More coments on ethics of alternative therapies.
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Animals↗
Biomedical subjects
J Goldberg
Publications and source records attributed to J Goldberg.
Hyperbaric oxygen for children with cerebral palsy: a randomised multicentre trial. HBO-CP Research Group.
BACKGROUND: The use of hyperbaric oxygen for children with cerebral palsy has spread worldwide, despite little scientific evidence of efficacy. We did a randomised trial to assess the efficacy and side-effects of this form of therapy in children with cerebral palsy. METHODS: 111 children with cerebral palsy aged 3-12 years were randomly assigned hyperbaric oxygen (n=57) or slightly pressurised room air (n=54). All children received 40 treatments over 2 months. Hyperbaric oxygen treatment was 1 h in 100% oxygen at 1.75 atmospheres absolute (ATA); children on slightly pressurised air received air at 1.3 ATA (the lowest pressure at which pressure can be felt, thereby ensuring the maintenance of masking). The main outcome measure was gross motor function. Secondary outcomes included performance in activities of daily living, attention, working memory, and speech. FINDINGS: For all outcomes, both groups improved over the course of the study, but without any difference between the two treatments. The score on the global gross motor function measure increased by 3.0% in the children on slightly pressurised air and 2.9% in those on hyperbaric oxygen. The mean difference between treatments was -0.40 (95% CI -1.69 to 0.90, p=0.544). Other changes were seen in speech, attention, memory, and functional skills. Ear problems occurred in 27 children treated by hyperbaric oxygen and in 15 treated with hyperbaric air (p=0.004). INTERPRETATION: In this study, hyperbaric oxygen did not improve the condition of children with cerebral palsy compared with slightly pressurised air. The improvement seen in both groups for all dimensions tested deserves further consideration.
Cerebral Palsy↗
Identification of a novel class of small-molecule antiangiogenic agents through the screening of combinatorial libraries which function by inhibiting the binding and localization of proteinase MMP2 to integrin alpha(V)beta(3).
The process of new blood vessel growth from existing vasculature, known as angiogenesis, is critical to several pathological conditions, most notably cancer. Both MMP2, which degrades the extracellular matrix (ECM), and integrin alpha(V)beta(3), which contributes to endothelial cell attachment to the ECM, are critically involved in this process. Recent findings have shown that MMP2 is localized in an active form on the surface of invasive endothelial cells based on its ability to directly bind integrin alpha(V)beta(3), suggesting that disrupting this protein--protein interaction may represent a new target for the development of angiogenesis inhibitors. The screening of small molecule libraries led to the identification of compounds which disrupt the MMP2--alpha(V)beta(3) interaction in an in vitro binding assay. A prototypical inhibitor was further found to prevent the degradation of the protein matrix without directly inhibiting MMP2 activity or disrupting the binding of alpha(V)beta(3) to its classical ECM ligand, vitronectin. The synthesis and screening of analogues and substructures of this lead compound allowed the identification of requisite structural features for inhibition of MMP2 binding to alpha(V)beta(3). This led to the synthesis of a more water-soluble derivative which maintains the in vitro biological properties and has potent antiangiogenic and antitumor activity in vivo, validating the target as one useful for therapeutic intervention.
Angiogenesis Inhibitors↗
Disruption of matrix metalloproteinase 2 binding to integrin alpha vbeta 3 by an organic molecule inhibits angiogenesis and tumor growth in vivo.
Matrix metalloproteinase 2 (MMP2) can associate with integrin alpha(v)beta3 on the surface of endothelial cells, thereby promoting vascular invasion. Here, we describe an organic molecule (TSRI265) selected for its ability to bind to integrin alphav(v)beta3 and block alpha(v)beta3 interaction with MMP2. Although disrupting alpha(v)beta3/MMP2 complex formation, TSRI265 has no effect on alpha(v)beta3 binding to its extracellular matrix ligand vitronectin and does not influence MMP2 activation or catalytic activity directly. However, TSRI265 acts as a potent antiangiogenic agent and thereby blocks tumor growth in vivo. These findings suggest that activated MMP2 does not facilitate vascular invasion during angiogenesis unless it forms a complex with alpha(v)beta(3) on the endothelial cell surface. By disrupting endothelial cell invasion without broadly suppressing cell adhesion or MMP function, the use of compounds such as TSRI265 may provide a novel therapeutic approach for diseases associated with uncontrolled angiogenesis.
