Risk factors for HPV detection in archival Pap smears. A population-based study from Greenland and Denmark

The most important risk factor for cervical cancer is genital infection with certain types of human papillomavirus (HPV). The presence of HPV was studied in archival smears from a random sample of women living in Greenland (GW) and Denmark (DW) having, respectively, a high risk and an intermediate risk for cervical cancer. Risk factors were also examined of the original 126 Danish and 129 Greenlandic archived smears collected during October and November 1988. 125 were located from each country including all abnormal smears. HPV DNA was isolated from the smears and detected by means of a consensus polymerase chain reaction (PCR) detecting a broad spectrum of genital HPV types. HPV was detected in all the abnormal smears and in 22 and 33% respectively of the cytological normal smears from DW and GW. Risk of HPV was significantly higher in smears from women who started sexual life relatively recently (respectively, < or = 4 and < or = 6 years ago in DW and GW) compared with > or = 10 years ago (adjusted prevalence-OR: 9.3; 95% CI: 2.2-39.2 in DW and 5.9; 95% CI: 1.4-25.3 in GW). Among other important risk factors were age in both areas, lifetime number of sex partners and current smoking in DW and ever and gonorrhoea in GW. This study confirms the usefulness of the method as all abnormal smears were positive and, furthermore, the predictors for HPV presence in the normal smears corroborate with those found in recent studies of HPV in fresh cervical swabs. Thus, this method can be useful for large-scale epidemiological studies of HPV DNA in already sampled material.     

Importance of functional measures in predicting mortality among older hospitalized patients

CONTEXT: Measures of physical and cognitive function are strong prognostic predictors of hospital outcomes for older persons, but current risk adjustment and burden of illness assessment indices do not include these measures. OBJECTIVE: To evaluate and validate the contribution of functional measures to the ability of 5 standard burden of illness indices (Charlson, Acute Physiology and Chronic Health Evaluation [APACHE] II, Disease Staging, All Patient Refined Diagnosis Related Groups, and a clinician's subjective rating) in predicting 90-day and 2-year mortality among older hospitalized patients. DESIGN: Two prospective cohort studies. SETTING: General medicine service, university teaching hospital. PATIENTS: For the development cohort, 207 consecutive patients aged 70 years or older, and for the validation cohort, 318 comparable patients. MAIN OUTCOME MEASURE: Death within 90 days and 2 years from the index admission. RESULTS: In the development cohort, 29 patients (14%) and 81 patients (39%) died within 90 days and 2 years, respectively. A functional axis was developed using 3 independent risk factors: impairment in instrumental activities of daily living, Mini-Mental State Examination score of less than 20, and shortened Geriatric Depression Scale score of 7 or higher, creating low-, intermediate-, and high-risk groups with associated mortality rates of 20%, 32%, and 60%, respectively (P<.001); the C statistic for the final model was 0.69. The corresponding mortality rates in the validation cohort, in which 59 (19%) and 138 (43%) died within 90 days and 2 years, respectively, were 24%, 45%, and 60% (P<.001); the C statistic for the final model was 0.66. For each burden of illness index, the functional axis contributed significantly to the predictive ability of the model for both 90 days and 2 years. When the functional axis and each burden of illness measure were analyzed in cross-stratified format, mortality rates increased progressively from low-risk to high-risk functional groups within strata of burden of illness indices (double-gradient phenomenon). The contributions of functional and burden of illness measures were substantive and interrelated. CONCLUSIONS: Functional measures are strong predictors of 90-day and 2-year mortality after hospitalization. Furthermore, these measures contribute substantially to the prognostic ability of 5 burden of illness indices. Optimal risk adjustment for older hospitalized patients should incorporate functional status variables.     

