Suppression of bladder hyperreflexia by intravesical resiniferatoxin.
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Administration, Intravesical↗
Biomedical subjects
C Silva
Publications and source records attributed to C Silva.
H3-receptor antagonists: synthesis and structure-activity relationships of para- and meta-substituted 4(5)-phenyl-2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazoles.
We report the synthesis, octanol/water partition coefficient (log P), dissociation constants (pKa), H3-receptor affinity (pKi in rat brain membranes, [3H]-N alpha-methylhistamine), and H3-antagonist potency (pA2 in guinea ileum, (R)-alpha-methylhistamine) of novel H3-receptor antagonists obtained by introducing a para or meta substituent on the phenyl ring of the lead compound 4(5)-phenyl-2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazole (3a). The substituents were chosen to obtain broad and uncorrelated variation in their lipophilic, electronic, and steric properties. The log P values of the neutral species cover almost 3 orders of magnitude (from 1.40 to 4.11). The pKa,2 values (protonation of the 2-thioimidazole fragment) vary from 3.13 to 4.34, indicating that this fragment, which incorporates the so-called polar group common to many H3-receptor antagonists, is neutral at physiological pH. The compounds had pKi values in a range too narrow (from 7.28 to 8.03) to derive QSAR equations. In one case (3g), a biphasic displacement curve was observed (pKi,1 = 8.53; pKi,2 = 6.90). The pA2 values ranged 2 orders of magnitude (from 6.83 to 8.87) and yielded a QSAR model (PLS) indicating that antagonist potency depends parabolically on lipophilicity and is decreased by bulky para substituents. The compounds of this series, therefore, maintain a fair-to-good affinity for rat brain H3-receptor and a fair-to-good H3-antagonist potency on guinea pig ileum, although varying markedly in their lipophilicity. The series thus appears as a good candidate for pharmacokinetic optimization leading to brain-penetrating H3-receptor antagonists.
Animals↗
Isochromosome 14q in refractory anemia.
Trisomy 14 in hematologic disease is a rare finding and is almost exclusively associated with myeloid cell lineage. We present a case of refractory anemia (MDS-RA) with the uncommon features of marked elliptocytosis and schistocytosis in the peripheral blood and isochromosome 14q. The analysis of the clinical outcome of this case and of others of myelodysplastic (MDS)/myeloproliferative syndromes with trisomy 14 as the sole abnormality suggests that it does not confer an unfavorable prognosis.
Aged↗
Clinical correlates of interferon gamma production in patients with tuberculosis.
To determine if the capacity to produce interferon (IFN) gamma is related to the clinical manifestations of tuberculosis, we correlated Mycobacterium tuberculosis-induced IFN-gamma production by peripheral blood mononuclear cells (PBMCs) with clinical, radiographic, and laboratory variables for 63 human immunodeficiency virus (HIV)-negative patients and 43 HIV-positive patients with tuberculosis. For HIV-negative patients whose chest radiographs showed moderately advanced disease, the mean IFN-gamma concentration +/- SD was 1,639 +/- 388 pg/mL, whereas that for patients with far-advanced disease was 327 +/- 100 pg/mL (P = .0001). For HIV-infected patients who had only pleuropulmonary disease, the mean IFN-gamma concentration was 1,002 +/- 257 pg/mL, whereas that for patients with disease outside the lungs and pleura was 149 +/- 55 pg/mL (P = .0004). Multivariate analysis confirmed that the radiographic extent of disease and the site of disease were the only independent predictors of IFN-gamma production in HIV-negative and HIV-infected patients (P < or = .001). We conclude that reduced IFN-gamma production by PBMCs is a marker of severe tuberculosis in both HIV-negative and HIV-infected patients with tuberculosis.
AIDS-Related Opportunistic Infections↗
Symptoms of post-traumatic stress disorder in abused women in a primary care setting.
