Complex taxonomy of the 'brush tail' peregrine earthworm Pontoscolex corethrurus.

Pontoscolex corethrurus is the most widespread earthworm species in tropical and sub-tropical zones and one of the most studied in soil science. Although, ecological interactions of P. corethrurus with its environment are well documented, the taxonomic status of the species remains unclear. In this study, we investigated phylogenetic relationships within the genus Pontoscolex, in particular focusing on morphologically indistinguishable (i.e., cryptic) lineages. A total of 792 specimens collected from 25 different countries and islands all over the world were analyzed using two mitochondrial (COI and 16S rDNA) and two nuclear (internal transcribed spacers 2 and 28S rDNA) markers, and a total of 11 morphological characters both internal and external were investigated in all genetically characterized lineages. A large-scale multilocus sequence data matrix was also obtained for Pontoscolex spp. specimens using the Anchored Hybrid Enrichment (AHE) method. Multilocus phylogenetic and phylogenomic analyses, combined with species delimitation methods; including single locus (mPTP, ABGD) and multilocus (BPP) approaches, revealed congruent results. Four cryptic species were supported within the P. corethrurus species complex, and four potentially new species within the genus Pontoscolex. One widespread lineage (L1), within P. corethrurus complex was observed in the current population of Fritz Müller's garden where P. corethrurus was first described in 1856. Cryptic lineages were observed in sympatry at several localities. This, in combination with observed heteroplasmy in COI gene in one population raises an important question of reproductive isolation between these species.

Clinical trial: a multicentre, randomized, double-blind, placebo-controlled, dose-finding, phase II study of subcutaneous interferon-beta-la in moderately active ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) pathophysiology is characterized by an imbalance between pro- and anti-inflammatory cytokines. Interferon (IFN)-beta-1a has potent immunoregulatory properties, including stimulation of host defence mechanisms and thus represents a potential treatment. AIM: To extend pilot data and identify a suitable dose of IFN-beta-1a to achieve endoscopically confirmed remission (ECR) in patients with moderately active UC and to evaluate safety. METHODS: In this multicentre, double-blind, placebo-controlled trial, adults with moderately active UC were randomized to IFN-beta-1a 44 or 66 microg, or placebo, subcutaneously three times weekly for 8 weeks, with a 4-week follow-up. RESULTS: Endoscopically-confirmed remission was observed in 23.4% [95% confidence interval (CI): 13.8-35.7] of placebo patients, 29.2% (95% CI: 18.6-41.8) of the IFN-beta-la 44 microg group and 20.0% (950% CI: 11.1-31.8) of the 66 microg group (P = 0.45). Improvements with IFN-beta-1a 44 microg were greater than with placebo for most secondary efficacy outcomes, although significance was not achieved. Placebo response rates were higher than expected from previous trials. Adverse events were similar to the known safety profile of IFN treatment. CONCLUSIONS: Interferon-beta-1a was generally well tolerated at the doses tested, but a significant therapeutic benefit in patients with UC was not observed.

"All citizens of the world can save a life" - The World Restart a Heart (WRAH) initiative starts in 2018.

"All citizens of the world can save a life". With these words, the International Liaison Committee on Resuscitation (ILCOR) is launching the first global initiative - World Restart a Heart (WRAH) - to increase public awareness and therefore the rates of bystander cardiopulmonary resuscitation (CPR) for victims of cardiac arrest. In most of the cases, it takes too long for the emergency services to arrive on scene after the victim's collapse. Thus, the most effective way to increase survival and favourable outcome in cardiac arrest by two- to fourfold is early CPR by lay bystanders and by "first responders". Lay bystander resuscitation rates, however, differ significantly across the world, ranging from 5 to 80%. If all countries could have high lay bystander resuscitation rates, this would help to save hundreds of thousands of lives every year. In order to achieve this goal, all seven ILCOR councils have agreed to participate in WRAH 2018. Besides schoolchildren education in CPR ("KIDS SAVE LIVES"), many other initiatives have already been developed in different parts of the world. ILCOR is keen for the WRAH initiative to be as inclusive as possible, and that it should happen every year on 16 October or as close to that day as possible. Besides recommending CPR training for children and adults, it is hoped that a unified global message will enable our policy makers to take action to address the inequalities in patient survival around the world.

