RESUMO
Objectives Home telemental health services have the potential to overcome many individual and systemic barriers to care facing military veterans with posttraumatic stress disorder. However, little is known about the home telemental health-related attitudes and experiences of highly underserved rural or ethnically, racially diverse veterans. This study evaluated whether ethnically/racially diverse U.S. veterans residing in the rural Pacific Islands would find the delivery of evidence-based treatment for posttraumatic stress disorder via home telemental health tablet devices useful and helpful. Method Clinicians located in a central urban location delivered Cognitive Processing Therapy for posttraumatic stress disorder directly into patients' homes via a tablet device and secure WiFi connection. Pre- and post-treatment measures were collected from a clinical sample of 47 veterans (average age: 49.3 years). Most (74.4%) self-identified as being of ethnic/racial minority background. Attitudinal, satisfaction, and usability scales were collected from home telemental health engaging ( n = 29) and non-engaging ( n = 18) veterans. Results Ratings on measures of home telemental health comfort, satisfaction with care, and usability were uniformly positive. Veterans were equally open to receiving mental health services at home via home telemental health or in the clinic. In the case of services for a physical problem, however, veterans preferred in-clinic care. Following treatment, veterans' attitudinal scores increased on items such as "There is enough therapist contact in home telemental health interventions." However, a small portion of veterans (7%) reported having technical or privacy concerns. Conclusion The provision of evidence-based posttraumatic stress disorder treatment directly into the patients' homes proved feasible and was well received by the large majority of rural ethnically/racially diverse veterans.
Assuntos
Terapia Cognitivo-Comportamental/métodos , Internet , Serviços de Saúde Mental , Satisfação do Paciente , Transtornos de Estresse Pós-Traumáticos/terapia , Telemedicina/métodos , Veteranos , Adulto , Computadores de Mão , Humanos , Masculino , Pessoa de Meia-Idade , Polinésia , População Rural , Estados UnidosRESUMO
OBJECTIVE: The objective was to evaluate the responsiveness of the Endometriosis Health Profile-30 (EHP-30) questionnaire in a Swedish sample. MATERIALS AND METHODS: Forty-two patients with endometriosis were included in a prospective observational study. MAIN OUTCOME MEASURES: The changes on the EHP-30 questionnaire after pertubation treatment were compared with the patients' self-estimated change in pain intensity. The responsiveness to change was evaluated with effect sizes and significance of change (paired t-test). The changes in scores between those who improved / not improved were compared with independent t-test. RESULTS: The changes in the scores were significant for all dimensions on the core questionnaire (p = 0.04-0.0002) for improved patients in contrast to the patients in the stable group where there were no significant changes in any dimension (p = 0.16-0.63). The effect sizes were large (> 0.8) on all core scales except for self-image (0.51) for the improved patients and small on all scales in the non-improved (stable) group (- 0.17-0.35). There were significant differences between the improved and the stable group considering change in most of the core EHP-30 scores. CONCLUSIONS: The EHP-30 is responsive to improvement on all core scales and is acceptable, understandable, and applicable in this Swedish sample.
Assuntos
Endometriose/psicologia , Qualidade de Vida , Adulto , Anestésicos Locais/uso terapêutico , Endometriose/terapia , Feminino , Humanos , Lidocaína/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Inquéritos e Questionários , SuéciaRESUMO
OBJECTIVES: An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE). MATERIALS AND METHODS: A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5. RESULTS: Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE. CONCLUSIONS: Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.
