Localizing and photosensitizing mechanism by tetra(3-hydroxyphenyl)porphin in vivo on human malignant melanoma xenografts in athymic nude mice

Observations on time-dependent localization of tetra(3-hydroxyphenyl)porphin (3-THPP) in human malignant melanoma transplanted to athymic nude mice from 1 to 120 h after intraperitoneal (i.p.) 10 mg kg^–1 b.w. administration were made by means of fluorescence microscopy. Fluorescence was found on the membrane of the melanoma cells and in the cytoplasm with a peak fluorescence intensity at 24 h post-injection of 3-THPP. The growth of the tumour cells was obviously inhibited at an early stage after PCT. Morphological changes of the tumour at various intervals after treatment by PCT with 3-THPP were also observed. Diffuse degeneration of the tumour cells with swelling of mitochondria and endoplasmic reticulum, heterochromatin aggregation and margination, etc., and subsequently diffuse necrosis with little or no the background of tumorous vascular response were found at an early stage after PCT. On the other hand, it was also observed that the necrosis of the melanoma areas was caused as a consequence of tumorous vascular injury at a later stage after PCT. Thus, two tumoricidal processes caused by PCT with 3-THPP were seen: a direct phototoxic action on tumour cells at an early stage after PCT and an indirect effect secondary to tumorous vascular injury at a later period after PCT.     

Outcome of a multicenter treatment program including autologous or allogeneic bone marrow transplantation for de novo acute myeloid leukemia

Abstract: The results of an intensive treatment program for patients 16–60 yr of age with de novo acute myeloid leukemia are presented. The patients were given conventional induction treatment with daunorubicin and cytarabine. Patients not entering complete remission (CR) after 1 course of daunorubicin/cytarabine were given 1 course of amsacrine/etoposide/cytarabine. Those entering complete remission received 3 consolidation courses using mitoxantrone, etoposide, amsacrine and cytarabine. One hundred and eighteen patients were enrolled. Complete remission was attained after 1–2 courses in 90 patients (76%). Another 6 patients reached CR after 3–4 induction courses for a total CR rate of 81%. If feasible, patients were offered either allogeneic or unpurged autologous bone marrow transplantation. Twenty-four patients underwent allogeneic bone marrow transplantation; 15 in first remission, 8 in second remission, 1 in early relapse. Thirty patients below 56 yr of age underwent autologous bone marrow transplantation in first remission. The overall probability of survival at 4 yr was 34%, and for patients below 40 yr of age 50%. Leukemia-free survival was 35% for the whole cohort of patients; 52% for patients below 40 yr of age. Patients undergoing allogeneic or autologous bone marrow transplantation in first remission had an overall survival of 86% and 47%, respectively, while the probability of leukemia-free survival in these groups was 87% vs. 40% at 4 yr. The CR rate and long-term results of this intensive treatment program compare favorably with other recent studies using intensive consolidation with allogeneic or autologous bone marrow transplantation or high dose cytarabine.     

Terminal deletion of chromosome 4p (4p16.3) shows a breakpoint between loci linked to Huntington disease

A 15-year-old boy with a terminal deletion of the short arm of chromosome 4 is described. The patient has a mild clinical phenotype that is incompatible with Wolf-Hirschhorn syndrome. Careful neurological examination including CT scan did not show any signs of Huntington disease. The chromosomal breakpoint was analyzed by means of polymorphic DNA probes localized close to the tentative Huntington (HD) locus. The breakage has occurred between D4S43 and D4S90 loci and thus deletes part of the chromosomal candidate regions for the HD locus. © 1992 Wiley-Liss, Inc.     

Combined radiotherapy and surgery in the treatment of neck node metastases from squamous cell carcinoma of the head and neck.

A prospectively recorded series of 107 patients with clinical neck node metastases from head and neck squamous cell carcinomas, treated in 1983-1988, and with initial local control, is evaluated. Eighty-eight patients received preoperative, and were operated 4-6 weeks after radiotherapy, and 19 received postoperative radiotherapy. Forty-four of the neck specimens in the preoperatively treated patients showed vital tumor tissue, 7 with positive and 37 with negative resection margins. Nine of the latter 37 patients died due to regional recurrence. Twenty-three of the preoperatively treated patients had no palpable residual tumor following radiotherapy, but histological examination showed vital tumor tissue in five, of whom two had N1 neck disease. The overall regional failure rate was 19%. Eleven patients (10%) died from local recurrence and 11 from distant metastases. Forty-one patients (38%) are alive without evidence of disease and three (3%) alive with disease (mean observation time 30 months). Combined treatment is recommended for all cases of neck node metastases.     

