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AA amyloidosis is the most serious potential complication of the inherited autoinflammatory syndromes and frequently results in end-stage renal failure. Although this complication is well recognized in familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, and Muckle-Wells syndrome, there is only 1 previous published report of its occurrence in hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). We report 2 further cases of patients with AA amyloidosis in HIDS, both of whom developed dialysis-dependent renal failure, and we describe the outcome of the first renal transplant in this setting. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGF-R) perturbation by receptor ligand(s), e.g., epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), or receptor-specific antibodies accentuates cisplatin-induced toxicity in tumor cells. This sensitization occurs only in tumor cells with high expression of EGF-R but not in those with low expression of EGF-R.Purpose: Therefore, we have studied the role of EGF-R expression on cisplatin-mediated cytotoxicity.Methods: MDA-468 human breast cancer cells were stably transfected with a p-chloramphenicol acetyl transferase (pact[p]-CAT) vector containing a 4.1-kilobase full-length antisense EGF-R complementary DNA. EGF-R content was assessed by 125I-EGF binding and EGF-R immunoblot assays. Cisplatin sensitivity was evaluated by (a) colony-forming assay in vitro, (b) xenograft growth in nude mice, (c) cell cycle distribution of propidium iodide-labeled DNA, (d) DNA fragmentation in agarose gels, and (e) terminal deoxynucleotidyl transferase (Tdt) fluorescence in situ. Cisplatin uptake was measured by atomic absorption spectroscopy, and the levels of drug-DNA intrastrand adducts were determined by a dissociation-enhanced fluoroimmunoassay that utilizes an antibody against cisplatin-modified DNA.Results: Selected clones (MDA-468/AS-EGFR) exhibited more than 90% loss of both 125I-EGF binding and receptor content determined by western blot analysis, whereas clones transfected with the vector alone (MDA-468/p-CAT) had EGF-R levels similar to those of the parent cells. By use of a colony-forming assay, the 1-hour IC50 (i.e., the concentration of drug required for 1 hour to achieve 50% cell kill) for cisplatin was 2 microM or less for parental and vector-transfected clones (n = 4), whereas it was 25 microM or more for all MDA-468/AS-EGFR clones (n = 3). MDA-468/p-CAT clones exhibited internucleosomal DNA fragmentation, enhanced Tdt-end labeling in situ, and G2 arrest 48 hours after a 1-hour incubation with 3-30 microM cisplatin. Under these conditions, apoptosis and G2 arrest were undetectable in all MDA-468/AS-EGFR clones. An MDA-468 subline selected after long-term treatment with a TGF-alpha-Pseudomonas exotoxin A fusion protein 40 lacked EGF binding and also exhibited cisplatin resistance (1-hour IC50: > 30 microM) compared with parental cells. This EGF-R-dependent difference in cisplatin response was confirmed in a nude mouse xenograft model by use of high- and low-EGF-R-expressing cell clones. Total intracellular drug accumulation after a 1-hour cisplatin exposure, as measured by atomic absorption spectroscopy, was identical in both groups of cells. Intrastrand drug-DNA adducts, however, were statistically higher in high EGF-R expressors than in low-EGF-R-expressing clones.Conclusions: These data indicate that a critical level of EGF-R signaling, which is amplified in some common human cancers, is necessary for cisplatin-mediated apoptosis in tumor cells and suggest an inhibitory effect of this pathway on the repair of cisplatin-damaged DNA. [ABSTRACT FROM AUTHOR]

Key words: GSGS; nephrotic syndrome; NSAID; topical drugs [ABSTRACT FROM PUBLISHER]

Key words: aminophylline; ciprofloxacin; drug interaction; erythromycin; overdose [ABSTRACT FROM PUBLISHER]

Abstract This is a correction to the following paper: Hague T, Petroczi A, Andrews PR, Barker J, Naughton DP: Determination of metal ion content of beverages and estimation of target hazard quotients: a comparative study. Chem Central J 2008, 2:13.