Abuse is a major source of trauma to women, and post-traumatic stress disorder (PTSD) results from exposure to extreme trauma. To describe the relationship between symptoms of PTSD and severity of abuse, an ethnically stratified cohort of 131 abused women in a primary care setting was interviewed. Symptoms of PTSD, both intrusion (i.e., trouble falling asleep, strong waves of feelings about the abuse) and avoidance (i.e., trying not to think or talk about the abuse, staying away from reminders of the abuse), were significantly (p < 0.01) correlated to severity of abuse, regardless of ethnicity. When asked about childhood physical or sexual abuse, women reporting physical abuse had significantly (p < 0.05) higher intrusion scores, whereas those reporting sexual abuse had significantly (p < 0.004) higher avoidance scores. Sixty-five percent of the women reported dreams, flashbacks, or terror attacks and had significantly (p < 0.001) higher mean results on both intrusion and avoidance. The need to offer abused women information about the connection between severity of abuse and symptoms of PTSD is discussed. We recommend that clinicians ask all abused women about dreams, flashbacks, or terror attacks to assess for further symptoms of PTSD.
Adolescent↗
Resource use by abused women following an intervention program: associated severity of abuse and reports of abuse ending.
Although violence against women is recognized as major public health problem, little is known about the effectiveness of interventions. To evaluate severity of abuse and use of community resources following an intervention program, 132 pregnant abused women received three counseling sessions in a prenatal setting. A comparison group of 67 abused women were offered a wallet-sized card listing community resources for violence. Resource use, severity of abuse, and reports of the abuse ending were measured for both groups at 6 and 12 months after delivery. Resource use was significantly (p < .001) related to severity of abuse, irrespective of whether the woman had received the intervention. Women using resources at 6 months were also users at 12 months. These findings indicate a "survivorship model" whereby abused women assertively and persistently seek a variety of community resources to end the abuse. The recommendation that primary care providers go beyond traditional identification and referral for abuse to coordination and evaluation of service delivery is discussed.
Adolescent↗
Desensitization of bladder sensory fibers by intravesical capsaicin has long lasting clinical and urodynamic effects in patients with hyperactive or hypersensitive bladder dysfunction.
PURPOSE: Capsaicin was used to treat symptomatic patients with hyperactive or hypersensitive bladders. MATERIALS AND METHODS: Capsaicin solution (1 mM.) was instilled into the bladder of 16 patients with spinal hyperreflexia, bladder instability or hypersensibility. RESULTS: Frequency decreased in 14 patients and continence was achieved in 10 of 14 incontinent cases. Mean first desire to void and maximal cystometric capacity increased significantly. These effects lasted for 6 to 12 months and were renewed following repeat treatment. CONCLUSIONS: Bladder afferent desensitization with capsaicin is promising in patients with motor or sensory bladder dysfunction, although initial pungency might limit its use.
Administration, Intravesical↗
Ligands of the histamine H3-receptor: new potent antagonists of the 2-thioimidazole type.
An overview of H3-receptor ligands is presented, with particular attention to antagonists. The protein binding of the classical H3-receptor antagonist thioperamide and its effect on in vivo distribution are discussed. A series of H3-receptor antagonists characterised by the presence of an imidazole ring, a spacer (ethylthio-, ethylamino-, propylthio- or propylamino-chain), a second heterocycle nucleus and a lipophilic group is described. Their H3-receptor antagonist potency has been measured on electrically stimulated guinea-pig intestine, and their affinity for central H3-receptor has been determined by competitive inhibition of [3H]N alpha-methylhistamine binding to rat cortex. Biphasic inhibition curves have been observed in some cases. Compounds endowed with interesting activity belong mostly to the class of 2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazole, having a phenyl or a cyclohexyl group.
Animals↗
[Detection of HIV antibodies in pooled sera].
The use of sera mixtures for the detection of HIV antibodies was studied in a population of low prevalence (0.006%), using the diagnosis systems of national production: Recombinant HIV UMELISA and RECHIV 1 + 2. The systems were evaluated with individual samples and mixtures of 5 and 10 sera from healthy blood donors and from HIV-1 and/or HIV-2 positive and undetermined persons. It was observed that the utilization of mixtures of 10 sera is not feasible; however, the use of mixtures of 5 affects neither the specificity nor the sensitivity of the systems studied.
