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Biomedical subjects

J Hart

Publications and source records attributed to J Hart.

At least 91 records · Page 5Linked to original sources

Disseminated histoplasmosis in an infant with acquired immunodeficiency syndrome.

Disseminated histoplasmosis has been recognized as a serious opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). However, cases reported in the literature have been predominantly in adult patients. Here we report an infant with AIDS who presented with fever, cough, rhinorrhea, hepatosplenomegaly, pancytopenia and coagulopathy, and died of respiratory failure. Autopsy revealed disseminated histoplasmosis involving multiple organs including lungs, intestines, liver, spleen, bone marrow, lymph nodes, kidneys, and meninges. The diagnosis was established based on histomorphology and confirmed by blood culture.

Acquired Immunodeficiency Syndrome↗

Right hemisphere speech perception revealed by amobarbital injection and electrical interference.

OBJECTIVE: To investigate the right hemispheric speech perception capabilities of an adult right-handed patient with seizures. METHODS: Consecutive, unilateral, intracarotid sodium amobarbital injections and left hemispheric electrical interference mapping were used to determine lateralization and localization of speech perception, measured as syllable discrimination. RESULTS: Syllable discrimination remained intact after left and right intracarotid sodium amobarbital injections. Language otherwise strongly lateralized to the left hemisphere. Despite evidence of bilateral speech perception capabilities, electrical interference testing in the left posterior temporal lobe impaired syllable discrimination. CONCLUSIONS: The results suggest a functionally symmetric, parallel system in the adult brain with preferential use of left hemispheric pathways for speech perception.

Adult↗

Victor Coxon, member, B.J.'s Black Tie Club at Palmer, 1936-1941.

The 1930's era was a turbulent time for B.J. Palmer who was proposing radical changes in chiropractic methodologies, i.e., the Hole-in-one upper cervical approach, neurocalometer examinations and heavy reliance on x-ray for vertebral listings. Palmer needed and found an inner circle of loyal supporters at the Fountain Head who were named the "Black Tie Club," identified at important Palmer functions wearing the flowing black tie--the Windsor. One such Black Tie Club member was Victor Coxon--a 1930 Palmer School graduate who passed away recently. The present article explores Coxon's assistant directorship of the B.J. Palmer Chiropractic Clinic, some of his many writings, as well as correspondence Dr. Coxon had with the author.

Chiropractic↗

Protein disorder and the evolution of molecular recognition: theory, predictions and observations.

Observations going back more than 20 years show that regions in proteins with disordered backbones can play roles in their binding to other molecules; typically, the disordered regions become ordered upon complex formation. Thought-experiments with Schulz Diagrams, which are defined herein, suggest that disorder-to-order transitions are required for natural selection to operate separately on affinity and specificity. Separation of affinity and specificity may be essential for fine-tuning the molecular interaction networks that comprise the living state. For low affinity, high specificity interactions, our analysis suggests that natural selection would parse the amino acids conferring flexibility in the unbound state from those conferring specificity in the bound state. For high affinity, low specificity or for high affinity, multiple specificity interactions, our analysis suggests that the disorder-to-order transitions enable alternative packing interactions between side chains to accommodate the different binding targets. Disorder-to-order transitions upon binding also have significant kinetic implications as well, by having complex effects on both on- and off-rates. Current data are insufficient to decide on these proposals, but sequence and structure analysis on two examples support further investigations of the role of disorder-to-order transitions upon binding.

Algorithms↗

Treatment with either anti-CD4 or anti-CD8 monoclonal antibodies blocks alphabeta T cell-mediated rejection of intestinal allografts in mice.

