Measurement of the concentration of three antituberculosis drugs in the focus of spinal tuberculosis

This is an experimental study on the distribution of antituberculosis drugs such as rifampin, isoniazid, and pyrazinamide in pathologic vertebrae of spinal tuberculosis in order to provide the regimen of chemotherapy and surgical treatment of spinal tuberculosis. The distribution of antituberculosis drugs in pathologic vertebral tissues matters greatly to the clinical effect of spinal tuberculosis’ treatment. However, few pharmacokinetic studies and clinical reports about the concentrations of antituberculosis drugs in vertebral foci have been published so far. Twenty-four patients with spinal tuberculosis were divided into sclerotic group (n = 15) or non-sclerotic group (n = 9) according to radiographic features of lesion. All patients received chemotherapy with 2HRZ/2·5H₂R₂Z₂ for a duration of 4.5 months. Four weeks after chemotherapy all patients underwent surgery and the specimen of serum, ilium, and pathologic vertebral tissues, including sclerotic wall, subnormal osseous tissue, and foci were obtained during operation in 120–130 and 180–190 min after oral intake in the morning, respectively. The levels of three drugs in the specimen were measured using HPLC method. The concentration levels of isoniazid, rifampin and pyrazinamide varied greatly in different tissues of spinal tuberculosis, of which the bactericidal concentration values of isoniazid and rifampin and fivefold minimal inhibitory concentration (MICs) of pyrazinamide were found in subnormal vertebral bone and self-contrast ilium, the MICs of all drugs were found in sclerotic wall outside foci, and undetected level was found in foci inside the sclerotic wall. To patients without vertebral sclerotic wall around the foci, the isoniazid in foci was of bactericidal level and rifampin and pyrazinamide in foci corresponded to the MICs respectively. The sclerotic bone of affected vertebra plays an important role in blocking the antituberculosis drug’s penetration into tuberculosis focus.     

脊柱结核病灶中抗痨药物浓度的测定

目的研究脊柱结核病椎各部位抗结核药物的分布特点,为脊柱结核化疗方案与手术治疗方法的改进提供理论依据。方法24例应用2SHRZ/2.5H2R2Z2(4.5个月)方案化疗结合手术治疗的脊柱结核患者,按有无病椎骨硬化分为硬化组和非硬化组。化疗第4周手术,依据手术取材时间分为术晨服药后120~130、180~190min两个时相点,取硬化组的病椎硬化壁、硬化壁外“亚正常骨”、硬化壁内结核病变组织和非硬化组的病椎结核病变组织、病变组织外“亚正常骨”以及两组患者的血浆、髂骨,采用高效液相色谱法测定上述样本的药物浓度。结果(1)吡嗪酰胺(PZA)和异烟肼(INH)各时相血药浓度与文献报道健康人单次服药的药时数据相近,利福平(RFP)则低25%,各药血药浓度高于髂骨及病椎组织中的药物浓度。(2)两组中“亚正常骨”与髂骨内的INH和RFP均达到了各自的杀菌浓度水平,PZA超过其细胞内酸性条件下MIC的5倍。三种药物各自在“亚正常骨”与自身对照的髂骨之间浓度相近。(3)硬化组中硬化壁的药物浓度仅为各药的最小抑菌浓度水平(MICs),远低于壁外围“亚正常骨”,壁内的结核病变组织中未检出上述三种药。(4)非硬化组结核坏死、干酪组织中RFP及PZA的浓度相当于各自的MICs,远低于其他组分,而INH却达到细胞内杀菌浓度。结论INH、RFP和PZA在脊柱结     