AIDS Serodiagnosis↗
On-site storage of high level nuclear waste: attitudes and perceptions of local residents.
No public policy issue has been as difficult as high-level nuclear waste. Debates continue regarding Yucca Mountain as a disposal site, and-more generally-the appropriateness of geologic disposal and the need to act quickly. Previous research has focused on possible social, political, and economic consequences of a facility in Nevada. Impacts have been predicted to be potentially large and to emanate mainly from stigmatization of the region due to increased perceptions of risk. Analogous impacts from leaving waste at power plants have been either ignored or assumed to be negligible. This paper presents survey results on attitudes of residents in three counties where nuclear waste is currently stored. Topics include perceived risk, knowledge of nuclear waste and radiation, and impacts on jobs, tourism, and housing values from leaving waste on site. Results are similar to what has been reported for Nevada; the public is concerned about possible adverse effects from on-site storage of waste.
Adult↗
Rat protein binding and cerebral phospholipid affinity of the H3-receptor antagonist thioperamide.
The binding of thioperamide, a known H3-receptor antagonist, to rat plasma and proteins and its affinity for rat cerebral phospholipids are investigated. Thioperamide is strongly bound to plasma proteins (95-80% at plasma concentrations of 3.5-400 micrograms mL-1), and its binding can be resolved into two components a high-affinity, saturable component and a non-specific component. The drug has a high affinity for cerebral phospholipids, with a partition coefficient of approximately 100 (log K = 2.06 +/- 0.14), which should promote brain penetration and accumulation. Protein binding and cerebral phospholipid affinity can suggest the explanation of some differences reported in the literature on thioperamide distribution data: at low plasma concentrations of the drug, its protein binding (95% at 3.5 micrograms mL-1) can prevent brain accumulation, while at higher concentrations the free plasma fraction suddenly increases (> 10% at 18 micrograms mL-1) and it allows passive distribution to lipophilic tissues such as brain tissue.
Animals↗
Testing for human immunodeficiency virus infection in patients with tuberculosis.
To investigate the utility of testing all tuberculosis patients for HIV infection in Los Angeles, we prospectively evaluated 183 hospitalized patients with acid-fast smear-positive tuberculosis who gave no history of HIV infection. HIV serologic testing was performed, and the presence of risk factors for HIV infection was assessed by interview and review of the medical record. Thirty-three patients (18%) were infected with HIV. Based on data obtained by interview, 124 (68%) of 183 patients had at least one risk factor for HIV infection. The most common risk factors were related to heterosexual transmission of HIV (prostitute contact, multiple sex partners, and a history of sexually transmitted disease). These risk factors were frequently not documented in the medical record. Among the 33 patients who were infected with HIV, 30 were identified by interviewing as having significant risk factors. We concluded that most tuberculosis patients in Los Angeles have risk factors for HIV infection and that systematic questioning does not identify risk factors in all HIV-infected tuberculosis patients. These data support current recommendations to screen all tuberculosis patients for HIV infection.
AIDS Serodiagnosis↗
HLA antigens typification in two Hispanic patients with thyrotoxic periodic paralysis.
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Child↗
[Gastric tuberculosis. A first case].
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Female↗
Biological studies on 1,2-benzisothiazole derivatives V. Antimicrobial properties of N-alkanoic, N-arylalkanoic and N-aryloxyalkanoic derivatives of 1,2-benzisothiazolin-3-one: QSAR study and genotoxicity evaluation.
