Lingual tonsillitis: an unusual presentation of mononucleosis.
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Biomedical subjects
Publications and source records attributed to M Russell.
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BACKGROUND: Squamoproliferative lesions are common in patients who are immunosuppressed, particularly in recipients of solid organ transplants. Histologic features in such biopsy specimens may differ from those of otherwise healthy patients. Actinic keratoses (AKs) in transplant recipients may possess pathologic characteristics that suggest that they arose in an immunosuppressed host. OBJECTIVE: We evaluated 30 randomly selected AKs from 25 recipients of solid organ transplants and compared their histologic features to those of 50 AKs from 45 patients who were not immunosuppressed. METHODS: Tissue samples were categorized by sex, patient age, and site of biopsy. Sixteen separate histologic criteria were evaluated in a blinded fashion in each specimen. Statistical analysis was performed between the two groups with and without controlling for the age of the patient. RESULTS: The transplant group was significantly younger (54.8 years) than the nontransplant group (70.0) and contained more men (88%) than women (51%). AKs from transplant recipients were statistically more likely to demonstrate bacterial colonization, confluent parakeratosis, hyperkeratosis, increased mitotic activity, and verrucous changes. After controlling for age only, hyperkeratosis failed to be more prevalent in the transplant group. CONCLUSION: Certain histopathologic features are more common in AKs of immunosuppressed transplant recipients and may be used to distinguish between those removed from otherwise healthy persons.
The current methodology for screening libraries of single-chain fragments of immunoglobulin variable domains (sFvs) utilizes bacterial phage systems. We have developed a unique in vivo selection protocol combining a modified yeast two-hybrid assay with a novel prey vector expressing sFvs. The viability of the system is demonstrated with the screen of a sFv library cloned into a yeast two-hybrid prey vector for molecules that target the bait ATF-2, a member of the CREB/ATF family of transcriptional regulatory proteins. The isolated sFv was capable of recognizing ATF-2 in vitro on Western blots and in vivo in mammalian cells.
Pertussis is increasingly being recognized as an important cause of cough illness in adolescents and adults. To evaluate the safety and immunogenicity of an adult formulation of a five-component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine combined with diphtheria and tetanus toxoids, we randomly allocated 749 healthy adolescents and adults from 12-54 years of age recruited from five Canadian communities to receive either tetanus-diphtheria vaccine (Td), acellular pertussis vaccine (aP) or combined diphtheria-tetanus-acellular pertussis vaccine (TdaP). Subjects and personnel were unaware of the vaccine allocation. Antibody levels were measured before and one month postimmunization; adverse events were collected at 24 and 72 h and 8 to 10 days. Adverse events were reported in similar frequency amongst the three vaccine groups. Moderate pain at the injection site was reported less frequently in the aP group than the TdaP group (10.7% compared to 19.4%; relative risk 0.6, 95% confidence interval 0.3-0.9). Chills were reported less frequently after Td (5.3%) than after TdaP (12.5%; relative risk 0.4, 95% confidence interval 0.2-0.9). There were no statistically significant differences between recipients of Td and TdaP in tetanus and diphtheria antitoxin levels achieved. Antibody response against Bordetella pertussis antigens was vigorous in all groups although recipients of aP alone had higher levels of antibody levels against pertussis toxoid, fimbriae, and agglutinins and lower antibody levels against pertactin than did TdaP recipients. We conclude that this adult formulation 5-component acellular pertussis vaccine is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.
The longitudinal relations among contact with one's social network (social contact), perceived social support, depression, and alcohol use were examined. An integrative model was developed from affect regulation theory and theories of social support and dysfunctional drinking. Data were obtained from a random sample of 1,192 adults. The 3-wave panel model was tested using structural equation modeling analysis. Results revealed that (a) social contact was positively related to perceived social support; (b) perceived social support was, in turn, negatively related to depression; and (c) depression was, in turn, positively related to alcohol use for 1 of 2 longitudinal lags. There was partial support for the feedback hypothesis that increased alcohol use leads to decreased contact with family and friends. Although the results generally supported the authors' hypotheses, the significant coefficients in the model were generally small in size.