Assuntos
Carbidopa/farmacocinética , Catecóis/farmacocinética , Levodopa/farmacocinética , Nitrilas/farmacocinética , Adulto , Carbidopa/administração & dosagem , Carbidopa/sangue , Catecóis/administração & dosagem , Catecóis/sangue , Estudos Cross-Over , Combinação de Medicamentos , Feminino , Humanos , Levodopa/administração & dosagem , Levodopa/sangue , Masculino , Nitrilas/administração & dosagem , Nitrilas/sangue , Comprimidos , Adulto JovemRESUMO
BACKGROUND: Endometriosis is a chronic inflammatory disease of unknown aetiology that can cause severe dysmenorrhea. Lignocaine has anti-inflammatory properties and exerts effects on nerve endings and intra-peritoneal macrophages. The objective of this study was to evaluate the effect of pertubation with Ringer-Lignocaine on dysmenorrhea in women with endometriosis. METHODS: A double-blind randomized controlled trial (RCT) was carried out at three sites in Stockholm, Sweden. Eligible patients had endometriosis as diagnosed by laparoscopy, dysmenorrhoic pain >VAS 50 mm (visual analogue scale) and patent Fallopian tubes. The study patients were randomized sequentially to preovulatory pertubations with placebo (n= 18) or study treatment (n= 24) during three consecutive menstrual cycles. The pertubation procedure comprised passing study solution through the uterine cavity and the Fallopian tubes via an intra-cervical balloon catheter. The effect on pain was evaluated with VAS scales before and after the treatments and up to nine menstrual cycles after the last pertubation. Success was defined as a reduction of ≥ 50% on the VAS scale after the third pertubation. The success rate between the treatment and the placebo group was compared with Fisher's exact test. RESULTS: In the intention-to-treat analysis, the success rate was 41.7% (10 of 24) in the treatment group compared with 16.7% (3 of 18) in the placebo group (P= 0.10, 95% CI -7.3 to 36.2%). In the per protocol analysis, the success rate in the treatment group was 45% (9 of 20) compared with 7.1% (1 of 14) in the placebo group (P= 0.024, 95% CI -2.6 to 44.8%). Of the nine patients in the lignocaine group who fulfilled the criteria for success after three pertubations, 4 (44%) had an effect persisting after nine months. The treatments were well tolerated. CONCLUSIONS: This small RCT indicates that pertubation with lignocaine is a non-hormonal treatment option for patients with dysmenorrhea and endometriosis. ClinicalTrials.gov identifier: NCT01329796.
Assuntos
Anestésicos Locais/uso terapêutico , Dismenorreia/tratamento farmacológico , Endometriose/complicações , Lidocaína/uso terapêutico , Adulto , Anestésicos Locais/administração & dosagem , Método Duplo-Cego , Dismenorreia/etiologia , Feminino , Humanos , Lidocaína/administração & dosagemRESUMO
Recombinant activated factor VIIa (FVIIa) is a bypassing agent used to treat bleeding episodes in haemophilia patients with inhibitors to factor VIII (FVIII) and factor IX. The pharmacological effect of FVIIa is short-lived and therefore with the recommended dose of 90 µg kg(-1), a bleeding episode is treated with multiple injections. A long-acting form of FVIIa that can ensure adequate haemostasis with a single infusion, without increasing the thrombotic risk, would therefore be beneficial. PEGylated liposomes (PEGLip) have been shown to bind FVIIa and to improve haemostatic efficacy in preclinical experiments. In the present phase I/II clinical trial, we assessed the safety and efficacy of PEGLip-formulated FVIIa in severe haemophilia A patients (FVIII≤1%) with inhibitors to FVIII. Each patient received one prophylactic infusion of standard FVIIa and one prophylactic infusion of PEGLip-formulated FVIIa. The order of the infusions was randomized and the two infusions were separated by a ten-day washout period. Efficacy assessed by thromboelastography revealed that PEGLip-FVIIa induced significantly shorter clotting times and produced higher clot firmnesses than standard FVIIa. Thrombin generation assays showed that PEGLip-FVIIa induced faster thrombin generation and higher peak levels of thrombin than standard FVIIa. These effects lasted up to 5 h postinfusion. Measurements of D-dimer, prothrombin fragment 1+2 and fibrinogen showed no significant differences between the PEGLip-FVIIa and standard FVIIa treatments. PEGLip-FVIIa therefore showed improved haemostatic efficacy without increased risk of thrombosis and may be further developed for the treatment for bleeding episodes in haemophilia patients with inhibitors.
Assuntos
Fator VIIa/farmacocinética , Fator VIIa/uso terapêutico , Hemofilia A/tratamento farmacológico , Inibidores dos Fatores de Coagulação Sanguínea , Estudos Cross-Over , Fator VIII/imunologia , Fator VIIa/administração & dosagem , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Hemofilia A/sangue , Humanos , Lipossomos/uso terapêutico , Tempo de Tromboplastina Parcial , Fragmentos de Peptídeos/sangue , Polietilenoglicóis/química , Precursores de Proteínas/sangue , Protrombina , Tromboelastografia , Trombina/metabolismoRESUMO
Family members are an integral part of a patient's cancer care from the moment the diagnosis is delivered to the conclusion of treatment. Family members bring with them a range of emotional reactions, interpersonal dynamics and expectations for the care the patient receives. This study is part of a multi-institutional project to continue to improve the process of cancer care. In this study, 19 focus groups (11 patient and 8 provider) were conducted concerning issues related to doctor-patient communication in eight cancer centers in the United States. The content of the conversations was analyzed and thematic categories emerged that highlight the various strengths and difficulties associated with family involvement. The focus groups' comments support the need for explicit conversations between professional caregivers, patients and their loved ones, in order to negotiate the expectations and needs of each team member. Implications for clinical practice and strategies for working with family members are offered.
