The Yb(2)Al(1-x)Mg(x)Si(2) series from a spin fluctuation (x = 0) to a magnetically ordered ground state (x = 1).

The structural and magnetic properties of Yb(2)Al(1-x)Mg(x)Si(2) (x = 0, 0.5 and 1), crystallizing in the tetragonal Mo(2)FeB(2)-type structure, are reported in this work. Yb(2)AlSi(2) exhibits a Pauli paramagnetic ground state arising due to spin/valence fluctuations induced by a significant Yb 4f conduction band hybridization. High-field magnetization (up to 120 kOe) indicates a nearly temperature-independent susceptibility of 8.6 × 10(-3) emu/Yb mol below 10 K. On the other hand, Yb ions in Yb(2)MgSi(2) order antiferromagnetically at a relatively high temperature T(N) of 9.5 K. The intermediate composition alloy Yb(2)Al(0.5)Mg(0.5)Si(2) is a Kondo lattice, antiferromagnet with T(N) = 5.5 K. The coefficient of the linear term of the electronic heat capacity, γ, of Yb(2)AlSi(2) is found to be 305 mJ mol(-1) K(-2), indicating a significant electronic mass enhancement due to strong electronic correlations. Below 12 K, an additional contribution to the heat capacity of the form T(3)lnT is observed. The (170)Yb Mössbauer spectra in the ordered state of Yb(2)MgSi(2) indicate a strong coupling of the 4f quadrupolar moment with the magnetic moment through a magneto-elastic coupling.

An unusual presentation of immotile-cilia syndrome with azoospermia: Case report and literature review.

Immotile-cilia syndrome is a rare disorder characterized by chronic recurrent sino-pulmonary infection, impaired tracheobronchial clearance, situs inversus in about 50% of cases, and living but immotile spermatozoa of normal morphology in semen analysis. In this report, we describe an unusual presentation of immotile-cilia syndrome with azoospermia in a 32-year-old male patient. The diagnosis was based on history of recurrent respiratory tract infection, bronchiectasis, maxillary sinusitis, hypoplasia of frontal sinuses, dextrocardia with situs inversus, impaired nasal mucociliary clearance, etc. Semen analysis revealed azoospermia without any evidence of obstruction in epididymides or vas deference. Normal spermatogenesis was seen on testicular biopsy.

Prevalence and risk factors for carcinogenic human papillomavirus infections in rural Rakai, Uganda.

OBJECTIVE: To investigate self-administered vaginal swabs for assessing prevalence and correlates of carcinogenic human papillomavirus (HPV) infection in rural Rakai, Uganda. METHODS: 1003 sexually experienced women enrolled in a community cohort provided self-administered vaginal swabs collected at annual, home-based surveys. Carcinogenic HPV prevalence, adjusted odds ratios (AOR), 95% confidence intervals (CI) and associated risk factors were determined. RESULTS: Carcinogenic HPV prevalence was 19.2%: 46.6% among HIV positive and 14.8% among HIV negative women (p<0.001). Type-specific prevalence ranged from 2.0% (HPV 16 and 52) to 0.2% (HPV 31). Age-specific HPV prevalence decreased significantly (p<0.001) among HIV negative women; however, the decrease among HIV positive women was not as pronounced (p = 0.1). Factors independently associated with carcinogenic HPV infection were HIV (AOR 4.82, CI 3.10 to 7.53), age (AOR 4.97, 95% CI 2.19 to 11.26 for 15-19 year olds compared to 40+ years), more than two sex partners in the past year (AOR 2.21, CI 1.10 to 4.43) and self-reported herpes zoster, candidiasis or tuberculosis (AOR 4.52, CI 1.01 to 20.31). Married women were less likely to have prevalent carcinogenic HPV (AOR 0.46, CI 0.30 to 0.70). CONCLUSIONS: HPV prevalence and correlates measured using self-administered vaginal swabs were similar to studies that use cervical samples. Thus, self-collection can be used as a substitute for cervical specimens and provide an important tool for research in populations unwilling to undergo pelvic exam.