Urachal tuberculosis

BACKGROUND: We report on an extremely rare case of urachal tuberculosis that was confirmed using a polymerase chain reaction test of paraffin-embedded material. METHODS/RESULTS: A 62-year-old man presented with pollakiuria. With a diagnosis of urachal abscess, the patient underwent en bloc resection of the cystic mass. A bacterial culture test of the content showed no organism. The histopathologic findings suggested urachal tuberculosis. The AMPLICOR polymerase chain reaction test by using paraffin-embedded sections revealed the existence of Mycobacterium tuberculosis in the resected tissue. The only positive finding in systemic screening examinations for tuberculosis was old tuberculosis scars in the upper right lung. It was supposed that hematogeneous spreading from the lung lesion may result in urachal tuberculosis after a long latent period. CONCLUSIONS: Although urachal tuberculosis is an extremely rare condition, tuberculosis must always be kept in mind when observing any infectious diseases.     

应用Xpert MTB/RIF对脊柱结核临床标本行结核分枝杆菌与利福平耐药性检测的验证性研究

 目的 采用Xpert MTB/RIF系统对系列脊柱结核临床标本进行结核分枝杆菌检出与利福平耐药基因rpoB突变检测,初步验证该项技术的可行性与准确性。方法 自全军结核病研究所标本库中筛选140份脊柱结核临床标本,对标本行前处理后采用Xpert MTB/RIF系统进行结核分枝杆菌与利福平耐药基因rpoB的突变检测,以培养结果及表型药敏试验为金标准,判断Xpert MTB/RIF检测的敏感度、特异度、95%置信区间及检测耗时。结果 对临床确诊为脊柱结核的140份临床标本,Xpert MTB/RIF系统的结核分枝杆菌阳性检出率为63.57% (89/140);在64份培养阳性标本中,Xpert MTB/RIF检测结核分枝杆菌的敏感度为98.44% (63/64);在76份培养阴性标本中,Xpert MTB/RIF检测结核分枝杆菌的敏感度为34.21% (26/76)。以表型药敏试验为金标准,采用Xpert MTB/RIF系统行利福平耐药性检测的敏感度为93.33% (28/30),特异度为94.12% (32/34)。Xpert MTB/RIF系统平均检测耗时为2.1 h (1.8~2.6 h)。结论 Xpert MTB/RIF是一种简便、快速、准确,且能够同时对脊柱结核临床标本行结核分枝杆菌检测与利福平耐药性检测的分子检测技术,具有潜在的临床应用价值。     

Identification of HIV patients with active pulmonary tuberculosis using urine based polymerase chain reaction assay

BACKGROUND: Despite the increased dissemination of tuberculosis among HIV infected patients, the diagnosis is difficult to establish. Traditional microbiological methods lack satisfactory sensitivity. We have developed a highly sensitive and specific nested polymerase chain reaction (PCR) capable of detecting Mycobacterium tuberculosis DNA in urine specimens and have used this test to examine urine specimens from HIV patients with active pulmonary tuberculosis. METHODS: Urine specimens from 13 HIV infected patients with microbiologically proven active pulmonary tuberculosis, 10 AIDS patients with non-tuberculous mycobacterial infection (documented by blood culture), 53 AIDS patients with no evidence of mycobacterial disease, and 80 healthy subjects (25 with positive skin test to purified protein derivative) were tested for M tuberculosis using PCR, acid fast staining (AFS), and culture. RESULTS: Of the urine specimens from patients with active tuberculosis, all tested positive by PCR, two by culture, and none by AFS. No reactivity was observed in urine specimens from patients with non-tuberculous mycobacterial infection. Of the 53 AIDS patients without mycobacterial infection, one had a positive urine PCR. Normal subjects were all negative. CONCLUSIONS: Urine based nested PCR for M tuberculosis may be a useful test for identifying HIV patients with pulmonary tuberculosis.     