The cytochrome P4501A1 (CYP1A1) enzyme is regulated at the transcriptional level and its expression is influenced by genetic factors, polymorphisms in the structural and regulatory genes, and by environmental factors such as exposure to polycyclic aromatic hydrocarbons (PAHs). To investigate the role of CYP1A1 in breast cancer, we studied CYP1A1 expression in breast tissue, thereby taking all possible modifying factors into account. We measured CYP1A1 expression in 58 non-tumor breast tissue specimens from both breast cancer patients (n = 26) and cancer-free individuals (n = 32) using a newly developed reverse transcription-polymerase chain reaction assay. CYP1A1 expression varied between specimens approximately 400-fold and was independent of age. CYP1A1 expression was somewhat higher in tissue from breast cancer patients than in that from cancer-free individuals, but this difference was not statistically significant. Analysis for CYP1A1 genetic polymorphisms revealed eight variants, seven in the cancer-free group and one in the patient group. The variant genotype was not a good predictor of expression level. We conclude that high CYP1A1 expression could be a risk factor for breast cancer and that the known CYP1A1 polymorphisms are not good predictors of CYP1A1 expression.
BACKGROUND: Pertussis is increasingly recognized as an important cause of cough illness in adolescents and adults. PURPOSE: To evaluate the safety and antibody response to a single dose of an adult formulation of a five component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine (aP) combined with diphtheria and tetanus toxoids (TdaP) and inactivated poliovirus vaccine (TdaP-IPV) in adolescents and adults and to assess the response to a second dose of the acellular pertussis vaccine in a subset of the adults. POPULATION AND SETTING: The study addressed 1207 healthy participants (736 adults and 466 adolescents) recruited in five Canadian communities. STUDY DESIGN: In a randomized, observer-blind, controlled clinical trial, adult participants received Td followed at a separate visit by aP, TdaP followed by IPV or TdaP-IPV; adolescents received Td-IPV followed at a separate visit by aP or TdaP-IPV. A subgroup of adults was given a booster of aP 1 month after TdaP. OUTCOME MEASURES: Antibody titers measured before and 1 month after each immunization; adverse events enumerated at 24 h, 72 h and 8 to 10 days. RESULTS: The aP vaccine given by itself was associated with adverse events less frequently than were Td, Td-IPV, TdaP or TdaP-IPV vaccines, but reaction rates did not differ significantly among the latter products. The antibody response against Bordetella pertussis antigens was vigorous in all groups, although adults given the TdaP-IPV vaccine had lower antibody titers against filamentous hemagglutinin, pertactin, diphtheria and tetanus antibodies than those given TdaP vaccine. Similarly adolescents given TdaP-IPV had lower antibody titers against pertussis toxin, filamentous hemagglutinin, fimbriae and agglutinins than those given Td-IPV and aP alone. A second dose of acellular pertussis vaccine was not associated with increased adverse events in adults but elicited increased antibody titers over that achieved by a single dose only against pertussis toxin. CONCLUSIONS: This adult formulation five component aP vaccine given as TdaP-IPV is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.
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Epidemiologic studies often rely on food frequency questionnaires (FFQs) to collect information on alcoholic beverage intake. However, estimation of alcohol intake using FFQs may be of some concern because of limited questions concerning alcohol intake. The authors compared estimates of alcohol intake during the 12-24 months prior to interview obtained from the Health Habits and History Questionnaire and the Harvard Semiquantitative Food Frequency Questionnaire with those from a more extensive alcohol questionnaire, the Drinking Pattern Questionnaire, among 133 healthy subjects (75 men, 58 women) aged 35-73 years, residents of western New York State. Data were collected in 1995 during two separate interviewer-administered computer-assisted interviews conducted approximately 2 weeks apart. For each questionnaire, average daily ounces (1 oz = 30 ml) of alcohol intake from alcoholic beverages were calculated as the product of the reported beverage-specific drink size (ounces) and the average daily frequency of intake multiplied by a factor representing the percentage of alcohol provided by each beverage. Estimates of total alcohol and liquor intake, but not of beer and wine intake, tended to be higher for the Drinking Pattern Questionnaire compared with the FFQs. Spearman's correlation coefficients ranged from 0.69 to 0.84. These results suggest that although the Drinking Pattern Questionnaire produced higher estimates than either FFQ, both FFQs provide a reasonable ranking of participants' alcohol intake.
