Finding a vaccine for human papillomavirus.
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Biomedical subjects
Publications and source records attributed to John Cox.
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BACKGROUND: Paget's disease of the breast is an uncommon cancer. "Breast cancer" management has evolved to include sentinel lymph node biopsy (SLNB). Our objective is to determine utilization of SLNB in the surgical algorithm of Paget's disease. METHODS: After institutional review board approval, a database review of patients with Paget's disease was conducted. Patient demographics, tumor characteristics, treatment including use of SLNB, and survival were reviewed. Patient characteristics and outcomes were analyzed by using contingency table chi-square, pooled t tests, and log-rank tests for comparisons. RESULTS: Fifty-four patients with Paget's disease were identified and divided into 2 cohorts (18 no SLNB and 36 SLNB). The mean age was 66 years for the no-SLNB group and 60 years for the SLNB group (P = .17). Paget's disease only was present in 33%, Paget's disease + DCIS in 41%, and Paget's disease + invasive cancer in 26%. The mean invasive tumor size was 1.62 cm in the no-SLNB group and 1.59 cm in the SLNB group (P = .96). For invasive disease, ER/PR status was similar, but Her2 was more likely to be overexpressed in SLNB (P = .04). Surgery choice ranged from "no surgery" to lumpectomy to mastectomy. Axillary staging was performed in 45 of 54 patients, with 11% in both cohorts having nodal disease. A sentinel lymph node was identified in 97% of patients. Five-year overall and disease-free survival was 100% in the no-SLNB group and 88% in the SLNB group (P = .97) and 76% in the no-SLNB group and 84% in the SLNB group (P = .88), respectively. CONCLUSIONS: Paget's disease remains rare but should be treated similar to other "breast cancer." SLNB should be performed to evaluate the axilla when invasive disease is identified or a mastectomy is planned.
Improvements in immunosuppression have increased patient and graft survival in transplant recipients. As a result, there is greater risk of neoplastic processes such as breast cancer. Treatment in this population is complicated by the necessary immunosuppression, vascular accesses, and transplant grafts. General surgeons may expect to encounter more of these complex patients in the community setting. We sought to evaluate the surgical treatment of breast cancer in patients with renal transplants. Hospital and private physician records were queried to identify patients who developed breast cancer after a renal or pancreatic/renal transplantation. These charts were reviewed for demographics, type of breast cancer and treatment, location of dialysis access, and complications. From June 1, 1994, to May 31, 2004, 14 patients were identified. Eight patients had functioning transplants. All patients underwent operative interventions. Ten patients underwent adjuvant treatment. Three had functioning transplants and chose not to risk the graft with cessation of immunotherapy. However, no patient with functioning transplants who underwent chemotherapy developed organ failure. Breast cancer after transplantation poses a unique dilemma. The threat of transplanted organ failure is a major concern to these patients and often supersedes adjuvant therapies.
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All known sequences of the DNA encoding the major cervical cancer-causing human papillomavirus type 16 (HPV16) L1 capsid protein contain initiation codons which would allow translation to begin at either nucleotide 5559 or 5637. However the formation of virus-like particles (VLPs) only occurs efficiently when the initiation codon at nucleotide 5637 is used for in vitro expression studies. This knowledge, in concert with the fact that virions have not been observed in HPV16-infected epithelium, raises the notion that the major L1 translation product in this HPV type may be largely confined to initiation at nucleotide 5559. Sequence analysis of various HPV types associated with particular clinical outcomes has revealed that L1 sequences of the major cervical cancer-associated viruses generally possess the ability to encode a longer translation product whilst the non-cancer-causing viruses do not. Equally intriguing, the upstream initiation codon is always separated by 78 nucleotides from the initiation codon that produces L1 protein which efficiently assembles into VLPs. We speculate that the longer L1 protein could play a role in the development of cervical carcinoma and that HPVs with the potential to cause cervical cancer may be identified by the presence of an in-frame ATG situated 78 nucleotides upstream.
