Thio TEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80

Summary A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thio TEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment. Thio TEPA and its primary metabolite, TEPA, were measured in plasma and urine using a sensitive and specific chromatographic assay. Large differences between patients were observed in the proportion of thio TEPA absorbed, ranging from 20%–78%. Peak plasma levels of thio TEPA were observed within 1 h of intravesical administration. By 2 h after administration the plasma levels of TEPA were similar to those of thio TEPA and, in contrast to those of the parent compound, remained at a similar level over the next 4 h. The rate of absorption of thio TEPA was not influenced by Tween 80, but it did cause statistically significant increases in mean peak plasma levels (from 101 to 154 ng/ml) and mean AUC values (from 0.376 to 0.496 g h per ml) and a decrease in the mean half-life (from 1.83 to 1.25 h). To obtain plasma levels similar to those achieved after instillation with thio TEPA alone, the dose should be reduced with Tween 80.     

Retrospective study of children born to HIV-1-infected mothers in a pediatric hospital in Argentina

The aim of this retrospective study, which included 103 children born to human immunodeficiency virus type 1 (HIV-1)- infected mothers, is to initiate a database on HIV-infected children, which has to date been unavailable in Argentina. All HIV-1 seropositive children admitted to the Pedro de Elizalde Children's Hospital in Buenos Aires from March 1, 1987, to December 31, 1992, were enrolled in this study. The number of patients enrolled dramatically increased each year during the period of study. Of the 60 infected children, 22 (36.66%) have died with a clinical diagnosis of HIV-1 infection; in 10 of those children HIV infection was also confirmed by P24 antigenemia and/or polymerase chain reaction (PCR): 20 qualified for the Centers for Disease Control and Prevention (CDC) P2D class (P2D1 = 7, P2D2 = 10, P2D3 = 3), 1 for P2C, and 1 for P2A, whose cause of death was pneumonia. The mean age of death was 14.8 months, 18 (82%) died before 18 months. When immunoglobulin G (IgG), IgM, and IgA levels were determined according to age and clinical status, significant differences (P < 0.005) were observed when both asymptomatic and symptomatic infected children (P1, P2) were compared with noninfected children (P3). A significant difference was also obtained between those children who qualified for P2 classification prior to 12 months of age who died early (at or prior to 25 months) and those who reached stage P2 after 12 months of age and have survived to date (X2 = 24.73, p < 0.0001; RR = 5.83, 2.52 < RR < 13.49).     

A comparison of sampling and analytical methods for assessing occupational exposure to diesel exhaust in a railroad work environment

Methods of assessing occupational exposure to diesel exhaust were evaluated in a railroad work environment. The American Conference of Governmental Industrial Hygienists (ACGIH)-recommended elemental carbon and respirable combustible dust methods of sampling and analysis for assessing diesel exhaust were included in the study. A total of 215 personal and area samples were collected using both size-selective (nylon cyclone and Marple) and non-size-selective samplers. The results demonstrate that the elemental carbon method is suitable for the railroad environment and the respirable combustible dust method is not. All elemental carbon concentrations measured were below the proposed ACGIH Threshold Limit Value (TLV) of 0.15 mg/m3. The concentrations of oxides of nitrogen (nitric oxide and nitrogen dioxide) were also found to be below their respective TLVs. There is no correlation between elemental carbon or respirable combustible dust and the oxides of nitrogen. The elemental carbon as fraction of total carbon is about 13 percent, except for onboard locomotives where it is about 24 percent. Comparison of elemental carbon and respirable combustible dust measurements showed consistent relationships for most sampling locations, with respirable combustible dust concentrations 12 to 53 times higher than the elemental carbon levels.     

Breast Carcinoma in Childhood and Adolescence: Case Report and Review of the Literature

Secretory breast carcinoma is a rare tumor originally described in children and adolescent women with a characteristic morphology and a controversial choice of treatment. We report an additional case of a 4-year-old girl with a breast tumor diagnosed as a secretory carcinoma without involvement of the axillary lymph nodes. The therapy consisted of simple mastectomy and low axillary dissection. She presented with a local recurrence near the surgical scar 8 months later, and a wide elliptical excision of the scar and underlying tissue was performed with subsequent radiotherapy of the surgical bed. This tumor has a relatively benign behavior and rarely metastasizes. A literature review revealed only 22 cases of breast carcinoma in childhood and adolescence. ▪     

Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group

BACKGROUND: The novel agent sirolimus (SRL; Rapamune; rapamycin) inhibits the immune response by a mechanism distinct from those of calcineurin antagonists or antimetabolites. This randomized, controlled, multicenter, single blind, phase II trial examined the combination of SRL, steroids, and full versus reduced doses of cyclosporine (CsA) for prophylaxis of acute renal allograft rejection. METHODS: A total of 149 recipients of mismatched cadaveric- or living-donor primary renal allografts were randomized into six groups. Three groups received placebo or 1 or 3 mg/m2/day SRL, as well as steroids and full-dose CsA (Sandimmune). Three groups received steroids, reduced-dose CsA (target trough level 50% of full-dose range), and 1, 3, or 5 mg/m2/day SRL. RESULTS: The incidence of biopsy-proven acute rejection episodes within the first 6 months after transplant was reduced from 32.0% in the control group to 8.5% in patients receiving SRL (1 or 3 mg/m2/day) and full-dose Sandimmune CsA (P=0.018). Similar low rates of acute rejection episodes were observed among non-African-Americans, but not African-Americans, treated with SRL and reduced-dose Sandimmune CsA. Despite the augmented immunosuppression, 1-year patient and graft survival rates did not differ significantly across groups. Adverse effects attributable to CsA, including hypertension and new-onset diabetes mellitus, were not exacerbated by SRL. Except for an increased incidence of pneumonia among patients receiving full-dose CsA and 3 mg/m2/day SRL, the incidences of opportunistic infections were similar in all treatment groups. Although SRL produced more frequent, but reversible, hematological and lipid abnormalities, it had no apparent nephrotoxic effects to exacerbate CsA-induced renal dysfunction. CONCLUSIONS: SRL in combination with CsA and steroids not only lowers the incidence of biopsy-proven acute renal allograft rejection episodes, but also may permit CsA sparing, at least among Caucasian patients, without an increased risk of rejection.     