Site-directed mutagenesis and steady-state kinetic analysis of mutant enzymes of human adenylate kinase

Infection of rats with the enteric, lumen-dwelling tapeworm Hymenolepis diminuta causes electric changes in host intestinal smooth muscle and decreased luminal transit. The mechanisms that stimulate host intestinal alterations during this nontissue invasive infection may include the tapeworm's biomass, its diurnal migratory behavior, a host immune-mediated response, or direct parasite stimulation of host motor activity. In vivo intestinal myoelectric activity was monitored to evaluate the following: (1) that reinfection with H. diminuta is influenced by host immune regulation and (2) that administration of tapeworm fractions to never-before-infected rats initiates an alteration of enteric smooth muscle activity. To address the first hypothesis, we determined that altered intestinal myoelectric activity patterns were no different and did not occur earlier in a second infection with H. diminuta than in a primary infection. The lack of either a change in myoelectric pattern or an earlier onset of intestinal myoelectric changes indicates that tapeworm-induced myoelectric activity is not anamnestically stimulated by host immunomodulatory mechanisms. Consistent with the second hypothesis, administration of either H. diminuta carcass homogenate or tegument-enriched fractions directly into the intestinal lumen of tapeworm-naive rats initiated myoelectric patterns previously characteristic of chronic H. diminuta infection. Additionally, the appearance of characteristic nonmigrating myoelectric patterns in uninfected rats administered tapeworm fractions indicates that a substance from H. diminuta acts as the triggering signal molecule for intestinal myoelectric alterations. These findings also indicate that neither the tapeworm's biomass nor its diurnal movement is required for initiation of H. diminuta-altered myoelectric patterns. We have shown that H. diminuta possess a signal molecule(s) that alters host enteric electric activity, and we suggest that these alterations may play an important role in the symbiotic rat-tapeworm interrelationship.     

Outpatient treatment of middle and lower ureteric stones: extracorporeal shock wave lithotripsy versus ureteroscopic laser lithotripsy

The aim of this retrospective study was to evaluate the efficacy of ureteroscopic lithotripsy (URSL) and extracorporeal shock wave lithotripsy (ESWL) in the treatment of middle and lower ureteric stones. From January 1996 to March 1997, 61 patients treated by URSL and 49 patients treated by ESWL were studied, both were conducted as outpatient procedures. URSL using Holmium laser and semirigid ureteroscope (Fr.8.5) performed under general anaesthesia had single session stone clearance rates of 100% and 95% for middle and lower stones respectively. There were 6 complications including 5 readmissions (2 febrile episodes, 2 severe pain spells, and 1 stent migration) and 1 stricture formation. ESWL using the Dornier MFL 5000 lithotriptor had a single session success rate of 51% and overall success rate of 78% after retreatment (retreatment rate 35%). No significant complication or readmission was noted. Seventy-two per cent of patients required intravenous fentanyl for pain control. The efficiency quotients calculated for the URSL group and the ESWL group were 97% and 58% respectively. In summary, in the treatment of middle and lower ureteric calculi, ESWL carries reasonable success rate, especially with retreatment; and minimal morbidity. On the other hand, URSL is highly effective in rapidly clearing the stones, a low risk of complication is noted. Both can be conducted as an outpatient treatment modality.     

An aminopeptidase regulates LPS stimulated interleukin-8 receptor on the surface of human neutrophils

A large number of inflammatory diseases are mediated by interleukin-8, an inflammatory neutrophil chemotactic agent. Since the cytokine acts through a cell surface receptor, detailed knowledge about the regulation of receptor expression is very important. We found that LPS in serum became activated and triggered the expression of IL-8 receptor by more than two folds within 30 min. After that period, the receptor attained normal level within 2 hr of SA-LPS stimulation. EDTA and bestatin could block this downregulation of IL-8 receptor. Intracellular Ca2+ level was increased till 45 min of SA-LPS stimulation and then the level was reduced. Addition of CaCl2 accelerated and depletion of Ca2+ inhibited the downregulation of the IL-8 receptor. The ligand could fully protect the loss of receptor from downregulation. It suggests that during SA-LPS stimulation, increase in intracellular Ca2+ level activates an aminopeptidase which presumably cleaves the N-terminal region of the receptor, critically essential for the function of IL-8. Thus the activated aminopeptidase regulates the functions of IL-8. The study is important for understanding the regulation of IL-8 receptor expression by LPS during bacterial infection.     