Abstract Background Considerable research has been directed towards the roles of metal ions in nutrition with metal ion toxicity attracting particular attention. The aim of this study is to measure the levels of metal ions found in selected beverages (red wine, stout and apple juice) and to determine their potential detrimental effects via calculation of the Target Hazard Quotients (THQ) for 250 mL daily consumption. Results The levels (mean ± SEM) and diversity of metals determined by ICP-MS were highest for red wine samples (30 metals totalling 5620.54 ± 123.86 ppb) followed by apple juice (15 metals totalling 1339.87 ± 10.84 ppb) and stout (14 metals totalling 464.85 ± 46.74 ppb). The combined THQ values were determined based upon levels of V, Cr, Mn, Ni, Cu, Zn and Pb which gave red wine samples the highest value (5100.96 ± 118.93 ppb) followed by apple juice (666.44 ± 7.67 ppb) and stout (328.41 ± 42.36 ppb). The THQ values were as follows: apple juice (male 3.11, female 3.87), stout (male 1.84, female 2.19), red wine (male 126.52, female 157.22) and ultra-filtered red wine (male 110.48, female 137.29). Conclusion This study reports relatively high levels of metal ions in red wine, which give a very high THQ value suggesting potential hazardous exposure over a lifetime for those who consume at least 250 mL daily. In addition to the known hazardous metals (e.g. Pb), many metals (e.g. Rb) have not had their biological effects systematically investigated and hence the impact of sustained ingestion is not known.

There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4-12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection., Competing Interests: CCS has received compensation as a member of a scientific advisory board for Novartis Pharmaceuticals and an educational grant from Napp Pharmaceuticals. CB received compensation for lecturing from Roche Products plc, and for a clinical advisory board for Quanta Dialysis Technologies. JH is on the Speakers Bureau for Novartis Pharmaceuticals, Terumo BCT and Add Medica; advisory boards for Imara, Global Blood Therapeutics, Novartis Pharmaceuticals and Novo Nordisk and has received travel grants from Imara and Resonance Health. JG has received an educational grant from Astellas Pharmaceuticals and is on an Advisory Board for Alexion Pharmaceuticals. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear., Methods: This retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010-June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression., Results: Steroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk)., Conclusions: Immunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.

Objective: We examined subsite- and histology-specific esophageal and gastric cancer incidence patterns among Hispanics/Latinos and compared them with non-Hispanic whites and non-Hispanic blacks., Methods: Data on newly diagnosed esophageal and gastric cancers for 1998-2002 were obtained from 37 population-based central cancer registries, representing 66% of the Hispanic population in the United States. Age-adjusted incidence rates (2000 US) were computed by race/ethnicity, sex, anatomic subsite, and histology. The differences in incidence rates between Hispanics and non-Hispanics were examined using the two-tailed z-statistic., Results: Squamous cell carcinoma accounted for 50% and 57% of esophageal cancers among Hispanic men and women, respectively, while adenocarcinoma accounted for 43% among Hispanic men and 35% among Hispanic women. The incidence rate of squamous cell carcinoma was 48% higher among Hispanic men (2.94 per 100,000) than non-Hispanic white men (1.99 per 100,000) but about 70% lower among Hispanics than non-Hispanic blacks, for both men and women. In contrast, the incidence rates of esophageal adenocarcinoma were lower among Hispanics than non-Hispanic whites (58% lower for men and 33% for women) but higher than non-Hispanic blacks (70% higher for men and 64% for women). Cardia adenocarcinoma accounted for 10-15% of gastric cancers among Hispanics, and the incidence rate among Hispanic men (2.42 per 100,000) was 33% lower than the rate of non-Hispanic white men (3.62 per 100,000) but 37% higher than that of non-Hispanic black men. The rate among Hispanic women (0.86 per 100,000), however, was 20% higher than that of non-Hispanic white women (0.72 per 100,000) and 51% higher than for non-Hispanic black women. Gastric non-cardia cancer accounted for approximately 50% of gastric cancers among Hispanics (8.32 per 100,000 for men and 4.90 per 100,000 for women), and the rates were almost two times higher than for non-Hispanic whites (2.95 per 100,000 for men and 1.72 per 100,000 for women) but about the same as the non-Hispanic blacks., Conclusion: Subsite- and histology-specific incidence rates of esophageal and gastric cancers among Hispanics/Latinos differ from non-Hispanics. The incidence rates of gastric non-cardia cancer are almost two times higher among Hispanics than non-Hispanic whites, both men and women. The rates of gastric cardia cancer are lower among Hispanics than non-Hispanic whites for men but higher for women. The rates of esophageal and gastric cardia adenocarcinomas are higher among Hispanics than non-Hispanic blacks.

