Ultrasonically guided percutaneous biopsy of peripheral pulmonary masses.

Ultrasonically guided percutaneous biopsy and aspiration of solid and cystic structures in the abdomen, neck, and pericardial space are common practice. The technique may be utilized for biopsy of peripheral pulmonary masses in contact with the chest wall, in order to assure accurate placement of the needle in the center of the mass, reduce the risk of pneumothorax, and eliminate the exposure to radiation that occurs with fluoroscopic guidance. Four patients had successful biopsies in this manner, without complications. Histologic studies revelaed malignant neoplasms in three and lipoid pneumonia in one.     

Fungal infections of the central nervous system in HIV-negative patients: Experience from a tertiary referral center of South India

Objective:

To describe the clinical, radiological, and cerebrovascular fluid (CSF) findings and the outcome of microbiologically or histopathologically proven fungal infections of the central nervous system (CNS) in HIV-negative patients.

Methodology and Results:

We identified definite cases of CNS mycosis by screening the medical records of our institute for the period 2000–2008. The clinical and imaging details and the outcome were abstracted from the medical records and entered in a structured proforma. There were 12 patients with CNS mycosis (i.e., 2.7% of all CNS infections treated in this hospital); six (50%) had cryptococcal infection, three (25%) had mucormycosis, and two had unclassified fungal infection. Four (33%) of them had diabetes as a predisposing factor. The common presentations were meningoencephalitis (58%) and polycranial neuritis (41%). Magnetic resonance imaging revealed hydrocephalus in 41% and meningeal enhancement in 25%, as well as some unusual findings such as subdural hematoma in the bulbocervical region, carpeting lesion of the base of the skull, and enhancing lesion in the cerebellopontine angle. The CSF showed pleocytosis (66%), hypoglycorrhachia (83%), and elevated protein levels (100%). The diagnosis was confirmed by meningocortical biopsy (in three cases), paranasal sinus biopsy (in four cases), CSF culture (in three cases), India ink preparation (in four cases), or by cryptococcal polysaccharide antigen test (in three cases). Out of the ten patients for whom follow-up details were available, six patients recovered with antifungal medications (amphotericin B, 1 mg/kg/day for the minimum period of 6 weeks) and/or surgical treatment. Four patients expired (only one of them had received antifungal therapy).

Conclusions:

Most patients with CNS mycosis recover with appropriate therapy, but the diagnosis and management of these rare infections remains a challenge to clinicians.     

Potential and limitations of lamivudine monotherapy in chronic hepatitis B: evidence from genotyping

Background: Current oral therapy for hepatitis B virus (HBV) is limited by the presence of resistance leading to resumption of higher levels of HBV replication. Therefore, there is a need for a better definition of the potential role and limitations of lamivudine or similar therapies, used alone. Aims: To examine the viability of lamivudine and similar monotherapies as a treatment strategy in chronic HBV in the face of the worldwide burden of disease. Methods: We have reviewed the role of lamivudine monotherapy in the treatment of chronic HBV in a single tertiary referral liver centre over a 9‐year period. We analysed the outcome in 90 patients where lamivudine has apparently conferred long‐term viral suppression and investigated the development of genotypic resistance in the absence of ostensible phenotypic resistance. Patients were subdivided into hepatitis B e antigen (HBeAg)‐positive and anti‐HBe‐positive groups. Results: Virtually all HBeAg‐positive patients who failed to seroconvert have progressed to combination antiviral therapy. Only 19%(7/36) of HBeAg‐negative patients have continued suppression without detectable genotypic change after 4 years of therapy. Conclusions: These data demonstrate that despite a relatively low level of viraemia in HBeAg‐negative patients, we could detect resistance mutations by direct sequencing in all patients with amplifiable HBV DNA. Our results suggest that for patients with ongoing replication at ‘amplifiable’ levels of HBV DNA, but <10⁵ copies/ml, genotypic selection is readily detectable. Lamivudine monotherapy has not sufficed for the overwhelming majority of patients.     

A Novel Approach to Testing for Average Bioequivalence Based on Modeling the Within-Period Dependence Structure

Bioequivalence trials are commonly conducted to assess therapeutic equivalence between a generic and an innovator brand formulations. In such trials, drug concentrations are obtained repeatedly over time and are summarized using a metric such as the area under the concentration vs. time curve (AUC) for each subject. The usual practice is to then conduct two one-sided tests using these areas to evaluate for average bioequivalence. A major disadvantage of this approach is the loss of information encountered when ignoring the correlation structure between repeated measurements in the computation of areas. In this article, we propose a general linear model approach that incorporates the within-subject covariance structure for making inferences on mean areas. The model-based method can be seen to arise naturally from the reparameterization of the AUC as a linear combination of outcome means. We investigate and compare the inferential properties of our proposed method with the traditional two one-sided tests approach using Monte Carlo simulation studies. We also examine the properties of the method in the event of missing data. Simulations show that the proposed approach is a cost-effective, viable alternative to the traditional method with superior inferential properties. Inferential advantages are particularly apparent in the presence of missing data. To illustrate our approach, a real working example from an asthma study is utilized.     