维生素D_3对报告载体荧光素酶表达的作用

目的：　研究１,２５－二羟维生素Ｄ３ 对结肠癌细胞系Ｃａｃｏ－２ 细胞中报告基因表达的作用,并探讨在报告载体ｐＧＬ２ 序列中存在潜在的抑制性维生素Ｄ应答元件（ＶＤＲＥ）的可能性。方法：　采用磷酸钙沉淀法将报告载体转染入Ｃａｃｏ－２ 细胞。Ｃａｃｏ－２细胞经不同浓度１,２５－二羟维生素Ｄ３ 处理后测定细胞裂解液中表达的荧光素酶活性。结果：　应用ｐＧＬ２ 报告载体时,当用ｐＳＧ５－ＶＤＲ表达载体共转染后,１,２５－二羟维生素Ｄ３显著地抑制Ｃａｃｏ－２ 细胞荧光素酶的表达（Ｐ＜ ０．０５）;而未使用该表达载体共转染则无抑制作用（Ｐ＞ ０．０５）。应用ｐＧＬ３ 报告载体时,不同浓度的１,２５－二羟维生素Ｄ３ 对ｐＬＧ３转染后Ｃａｃｏ－２ 细胞表达的荧光素酶活性均无显著抑制作用（Ｐ＞ ０．０５）,该作用不依赖是否存在有ｐＳＧ５－ＶＤＲ表达载体共转染。结论：１,２５－二羟维生素Ｄ３ 对报告载体ＰＧＬ２ 荧光素酶表达具有抑制作用,而对ｐＧＬ３ 则否;类似人类ＰＴＨ基因中的潜在抑制性ＶＤＲＥ存在于报告载体ｐＧＬ２,在ｐＧＬ３ 中该ＶＤＲＥ业已改变。     

HIV-1 and hepatitis B virus infections in adolescents lodged in security institutes of Buenos Aires

The goal of this study was to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) infections in street youth lodged in security institutes, from February 1992 to March 1995, to correlate these infections with nontherapeutic drug use, and to compare these results with a previous study done in a similar population. A total of 1460 white adolescents, 276 females and 1184 males, were enrolled (mean age 16.6 years). Prevalence of HIV-1 was 4.58% and of HBV was 6.78%. The prevalence of dual HIV-1/HBV infection was 1.91%; the prevalence of HBV infection was significantly higher in HIV-positive subjects (p < 0.0000000, chi 2 = 136.17, OR = 13.37) than in those not infected with HIV-1. Prevalences were higher in males. Intravenous drug addiction proved to be a significant risk factor for both viruses (HIV-1, p < 0.0000000, chi 2 = 171.34, OR = 16.84; HBV, p = 0.000044, chi 2 = 16.67, OR = 3.17); 6.43% of the total population were intravenous drug users. Comparison of the current results with our previous study (1989-1992) showed that the prevalence of HIV-1, HBV, and concurrent HIV/HBV as well as intravenous drug addiction has decreased significantly in our current cohort (chi 2 = 134.85, p < 0.0000000; chi 2 = 126.62, p < 0.0000000; chi 2 = 110.05, p < 0.0000000; and chi 2 = 158.3, p < 0.0000000) respectively. Progress appears to have been made in the fight against acquired immunodeficiency syndrome (AIDS), and promising results have been obtained. However, if further viral spread is to be avoided, the emphasis on prevention should be energetically maintained.     

Prenatal development of human palatine glands: a structural and cytochemical study

The histogenesis of the salivary glands was structurally and cytochemically studied in human embryos and fetuses during the period of 8 to 32 weeks of intrauterine life. Glandular buds appeared at about 12 weeks of embryonic development. The rounded distal ends of the epithelial cords and neighbouring mesenchyma showed small and abundant PAS positive and alcianophilic granules. At age 14 weeks the secretory end pieces and the duct system were seen at different morphologic and structural stages of a differentiation. Mucous acini with scanty mixed acini predominated and serous acini appeared occasionally. From 20 to 24 weeks the mucous acini stained with toluidine blue featured different degrees of metachromasia even in the case of cells of the same acinus. In the ducts it was also possible to identify metachromatic cells intermingled with basophilic cells in the epithelial coat. These findings suggest that the palatine glands present typical histophysiological material from 14 to 20 weeks. The presence of PAS positive, alcianophilic and metachromatic secretory substance in the acinar lumen and the luminal content of ducts suggests that mucin secretion begins during intrauterine life.