Assuntos
Adaptação Psicológica , Família/psicologia , Grupos Focais , Neoplasias/psicologia , Equipe de Assistência ao Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Cuidadores/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Papel do DoenteRESUMO
The pharmacokinetics of a second-generation recombinant B-domain deleted factor VIII (FVIII) preparation (r-VIII SQ) were studied in 36 patients with severe hemophilia A. In contrast to full-length recombinant FVIII, no albumin needs to be added to stabilize the final formulation of this B-domain deleted FVIII preparation. The in vivo recovery and half-life of r-VIII SQ were similar to those of plasma-derived (pd) FVIII (mean half-life of r-VIII SQ, 11.7 h). The volume of distribution and clearance were slightly, but significantly, higher for r-VIII SQ than for pdFVIII (p < 0.05). Peak plasma levels of FVIII were consistently related to the administered dose of r-VIII SQ (r = 0.94, p < 0.0001). The pharmacokinetic profile of r-VIII SQ remained essentially unchanged in a dose range of 25-100 IU/kg body weight and could be reproduced after repeated doses. r-VIII SQ was well tolerated. In conclusion, deletion of the B-domain of FVIII does not influence its in vivo pharmacokinetics.
Assuntos
Fator VIII/farmacocinética , Hemofilia A/tratamento farmacológico , Fragmentos de Peptídeos/farmacocinética , Adolescente , Adulto , Estudos Cross-Over , Fator VIII/efeitos adversos , Fator VIII/uso terapêutico , Meia-Vida , Hemofilia A/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacocinética , Proteínas Recombinantes de Fusão/uso terapêutico , Segurança , Deleção de Sequência , Método Simples-CegoRESUMO
Recombinant molecules similar to the smallest active plasma-derived factor VIII molecule, a complex of an 80-kDa and a 90-kDa polypeptide chain lacking the B domain, have been produced using various factor VIII cDNA constructs in order to obtain primary translation products which were efficiently processed into the 80 + 90-kDa complex. Three types of single-chain cDNAs encoding B-domain-deleted derivatives factor VIII were designed, taking account of sites at Arg740 and Glu1649, assumed to be important for processing factor VIII. In the type 1 constructs, either Arg747, Arg752, or Arg776 in the N-terminal region of factor VIII B domain was fused to the N-terminus (Glu1649) of the 80-kDa subunit. In the type 2 construct r-VIII SQ, Ser743 was fused to Gln1638, creating a link of 14 amino acids between the C-terminus (Arg740) of the 90-kDa chain and N-terminus of the 80-kDa chain, whereas in type 2 r-VIII RH, Arg747 was fused to His1646. In the type 3 constructs, the B-domain was completely removed or replaced with 1-4 Arg residues. After expression in Chinese hamster ovary cells, the type 1 derivatives and the type 3 derivatives with 0-2 Arg residues inserted were found to be only partially processed and contained a large amount of the 170-kDa primary translation product. In contrast, most of the type 2 derivatives r-VIII SQ and r-VIII RH and the type 3 derivatives r-VIII R4 and r-VIII R5 containing three or four extra Arg residues preceding the N-terminus of the 80-kDa chain were processed into the desired 80 + 90-kDa chain complexes. The feature common to the most efficiently processed factor VIII deletion derivatives was that they contained the recognition motif for proteolytic cleavage by the membrane-bound subtilisin-like protease furin, which is expressed in most types of cells; that is, basic amino acid residues at positions -1 and -4 relative to the cleavage site at Glu1649. Biochemical studies of r-VIII SQ and r-VIII R5, two of the most effectively processed factor VIII derivatives, showed that both proteins had a normal factor VIII cofactor function, and had N- and C-termini of the 80-kDa and 90-kDa chains corresponding to those found in plasma-derived factor VIII.
Assuntos
Fator VIII/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Células CHO , Cricetinae , Fator VIII/biossíntese , Fator VIII/metabolismo , Deleção de Genes , Técnicas de Transferência de Genes , Dados de Sequência Molecular , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Hypnosis has been used successfully in treating cancer patients at all stages of disease and for degrees of pain. The experience of pain is influenced not only by physiological factors stemming from disease progression and oncological treatment, but also from psychosocial factors including social support and mood. Each of these influences must be considered in the successful treatment of pain. The successful use of hypnosis also depends upon the hypnotizability of patients, their particular cognitive style, their specific motivation, and level of cognitive functioning. While most patients can benefit from the use of hypnosis, less hypnotizable patients or patients with low cognitive functioning need to receive special consideration. The exercises described in this chapter can be successfully used in groups, individual sessions, and for hospice patients confined to bed. Both self-hypnosis and therapist guided hypnosis exercises are offered.