Evaluation of adjunctive tests for cervical cancer screening in low resource settings.

BACKGROUND: Visual inspection of cervix after application of acetic acid (VIA) is an effective screening tool for cervical cancer in low resource settings, but its low specificity leads to high referral rates. Adjunctive testing may overcome this drawback. AIMS: This pilot study was aimed to assess test performances of VIA, human papillomavirus (HPV) testing and Pap smear, individually and in simulated combinations, to determine the probable best screening option. SETTING AND DESIGN: Gynecology outpatient department (OPD); cross-sectional study. MATERIALS AND METHODS: One hundred women with complaints of irregular vaginal bleeding or discharge, post coital bleeding or unhealthy cervix on examination underwent Pap smear, HPV testing, VIA, colposcopy and biopsy, if indicated, in this screening order. STATISTICAL ANALYSIS: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each of the tests with a biopsy result of > or =HSIL taken as the gold standard. Simulated parallel and sequential combinations for VIA/Pap, VIA/HPV and HPV/Pap were calculated and compared with individual test performance. RESULTS: Prevalence of abnormal Pap smears was 5%, VIA positive 51% and HPV positive 16%. Sensitivity and specificity of VIA were 100% and 53.3% respectively. For HPV and Pap tests corresponding figures were 85.7%, 89.7% and 50%, 98.9% respectively. The best simulated combination with a balance of sensitivity and specificity was of VIA followed by HPV testing (sensitivity 85.7%, specificity 95.4%). CONCLUSION: Addition of HPV testing to VIA can increase the specificity of VIA, thereby reducing the referral rates without compromising the sensitivity of the test.

Double-blind, randomised, controlled trial assessing controller medications in asthma.

BACKGROUND: The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids. OBJECTIVES: The study aimed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone. METHODS: Ninety patients with incompletely controlled asthma were allocated, in a randomised, double-blind fashion, to one of three treatment groups: group A: double dose of inhaled budesonide (400 microg b.i.d.), group B: 400 mg oral sustained-release theophylline plus budesonide (200 microg b.i.d.) and group C: 10 mg montelukast plus budesonide (200 microg b.i.d.). The primary endpoints were forced expiratory volume in 1 s (FEV(1)) and mean morning peak expiratory flow rate (PEFR). RESULTS: All three groups had improved FEV(1) and PEFR at 8 weeks (p < 0.001). Group C increased their PEFR by 18.7 l/min (95% confidence interval, CI, 12.4-25.1) more than group A and by 19.8 l/min (95% CI 13.4-26.1) more than group B (both p = 0.001). Similarly, group C had a 114 ml (95% CI 45-183 ml) greater improvement in FEV(1) than group A and a 95 ml (95% CI 26-164 ml) greater improvement than group B (both p = 0.01). CONCLUSIONS: Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters than high-dose budesonide treatment or addition of theophylline.

Absence of human papillomavirus in esophageal carcinomas from southwestern Kenya.

Esophageal squamous cell cancer is highly prevalent in south-western Kenya. The role of human papillomavirus (HPV) in esophageal cancers from this region was evaluated. Biopsies of 29 esophageal squamous cell cancers were assayed for HPV DNA sequences by reverse line blot polymerase chain reaction, using 27 HPV type-specific probes. Viral sequences were found in none of the specimens. These results suggest the HPV is unlikely to be an etiologic factor for esophageal squamous cell cancers in this region.

Poliovirus vaccination during pregnancy, maternal seroconversion to simian virus 40, and risk of childhood cancer.