Quality attributes of black olives as affected by different darkening methods

Olives can be darkened by different methods, some of which utilize chemicals and even dyes in some locations. The present study was carried out to evaluate the different darkening methods in terms of acceptance and safety of blackened olives. Olives were blackened naturally (on the tree) as well as artificially. For the latter, air oxidation was conducted on both mature and green olives using different alkalis. Moreover, blackening with nigrosine and hematin dyes was applied, since consumers prefer the appearance of such olives as well as their low price. The artificially blackened olives were compared to their naturally blackened counterparts regarding colour (subjectively and objectively), penetration reading, shrinkage percent and heavy metals content (iron, cadmium and lead). Data showed comparable colour intensity for olives blackened with 4% Na₂CO₃ followed by air oxidation for 120 h to those blackened with nigrosine and hematin. Notwithstanding, treatment with Na₂CO₃ resulted in the lowest shrinkage percent and heavy metal contents of olives, compared to those treated with other alkalis or dyes. Olives treated with Na₂CO₃ most closely resembled those which had been naturally blackened. Immersing Na₂CO₃-treated olives in sunflower oil for 1 s prior to air-oxidation significantly lowered the shrinkage percent of olives.     

HRAD1 and MRAD1 encode mammalian homologues of the fission yeast rad1(+) cell cycle checkpoint control gene

Eukaryotic cells arrest at the G2checkpoint in the presence of DNA damage or incompletely replicated DNA. This cell cycle checkpoint prevents the development and propagation of genomic instability. In the fission yeast, this process requires the action of a number of genes, including rad1(+) . We report here the identification of human and mouse cDNAs that exhibit extensive sequence homology to rad1(+) . The human gene, called HRAD1 , encodes a 282 amino acid protein that is 27% identical and 53% similar to yeast Rad1p. The human homologue maintains its sequence similarity over the full length of the protein, including the three proposed 3'-->5' exonuclease domains, and the leucine rich repeat region. The mouse gene, called MRAD1 , encodes a 280 amino acid protein that is 90% identical and 96% similar to HRAD1 at the amino acid level. Expression of HRAD1 in yeast rad1 mutants partially restores radiation resistance and G2checkpoint proficiency to these mutants. Evolutionaryconservation of structure between HRAD1 , MRAD1 , rad1(+), Saccharomyces cerevisiae RAD17 and the Ustilago maydis REC1 checkpoint genes suggests that the function of the encoded proteins is conserved as well. The ability of HRAD1 to partially complement yeast rad1 mutants suggests that this gene is required for G2checkpoint control in human cells.     

Antiprogestins mediate differential effects on glucocorticoid receptor remodeling of chromatin structure

We examined the mechanism(s) by which the progesterone receptor (PR) is able to inhibit glucocorticoid receptor (GR) activation from the mouse mammary tumor virus (MMTV) promoter in vivo. Using specific hormone antagonists, we demonstrate that the PR complexed with an type II antiprogestin blocks glucocorticoid-induced activation of the MMTV promoter. However, when complexed with a type I antiprogestin the PR is unable to block glucocorticoid-induced activation. PR repression of GR activity results from the inhibition of the ability of the GR to remodel chromatin such that the antiprogestin-occupied/PR prevents the glucocorticoid induced assembly of a preinitiation complex at MMTV promoter. These experiments suggest that the specific chromatin organization of the MMTV promoter provides a mechanism for regulating cross-talk between the GR and PR in vivo.     

Risk factors for HIV infection in a rural cohort in Zimbabwe: a pilot study

OBJECTIVE: To identify demographic, sexual behavioural and cultural risk factors for human immunodeficiency virus (HIV) infection in a rural community in Zimbabwe. DESIGN: Prospective study. SETTING: Rural area in Zimbabwe. SUBJECTS: 207 subjects (81 males, 126 females) mean age 31.6 years (SD 15.3), range 12 to 76 years living in the area. MAIN OUTCOME MEASURES: HIV seropositivity and seroconversion, exposure or no exposure to risk factor. RESULTS: Prevalence of HIV was 7.7% and was associated with being divorced or widowed [Odds ratio (OR) 4.26, 95% confidence interval (CI) 1.17 to 14.97] and past history of sexually transmitted diseases (STDs) [(OR 3.54, 95% CI 1.31 to 9.89)]. Seroconversion rate was 3.6% per year and was associated with history of STD [Relative Risk (RR) 13.22, 95% CI 1.15 to 156.1)] during the follow up period. Individuals over 20 years of age, those reporting one or more sexual partners, those reporting irregular use of condoms and those scarified were at greater risk than their counterparts. Individuals who reported being circumcised were at slightly lesser risk than those who did not report circumcision. CONCLUSION: STDs were major determinants of HIV transmission in the study area. In addition being divorced or widowed was a risk factor for HIV infection. Scarification, tattooing and circumcision require further investigations.