Modulation of osteoclastogenesis induced by nucleoside reverse transcriptase inhibitors

Osteopenia is a common and debilitating side-effect of HAART, yet little is known concerning the effects of HAART on bone metabolism. We reported previously that zidovudine (AZT) stimulates osteoclastogenesis in vitro and causes osteopenia in mice. Here, we confirmed that the AZT-induced osteoclastogenesis is dependent on RANKL in that osteoclastogenesis is blocked by osteoprotegestin. Alendronate, which is used for the treatment of osteopenia and osteoporosis, failed to inhibit AZT-induced osteoclastogenesis in vitro. Osteoclastogenesis in vitro was not affected by tumor necrosis factor-alpha. Two other NRTI drugs, ddl and 3TC, also induced osteoclastogenesis in vitro and induced osteopenia in mice. The osteopenia was associated with an elevation of parameters of osteoclasts, but not with osteoblasts. Combinations of the NRTIs did not result in additive or synergistic effects in vitro or in vivo. Finally, AZT induced osteoclastogenesis of human osteoclast precursors in a RANKL-dependent manner. This in vitro osteoclastogenesis assay using human peripheral blood mononuclear cells could be useful in evaluating bone turnover and the risk of developing osteopenia in AIDS patients on HAART.     

Eosinophilic cystitis: eight cases report and literature review

Historically, eosinophilic cystitis is a rare disorder of bladder inflammation with eosinophils infiltration diagnosed by pathologic examination. The etiology is unclear despite the past identification of many factors contributing to this disease. Eight patients with eosinophilic cystitis were reported. The intact history, clinical manifestation, radiological examination and response to therapy were all evaluated. The results showed that 7 patients developed hematuria, 6 patients were with dysuria, 4 patients with frequency and 4 patients with urine retention. Seven patients had abnormal urinalysis but no positive finding in culture. Radiological findings revealed that one patient had bladder mass lesions and upper urinary tract dilation. Cystoscopic examination was performed in every patient and showed mass-like, edematous, ulcerative or hyperemic mucosa lesions. Cold-cup biopsy or transurethral resection of bladder lesions were all performed and could be the first priority to be considered. However, partial or total cystectomy should be taken into consideration when simple treatment failed to resolve this problem. Additionally, antihistamines, steroids or antibiotics are given to control the clinical symptoms. The results of these treatments were good except for one case who suffered from recurrence but recovered after simple operation and oral therapy. Although good results were found concerning treatment, long-term follow-up is necessary.     

Biguanide-associated lactic acidosis. Case report and review of the literature.

PURPOSE--The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis. PATIENT--We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia. RESULTS--Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital. CONCLUSIONS--Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.     

肺部肿瘤致异位ACTH综合征7例报告并文献复习

目的探讨肺部肿瘤致异位促肾上腺皮质激素（ACTH）综合征的临床特点。方法回顾性分析2000年11月～2009年12月解放军总医院内分泌科收治并确诊的7例肺部肿瘤致异位ACTH综合征患者的临床资料。结果高血压、糖尿病、低血钾、水肿为最常见的临床表现,多缺乏典型库欣综合征的体征;血ACTH和皮质醇、24 h尿游离皮质醇水平升高,皮质醇分泌均不被小剂量及大剂量地塞米松抑制试验所抑制;胸部薄层CT扫描能发现多数肺部病变;手术切除肺部病变、小细胞肺癌化疗效果较好;肾上腺切除为控制高皮质醇血症的有效手段。结论肺部肿瘤是导致异位ACTH综合征的常见病因,对于ACTH依赖性库欣综合征的患者应常规行胸部薄层CT来筛查肺部病变。     

Paraneoplastic rheumatic syndromes: report of eight cases and review of literature

Malignant neoplasms are associated with a wide variety of paraneoplastic rheumatological syndromes. The paraneoplastic nature should be based on specific criteria. We report a series of eight cases of paraneoplastic rheumatic syndromes revealing an underlying neoplasia. Our series consists of six men and two women, with a mean age of 46.1 (20-69?years). The first case is a hypertrophic osteoarthropathy of Pierre Marie that occurred in a 20-year-old man 1?month after treatment for his nasopharyngeal carcinoma; the paraclinical examinations showed lung and bone metastasis. The second case is that of a bilateral shoulder-hand syndrome revealing an invasive squamous cell carcinoma of the cervix in a 63-year-old woman. The third case involved a 69-year-old patient who had surgery 2?years ago for prostate adenocarcinoma and presented with polymyalgia rheumatica revealing bone metastasis. We also report two cases of leukemia in adults revealed by polyarthritis. The sixth observation is that of a paraneoplastic scleroderma that occurred concomitantly with prostate cancer. The seventh case of an acute arthritis showed a B lymphoma. The eighth case is that of a 52-year-old patient who presented with inflammatory arthralgias, and digital clubbing revealing a squamous cell carcinoma of the skin. Paraneoplastic rheumatism remains a rare event, but knowledge of it is essential for early diagnosis of underlying cancer.     

Severe lactic acidosis in association with reverse transcriptase inhibitors with potential response to L-carnitine in a pediatric HIV-positive patient

We report a case of life-threatening lactic acidosis in a 10-year-old male with HIV stage B2 infection, presumed to be vertically acquired. This occurred after several months of therapy with d4t, ddl, and nevirapine. His most recent CD4 count was 347 cells per microliter and viral load 16,000 copies per milliliter 3 weeks prior to admission. The peak lactic acid level was 12.4 mmol/L. Although multiple therapeutic interventions took place, the patient showed rapid improvement and resolution temporally associated with the administration of levocarnitine.     

