Sensing at terahertz frequency domain using a sapphire whispering gallery mode resonator.

In this Letter, we experimentally demonstrate a terahertz (THz) whispering gallery mode (WGM) sensor based on a sapphire WGM resonator. The fundamental mode at 129.49 GHz with a Q-factor of 4.63×103 is used to study its sensitivity to adsorbed molecules. The efficiency of our sensor to detect rhodamine 6G dye molecules in a polyvinyl alcohol matrix at room temperature has been manifested, and a detection sensitivity of 25 parts per million has been achieved. Also, we report an analytical approach based on coupled-mode theory between the waveguide mode and the spherical resonator mode to evaluate the absorption coefficient of the adsorbed molecule on the resonator. The model is modified to evaluate optical constants of materials. The results obtained have been verified by continuous-wave THz transmission results. The results are of importance in sensing, metrology, and material characterization.

Usefulness of multiplex PCR in the diagnosis of genital tuberculosis in females with infertility.

The purpose of this investigation was to evaluate the usefulness of multiplex polymerase chain reaction (m-PCR) in detecting uterine tuberculosis in women with infertility. In a prospective study, endometrial curetting from 620 females with infertility were investigated using laparoscopy, hysteroscopy, histopathology, smear microscopy, mycobacterial culture in BACTEC MGIT™ 960, and in-house m-PCR. The mean age of the women was 29.75 ± 4.66 years. The majority (596) sought medical attention for infertility; of them, 455 (76.34 %) presented with primary and 141 (23.65 %) with secondary infertility. A total of 158 (25.48 %) women were diagnosed as having uterine tuberculosis by at least one of the diagnostic methods. Among them, laparoscopy was positive in 46 (29.11 %), hysteroscopy in 77 (48.73 %), histopathology in only 8 (5.06 %), smear for acid fast bacilli in 4 (2.53 %), and liquid culture in 24 (15.18 %) patients. The in-house m-PCR was positive in 135 (85.44 %) women. Of these, 129 (95.55 %) samples were positive for Mycobacterium tuberculosis, while 6 (4.44 %) were positive for non-tuberculous mycobacterial DNA. Of the 129 M. tuberculosis PCR-positive women, 112 received anti-tubercular treatment and 23 of these conceived and fell pregnant after the completion of treatment. For the diagnosis of uterine tuberculosis, m-PCR was found to be the most efficient diagnostic tool compared to the other methods.

Cost-effectiveness of linezolid vs vancomycin in suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany.

BACKGROUND: The oxazolidinone antibiotic linezolid has demonstrated efficacy in treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In a retrospective analysis of two prospective randomized clinical trials in patients with nosocomial pneumonia (NP), initial therapy with linezolid produced significantly better clinical cure and survival rates than vancomycin in the subset of patients with documented MRSA infection. This study was designed to evaluate the economic impact of these clinical outcomes from the perspective of the German health care system to determine the use of these regimens in the light of limited resources and rising costs. METHODS: A decision-analytic model using clinical trial data was developed to examine the costs and outcomes of treatment with linezolid or vancomycin in hospitalized patients with NP caused by suspected MRSA. The model followed an average patient from initiation of empiric treatment until treatment success, death, or second-line treatment failure. Local treatment patterns and resource use were obtained from a Delphi panel. Costs were taken from published sources. Outcomes included total cost per patient, cost per additional cure, cost per death avoided, and cost per life-year gained. RESULTS: The model calculated that linezolid was associated with an 8.7% higher cure rate compared with vancomycin (73.6% vs 64.9%, respectively). Average total costs per episode for linezolid- and vancomycin-treated patients were 12,829 and 12,409, respectively. Death rates were 13.2% lower with linezolid than with vancomycin (20.7% vs 33.9%), resulting in an average of 2.3 life-years gained per linezolid-treated patient in a 65-year-old cohort (14.0 life-years vs 11.7 life-years). With linezolid, incremental costs per death avoided and per patient cured were 3,171 and 4,813, respectively. The base case estimated a similar mean length of stay for both drugs (11.2 vs 10.8 days). One-way sensitivity analyses did not change the overall results. CONCLUSION: The model estimated a higher clinical cure (+8.7%) and survival (+13.2%) for linezolid compared with vancomycin at an incremental cost of 420 per treatment episode. The cost-benefit profile suggests that linezolid could be considered a cost-effective alternative to vancomycin in the treatment of patients with NP caused by suspected MRSA in Germany.