Assuntos
Hipnose/métodos , Manejo da Dor , Autocuidado/métodos , Humanos , Dor/psicologia , Autocuidado/normasAssuntos
Antineoplásicos/administração & dosagem , Cateterismo Venoso Central , Cateteres de Demora , Leucemia/tratamento farmacológico , Adolescente , Adulto , Idoso , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Much evidence indicates that urinary 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG) is an insensitive measure of central norepinephrine metabolism. This conclusion, however, seems to apply mainly to total urinary MHPG, since previous findings point to the possibility that the major proportion of urinary MHPG sulfate originates in the CNS, while most urinary MHPG glucuronide originates in peripheral organs. To examine this hypothesis, experiments were performed by which we altered MHPG turnover in man at two different stages: firstly, strong physical exercise (ergometer) increased the urinary excretion rate of MHPG glucuronide and not that of MHPG-sulfate; secondly, ethanol (l g/kg), which is known to block the metabolism of MHPG to vanilmandelic acid in the liver, increases the urinary excretion rate of the glucuronide and not that of sulfate. Both experiments indicate that alteration of peripheral norepinephrine turnover changes the urinary excretion of MHPG glucuronide only and not that of sulfate, thus providing strong, albeit indirect, evidence for a primarily central origin of MHPG sulfate. Preliminary experiments in 32 depressed patients showed little difference in both MHPG fractions compared with healthy controls, apart from a slightly reduced excretion rate of glucuronide. These findings fail to provide any evidence of central, and only small changes in peripheral norepinephrine metabolism in depression.
Assuntos
Encéfalo/metabolismo , Transtorno Depressivo/urina , Glicóis/urina , Metoxi-Hidroxifenilglicol/urina , Norepinefrina/metabolismo , Receptores Adrenérgicos/metabolismo , Adulto , Feminino , Humanos , Masculino , Metoxi-Hidroxifenilglicol/análogos & derivados , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
A variant mouse plasmacytoma (MPC)-associated translocation chromosome has arisen by pericentric inversion and exchange of the distal segments of a Robertsonian 6;15 fusion chromosome in the CAK TEPC 1198 mouse plasmacytoma, as described earlier. In situ hybridization was performed on the normal and the inverted Rb chromosomes, using myc and kappa probes. On the normal Rb chromosome, myc was in the 15 D2/3 region, whereas kappa hybridized in the 6 C2 area, as expected. On the inverted Rb chromosome, myc remains on the centrometric side of the translocation breakpoint on the chromosome 15-derived portion, whereas kappa has moved to the chromosome 6-derived segment that joined the same breakpoint on the telomeric side. Taken together with our recent demonstration that the murine c-myc locus is oriented 'head up' on chromosome 15, and with the results of Cory and co-workers concerning the relationship between the kappa gene and the associated pvt-1 region in the CAK TEPC 1198 tumor, the following conclusions can be drawn: (i) in the variant translocation of the CAK TEPC 1198 MPC, the breakage occurs 3' of the c-myc gene, as in the human Burkitt lymphoma-associated variant translocations; (ii) the pvt-1 gene on chromosome 15 is distal to the myc gene; (iii) the kappa light chain locus is oriented 'head up' on mouse chromosome 6 and faces pvt-1 and, beyond it, c-myc, in a head-to-tail configuration.
Assuntos
Genes , Variação Genética , Cadeias kappa de Imunoglobulina/genética , Oncogenes , Plasmocitoma/genética , Translocação Genética , Animais , Linhagem Celular , Bandeamento Cromossômico , Inversão Cromossômica , Mapeamento Cromossômico , Cariotipagem , Metáfase , Camundongos , Camundongos Endogâmicos AKR , Hibridização de Ácido Nucleico , Plasmocitoma/imunologiaRESUMO
A new technique was developed for in situ hybridization on isolated murine chromosomes. The safety and relative rapidity of the method is due to the ready availability of large numbers of isolated "target" chromosomes with well preserved morphology. Its applicability was demonstrated by mapping c-myc to band 15D of Robertsonian (6;15) fusion chromosomes. This localization coincides with the cytogenetic mapping of the translocation breakpoints in mouse plasmacytomas that carry the typical rcpt (12;15) translocation.
