Non-granulomatous Interstitial Nephritis in a Chinese Man with Sarcoidosis

Clinical renal involvement in sarcoidosis is rare and has not been previously reported in Chinese patients. We report a case of non-granulomatous interstitial nephritis that presented with acute renal failure in a Chinese man with underlying sarcoidosis. Use of prednisolone led to dramatic renal improvement and partial resolution of his asymptomatic lung parenchymal lesions. Unfortunately, the patient subsequently died of cryptococcal meningitis and episodes of nosocomial pneumonia. One should closely monitor a patient with a presumptive diagnosis of sarcoidosis after embarking on treatment since infections like tuberculosis may mimic or coexist with the disease. This is particularly important in areas where sarcoidosis is exceedingly rare

Area-efficient capacitor-free low-dropout regulator

An area-efficient capacitor-free low-dropout regulator based on a current-feedback frequency compensation technique is disclosed. An implementation of a current feedback block with a single compensation capacitor is used to enable capacitance reduction. The resultant low-dropout regulator does not generally require an off-chip capacitor for stability and is particularly useful for system-on-chip applications

Prospective randomized study of thrice weekly six-month and nine-month chemotherapy for cervical tuberculous lymphadenopathy

The aim of this study is to compare the efficacy of a thrice weekly 6- month regimen, 4S3H3R3Z3/2H3R3 (which consists of an initial 4 months of streptomycin (S), isoniazid (H), rifampicin (R), and pyrazinamide (Z) followed by 2 months of isoniazid and rifampicin), with o thrice weekly 9- month regimen, 4S3H3R3Z3/5H3R3 (which consists of an initial 4 months of streptomycin, isoniazid, rifampicin, and pyrazinamide followed by 5 months of isoniazid and rifampicin), in the treatment of cervical tuberculous lymphadenopathy. A total of 113 patients were recruited between August 1987 and December 1993. Twenty-two patients were excluded from the analysis because of defaulting treatment or modification of regimen. Ninety- one patients were included in the analysis. Forty-three patients were given the 6-month regimen, and 48 patients were given the 9-month regimen. Two (5%) patients of the 6-month regimen and one (2%) patient of the 9-month regimen had primary failure after completion of treatment (relative risk, 2.23; 95% confidence interval, 0.21 to 23.76). Of the 88 patients who had initial clinical remission after completion of treatment, the 5-year actuarial remission rates were 89% for the 6-month regimen and 90% for the 9-month regimen (Wilcoxon, p = 0.44). There were no significant differences of both primary failure rate and 5-year actuarial remission rate of the two regimens. The 6-month regimen is recommended as the initial treatment of tuberculous lymphadenopathy.link_to_subscribed_fulltex

Pathological basis of surgery in the management of postradiotherapy cervical metastasis in nasopharyngeal carcinoma

Radical neck dissection was performed on 43 patients with nasopharyngeal carcinoma in whom persistent or recurrent cervical metastasis developed after radiotherapy. The pathologic nature of the tumor in the cervical lymph nodes was studied with step serial sectioning of the entire radical neck dissection specimen at 3-mm intervals. In 70% of patients, more tumor-harboring lymph nodes were detected in the specimen when compared with clinical examination. The extensive behavior of the tumor in the cervical metastases was reflected by the presence of extracapsular spread in 70% of the lymph nodes and the existence of isolated clusters of tumor cells in 35% of the specimens studied. Tumor tissue lying in close proximity to the spinal accessory nerve was demonstrated in 27.5% of the specimens, and 72% of the tumor-bearing lymph nodes were located in the posterior triangle. Radical neck dissection is recommended as the salvage procedure for these patients.link_to_subscribed_fulltex

Genetic mechanisms of co-emergence of INH-resistant Mycobacterium tuberculosis strains during the standard course of antituberculosis therapy

ABSTRACTThe incidence of isoniazid (INH) resistant Mycobacterium tuberculosis is increasing globally. This study aimed to identify the molecular mechanisms behind the development of INH resistance in M. tuberculosis strains collected from the same patients during the standard course of treatment. Three M. tuberculosis strains were collected from a patient before and during antituberculosis (anti-TB) therapy. The strains were characterized using phenotypic drug susceptibility tests, Mycobacterial Interspersed Repeated Unit-Variable-Number Tandem Repeats (MIRU-VNTR), and whole-genome sequencing (WGS) to identify mutations associated with INH resistance. To validate the role of the novel mutations in INH resistance, the mutated katG genes were electroporated into a KatG-deleted M. tuberculosis strain (GA03). Three-dimensional structures of mutated KatG were modeled to predict their impact on INH binding. The pre-treatment strain was susceptible to INH. However, two INH-resistant strains were isolated from the patient after anti-TB therapy. MIRU-VNTR and WGS revealed that the three strains were clonally identical. A missense mutation (P232L) and a nonsense mutation (Q461Stop) were identified in the katG of the two post-treatment strains, respectively. Transformation experiments showed that katG of the pre-treatment strain restored INH susceptibility in GA03, whereas the mutated katG genes from the post-treatment strains rendered negative catalase activity and INH resistance. The protein model indicated that P232L reduced INH-KatG binding affinity while Q461Stop truncated gene transcription. Our results showed that the two katG mutations, P232L and Q461Stop, accounted for the co-emergence of INH-resistant clones during anti-TB therapy. The inclusion of these mutations in the design of molecular assays could increase the diagnostic performance.IMPORTANCEThe evolution of drug-resistant strains of Mycobacterium tuberculosis within the lung lesions of a patient has a detrimental impact on treatment outcomes. This is particularly concerning for isoniazid (INH), which is the most potent first-line antimycobacterial drug. However, the precise genetic factors responsible for drug resistance in patients have not been fully elucidated, with approximately 15% of INH-resistant strains harboring unknown genetic factors. This raises concerns about the emergence of drug-resistant clones within patients, further contributing to the global epidemic of resistance. In this study, we revealed the presence of two novel katG mutations, which emerged independently due to the stress exerted by antituberculosis (anti-TB) treatment on a parental strain. Importantly, we experimentally demonstrated the functional significance of both mutations in conferring resistance to INH. Overall, this research sheds light on the genetic mechanisms underlying the evolution of INH resistance within patients and provides valuable insights for improving diagnostic performance by targeting specific mutations