Adenovirus-mediated p53 gene therapy in nasopharyngeal cancer

EBV-associated nasopharyngeal cancer (NPC) occurs with high frequency in China and is a major cause of morbidity and mortality. To explore the potential use of adenovirus-mediated tumor suppressor p53 gene therapy In NPC, we first examined the in vitro effects of p53 introduced into the NPC cell lines RPMI 2650, Fadu and Detroit 562. p21(WAF1/CIP1) induction by chemotherapy was used as a functional assay which revealed that RPMI 2650 expresses wild-type p53 whereas Fadu and Detroit 562 encode mutant p53. Infection with p53-expressing adenovirus (Ad-p53) induced apoptosis and inhibited cell growth in all three NPC cell lines, regardless of the endogenous p53 status. Adenovirus infectivity was greatest in RPMI 2650 cells, with 100% of the cells expressing beta-galactosidase following Ad-LacZ infection using an MOI of 100, as compared to 20-30% infectivity with the other NPC lines. Using RPMI 2650 cells injected into nude mice, we developed an animal model for nasopharyngeal cancer. Established tumors (0.6-0.8 cm) were injected with 5x10(9) PFU Ad-LacZ, Ad-p53 or PBS in a 100 mu l volume. We found evidence for in vivo expression of beta-galactosidase or p53 and p21 up to two weeks following Ad-LacZ or Ad-p53 virus injection respectively. Objective regression of tumor size was observed at two weeks in 4/6 Ad-p53-treated tumors, but not in Ad-LacZ or PBS-treated tumors. The results provide an animal model for human nasopharyngeal cancer, and indicate a potential use of p53 in its therapy in vivo.     

Timing of surgery for common pediatric surgical conditions

Depending upon various factors the surgical procedures in childhood are divided into three groups—immediate, intermediate and elective. The timing of surgery is probably the most important factor governing the outcome of surgical correction in pediatric surgery. With continuing research and clinical experience our understanding of the various conditions have improved and with that has come a change in the optimum timing of many surgical procedures. This paper highlights the best timing of surgery for some of the commoner pediatric surgical procedures and the reasons behind these so that the children may be referred to pediatric surgeons in time.     

Carcinoma of the maxillary antrum — A 10 year experience

A retrospective analysis was performed of 250 cases of carcinoma of the maxillary antrum seen over a 10 years period (1975–1984). 98.24% patients were seen in T3 and T4 stages (UICC 1985). 40.7% patients presented with clinically palpable nodes. 42.9% patients were treated by radical radiation and 18.6% by a combination of preoperative radiation followed by surgery. Rest 38.5% patients were treated with palliative intention. Three year disease free survival was 39.58% with radiation alone and 51.91% with combined modality treatment which includes patients salvaged by surgery. Failures were mainly at the local site, 75.86% with radiation alone and 60% with combined modality treatment. Combined modality treatment, preferably preoperative radiation followed by radical surgery, gives the best results in the management of carcinoma of the maxillary antrum.     

Volumetric control of continuous haemodialysis in multiorgan failure.

The authors have developed a system for volumetric control of continuous haemodialysis. The article describes this system and reports its successful use in providing renal support in the intensive care unit to 10 patients with multiorgan failure. In addition to providing effective treatment of uraemia, it permits the precise control of fluid balance in a prospective manner ("dial-up" fluid balance) while reducing nursing workload.     

Papillary thyroid carcinoma in a thyroglossal cyst

The incidence of Papillary Thyroid Carcinoma in a Thyroglossal Cyst is rare. Only about 160 cases have been reported in the last 85 years. We report a case of Thyroglossal Cyst who underwent Sistrunk ’s Operation. The Cyst was reported to contain a focus of papillary thyroid carcinoma. In the absence of metastases in thyroid gland and neck nodes, only thyroid suppression with Thyroxine was given. After I year of follow-up there are no metastases. The importance of Sistrunk’s operation lies not only in complete removal of Thyroglossal Cyst but also in management of small foci of Papillary thyroid Carcinoma.     

Midline granuloma in infant

Midline Granuloma is a very uncommon disease characterised by localised inflamation, destruction and often mutilations of the tissues of the upper respiratory tract and face. This unique case is being reported for its rarity having the complete destruction of the external nose and part of the upper lip.     

A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma.

PURPOSE: Localized pancreatic carcinoma is rarely resectable and is resistant to conventional therapies. ONYX-015 (dl1520) is an E1B-55kD gene-deleted replication-selective adenovirus that preferentially replicates in and kills malignant cells. Endoscopic ultrasound (EUS) has the potential to conveniently and accurately deliver local therapy to the pancreas. Therefore, we undertook a trial of the feasibility, tolerability, and efficacy of EUS injection of ONYX-015 into unresectable pancreatic carcinomas. EXPERIMENTAL DESIGN: Twenty-one patients with locally advanced adenocarcinoma of the pancreas or with metastatic disease, but minimal or absent liver metastases, underwent eight sessions of ONYX-015 delivered by EUS injection into the primary pancreatic tumor over 8 weeks. The final four treatments were given in combination with gemcitabine (i.v., 1,000 mg/m(2)). Patients received 2 x 10(10) (n = 3) or 2 x 10(11) (n = 18) virus particles/treatment. RESULTS: After combination therapy, 2 patients had partial regressions of the injected tumor, 2 had minor responses, 6 had stable disease, and 11 had progressive disease or had to go off study because of treatment toxicity. No clinical pancreatitis occurred despite mild, transient elevations in lipase in a minority of patients. Two patients had sepsis before the institution of prophylactic oral antibiotics. Two patients had duodenal perforations from the rigid endoscope tip. No perforations occurred after the protocol was changed to transgastic injections only. CONCLUSIONS: This study indicates that ONYX-015 injection via EUS into pancreatic carcinomas by the transgastic route with prophylactic antibiotics is feasible and generally well tolerated either alone or in combination with gemcitabine. Transgastric EUS-guided injection is a new and practical method of delivering biological agents to pancreatic tumors.     

The Impact of Diabetes on Workforce Participation: Results from a National Household Sample

Objective. Diabetes is a highly prevalent condition that results in substantial morbidity and premature mortality. We investigated how diabetes-associated mortality, disability, early retirement, and work absenteeism impacts workforce participation.
Data Source. We used the Health and Retirement Study (HRS), a national household sample of adults aged 51–61 in 1992, as a data source.
Study Design. We conducted cross-sectional analyses on the baseline HRS data, and longitudinal analyses using data from eight years of follow-up. We used two-part regression models to estimate the adjusted impact of diabetes on workforce participation, and then estimated the economic impact of diabetes-related losses in productivity.
Principal Findings. Diabetes is a significant predictor of lost productivity. The incremental lost income due to diabetes by 1992 was $60.0 billion over an average diabetes duration of 9.7 years. From 1992 to 2000, diabetes was responsible for $4.4 billion in lost income due to early retirement, $0.5 billion due to increased sick days, $31.7 billion due to disability, and $22.0 billion in lost income due to premature mortality, for a total of $58.6 billion dollars in lost productivity, or $7.3 billion per year.
Conclusions. In the U.S. population of adults born between 1931 and 1941, diabetes is associated with a profound negative impact on economic productivity. By 1992, an estimated $60 billion in lost productivity was associated with diabetes; additional annual losses averaged $7.3 billion over the next eight years, totaling about $120 billion by the year 2000. Given the rising prevalence of diabetes, these costs are likely to increase substantially unless countered by better public health or medical interventions.