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1.
Saudi Med J ; 42(9): 981-985, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34470836

RESUMO

OBJECTIVES: To investigate the ethmoid infundibulum (EI) and maxillary sinus natural ostium (MSNO) dimensions in normal sinuses of the Asian population; identified variation between sides, gender, and age groups; and to assess the effects of such variation on the measurements. METHODS: We assessed EI dimension and MSNO diameter in computed tomography (CT) scans of the normal paranasal sinus of 100 patients who underwent trans-sphenoid endoscopic surgery. We compared demographic data and multiple anatomical variations. RESULTS: The gap difference in EI length between the right and left sides significantly differed from 0 (0.47±1.38 mm). We found wider EI in people aged ≥60 years (2.44±0.59 mm), compared to people aged <60 years (2.25±0.31 mm). Ethmoid infundibulum length was greater among individuals with Haller cells (8.84±1.56 mm) than in individuals without them (7.92±1.47 mm). Furthermore, MSNO diameter was greater with accessory ostium (3.48±0.77 mm versus 3.02±0.72 mm, presence versus accessory ostium absence). CONCLUSION: Multiple factors may affect EI and MSNO dimensions. Ethmoid infundibulum length differed between both sides. Ethmoid infundibulum width differed between individuals aged ≥60 years and individuals aged <60 years. Haller cells and accessory ostium presence were associated with significant differences in those measurements.


Assuntos
Endoscopia , Seio Maxilar , Humanos , Seio Maxilar/diagnóstico por imagem , Hipófise , Tomografia Computadorizada por Raios X
2.
Med J Malaysia ; 76(4): 597-599, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34305129

RESUMO

Giant splenic cyst is rare disorder affecting the spleen. As the occurrence is so in-frequent that the diagnosis preoperatively remains a challenge. We report a 12-year-old boy who presented to Sarawak General Hospital, Malaysia with left upper abdominal pain initially mistaken as a complex left liver cyst. He underwent surgery which turned out to be a giant splenic cyst and underwent laparotomy and total splenectomy. He was discharged well and remains asymptomatic after 6 months postoperative follow up.


Assuntos
Cistos , Laparoscopia , Esplenopatias , Criança , Cistos/diagnóstico por imagem , Cistos/cirurgia , Humanos , Masculino , Esplenectomia , Esplenopatias/diagnóstico por imagem , Esplenopatias/cirurgia
3.
Med J Malaysia ; 74(3): 243-245, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31256184

RESUMO

Epiphrenic oesophageal diverticulum is a rare disorder affecting the distal oesophagus. Surgical techniques for this condition evolve over time from open transthoracic and trans-abdominal approaches to minimally invasive surgery. We report a case of an 82-year-old male who presented with symptomatic epiphrenic oesophageal diverticulum over the last 1 year. He underwent laparoscopic transhiatal diverticulectomy, myotomy and anterior partial fundoplication and was discharged well. He remains asymptomatic after a follow-up of 6 months.


Assuntos
Divertículo Esofágico/diagnóstico , Divertículo Esofágico/cirurgia , Fundoplicatura , Laparoscopia , Idoso de 80 Anos ou mais , Humanos , Masculino
5.
Aliment Pharmacol Ther ; 46(3): 213-224, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28612983

RESUMO

BACKGROUND: Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. AIM: To determine whether FMT is effective and safe for the induction of remission in active UC. METHODS: Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). RESULTS: There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. CONCLUSIONS: Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.


Assuntos
Colite Ulcerativa/terapia , Transplante de Microbiota Fecal/métodos , Fezes , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão
6.
Int Endod J ; 48(8): 736-46, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25130364