Background: Adult patients with idiopathic hypogonadotropic hypogonadism (IHH) typically present with absent puberty and therefore have prepubertal testes. IHH is recognized as one of the few curable causes of male infertility and is often effectively treated with either gonadotropins or pulsatile GnRH therapy. The objective of this study was to determine the structure of the testis prior to initiation of treatment., Methods and Results: Eight adult IHH patients with prepubertal testes (<4 ml), with no previous gonadotropin therapy and with no history of cryptorchidism underwent open bilateral testicular biopsy prior to the initiation of hormonal treatment. The testes of all patients showed seminiferous cords separated by interstitium composed of blood vessels, connective tissue cells and collagen fibres but typical adult Leydig cells were absent. The cords contained only Sertoli cells and early type A spermatogonia. The spermatogonia mostly resided in the centre of the cords and were often large, typical of gonocytes. Sertoli cells appeared immature with ovoid nuclei devoid of infoldings and cytoplasm that lacked polarity. Tight junctional complexes commonly found connecting adult Sertoli cells were lacking., Conclusions: These results demonstrate that the immature testes from patients with the severe form of IHH possess early spermatogonia that could possibly reinitiate spermatogenesis with appropriate hormone stimulation. Therefore, the immature testis of this IHH subset resembles those of prepubertal boys and may provide important biologic and genetic insights into testicular development.

This study investigated treatment patterns among Louisiana residents diagnosed with clinically localized prostate cancer in 2001 and factors that may be associated with the treatment. The differences in the initial treatment between 1997 and 2001 were also examined. The data were collected from hospital medical records, supplemented by information from freestanding radiation centers and physicians' offices. We assessed the associations of initial treatment with demographic factors such as age, race, health insurance status, type of healthcare facility, area of residence, county poverty, and clinical factors such as Gleason score, PSA, and comorbidity in univariate and logistic multivariate regression analyses. Our study found that patients clinically diagnosed with localized prostate cancer in 2001 received the following treatments: radical prostatectomy (41.4%), radiation (29.7%), hormone (16.2%), or watchful waiting (11.9%). White patients, older patients, patients with private insurance and patients diagnosed or treated in hospitals were more likely (p < 0.05) to receive aggressive therapy (i.e., radical prostatectomy or radiation) than others after controlling for the demographic and clinical factors. Poverty level and comorbidity were inversely associated with receiving aggressive therapy in univariate analysis. But after adjusting for other factors, these associations were no longer statistically significant. Patients with elevated PSA and high Gleason scores were less likely to receive radical prostatectomy even after the adjustment. From 1997 to 2001, utilization of radiation and hormonal therapies increased, and watchful waiting decreased among newly diagnosed prostate cancer patients. Utilization of radical prostatectomy showed no significant change over time.

This study examined treatment patterns among Louisiana residents diagnosed with stage III colon cancer in 2001 and factors that may be related to the receipt of chemotherapy. The data were collected from hospital medical records, supplemented by information from physician offices. We examined the association of chemotherapy with race (whites and blacks), gender, health insurance status (private versus public/none), hospital type (hospitals with a cancer program approved by the Commission on Cancer of the American College of Surgeons [COC hospital] versus other hospitals [non-COC hospital]), comorbidity, area of residence (rural versus urban), and level of poverty of the area (high poverty versus low poverty) in univariate analyses and logistic multivariate regression models. Our study found that all patients received cancer-directed surgery, and 66% received postoperative chemotherapy. The percentages of patients receiving chemotherapy were similar among race/gender groups. Patient age and hospital type were significantly associated with the receipt of chemotherapy even adjusting for other factors studied. The percentage of patients who received chemotherapy decreased with advancing age, and patients who were diagnosed at COC hospitals had a higher likelihood of receiving chemotherapy than their counterparts diagnosed at non-COC hospitals. Poverty and comorbidity were inversely associated (statistically significant) with the receipt of chemotherapy in univariate analysis. After adjusting for other factors, these associations were no longer significant. Although patients with private insurance were more likely to have chemotherapy than those with public insurance or no insurance, the difference was not significant. No difference was found in the receipt of chemotherapy between rural and urban patients.