BACKGROUND: Investigators have commented on the apparent high prevalence of psychiatric symptoms in pregnancy. In Malta there is lack of epidemiological data and therefore, the prevalence of depression during pregnancy and at 8 weeks postpartum among a community sample of Maltese women was carried out. METHOD: A random sample of 239 pregnant women were interviewed at booking using a detailed sociodemographic history, the revised version of the clinical interview schedule (CIS-R) and Maltese translation of the Edinburgh postnatal depression scale (EPDS). The CIS-R was again administered over the phone at 36 weeks and the EPDS sent by post. At 8 weeks postpartum, the CIS-R, modified version of the social maladjustment schedule and the EPDS were again administered to 95.8% of women. RESULTS: The point prevalence of depression meeting ICD-10 research criteria was 15.5% at booking, 11.1% in the third trimester and 8.7% postpartum of which only 3.9% had an onset since delivery. CONCLUSIONS: The low rate of new onset postpartum depression compared with other studies in our sample may be attributable to the social support available to women living in a cohesive Catholic island community. LIMITATION: The follow-up was limited to 8 weeks postpartum. No control group was used to compare the prevalence of depression in women who did not recently have a baby.
Immunostimulating complex (ISCOM) vaccines are particulate antigen delivery vehicles composed of saponin, cholesterol, phospholipid and immunogen. Here we illustrate that ISCOM-based vaccines represent an attractive modality for the development of anti-cancer vaccines. Using murine models and a model cancer antigen, ISCOM vaccines were shown to induce potent CD8 T cell responses, to mediate protection in three different tumor models, to promote Th1-biased immunity, and to induce CD8 T cell responses in the absence of CD4+ T cell help. The former three activities were also found to be substantially improved when the vaccine antigen was associated with the ISCOM structure. Furthermore, the presence in vivo of pre-existing antibodies against the vaccine antigen did not inhibit CD8 T cell induction by the ISCOM vaccine. Although vaccination was effective against challenge with vaccine-antigen expressing tumors, no activity against neighboring vaccine-antigen negative tumor cells was observed, indicating that determinant spreading or bystander activity does not lead to significant anti-cancer activity.
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Mucosal delivery of inactivated vaccines that are able to elicit protective immune responses against respiratory diseases has been a long time goal of vaccinologists. Such vaccines would enable a more appropriate means of vaccination against respiratory diseases than those currently delivered by a parenteral route. The intranasal delivery of inactivated influenza vaccine plus the ISCOMATRIX (IMX) adjuvant, simply mixed together, was able to induce serum haemagglutination inhibition (HAI) titres in mice far superior to those obtained with unadjuvanted vaccine delivered subcutaneously. Furthermore, the IMX adjuvanted vaccine delivered intranasally induced mucosal IgA responses in the lung, nasal passages and large intestine, together with high levels of serum IgA. Intranasal delivery of IMX adjuvanted influenza vaccine in sheep gave antibody responses in both serum and nasal secretions that surpassed the levels obtained with unadjuvanted vaccine administered subcutaneously. These observations suggest that it may be possible to induce effective immunity to influenza in humans by intranasal vaccination with an IMX adjuvanted inactivated vaccine.
BACKGROUND: This prospective cohort study assessed the cost-effectiveness of treating 30 women with postnatal depression (PND) at a specialised psychiatric Parent and Baby Day Unit (PBDU), compared to 30 women treated using routine primary care (RPC). METHODS: Following recruitment, the women were assessed on three occasions (initially, 3- and 6-months), using a variety of social and psychiatric outcome measures. Direct and indirect costs were collated using structured interviews, retrospective analysis of case notes and routinely collated NHS cost data. Sensitivity analysis was also carried out. RESULTS: There was no significant difference between the women in the two groups initially in terms of their socio-demographic characteristics, or scores on the outcome measures. However, at 6-months, 21 women in the PBDU group were no longer depressed compared to only seven women in the RPC group. The total cost was 46,211 pounds for the PBDU group and 18,973 pounds for the RPC group. Moving from RPC to a PBDU would involve an additional expenditure of 27,238 pounds (46,211-18,973) whilst delivering 14 more positive outcomes. The move from RPC to PBDU would incur an additional cost per successfully treated woman of 1945 pounds (27,238/14). This compares favourably with the current cost per successfully treated woman in the RPC group of 2710 pounds (18,973/7). CONCLUSIONS: RPC is dominated on the grounds of cost-effectiveness by PBDU treatment and so PBDU treatment should be recommended to health care decision-makers. LIMITATIONS OF THE STUDY: The results were sensitive to the inclusion of primary care contacts and the costs of medication.
