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1.
Brain Inj ; 33(7): 932-940, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31017474

RESUMO

Primary Objective: To advance knowledge about the value of the Center for Epidemiologic Studies - Depression scale (CES-D) for depression screening in military service members with a history of mild traumatic brain injury (mTBI). Research Design: Retrospective data from 336 military service members with a history of mTBI were extracted from a TBI Repository at a large military medical center. Participants included in this study screened positive for mTBI in a primary care clinic or soldier readiness processing center and were enrolled in the TBI repository from November 6, 2014 to May 31, 2017. At the time of enrollment, participants completed the CES-D and their electronic medical records (EMR) were searched for diagnoses of depressive disorders. Methods and Procedures: Receiver-operating characteristic (ROC) analysis of the CES-D was used to discriminate cases with and without depression diagnoses. Main Outcomes and Results: Area under the ROC curve (AUC) was .897. Sensitivity (.824) and specificity (.826) were maximized at a cut score of 18 or greater, slightly higher than the standard cut of 16 established for civilian samples. Conclusions: Results suggest that the CES-D is a valid screening instrument for depressive disorders in military samples with a history of mTBI.


Assuntos
Concussão Encefálica/complicações , Depressão/diagnóstico , Militares/psicologia , Adulto , Depressão/etiologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
2.
Br J Radiol ; 82(977): 412-20, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19386960

RESUMO

The aim of this study was to investigate the use of time to maximum enhancement (t(max)) for each voxel in contrast-enhanced MRI (CE-MRI) as a non-invasive tool to determine areas of necrosis following treatment of liver tumours with high-intensity focused ultrasound (HIFU) and, having established the utility of t(max) maps, to develop a three-dimensional (3-D) representation to display this information concisely. 3-D T(1) weighted fast spoiled gradient echo images of the liver were acquired before and after administration of contrast agent. The CE-MR images were aligned to the pre-contrast volume and an estimate of t(max) was obtained for each voxel. Such pre- and post-contrast image sets were acquired before and after ablation. The t(max) maps before and after HIFU treatment were correlated with the procedure notes, radiological reports and gross histological specimen. Finally, 3-D t(max) maps of the whole liver were reconstructed to show all areas of abnormal tissue perfusion. Normal, healthy liver tissue uniformly enhances maximally after approximately 1 min. The computed t(max) maps accurately delineated areas of abnormal contrast agent uptake, corresponding to tumour deposits. Changes in t(max) and non-enhancing voxels after treatment correlate well with volumes targeted during ablation and the necrotic regions seen on gross histological specimens. Alignment of the contrast-enhanced images with the pre-contrast volume greatly improved the conspicuity of the t(max) maps. We conclude that t(max) maps and their 3-D views can be used as a non-invasive tool to assess and potentially to quantify the success of HIFU ablation, and concisely represent the large number of CE-MRI data.


Assuntos
Neoplasias Hepáticas/terapia , Terapia por Ultrassom/métodos , Técnicas de Ablação/métodos , Meios de Contraste , Humanos , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
3.
Br J Radiol ; 81(967): 564-71, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18559903

RESUMO

Cancer therapies usually depend on cross-sectional imaging for the assessment of treatment response. This study was designed to evaluate the ability of MRI to predict zones of necrosis following the use of high-intensity focused ultrasound (HIFU) to treat liver metastases. Patients with liver metastases, who had been scheduled for elective surgical resection of their tumours, were recruited to this non-randomized Phase II study. In each case, a proportion of an index liver tumour target was ablated. The response to HIFU was assessed after 12 days using contrast-enhanced MRI and compared directly with histological analysis at the time of surgery. Eight patients were treated, of whom six were subsequently assessed with both MRI and histology. There were no major complications. MRI predicted complete ablation in three cases. In each case, histological analysis confirmed complete ablation. In one case, the region of ablation observed on MRI appeared smaller than predicted at the time of HIFU, but histology revealed complete ablation of the target region. The predominant characteristic of HIFU-ablated tissue was coagulative necrosis but heat fixation was evident in some areas. Heat-fixed cells appeared normal under haematoxylin and eosin staining, indicating that this is unreliable as an indicator of HIFU-induced cell death. This study demonstrates that HIFU is capable of achieving selective ablation of pre-defined regions of liver tumour targets, and that MRI evidence of complete ablation of the target region can be taken to infer histological success.


