours of presentation to an emergency department) combined with transvaginal ultrasound is effective in diagnosing ectopic pregnancy.

Chorionic Gonadotropin

Neuroleptic prescriptions for acutely ill geriatric patients.

BACKGROUND: Use of neuroleptic medication by the general population of acute care hospitals and in geriatric populations in long-term care has been described. This study examines the use of neuroleptics in acutely ill medical/surgical geriatric patients. METHODS: Chart review was performed for geriatric patients prescribed a neuroleptic drug during a 2-month study period. Patient characteristics, indications for drug use, and evaluations of cognitive or behavioral dysfunction were noted. For the patients who received only haloperidol, the type of order was described and prescription strategies were identified. RESULTS: Ninety-one (10.7%) of 848 patients received a neuroleptic order. They were older and stayed longer than the rest of the geriatric population. Fifty-eight percent were demented or delirious but 31.9% were simply described as agitated or had no reason identified for drug use. Haloperidol was the sole neuroleptic prescribed for 91.2% of patients. The rationale behind the strategies for drug prescription (loading, maintenance, sporadic) was not clear. CONCLUSION: This study raises concerns about the quality of documentation around drug use and the adequacy of diagnostic evaluation prior to drug prescription. The strategies of drug treatment do not consistently reflect a working knowledge of the pharmacology of the drug or a diagnosis-based plan of treatment. Future research should focus on physician education and the efficacy of diagnosis and management of the agitated elder.

Acute Disease

Characterization of MHC class I restricted cytotoxic T cell responses to tax in HTLV-1 infected patients with neurologic disease.

To understand the nature of the cytotoxic T cell response generated in human T lymphotropic virus type 1 (HTLV-1)-infected patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, we cloned CTL from the peripheral blood and cerebrospinal fluid from patients with neurologic diseases and demonstrated the presence of HLA-A2, A3, and B14 restricted responses to the HTLV-1 p40x (tax) protein. We identified the minimal amino acid residues within the epitopes required for binding and recognition by HLA-A2- and B14-restricted CTL, identified the critical residues within the peptide sequence defining the HLA-A2-restricted response, and demonstrated that CTL can lyse T cells infected with HTLV-1. This study shows that the CTL response to HTLV-1 tax in patients with neurologic diseases is heterogenous in nature and is not confined to patients of a single HLA haplotype or to a specific region of the tax protein.

Amino Acid Sequence

Atypical human T-cell lymphotropic virus type-I-associated T-cell lymphoma in a low-prevalence Alaska Native population. Implications for disease surveillance.

An atypical case of adult T-cell leukemia/lymphoma (ATL) associated with human T-cell lymphotropic virus type I (HTLV-I) occurred in a 46-year-old Inupiat Eskimo man with no behavioral risk factors for HTLV-I infection. The case was characterized by lack of atypical circulating lymphocytes, hypercalcemia, and opportunistic infections; and by complete remission of the initial renal parenchymal lymphoma. The lymphoma cells had a helper T-cell (CD4) immunophenotype. Serum antibodies to HTLV I/II, detected by Western immunoblot, were identified in specimens collected 31 months before the onset of illness, at the time of diagnosis, and up to 37 months later, shortly before the patient's death. Polymerase chain reaction was used to identify HTLV-I DNA in peripheral blood mononuclear cells and in lymphoma in involved skin. Clinicians should be alert to sporadic cases of both atypical and classic ATL, even in populations in which the prevalence of HTLV-I infection is low.

Alaska

High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease.

The frequencies of human T cell lymphotropic virus type 1 (HTLV-1)-specific CD8+ precursor cytotoxic T lymphocytes (pCTL) were quantitated from lymphocytes obtained from the peripheral blood and cerebrospinal fluid (CSF) of infected individuals with and without HTLV-1-associated neurological disease. An estimate of the pCTL was obtained by separating CD8+ cells, plating these cells in limiting dilution, and testing wells for HTLV-1 specific lysis. Targets consisted of autologous lymphoblastoid cell lines (LCL) infected with vaccinia constructs expressing HTLV-1 gene products or LCL pulsed with HTLV-1 synthetic peptides. In patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the frequency of HTLV-1 p40X-specific pCTL was at least 40-280-fold higher than in asymptomatic HTLV-1-infected individuals. All HAM/TSP patients (five of five) predominantly recognized HTLV-1 products encoded within the pX region. Lower pCTL to env were demonstrated in three patients, and only one of five HAM/TSP patients had pCTL to gag. A synthetic peptide corresponding to the tax region of HTLV-1 (peptide 11-19, amino acid sequence LLFGYPVYV) was recognized in association with human histocompatibility leukocyte antigen (HLA)-A2 in two HLA-A2 HAM/TSP patients with a high CD8+ pCTL frequency of 1/325 and 1/265, respectively. A second immunodominant region of HTLV-1 tax (peptide 90-55, amino acid sequence VPYKRIEEL) was identified to be restricted by HLA-B14 in two HLA-B14 HAM/TSP patients with a CD8+ pCTL frequency of 1/640 and 1/1,125, respectively. Lymphocytes from the CSF of a patient with HAM/TSP also showed a pCTL frequency against p40X of similar magnitude to that demonstrated from peripheral blood lymphocytes (PBL). The HLA-A2-mediated CSF pCTL activity to the immunodominant tax-specific peptide 11-19 was also comparable to pCTL from PBL. These results indicate that an extremely high pCTL frequency to HTLV-1 tax-encoded peptides may be related to pathogenesis of myeloneuropathy associated with HTLV-1.

Adult

Isolation of HTLV-II from a patient with chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis.

An increasing spectrum of diseases has been shown to be associated with the human T-cell lymphotropic virus type I (HTLV-I), most notably a chronic, progressive myelopathy termed HTLV-I--associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia. HTLV-II is a close relative of HTLV-I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV-I--associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV-II in the absence of any other detectable human retrovirus. Antibodies to HTLV were detected in both serum and cerebrospinal fluid, with typical HTLV-II banding patterns on Western blots. HTLV-II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of this virus revealed a 99.5% homology with prototype HTLV-II. These results serve to alert the medical community to the possibility that in addition to HTLV-I, HTLV-II may be associated with a neurological disorder.

Brain