Cost-effectiveness of linezolid versus vancomycin for hospitalized patients with complicated skin and soft-tissue infections in France.

UNLABELLED: Studies have shown similar clinical cure rates and shorter length of hospitalization when using linezolid compared to vancomycin in patients with complicated skin and soft-tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVE: This study had for aim to compare the cost-effectiveness of linezolid versus vancomycin in French healthcare settings. METHOD: A decision-analytic model followed an average patient from the initiation of an empiric treatment until cure, death or second-line treatment failure. A clinical data probability was obtained from clinical trials, resource utilization data (including treatment duration and length of hospitalization) and prevalence of MRSA was obtained from a Delphi panel, and costs from published sources. RESULTS: First-line cure rate for linezolid-treated patients was 90.7% versus 85.5% for vancomycin; the total cure rates after two lines of treatment were 98.5% and 98.0%, respectively. The average total cost was 7,778euro for linezolid versus 8,777euro for vancomycin. The mean estimated length of hospitalization after two lines of treatment was 10.7 days for linezolid versus 13.3 days for vancomycin. The increased effectiveness and reduced cost lead to more frequent prescription. This did not change after one-way sensitivity analyses. CONCLUSION: Linezolid may be considered as a cost-effective treatment for patients with complicated skin and soft-tissue infections suspected to be MRSA related in France.

Clinical relevance of HBV DNA load in patients with chronic hepatitis B infection.

BACKGROUND: Hepatitis B virus (HBV) DNA detection and quantification are now playing an increasing role in the assessment of disease activity and response to therapy. However, viraemia levels which define various stages of HBV infection have not yet been established. AIM: To define viraemia levels which describe various stages of chronic hepatitis B virus infection. METHODS: In a retrospective study, stored sera samples of chronic hepatitis B virus (CHB) infected patients registered at AIIMS liver clinic, from January 1996 to June 2005 were subjected to competitive, quantitative PCR analysis. RESULTS: The median HBV DNA load was lowest among carriers and highest among patients with chronic hepatitis B [0 (0-8) vs. 7 (0-12) log10 copies/ml, respectively; p<0.05]. As compared to chronic hepatitis patients the DNA load was also lower among cirrhotics [7 (0-12) vs. 4.5 (0-8) log10 copies/ml, respectively; p<0.05] and hepatocellular cancer patients [ 7(0-12) vs. 0 (0-8) log10 copies/ml, respectively; p<0.05]. Patients with carriers had a DNA load which was significantly lower than e antigen negative CHB [0 (0-8) vs. 6 (0-10) log10 copies/ml; p<0.05] or e antigen positive CHB [0 (0-8) vs 8 (0-12) log10 copies/ml; p<0.05]. A threshold of 3.5 log10 copies/ml had sensitivity and specificity of 83% and 58% respectively in differentiating carriers from e antigen negative CHB. There was a strong positive correlation of HBV DNA load with inflammatory grade (R=0.334; p=0.0001), fibrosis stage (R=0.276; p=0.001) and ALT levels (R=0.378; p=0.0001). 82% (9/11) of those who lost e antigen had a decline in HBV DNA levels to <5 log10 copies/ml, whereas only 12.5% (1/8) of those who did not lose e antigen had a decline in DNA load below this level. CONCLUSIONS: HBV DNA viraemia levels correlate positively with the inflammatory grade, fibrosis stage and ALT levels. Most patients who loose e antigen have a decline in DNA load to below 5 log10 copies/ml. Further prospective studies employing repeated measurements are required to define a threshold to differentiate between HBV carriers and e antigen negative CHB.

