A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine

The object of our study is to project the impact of a prophylactic vaccine against persistent human papillomavirus (HPV)-16/18 infection on age-specific incidence of invasive cervical cancer. We developed a computer-based mathematical model of the natural history of cervical carcinogenesis to incorporate the underlying type-specific HPV distribution within precancerous lesions and invasive cancer. After defining plausible ranges for each parameter based on a comprehensive literature review, the model was calibrated to the best available population-based data. We projected the age-specific reduction in cervical cancer that would occur with a vaccine that reduced the probability of acquiring persistent infection with HPV 16/18, and explored the impact of alternative assumptions about vaccine efficacy and coverage, waning immunity and competing risks associated with non-16/18 HPV types in vaccinated women. The model predicted a peak age-specific cancer incidence of 90 per 100,000 in the 6th decade, a lifetime cancer risk of 3.7% and a reproducible representation of type-specific HPV within low and high-grade cervical precancerous lesions and cervical cancer. A vaccine that prevented 98% of persistent HPV 16/18 was associated with an approximate equivalent reduction in 16/18-associated cancer and a 51% reduction in total cervical cancer; the effect on total cancer was attenuated due to the competing risks associated with other oncogenic non-16/18 types. A vaccine that prevented 75% of persistent HPV 16/18 was associated with a 70% to 83% reduction in HPV-16/18 cancer cases. Similar effects were observed with high-grade squamous intraepithelial lesions (HSIL) although the impact of vaccination on the overall prevalence of HPV and low-grade squamous intraepithelial lesions (LSIL) was minimal. In conclusion, a prophylactic vaccine that prevents persistent HPV-16/18 infection can be expected to significantly reduce HPV-16/18-associated LSIL, HSIL and cervical cancer. The impact on overall prevalence of HPV or LSIL, however, may be minimal. Based on the relative importance of different parameters in the model, several priorities for future research were identified. These include a better understanding of the heterogeneity of vaccine response, the effect of type-specific vaccination on other HPV types and the degree to which vaccination effect persists over time.     

Variation in restriction fragment length polymorphisms among serial isolates from patients with Trichophyton rubrum infection

Molecular genotyping of strains of Trichophyton rubrum and T. mentagrophytes from patients with onychomycosis of the toes was performed to ascertain whether the fungal genotype changes over the course of time as sequential samples were obtained from patients receiving antifungal therapy and during follow-up. Sixty-six serial strains of T. rubrum and 11 strains of T. mentagrophytes were obtained from 20 patients (16 patients with T. rubrum, 4 with T. mentagrophytes) who were treated with oral antifungal therapy and observed over periods of up to 36 months. These strains were screened for genetic variation by hybridization of EcoRI-digested genomic DNAs with a probe amplified from the small-subunit (18S) ribosomal DNA and adjacent internal transcribed spacer regions. A total of five restriction fragment length polymorphism (RFLP) types were observed among 66 strains of T. rubrum. Two major RFLP types, differentiated by one band shift, represented 68% of the samples. None of the patients had a unique genotype. More than one RFLP type was often observed from a single patient (same nail) over a period of 1, 2, or 3 years, even in cases that did not appear cured at any time. Samples taken from different nails of the same patient had either the same or a different genotype. The genotypic variation did not correspond to any detectable phenotypic variation. Furthermore, no correlation was observed between the efficacy of the treatment administered and the genotype observed. While the DNA region studied distinguished among T. rubrum, T. mentagrophytes, and T. tonsurans, intraspecific RFLP variation was observed for T. rubrum and T. mentagrophytes strains. While independent multiple infection and coinhabitation of multiple strains may explain the presence of different genotypes in a nail, microevolutionary events such as rapid substrain shuffling, as seen in studies of repetitive regions in Candida species, may also produce the same result. The recovery of multiple strains during the course of sequential sampling of uncured patients further suggests that the typing system is not able to distinguish between relapse or reinfection, ongoing infection, and de novo infection.     

Pericardiectomy for constrictive pericarditis: is prolonged inotropic support a bad omen?