RESUMO

AIM: To compare four gutta-percha filling techniques in simulated C-shaped canals based on filling quality at three cross-sectional levels, filling time and the apical extrusion of gutta-percha. METHODOLOGY: Forty resin simulated C-shaped canals were constructed and filled using one of four techniques: cold lateral compaction (LC), ultrasonic compaction (UC), single cone with injectable gutta-percha (Obtura II(™) ) (IT) and core-carrier (Thermafil(®) ) (CC). Cross sections were made at 1 (L1), 3 (L3) and 6 (L6) mm from the canal terminus. Areas of gutta-percha, sealer and voids in each cross section were measured using an image analysis system. Data were analysed using a univariate general linear model and post hoc test (Dunnett's T3). Data on time taken to fill canals was evaluated using the Bonferroni post hoc test. RESULTS: CC had more gutta-percha and less sealer compared with IT at L1 (P < 0.05). LC had marginally significantly less gutta-percha than CC at this level (P = 0.049). At level 3 mm, significantly more gutta-percha and less sealer were present in IT compared with LC (P < 0.05). The techniques showed no difference in quality at L6. The time for LC (20.72 min) was three times longer than for both IT (6.11 min) and CC (6.67 min), whereas for UC (26.92 min), it was four times longer (P < 0.001). Finally, the four techniques were not different in the occurrence of apical extrusion of gutta-percha. CONCLUSIONS: The core-carrier technique was the most effective technique when assessed by gutta-percha area in this simulated C-shaped canal.


Assuntos
Guta-Percha/química , Materiais Restauradores do Canal Radicular/química , Preparo de Canal Radicular/instrumentação , Humanos , Técnicas In Vitro , Teste de Materiais , Dente Molar , Propriedades de Superfície , Fatores de Tempo
7.
Laryngoscope ; 125(1): 92-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25131000

RESUMO

OBJECTIVES: Postoperative periorbital edema and ecchymosis following rhinoplasty can result in dissatisfaction for both the surgeon and the patient. The goal of this study was to perform a systematic review of the literature on the efficacy of steroids on edema and ecchymosis during rhinoplasty. DATA SOURCES: MEDLINE, SCOPUS, and Cochrane database. REVIEW METHODS: Two authors independently searched the databases from their inception of article collection to February 2014. Studies comparing perioperative steroid administration (steroid group) with no treatment (control group) where the outcomes of interest were edema and ecchymosis on postoperative days were included in the analysis. Overall, a total of nine trials met the inclusion criteria of this study, with a total sample size of 312 patients. RESULTS: The lower and upper eyelid edema during the 7 days postoperatively was statistically decreased in the steroid group versus control group. The lower and upper eyelid ecchymosis in the steroid group was significantly decreased in comparison to the control group for the first 4 days follow surgery. Regarding the outcome comparison between single-dose and multiple-dose administration of steroids, the multiple-dose administration decreased edema and ecchymosis significantly compared to single-dose administration after the fourth day. CONCLUSIONS: Perioperative administration of steroid during rhinoplasty could reduce the level of edema and eyelid ecchymosis. Multiple-dose administration of steroids has more advantages in terms of the outcomes of late postoperative edema and ecchymosis compared to a single-dose regimen.


Assuntos
Corticosteroides/administração & dosagem , Equimose/tratamento farmacológico , Edema/tratamento farmacológico , Doenças Palpebrais/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Rinoplastia/efeitos adversos , Adolescente , Corticosteroides/efeitos adversos , Adulto , Betametasona/administração & dosagem , Betametasona/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Hemorragia Pós-Operatória , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Laryngoscope ; 124(11): 2470-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24623575

RESUMO

OBJECTIVES/HYPOTHESIS: The increased number of endoscopic endonasal transsphenoidal approaches (EETSA) has been associated with sinonasal complications such as olfactory dysfunction. Current studies have compared preoperative and postoperative olfactory function according to surgical type and age. STUDY DESIGN: Retrospective review of medical records at a tertiary referral center. METHODS: Patients were divided into two groups according to surgical type and into four groups according to age. The two surgical groups were defined based on the bilateral nasoseptal flap technique (group A: right conventional nasoseptal flap and left modified nasoseptal rescure flap; group B: bilateral modified nasoseptal rescue flap). The four age groups were ≤ 30, 31-45, 46-60, and ≥ 61 years. Patients underwent preoperative olfactory function evaluation using a visual analogue scale (VAS), the Connecticut Chemosensory Clinical Research Center Test (CCCRC), and the Cross-Cultural Smell Identification Test (CCSIT). Repeat testing was performed 6-months postoperatively. RESULTS: A total of 226 patients who underwent binostril four-hand EETSA were included in this study. In both groups A and B, the olfactory function was significantly decreased according to CCCRC and CCSIT scores (P < 0.05). The VAS scores were significantly decreased in both groups (P < 0.05). The symptom scores and olfactory test results were significantly changed in >30-year-old patients who had undergone EETSA. CONCLUSION: EETSA might contribute to olfactory dysfunction independent of surgery type. In addition, age may affect the restoration of olfaction after EETSA. Patients who plan to undergo EETSA must be informed that their olfaction may be impaired. LEVEL OF EVIDENCE: 4.