Farm Work is Dangerous for Teens: Agricultural Hazards and Injuries Among North Carolina Teens

Children who work in agriculture suffer more than 23,000 injuries and 300 fatalities on American farms every year. Using survey data collected from a random sample of working teens (ages 14 to 17) in North Carolina, the authors analyze the farm-based hazard exposure and injury experiences of teens who work on farms. The group of farmworking teens (N = 141) is 72 percent male, has a mean age of 16.6 years, and is, on average, in the 10th grade. The data show that teens working on farms in North Carolina are exposed to significant safety hazards throughout their farmworking careers. A majority of the respondents in this group of farmworkers reported exposure to tractors, large animals, all-terrain vehicles, farm trucks, and rotary mowers, and more than one-third reported exposure to pesticides and tobacco harvesters. Common reported injuries include insect stings, cuts, burns, and falls. The researchers find that gender, age, and farmwork experiences are related to variations in types of hazards to which teens are exposed and in the types of injuries they suffer. These variables also are related to the overall complexity of the teens' farmwork experiences and the burden of injury endured by teens.     

The significance of HIV antigen and HIV antibodies specific against envelope and core proteins in serum of HIV-infected hemophiliacs

Serial serum samples from the 21 HIV-infected Norwegian hemophiliacs have been assayed for the presence of HIV antigen and antibodies to HIV specific for the core protein p24 and the envelope protein gp41. HIV antigen was detected in 4 patients, of whom 3 have developed AIDS to date. HIV antigen appeared in serum 10 to 24 months before the diagnosis in these patients. Antibodies to gp41 was a constant finding. Antibodies to p24 disappeared from the serum in 1 patient who developed AIDS and from 3 persons free of symptoms related to the HIV infection. The detection of HIV antigen in HIV antibody-positive hemophiliacs appears to be of considerable prognostic significance.     

Synthetic env gp41 peptide as a sensitive and specific diagnostic reagent in different stages of human immunodeficiency virus type 1 infection

An enzyme immunoassay (EIA) for serum antibodies to human immunodeficiency virus type 1 (HIV-1), based on the synthetic pentadecapeptide SGKLICT-TAVPWNAS, a segment of the transmembrane glycoprotein (gp41) of the virus, was developed and tested for sensitivity and specificity. Sera of 152 individuals at various stages of HIV-1 infection, including two prospectively and six retrospectively studied patients exposed to HIV-1 but seronegative on initial testing in whole-virus EIA and immunoblotting, were screened with the gp41 peptide antibody EIA. The reference population consisted of 1,000 healthy HIV-1 antibody-negative blood donors. In addition, five individuals with antibodies to HIV-2 were studied. Antibodies to the synthetic peptide were detected in 100% of those with asymptomatic infection. Only one patient with LAS failed to react in the peptide EIA. Patients with HIV-2 infection did not react in this test. The peptide antibodies appeared rapidly after infection, were detectable at the time when seroconversion was observed by immunoblotting, and preceded reactivity in whole-virus EIA. Sera of seven patients with verified HIV-1 infection did not react with gp41 in immunoblotting, although antibodies were readily detectable in the gp41 peptide EIA.     

Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV Family Study.

BACKGROUND: The natural history of genital human papillomavirus infection is well known, but nearly nothing is known about the outcome of oral HPV-infection. OBJECTIVES AND STUDY DESIGN: To study natural history of oral HPV in spouses during the follow-up 331 women (mean 25.5+/-3.4 years) and 131 men (mean 28.8+/-5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization using a cocktail of 12 high-risk (HR) oligoprobes. RESULTS: The detection rate of HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was closely related (odds ratio 4.3; 95% confidence interval 1.6-12.0; P=0.006). Persistent oral infection in one spouse was a significant risk factor (odds ratio 10.0; 95% confidence interval 1.5-68.7; P=0.005) for oral HR HPV persistence in the other partner. Cumulative incidence of new HR HPV infections was identical in both spouses, while men seemed to clear their infection more rapidly. In univariate survival analysis, the partner's oral or genital HPV status, oral sex habits or age did not predict clearance or acquisition of oral HR HPV. CONCLUSION: Natural history of HPV infection in oral mucosa mimics that of genital HPV infection. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection 10-fold in the other spouse.