Assuntos
Mapeamento Cromossômico , Hibridização de Ácido Nucleico , Animais , Autorradiografia , Linhagem Celular , Marcadores Genéticos , Cariotipagem , Linfoma/genética , Camundongos , Camundongos Endogâmicos AKR , Oncogenes , Neoplasias do Timo/genética , Translocação GenéticaRESUMO
An ouabain- and thioguanine-resistant subline (TIKAUT) of spontaneous AKR lymphoma, TKA, was trisomic for chromosome 15 and contained a single 33 kb EcoRI fragment, containing the oncogene c-myc. The original TKA lymphoma and derived in vitro line contained the same 33 kb fragment, as well as a normal 22 kb fragment. It has been concluded that the original 15-trisomic TKA tumor has duplicated a 15-chromosome that contained the changed fragment, while maintaining the normal fragment as well. Subsequently, in the derived TIKAUT line, the changed chromosome duplicated again, giving rise to three copies, and the normal homologue was eliminated altogether. This confirms our earlier somatic hybrid study showing that the duplicated 15-chromosome of a T-cell leukemia confers an advantage on the cell that favors tumorigenicity, whereas the normal homologue exerts a counteracting influence. Therefore, in the course of tumor progression, the changed chromosome tends to be amplified, whereas its normal homologue tends to be eliminated.
Assuntos
Enzimas de Restrição do DNA/genética , Leucemia Experimental/genética , Linfoma/genética , Oncogenes , Trissomia , Animais , Linhagem Celular , Bandeamento Cromossômico , Mapeamento Cromossômico , DNA de Neoplasias/análise , Desoxirribonuclease EcoRI , Resistência a Medicamentos , Cariotipagem , Camundongos , Camundongos Endogâmicos AKR , Mutação , Hibridização de Ácido Nucleico , Ouabaína , Linfócitos T , TioguaninaRESUMO
The most common chromosomal aberration in murine T-cell lymphomas is trisomy of chromosome 15. It has now been shown that the chromosomal region 15E exhibits a variant early replication banding pattern after 5-bromo-deoxyuridine labeling during part of the preceding S-phase. This variation is restricted to T-cell tumors. Plasmacytomas bearing the specific translocation t(12;15) show a normal early replication banding pattern of chromosome 15. In T-cell tumors all three chromosomes 15 of one cell are of the same variant banding type. In hybrids between tumor and nontumor cells, the number of cells expressing the variant early replication banding pattern is related to the degree of malignancy. Chromosomes 15 in one cell never expressed the variant and the normal banding pattern simultaneously. All five to six chromosomes 15 from one hybrid cell are of the same banding type irrespective of their parental origin. With respect to the type of early replication banding pattern, there is complete reversibility; tumor-parent-derived chromosomes 15 change to normal, and normal-parent-derived chromosomes 15 change to tumor.
Assuntos
Aberrações Cromossômicas , Células Híbridas/citologia , Leucemia Experimental/genética , Linfócitos T/citologia , Animais , Divisão Celular , Bandeamento Cromossômico , Fibroblastos/citologia , Cariotipagem , Leucemia Experimental/patologia , Metáfase , Camundongos , Camundongos Endogâmicos CBARESUMO
Two B-cell-derived tumours, human Burkitt's lymphoma (BL) and murine plasmacytoma (MPC), are regularly associated with a distinctive form of chromosomal translocation (for reviews see refs 1, 2). In BL, the distal portion of chromosome 8 breaks off and is transposed, in most cases, to chromosome 14, known to carry the immunoglobulin heavy-chain locus. In about 5% of the cases the same distal part of the chromosome 8 has moved to either chromosome 2 or 22, to the neighbourhood of the kappa or the lambda locus, respectively. In MPC the distal region of chromosome 15 is transposed to the chromosome 12, known to carry the immunoglobulin heavy-chain locus, or enters into reciprocal exchange with the kappa locus-carrying chromosome 6 (ref. 7). Several laboratories have located c-myc, the cellular homologue of the MC29 retroviral oncogene v-myc, to human chromosome 8 (refs 8-10) and mouse chromosome 15 (refs 11-13). It has also been shown that the BL- and MPC-associated translocations remove the c-myc gene from its original site and transpose it into or close to one of the immunoglobulin gene clusters. In view of the above findings we also looked for possible involvement of the c-myc gene in a B-cell-derived tumour of a third species, the rat. Rat immunocytomas of spontaneous origin carry a reciprocal translocation between chromosomes 6 and 7 (ref. 17). Here we have localized the c-myc locus to chromosome 7 of the rat. Moreover, we have found that the c-myc gene was rearranged in four of five immunocytomas carrying the characteristic chromosomal translocation.