Cervical collars and immobilisation: A South African best practice recommendation.

INTRODUCTION: The consequences of spinal injury as a result of trauma can be devastating. Spinal immobilisation using hard trauma boards and rigid cervical collars has traditionally been the standard response to suspected spinal injury patients even though the risk may be extremely low. Recently, adverse events due to the method of immobilisation have challenged the need for motion restriction in all trauma patients. International guidelines have been published for protection of the spine during transport and this article brings those guidelines into the South African context. RECOMMENDATIONS: Trauma patients need to be properly assessed using both an approved list of high and low risk factors, as well as a thorough examination. They should then be managed accordingly. Internationally validated assessment strategies have been developed, and should be used as part of the patient assessment. The method of motion restriction should be selected to suit the situation. The use of a vacuum mattress is the preferable technique, with the use of a trauma board being the least desirable. CONCLUSION: The need for motion restriction in suspected spinal injury should be properly evaluated and appropriate action taken. Not all trauma patients require spinal motion restriction.

INTRODUCTION: Les conséquences des lésions de la moelle épinière suite à un traumatisme peuvent être dévastatrices. L'immobilisation de la colonne vertébrale au moyen d'une planche dorsale rigide et de minerves rigides constituait par le passé la réponse standard aux patients que l'on suspectait de souffrir de lésions de la moelle épinière, même si le risque pouvait être extrêmement faible. Récemment, des événements indésirables qui se sont produits du fait de cette méthode d'immobilisation ont remis en question la nécessité de restreindre les mouvements chez tous les patients victimes de traumatisme. Des directives internationales ont été publiées sur la protection de la colonne vertébrale au cours du transport, et cet article adapte ces directives au contexte sud-africain. RECOMMANDATIONS: Les patients victimes de traumatisme doivent être adéquatement évalués en utilisant une liste approuvée de facteurs de risques faibles et élevés, et en procédant à un examen approfondi. Ils devraient être pris en charge en conséquence. Des stratégies d'évaluation validées au niveau international ont été développées, et devraient être utilisées dans le cadre de l'évaluation du patient. La méthode de restriction des mouvements devrait être sélectionnée en fonction de la situation. L'utilisation d'un matelas immobilisateur à dépression constitue la technique privilégiée, l'utilisation d'une planche dorsale étant la moins recommandée. CONCLUSION: La nécessité de restreindre les mouvements en cas de suspicion de lésions de la moelle épinière devrait être adéquatement évaluée et des mesures appropriées doivent être prises. Il n'est pas nécessaire de restreindre les mouvements de la colonne vertébrale chez tous les patients de traumatisme.

Effect of calcium phosphate addition to fluoride containing dental varnishes on enamel demineralization.

BACKGROUND: The aim of this study was to evaluate the ability of calcium phosphate and fluoride containing varnishes to inhibit enamel demineralization. METHODS: Six varnishes were selected for analysis: (1) Enamel Pro containing amorphous calcium phosphate; (2) Clinpro White containing functionalized tricalcium phosphate (fTCP); (3) MI Varnish containing casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP); (4) Duraphat (first no added calcium control); (5) Profluorid (second no added calcium control); and (6) placebo (no added calcium or fluoride control). Human enamel slabs (36) were each cut into half-slabs and covered with one of the six dental varnishes to create a window. The half-slabs were then individually immersed in a polyacrylate demineralization buffer pH 4.8 for four days at 37 °C with a change of solution each day. Mineral content was determined using transverse microradiography. RESULTS: All fluoride-containing varnishes significantly inhibited enamel demineralization when compared with the placebo varnish. However, out of the calcium phosphate and fluoride containing varnishes only MI Varnish, containing fluoride and CPP-ACP was superior to the fluoride-alone varnishes. MI Varnish also released the highest levels of calcium, phosphate and fluoride ions. CONCLUSIONS: MI Varnish containing fluoride and CPP-ACP was superior to the other varnishes in protecting against enamel demineralization.

Intrapallidal lipopolysaccharide injection increases iron and ferritin levels in glia of the rat substantia nigra and induces locomotor deficits.

