Antibodies to prion protein inhibit human colon cancer cell growth.

A putative role for prion protein (PrP) in apoptosis has been implicated. This function was investigated to test whether antibodies to PrP could induce apoptosis and be utilised in the treatment of cancers. Various antibodies to PrP were screened in MTT proliferation assays with HCT 116 colon cancer cells. Antibodies were shown to have varying degrees of anti-proliferative activity, with 3F4 and 6D11 essentially inactive, compared to other highly active antibodies. Surprisingly, BAR221 and F89/160.1.5 antibodies were particularly potent and afforded >40% reduction in proliferation at 50 microg/ml. In combination therapy experiments, antibodies to PrP enhanced the effect of irinotecan, 5-FU, cisplatin and doxorubicin to varying degrees. Use of PrP antibody in vitro resulted in increased apoptosis as measured by reduced Bcl-2 expression. In different colon cancer cell lines, antibody effectiveness correlated with tumour aggressiveness. Remarkably, in an in vivo nude mouse bearing human HCT 116 xenografts, tumour growth was inhibited by treatment with PrP antibody. Forty-seven days after treatment, at 9 mg/kg antibody in combination with irinotecan, tumour sizes were approximately 33% smaller compared to animals receiving irinotecan alone. The data suggest a potential pharmacological application for PrP antibodies in combination chemotherapy.

Declining immune function in children and adolescents with hemophilia and HIV infection: effects on neuropsychological performance. Hemophilia Growth and Development Study.

OBJECTIVE: To determine whether declines in immune functioning are associated with changes in neuropsychological performance in children and adolescents with hemophilia who are infected with the human immunodeficiency virus (HIV). METHODS: Participants were 333 males with hemophilia, ages 6-19 years at entry. A baseline and four annual neuropsychological evaluations were given. A longitudinal growth curves analysis of data was performed to detect changes associated with declining immune function. The cohort was stratified into four groups: (1) HIV- (n = 126); (2) HIV+, average of first two and last two CD4 counts > or = 200, (n = 106; High CD4 group); (3) HIV+, average first two counts > or = 200, average last two counts < 200 (n = 41; CD4 Drop group); and (4) HIV+, average first two and last two counts < 200 (n = 60; Low CD4 group). RESULTS: There were significant differences among the four groups over time in nonverbal intelligence, perceptual/performance skills, nonverbal memory, academic achievement, and language. The Low CD4 group consistently showed the greatest decrement in performance. On measures showing a practice effect for repeated measurements, the Low CD4 group participants' scores remained stable over time, suggesting opposing effects of practice and HIV-related declines. Lowered academic performance relative to IQ was found in all groups. CONCLUSIONS: Declines in neuropsychological functioning are directly related to declines in immune functioning in HIV+ children, adolescents, and young adults with hemophilia. Hemophilia itself may be a risk factor for academic underachievement.

Hemophilia growth and development study: relationships between neuropsychological, neurological, and MRI findings at baseline.

OBJECTIVE: To determine the effects of human immunodeficiency virus (HIV) infection on children's development by identifying neurological and environmental variables associated with neuropsychological measures of cognitive development in HIV-seronegative (HIV-) and HIV-seropositive (HIV+)children and adolescents with hemophilia. METHODS: Participants (N = 298; 60% HIV+) were males ages 7-19 years enrolled in the Hemophilia Growth and Development Study (HGDS). Least squares modeling was used to determine whether there was a difference at baseline in mean neuropsychological test scores by HIV status, age, and neurological baseline findings, adjusting for selected environmental and medical history variables. RESULTS: The participants were within age expectations for general intelligence. Variables associated with lowered neuropsychological performance included academic problems, coordination and/or gait abnormalities, parents' education, and previous head trauma. CONCLUSIONS: Hemophilia-related morbidity has a subtle adverse influence on cognitive performance. HIV infection was not associated with neuropsychological dysfunction in this group even when MRI abnormalities were present.

Marshmallows cause an outbreak of infection with Salmonella enteritidis phage type 4.

Thirty-six cases of Salmonella enteritidis phage type (PT) 4 infection, mainly in children, were notified in one local authority in the two weeks beginning on 23 October 1995. Twenty-four cases and 42 controls nominated by cases were included in a case control study, which showed a significant association between illness and the consumption of marshmallow confectionery from a bakery. S. enteritidis PT4 was isolated from samples of the marshmallow, and all isolates had the same plasmid and pulsed field gel electrophoresis profiles. The marshmallow had been made using raw egg white, which shows that not all caterers follow the Department of Health's advice.