Assuntos
Endoscopia/efeitos adversos , Transtornos do Olfato/etiologia , Procedimentos de Cirurgia Plástica/métodos , Neoplasias da Base do Crânio/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Adulto , Distribuição por Idade , Estudos de Coortes , Endoscopia/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/cirurgia , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/fisiopatologia , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/fisiopatologia , Cuidados Pré-Operatórios/métodos , Prognóstico , Procedimentos de Cirurgia Plástica/efeitos adversos , República da Coreia , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Neoplasias da Base do Crânio/patologia , Seio Esfenoidal/cirurgia , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
9.
Dalton Trans ; 43(1): 311-6, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24101033

RESUMO

Er-doped BiVO4 are synthesized by means of a surfactant free microwave assisted hydrothermal method having good photoactivities under sun-like excitation for the degradation of methylene blue. From the structural and morphological characterization, it has been stated that the presence of Er(3+) induces a slight stabilization of the tetragonal phase, probably due to its incorporation in the BiVO4 lattice. The best photocatalytic performances were attained for the samples with Er(3+) content higher than 3 at%. The occurrence of the Er(3+) doped tetragonal BiVO4 clearly induces higher photocatalytic activities. The existence of a luminescence process has been related with the enhanced photoactivity observed.

10.
Singapore Med J ; 52(5): 330-4; quiz 335, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21633765

RESUMO

Atrioventricular (AV) block comprises a spectrum of cardiac conduction delays with varying clinical presentations. It is commonly encountered in both hospital as well as ambulatory settings, and recognition of the type of AV conduction delay is essential for appropriate subsequent management. The electrocardiogram is a key tool for identification of patients with AV conduction delays. Contrasting management strategies should be employed for differing levels of conduction block.


Assuntos
Bloqueio Atrioventricular/fisiopatologia , Eletrocardiografia/métodos , Idoso , Angiografia Coronária/métodos , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Marca-Passo Artificial , Radiografia Torácica/métodos
11.
Singapore Med J ; 52(2): 68-71; quiz 72, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21373729

RESUMO

It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy and bundle branch block. In addition, ECG can aid in the localisation of the accessory pathway. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions and the institution of appropriate management.


Assuntos
Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Síndrome de Wolff-Parkinson-White/fisiopatologia , Adulto , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Wolff-Parkinson-White/diagnóstico
12.
Urology ; 75(6): 1460-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19963247

RESUMO

OBJECTIVES: To investigate whether the presence of detrusor overactivity (DO) influences storage symptoms after photoselective laser vaporization of the prostate (PVP) for benign prostatic hyperplasia (BPH). METHODS: A total of 149 patients who underwent PVP were included in this retrospective study. All patients underwent a preoperative evaluation including multichannel video urodynamics. The efficacy of the PVP was assessed at 1, 3, 6, and 12 months postoperatively using the International Prostate Symptom Score (IPSS), uroflowmetry, postvoid residual urine volume, and 3-day frequency-volume charts (FVC). The patients were stratified into 2 groups (DO group vs non-DO group). RESULTS: The IPSS and FVC showed that the storage symptoms were reduced significantly after the PVP in both groups (P<.05). Starting from 6 months after the PVP, the DO group (n=39) showed a significantly greater reduction in the subtotal storage symptom score than the non-DO group (n=110). When the improvement of storage symptoms was defined as a reduction of >or=50% in the subtotal storage symptom scores, the percentage of patients with improvement in the storage symptoms at 1, 3, 6, and 12 months after the PVP was 13.9%, 25.9%, 47.8%, and 52.9% in the DO group, and 22.2%, 24.4%, 33.3%, and 33.3% in the non-DO group, respectively. CONCLUSIONS: Our results show that storage and voiding symptoms significantly improved after the PVP. In addition, we found that men with DO might show more improvement of storage symptoms, after the PVP, than men without DO.