Data from numerous studies show that lumpectomy (breast-conserving therapy) plus radiation therapy provides survival equivalent to that following mastectomy (either modified radical or radical mastectomy) for patients with ductal carcinoma in situ (DCIS). According to the data from the National Cancer Data Base and the Surveillance Epidemiology End Results (SEER) Program, use of lumpectomy among female DCIS patients has increased dramatically over the last decade. This study examined population-based trends in treatment for DCIS among Louisiana women and compared the trends with the SEER data. Our data revealed that the percentage of the DCIS patients who received a lumpectomy increased from 34.3% in 1988-1991 to 53.7% in 1996-1999 in Louisiana (p<0.05) while DCIS patients who received a modified radical mastectomy decreased from 51.7% to 26.1% (p<0.05). Increasing use of lumpectomy was seen across all races, age groups, rural/urban areas, and poverty-level areas. Utilization of lumpectomy was about the same for white and African-American women but varied by age group, rural/urban area, and poverty level. Female DCIS patients residing in rural areas or high poverty level areas were less likely to receive a lumpectomy than those residing in urban or affluent areas. Among the patients who had a lumpectomy, 34.4% received post-lumpectomy radiotherapy in the first study period (1988-1991) and 49.7% in the last study period (1996-1999). In Louisiana, utilization of post-lumpectomy radiotherapy decreased with advancing age. Despite the increase in use of lumpectomy, its utilization remained approximately 10% lower than in the SEER areas throughout the study period. A similar deficit was observed for post-lumpectomy radiation therapy.

Delayed graft function (DGF) in renal transplantation using non-heart-beating donors (NHBDs) usually exceeds 80%. There is debate whether DGF in this subgroup is associated with poor long-term outcome. Between 1 January 1988 and 31 January 2000, 130 of 158 (82.3%) NHBD graft recipients with functioning grafts transplanted within our regional NHBD programme developed DGF. Overall graft survival and graft survival censored for recipient death was 113/130 (86.9%) versus 113/121 (93.4%) at year 1, 55/84 (65.5%) versus 55/64 (85.9%) at year 5 and 18/40 (45.0%) versus 18/28 (64.3%) at year 10 after transplantation. Seventeen grafts (13.1%) were lost due to rejection or graft nephropathy. Nine of these kidneys failed during the 1st year. Twenty-seven patients (20.8%) died with functioning grafts, eight within the 1st year after transplantation. In those patients who survived, DGF was associated with excellent long-term outcome in this study. The number of grafts lost due to recipient death exceeded those lost due to rejection or graft nephropathy.

Utilizing data from the Louisiana Tumor Registry, cancer incidence among children younger than 15 years of age is presented by major cancer type, according to the primarily histology-based International Classification of Childhood Cancer scheme. Cases include those diagnosed and/or treated at any hospitals and medical facilities in Louisiana, St. Jude Children's Research Hospital in Memphis, M.D. Anderson in Houston, and from neighboring states. Rates were age-adjusted, presented as rates per million, and were compared to the combined rates of the Surveillance, Epidemiology, and End Results (SEER) Program. The significance of rate differences were assessed at 0.05 level. From 1988-1996, about 125 children were diagnosed with cancer each year. In general, rates are higher in younger than older children, males than females, and white children than African-American children. The five most common childhood cancers are: leukemias (28% of total cases), central nervous system malignancies (22%), lymphomas (13%), renal tumors (8.4%), and soft tissue sarcomas (7.6%). Major findings of these cancers and their associated risk factors are presented.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among Louisiana women. The incidence data from Louisiana Tumor Registry were used to calculate breast cancer incidence rates, which were compared with the combined rates from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. Breast cancer mortality rates for Louisiana were compared with the US death rates from the National Center for Health Statistics (NCHS). Our data revealed that Louisiana women were not at a higher risk for developing breast cancer than women in the SEER areas, but that mortality rates in Louisiana were not correspondingly low. Although the percentage of cases diagnosed at an early stage (in situ and localized) increased in Louisiana from 1988 through 1997, the average in Louisiana was still below the level for the SEER areas (65.9% and 71.6%) in 1993-1997. The rates of in situ breast cancer significantly increased (on average 5.3% for whites per year and 7.1% for blacks), and localized breast cancer also significantly increased (2.6% for whites and 2.5% for blacks), while the incidence of distant stage breast cancer significantly decreased (3.4% for whites and 2.0% for blacks). Compared with white women, black women still were less likely to be diagnosed with early stage breast cancer in 1993-1997 (56.4% and 68.9%). Women residing in the parishes with high percentages of persons in poverty were less likely to be diagnosed with early stage of disease.