The ligase chain reaction as a primary screening tool for the detection of culture positive tuberculosis

BACKGROUND: The ligase chain reaction Mycobacterium tuberculosis assay uses ligase chain reaction technology to detect tuberculous DNA sequences in clinical specimens. A study was undertaken to determine its sensitivity and specificity as a primary screening tool for the detection of culture positive tuberculosis. METHODS: The study was conducted on 2420 clinical specimens (sputum, bronchoalveolar lavage fluid, pleural fluid, urine) submitted for primary screening for Mycobacterium tuberculosis to a regional medical microbiology laboratory. Specimens were tested in parallel with smear, ligase chain reaction, and culture. RESULTS: Thirty nine patients had specimens testing positive by the ligase chain reaction assay. Thirty two patients had newly diagnosed tuberculosis, one had a tuberculosis relapse, three had tuberculosis (on antituberculous therapy when tested), and three had healed tuberculosis. In the newly diagnosed group specimens were smear positive in 21 cases (66%), ligase chain reaction positive in 30 cases (94%), and culture positive in 32 cases (100%). Using a positive culture to diagnose active tuberculosis, the ligase chain reaction assay had a sensitivity of 93.9%, a specificity of 99.8%, a positive predictive value of 83.8%, and a negative predictive value of 99.9%. CONCLUSIONS: This study is the largest clinical trial to date to report the efficacy of the ligase chain reaction as a primary screening tool to detect Mycobacterium tuberculosis infection. The authors conclude that ligase chain reaction is a useful primary screening test for tuberculosis, offering speed and discrimination in the early stages of diagnosis and complementing traditional smear and culture techniques.     

脊柱结核病灶清除并椎间支撑植骨术后并发症的防治

目的 探讨脊柱结核病灶清除并椎间支撑植骨术后并发症的防治方法.方法 2000年1月—2015年12月,宁夏医科大学总医院采用病灶清除并椎间支撑植骨术治疗脊柱结核患者326例.通过术后X线片、MRI及CT分析植骨融合情况及植骨相关并发症发生情况.结果 所有患者术后化疗3～36(7.89±5.92)个月,结核灶全部治愈、植骨融合后停药,无新的结核灶形成.共使用348个植骨材料,其中髂骨290个,多根肋骨捆绑20个,肋髂骨捆绑26个,钛网12个.术后植骨融合过程中发生植骨倾斜9例(2.8％),植骨骨折8例(2.5％)、植骨吸收4例(1.2％)、植骨下沉3例(0.9％)、植骨移位1例(0.3％)、假关节形成1例(0.3％),相应给予延长制动时间、辅助外固定、再次手术彻底清除病灶或硬化骨、延长用药时间等措施,直至植骨融合、病灶治愈.结论 脊柱结核病灶清除并椎间支撑植骨术后植骨融合过程中可能出现植骨块倾斜、骨折、吸收、下沉、移位及假关节形成等并发症,应注意预防并给予相应处理,促进病灶治愈和植骨融合.     

Mycobacterium tuberculosis DNA in tissues affected by sarcoidosis

BACKGROUND: Although some studies have reported the presence of Mycobacterium tuberculosis (MTb) DNA in tissues affected by sarcoidosis, the data are conflicting. The aim of this study was to collect prospectively tissue from patients with sarcoidosis in whom tuberculosis had been excluded, and to use polymerase chain reaction (PCR) to search for DNA sequences specific for MTb. METHODS: Fresh tissue samples (node or lung biopsy) taken from 23 patients with newly diagnosed sarcoidosis, 10 with other respiratory disease, and four patients with culture positive tuberculosis were analysed using PCR to amplify a 123 bp fragment of IS6110, the insertion element present in MTb, and nested PCR to further amplify an 85 bp sequence within the 123 bp product. DNA was also extracted from formalin fixed tissue from eight additional patients with sarcoidosis. RESULTS: MTb DNA was not detected in any of the tissue samples from patients with sarcoidosis or other respiratory disease but was found in all four patients with tuberculosis. CONCLUSIONS: This study has shown the absence of MTb DNA in lymph node and lung biopsy samples from patients with sarcoidosis. MTb is therefore unlikely to be a factor in the pathogenesis of this disease.     