Assuntos
Neoplasias Hepáticas/terapia , Terapia por Ultrassom/métodos , Idoso , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Radiografia , Segurança , Resultado do Tratamento , Terapia por Ultrassom/efeitos adversos
4.
Int J Hyperthermia ; 23(2): 173-82, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17578341

RESUMO

In recent years high intensity focused ultrasound (HIFU) has received increasing interest as a non-invasive modality for the treatment of tumours of solid organs. Surgeons continue their quest to find the optimal technique whereby a diseased organ can be treated with a minimum of damage to the patient, while providing a comprehensive treatment to produce either cure or resolution of symptoms. Two of the areas in which HIFU is beginning to establish itself as a real therapeutic alternative, are in the treatment of abdominal and gynaecological disease. In this paper, we will review the literature available regarding the use of HIFU in the treatment of various organs: liver, kidney, pancreas, bladder, uterus and vulva.


Assuntos
Abdome , Doenças dos Genitais Femininos/terapia , Terapia por Ultrassom/métodos , Feminino , Humanos , Neoplasias Renais/terapia , Leiomioma/terapia , Neoplasias Pancreáticas/terapia , Neoplasias da Bexiga Urinária/terapia , Neoplasias Uterinas/terapia
5.
Br J Cancer ; 93(8): 890-5, 2005 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-16189519

RESUMO

High-intensity focused ultrasound (HIFU) provides a potential noninvasive alternative to conventional therapies. We report our preliminary experience from clinical trials designed to evaluate the safety and feasibility of a novel, extracorporeal HIFU device for the treatment of liver and kidney tumours in a Western population. The extracorporeal, ultrasound-guided Model-JC Tumor Therapy System (HAIFU Technology Company, China) has been used to treat 30 patients according to four trial protocols. Patients with hepatic or renal tumours underwent a single therapeutic HIFU session under general anaesthesia. Magnetic resonance imaging 12 days after treatment provided assessment of response. The patients were subdivided into those followed up with further imaging alone or those undergoing surgical resection of their tumours, which enabled both radiological and histological assessment. HIFU exposure resulted in discrete zones of ablation in 25 of 27 evaluable patients (93%). Ablation of liver tumours was achieved more consistently than for kidney tumours (100 vs 67%, assessed radiologically). The adverse event profile was favourable when compared to more invasive techniques. HIFU treatment of liver and kidney tumours in a Western population is both safe and feasible. These findings have significant implications for future noninvasive image-guided tumour ablation.


Assuntos
Neoplasias Renais/terapia , Neoplasias Hepáticas/terapia , Terapia por Ultrassom/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Terapia por Ultrassom/efeitos adversos
7.
Ultrasonics ; 42(1-9): 931-5, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15047409

RESUMO

High-intensity focused ultrasound (HIFU) has been investigated as a tool for the treatment of cancer for many decades, but is only now beginning to emerge as a potential alternative to conventional therapies. In recent years, clinical trials have evaluated the clinical efficacy of a number of devices worldwide. In Oxford, UK, we have been using the JC HIFU system (HAIFU Technology Company, Chongqing, PR China) in clinical trials since November 2002. This is the first report of its clinical use outside mainland China. The device is non-invasive, and employs an extracorporeal transducer operating at 0.8-1.6 MHz (aperture 12-15 cm, focal length 9-15 cm), operating clinically at Isp (free field) of 5-15 KWcm(-2). The aims of the trials are to evaluate the safety and performance of the device. Performance is being evaluated through two parallel protocols. One employs radiological assessment of response with the use of follow-up magnetic resonance imaging and microbubble-contrast ultrasound. In the other, histological assessment will be made following elective surgical resection of the HIFU treated tumours. Eleven patients with liver tumours have been treated with HIFU to date. Adverse events include transient pain and minor skin burns. Observed response from the various assessment modalities is discussed.


Assuntos
Neoplasias Hepáticas/terapia , Terapia por Ultrassom/métodos , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Microesferas , Fosfolipídeos , Hexafluoreto de Enxofre , Resultado do Tratamento
8.
Int J Gynecol Cancer ; 13(6): 889-93, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14675329

RESUMO

The objective of this study was to design and implement a maximum surgical blood order schedule (MSBOS) within a specialist gynecological oncology department in a tertiary referral center and evaluate its impact on the cross-match to transfusion ratio (CTR). A retrospective case note audit was undertaken to identify common operations performed within the unit and their transfusion requirements. The efficiency of blood usage was assessed using the CTR, and an MSBOS was devised and implemented. A prospective audit of preoperative blood cross-matching and subsequent blood usage was then performed for consecutive elective operations in the unit, to assess the effect of the MSBOS. The retrospective study of 222 cases demonstrated a CTR of 2.25 equivalent to 44% usage of cross-matched blood. Ninety two percent of operations performed within the unit could be incorporated into an MSBOS. The prospective study of 207 cases demonstrated a significantly reduced CTR of 1.71 or 59% blood usage (chi2 = 12.4, P < 0.001). This equates to a saving of 102 units of blood over the 15 months prospective audit. Protocol adherence was 77%. No patient was adversely affected by the adoption of the MSBOS. We conclude that an MSBOS can be safely introduced into a gynecological oncology department resulting in significant financial savings.