Increasing evidence suggests that abnormal iron handling may be involved in the pathogenesis of Parkinson's disease. The present study investigates the role of iron and the iron-storage protein ferritin in inflammation-induced degeneration of dopaminergic neurons of the substantia nigra pars compacta. Injection of lipopolysaccharide into the globus pallidus of young and middle-aged rats substantially decreased tyrosine hydroxylase immunostaining in substantia nigra pars compacta four weeks after injection. Loss of tyrosine hydroxylase expression was accompanied by increased iron and ferritin levels in glial cells of the substantia nigra pars reticulata. Despite greater increases in nigral iron levels, ferritin induction was less pronounced in older rats, suggesting the regulation of ferritin was compromised with age. Automated movement tracking analyses showed that young rats recovered from LPS-induced locomotor deficits within four weeks, yet older rats failed to improve on measures of speed and total distance moved. Intrapallidal lipopolysaccharide injection also increased expression of alpha-synuclein and ubiquitin in tyrosine hydroxylase-positive neurons of the substantia nigra pars compacta. These results suggest that pallidal inflammation significantly increases stress on dopamine-containing neurons in the substantia nigra pars compacta. Alterations in nigral iron levels and protein handing may increase the vulnerability of nigral neurons to degenerative processes.

Sequences with the potential to form stem-and-loop structures are associated with coding-region duplications in animal mitochondrial DNA.

Tandem duplications of gene-encoding regions occur in the mitochondrial DNA (mt DNA) of some individuals belonging to several species of whiptail lizards (genus Cnemidophorus). All or part of the duplicated regions of the mtDNAs from five different species were sequenced. In all, the duplication endpoints were within or immediately adjacent to sequences in tRNA, rRNA or protein genes that are capable of forming energetically stable stem-and-loop structures. In two of these mtDNAs, the duplication endpoints were also associated with a direct sequence repeat of 13 bp. The consistent association of stem-and-loop structures with duplication endpoints suggests that these structures may play a role in the duplication process. These data, combined with the absence of direct or palindromic repeats at three of the pairs of duplication endpoints, also suggest the existence of a mechanism for generating de novo duplications that is qualitatively different from those previously modeled.

The physical properties and ion release of CPP-ACP-modified calcium silicate-based cements.

BACKGROUND: This study investigated the physical properties and ion release of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-modified calcium silicate-based cements (CSCs) and compared the properties of a trial mineral trioxide aggregate (MTA) with two commercially available CSCs, Biodentine(™) and Angelus(®) MTA. METHODS: The setting time, solubility, compressive strength and Vickers surface microhardness of the three CSCs incorporated with 0%, 0.5%, 1.0%, 2.0% and 3.0% (w/w) CPP-ACP were investigated. Release of calcium (Ca(2+) ), phosphate ions (Pi ) and pH of the test cements were measured after 24, 72, 168 and 336 h of storage. RESULTS: The addition of up to 1.0% CPP-ACP into Biodentine(™) and 0.5% into the other cements did not adversely affect their physical properties except for the setting time. The addition of 0.5% CPP-ACP increased Ca(2+) released from Biodentine(™) (after 168 and 336 h), Angelus(®) MTA (after 168 h) and the trial MTA (after 72 h). The addition of 1.0-3.0% CPP-ACP increased Ca(2+) and Pi released from all the cements. Biodentine(™) released more Ca(2+) particularly in the early stages and showed shorter setting time and higher mechanical properties than the other cements. The mechanical properties of Angelus(®) MTA and the trial MTA were similar. All the cements produced highly alkaline storage solutions. CONCLUSIONS: Up to 1.0% CPP-ACP in Biodentine(™) improves Ca(2+) and Pi release and 0.5% CPP-ACP in Angelus(®) MTA and the trial MTA improves Ca(2+) release without altering the mechanical properties and solubility. The addition of CPP-ACP into CSCs prolonged the setting time.

Behavioral and biologic evidence of persistent high-risk behavior in an HIV primary care population.