Effects of the argon laser on primary tooth pulpotomies in swine.

This study evaluated the clinical, radiographic, and histologic effects of the HGM PC Oralase argon laser on vital pulps of swine teeth. Pulpotomies were performed in vivo on 42 primary teeth from three young pigs and observed for 7 or 60 days. For each time period nine experimental teeth received an argon laser dose of 1 W, 2 sec (24.88 J/cm2), and nine experimental teeth received a dose of 2 W, 2 sec (49.74 J/cm2). Controls consisted of three teeth for each time period and did not receive exposure from the argon laser. There were no significant differences noted between the two energy densities with respect to clinical, radiographic, or histological parameters for either time period. All soft tissues remained normal and all teeth exhibited normal mobility at weekly assessments. Other than physiologic root resorption, there were no differences in pre- and postoperative radiographs in the 7 day sample; calcifications coinciding to dentinal bridges were visible radiographically in 8 of the 60-day samples. Reparative dentin formation was noted histologically in a total of 9 roots in the 7-day group and in 13 roots in the 60-day group. With the exception of teeth which had early restoration loss with resultant bacterial contamination, all other pulps appeared to retain their vitality and capability of normal pulpal healing. Use of the argon laser at the parameters described in this study did not appear to be detrimental to pulpal tissues.

The effect of glutaraldehyde pulpotomy treatment on pulpal enzymes.

The enzymes lactate dehydrogenase (LD), succinate dehydrogenase (SD), alkaline phosphatase (AP), and glucose-6-phosphate dehydrogenase (G-6-PD) were evaluated at specific locations in pulp tissue following glutaraldehyde pulpotomies. Pulpotomies were performed on maxillary first molars in 40 rats after sacrifice at times 0, 24 hr, seven days, or one month, and experimental teeth were treated with 6% buffered glutaraldehyde. Teeth were prepared for frozen sectioning and the sections were subjected to incubation media to detect each enzyme. Significant differences were found regarding the location of staining and the time intervals at which stain was present or absent. Staining for LD and AP was the most intense throughout the four observation time periods, though staining for these enzymes as well as for G-6-PD had begun to diminish by day seven in the coronal thirds. Staining was completely absent in the coronal thirds at one month but remained in the middle and apical thirds throughout one month. SD was the only enzyme that was totally absent in the coronal third at seven days and totally absent in the middle third at one month. These findings suggest that LD, AP, and the biochemical mechanisms that they represent remain active longer than SD and G-6-PD following exposure to glutaraldehyde. This information is important in identifying mechanisms that are important for repair, healing, and recovery following pulpal injury.

Comparison of two ultrasonic cleaning units for deterioration of cutting edges and debris removal on dental burs.

The effects of two ultrasonic cleaning units on surface deterioration and cleaning effectiveness of dental burs were compared in this study. The units tested were the Dextrex Model L 503B (Dextrex Chemical Industries, Inc., Bowling Green, KY) industrial ultrasonic unit and a conventional dental ultrasonic unit L & R T-21 B (L & R Manufacturing Co., Kearny, NJ). SEM photomicrographs of the burs were made before cleaning; and burs were processed for 10 min in each unit. Forty-eight new burs (24 #1/2A diamond and 24 #330 carbide) contaminated with human blood and 48 burs contaminated with tooth debris following cavity preparation were used to evaluate cleanliness. To assess deterioration, 48 new burs were evaluated for changes in the number of diamond chips or pits (carbide burs) and color changes following ultrasonic cleaning. Neither unit sufficiently cleaned the burs, as evidenced by remnants of remaining blood and debris on the burs. The loss of diamond chips was statistically significant for the burs processed in the Dextrex unit (P < 0.001) as well as for burs processed in the L & RT 21-B unit (P < 0.01). The mean number of pits was significant in carbide burs processed in both units as well (Dextrex unit: P < 0.01; L & RT-21 B unit: P < 0.001). No differences were noted in color changes for any of the burs in either unit. These data showed that the industrial-type unit was no more effective in cleaning dental burs than the conventional unit, though both units caused significant amounts of deterioration in the cutting surfaces.

Reflex sympathetic dystrophy and electroacupuncture.