BACKGROUND: Rejection is the major barrier preventing the more widespread application of intestinal transplantation as treatment for intestinal failure. For this study, a one-way host-versus-graft murine model was used to investigate the contribution of T cell subsets to the rejection of allogeneic intestinal allografts. METHODS: Intestinal grafts consisting of the donor jejunum and ileum were procured from C57BL/6J (syngeneic group) and B6C3F1/J (C57BL/6 x C3H/HeJ, allogeneic group) mice. These grafts were then transplanted into (1) normal, (2) antibody-treated, or (3) genetically mutated C57BL/6 mice. Mice were killed at predetermined intervals and the grafts assessed for rejection by a blinded pathologist. RESULTS: No syngeneic mice demonstrated any evidence of rejection. In contrast, the recipients of allografts experienced progressive rejection. Recipient mice treated with tacrolimus developed significantly less severe allograft rejection. None of the alphabeta T cell-deficient recipient mice (T cell receptor beta chain knockout mice) experienced allograft rejection with follow-up ranging from 8 to 28 days. However, mice deficient in gammadelta T cells (T cell receptor delta chain knockout mice) rejected intestinal allografts in a manner indistinguishable from normal recipients. In order to investigate the role of CD4+ and CD8+ T cells, recipient mice were treated 2 days before transplantation with depleting monoclonal antibodies specific for either CD4+ cells or CD8+ cells. Depletion of either population of cells significantly inhibited allograft rejection. CONCLUSIONS: These data demonstrate that rejection of intestinal allografts in the murine model was absolutely dependent on alphabeta but not gammadelta T cells. Furthermore, both CD4+ and CD8+ T cells were necessary for small bowel allograft rejection. Additional studies will be required to determine whether the effects of monoclonal antibody treatment were due solely to depletion of T cells or were mediated at least in part through an active process that altered the functional properties of the targeted T cell subset.

Animals↗

Hyaluronic acid induces tumour necrosis factor-alpha production by human macrophages in vitro.

Foetal wounds heal with minimal or no scar formation. High levels of hyaluronic acid (HA) have been implicated as a contributory factor. Macrophages are essential for normal wound healing, a role facilitated by secretion of an array of cytokines. Of these, tumour necrosis factor alpha (TNF-alpha) has been shown to reduce wound collagen levels and thus scarring. This study examines the ability of HA to stimulate TNF-alpha production by human macrophages. The human U937 myelomonocytic cell line was differentiated into DU937 adherent macrophages. DU937 monolayers were exposed to HA at concentrations of 0.1, 1, 10 and 100 micrograms/ml. Conditioned media from HA-exposed monolayers were assayed for TNF-alpha activity using a standard L929 fibroblast bioassay. TNF-alpha activities of HA-exposed DU937 culture supernatants were compared to those of controls and expressed as % cytotoxicity. Exposure of macrophages to HA at concentrations of 10 micrograms/ml and 100 micrograms/ml significantly stimulated TNF-alpha production, as demonstrated by % cytotoxicities expressed as median (interquartile range) of 33.5 (29-34.5)% (P = 0.03) and 77.5 (67-85)% (P = 0.029) respectively (Mann-Whitney U test). This effect was specifically associated with TNF-alpha generated during HA exposure, as these cytotoxic effects could be abolished by addition of anti-TNF-alpha antibody, reducing cytotoxicity to 9 (6.5-13.5)% and 8.5 (6-12)% respectively. These observations indicate that HA stimulates TNF-alpha production by human macrophages. TNF-alpha is known to downregulate fibroblastic collagen synthesis within experimental wounds. We suggest that the high levels of HA within foetal wounds may play a part in limiting fibroplasia, and thereby limit scarring, via an upregulation of TNF-alpha production from wound macrophages.

Animals↗

Serum vitamin E decreases in HIV-seropositive subjects over time.

Vitamin E is an important lipid soluble antioxidant that has a number of crucial functions including protecting lipids from oxidative damage. It also may play an important role in enhancing the immune response in subjects with Human Immunodeficiency Virus (HIV) infection. The current study measured the serum level of vitamin E in 121 HIV seropositive subjects with no prior pulmonary complications. Although the mean level was normal at 9.0 +/- 0.5 microg/ml, 22.3% of the subjects had a deficient level of less than 5 microg/ml. In addition, 42 subjects were studied longitudinally and serum vitamin E levels were determined at baseline and 12 months later. The mean serum vitamin E level in this group significantly decreased after 12 months compared with baseline levels (5.9 +/- 0.5 microg/ml compared with 9.6 +/- 0.9 microg/ml, p = 0.001). The CD4 counts also were significantly decreased after 12 months (460.6 +/- 36.0 cells/mm3 versus 390.5 +/- 37.7 cells/mm3, p = 0.032). No significant correlations were observed between the decrease in serum vitamin E and the change in CD4 count, body mass index (BMI), or serum albumin levels over the 12-month period. In conclusion, a significant portion of HIV-seropositive subjects have a deficiency in serum vitamin E early in the course of their disease. Furthermore, there is a significant decrease in serum vitamin E levels in these subjects over 12 months.