Sixty-seven patients who underwent pericardiectomy for constrictive pericarditis at JIPMER, Pondicherry between 1987 and 1998 were the subjects of the study. Pre-operatively 70% of cases were in the New York Heart Association classes III and IV categories with clinical signs suggestive of constriction ie, raised jugular venous pressure in 99%, pleural effusion in 77%, pedal oedema in 61% and ascites in 55% of the cases. Seventy-five per cent of the cases underwent pericardiectomy through a median sternotomy and the rest via left anterolateral thoracotomy. Low cardiac output was evidenced in 70% of cases postoperatively which was managed by early institution and prolonged use of inotropes. There was 9% mortality especially in the early part of the experience. Tuberculous pathology was confirmed histologically in 57% cases. Sixty-three per cent of cases are presenting in follow-up in New York Heart Association class I. Prolonged use of inotropes instituted early in postoperative period is recommended to prevent postoperative ventricular dysfunction with adrenaline being the preferred inotrope. It is concluded that postoperative New York Heart Association class and long term survival were not significantly influenced by pre-operative New York Heart Association class, operative approach or peri-operative low cardiac output syndrome requiring prolonged inotropic support.     

Periurethral collagen injection for stress incontinence with and without urethral hypermobility

OBJECTIVE: To compare the use of periurethral collagen injection in the treatment of female stress urinary incontinence due to intrinsic sphincter deficiency in women with and without urethral hypermobility. METHODS: A retrospective review was performed of 60 periurethral collagen injections performed on 40 consecutive women from January 1996 to December 1997. A review of the office chart and operative notes was performed to obtain demographic, urodynamic, and procedural data. Outcome data were obtained by personal or telephone interview, using patients' subjective assessments including an analog satisfaction scale. RESULTS: Nine of 40 patients (23%) had urethral hypermobility. Compared with patients without hypermobility, patients with hypermobility required a similar number of procedures (a mean of 1.9 compared with 1.4, P = .13) and required similar amounts of collagen on the first injection (5.6 mL compared with 5.3 mL, P = .69). Preoperative urodynamic parameters were similar in both groups. Rates of subjective dryness were equivalent in patients with and without hypermobility at 1 month (76% and 46%, P = .24) and at 6 months (71% and 32%, P = .09) following initial injection. A post hoc power analysis was performed to evaluate the primary study measures of continence at 1 and 6 months, and number of collagen injections. This revealed that a sample size of 40 patients would be sufficient to detect a 2.5-fold difference in number of injections and a 3-fold difference in subjective dryness. CONCLUSION: Coexisting urethral hypermobility should not preclude the use of collagen injections in women with stress urinary incontinence.     

Nasal tip metastasis: an unusual site and mode of spread in anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is the most aggressive and lethal form of thyroid malignancy which is difficult to treat. At the time of diagnosis, majority of patients have distant metastases most commonly in lung, bone, and liver. However nasal tip metastasis is not reported in literature. Implantation of malignant cells on nasal tip is also unknown. We hereby report an interesting and unusual mechanism for nasal tip metastasis in a patient with ATC.     

Invasive nosocomial aspergillosis associated with heart failure and complete heart block following recovery from dengue shock syndrome.

OBJECTIVE: To report a case of invasive aspergillosis, associated with complete heart block and heart failure, in an immunocompetent child recovering from dengue shock syndrome. DESIGN: Case report and literature review. SETTING: Pediatric intensive care unit in a tertiary care center. PATIENT AND RESULTS: A 9-yr-old boy was admitted to our pediatric intensive care unit with dengue shock syndrome, for which he was successfully managed. During the recovery phase, the child developed recurrence of fever and signs of congestive heart failure. Thereafter, he developed complete heart block and died. Myocardial biopsy revealed myocarditis and invading fungal elements with branching septate hyphae suggestive of Aspergillus. A renal biopsy specimen also showed glomerular invasion with Aspergillus and patchy necrosis. This suggested the diagnosis of invasive aspergillosis. CONCLUSIONS: This case highlights an unusual manifestation of invasive aspergillosis in a critically ill immunocompetent child.     

蛇胆汁中牛磺胆酸含量测定方法的比较研究

目的：比较分析了３种测定蛇胆汁中主要成分牛磺胆酸含量的方法,制定科学合理统一的质量标准。方法：用薄层层析－磷钼酸比色法、薄层扫描法及高效液相色谱法对蛇胆汁中主要成分牛磺胆酸进行测定,并将结果进行比较分析。结果：薄层层析－磷钼酸比色法、薄层扫描法及高效液相色谱法的含量测定结果有一定差异,平均回收率分别为９７．４８％,９８．５１％和１００．３４％,ＲＳＤ分别为４．６％,４．３％和１．５％。结论：高效液