Kartagener综合征3例分析并文献复习

目的 供临床医师提高对Kartagener综合征早期诊断和治疗.方法 通过3例病史、临床表现、影像学、彩超、心电图等检查明确诊断进行分析和文献复习.结果 Kartagener综合征是一种少见的常染色体隐性遗传性疾病.症状为:副鼻窦炎一支气管扩张一内脏转位三联征,其临床表现为反复咳嗽、咯脓痰、咯血等肺部表现,同时伴副鼻窦炎.结论 在内脏转位的患者中若出现支气管扩张症状及影像学表现,应想到Kartagener综合征的可能.     

Metabolic activation of nucleoside and nucleotide reverse transcriptase inhibitors in dendritic and Langerhans cells

BACKGROUND: Langerhans cells and interstitial dendritic cells are the earliest targets for HIV infection through sexual transmission of HIV. Metabolism of nucleoside analogues markedly differs in proliferating T lymphocytes and resting monocyte/macrophages, and thus their antiviral efficacy can substantially differ between both cell types. METHODS: The metabolism of radio-labelled zidovudine (ZDV), lamivudine (3TC) and tenofovir (PMPA) to their antivirally active metabolites was studied in primary cells, representative of early in vivo targets of HIV [i.e. monocyte-derived dendritic cells (MO-DC), MO-derived Langerhans cells (MO-LC), PHA/IL-2-activated T-blast cells] as well as in a laboratory T-lymphocyte (CEM) cell line. RESULTS: Whereas lamivudine metabolism to its active triphosphate derivative (3TC-TP) did not markedly differ between T-cells and MO-derived LC and DC, zidovudine was much better converted to ZDV-TP in T-cells than in MO-LC and MO-DC. In contrast, tenofovir was markedly more abundantly converted to its antivirally active diphosphate metabolite PMPApp in MO-DC and MO-LC than zidovudine and lamivudine. CONCLUSION: Our metabolic data suggest that tenofovir may be superior to zidovudine and lamivudine for inhibition of HIV replication in dendritic/Langerhans cells, the first-line cell types targeted by a primary HIV infection.     

Gitelman syndrome: report of three cases and literature review

Gitelman syndrome (GS) is a rare autosomal recessive, inherited renal tubular disorder. Herein, we report three cases of GS, one sporadic case and two siblings. They have typical laboratory findings, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. All of them were treated with oral potassium and magnesium supplements. They received regular pediatric clinic follow-up to check electrolytes and monitor development. These three cases reminded us that doctors should be alert to unexplained hypokalemia, which is usually the initial presentation of GS.     

溶血隐秘杆菌致Lemierre综合征一例并文献复习

 目的 提高对溶血隐秘杆菌致Lemierre综合征的认识及诊治水平。
方法 分析1例溶血隐秘杆菌致Lemierre综合征的临床特点,并进行文献复习。
结果 患者男,无诱因发热伴咽痛,体检发现左侧扁桃体充血、肿大,血常规正常,X线胸部正位片未见异常。初步诊断：急性扁桃体炎（左侧）。予青霉素+阿奇霉素治疗后,症状加重,查白细胞计数13.59×10⁹/L,中性粒细胞比例0.933,血小板计数7.4×10⁹/L;TBil 54.3 mmol/L,DBil 28.3 mmol/L,AST 127 IU/L,ALT 82 IU/L,血清白蛋白19.3 g/L。血培养结果为溶血隐秘杆菌,改静脉滴注哌拉西林-他唑巴坦治疗后体温恢复正常。随后患者出现左侧颈内静脉血栓形成,予抗凝治疗。出院后2个月和4个月时随访患者,未见异常。检索文献3例,结合本例共4例,4例患者均为男性,年龄19～54岁,均以咽痛和发热为首发和主要症状,均伴有颈部疼痛;咽炎2例,扁桃体周围渗出或脓肿各1例,皮疹2例;血白细胞计数均升高,血小板计数均下降,肝功能损伤3例,急性肾衰竭2例,急性呼吸衰竭1例;首查X线胸片均正常,病情进展后胸部X线或CT提示双肺周边多发结节高密度影伴空洞形成3例,局灶或楔形浸润影1例,胸腔积液1例;血培养结果提示单一溶血隐秘杆菌2例,溶血隐秘杆菌和坏死梭形杆菌复合感染2例;4例患者均应用青霉素+酶抑制剂治疗有效;有血栓者予抗凝治疗;无死亡病例。
结论 Lemierre综合征临床特点有原发口咽部感染、脓毒血症、感染性或栓塞性颈静脉炎及至少一处远处化脓灶,早期诊断、及时治疗可降低溶血隐秘杆菌致Lemierre综合征病死率。     

Castleman's disease and lymphoma: report of eight cases in HIV-negative patients and literature review

Castleman's disease (CD) is a rare atypical lymphoproliferative disorder associated with a risk of developing malignant lymphoma. We have recorded 8 HIV-negative patients presenting this association, 6 with non-Hodgkin's lymphoma (NHL) and 2 with Hodgkin's disease (HD). After literature review, we analyzed all reported cases of association CD-NHL (n = 23) and CD-HD (n = 27). NHL is more often associated with multicentric CD, its diagnosis being concurrent with CD diagnosis or occurring within 2 years. B-NHL is predominant (71%), and mantle cell lymphoma represents 40% of these B-NHL cases. NHL displays an aggressive course and is liable for death, especially in multicentric CD. HD occurs in localized CD of plasma cell type, usually in the same areas, is more often of interfollicular subtype, and its clinical course seems better than NHL. The association of CD and lymphoma seems to be more than coincidental, and its pathogenesis is discussed.