BACKGROUND: Epidemiologic studies have demonstrated that individuals who eat more fruits and vegetables and/or have high levels of serum beta-carotene have a lower risk of cancer, especially lung cancer. However, recent human intervention studies using beta-carotene supplements have shown an increase in the risk of lung cancer among smokers and asbestos workers. In this study, we used an animal model system to evaluate the hazard associated with a combination of high-dose beta-carotene supplementation and tobacco smoking. METHODS: Ferrets were given a beta-carotene supplement, exposed to cigarette smoke, or both for 6 months. Cell proliferation and squamous metaplasia in lung tissue were assessed by examination of proliferating-cell nuclear antigen expression and histopathologic examination, respectively. beta-Carotene and retinoid concentrations in lung tissue and plasma samples were analyzed by high-performance liquid chromatography. Expression of genes for retinoic acid receptors (RARs) and activator protein-1 (encoded by the c-Jun and c-Fos genes) in lung tissue specimens was examined by western blotting. RESULTS: A strong proliferative response in lung tissue and squamous metaplasia was observed in all beta-carotene-supplemented animals, and this response was enhanced by exposure to tobacco smoke. When compared with control groups, all three treatment groups had statistically significantly lower concentrations of retinoic acid in lung tissue, and they exhibited 18%-73% reductions in RARbeta gene expression; however, RARalpha and RARgamma gene expression was not reduced. Ferrets given a beta-carotene supplement and exposed to tobacco smoke had threefold to fourfold elevated expression of the c-Jun and c-Fos genes. CONCLUSIONS: Diminished retinoid signaling, resulting from the suppression of RARbeta gene expression and overexpression of activator protein-1, could be a mechanism to enhance lung tumorigenesis after high-dose beta-carotene supplementation and exposure to tobacco smoke.
After a decade of research, the parent-held Personal Child Health Record was introduced in some parts of the United Kingdom in 1991, coinciding with the enforcement of the Children Act 1989. It was designed as the main record of a child's health and development, to be used until adulthood and to be held by parents. Several Health Care Trusts have since discovered a need to maintain parallel records in the best interests of children. Barnet introduced the 'Joint Professional Record' in 1995 for selected children, such as children on the Child Protection Register. The Joint Professional Record (JPR) is a single, clinic-held, parallel record for multidisciplinary use. We undertook a programme of audit and staff seminars to develop and evaluate use of the JPR. We discuss, below, the impact of this record on professional working relationships and consider the implications of its use as a confidential record and within our policy of working in partnership with parents. In our experience, the JPR has proved a useful adjunct to clinical supervision in the arena of Child Protection and is appropriately used for children in need of protection and those with 'special needs'.
Glycosylphosphatidylinositol-specific phospholipase C (GPtdIns-PLC) is found in the protozoan parasite Trypanosoma brucei. A region of protein sequence similarity exists between the protozoan enzyme and eubacterial phosphatidylinositol-phospholipases C. The functional relevance of Cys80 and Gln81 of GPtdIns-PLC, both in this region, was tested with a panel of mutations at each position. Gln81Glu, Gln81Ala, Gln81Gly, Gln81Lys and Gln81Leu mutants were inactive. Cleavage of GPtdIns was detectable in Gln81Asn, although the specific activity decreased 500-fold, and kcat was reduced 50-fold. Thus an amide side-chain at residue 81 is essential for catalysis by GPtdIns-PLC. Sulfhydryl reagents inactivate GPtdIns-PLC, suggesting that a Cys could be close to the enzyme active site. Surprisingly, p-chloromercuriphenyl sulfonate (p-CMPS) is significantly more potent than N-ethylmaleimide, the less bulky compound. This knowledge prompted us to test whether replacement of Cys80 with an amino acid possessing a bulky side-chain would inactivate GPtdIns-PLC: Cys80Ala, Cys80Thr, Cys80Phe, Cys184Ala, and Cys269-270-273Ser were constructed for that purpose. Cys80Phe lacked enzyme activity, while Cys80Ala, Cys80Thr and Cys269-270-273Ser retained 33 to 100% of wild-type activity. Interestingly, the Cys80Ala and Cys80Thr mutants became resistant to p-CMPS, as predicted if the sulfhydryl reagent reacted with Cys80 in the wild-type enzyme to form a cysteinyl mercurylphenylsulfonate moiety, a bulky adduct that inactivated GPtdIns-PLC, similar to the Cys80Phe mutation. We conclude that a bulky side-chain (or adduct) at position 80 of GPtdIns-PLC abolishes enzyme activity. Together, these observations place Cys80 and Gln81 at, or close to, the active site of GPtdIns-PLC from T. brucei.