Angiogenesis Inhibitors↗
Prevalence of HTLV-I-associated T-cell lymphoma.
In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials.
Black or African American↗
Cytokine receptor dimerization and activation: prospects for small molecule agonists.
Ligand-induced dimerization of cell surface receptors has emerged as a general mechanism for the initiation of signal transduction. A number of therapeutically important receptor families are believed to be activated by this process. Recently available structural information, particularly for the erythropoietin receptor, has provided insight into the mechanism of receptor activation. These findings have also revealed important constraints on the nature of receptor-agonist complexes. The prospects of discovering small-molecule mimetics of such receptor agonists are discussed, including strategies which have led to the identification of a small number of peptide and non-peptide cytokine mimetics.
Animals↗
Genetic and environmental influences on the relationship among combat exposure, posttraumatic stress disorder symptoms, and alcohol use.
The role of genetic and environmental influences on the relationship between combat exposure, posttraumatic stress disorder (PTSD) symptoms, and alcohol use were examined in 4072 male-male twin pairs who served in the United States military during the Vietnam era (1965-1975). Results indicate that the relationship between combat and alcohol use and between PTSD symptom factors and alcohol use were both substantially influenced by genetic factors. Findings are most consistent with a shared vulnerability model for the etiology of the association between PTSD symptoms and alcohol use. Specific unique environmental factors were more important than genetic factors for PTSD symptoms, and both factors were equally important for alcohol use. Further support is also found for the role of the unique environment in PTSD symptoms.
Alcoholism↗
Superovulation and intrauterine insemination in cases of treated mild pelvic disease.
PURPOSE: Our purpose was to examine the effect of treated mild pelvic disease on the outcome of superovulation with intrauterine insemination (SO/IUI). METHODS: Three hundred cycles of SO/IUI were retrospectively reviewed for 118 women with laparoscopically treated minimal/mild endometriosis and 67 cycles for 28 women with minimal/mild distal tubal disease/adnexal adhesions and compared with 265 cycles in 111 couples with idiopathic infertility. RESULTS: The monthly fecundity rate (MFR) of 6.8% and live birth rate (LBR) of 6% in the endometriosis group were significantly lower (P = 0.002) than those in the idiopathic infertility group (MFR = 13.5%, LBR = 12.1%). The 10.9% MFR and 7.5% LBR in the minimal/mild tubal/adnexal disease were not significantly different from those in the other two groups. CONCLUSIONS: MFR and LBR were higher after SO/IUI in idiopathic infertility compared to those for treated mild/minimal endometriosis or mild/minimal tubal/adnexal adhesions. However, SO/IUI still remains a reasonable option for both these groups prior to IVF-ET.
Adnexal Diseases↗
A twin study of the association between pathological gambling and antisocial personality disorder.
Many individuals with a history of pathological gambling (PG) also have a history of engaging in antisocial behaviors, and this has often been interpreted as a result of the former causing the latter. In a sample of 7,869 men in 4,497 twin pairs from the Vietnam Era Twin Registry, the authors examined (a) the association between PG and antisocial personality disorder (ASPD), (b) the extent to which PG might be differentially associated with childhood conduct disorder (CD) and adult antisocial behavior (AAB), and (c) the contribution of genetic and environmental factors to the association of PG with ASPD, CD, and AAB. PG was significantly associated with all 3 antisocial behavior disorders, and the association of PG with ASPD, CD, and AAB was predominantly explained by genetic factors. The results of this study suggest that the greater-than-chance co-occurrence of PG and antisocial behavior disorders is partially due to their sharing a common genetic vulnerability. The antisocial behavior observed among many individuals with PG probably cannot be interpreted as being simply a consequence of the PG.