Rodent and nonrodent toxicology studies are currently expected to support Phase I trials of antineoplastic drugs in the United States. To determine the predictive value of these studies, we initiated a project to compare preclinical and clinical toxicity data within various drug classes. The first class analyzed was the platinum anticancer drugs. Twelve platinum analogues that had both preclinical (mice, rats and/or dogs) and clinical data from matching drug administration schedules were identified. The rodent LD10 (the dose that causes lethality in 10% of treated animals) or dog toxic dose high (a dose that when doubled causes lethality in dogs) correlated well with the human maximally tolerated dose on a mg/m2 basis. For every platinum analogue investigated, one-third the rodent LD10 or one-third the dog toxic dose high in mg/m2 gave a starting dose and a first escalation dose that did not exceed the clinical maximally tolerated dose. The dose-limiting toxicities in patients were previously observed in 7 of 7, 7 of 8, and 9 of 11 mouse, rat, and dog studies, respectively. Our data indicate that mice, rats, and dogs all had value in predicting a safe starting dose and the qualitative toxicities in humans for platinum anticancer compounds. The efficiency of Phase 1 trials could have been improved without sacrificing patient safety by allowing higher starting doses for this drug class than conventionally permitted.

New developments in the Louisiana Tumor Registry (LTR) over the past 3 years have enhanced the operation of the LTR and broadened its functions. Recent funding for numerous special studies and research collaborations have expanded the registry activities from data collection and special etiologic studies to more completely address the mandates of registry law, which require the LTR to participate in studies of cancer causes, treatment, and survival in order to reduce cancer morbidity and mortality in Louisiana.

Cancer of the colon and rectum ranks fourth for incidence and second for mortality among Louisiana residents. Incidence rates calculated from Louisiana Tumor Registry data for 1991-95 show that whites in Louisiana were diagnosed with colon cancer at approximately the same rates as those in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, but rates for African Americans were significantly lower in Louisiana than nationally. For rectal cancer, Louisiana incidence rates approximate the national rates for all but African-American males, whose rate was significantly lower. Mortality rates for colon and rectal cancer in Louisiana were comparable to the SEER rates, suggesting Louisiana blacks, once diagnosed, have a poorer survival than their national counterparts. Risk factors for colorectal cancer and guidelines for screening are discussed, as is an upcoming study of patient care for colon cancer.

We examined the correlation between response to platinum-based chemotherapy and expression of glutathione S-transferase (GST), gamma-GGT (both by immunohistochemistry) and gamma-GCS (by in situ hybridization) in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (CR, PR) for patients with low GST scores was 88% (21 of 24), while among the patients with high GST scores, the overall response rate was 19% (6 of 32, P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST score was 70% (7 of 10), while among the patients with high GST scores, the overall response rate was 8.7% (2 of 23), P < 0.001). In contrast, both gamma-GCS and gamma-GGT showed a range of expression in these samples, but there was no significant correlation with treatment response. We conclude that GST expression correlates well with response to platinum based chemotherapy in head and neck cancer.