Induction chemotherapy in non-metastatic high grade osteo sarcomas--results of pilot study at Cancer Institute (WIA), Madras.

Twelve patients with high grade osteosarcomas of the extremities were treated with two cycles of induction chemotherapy using adriamycin and cis-platinum and sandwich radiation between the two cycles (4000 rads). Ten patients underwent amputation or disarticulation, two patients had wide excision followed by endoprosthesis. The specimen was assessed for grade of necrosis. The Disease Free Survival at a minimum follow-up period of 26 months and median follow-up period of 35.5%. All the five patients who developed distant metastases had shown only a grade I necrosis in the tumour.     

Detection of egg drop syndrome virus antigen or genome by enzyme-linked immunosorbent assay orpolymerase chain reaction

Mouse monoclonal antibodies (mAbs) were produced against an Indian isolate of egg drop syndrome (EDS)virus and characterized. Four hybridoma clones were secreting mAbs that bound to a 100 kDa protein,presumably the hexon protein. These mAbs were found to cross-react with two other Indian isolates of EDSvirus and to the reference UK 127 strain. Three of these mAbs were mapped to the same epitope compared withthe other mAb (F8), which bound to a different epitope. An antigen-capture enzyme-linked immunosorbentassay (AC-ELISA) was developed using the F8 mAbs as capture antibody and polyclonal chicken serum againstEDS virus as detection antibody. A polymerase chain reaction (PCR) was used to detect the EDS viral genome.Following experimental infection of oestrogen-treated chickens with EDS virus, cloaca1 swabs, oviduct, uterusand spleen were collected at different days post-infection and used in both AC-ELISA and PCR, directly andafter a single passage in embryonated duck eggs. The sensitivity and specificity of antigen detection by ACELISAor PCR was 95% and 98%, respectively. For diagnosis of EDS viral infections, PCR is recommendeddue to its ease and the lack of requirement of prepared reagents such as mAbs or conjugates. We recommendthat PCR be performed directly on boiled tissue homogenates. Any negative samples may be passaged inembryonated duck eggs and the allantoic fluids tested by PCR before a conclusive negative diagnosis is given.     

Extended indications for functional limb-sparing surgery in extremity sarcoma using complex reconstruction.

From 1980 to 1991, 29 patients underwent complex reconstruction following extremity sarcoma resection. Soft tissue was the site of origin in 15 patients (52%) and bone was the site of origin in 14 patients (48%), with 20 sarcomas (69%) in the lower extremity. Resection consisted of the following procedures: extended anatomical soft-tissue resections (21 patients [72%]), bone resections (18 patients [62%]), and joint resections (14 patients [48%]). Reconstruction involved the following: myocutaneous flaps (20 patients [69%]), joint prosthesis (eight patients [28%]), and bone reconstruction (15 patients [52%]). There was no surgical mortality; one patient required an amputation owing to surgical complications. The site of the first failure was local (four [31%] of 13 patients), lung (five patients [38%]), others (four patients [31%]). At a median follow-up of 23 months, 18 patients (62%) had no evidence of disease, 27 (93%) had no local disease, 21 (72%) had good extremity function, three (10%) had major disabilities, and five (17%) underwent amputations. Local control improved when the margin of resection was larger than 10 mm. Disease-free survival was 67% at 3 years. Overall survival was 51% at 5 years. Tumor size was an independent predictor of overall survival. Local recurrence did not affect overall survival.     

BORIS,a novel male germ-line-specific protein associated with epigenetic reprogramming events,shares the same 11-zinc-finger domain with CTCF,the insulator protein involved in reading imprinting marks in the soma

CTCF, a conserved, ubiquitous, and highly versatile 11-zinc-finger factor involved in various aspects of gene regulation, forms methylation-sensitive insulators that regulate X chromosome inactivation and expression of imprinted genes. We document here the existence of a paralogous gene with the same exons encoding the 11-zinc-finger domain as mammalian CTCF genes and thus the same DNA-binding potential, but with distinct amino and carboxy termini. We named this gene BORIS for Brother of the Regulator of Imprinted Sites. BORIS is present only in the testis, and expressed in a mutually exclusive manner with CTCF during male germ cell development. We show here that erasure of methylation marks during male germ-line development is associated with dramatic up-regulation of BORIS and down-regulation of CTCF expression. Because BORIS bears the same DNA-binding domain that CTCF employs for recognition of methylation marks in soma, BORIS is a candidate protein for the elusive epigenetic reprogramming factor acting in the male germ line.