Adult↗
A model for potential tumor immunotherapy based on knowledge of immune mechanisms responsible for spontaneous abortion.
Attempts to treat various cancers by immunotherapy have been tried for about 50 years. Most studies have focused on improving cytotoxic T lymphocyte (CTL) responses against various tumors. Immunotherapy has been both active and passive, and results have been modest at best. Spontaneous abortion (SAB) of pregnancies could in some ways resemble remission of a tumor. Both tumors and conceptusses are faced with a similar problem -- how to grow in a host in a vascular rich area, and yet escape immune surveillance despite both entities being an allogenic stimulus. In general, the fetus is far more immunogenic than a spontaneous tumor, and yet abortuses seem to avoid CTL responses but are sometimes invaded by natural killer (NK) cells. There are data suggesting that SAB will occur if there is inhibition of production of an immunosuppressive protein called progesterone-induced blocking factor (PIBF). This protein inhibits NK cell cytolysis and influences TH2 cytokine dominance over TH1. If some tumors avoid NK cell destruction through a PIBF mechanism, perhaps an active rejection of these tumors could be achieved by inhibiting PIBF production by treating with a progesterone receptor antagonist. Passive immunization could also be considered by conjugative radionuclide or toxic chemical to a PIBF antibody which may be tumor specific since PIBF is not produced in normal tissue. The first step should be to see if PIBF can be detected in the peripheral circulation in patients with certain tumors.
Abortion, Spontaneous↗
Gluteal necrotizing myofascitis: an unusual delayed complication of abdominal sacrocolpopexy.
Persistent low back pain developed in a 51-year-old woman after she had undergone abdominal sacrocolpopexy. Four months postoperatively, necrotizing myofascitis developed in her gluteal muscles. The infected mesh, which had eroded into the vagina, was removed. Cultures of the infected mesh and abscesses grew common vaginal flora, including Gardnerella vaginalis and Actinomyces.
Back Pain↗
Monozygotic twins discordant for chronic fatigue syndrome: regional cerebral blood flow SPECT.
PURPOSE: To evaluate the relationship between regional cerebral blood flow (rCBF) and chronic fatigue syndrome (CFS) in monozygotic twins discordant for CFS. MATERIALS AND METHODS: The authors conducted a co-twin control study of 22 monozygotic twins in which one twin met criteria for CFS and the other was healthy. Twins underwent a structured psychiatric interview and resting technetium 99m-hexamethyl-propyleneamine oxime single photon emission computed tomography of the brain. They also rated their mental status before the procedure. Scans were interpreted independently by two physicians blinded to illness status and then at a blinded consensus reading. Imaging fusion software with automated three-dimensional matching of rCBF images was used to coregister and quantify results. Outcomes were the number and distribution of abnormalities at both reader consensus and automated quantification. Mean rCBF levels were compared by using random effects regression models to account for the effects of twin matching and potential confounding factors. RESULTS: The twins with and those without CFS were similar in mean number of visually detected abnormalities and in mean differences quantified by using image registration software. These results were unaltered with adjustments for fitness level, depression, and mood before imaging. CONCLUSION: The study results did not provide evidence of a distinctive pattern of resting rCBF abnormalities associated with CFS. The described method highlights the importance of selecting well-matched control subjects.
Adult↗
Spontaneous depression versus biphasic cycling.
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Antidepressive Agents↗
Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.
Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler.
Administration, Inhalation↗
Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: fact or artifact?