OBJECTIVE: To define the prevalence of gonorrhea, chlamydial infection, and high-risk sexual behavior in an HIV primary care clinic. DESIGN: Subjects enrolling in this cross-sectional study answered a brief interviewer-administered questionnaire and provided a urine sample for gonorrhea and chlamydia testing. SETTING: A large urban HIV primary care clinic. PARTICIPANTS: HIV-infected patients presenting for a scheduled medical visit from June 1997 to April 1998. MAIN OUTCOME MEASURES: Prevalence of self-reported high-risk sexual behavior and gonorrhea and chlamydial infection. RESULTS: Of 691 patients consenting to the study over a 10-month period, 58% reported sexual activity in the past 90 days, 7.4% reported multiple sexual partners in the past month, and 34.6% did not use a condom at last sexual encounter. Overall, 4.6% reported a history of either gonorrhea or a chlamydial infection in the past year. Of 637 giving a urine sample for testing, the prevalence of chlamydial infection was 2.4%; the prevalence of gonorrhea was 1.6%. Overall, 7.5% of those screened had either current or recent (within 1 year) gonorrhea or chlamydial infection. Current or recent gonorrhea or chlamydial infection was not associated with age, gender, HIV transmission risk, CD4 cell count, HIV viral load, symptoms, or self-reported risk behavior. CONCLUSION: High-risk sexual behavior and unrecognized sexually transmitted diseases (STD) are common among HIV-infected persons followed in primary medical care. Enhanced detection of treatable STD among this population coupled with improved risk-reduction counselling may be important clinical practice measures that can curb the spread of HIV.

Effectiveness of supervised, intermittent therapy for tuberculosis in HIV-infected patients.

OBJECTIVE: To evaluate the effectiveness of supervised therapy for tuberculosis (TB) in patients with HIV infection. DESIGN: Retrospective, chart review. PATIENTS: Patients with TB and HIV infection. SETTING: Urban, public TB clinic. MAIN MEASURES AND RESULTS: A total of 107 patients with TB and HIV infection were studied. Most were men (78%), African American (91%), uninsured or on Medicaid (88%), and 67% were injecting drug users. TB was diagnosed before AIDS in 31% of subjects, at the time of AIDS in 32%, and after AIDS in 37%. Clinical features varied by stage of HIV disease. Sixteen patients received no therapy and died before TB was diagnosed, 10 died during the first 8 weeks of treatment. Seventy-eight patients received > 8 weeks therapy, of whom 48 (62%) were given directly observed therapy twice weekly and 30 (38%) received self-administered daily therapy. Patients who received directly observed therapy were more likely to complete 6 months of therapy (96 versus 76%, P = 0.02) and more likely to survive after therapy ended (85 versus 57%, P = 0.01). By logistic regression, directly observed therapy, AIDS diagnosed before TB, and age were significantly associated with survival outcome. CONCLUSION: Directly observed therapy for TB in patients with HIV infection is highly effective and associated with better adherence to therapy and survival.

Diagnostic accuracy of three clinical case definitions for advanced HIV disease.

OBJECTIVE: To assess the accuracy of three clinical case definitions for advanced HIV disease: the World Health Organization (WHO) case definition, and the original and revised Caracas case definitions. DESIGN: Retrospective chart review. SETTING: A clinic for patients with all stages of HIV infection at the Johns Hopkins Hospital, Baltimore, [correction of Bethesda] Maryland, USA, a tertiary care university hospital. PATIENTS, PARTICIPANTS: Two hundred and twenty-four HIV-positive adults who underwent initial evaluation between 1 January 1990 and 31 December 1990. MAIN OUTCOME MEASURES: A score for each definition was assigned based on initial evaluation. The sensitivity, specificity, and predictive values were calculated using the Centers for Disease Control (CDC) staging criteria, and results were correlated with total CD4 cell counts. RESULTS: The sensitivities of the WHO, and the original and revised Caracas definitions were 40, 67, and 60%, respectively, using CDC disease stage IV as a positive standard. Specificities were between 99 and 100%, using CDC stage II-III disease as a negative standard. Mean CD4 cell counts for patients with positive scores were 184, 160, and 158 x 10(6)/l, respectively, compared to 191 x 10(6)/l for CDC stage IV patients. Sensitivity was lower when the positive standard was expanded to include all patients with CD4 cell counts less than 200 x 10(6)/l. CONCLUSIONS: In our study population, case definitions were specific, but only moderately sensitive for advanced HIV disease. Prospective studies should be conducted in diverse geographic regions, using lymphocyte or CD4 cell counts when possible.