Assuntos
Transfusão de Componentes Sanguíneos/economia , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Tipagem e Reações Cruzadas Sanguíneas/economia , Tipagem e Reações Cruzadas Sanguíneas/normas , Procedimentos Cirúrgicos em Ginecologia , Bancos de Sangue/economia , Bancos de Sangue/normas , Perda Sanguínea Cirúrgica , Redução de Custos , Eficiência Organizacional , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Oncologia , Cuidados Pré-Operatórios , Estudos Prospectivos , Estudos Retrospectivos , Segurança , Resultado do Tratamento , Revisão da Utilização de Recursos de Saúde
9.
Br J Radiol ; 76(909): 590-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14500272

RESUMO

For 50 years, high intensity focused ultrasound (HIFU) has been a subject of interest for medical research. HIFU causes selective tissue necrosis in a very well defined volume, at a variable distance from the transducer, through heating or cavitation. Over the past decade, the use of HIFU has been investigated in many clinical settings. This literature review aims to summarize recent advances made in the field. A Medline-based literature search (1965-2002) was conducted using the keywords "HIFU" and "high intensity focused ultrasound". Additional literature was obtained from original papers and published meeting abstracts. The most abundant clinical trial data comes from studies investigating its use in the treatment of prostatic disease, although early research looked at applications in neurosurgery. More recently horizons have been broadened, and the potential of HIFU as a non-invasive surgical tool has been demonstrated in many settings including the treatment of tumours of the liver, kidney, breast, bone, uterus and pancreas, as well as conduction defects in the heart, for surgical haemostasis, and the relief of chronic pain of malignant origin. Further clinical evaluation will follow, but recent technological development suggests that HIFU is likely to play a significant role in future surgical practice.


Assuntos
Terapia por Ultrassom/métodos , Doenças Mamárias/terapia , Feminino , Previsões , Humanos , Nefropatias/terapia , Hepatopatias/terapia , Masculino , Doenças Prostáticas/terapia , Terapia por Ultrassom/instrumentação , Terapia por Ultrassom/tendências , Ultrassom Focalizado Transretal de Alta Intensidade/métodos , Ultrassom Focalizado Transretal de Alta Intensidade/tendências , Doenças da Bexiga Urinária/terapia
11.
J Natl Med Assoc ; 86(2): 141-4, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8169990

RESUMO

A review of 313 intraoperative consultations and/or frozen section evaluations of neoplasms of the ovary was conducted. The intraoperative diagnosis of benign or malignant was compared with the diagnosis found at permanent section. Only six cases were deferred to permanent section. The overall accuracy was 93.9%. The sensitivity was 72.7%, and this was explained by the high proportion of borderline or low malignant cell tumors in this series. The specificity and predictive values were in excess of 95%. Thirteen cases were diagnosed incorrectly at intraoperative consultation. Eight of these were judged to be sampling errors, one was due to poor technical quality, and four were attributed to interpretation errors. Intraoperative consultation is, and should continue to be, a valuable tool in the evaluation of ovarian neoplasms.


Assuntos
Cuidados Intraoperatórios , Neoplasias Ovarianas/diagnóstico , Erros de Diagnóstico , Feminino , Secções Congeladas , Humanos , Neoplasias Ovarianas/cirurgia , Valor Preditivo dos Testes , Encaminhamento e Consulta , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
12.
J Natl Med Assoc ; 85(2): 117-9, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8441187

RESUMO

Two hundred eighty-nine patients were evaluated over a 23-month period to assess the efficacy of postcone biopsy endocervical curettage at the time of cervical conization. One hundred eleven patients were excluded because the endocervical curettage was insufficient or not performed, the final pathology on the cone biopsy and endocervical curettage revealed no dysplasia or cancerous process, or the endocervical margins were not assessed, leaving a total of 178 patients in the study population. A negative conization endocervical margin virtually assures no disease in the upper endocervical canal. The negative predictive value in this study population was 97%. We conclude that routine endocervical curettage is unnecessary for most patients and should be primarily considered for patients who are postmenopausal or for those receiving suboptimal conizations.