Polymorphism of the human c-abl gene: relation to incidence and course of chronic myelogenous leukemia.

Abnormalities in structure and expression of the proto-oncogene c-abl have been implicated in the genesis of chronic myelogenous leukemia (CML). We studied leukemic cell DNA from 42 CML patients for evidence of rearrangement and/or amplification of c-abl analogous to that described in the CML cell line K562. Using the enzymes Bgl II, Pst I, Xba I, seven patients demonstrated an atypical Southern blot pattern similar to that found in K562. Analysis of DNA from normal controls and skin fibroblast from one of the seven patients established that the atypical blot pattern was due to a restriction fragment length polymorphism rather than a gene rearrangement. Further analysis revealed that c-abl exists as two alleles, A and B, yielding three genotypes: AA, AB and BB. Inheritance was Mendelian. With respect to allele A, allele B contains a deletion of about 1 kb lying in a intronic region in close proximity to highly repetitive Alu sequences and the sequence coding for phosphotyrosine of the c-abl protein. K562 and the seven patients with similar Southern patterns were identified as AB heterozygotes. In K562, only the A allele was amplified. The frequencies of AA and AB genotypes in 37 Caucasian CML patients were 81.1% and 18.9% and in 57 unrelated normal Caucasian controls 87.7% and 12.3%, not significantly different. The BB genotype was identified in less than 1% of Caucasians. Of note, five AB patients who developed a terminal blast crisis demonstrated a 4:1 lymphoid:myeloid crisis ratio in contrast to a 2:7 lymphoid:myeloid crisis ration in nine AA patients and a similar ratio in mixed AA and AB historical controls. Otherwise, CML patients with AA and AB genotypes manifested similar clinical parameters. No patients demonstrated amplification of c-abl and analysis of four AB patients for loss of one c-abl allele during the course of their disease was negative. Thus, amplification of c-abl and loss of one c-abl allele are both infrequent in CML and do not play a significant role in the course of the disease.

Alzheimer's disease and related dementias increase costs of comorbidities in managed Medicare.

OBJECTIVES: To analyze the relationship between comorbid conditions and costs for patients with AD and related dementias (ADRD) in a Medicare managed care organization (MCO). To derive implications for improving management of patients with ADRD. METHODS: Retrospective analysis was carried out on administrative data for 3,934 patients with ADRD and 19,300 age/sex-matched control subjects enrolled in a large Medicare MCO. Patients with ADRD were identified from diagnoses on medical claims and encounter data for a 2-year period. Control subjects were selected from health plan members without dementia. Comorbid conditions were based on the diagnostic classifications from the Charlson comorbidity index. Health care costs and utilization for MCO-covered services for cases were compared with those of control subjects. RESULTS: Prevalence of ADRD was 4.4%, substantially higher than reported in previous studies of Medicare managed care and similar to population-based estimates. After controlling for comorbid conditions, age, and sex, annual costs were $4,134 higher for ADRD patients, resulting in excess costs of $16 million to the MCO. For the 10 most prevalent comorbidities in ADRD patients, adjusted costs were higher for ADRD patients compared with control subjects with the same condition. Higher costs were attributable to higher inpatient and skilled nursing facility utilization. CONCLUSIONS: In this study, prevalence rates for ADRD mirrored population estimates. Costs for patients with ADRD in this Medicare MCO varied considerably by comorbid condition and were substantially higher for patients with both AD and comorbid diseases commonly targeted for disease management, indicating that AD increases costs through effects on the management of comorbid illnesses. These findings indicate that better treatment and care management of AD could reduce the costs of comorbid illnesses commonly experienced by the frail elderly.

The nature and significance of liver cell vacuolation following hepatocellular injury--an analysis based on observations on rats rendered tolerant to hepatotoxic damage.