结核分枝杆菌快速培养和常规药敏试验在脊柱结核治疗中的应用

目的 探讨BACT/ALERT 3D系统快速培养和绝对浓度法药敏试验对指导脊柱结核个体化化疗的应用价值,分析研究脊柱结核耐药情况.方法 根据临床表现、影像学表现、病理检查,50例患者诊断为脊柱结核,并接受手术治疗.收集术中所取脓液、干酪样组织.低温避光保存,8 h内送检,常规处理后接种液体培养基,使用BACT/ALERT 3D系统进行分枝杆菌快速培养.培养阳性者接种PNB和TCH培养基进行菌种鉴定,并将细菌接种至含药改良罗氏培养基,按绝对浓度法进行11种常用一线和二线抗结核药物药敏试验.结果 50例标本培养阳性21例(42%),人型结核杆菌19例,牛型结核杆菌2例.结核杆菌培养和药敏试验平均耗时41 d(28～58 d).其中耐药11例(52.4%),异烟肼耐药4例(19.0%),利福平和乙胺丁醇各1例(4.8%),链霉素3例(14.3%),力克肺疾2例(9.5%),左氧氟沙星8例(38.1%).结论 结核分枝杆菌快速培养和常规药敏试验准确度高,费用低,可检测常用一线和二线药物的敏感性,适用于指导脊柱结核个体化化疗方案的制定.异烟肼、利福平、吡嗪酰胺、乙胺丁醇或(和)链霉素联合用药方案对多数初治脊柱结核患者有效.     

Extrapulmonary tuberculosis in a patient with septic shock

A 61-year-old woman who was negative for type 1 human immunodeficiency virus developed vertebral osteomyelitis and skin lesions due to sepsis by Staphylococcus aureus. Microscopic examination of the skin showed alcohol-resistant acid-fast bacilli. A polymerase chain reaction (PCR) assay for Mycobacterium tuberculosis was positive for skin and spinal samples, although the cultures were negative. The diagnosis of M. tuberculosis infection is difficult, particularly when the disease is extrapulmonary. Rapid diagnostic tests that use PCR identify the DNA of the bacillus with greater sensitivity than microscopic examination and can give results within 24 hours of receipt of a sample. We analyze the utility of PCR for diagnosing extrapulmonary tuberculosis.     

核酸体外扩增技术诊断骨结核病的临床研究及应用价值

目的 探讨核酸体外扩增(polymerase chain reaction,PCR)技术在骨结核病诊断与鉴别诊断中的应用价值。方法 对60例骨结核病标本与30例非骨结核病标本分别进行核酸体外扩增技术,抗酸染色镜检及结核杆菌分离培养法检测结核杆菌,分析影响核酸体外扩增技术结果的相关因素及处理方法。结果 骨结核标本结核杆菌检出阳性率:PCR法83％,抗酸染色镜检法3％,培养法7％。非骨结核标本结核杆菌检出阳性率:PCR法10％,其他方法均未检出,经统计学处理P<0.005,PCR法与镜检法及培养法相比较差异具有显著性。结论 PCR技术是一种快速、敏感、简便、特异的检测骨结核标本结核杆菌的方法,明显优于镜检法及培养法,在骨结核的诊断与鉴别诊断中有重要价值。     

Rapidly developing T-cell posttransplantation lymphoproliferative disorder

Posttransplantation lymphoproliferative disorder (PTLD) of T-cell origin has been rarely described in chronically immunosuppressed allograft recipients. We report a case of renal PTLD of a T lineage that occurred shortly after transplantation under a triple-immunosuppressive regimen. Renal graft biopsy performed 58 days posttransplantation showed extensive interstitial infiltrates of polymorphic lymphoid cells, which expressed the UCHL-1 and CD3 markers for T-cell lineage. The clonal nature of the T cells in renal tissue was identified by showing rearrangement of the T-cell receptor γ chain genes using a polymerase chain reaction (PCR). DNA extracted from the graft biopsy specimen did not show the sequences of human T-cell leukemia virus type 1 (HTLV-1) by PCR. Signals for Epstein-Barr virus (EBV) infection in renal tissue were not shown by in situ hybridization. After the reduction of immunosuppressive therapy, regression of PTLD lesion and development of rejection were shown in the second graft biopsy and graftectomy specimen. The extreme rarity of rapidly developing T-cell PTLD in a renal allograft prompted us to write this report.     