N-alkanoic, N-arylalkanoic and N-aryloxyalkanoic acids of 1,2-benzisothiazolin-3-one, esters and amides of N-arylalkanoic and N-aryloxyalkanoic acids and 1,1-dioxide derivatives of N-arylalkanoic acids and esters were investigated in vitro antimicrobial activity. N-arylalkanoic and N-aryloxyalkanoic acids (compounds 4-12) and their esters and amides (compounds 13-26) exhibited a good antimicrobial activity against Gram positive bacteria, with several compounds showing potencies 10-20 times higher than 1,2-benzisothiazolin-3-one. None of the chemicals tested inhibited the growth of E. coli. Yeasts and moulds possess a considerable susceptibility to compounds 12-23. The logP (octanol-water) of esters and amides of N-arylalkanoic and N-aryloxyalkanoic acids were measured by the shake-flask technique and the potencies against Gram positive bacteria of the compounds tested was related to their lipophilicity. QSAR analysis showed a bilinear relation, with a logD0 around 3 for the activity on B. subtilis. The phenoxyacetic and phenoxybutyric acid derivatives are positive outliers, showing a potency higher than that predicted from their lipohilicity. The most active compounds were further tested against different Gram positive bacteria and moulds, including Bacilli, Sarcina lutea, Staphylococcus epidermidis, Candida spp. and dermatophytes. The antibacterial and antifungal activity was specific for 1,2-benzisothiazolin-3-ones, the corresponding 1,1-dioxide derivatives being inactive. The genotoxic properties of the compounds studied were evaluated by the Bacillus subtilis rec-assay and Salmonella-microsome test. None of the compounds showed DNA-damaging or mutagenic activity.
Animals↗
[Chronic inflammatory demyelinating polyneuropathy. Report of six cases].
Chronic inflammatory demyelinating polyneuropathy is a heterogeneous disease characterized by symmetrical motor and sensitive alterations, absence of tendon reflexes and increased cerebrospinal fluid protein levels. We report 6 patients with the disease, (three males) aged 41 to 70 years old. Four had the classical presentation and two had an asymmetrical paresis, that predominated in superior limbs. These patients had a proximal block with scarce prolongation of distal nerve conduction velocity. In all patients, underlying illnesses were discarded with a full diagnostic work up. Subjects were followed from 2 to 14 months after the diagnosis. In all, treatment with steroids improved muscle strength and sensitivity.
Adult↗
Phase I clinical trial in cancer patients of a new monoclonal antibody FC-2.15 reacting with tumor proliferating cells.
FC-2.15 is a new murine IgM monoclonal antibody (MAb) that recognizes previously undescribed antigens present in proliferating breast cancer cells and normal peripheral granulocytes. A phase I clinical trial was performed in 11 patients with advanced cancer (breast, 5; colon, 2; melanoma, 1; lung, 1; medullary thyroid, 1; skin squamous carcinoma, 1). FC-2.15 was administered by i.v. infusion every other day; eight patients received four infusions, two patients three infusions and one patient received two infusions. One patient received two cycles of treatment. Total doses of MAb ranged between 2.5 and 5 mg/kg. Maximal FC-2.15 serum concentrations for different patients ranged between 1.3 and 7.5 micrograms/ml, and the serum half-life (t1/2-alpha) was approximately 7-9 h. All patients developed human anti-murine antibody. The most consistent toxicity (10 of 11 patients) was a profound and selective neutropenia that occurred within 1 h after the start of each infusion and reversed within 1 h after its discontinuation. Other frequent side effects included fever and chills that were easily manageable. Only two patients needed dose reduction or treatment interruption. The patient who received two treatment cycles did not develop allergic reactions. An objective partial response, consisting of a sustained (4 months) > 50% reduction of breast carcinoma liver metastases, was observed.
Adult↗
[Major histocompatibility system as a risk factor for alcoholic liver disease].
Several associations between alleles of the major histocompatibility system and alcoholic liver disease have been described. However, these are weak and change from one population to another. The aim of this work was to search for a possible genetic risk factor for alcoholic liver disease among Chilean alcoholics. We studied blood groups, serum proteins and HLA antigens in 39 alcoholic cirrhotics, 104 asymptomatic alcoholics and 44 non alcoholic controls. Asymptomatic alcoholics were also subjected to a percutaneous liver biopsy that showed moderate to severe histological liver damage in 46 subjects (44%). No differences in the studied genetic markers, were found among the four groups. It is concluded that this study does not confirm previously reported associations between genetic markers and alcoholic liver disease.
Adult↗