Swelling with nonlipid cytoplasmic vacuolation of diffusely distributed hepatocytes is seen consistently after mild acute and subacute liver injury. Several lines of evidence point to the possibility that this change may reflect a cellular adaptation beneficial to the host, rather than a degenerative change. The nature and significance of this morphological manifestation were tested in batches of albino rats given small doses of a variety of hepatotoxins, some of which were subsequently challenged with a large highly necrogenic dose of carbon tetrachloride (CCl4). Morphological and biochemical investigations showed that cytoplasmic vacuolation of liver cells following low doses of toxins was due to excess accumulation of glycogen, predominantly of the monoparticulate form. These cells lacked features of degeneration or regeneration and were much less susceptible to injury by the large dose CCl4, as assessed by structural and serum enzyme analyses. This tolerance to toxic damage seemed to be associated with excess accumulation of intracellular glycogen. We conclude from these and other observations on animal and human livers that many of the vacuolated hepatocytes seen in liver injury are cells adaptively altered to resist further insult rather than cells undergoing hydropic degeneration, as is commonly believed.

Development and validation of the Self-Esteem And Relationship (SEAR) questionnaire in erectile dysfunction.

Development and validation of a patient-reported measure of psychosocial variables in men with erectile dysfunction (ED) is described. Literature review, focus groups, and medical specialists identified 86 potential items. Redundant, ambiguous, or low item-to-total correlation items were removed. Data from 98 men reporting diagnosed ED and 94 controls assisted in final item selection and psychometric evaluation. Treatment responsiveness was evaluated in 93 men with ED in a 10-week open-label trial of sildenafil citrate (Viagra). The 14 chosen items resolved into two domains: Sexual Relationship (eight items) and Confidence (six items), the latter comprising Self-Esteem (four items) and Overall Relationship (two items) subscales. The resulting Self-Esteem And Relationship (SEAR) questionnaire demonstrated validity and reliability. The intervention study demonstrated responsiveness to beneficial treatment with significant improvement in scores (P=0.0001). The SEAR questionnaire possesses strong psychometric properties that support its validity and reliability for measuring sexual relationship, confidence, and particularly self-esteem.

Prevalence, costs, and treatment of Alzheimer's disease and related dementia: a managed care perspective.

BACKGROUND: The number of patients with Alzheimer's disease (AD) and related dementia treated in managed care organizations (MCOs) is increasing, and this trend is expected to continue. Therefore, it is critical that MCOs develop disease management strategies for this population. OBJECTIVE: To review the literature on the prevalence, costs, and treatment of AD and related dementia. STUDY DESIGN: Review of published articles from MEDLINE and peer-reviewed journals. RESULTS: Prevalence of AD and related dementia is approximately 5.7% among those aged 65 and older. Prevalence data from claims-based studies of AD in managed care are lower, ranging from 0.55% to 0.83%. Costs for formal care average $27,672 per patient annually, with long-term care being the most costly component. Annual costs for informal care are estimated to be $10,400 to $34,517 per patient. Additional costs associated with AD include lost wages and productivity of patients and caregivers and costs associated with increased morbidity of caregivers. Donepezil treatment is well tolerated and has been extensively tested and evaluated in clinical settings. Early diagnosis and treatment of AD with donepezil has been shown to slow cognitive decline in AD. Although study findings regarding the cost offsets of donepezil-treated patients to date are mixed, there is a growing body of evidence to support the inclusion of this and other therapies into an MCO's AD treatment armamentarium. CONCLUSIONS: It is unlikely that MCOs will escape the increased prevalence and costs associated with AD. Opportunities exist through patient management programs targeted toward early diagnosis, effective use of medications, control of comorbidities, and patient and family support to partially offset these costs while providing quality patient care.

Studies on stibanate resistant Leishmania donovani isolates of Indian origin.