Because of the high density of industries along the Lower Mississippi River, there is a concern about adverse impact on health, including cancer, among residents in these parishes. This study provides an update of cancer incidence in the Industrial Corridor for the period 1989-93. Age-adjusted cancer incidence rates were calculated for the seven-parish study area from Baton Rouge down to, but not including, New Orleans. Rates were also computed for the entire state of Louisiana and for the combined Surveillance, Epidemiology and End Results (SEER) program. Cancer incidence rates for the Industrial Corridor are either similar to, or lower than, the combined SEER rates for most of the common cancers as well as for rare tumors. The only two exceptions are lung cancer in white males and kidney cancer in white females that are significantly elevated when compared to the SEER averages. Significantly lower rates are found among white males for cancers of kidney, brain, and nervous system, and melanoma; among black males, cancers of all sites combined, oral cavity, stomach, rectum, and prostate, Hodgkin's disease, and non-Hodgkin's lymphoma; among white females, cancers of all sites combined, cervix, uterine corpus, ovary, bladder, and melanoma; and among black females, cancers of all sites combined, oral cavity, lung, breast, ovary, and melanoma. The persistent excess of lung cancer has led to the development of a multi-agency project to evaluate the impact of potential environmental exposures, genetic susceptibility, and their interactions on lung cancer risk. The findings also confirm the urgent need to include and strengthen tobacco prevention and cessation programs in our cancer control activities.

This paper highlights the major findings from the recently released volume of the Louisiana Tumor Registry monograph series: Cancer Incidence in Louisiana, 1988-1992. One out of three Louisiana residents will develop cancer in his or her lifetime. Lung cancer remains the most common cancer for all races, both genders combined. Lung cancer rates for women continue to rise substantially (20% over the previous 5-year period) and African-American men in the Acadiana Region have the state's highest lung cancer rate. The number of prostate cancer cases has surpassed that of lung cancer for the first time in Louisiana men; the sizable increase since 1983 (about 50%) in prostate cancer likely reflects the recent aggressive screening by the PSA test. Breast cancer remains the most common cancer among Louisiana women and incidence rates have increased about 20% over the previous 5-year period. Geographic comparisons show that the New Orleans Region continues to have rates higher than state averages, and a clear pattern of high cancer risk has emerged for the Acadiana region. The Central Louisiana and the Baton Rouge Regions have rates lower than state averages.

The glutathione S-transferases (GSTs) play an important role in the cell's defense against toxic substances. The GSTs are a family of enzymes produced by several genes that interact with distinct but overlapping substrates and that may play a role in resistance of tumor cells to several chemotherapeutic agents. We examined the correlation between expression of GSTs determined by immunohistochemistry and clinical response to platinum-based chemotherapy in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (complete response + partial response) for patients with low GST scores was 88% (21 of 24), whereas among the patients with high GST scores, the overall response rate was 19% (6 of 32; P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 23 patients treated with neoadjuvant chemotherapy, the overall response rate for patients with low GST scores was 100% (14 of 14), whereas among the patients with high GST scores, the overall response rate was 44% (4 of 9; P = 0.002). Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST scores was 70% (7 of 10), whereas among the patients with high GST scores, the overall response rate was 8.6% (2 of 23; P < 0.001). We conclude that GST expression correlates well with response to platinum-based chemotherapy in head and neck cancer.

The effect of the tyrosine kinase inhibitor genistein on the accumulation of cisplatin (DDP) was investigated in DDP-sensitive and -resistant human 2008 ovarian carcinoma cell lines. DDP accumulation after a 1-h exposure was maximally increased by concurrent 40 micrometer genistein. The maximal stimulation of accumulation was observed after 2 h of total genistein exposure and was 83 +/- 13% (n = 5) higher than controls. With resistant C13(*) cells, however, the stimulation of accumulation was delayed until 4 h and was increased only 46 +/- 18% compared to controls. Revertant RH4 cells that retained the accumulation defect behaved like the C13(*) cells. Genistein stimulated [3H]mannitol accumulation (a marker of passive permeability) by 43 +/- 9% (n = 3) in 2008 cells, and the effect was maximal after 2 h of total genistein exposure. Changes in [3H]mannitol accumulation in 2008 parent cells were highly correlated with DDP accumulation (r = 0.9010). These experiments also revealed that [3H]mannitol accumulation after 2 h in C13(*) cells was reduced 38% compared to 2008 cells, a decrease that reflected the DDP accumulation defect. Fluid-phase pinocytosis determined with lucifer yellow CH as a marker showed no difference between 2008 and C13(*) cells and no effect of genistein. Genistein was demonstrated to clearly inhibit protein-tyrosine phosphorylation initiated by the epidermal growth factor receptor kinase. Differences were noted in the phosphotyrosine pattern between the 2008 and C13(*) cells. Under the conditions that had the maximal effect on DDP accumulation in 2008 cells, genistein decreased the IC50 of DDP 8.2-fold in 2008 cells and 4.7-fold in C13(*) cells. We conclude that: (a) genistein stimulates DDP accumulation by modulating the passive permeability of the plasma membrane; (b) C13(*) cells are less permeable to passively diffusing small molecules, which offers a mechanism for the DDP accumulation defect without invoking carrier proteins; (c) the effect of tyrosine kinase inhibition on passive permeability is altered in C13(*) cells; and (d) pinocytosis contributes insignificantly to DDP accumulation. Genistein, a dietary isoflavone, thus seems to be a promising clinical candidate for combination with DDP.