Assuntos
Terapia a Laser/métodos , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Bexiga Urinária Hiperativa/cirurgia , Idoso , Estudos de Coortes , Seguimentos , Humanos , Terapia a Laser/instrumentação , Lasers de Estado Sólido/uso terapêutico , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Fosfatos/uso terapêutico , Probabilidade , Hiperplasia Prostática/diagnóstico , Prostatismo/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Titânio/uso terapêutico , Resultado do Tratamento , Bexiga Urinária Hiperativa/diagnóstico , Urodinâmica , Volatilização
13.
BJU Int ; 98(5): 1114-7, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17034613

RESUMO

OBJECTIVE: To investigate the effects of ovariectomy and oestrogen replacement on the function and expression of Rho-kinase in rat bladder smooth muscle, as the actual effects of oestrogen deprivation on bladder smooth muscle are unclear. MATERIALS AND METHODS: Female Sprague-Dawley rats were placed into one of three groups: sham-operated, bilateral ovariectomy-only, and bilateral ovariectomy plus oestrogen replacement groups. In the last group, oestrogen was replaced by weekly injection of beta-estradiol 17-cypionate (250 microg/kg subcutaneously for 6 weeks) beginning at 1 week after ovariectomy, whereas the other groups received vehicle-only injections for 6 weeks. After treatment, the bladder was removed for muscle strip studies to evaluate the effects of Y-27632, a specific inhibitor of Rho-kinase, on baseline tension and carbachol-induced tonic contractions. Also, the protein expression of RhoA and Rho-kinase isoenzymes was assessed by Western blot analysis. RESULTS: Of the three groups, incubation with 10 microm Y-27632 resulted in the largest decrease in baseline tension of strips from the bilateral ovariectomy-only group, but this was not statistically significant (P > 0.05). For carbachol-induced tonic contractions, strips from the bilateral ovariectomy-only group were attenuated the most among the three groups after adding Y-27632 (P < 0.05). However, there were no significant differences in the levels of RhoA and the two Rho-kinase isoenzymes in bladder tissues from the three groups. CONCLUSION: Our data show that oestrogen might inhibit the function of Rho-kinase in bladder smooth muscle, while having no significant effect on its expression. This finding might help to explain the greater incidence of urinary tract symptoms suggestive of overactive bladder after the menopause in women.


Assuntos
Terapia de Reposição de Estrogênios , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Músculo Liso/enzimologia , Ovariectomia , Proteínas Serina-Treonina Quinases/fisiologia , Bexiga Urinária/enzimologia , Animais , Western Blotting , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Músculo Liso/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Quinases Associadas a rho
15.
BJU Int ; 96(9): 1403-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16287466

RESUMO

OBJECTIVE: To investigate the effects of glycine on the recovery of bladder smooth muscle contractility after acute urinary retention. MATERIALS AND METHODS: Bladder overdistension was induced in Sprague-Dawley rats by an infusion of saline (twice the threshold volume), maintained for 2 h. From 15 min before emptying of the bladder until 2 h after, saline or glycine solution was infused i.v. At 30 min, 2 h and 1 week after bladder emptying, samples of bladder tissue were taken for muscle strip study, malondialdehyde (MDA) assay, ATP assay, Western blotting for apoptosis-related molecules (Bcl-2, Bax, Caspase-3), and histological analysis including terminal deoxynucleotidyl transferase-mediated nick-end labelling staining. The results were compared among normal control, saline-treated and glycine-treated rats. RESULTS: In the glycine-treated group, muscle strip contractile responses induced by electrical-field stimulation and carbachol were both significantly greater at 1 week after bladder emptying than in the saline-treated group. The results of the ATP assay appeared to correspond with those of the muscle strip study. The saline-treated group had significantly higher MDA levels at 30 min after bladder emptying than the glycine-treated group. At 2 h after bladder emptying, there was significantly more apoptosis and greater leukocyte infiltration in the saline-treated group than in the glycine-treated group. While pro-apoptotic Bax and caspase-3 were down-regulated, Bcl-2 was up-regulated in the glycine-treated group. CONCLUSION: Glycine infusions might improve the contractile responses of bladder smooth muscle after acute urinary retention by reducing oxidative damage and apoptosis.