PIP: The 1st case definition for AIDS was developed by the Centers for Disease Control (CDC) in 1982. WHO adopted CDC definitions for use in some countries and also developed a clinical case definition where HIV serology tests were not feasible. A multivariate analysis of data of Brazilian AIDS patients with positive HIV serology provided the basis for the Caracas definition in 1989 and it subsequent revision. The accuracy of these 3 clinical definitions was evaluated to see their predictive value in an advanced stage of AIDS. The records of 224 HIV-positive adults were reviewed in 1990. Scores were assigned to various symptoms. 80% of men and 20% of women with a median age of 33 years; 1/4 were white and 2/3 were black. 1/3 were homosexuals and 1.2 were iv drug users. 139 were asymptomatic (CDC stage I-II) and 85 were symptomatic (CDC stage IV). 58 patients had total CD4 cell counts of over 500 x 1 million/1; 91 had 200-500 x 1 million/l; and 70 had 200 x 1 million/1. 48 were taking zidovudine and Pneumocytis carinii drugs. The sensitivities of the WHO, original Caracas definition, and revised Caracas definition were 40%, 67%. and 60%, respectively, with 99-100% specificities and positive predictive values of 97-100%. The mean CD4 cell counts for the WHO, original and revised Caracas definitions were 184, 160, and 158 x 1 million/1, respectively, compared with 199 x 1 million/1 of patients with CDC stage IV disease. The predictive values of the 3 definitions for CD4 cell counts 200 x 1 million/1 reached 62%, 73%, and 71% vs. only 59% for CDC stage IV patients. The combination of stage IV symptoms or a CD4 cell count 200 x 1 million/1 produced sensitivities of 31%, 53%, and 47%, respectively, with 100% specificity and positive predictive values. The definitions were highly specific, but only moderately sensitive for advanced AIDS; the Caracas definitions were more sensitive than the WHO definition.

Impact of the 1993 revision of the AIDS case definition on the prevalence of AIDS in a clinical setting.

OBJECTIVE: To determine the impact of the 1993 revision of the Centers for Disease Control and Prevention (CDC) AIDS surveillance case definition on the prevalence of AIDS. DESIGN: Review of prospectively collected baseline clinical and demographic data on HIV-infected patients presenting for care between December 1988 and May 1991. SETTING: The HIV Clinic of the Johns Hopkins Hospital, an urban, primary care institution. MAIN OUTCOME MEASURE: Diagnosis of AIDS by the 1987 (specific indicator diseases) or the 1993 (indicator diseases, pulmonary tuberculosis, recurrent bacterial pneumonia, cervical carcinoma, or CD4 lymphocyte count < 200 x 10(6)/l) CDC case definition. RESULTS: Of 955 patients evaluated, 122 (13%) had AIDS by the 1987 case definition at presentation. An additional 126 (13%) met the 1993 but not the 1987 case definition. Patients meeting only the 1993 case definition were more likely to be female [28 versus 14%; odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2-3.0; P = 0.01] and intravenous drug users (40 versus 26%; OR, 2.0; 95% CI, 1.1-3.3; P = 0.02) than patients meeting the 1987 case definition. Fifty-five per cent of patients meeting only the 1993 case definition were asymptomatic, and 7% (nine patients) had new indicator diseases but CD4 counts > 200 x 10(6)/l. Median time to progression from a diagnosis of AIDS by the 1993 case definition to diagnosis by the 1987 case definition was 435 days. Patients with AIDS by the 1987 case definition had a median survival of 594 days from presentation (2-year survival, 42%), while median survival time for patients with AIDS by the 1993 case definition only was 947 days (2-year survival, 60%; P < 0.005). CONCLUSIONS: The proposed 1993 revision of the AIDS surveillance case definition would double the number of prevalent AIDS cases, with significant increases in the proportion of cases who are female, intravenous drug users, or asymptomatic. Survival of patients meeting the 1993 case definition is significantly longer than that of patients meeting the 1987 case definition. The new AIDS case definition will have a major impact both on AIDS surveillance and on medical and social service programs that use diagnosis of AIDS as a criterion for eligibility for services.

Racial heterogeneity of HIV antigenemia in people with HIV infection.