Studies with 26 clones of L. donovani promastigotes derived from three different Indian isolates indicated that wild type parasites are mixture of stibanate sensitive and resistant cells. Both forms of the parasite were resistant to the drug. Infection with resistant parasites appears to be the primary reason of high rate of pentavalent antimony unresponsiveness among Indian kala-azar patients. It was observed that the resistant parasites originated as a result of irregular and often incomplete treatment of kala-azar patients with pentavalent antimonials.

Mechanism of complement-independent and antibody-mediated killing of Leishmania donovani promastigotes.

Immune serum raised against flagellar fraction of Leishmania donovani isolate UR6 has profound lethal effect on the in vitro growth of the parasite. Lethal effect of immune serum was also examined using two other isolates of L. donovani, namely DD8 and AG83. It was observed that immune serum is equally effective against UR6 and DD8 but has no effect on AG83 promastigotes. Parasite killing is mediated by Leishmania-specific antibodies in the absence of complement or any other factors present in rabbit serum. Results indicate that the lethal effect of immune serum is due to impairment in membrane function leading to inhibition in uptake of essential nutrients needed for growth and survival of parasites.

Euglenoid blooms in the floodplain wetlands of Barak Valley, Assam, North eastern India.

Red blooms of Euglena sp. in the floodplain wetland ecosystems of Barak Valley, Assam, India, were found to be induced by high concentrations of NH3-N, NO3, Fe, Mg and to some extent, PO4, Cu and Zn in their water. The trace elements were rapidly accumulated by the bloom organisms to high levels, whereby their concentrations in the water declined, leading to a collapse of the bloom, which tended to reappear as decomposition again led to the release of the nutrients. The bloom also harboured fairly high density of certain other algae and zooplankton, thereby acting as a sub-system within the wetland ecosystem. The bloom is non-toxic and is exploited as a fish food by the fish-farmers who artificially induce a bloom for augmenting the growth of surface-feeding species of fishes.

Human papillomavirus testing for suspected cervical cancer patients from Southern Assam by fast-PCR.

World-wide epidemiological studies have shown that cancer of the uterine cervix is the second most common malignant disease in women. Virtually every cervical cancer (99.7%) is HPV-positive, indicating that the presence of HPV is an obligatory element in their development. The present study was conducted by Fast-PCR (within 15 min.) based diagnosis of HPV 16 and HPV 18 infection amongst patients of suspected cervical cancer, confirmed by cytological methods. Twelve women, out of a total of fifty studied cases who had positive cervical pap smears (24%) were found to be positive for HPV 16/HPV 18 infection when PCR based technique was applied. The results indicate, perhaps, a greater specificity of PCR based diagnosis, or presence of other HPV subtypes as etiological factors in the present study group confined to Southern Assam.

Host restriction of Friend leukemia virus: gag proteins of host range variants.

The host response to murine ecotropic leukemia viruses is mainly controlled by the mouse Fv-1 gene. This locus controls virus replication at an intracellular stage and prevents provirus integration. Biological studies suggest that the Fv-1 effector molecule recognizes at least one virion structural protein. We have produced host range variants of B-tropic Friend murine leukemia virus in order to study the primary structure of potential viral target proteins. Our results show that conversion of B-tropism to NB-tropism is associated with changes in the primary structure of three gag proteins--p15, p12, and p30. These results suggest that host range conversion is due to a recombinational event, presumably between the parental virus and an endogenous murine virus. They also open the possibility that p12 and p30 may be involved in host range restriction.

Fv-1 host restriction of Friend leukemia virus: oligonucleotide analysis of host range variants.