Rapid diagnosis of genitourinary tuberculosis by polymerase chain reaction and non-radioactive DNA hybridization

OBJECTIVE: To establish a polymerase chain reaction (PCR) assay for the rapid detection and identification of mycobacteria in urine, and to assess the value of such assay in routine laboratory diagnosis of genitourinary tuberculosis. MATERIALS AND METHODS: Urine specimens from 1000 patients with clinical suspicion of urinary tuberculosis were examined. Two assays for the detection and identification of Mycobacterium tuberculosis (M. tuberculosis) complex and mycobacteria other than tuberculosis (MOTT) by non-radioactive DNA hybridization of PCR-product were applied. The first assay used PCR primers and probe derived from M. tuberculosis species-specific DNA insertion sequence, IS6110. The second utilized mycobacterium genus-specific sequence encoding ribosomal ribonucleic acid (16S rRNA). The results obtained by PCR were compared with those obtained by standard microbiological methods, acid-fast bacilli (AFB) stain and culture. RESULTS: Compared with cultures, the sensitivity of AFB staining was 52.07% and the specificity was 96.7%. In comparison to the results of culture, the overall sensitivity and specificity of the IS6110-PCR assay was 95.59% and 98.12% respectively. While the corresponding results for the 16S rRNA gene-PCR were 87.05% and 98. 9%. CONCLUSION: The high sensitivity and specificity in addition to the potential for rapid detection of mycobacteria, makes this test a useful tool in the clinical management of mycobacterial infection in urine. Urine specimens may contain M. tuberculosis and/or other mycobacteria; therefore, there are advantages in using genus-specific primers in parallel with species-specific primers in PCR assay.     

Polymerase chain reaction can detect bacterial DNA in aseptically loose total hip arthroplasties

Identifying low-grade infection in failed total hip arthroplasties is an important but difficult task. This study investigated the ability of the polymerase chain reaction to identify low-grade infection during revision of total hip arthroplasties that failed from aseptic causes. One hundred thirteen specimens from 31 total hip arthroplasties revised for aseptic loosening were compared with 105 control specimens from 28 primary total hip arthroplasties. All surgeries were done in laminar flow operating rooms. No primary or revision specimen had positive microbiologic cultures. No revision specimen had histologic evidence suggestive of infection. Using the polymerase chain reaction with a detection threshold of 10 organisms per cubic centimeter of specimen, bacterial DNA was identified in 39 of 85 revision tissue specimens (46%) compared with 18 of 84 primary tissue specimens (21.4%). Bacterial DNA was identified in the synovial fluid of three specimens taken from 28 revision total hip arthroplasties (10.7%) and in two specimens taken from 21 primary total hip arthroplasties (9.5%). As multiple specimens were sent for each hip, a maximum of 16 of 31 revision total hip arthroplasties (52%) and eight of 28 primary total hip arthroplasties (29%) were considered to be infected. Bacterial DNA can be found in many specimens obtained from revised total hip arthroplasties considered to be aseptically loose. Because bacterial DNA identified at primary total hip arthroplasty was assumed to be attributable to contamination rather than present in healthy tissues, the overall specimen contamination rate of 19% and case contamination rate of 29% indicate that the polymerase chain reaction has poor specificity at this sensitivity level for diagnosing infection in revision total hip arthroplasty.     