We compared the prevalence of HIV p24 antigenemia in black and white US patients with HIV infection. The prevalence of HIV antigenemia increased with severity of HIV disease (P less than 0.001). In all clinical categories, whites were more likely to be HIV-antigenemic than blacks (overall prevalence 38 versus 18%; P less than 0.01). Anti-p24 antibodies were detected in a higher proportion of blacks (84%) than whites (65%; P = 0.02). Blacks had significantly higher total serum immunoglobulin levels than whites (median 3.8 versus 3.2 mg/dl; P less than 0.00001). Racial differences in HIV antigen expression may result from differences in humoral response to HIV infection. These differences should be considered when HIV antigen is used as a surrogate marker in clinical trials.

Functional status of persons with HIV infection in an ambulatory setting.

The objective of this project was to study the functional status of HIV-infected persons seen in an ambulatory care setting. We reviewed baseline clinical and demographic data on patients with HIV infection presenting for care between December 1988 and May 1991 at the HIV Clinic of the Johns Hopkins Hospital, an urban, primary care institution. Functional status was assessed at baseline in a comprehensive psychosocial assessment. Patients were asked to report on their ability to perform six activities of daily living (ADL) and nine instrumental activities of daily living (IADL). The main outcome measures were dependency in one or more ADL and death as ascertained by review of clinic death records and Maryland State Death Registries. All 728 patients had assessments of functional status. Of these, 18% reported dependencies in one or more activity, with most of these (14%) reporting dependencies in IADLs only. Dependencies were more common in persons with an AIDS diagnosis (32% vs. 15%, p < 0.001). The majority of the dependencies reported by AIDS patients were also in IADLs. Mean CD4 counts were lower for persons reporting dependencies than for those who reported no dependencies (p = 0.02). No independent associations were found between functional limitation and demographic variables. The risk of death was greater in patients with dependencies than in patients with no dependencies, even when adjusting for CD4 count and AIDS diagnosis (O.R. = 2.32, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Protection by cysteine esters against chemically induced pulmonary oedema.

Perfluoroisobutene (PFIB) is a hydrophobic reactive gas produced by the pyrolysis of polytetrafluoroethane which induces pulmonary oedema similar to that induced by phosgene when inhaled. When a lethal dose is inhaled by Porton strain rats total non-protein thiol (NPSH) and glutathione (GSH) in the lung are reduced by between 30 and 49%, respectively. If the endogenous levels of thiols in the lung are reduced by pretreatment with buthionine sulfoximine (BSO) 16 hr before exposure to PFIB, the rats become more susceptible to the effects of the gas. The effect of BSO pretreatment on toxicity was prevented by pretreatment 30 min before exposure, with 5 mmol/kg N-acetylcysteine (NAc). NAc increased the levels of cysteine (CySH) in the lung by 150% and GSH was unaffected. Similarly pretreatment with 3 mmol/kg CySH also protected against toxicity and raised CySH levels by 100%. A series of cysteine esters and cystine dimethyl ester (CDME) have been synthesised which selectively raise lung levels of CySH in the rat lungs after intraperitoneal (i.p.) injection. The methyl ester and CDME raised lung levels of CySH by 4000 and 2000%, respectively, 10 min after i.p. injection whilst GSH levels remained unchanged. Cysteine isopropyl ester raised lung levels of CySH by 10,600% but liver levels by only 1400%. All esters except the t-butyl ester (CTBE) also raised maximal plasma levels of NPSH by up to 500%; however, when NAc was injected plasma levels increased by over 1500%. Rats treated with these esters at 3 mmol/kg and with NAc at 5 mmol/kg were protected against lethal doses of PFIB in all cases except when CTBE was used. It appears that these cysteine esters may distribute preferentially into the lung, unlike NAc. The selective enhancement of pulmonary CySH levels may provide a method for the protection of lungs against inhaled reactive toxicants by increasing intracellular CySH. Levels of CySH may also be raised in epithelial lining fluid thus reducing access of gaseous toxicants to pulmonary tissue.

Transforming growth factor-beta enhances the ultraviolet-mediated stress response in p53-/- keratinocytes.