Background: Although immunodeficiency predisposes to CAPD peritonitis with fungal or unusual organisms, the role of immunosuppression as a predisposing factor for CAPD peritonitis, as well as the outcome of such episodes, remains uncertain., Methods: The incidence, spectrum of infectious organisms, and outcome of CAPD peritonitis was retrospectively reviewed in 39 immunosuppressed and 146 non-immunosuppressed patients treated with CAPD over the calendar year 1993., Results: Immunosuppressed patients were younger (mean 44 vs 57 years, P<0.001) and had an increased incidence of previous transplantation, glomerulonephritis, systemic lupus erythematosus, and vasculitis. Immunosuppressed patients had more episodes of peritonitis (69/29 patients vs 99/147, P<0.001), required more frequent hospital admission (25/39 vs 33/146, P<0.001), had more days off CAPD (331 vs 242, P<0.001), and required more laparotomies to remove infected CAPD catheters (11/39 vs 14/146, P<0. 01). Immunosuppression was associated with increased infection due to S.aureus and fungi, which may have contributed towards increased morbidity in this group. Current immunosuppression or a recent history of immunosuppression appeared to be equally potent risk factors for infection. There was a trend for the incidence of infection to parallel the aggressiveness of immunosuppression., Conclusions: Immunosuppression is an important risk factor for CAPD peritonitis. A high index of suspicion for infection and aggressive chemotherapy are mandatory. CAPD may not be the initial therapy of choice in this high-risk group.

Cancer mortality rates in South Louisiana are higher than the national averages, leading to the area's designation as a "cancer corridor". This study was conducted to assess whether incidence data substantiate the reputation derived from mortality statistics. Age-adjusted cancer incidence rates for 1983-1987 were calculated for South Louisiana as a whole, for five regional divisions of it, and for the combined nine areas of the Surveillance, Epidemiology, and End Results (SEER) program. Significantly lower (p < 0.0001) incidence rates were found in South Louisiana among white females, black males, and black females for cancers of all sites combined; among women of both races for cancer of the breast; among men of both races for cancers of the colon and prostate; and among whites of both sexes for melanoma and rectal cancer. South Louisiana incidence rates were significantly higher than the SEER rates only for lung and larynx cancers in white males. The excess of lung cancer was statistically significant in four out of five regions while the laryngeal cancer excess was significant only in the New Orleans area. The excessive mortality rates reported for South Louisiana are not the result of excessive incidence. These results indicate poorer cancer prognosis in this region, a phenomenon that deserves more scrutiny by the health profession.

Data from the Louisiana Tumor Registry, Louisiana Vital Statistics Division, and the SEER program of the National Cancer Institute were explored to evaluate reasons for elevated cancer death rates in the absence of elevated cancer incidence in Louisiana. The results indicate that cancer patients in South Louisiana are more likely to be diagnosed with advanced stage disease than SEER patients. The Louisiana-SEER differences are greater for blacks than whites, and black patients are more likely to have advanced stage cancer than whites in Louisiana as well as in the SEER program. Of particular interest and concern is the finding that the increased risk of advanced stage disease in Louisiana is significant for cancers which can be detected early and, if so, effectively treated: colon, breast, and cervix. The findings reinforce the need for cancer control programs.