Reflex sympathetic dystrophy (RSD) is a painful and progressively debilitating condition. Untreated, it leads to changes in the patient's lifestyle that are consistent with chronic pain syndrome. This general overview of contributing factors, signs and symptoms, diagnosis, and treatment of RSD presents three consecutive cases for which electroacupuncture (EA) proved to be an effective treatment for RSD pain. Possible underlying neuroanatomical mechanisms of RSD are addressed and the scientific basis for EA is considered briefly.

Comparison of antimicrobial and cytotoxic effects of glutaraldehyde and formocresol.

The in vitro antimicrobial and cytotoxic concentrations of glutaraldehyde and formocresol were determined. Minimal antimicrobial concentrations of these two agents against selected microbial flora reported in carious primary teeth were 3.125% for glutaraldehyde and 0.75% for formocresol. At a doubling of these concentrations, most organisms, except Candida albicans, Staphylococcus epidermidis, and Streptococcus mutans, were killed by both substances in 30 seconds. Cytotoxicity was evaluated on tissue cultures of pulp fibroblasts and HeLa cells at minimal cidal concentrations and at 10- and 100-fold dilutions. Exposure of pulp fibroblasts and HeLa cells to formocresol and indirect exposure to vapors caused the cells to become atrophic and to form a less dense tissue pattern. Cells directly exposed to glutaraldehyde retained their normal cell shape and tissue pattern, whereas cells indirectly exposed to vapors continued to proliferate. These data showed effective antimicrobial activity at concentrations of 3.125% glutaraldehyde and 0.75% formocresol and suggested that glutaraldehyde may exert a less cytotoxic effect on the immediate and surrounding tissues when used as a pulpotomy agent.

A direct surgical approach to correct the inverted nipple.

Inverted nipples are cosmetically unpleasing to the patient and can become inflamed due to mechanical difficulty with cleaning the nipple-areola complex. A surgical technique for the permanent repair of inverted nipples is described. The rationale for the surgical approach is that the major pathophysiologic basis for nipple inversion is shortened lactiferous ducts. Briefly outlined, under local anesthesia, the nipple is everted with a skin hook and held in gentle traction while a small incision is made on each side at the nipple-areola junction. Breast ducts are then divided by sharp dissection, and a drain is inserted through the tunnel under the nipple. The drain is removed in 7 to 10 days. The patient must be informed before the procedure that breast-feeding will not be possible afterward because breast ducts will be permanently divided. Advantages to the procedure are (1) no scars on the areola, (2) no stricture from sutures, (3) adequate blood and nerve supply to the nipple, and (4) decreased risk of hematoma.

Cognitive and physiological responsiveness of abused children.

Videotaped scenes of everyday events were shown to hospitalized abused and nonabused children and to a nonhospitalized peer group. The children's heart rates were taken as they viewed the scenes and they responded to questions about the content of the scenes. The hospitalized children reacted to the scenes with a larger decrease in heart rate than did the nonhospitalized children. The abused children reported more negative outcomes to the scenes, more negative feelings, and that they had experienced the events depicted more often than did either group of nonabused children.

Neonatal responsiveness as a function of maternal contact and obstetrical drugs.

This work was designed to study changes in neonatal behavior during the first two days of life. Infants in Part I were from middle-class backgrounds. Half of these infants had unrestricted maternal contact during the first two days of life, the other half had contact with their mothers only at feeding time. Infants in Part II were from low socio-economic backgrounds. They were cared for entirely by the nursery staff during the first two days of life, so that differences in maternal style did not affect their behavior. Half of these babies were born to mothers who received 50 mg meperidine during labor, half to mothers who received no meperidine. This work provided evidence for the sensitivity of the neonate during the first two days of life. Both those infants who received unrestricted maternal contact and those whose mothers had received no obstetrical drugs exhibited more behavioral change than those who received low maternal contact or whose mothers had received meperidine during labor. High maternal contact and absence of obstetrical drugs also resulted in increased sensitivity to some environmental stimuli.

Self-recognition in retarded children.

This study was designed to investigate the relationship between cognitive and affective development. Young preverbal retarded children watched TV images of themselves with faces marked or unmarked and of a peer whose face was marked. We used the objective technique of increased mark-directed responses as evidence of self-recognition and rated the children's reactions as they watched these images. The emergence of self-recognition was closely tied to the maturity of the children's general responsiveness to their reflections. The Down's syndrome children made a broad range of responses, including the curiosity and self-conscious behaviors characteristic of normal children during the second year of life, and all except one of these children showed evidence that they recognized their images. In contrast, the range of behaviors displayed by multihandicapped children was greatly restricted and similar to children in the first year of life. Less than half of these children showed an emergence of self-recognition.