Prevalence of drug resistance under the DOTS strategy in Hyderabad, South India, 2001-2003.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid (INH) and rifampicin (RMP), is considered a threat to TB control. Implementation of DOTS ensures high cure rates and prevents MDR. OBJECTIVE: To study the prevalence of MDR-TB from a retrospective analysis of the data in a tuberculosis unit where DOTS was implemented over a period of 6 years through public private mix (PPM). METHODS: Drug susceptibility testing of Mycobacterium tuberculosis samples isolated from the cultures of newly registered and retreatment sputum smear-positive cases during 2001-2003. RESULTS: During the study, 909 sputum-positive cases were registered and analysed. Of these, 714 were new and 195 were retreatment sputum-positive cases. INH resistance was found in 3.2% (23) of new and 9.2% (18) of retreatment cases. RMP resistance was present in 1.5% (11) of new and 7.2% (14) of retreatment cases. MDR was present only in 0.14% (1) of new and 2% (4) of retreatment cases. New cases had cure rates of 96% compared to 85% in retreatment cases. CONCLUSION: The prevalence of MDR-TB is low where success rates are high.     

DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime

Recently, a vaccine consisting of DNA priming followed by boosting with modified vaccinia Ankara (MVA) has provided long-term protection of rhesus macaques against a virulent challenge with a chimera of simian and human immunodeficiency viruses. Here, we report studies on the development of the DNA component for a DNA/MVA HIV vaccine for humans. Specifically, we assess the ability of a codon-optimized Gag-expressing DNA and two noncodon-optimized Gag-Pol-Env-expressing DNAs to prime the MVA booster dose. The codon-optimized DNA expressed virus-like particles (VLPs), whereas one of the noncodon-optimized DNAs expressed VLPs and the other expressed aggregates of HIV proteins. The MVA boost expressed Gag-Pol and Env and produced VLPs. Immunogenicity studies in macaques used one intramuscular prime with 600 microg of DNA and two intramuscular boosts with 1 x 10(8) pfu of MVA at weeks 8 and 30. The codon-optimized and noncodon-optimized DNAs proved similar in their ability to prime anti-Gag T cell responses. The aggregate and VLP-expressing Gag-Pol-Env DNAs also showed no significant differences in their ability to prime anti-Env Ab responses. The second MVA booster dose did not increase the peak CD4 and CD8 T cell responses, but increased anti-Env Ab titers by 40- to 90-fold. MVA-only immunizations elicited 10-100 times lower frequencies of T cells and 2-4 lower titers of anti-Env Ab than the Gag-Pol-Env DNA/MVA immunizations. Based on the breadth of the T cell response and a trend toward higher titers of anti-Env Ab, we are moving forward with human trials of the noncodon-optimized VLP-expressing DNA.     

Metachronous Multiple Primary Malignant Neoplasms of the Stomach and the Breast: Report of Two Cases With Review of Literature

Multiple primary malignant neoplasm is the occurrence of a second primary malignancy in the same patient within 6 months of the detection of first primary (synchronous), or 6 months or more after primary detection (metachronous). Multiple primary malignant neoplasms are not very frequently encountered in clinical practice. The relative risk for a second primary malignancy increases by 1.111-fold every month from the detection of the first primary malignancy in any individual. We present 2 patients treated for carcinoma of the breast who developed a metachronous primary malignancy in the stomach to highlight the rare occurrence of multiple primary malignant neoplasms. These tumors were histologically dissimilar, with distinct immunohistochemical parameters. The importance lies in carefully identifying the second primary malignancies, not dismissing them as metastases, and treating them accordingly.Key words: Breast neoplasms, Stomach neoplasms, Neoplasms, Second primaryBreast cancer is the most common malignancy among women worldwide. With proper screening, earlier detection, and improved treatment, survival has greatly increased, with the result that there is now a large population of women with a present or past history of breast cancer. This has led to an increased detection of second primary malignancies among these women. The relative risk for a second primary malignancy increases by 1.111-fold every month from the detection of the first primary malignancy in any individual.¹ Several authors have reported on a lesion in the stomach being labeled as a second primary malignancy and subsequently found to be metastasis. When the primary breast tumor is positive for estrogen and progesterone receptors (ER/PRs) and the stomach tumor is ER/PR negative, the diagnosis is established easily.² However, studies have shown that some primary gastric cancers can have ER/PR positivity. Further, if the primary breast lesion is ER/PR negative, the same cannot be used as a marker. Here, we present 2 breast cancer patients who developed second primary malignancies in the stomach and the final diagnosis was established based on histopathology and immunohistochemistry.     

Evaluation of Bone Density Around the Implants Placed Using Drilling Technique and Bone Expansion Technique: An In vivo Study

Bone density is a key parameter in determining the surgical procedure of implant placement and for the predictability of successful implant treatment. Several clinical studies have shown lower survival rates of implants in maxilla which was attributed to poor bone quality. The present study compared the variations in the pre-operative and post-operative bone density values in Hounsfield units using CT between drilling technique and bone expansion technique at 0.25 and 1.0 mm sections at two sites which were selected in maxillary arch between the second premolar regions of either quadrants and results have shown bone expansion technique is superior to drilling technique in division III bone.     

Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results

BackgroundProgrammed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy.MethodsTwenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale.ResultsEnrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was >10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO.ConclusionNivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.