Adult↗

Peripheral-type benzodiazepine receptor ligands modulate human natural killer cell activity.

Following our earlier work, we evaluated the in vitro effect of ligands active at the peripheral-type benzodiazepine receptors on human natural killer cell activity. Peripheral blood mononuclear cells were incubated with benzodiazepine receptor ligands. After 4 h we observed a nonspecific inhibition of natural killer cell activity induced by both peripheral (Ro5-4864 and PK 11195) and central (clonazepam) benzodiazepine receptor ligands; after 24 h, the suppressive activity was specific to peripheral and mixed (diazepam) ligands, and the central-type ligand had no effect. This significant, specific suppression of NK cell activity was completely reversed by the addition of human recombinant interleukin-2 or human leukocyte interferon. Our research provides additional information on the immunomodulatory effects of peripheral-type benzodiazepine ligands. Further studies are needed to clarify the underlying mechanism of natural killer cell inhibition and to determine the clinical implications of these findings.

Humans↗

Increased living donor volunteer rates with a formal recipient family education program.

We have generally encouraged living donation among our kidney recipients. However, an examination of our clinical practice revealed inconsistencies in the depth and content of information transmitted to kidney recipient families regarding living donation. We therefore initiated a structured education program, including an educational video, to ensure that all recipient families would receive a similar exposure to a standard block of information. After the program had been functioning for over a year, we compared the living donor (LD) volunteer rates between the 3-year period before (BEFORE) and the 18 months after (AFTER) initiation of the formal education program. There were 1,363 patients registered on our kidney transplantation waiting list during the 54-month study period (757 white [56%] and 580 black [43%]). We found that 33.4% of the kidney transplant candidates in the period BEFORE the LD education program had at least one potential LD tissue typed, compared with 39.4% in the period AFTER starting the program (P = 0.03). The increase in the proportion of patients with potential donors was greatest among the black (P < 0.05) and elderly (P < 0.01) registrants, which were the groups with the lowest volunteer rates before the program began. Among the registrants with at least one potential donor, the percentage of registrants who ultimately received an LD transplant was highly correlated with the number of donors (R = 0.98). The rate of LD kidney transplantation was significantly higher (P = 0.02) for the patients referred in the period AFTER initiation of the LD education program compared with the period BEFORE the program. The 1- and 3-year graft survival rates for the 170 LD transplants performed in these patients were 96.9% and 93.2%, respectively. These were significantly better than the corresponding 83.9% and 71.4% rates for the 341 kidney transplants from cadaver donors in these registrants (P < 0.001). Black recipients of LD transplants had graft survival rates comparable to whites; the 3-year graft survival rate for LD transplants was 93.9% in whites and 90.6% in blacks (P = NS). We conclude that living kidney donor volunteer rates can be improved by a formal family education program, especially for subgroups of patients with low volunteer rates. A substantial benefit is derived by black patients, who generally experience low graft survival rates with cadaver-donor kidneys. A local formal LD education program is a useful adjunct to national organ donation campaigns.

Adult↗

Do drug costs affect physicians' prescription decisions?

OBJECTIVE: To study the impact of the cost of pharmaceuticals on physicians' decisions about drug prescription. DESIGN: A simulation protocol for the treatment of two patients, one with mild and the other with a severe form of urinary tract infection (UTI), was designed. Thirty family physicians in outpatient clinics and 30 physicians in the internal medicine wards of a Community Hospital participated in the project. They had to prescribe treatment for the patients twice: at phase I, when the drug cost was unknown, and at phase II, after 2 months, when the price of the drugs was brought to their attention. The physicians selected the medication from a list of drugs commonly used for the treatment of UTIs. RESULTS: Analysis of the findings indicates that an awareness of drug costs affects prescription decisions among physicians in hospital wards, whereas family physicians showed a preference for less expensive drugs even before they were informed about drug costs. An extrapolation of the results shows that knowledge about the cost of the drugs usually administered for treatment of UTI, could save at least IS 112,883 ($34,207) a month to Kupat Holim Klalit (KHK) the health insurance institution to which the outpatient clinics and the hospital belong. CONCLUSIONS: When economic aspects of healthcare are considered, information on drug costs may be an important factor in physicians' decision-making processes and for saving pharmaceutical expenses.