Value of tissue biopsy in bone and joint tuberculosis

This study discusses the difficulties in making the diagnosis of bone and joint tuberculosis and underlines the diagnostic value of tissue biopsy from the site of the suspected tuberculosis lesion. Fifty-two patients, suffering from this disease, underwent treatment at our hospital between 1980-1986. In 27 cases (51%) the diagnosis was made on the basis of the clinical picture and various tests not including biopsy. The other 25 cases (48%) required a biopsy, and tissue specimens were sent for histological examination and culture with the L?wenstein-Jensen medium. In 9 (17.3%) patients the biopsy was performed early, while in another 16 (30.8%) patients there was a delay (23 months on average). From the total of 25 biopsies the histological examination showed findings compatible to tuberculosis in 23 (92%), while the culture of the same material was positive only in 10 (40%). The high rate of diagnostic accuracy with the biopsy, proves that this method is probably the most useful one for the diagnosis of bone and joint tuberculosis and emphasizes the need to use this method more often.     

单核细胞趋化蛋白-1基因多态性对脊柱结核易感性的影响

[目的]分析趋化因子单核细胞趋化蛋白-1(MCP-1)启动子区362基因型频率和等位基因多态性与中国湖南省汉族人群脊柱结核易感性的关系.[方法]选取2007年12月～2010年12月本院收治的湖南汉族新发脊柱结核患者166例(病例组)及健康志愿者200例(对照组),应用聚合酶链式反应(PCR)和DNA直接测序法检测两组患者MCP -1 - 362位点的多态性,并进行MCP -1基因分型.[结果]MCP -1 - GG、GC、CC三种基因型在病例组和对照组中的分布频率分别为18.1％、42.8％、39.2％和25.5％、48.0％、26.5％.两组组间比较有显著性差异(P＜0.05),其中MCP -1 - CC基因型在病例组中的分布频率明显高于对照组,比值比(odds ratio,OR)为1.478,其95％可信区间(confidence interval,CI)为1.096～1.992.[结论]在湖南汉族人群中,MCP -1 - 362位点CC基因型可能与脊柱结核的易感性相关.     

Comparison of polymerase chain reaction amplification of two mycobacterial DNA sequences, IS6110 and the 65kDa antigen gene, in the diagnosis of tuberculosis.

BACKGROUND: Knowledge of the sequences of mycobacterial genes and the availability of DNA amplification techniques have raised the possibility that identification of mycobacterial DNA may offer a rapid and specific diagnostic test for tuberculosis. The correlation between the presence of Mycobacterium tuberculosis DNA and clinical tuberculosis, however, is not known. This study compared the results of polymerase chain reaction amplification of two M tuberculosis DNA sequences, IS6110 and the gene encoding the 65kDa heat shock protein (65kDa Ag), from sputum, bronchoscopy washings, and bronchoalveolar lavage fluid and related these findings to the presence of active and past tuberculosis. METHODS: Highly specific primers were used for amplification of IS6110 and 65kDa Ag DNA. Analysis was performed on one or more samples from 87 patients. RESULTS: IS6110 DNA was identified in samples from all six patients with active tuberculosis, from 15 to 18 patients with past tuberculosis, from five of nine contacts of patients with tuberculosis, and from nine of 54 patients with lung disease unrelated to tuberculosis. The 65kDa Ag DNA was identified in samples from all patients with active and past tuberculosis, from contacts of patients with tuberculosis, and from 14 of 42 patients with non-tuberculous lung diseases. CONCLUSION: These data suggest that the presence of IS6110 DNA correlates more closely with a tuberculosis related diagnosis than that of 65kDa Ag DNA and that both DNAs are found in most subjects with past tuberculosis or contacts of patients with tuberculosis. This may limit the clinical usefulness of these tests.     