Before 1963, poliovirus vaccine produced in the United States was contaminated with simian virus 40 (SV40), which causes cancer in animals. To examine whether early-life SV40 infection can cause human cancer, the authors studied 54,796 children enrolled in the US-based Collaborative Perinatal Project (CPP) in 1959-1966, 52 of whom developed cancer by their eighth birthday. Those children whose mothers had received pre-1963 poliovirus vaccine during pregnancy (22.5% of the children) had an increased incidence of neural tumors (hazard ratio = 2.6, 95% confidence interval: 1.0, 6.7; 18 cases) and hematologic malignancies (hazard ratio = 2.8, 95% confidence interval: 1.2, 6.4; 22 cases). For 50 CPP children with cancer and 200 CPP control children, the authors tested paired maternal serum samples from pregnancy for SV40 antibodies using a virus-like particle enzyme immunoassay and a plaque neutralization assay. Overall, mothers exhibited infrequent, low-level SV40 antibody reactivity, and only six case mothers seroconverted by either assay. Using the two SV40 assays, maternal SV40 seroconversion during pregnancy was not consistently related to children's case/control status or mothers' receipt of pre-1963 vaccine. The authors conclude that an increased cancer risk in CPP children whose mothers received pre-1963 poliovirus vaccine was unlikely to have been due to SV40 infection transmitted from mothers to their children.

Human papillomavirus, p53 and cyclin D1 expression in oropharyngeal carcinoma.

Forty-two specimens from oropharyngeal (tonsil and base of tongue) squamous cell carcinoma patients (SCC) were studied for presence of HPV 16 by in situ hybridization and by immunohistochemistry for p53 and Cyclin D1 protein overexpression. Thirty-one per cent of cases were HPV-16 positive, which correlates with the prevalence reported worldwide. 74% of cases showed p53 protein overexpression and 79% showed Cyclin D1 overexpression. There was no correlation between HPV status and either p53 or Cyclin D1 overexpression (P>0.05). These three variables also did not correlate with factors such as grade of the tumour, stage of the disease or lymph nodal metastasis at presentation.

Prevalence and determinants of human papillomavirus genital infection in men.

Four-hundred-forty-five husbands of women with invasive cervical carcinoma, 165 of women with in situ cervical cancer, and 717 of control women (age range 19-82 years) were interviewed and a sample of exfoliated cells from the penis obtained in seven case-control studies conducted by the International Agency for Research on Cancer. The characteristics of human papillomavirus-positive and human papillomavirus-negative husbands were compared using odds ratios and 95% confidence intervals. Thirteen per cent of the husbands of control women, 18% of the husbands of women with invasive cervical carcinoma, and 21% of the husbands of in situ cervical carcinoma women were positive for penile human papillomavirus DNA. Human papillomavirus 16 was detected in 45 husbands, human papillomavirus 18, 31 or 33 in 19, and human papillomavirus 6/11 in 6, but the majority of human papillomavirus infection (158) was with other or unspecified human papillomavirus types. The same human papillomavirus type was seldom identified in both husband and wife. The strongest variation in penile human papillomavirus infection was by country, with percentages among the husbands of control women ranging between 3% in Spain and 39% in Brazil. Having had over 50 lifetime sexual partners, compared with only one, was associated with an odds ratio of 2.3.

The causal relation between human papillomavirus and cervical cancer.

The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.

Study of drug resistance in previously treated tuberculosis patients in Gujarat, India.