Anti-Bacterial Agents↗

Ultrastructure of human colostral cells.

The ultrastructural architecture of colostral cells of mothers of pre- and full-term infants is described. The polymorphonuclears were engaged in vivid phagocytosis of fat droplets. Similar findings were observed on the macrophages. The lymphocytes appeared normal in size and ultrastructure. A small number of eosinophils and basophils were also detected. The number of colostral cells was higher in the colostrum of mothers of preterm newborns. The number of the cells in the colostrum in mothers of both groups decreased with advancement of lactation.

Animals↗

Candida (Torulopsis glabrata) liver abscesses eight years after orthotopic liver transplantation.

The authors report the case of a 48-year-old man in whom candida (Torulopsis glabrata) liver abscesses developed 8 years after liver transplantation. After a week of fever, computed tomography and Doppler ultrasonography showed several fluid-filled loculations in the left lobe of the liver and hepatic arterial stenosis. Aspirates from the abscesses contained T. glabrata organisms. This complication probably developed because hepatic arterial stenosis resulted in bile infarcts (bilomas), which were contaminated via the biliary tract with candida from the biliary-enteric anastomosis. Catheter drainage and administration of amphotericin B for 10 weeks permitted successful retransplantation. T. glabrata liver abscesses, a life threatening complication that can occur long after liver transplantation, can be successfully managed by aggressive medical treatment followed by retransplantation.

Candidiasis↗

Do permanent pacemakers need an insulative coating? Results of a prospective randomized double-blind study.

During conventional manufacturing of implanted pulse generators (IPGs), an insulative coating is often applied to prevent local muscle stimulation and myopotential sensing in unipolar pacing. This can limit the orientation of the IPG into its pocket, be a potential source of muscle stimulation via coating scratches, and result in an increase in IPG production costs. We hypothesized that advances in the design and construction of current IPGs and leads obviates the need for an insulative coating of the IPG. Using a double-blind prospective randomized design, 39 patients were implanted with either coated or uncoated otherwise identical IPGs (19 dual, 20 single chamber). All testing was done in unipolar and bipolar mode in both channels. A strength-duration curve for muscle stimulation was constructed for all patients with muscle stimulation. Myopotential sensing was established during isometric exercise. At 6-month follow-up when tested in unipolar mode, 3 of 15 (20%) patients with coated IPGs and 3 of 20 (15%) with uncoated IPGs had muscle stimulation at 5.0 V/1.5 ms or lower (P = NS). No patients in either population had muscle stimulation at their normally programmed output. Myopotential sensing occurred in all patients in unipolar mode at a mean of 2.29 +/- 1.3 mV and 2.73 +/- 1.14 mV for coated versus uncoated, respectively (P = NS). The statistical power of these negative observations was 80%. An insulative coating for pacemakers does not appear to alter sensing performance or cause a significant difference in the occurrence or characteristics of muscle stimulation.

Adult↗

Alveolar fluid glutathione is not reduced in asymptomatic HIV-seropositive subjects.