非典型胸腰椎结核的临床诊断和手术治疗

目的:总结和分析非典型胸腰椎结核的临床诊断和手术治疗特点,为非典型脊柱结核的诊治提供参考。方法:回顾性分析我院骨科2013年12月~2018年12月明确诊断并手术治疗的脊柱结核患者资料,根据影像学特点筛选出非典型胸腰椎结核13例,男8例,女5例,年龄20~71岁(44.2±18.7岁)。2例以腹股沟区包块为首发表现,2例患者以发热和咳嗽首发症状,其余患者均以腰背痛首发症状。术前疼痛视觉模拟评分(visual analogue scale,VAS)为5~8分(6.2±0.8分)。神经功能Frankel分级C级1例,D级3例,E级9例。术前均行X线片、CT和MRI检查,影像学上未见明显椎间隙狭窄、后凸畸形,CT可见不同程度的椎体骨破坏或囊性变、边缘硬化灶、“磨玻璃”样改变,MRI表现为椎体破坏、炎症水肿和椎旁脓肿改变。4例行正电子发射计算机断层显像(positron emission tomography-computer tomography,PET-CT)检查,10例行T细胞酶联免疫斑点试验(enzyme-linked immuno Spot,ELISPOT)检查均为阳性,4例术前行病灶活检。术前四联抗结核药物治疗至少1~2周,根据病灶位置及椎体破坏情况,7例行后路手术,6例行前后路联合手术。术后继续采用标准疗程抗结核药物治疗。结果:非典型胸腰椎结核患者占同期手术治疗脊柱结核的20.3%(13/64)。胸椎6例,腰椎5例,胸腰椎均累及2例。根据CT及MRI影像学分类,单脊椎型2例,椎间盘型1例,多脊椎连续型10例。手术时间130~260min(177.7±43.0min),出血量400~1000ml(638.5±198.1ml),无术中并发症。手术清除病灶组织均送病理检查,报告为肉芽肿性病变和/或凝固性坏死;结核菌涂片和培养各有1例阳性。术后伤口感染1例,经清创后好转。术后随访12~72个月(45.1±22.2个月),随访期间钛网移位1例,因无明显症状,未翻修,术后32个月随访无继续移位及内固定断裂;其余患者末次随访时均无内固定断裂。植骨在术后3~6时可见融合,随访期间无复发病例。术后疼痛及神经功能均有明显改善,末次随访时VAS评分1~4分(1.8±0.9分),神经功能Frankel分级末次随访均为E级。结论:非典型胸腰椎结核确诊需多种诊断手段相结合,手术结合抗结核药物治疗可取得较好的疗效。     

Detection of human papillomavirus in the prostate by polymerase chain reaction and in situ hybridization.

Human papillomavirus is associated with a variety of anogenital lesions, including genital warts, precancers and cancers. In male patients human papillomavirus has been identified in proliferative lesions ranging from penile and urethral warts to penile and prostatic cancers. We examined the association of human papillomavirus deoxyribonucleic acid (DNA) in 84 prostate tissue specimens. Specimens were selected from radical prostatectomy, transurethral resection or transrectal biopsy procedures. A total of 60 formalin-fixed, paraffin-embedded tissues (24 prostate cancer specimens, 16 benign prostatic hyperplasia specimens and 20 normal specimens) was examined by polymerase chain reaction and in situ hybridization. Also, 24 gelatin-embedded frozen prostate cancer specimens were examined for human papillomavirus DNA by polymerase chain reaction. Of the specimens 69 were deemed adequate for polymerase chain reaction analysis, whereas all 60 paraffin-embedded tissues were sufficient for in situ hybridization. Human papillomavirus DNA was detected in 2 normal tissues and 6 prostate cancers using polymerase chain reaction. None of the benign prostatic hyperplasia specimens was positive for human papillomavirus. Human papillomavirus typing results indicated that virus type 16 was present in each of the 8 positive specimens. Confirmation of the presence of human papillomavirus was obtained for 1 of the prostate cancers by nonisotopic in situ hybridization with biotinylated human papillomavirus genomic probes. The low prevalence of human papillomavirus in this study population does not strongly support an etiological role for the virus in prostate cancer.