The prognostic importance of c-myc oncogene expression in head and neck melanoma

Melanomas of the head and neck have a poorer prognosis than melanomas arising at other cutaneous sites. To study the biology of this disease, the expression of the c-myc oncogene was studied in tumors from 97 patients with head and neck melanoma using the technique of flow cytometry. Survival analysis revealed that stratification of patients according to oncogene expression provided a prognostic marker with shorter overall survival in tumors with high nuclear c-myc oncoprotein positivity (log-rank test, chi2 = 8.77, p < 0.005). Multifactorial analysis using Cox's proportional hazards model revealed nuclear c-myc oncoprotein to be an independent prognostic marker (log-rank test, chi2 = 8.82, p = 0.005). These results support the authors' previous studies of the prognostic value of c-myc expression in melanoma and suggest that estimation of c-myc oncoprotein may be of clinical importance in identifying high-risk patients.     

Characterization of allelic and nucleotide variation between the RAGE gene on chromosome 6 and a homologous pseudogene sequence to its 5' regulatory region on chromosome 3: implications for polymorphic studies in diabetes.

Activation of the receptor for advanced glycation end products (RAGE) appears to be a key mechanism in the pathogenesis of diabetic vascular disease, making RAGE a candidate gene for investigation. RAGE is located in the major histocompatibility complex locus on chromosome 6, which contains a multitude of overlapping and duplicated genes involved predominantly in inflammatory and immune responses. The RAGE 5' flanking region from -505 in a 5' direction overlaps with PBX2, a gene that has a pseudogene copy on chromosome 3, making any studies of polymorphisms in this duplicated region potentially fraught with error. In this study we have addressed these issues by confirming RAGE as a predominantly single-copy gene and PBX2 to have two gene copies in the haploid human genome. We have characterized the gene:pseudogene differences between RAGE/PBX2 on chromosome 6 and PsiPBX2 on chromosome 3, which include a change from C to A at position -1139 RAGE/+2298 PBX2, previously reported as a polymorphism. Single chromosome-specific DNA amplification of the duplicated region has clarified five polymorphisms to be on chromosome 3 and one (at -1202 RAGE/+2234 PBX2) to be on chromosome 6. In conclusion, this study provides essential data for the study of RAGE and its genetics.     

Intestinal permeability in the newborn

Passive intestinal permeability in 33 newborn babies was studied using feeds containing lactulose and mannitol. Each marker is thought to pass across the gut wall by a different route; lactulose by a paracellular and mannitol by a transcellular pathway. Neither is metabolised and both are wholly and solely excreted by the kidney; urinary recovery is a measure of the intestinal uptake. Babies born before 34 weeks' gestation exhibited a higher intestinal permeability to lactulose than more mature babies, and all preterm babies showed an appreciable decline in lactulose absorption during the first week of oral feeds. Babies of 34 to 37 weeks' gestation achieved a 'mature' intestinal permeability to lactulose within four days of starting oral feeds. These findings may reflect the immaturity of the gut of the preterm baby rather than a process essential to adaptation to enteral nutrition.     

Elemental mercury exposure among children of thermometer plant workers

Because evidence of mercury exposure was found among workers of a mercury thermometer-manufacturing plant in March 1984, the Vermont Department of Health studied the workers' children for both exposure to mercury and evidence of mercury toxicity. The median urine mercury level of 23 workers' children was 25 micrograms/L. This was significantly higher than the level (5 micrograms/L) among 39 children randomly selected from nonworkers' households in the same community (P less than .001). Mercury-in-air levels measured in workers' homes were higher than those measured in control homes. A significant correlation was found between the urine mercury levels of the workers' children and the urine mercury levels of their working parents. No child had frank mercury toxicity. No evidence of neurologic toxicity among exposed children was discovered by a pediatric neurologist who examined these and unexposed children without knowledge of their exposure status. This is the first report demonstrating mercury exposure in children of mercury workers. Although toxic effects of mercury were not demonstrated at these levels of exposure, children of mercury workers are at risk for mercury exposure and potential mercury toxicity.     

Interleukin 2 receptor expression in patients with head and neck squamous carcinoma. Effects of thymosin alpha 1 in vitro

Altered cellular immunity in patients with advanced head and neck cancer includes impairments in lymphokine production, blastogenesis, in vitro cytotoxicity, and T-cell levels. Recent evidence for the potential importance of in lymphokine interleukin 2 (IL-2) in patients with cancer prompted a study of the kinetics of IL-2 receptor expression on lymphocytes from patients with untreated advanced head and neck cancer and normal subjects and an evaluation of the in vitro effects of the T-cell immune-reconstituting peptide, thymosin alpha 1. Concanavalin A-stimulated IL-2 receptor expression was maximal after 72 hours and was higher in normal subjects than in patients. This was due to lower levels of helper/inducer (CD4) cells expressing IL-2 receptors in the patients compared with the normal subjects. Thymosin alpha 1 further decreased levels of IL-2 receptor-positive (both CD4 and CD8) cells at 48 and at 72 hours. At 96 hours, levels of IL-2 receptor-positive cells and proportions of cells in G2 and M phases of the cell cycle were similar among both groups of subjects. Simultaneous cell kinetic studies indicated that thymosin alpha 1 down regulation of IL-2 receptors was not due to an effect on proliferation and that differences in IL-2 receptor expression at 72 hours among normal subjects and the patients with cancer were more likely related to differences in cell proliferation kinetics.     