Glutathione is an important antioxidant tripeptide that is found in high concentrations in the epithelial lining fluid (ELF) of the lung. Previous investigators demonstrated a deficiency of glutathione (GSH) in the epithelial lining fluid of human immunodeficiency virus (HIV)-seropositive patients. The current investigation performed bronchoalveolar lavage (BAL) on 59 asymptomatic HIV-seropositive subjects (mean CD4: 365.9 +/- 31.2 cells/mm3) and 12 normal control subjects. The volume of ELF and the concentration of glutathione and oxidized glutathione were determined. The concentration of total GSH in ELF was not significantly different in HIV-seropositive individuals compared with normal subjects (628.1 +/- 63.9 microM versus 499.9 +/- 86.0 microM, p = 0.38). However, there was a significantly higher concentration of ELF GSH in HIV-seropositive cigarette smokers (n = 30) compared with nonsmokers (n = 29) (800.3 +/- 107.7 microM versus 443.6 +/- 45.3 microM, p = 0.004). The percentage of total GSH in the oxidized form (GSSG) was similar in both the HIV-seropositive and the normal subject groups (3.4 +/- 0.3% versus 3.0 +/- 0.4%, p = 0.559). There were no significant correlations between ELF GSH or GSSG concentrations and age, CD4 count, or pulmonary function. There was, however, a significant negative correlation between BAL lymphocyte percentage and GSH. The current study suggests that for those patients whose HIV infection is at a relatively early phase, the levels of GSH in the lung ELF are normal.

Adult↗

Object shape processing in the visual system evaluated using functional MRI.

We used functional MRI (fMRI) to determine the cortical regions activated during processing of visual object shape in humans in six men and three women, using a paradigm with a baseline condition of simple shape detection and an activated condition of object/nonobject shape discrimination. Eight of the nine subjects studied showed significant signal changes. Seven of eight showed changes in the occipital lobes (five bilateral, two right only, one left only). All eight subjects with signal changes exhibited changes in the parietal lobes bilaterally. In the occipitotemporal gyri, there were signal changes bilaterally in seven subjects and unilaterally, on the right, in one. Activation-related fMRI signal increases were also present in the posterior superior and middle temporal gyri in seven of the subjects, with four showing bilateral signal changes, two showing signal changes on the left only, and one only on the right. The data strongly suggest that processing of object shape information in humans activates both the ventral and dorsal visual processing pathways ("what" and "where" pathways), described previously both in humans and in nonhuman primates.

Adult↗

Alveolar fluid glutathione decreases in asymptomatic HIV-seropositive subjects over time.

BACKGROUND: Initial investigations demonstrated a deficiency of glutathione (GSH) in the epithelial lining fluid (ELF) of HIV-seropositive patients. In a recent study, our laboratory was unable to document such a deficiency. The current study was performed in an attempt to reconcile those disparate findings. STUDY OBJECTIVES: To determine if ELF GSH decreases over time in asymptomatic HIV-seropositive subjects. DESIGN: Prospective, longitudinal study. SETTING: Major university medical center. PATIENTS OR PARTICIPANTS: Thirty-three asymptomatic HIV-seropositive volunteers. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: BAL was performed on 33 asymptomatic HIV-seropositive subjects at baseline, 6 months later, and 12 months later. The volume of ELF and the concentration of GSH and oxidized GSH were determined. The concentration of total GSH in ELF was 689.0+/-100.4 microM. This significantly decreased when measured 6 and 12 months later (355.9+/-41.7 microM, and 397.9+/-52.7 microM, respectively, p=0.01, compared with baseline, both comparisons). Significant decreases were also noted in the HIV-seropositive subjects who smoked cigarettes (baseline--762.6+/-142.4 microM; 6 months--373.7+/-45.9 microM; 12 months--459.3+/-73.8 microM, p<0.03, for baseline vs 6 months, and baseline vs 12 months). In nonsmoking HIV-seropositive subjects, there was a decrease in ELF GSH over time, but it did not reach statistical significance (baseline--589.1+/-138.2 microM; 6 months--335.3+/-74.1 microM; 12 months--345.8+/-74.0 microM, p>0.1, all comparisons). The percentage of total GSH in the oxidized form was similar at all three time points (baseline--3.8+/-0.5%; 6 months--3.1+/-0.5%; 12 months--3.9+/-0.9%, p>0.1, all comparisons). CONCLUSIONS: The current study demonstrates that the GSH level in ELF is significantly decreased in HIV-seropositive subjects 6 and 12 months after the initial determination.

Adult↗

A global perspective: technology in home care. Discussion.

Technological advances are changing the way the world shares information and conducts daily business, CARING asked home care colleagues around the world to respond to a question about technology's role in home care delivery. Although the degree of technology's involvement differs from country to country, each country is aware of the possibilities and is looking toward the future.

Computer Communication Networks↗