The Fv-1 murine gene controls predominantly the replication of leukemia viruses of murine cells. Forced passage by B-tropic Friend leukemia virus in the restrictive host cells (NIH, Fv-1n/n) results in viral progeny capable of replicating efficiently in murine cells of any Fv-1 type, which are denoted as NB-tropic virus. We have studied the RNase T1-resistant oligonucleotide pattern of a series of NB-tropic Friend virus isolates and have been able to show changes from the parental B-tropic virus which occur at the 5' end of the genome. Cloned NB-tropic virus falls into three classes, demonstrating either four, one, or no apparent changes in the genome. These results suggest the possibility that conversion to NB tropism occurs by a recombination mechanism but, since change to NB tropism can occur without any observable oligonucleotide alteration, they do not confirm that any single oligonucleotide is diagnostic of NB tropism.

Regulation of 2,4,5-trichlorophenoxyacetic acid and chlorophenol metabolism in Pseudomonas cepacia AC1100.

The expression of the degradative genes encoding 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), 2,4,5-trichlorophenol (2,4,5-TCP), and pentachlorophenol (PCP) dechlorination in a 2,4,5-T-degrading strain of Pseudomonas cepacia was examined during growth on alternate carbon sources. The dechlorination mechanisms for all three compounds were expressed in 2,4,5-T- and 2,4,5-TCP-grown cells but were not expressed in cells grown on succinate, glucose, or lactate. The addition of 2,4,5-TCP or PCP to cells grown on succinate or lactate resulted in the expression of the 2,4,5-TCP dechlorination mechanism in resting cells after 1-h lag. This expression was prevented by the presence of chloramphenicol in the resting cell suspension. Succinate-plus-PCP-grown resting cells preincubated with 2,4,5-TCP fully induced the trichlorophenol dechlorination system and partially induced the PCP dechlorination system. Preincubation of succinate-plus-PCP-grown resting cells with PCP induced neither the 2,4,5-TCP nor the PCP dechlorinating system. Succinate-grown resting cells converted 2,4,5-T to 2,4,5-TCP even in the presence of chloramphenicol. Thus, the data indicate that the enzyme(s) which converts 2,4,5-T to 2,4,5-TCP is constitutively expressed, whereas those that convert 2,4,5-TCP to central intermediates are induced by 2,4,5-TCP but not by 2,4,5-T or PCP and are repressed in the presence of an alternate carbon source.

Metabolism of Halophenols by 2,4,5-trichlorophenoxyacetic acid-degrading Pseudomonas cepacia.

Resting cells of 2,4,5-trichlorophenoxyacetic acid-grown Pseudomonas cepacia AC1100 were able to completely and rapidly dechlorinate several chlorine-substituted phenols, including 2,4,5-trichlorophenol, 2,3,4,6-tetrachlorophenol, and pentachlorophenol. Several other trichlorophenols were only partially dechlorinated. The evidence suggests that 2,4,5-trichlorophenol is an intermediate in the degradation of 2,4,5-trichlorophenoxyacetic acid by strain AC1100. Moreover, although strain AC1100 was isolated by selection for growth on a chlorinated aromatic compound, brominated and fluorinated analogs were efficiently dehalogenated by strain AC1100 resting cells, whereas an iodinated analog was poorly dehalogenated.

The mechanism of interallelic complementation at the INO1 locus in yeast: immunological analysis of mutants.

The ino1 locus of yeast has been demonstrated to be the structural gene for the repressible enzyme, L-myo-inositol-1-phosphate synthase (Donahue and Henry 1981 a). We have screened a large number of allelic representatives of the ino1 locus for the presence of protein which cross reacts with antibody produced in response to purified wild type inositol-1-phosphate synthase. Approximately 50% of all ino1 representatives screened by immunoprecipitation produce a protein of 62,000 molecular weight, identical in size to the wild type enzyme subunit. These mutants (termed crm+) were tested for expression of the 62,000 MW protein under conditions which are repressing for the wild type enzyme (greater than 25 microM exogenous inositol). The protein produced by the crm+ mutants, like the active enzyme in wild type yeast, is repressed in the presence of high levels of exogenous inositol. In addition, we have reassessed the interallelic complementation pattern observed among mutants at the ino1 locus. The entire pattern of interallelic complementation is temperature sensitive.