BACKGROUND: Focused assessment with sonography for trauma (FAST) as a screening tool in the evaluation of blunt abdominal trauma will lead to underdiagnosis of abdominal injuries and may have an impact on treatment and outcome in trauma patients. METHODS: From October 2001 to June 2002, a protocol for evaluating hemodynamically stable trauma patients with suspected blunt abdominal injury (BAI) admitted to our institution was implemented using FAST examination as a screening tool for BAI and computed tomographic (CT) scanning of the abdomen and pelvis as a confirmatory test. At the completion of the secondary survey, patients underwent a four-view FAST examination (Sonosite, Bothell, WA) followed within 1 hour by an abdominal/pelvic CT scan. The FAST examination was considered positive if it demonstrated evidence of free intra-abdominal fluid. Clinical, laboratory, and imaging results were recorded at admission, and FAST examination results were compared with CT scan findings, noting the discordance. RESULTS: Patients with suspicion for BAI were evaluated according to protocol (n = 372). Thirteen cases were excluded for inadequate FAST examinations, leaving 359 patients for analysis. There were 313 true-negative FAST examinations, 16 true-positives, 22 false-negatives, and 8 false-positives. Using CT scanning as the confirmatory test for hemoperitoneum, FAST examination had a sensitivity of 42%, a specificity of 98%, a positive predictive value of 67%, a negative predictive value of 93%, and an accuracy of 92%; chi analysis showed significant discordance between FAST examination and CT scan (5.85%, < 0.001). Six patients with false-negative FAST examinations required laparotomy for intra-abdominal injuries; 16 patients required admission for nonoperative management of injury. Of the 313 true-negative FAST examinations, 19 patients were noted to have intra-abdominal injuries without hemoperitoneum and 11 patients were noted to have retroperitoneal injuries. CONCLUSION: Use of FAST examination as a screening tool for BAI in the hemodynamically stable trauma patient results in underdiagnosis of intra-abdominal injury. This may have an impact on treatment and outcome in trauma patients. Hemodynamically stable patients with suspected BAI should undergo routine CT scanning.
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BACKGROUND: To document the technical aspects, outcome and lessons learnt during the learning curve phase of implementing laparoscopic splenectomy, by comparing the results before and after the introduction of a standardized technique. METHODS: We present a retrospective and prospective review of laparoscopic splenectomies over a 4-year period. Two chronological periods were studied, before and after the implementation of a standardized technique of a laparoscopic splenectomy involving: (i) hilar dissection with ultrasonic shears; (ii) two experienced laparoscopic surgeons; and (iii) trained dedicated equipment and staff using a checklist approach in the preparation and conduct of the operation. Two groups of patients were studied relating to the periods before and after the implementation of a standardized technique. Statistical methods used were the Wilcoxon's rank sum test and the two-sample test. RESULTS: Thirty-one laparoscopic splenectomies were attempted. The most common indication was for idiopathic thrombocytopenic purpura. When comparing the early phase (n = 15) with the standardized technique phase (n = 16), there was a significant reduction in conversion rates (40% vs 6%), operating times (218 min vs 171 min), complication rates (6 cases including 1 death vs none) and length of stay (11 days vs 4 days). The results were significant for reduction in hospital stay, conversion rates and complications rates. CONCLUSIONS: A reduction in conversion rates, operating time, morbidity and length of stay was realized during the learning curve of implementing laparoscopic splenectomy by adopting a standardized technique. This technique involved hilar dissection using the ultrasonic shears, two experienced laparoscopic surgeons performing the surgery, dedicated equipment and trained staff using the checklist approach. We recommend such a standardized technique in performing laparoscopic splenectomy.
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