Replication of results is an important issue in studies of diet and disease, possibly dependent on data collection method. We compared assessments from the Health Habits and History Questionnaire (HHHQ), the Harvard Semiquantitative Food Frequency Questionnaire (HFFQ), and the New York State Cohort Food Frequency Questionnaire (CFFQ) for estimates of daily intakes of energy, protein, carbohydrates, total fat, dietary fiber, cholesterol, vitamins A, C, and E, and carotenoids. Fifty-nine men and 50 women aged 35-73 years completed the HHHQ and HFFQ as interviews and the 44-food CFFQ as a self-administered mailed questionnaire. Comparability was assessed with Spearman correlation coefficients. Quantitation of nutrient intake differed by nutrient, questionnaire, and nutrient calculation method. Ranking on energy and macronutrient intake for the HHHQ and HFFQ ranged from 0.62 to 0.80; ranking for micronutrient intake ranged from 0.56 to 0.80. For the CFFQ with the HHHQ or HFFQ, correlations ranged between 0.29 and 0.62. The CFFQ performs comparably to the HHHQ and HFFQ for some, but not all, nutrients; our results suggest that the HHHQ and HFFQ can be used interchangeably with reasonable confidence in studies of diet and disease.
Both alcohol use and stress appear to increase blood pressure. In addition, stress is associated with increased alcohol use. To investigate these relationships, researchers interviewed representative samples of the black and non-black adult household populations in Erie County, New York, in 1986, 1989, and 1993. The results support a causal relationship between stress and alcohol use and point to a number of factors that influence this relationship. Significant relationships between changes in alcohol use and blood pressure were also found. Although the researchers found little evidence for a direct effect of stress on blood pressure, stress related to family life, anxiety, and depression was associated with an increased risk for hypertension.
STUDY OBJECTIVE: "Suicide by cop" is a term used by law enforcement officers to describe an incident in which a suicidal individual intentionally engages in life-threatening and criminal behavior with a lethal weapon or what appears to be a lethal weapon toward law enforcement officers or civilians to specifically provoke officers to shoot the suicidal individual in self-defense or to protect civilians. The objective of this study was to investigate the phenomenon that some individuals attempt or commit suicide by intentionally provoking law enforcement officers to shoot them. METHODS: We reviewed all files of officer-involved shootings investigated by the Los Angeles County Sheriff's Department from 1987 to 1997. Cases met the following criteria: (1) evidence of the individual's suicidal intent, (2) evidence they specifically wanted officers to shoot them, (3) evidence they possessed a lethal weapon or what appeared to be a lethal weapon, and (4) evidence they intentionally escalated the encounter and provoked officers to shoot them. RESULTS: Suicide by cop accounted for 11% (n=46) of all officer-involved shootings and 13% of all officer-involved justifiable homicides. Ages of suicidal individuals ranged from 18 to 54 years; 98% were male. Forty-eight percent of weapons possessed by suicidal individuals were firearms, 17% replica firearms. The median time from arrival of officers at the scene to the time of the shooting was 15 minutes with 70% of shootings occurring within 30 minutes of arrival of officers. Thirty-nine percent of cases involved domestic violence. Fifty-four percent of suicidal individuals sustained fatal gunshot wounds. All deaths were classified by the coroner as homicides, as opposed to suicides. CONCLUSION: Suicide by cop is an actual form of suicide. The most appropriate term for this phenomenon is law enforcement-forced-assisted suicide. Law enforcement agencies may be able to develop strategies for early recognition and handling of law enforcement-forced-assisted suicide (suicide by cop). Health care providers involved in the evaluation of potentially suicidal individuals and in the resuscitation of officer-involved shootings should be aware of law enforcement-forced-assisted suicide as a form of suicide.
Safety, immunogenicity and lot consistency of five-component pertussis combination vaccine (CPDT-IPV//PRP-T) in infants were compared to that of whole cell pertussis combination vaccine (DPT-IPV//PRP-T), as were separate and combined injections of CPDT-IPV and PRP-T. No significant differences in adverse event rates were observed between lots of CPDT-IPV//PRP-T or between separate or combined injections of CPDT-IPV and PRP-T. Minor differences in antibody responses were observed between lots of component pertussis vaccine. Higher concentrations of diphtheria and tetanus antitoxins were induced by separate than by combined injection of CPDT-IPV and PRP-T, but no other differences in immunogenicity were observed. Adverse reactions were more than twice as frequent after whole cell than after component pertussis vaccines. Antibody responses to pertussis toxoid, filamentous hemagglutin and pertactin were significantly greater after component vaccines, while the response to type 3 poliovirus was higher after whole cell vaccine. No significant differences were observed for other vaccine components. CPDT-IPV//PRP-T was safe and immunogenic in infants. Antibody results were similar to those observed in a Swedish field trial that demonstrated CPDT to be 85% effective in preventing clinical pertussis.