Assuntos
Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Colo do Útero/patologia , Diagnóstico Diferencial , Dilatação e Curetagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia
13.
Genomics ; 13(1): 176-88, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1577481

RESUMO

We have obtained and sequenced the coding sequence of the mouse cardiac alpha-myosin heavy chain (Myhc alpha) from the A/J, BALB/cByJ, C57BL/6J, and DBA/2J inbred mouse strains. Overlapping cDNA sequences were obtained using RNA-PCR and anchor-PCR techniques for these studies. In the A/J mouse strain, the full-length message is 5989 bp long and encodes for a protein consisting of 1938 amino acids (Mr 223,689). The protein deduced sequence of the A/J Myhc alpha was compared with corresponding sequences of human and rat Myhc alpha and beta. These results demonstrated that the mouse Myhc alpha is highly conserved and has maintained the alpha-isoform-specific divergent cluster observed in other Myhc alpha proteins. One difference was the loss of a glutamine at residue 1932, which is due to a change in an RNA splicing site sequence. Allelic variability was observed in both nucleotide and amino acid sequences among the four different inbred mouse strains and generally appears to be random in nature. Three of the nucleotide changes resulted in a different amino acid, while the remaining 46 were silent substitutions.


Assuntos
Alelos , Miosinas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Miocárdio/química , Miosinas/química , Oligodesoxirribonucleotídeos/genética , Reação em Cadeia da Polimerase , Homologia de Sequência do Ácido Nucleico
14.
Chest ; 99(5): 1203-7, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-2019179

RESUMO

The atrial myxoma is a primary tumor of the heart which may have an uncertain clinical course. In this study, we performed flow cytometric DNA analysis of 15 paraffin-embedded atrial myxomas and correlated DNA ploidy status and proliferative fraction with clinical findings. Twelve of 15 cases (80 percent) were diploid and the remaining three cases (20 percent) were aneuploid. Two patients with aneuploid histograms were free of tumor at the time follow-up; the third patient experienced local tumor recurrence and metastases. Five patients with diploid myxomas demonstrated an elevated (greater than or equal to 17 percent) proliferative cell cycle fraction; four of these patients experienced embolic phenomenon or tumor recurrence. This pilot study suggests that an atrial myxoma with either aneuploid DNA content or elevated proliferative fraction may be associated with aggressive biologic behavior.


Assuntos
DNA de Neoplasias/análise , Neoplasias Cardíacas/genética , Mixoma/genética , Aneuploidia , Feminino , Citometria de Fluxo , Átrios do Coração , Humanos , Masculino , Projetos Piloto
15.
Arch Oral Biol ; 35(6): 431-4, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2196868

RESUMO

The suitability of using the cytokine TNF as an indicator of periodontal disease was assessed. Gingival crevicular fluid was collected from 162 sites on filter strips and analysed for TNF by ELISA. About 21% of the sites contained TNF: the amount recovered per site ranged from 0.2 to 998.8 fmol with a median value of 3.7 fmol. The periodontal disease status of each site was documented by recording the gingival and plaque indices, and by measuring pocket depth. About 62% of TNF-containing sites had a gingival index of 1, 76% had a plaque index of 0 or 1, and 47% had pockets of 3 mm or less. When the periodontal status of sites with and without TNF was compared by chi 2 analysis, no significant differences were found. These findings suggest that TNF may be found in sites prior to clinically observable disease and therefore may prove to be a suitable indicator for periodontal disease.


Assuntos
Líquido do Sulco Gengival/metabolismo , Gengivite/metabolismo , Doenças Periodontais/metabolismo , Fator de Necrose Tumoral alfa/análise , Ensaio de Imunoadsorção Enzimática , Humanos , Índice Periodontal , Bolsa Periodontal/metabolismo
16.
Ann Acad Med Singap ; 18(2): 174-7, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2751233

RESUMO

This is a retrospective study of 525 posterior chamber implants in diabetics performed by A S M Lim and B C Ang of Singapore. The patients were reviewed by visiting ophthalmologists--J E Kennedy (Sydney), M Ngui (East Malaysia) and P M Hart (Belfast). This study did not show any significant difference in the complication of post-operative visual acuity between diabetics and non-diabetics. 95% obtained 6/12 vision or better when pre-existing disease was excluded. It also showed that posterior chamber implants can be inserted in eyes with maculopathy or proliferative retinopathy if laser treatment was effectively done before or after surgery.