Comparative healing of surgical incisions created by a standard "bovie," the Utah Medical Epitome Electrode,and a Bard-Parker cold scalpel blade in a porcine model: a pilot study

A comparative study of skin incision healing using a standard "bovie" and a new design electroscalpel, Utah Medical Products Epitome Electrode (Midvale, UT), was conducted in a porcine model. Wounds were evaluated objectively at 14 and 28 days after surgery using wound bursting strength measurements and histologic wound scoring. Each electrosurgical device was compared with wound healing of cold scalpel incisions as the gold standard using the same criteria. Statistical differences of healing between the bovie and the Epitome indicating preferential healing for the Epitome wounds were demonstrated for bursting strength at 14 days (p = 0.002). Comparisons of the measured "zone of coagulation necrosis" produced by the electroscalpels demonstrated significantly decreased thermal tissue damage favoring the Epitome (p = 0.0003). Greater differences in wound healing favoring the cold scalpel occurred in comparisons of bovie with cold scalpel than Epitome with cold scalpel, and overall results demonstrated healing for the Epitome wounds closely approximated that for cold scalpel. The authors conclude that this new generation electroscalpel provides measurable improvements in incisional wound healing compared to established electrosurgical technology.     

Once-daily therapy for streptococcal pharyngitis with amoxicillin

OBJECTIVE: An orally administered antimicrobial regimen for the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis given once rather than multiple times each day would be more convenient and might result in improved patient compliance. The purpose of this study was to evaluate the effectiveness of once-daily amoxicillin in the treatment of GABHS pharyngitis. PATIENTS: Children presenting to a private pediatric office with GABHS pharyngitis. DESIGN: Patients were randomly assigned to receive orally either amoxicillin (750 mg once daily) or penicillin V (250 mg three times a day) for 10 days. Compliance was monitored by urine antimicrobial activity. OUTCOMES: Outcomes were measured by impact on the clinical course, eradication of GABHS within 18 to 24 hours, and bacteriologic treatment failure rate as determined by follow-up throat cultures 4 to 6 and 14 to 21 days after completing therapy. GABHS isolates were serotyped to distinguish bacteriologic treatment failures (same serotype as initial throat culture) from new acquisitions (different serotypes). RESULTS: During the 16 months of this study, 152 children between 4 and 18 years of age (mean, 9.9 years) were enrolled; 79 children were randomly assigned to receive once-daily amoxicillin and 73 were assigned to receive penicillin V three times a day. The children in the two treatment groups were comparable with respect to age, duration of illness before initiation of therapy, compliance, and signs and symptoms at presentation. There was no significant difference in the clinical or bacteriologic responses of the patients in the two treatment groups at the 18- to 24-hour follow-up visit. Bacteriologic treatment failures occurred in 4 (5%) of the 79 patients in the amoxicillin group and in 8 (11%) of the 73 patients in the penicillin V group. CONCLUSIONS: These data demonstrate that once-daily amoxicillin therapy is as effective as penicillin V therapy given three times a day for the treatment of GABHS pharyngitis, and if confirmed by additional investigations, once-daily amoxicillin therapy could become an alternative regimen for the treatment of this disease.     

The effect of restricted nutrition on uterine macrophage populations in mice

The abundant macrophage populations present in the endometrium are implicated in the tissue remodelling events and immunological changes necessary for pregnancy. Using two regimens of restricted nutrition (95 and 88% of ad libitum intake for 19 days), we have shown that moderately reduced food consumption can dramatically alter the number of endometrial macrophages and their immunoaccessory function in mice. Restricted nutrition also interfered with the estrous cycle, but the effects on endometrial macrophages were more extensive and qualitatively different than could be explained by diminished ovarian steroid hormone activity. Significantly less F4/80+ and Ia+ cells were found in the endometrium of food restricted mice than in ad libitum mice at the same estrous cycle stage. In the more severely restricted mice the losses were even greater than those seen after ovariectomy. In ad libitum fed animals, uterine but not peritoneal macrophages showed an ovarian hormone-dependent inhibitory phenotype in a splenocyte mitogenesis assay. Macrophages derived from both locations exhibited greater immunostimulatory activity following restricted nutrition. We conclude that endometrial macrophage populations are influenced by nutritional status and this may be mediated through both steroid hormone-dependent and -independent mechanisms. Nutritionally induced aberrations in the number or behaviour of endometrial macrophages during the estrous cycle or in early pregnancy could have important implications for the quality of the pre- and peri-implantation environment and the maternal immune response to pregnancy.