Assuntos
Glicinérgicos/farmacologia , Glicina/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Retenção Urinária/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Feminino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley
16.
BJU Int ; 95(7): 1086-90, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15839938

RESUMO

OBJECTIVES: To investigate the roles of glutathione and glutathione-S-transferase (GST) in cisplatin-resistance mechanisms in human bladder cancer, by using glutathione-depleting or GST-blocking agents. MATERIALS AND METHODS: Cisplatin-resistant human bladder cancer cell lines were established by continuous exposure of T24 cells to increasing concentrations of cisplatin. Buthionine sulphoximine (BSO), ethacrynic acid and indomethacin were used to deplete glutathione or block GST. Intracellular glutathione content, GST activity and cisplatin cytotoxicity were determined after exposing parental and drug-resistant cell lines to these agents. RESULTS: Intracellular glutathione content and GST activity were significantly decreased, and cisplatin cytotoxicity significantly enhanced, in both parental and resistant cell lines by glutathione-depleting or GST-blocking agents. However, the resistance of cisplatin-resistant cell lines did not fully recover to that of the parental cells with combined BSO and indomethacin. CONCLUSIONS: Both increased glutathione content and GST activity are significant in the cisplatin resistance of human bladder tumour cells. Because BSO, ethacrynic acid and indomethacin caused a partial recovery of resistance in the cisplatin-resistant cell line, further studies are needed to investigate their efficacy for treating patients with metastatic bladder carcinoma resistant to cisplatin.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Glutationa Transferase/antagonistas & inibidores , Glutationa/antagonistas & inibidores , Neoplasias da Bexiga Urinária/tratamento farmacológico , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/farmacologia , Humanos , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/enzimologia
17.
Antiviral Res ; 28(2): 121-31, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8585766

RESUMO

The magnitude and duration of the antiviral and clinical effect of alpha-interferon was measured in healthy volunteers. A single 3 million unit intramuscular dose of interferon was given either alone (controls) or after 72 h of concomitant medications. These medications included either aspirin (650 mg every 4 h), acetaminophen (650 mg every 4 h), or prednisone (40 mg per day). Peripheral blood mononuclear cells were assayed for resistance to vesicular stomatitis virus infection and induction of 2'-5'-oligoadenylate synthetase activity as evidence of interferon's antiviral effect. Co-administration of acetaminophen increased both antiviral parameters by more than 70% (P < 0.05) and reduced symptoms after interferon dosing, compared to controls. Aspirin and prednisone did not demonstrate any significant differences from controls in antiviral effect. As a group, acetaminophen, aspirin, and prednisone reduced the clinical symptoms by 47% compared to controls (P = 0.03) after interferon dosing, although individual drug comparisons failed to reach statistical significance. Independent of treatment group, the changes in antiviral markers after interferon dosing correlated closely with each other (r = 0.72, P < 0.001), but neither correlated with symptoms or fever (r < 0.30, P > 0.05). Acetaminophen enhances the antiviral effects of a single intramuscular dose of alpha-interferon, considering the parameters measured in these healthy volunteers.


Assuntos
Acetaminofen/farmacologia , Antivirais/farmacologia , Aspirina/farmacologia , Interferon-alfa/farmacologia , Prednisona/farmacologia , Infecções por Rhabdoviridae/tratamento farmacológico , Vírus da Estomatite Vesicular Indiana/efeitos dos fármacos , 2',5'-Oligoadenilato Sintetase/biossíntese , Adulto , Sinergismo Farmacológico , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/enzimologia , Fatores de Tempo
18.
Artigo em Inglês | MEDLINE | ID: mdl-7552520