SETTING: Department of Tuberculosis and Chest Diseases and State Tuberculosis Diagnosis and Training Centre (STDTC), a DOTS centre in Ahmedabad, Gujarat State, India. The study was carried out by retrospectively reviewing patient data between January 2000 and August 2001. OBJECTIVE: To evaluate the pattern of drug resistance among previously treated tuberculosis patients who remained symptomatic or smear-positive despite receiving anti-tuberculosis drugs under DOTS for a minimum of 5 months. DESIGN: A total of 1472 pulmonary tuberculosis patients who had taken anti-tuberculosis treatment were evaluated retrospectively with respect to their drug resistance pattern by sputum culture for acid-fast bacilli (AFB) and sensitivity testing with isoniazid, rifampicin, streptomycin and ethambutol (E). RESULT: Of the 1472 patients evaluated, 804 (54.6%) were treatment failure cases and 668 (45.4%) were relapse cases; 822 patients (373 failure and 449 relapse) were culture-positive. Of these 822 patients, 482 (58.64%, 261 failure and 221 relapse) were resistant to one or more drugs. Resistance to one drug was observed in 86 patients (10.46%), to two drugs in 149 (18.13%), to three drugs in 122 (14.84%) and to four drugs in 125 (15.21%). Single drug resistance was most commonly seen with isoniazid (62 patients, 7.5%), followed by streptomycin (12 patients, 1.4%), rifampicin (eight patients, 0.97%) and ethambutol (four patients, 0.4%). Resistance to isoniazid plus rifampicin alone was seen in 76 patients (9.2%). CONCLUSION: Drug resistance is a major problem in the treatment of pulmonary tuberculosis. Detection of drug resistance patterns and treatment with second-line anti-tuberculosis drugs in appropriate regimens are necessary in the treatment of failure and relapse cases in order to reduce the emergence of multidrug-resistant tuberculosis.

Adeno-associated virus seropositivity and HPV-induced cervical cancer in Spain and Colombia.

Extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (AAV) can have antioncogenic activity and may be protective factors for the development of cervical cancer. To examine the association between AAV-2 IgG antibodies and cervical neoplasia in Spain and Colombia, we tested for AAV-2 antibodies using an ELISA assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinic-based controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA was detected in cervical exfoliated cells by polymerase chain reaction using HPV-L1 and GP5+/6+ consensus primers. The prevalence of AAV-2 antibody titers >100 was significantly lower in invasive cervical cancer cases than control participants. When comparing women with invasive cancer with controls or with CIN III cases, a pattern of decreasing cervical cancer risk with increasing AAV-2 titers was observed. Elevated AAV antibody titers (>100) were inversely associated with invasive cervical cancer (OR 0.3; 95% CI 0.1-0.7), although results were not statistically significant after controlling for HPV (OR 0.4; 95% CI 0.1-1.6). In contrast, AAV-2 antibodies were not significantly associated with the risk of CIN III (OR 1.4; 95% CI 0.3-6.8). These results provide supportive evidence that AAV infection may be a protective factor for the development of invasive cervical cancer. Alternatively, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be due to an immunosuppressive effect of cervical cancer on AAV antibody response. To investigate whether a direct viral interaction is occurring, future studies should aim to resolve at what frequency AAV is found in the genital tract and to clarify further whether AAV may infect the same HPV-positive cells in the cervix.

Evaluation of use of a single intravaginal swab to detect multiple sexually transmitted infections in active-duty military women.

The accuracy and suitability of use of a single intravaginal swab (SIS) for polymerase chain reaction detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and human papillomavirus infection was assessed in a cross-sectional study of 841 active-duty military women. The SIS, compared with standard diagnostic tests, allowed detection of more gonorrhea, more chlamydial infection, and more trichomoniasis. Sensitivity and specificity of SIS detection compared with adjudicated true-positive diagnoses were 95.8% and 97.8%, respectively, for gonorrhea, 94.6% and 99.3% for chlamydial infection, and 92.2% and 98.2% for trichomonal infection. Results with SISs were comparable to those with cervical swabs tested for human papillomavirus. Assay of clinician-collected and self-collected SISs yielded prevalences similar to those of standard diagnostic tests for all sexually transmitted infections. Therefore, the use of SISs is acceptable for the simultaneous diagnosis of multiple sexually transmitted infections and has potential for use as a self-administered diagnostic tool with widespread applicability among women.

Diagnosis of human papillomavirus infection by dry vaginal swabs in military women.