This study examined the effects of exhaustive exercise on cognitive functioning among 21 monozygotic twin pairs discordant for chronic fatigue syndrome (CFS). The co-twin control design adjusts for genetic and family environmental factors not generally accounted for in more traditional research designs of neuropsychological function. Participants pedaled a cycle ergometer to exhaustion; maximum oxygen output capacity (VO2max) as well as perceived exertion were recorded. Neuropsychological tests of brief attention and concentration, speed of visual motor information processing, verbal learning and recognition memory, and word and category fluency were administered with alternate forms to participants pre- and postexercise. The preexercise neuropsychological test performance of CFS twins tended to be slightly below that of the healthy twin controls on all measures. However, twins with CFS did not demonstrate differential decrements in neuropsychological functioning after exercise relative to their healthy co-twins. Because exercise does not appear to diminish cognitive function, rehabilitative treatment approaches incorporating exercise are not contraindicated in CFS.
Adult↗
Relationships between use of television during meals and children's food consumption patterns.
OBJECTIVE: We examined relationships between the presence of television during meals and children's food consumption patterns to test whether children's overall food consumption patterns, including foods not normally advertised, vary systematically with the extent to which television is part of normal mealtime routines. METHODS: Ninety-one parent-child pairs from suburbs adjacent to Washington, DC, recruited via advertisements and word of mouth, participated. Children were in the fourth, fifth, or sixth grades. Socioeconomic data and information on television use were collected during survey interviews. Three nonconsecutive 24-hour dietary recalls, conducted with each child, were used to construct nutrient and food intake outcome variables. Independent sample t tests were used to compare mean food and nutrient intakes of children from families in which the television was usually on during 2 or more meals (n = 41) to those of children from families in which the television was either never on or only on during one meal (n = 50). Multiple linear regression models, controlling for socioeconomic factors and other covariates, were used to test strength of associations between television and children's consumption of food groups and nutrients. RESULTS: Children from families with high television use derived, on average, 6% more of their total daily energy intake from meats; 5% more from pizza, salty snacks, and soda; and nearly 5% less of their energy intake from fruits, vegetables, and juices than did children from families with low television use. Associations between television and children's consumption of food groups remained statistically significant in multiple linear regression models that controlled for socioeconomic factors and other covariates. Children from high television families derived less of their total energy from carbohydrate and consumed twice as much caffeine as children from low television families. There continued to be a significant association between television and children's consumption of caffeine when these relationships were tested in multiple linear regression models. CONCLUSION: The dietary patterns of children from families in which television viewing is a normal part of meal routines may include fewer fruits and vegetables and more pizzas, snack foods, and sodas than the dietary patterns of children from families in which television viewing and eating are separate activities.
Adult↗
Comorbid clinical conditions in chronic fatigue: a co-twin control study.
OBJECTIVES: Chronically fatiguing illness, defined as fatigue for at least 6 months, has been associated with various physical health conditions. Our objective was to determine whether there is a significant relationship between chronically fatiguing illness and 10 clinical conditions that frequently appear to be associated with fatigue, adjusting for the potentially confounding effects of psychiatric illness. DESIGN: A co-twin control study controlling for genetic and many environmental factors by comparing chronically fatigued twins with their nonfatigued co-twins. SETTING: A nationally distributed volunteer twin registry. PARTICIPANTS: The study included 127 twin pairs in which one member of the pair experienced fatigue of at least 6 months' duration and the co-twin was healthy and denied chronic fatigue. Fatigued twins were classified into 3 levels using increasingly stringent diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: Twins reported on a history of fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, temporomandibular disorder, interstitial cystitis, postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these comorbid clinical conditions was significantly higher in the fatigued twins compared to their nonfatigued co-twins. Most notably, compared to their nonfatigued co-twins, the chronically fatigued twins had higher rates of fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The strongest associations were observed between chronic fatigue and fibromyalgia (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder (all with odds ratios > or = 4). Regression analysis suggested that the number of comorbid clinical conditions associated with chronic fatigue could not be attributed solely to psychiatric illness. CONCLUSIONS: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention.
Adult↗