RESUMO

The Inter-Company Collaboration for AIDS Drug Development (ICC) represents a collaborative effort among member companies to facilitate the conduct of clinical trials on AIDS drugs. One of the goals of the ICC is to expedite the development of combination antiretroviral therapy through data and compound sharing. Recently, the ICC formed a consensus master protocol to evaluate rapidly the safety and efficacy of triple-drug combinations of antiretroviral therapy for treatment of HIV-infected patients. This concept builds upon historical work with combination chemotherapy that resulted in treatments to successfully control chronic immunosuppressive, infectious or malignant diseases, such as tuberculosis, leprosy, childhood acute lymphoblastic leukemia, and Hodgkin's lymphoma. Because of limitations on potency and the continuing emergence of drug resistance seen with use of currently available antiretroviral agents in monotherapy and two-drug combination regimens, triple-combination regimens should represent a more promising approach to maximize antiviral activity, maintain long-term efficacy, and reduce the incidence of drug resistance. The ICC master protocol is a randomized, controlled, double-blind study with a treatment duration of 52 weeks. Patients eligible to enroll in this study must have documented HIV infection, with CD4 counts between 200 and 500 cells/mm3, and no history of antiretroviral therapy. The first four triple-drug combinations will be evaluated in two trials. These regimens have been selected based on encouraging data from laboratory and clinical studies. Each ICC trial will consist of three arms, with 75 patients per arm. Protocol ICC 001 will include AZT + zalcitabine (ddC) + saquinavir, AZT + ddC + nevirapine, and AZT + ddC as the control arm.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Antivirais/uso terapêutico , Protocolos Clínicos , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos de Coortes , Método Duplo-Cego , Quimioterapia Combinada , Humanos
19.
Ann Intern Med ; 118(10): 762-9, 1993 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-8097082

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of zalcitabine (also known as dideoxycytidine [ddC]) in patients with advanced human immunodeficiency virus (HIV) infection. DESIGN: Open-label, randomized study. SETTING: AIDS Clinical Trials Units, university-affiliated medical centers, and private practice groups. PATIENTS: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex who had tolerated zidovudine for 48 weeks or more. INTERVENTION: Fifty-nine patients received zidovudine (500 to 1200 mg/d) and 52 patients received zalcitabine (2.25 mg/d). MEASUREMENTS: The primary end points were survival and time to an AIDS-defining event or death. RESULTS: Because significantly more patients withdrew from zidovudine therapy, the median duration of treatment was greater in the zalcitabine group than in the zidovudine group (279.0 days compared with 174.5 days; P = 0.001). The estimated 12-month, event-free probabilities were 53% for the zalcitabine group and 57% for the zidovudine group (relative risk, 1.02; 95% CI, 0.5 to 2.2). The estimated 12-month survival rates were 81% for the zalcitabine group and 75% for the zidovudine group (relative risk, 1.39; CI, 0.5 to 3.8). The rate of decline in CD4 lymphocyte counts was significantly slower in the zalcitabine group than in the zidovudine group (-0.08 cells/day compared with -0.17 cells/day). Patients in the zalcitabine group had gained an average of 0.5 kg at week 20 and 0.4 kg at week 24, whereas patients in the zidovudine group had lost an average of 1.8 kg at week 20 and 2.4 kg at week 24 (P = 0.04 and P = 0.05, respectively). Moderate to severe peripheral neuropathy and ulcerative stomatitis occurred in 10 and 9 patients, respectively, in the zalcitabine group. CONCLUSIONS: The sample size for this study was smaller than planned, and no differences in survival and clinical end points were found. Slower rates of decline in CD4 lymphocyte counts and weight, however, were noted for the zalcitabine group.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1 , Zalcitabina/uso terapêutico , Zidovudina/uso terapêutico , Adulto , Peso Corporal/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Feminino , Proteína do Núcleo p24 do HIV/efeitos dos fármacos , Infecções por HIV/imunologia , Humanos , Contagem de Leucócitos , Masculino , Análise de Regressão , Índice de Gravidade de Doença , Taxa de Sobrevida , Zalcitabina/efeitos adversos , Zidovudina/efeitos adversos
20.
Ann Intern Med ; 118(5): 321-30, 1993 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8094279

RESUMO

OBJECTIVE: To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. DESIGN: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. SETTING: Outpatient clinics of 12 AIDS Clinical Trials Units. PATIENTS: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (> or = 70 pg/mL). INTERVENTION: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. MEASUREMENTS: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). RESULTS: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. CONCLUSIONS: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.


Assuntos
Complexo Relacionado com a AIDS/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Zalcitabina/administração & dosagem , Zidovudina/administração & dosagem , Linfócitos T CD4-Positivos/efeitos dos fármacos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Proteína do Núcleo p24 do HIV/efeitos dos fármacos , Doenças Hematológicas/induzido quimicamente , Humanos , Contagem de Leucócitos , Masculino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Aumento de Peso/efeitos dos fármacos , Zalcitabina/efeitos adversos , Zidovudina/efeitos adversos
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