Assuntos
Catarata/complicações , Complicações do Diabetes , Lentes Intraoculares , Adulto , Fatores Etários , Idoso , Retinopatia Diabética/complicações , Retinopatia Diabética/patologia , Feminino , Humanos , Terapia a Laser , Fotocoagulação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Acuidade Visual
17.
Appl Environ Microbiol ; 51(5): 956-62, 1986 May.
Artigo em Inglês | MEDLINE | ID: mdl-3524456

RESUMO

The effects of eluent composition, pH, and chaotropic agents on the recovery of T2, MS2, and indigenous coliphages from various foods were investigated. Additionally, methods of sample suspension and clarification were evaluated for coliphage recovery and application to various foods. Clarified sample suspensions were assayed for coliphages with a modified agar layer technique and appropriate Escherichia coli hosts. Centrifugation and polypropylene mesh filtration were more rapid and effective than glass wool filtration for clarification of sample suspensions and subsequent recovery of coliphages. Blending, stomaching, and shaking procedures were generally comparable for sample liquefaction and release of coliphages from foods. Complex basal eluents, EC medium and 1% casein, were generally more effective than a less complex eluent, phosphate buffer, for elution of coliphages from foods. For most foods, incorporation of sodium chloride or chaotropic agents, i.e., sodium trichloroacetate, urea, Tween 80, Triton X-100, and sodium nitrate, into basal eluents did not enhance recovery of coliphages. Indigenous coliphage recovery was not affected by sample suspension pH over a range of 6.0 to 9.0. With an optimal procedure, i.e., EC medium eluent, blending, and centrifugation, the recovery of T2 and MS2 ranged from 48 to 81% and from 58 to 100%, respectively, depending on the food type.


Assuntos
Colífagos/isolamento & purificação , Microbiologia de Alimentos , Animais , Técnicas Bacteriológicas , Bovinos , Centrifugação , Galinhas , Colífagos/crescimento & desenvolvimento , Meios de Cultura , Escherichia coli/análise , Filtração , Conservação de Alimentos , Concentração de Íons de Hidrogênio , Carne , Suínos , Verduras
18.
Aust N Z J Ophthalmol ; 13(4): 349-54, 1985 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3833294

RESUMO

We undertook a survey of all intraocular lenses (IOLs) implanted by two surgeons from 1976 up to the end of 1983. Of the 967 implants, 164 were excluded because of lack of adequate follow-up. Of the remaining 803 cases there were 104 anterior chamber lenses, 185 iris-supported lenses, and 514 posterior chamber lenses. The overall final visual acuity was 6/12 or better in 740 cases (92.2%). Of the remaining 63 cases, 32 had pre-existing disease or associated conditions not directly related to the operation. By analysing the results within each major group of IOL we found that the posterior chamber IOLs had the best final visual acuity (94.4% 6/12 or better) and fewer postoperative complications. The major problems with iris-supported IOLs were corneal decompensation and cystoid macular oedema.


Assuntos
Lentes Intraoculares , Adulto , Idoso , Câmara Anterior/cirurgia , Feminino , Seguimentos , Humanos , Iris/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Desenho de Prótese , Acuidade Visual
19.
Cancer ; 51(11): 2152-6, 1983 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-6839303

RESUMO

A series of 204 melanoma patients were studied six months or longer after regional lymph node dissection of the neck (N = 48), axilla (N = 98) and groin (N = 58) in order to determine the degree of morbidity and analyze for risk factors associated with these procedures. Only one-quarter of the patients experienced wound-related, short-term complications that were common at all sites; however, these rarely resulted in long-term functional deficits. Seromas (22%), temporary nerve dysfunction or pain (14%), and wound infections (6%) were the most frequent short-term complications. Wound complications extended the mean hospital stay by 0.6 to 4.8 days. Residual lymphedema of the leg was measurable in 26% of groin dissection patients after six months or longer; most of the edema was confined to the thigh. Only 8% of patients had significant functional deficit from lymphedema. The risk of developing at least one complication for all patients was increased for obese patients (P = 0.05) and increasing age (P = .01). These risk factors should be considered when evaluating melanoma patients for regional lymph node dissection.


Assuntos
Excisão de Linfonodo/efeitos adversos , Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Adolescente , Adulto , Idoso , Axila , Feminino , Humanos , Tempo de Internação , Excisão de Linfonodo/mortalidade , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Readmissão do Paciente , Risco
20.
Va Dent J ; 50(5): 22-5, 1973 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-4519862
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