OBJECTIVE: Human papillomavirus (HPV) assays are likely to be used with increasing frequency in clinical management of women with abnormal Papanicolaou smears and in cervical cancer screening. Our objective was to simplify the method of collection of female genital tract specimens. The utility of vaginal dry swabs for HPV diagnosis was evaluated. METHODS: Specimens for cytology and for HPV identification were collected by a clinician from 189 female soldiers attending a military clinic. Three methods of specimen collection for HPV identification were compared: a vaginal dry swab (v-DRY), and vaginal and cervical swabs placed into specimen transport medium (v-STM and c-STM). Swabs were shipped to a STD laboratory for processing. Specific HPV types were identified by a consensus primer based PCR based method. Results from 165 women were evaluable. RESULTS: HPV prevalence by the three methods was similar and ranged from 44.8% to 50.9%. 53 (32.1%) women were HPV positive and 60 (36.4%) women were HPV negative by all three collection methods. With respect to the risk categories of specific HPV types, there was greater agreement between the results from the two vaginal (v-DRY and v-STM) samples (kappa values of 0.69-0.81) than between the cervical (c-STM) and either of the vaginal samples (kappa values of 0.37-0.55). The HPV yield from c-STM was somewhat greater than that from the vaginal specimens but the correlation between cytological abnormalities and HPV was high for all three methods. CONCLUSION: A dry vaginal swab may be an acceptable method of specimen collection for HPV diagnosis.

Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers.

There is increasing molecular and epidemiologic evidence that human papillomavirus (HPV) is associated with a distinct subset of head and neck squamous cell carcinomas. The strength and consistency of HPV DNA presence in oropharyngeal cancers bolster the argument that this association is likely causal. HPV-positive tonsillar cancer in particular is emerging as a specific disease entity with distinct molecular, pathologic, and clinical characteristics. Recent data suggest that the incidence of tonsillar carcinoma in the United States is increasing, despite a decline in tobacco use, supporting the existence of other important risk factors such as HPV infection. Individuals with a history of an HPV-associated anogenital cancer and HIV-infected men are at increased risk for tonsillar carcinoma. This review focuses on the recent literature (since 1998) investigating the relationship between HPV and head and neck cancer development, using the current paradigm for causal inference in epidemiologic research attributed to Sir A. Bradford Hill. Data examining the association of HPV with pathogenesis of head and neck squamous cell carcinoma before 1999 were previously reviewed in this journal.

Epidemiology of HPV infection among Mexican women with normal cervical cytology.

Cervical cancer is caused by human papillomavirus (HPV) and is the most common cancer among Mexican women, but no population-based studies have reported the prevalence and determinants of HPV infection in Mexico. A population-based study was carried out between 1996 and 1999, based on an age-stratified random sample of 1,340 women with normal cytologic diagnoses from 33 municipalities of Morelos State, Mexico. The prevalence of cervical HPV DNA was determined by reverse line blot strip assay to detect 17 cancer-associated and 10 non-cancer-associated HPV types. Two peaks of HPV DNA prevalence were observed. A first peak of 16.7% was observed in the age group under 25 years. HPV DNA prevalence declined to 3.7% in the age group 35-44 years, then increased progressively to 23% among women 65 years and older. Cancer-associated HPV types were the most common in all age groups; non-cancer-associated HPV types were rare in the young and became more common linearly with age. Twenty-four types of HPV were detected; HPV 16, HPV 53, HPV 31 and HPV 18 were the most common, but none was present in more than 1.7% of subjects. The main determinant of infection with both cancer-associated and non-cancer-associated HPV types was the number of sexual partners in all age groups. Less-educated women were at an increased risk of infection with cancer-associated but not with non-cancer-associated HPV types; low socioeconomic status was associated with detection of non-cancer-associated HPV types. Among young women an increasing number of pregnancies was associated with lower HPV detection and among older women low socioeconomic status was related to increased HPV detection, particularly for the age group 35-54 years. Among women with cancer-associated HPV types, there was a higher intensity of polymerase chain reaction signal in younger than in older age groups (p < 0.001). We present additional evidence for the sexually transmitted nature of HPV infection, regardless of age group and HPV type. We confirm previous findings of a second peak of high-risk HPV infections in postmenopausal women, in this case with a clear predominance of cancer-associated HPV types. In populations with this pattern, which can be related to reactivation of latent HPV infections or high previous exposure in older women, screening with HPV testing can have a reduced specificity among older women if proper cut-off points for HPV positivity are not used. Longitudinal studies of immune responses to HPV infection in different age groups are warranted.

Investigation of the SV40--human cancer association: look for the full signature of the virus.

In the controversy about the association of simian virus 40 with human cancers, the greatest problem is the ascertainment of SV40 exposure. This difficulty would be resolved if one were to look for all components of SV40 infection. How does SV 40 circulate in the human community? Do cancer patients with SV40-positive tumors have serological correlates of SV 40 infection and of SV40-induced cancer? SV40 association with a cancer should be studied in the context of the known risk factors for that cancer. The tumor cell-virus relationship should be characterized with respect to viral integration and viral localization to the tumor cell. Specimens should be masked and the assays should include panels of specimens to estimate analytic sensitivity and specificity. In view of the rarity of some of the tumors reported to be associated with SV40, a multi-institutional investigation initiated and coordinated by the NIH would be most effective.

Detection and quantitation of human papillomavirus (HPV) DNA in the sera of patients with HPV-associated head and neck squamous cell carcinoma.

The human papillomavirus (HPV) has been implicated as an etiological factor in a subset of head and neck squamous cell carcinoma (HNSCC). Because circulating tumor DNA has previously been detected in the sera of patients with advanced HNSCC (stage III or IV), we hypothesized that HPV DNA might be present in the sera of HPV-positive HNSCC patients. Serum DNA extracts from 70 patients with HNSCC were screened for HPV using conventional PCR and a real-time quantitative assay. All samples subjected to conventional PCR were further tested by dot blot hybridization, and positives were confirmed by Southern blotting. Paired tumor DNA from archived tissues was then similarly screened for HPV genomic material (n = 51) or tested by in situ hybridization (n = 19). HPV-16 DNA was detected with L1 primers in 0 of 65 sera and in 15 of 70 (21%) tumors. Conventional PCR with E7 primers and Southern blot hybridization detected HPV-16 DNA in four (6%) sera. Using real-time quantitative PCR, six samples were found to contain various levels of circulating HPV DNA (mean, 12 copies/ml; range, <1-35.) All six serum-positive patients had corresponding tumors positive for E7. Four of these patients with HPV-positive tumors later developed distant metastases, suggesting that HPV DNA in serum may represent occult hematogenous spread of cancer cells in this subset of patients. Although a much larger prospective trial is required, the presence of HPV genomic material in serum DNA of HPV-positive HNSCC patients may serve as a useful marker of early metastatic disease.

Intra-laboratory reproducibility of human papillomavirus identification in cervical specimens by a polymerase chain reaction-based assay.

BACKGROUND: polymerase chain reaction (PCR)-based assays for human papillomavirus (HPV) sequences are in wide use in clinical and epidemiological studies. The reproducibility of these assays is not extensively studied. OBJECTIVES: to estimate the intra-laboratory reproducibility of generic and type-specific HPV diagnoses by the MY09/MY11/HMB01 consensus L1 primer-based PCR assay. STUDY DESIGN: systematically collected specimens (n=207) were masked and retested. RESULTS: when specimens negative in both initial and repeat assays were excluded from analysis, the diagnostic reproducibility was 98. 6% for beta-globin, 90.7% for generic HPV (any HPV type), and 76.9% for type-specific HPVs. The reproducibility of type-specific diagnosis increased with increase in signal strength in the hybridization reaction of the initial assay. When a specimen contained five or more HPV types in the initial assay, it was rare to identify all of the HPV types in the repeat assay. CONCLUSIONS: the degree of reproducibility of the PCR diagnosis should be taken into account in the interpretation of HPV data in clinical and epidemiological studies.