Skin cancer is the most common tumor type in Caucasians, with an incidence that approaches the lifetime risk for all other cancer subtypes combined. The most common predisposing factor in the development of non-melanoma skin cancer is exposure to ultraviolet (UV) radiation in sun-light. UV radiation activates c-Jun amino-terminal kinases (JNK); this kinase pathway is involved in UV-mediated apoptosis and phosphorylation of c-Jun, all of which are part of the cellular stress response. Transforming growth factor-beta1 (TGF-beta1) is an important negative regulator of keratinocyte proliferation and has other pleiotropic effects in these cells. The purpose of these investigations was to decide whether TGF-beta1 activated c-Jun amino-terminal kinases in a spontaneously immortalized human keratinocyte cell line, HaCaT, and if TGF-beta1 modulated the activation of JNK in keratinocytes exposed to ultraviolet C (UVC) radiation. Results from these investigations showed that TGF-beta1 (10 ng/ml) activated JNK within 5 min. Pretreatment with TGF-beta1 enhanced UV-mediated JNK activation and was time- and UV-dose-dependent. Pretreatment with TGF-beta1 also enhanced activity of the c-Jun promoter-reporter construct, TRE(x5)-CAT. These results suggested that TGF-beta1 modulates the response of keratinocytes to ultraviolet radiation and implicates TGF-beta1 as a potential mediator the cellular of stress response in keratinocytes.

The impact of prophylaxis on outcome and resource utilization in Pneumocystis carinii pneumonia.

STUDY OBJECTIVE: Pneumocystis carinii pneumonia (PCP) is a major late complication of HIV infection associated with morbidity and mortality. Because chemoprophylaxis is highly effective, cases of PCP can be viewed as failures in the management of HIV disease. METHODS: We reviewed demographic, clinical, and cost data for all cases of confirmed HIV-related PCP at The Johns Hopkins Hospital in 1991 to determine consequences of missed prophylaxis. We also analyzed hospital discharge data for Maryland in 1991 to assess hospital charges, length of stay, and outcome for all patients with a principal diagnosis of HIV-related PCP. RESULTS: Pneumocystis carinii pneumonia was diagnosed in 79 patients. Of the 79 patients, 61 (77%) did not receive prophylaxis, including 26 who were not previously known to have HIV infection, 17 who did not have prophylaxis prescribed, and 18 who had prophylaxis prescribed, but were not compliant with the regimen. Patients not taking prophylaxis accounted for all 12 deaths ascribed to PCP. This group also accounted for 85% of the hospital days, 100% of the ICU days, and 89% of the inpatient charges. The total hospital charges were $849,540. Extrapolation of these figures for the state of Maryland suggest that the failure to receive prophylaxis in 1991 resulted in 62 patient deaths and a cost of approximately $4.7 million. CONCLUSION: Patients who developed PCP despite prophylaxis had a better outcome and used fewer resources than patients not receiving preventive therapy. This study emphasizes the impact of PCP prophylaxis on the morbidity, mortality, and economics of HIV health care.

NMR studies of a novel calcium, phosphate and fluoride delivery vehicle-alpha(S1)-casein(59-79) by stabilized amorphous calcium fluoride phosphate nanocomplexes.

The repair of early tooth enamel lesions has been recently demonstrated by tryptic phosphopeptides derived from milk caseins that associate with amorphous calcium phosphate (ACP) forming stable complexes. These casein phosphopeptides (CPP), containing the cluster sequence-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-, form calcium phosphate delivery vehicles that retard enamel demineralization and promote remineralization. Recently, we have shown that these peptides also stabilize calcium fluoride phosphate as soluble complexes. These complexes designated CPP-ACFP, have the potential to provide superior clinical efficacy in preventing dental caries and treating and repairing early stages of disease. In an approach to determine the ultrastructure of the casein phosphopeptide-amorphous calcium fluoride phosphate complexes, we have studied the structure of the predominant peptide alpha(S1)-CN(59-79) bound to ACFP using nuclear magnetic resonance (NMR) spectroscopy and X-ray diffraction. The alpha(S1)-CN(59-79) peptide stabilized calcium fluoride phosphate as amorphous nanocomplexes with a hydrodynamic radius of 2.12+/-0.26 nm. The nanocomplexes exhibited stoichiometry of one peptide to 15 calcium, nine phosphate and three fluoride ions. Sequence-specific resonance assignments were determined for the peptide alpha(S1)-CN(59-79) complexed to the ACFP. The secondary structure of the peptide alpha(S1)-CN(59-79) was characterized by sequential (i, i+1), medium-range (i, i+2) nOes and H alpha chemical shifts. The spectral data were compared with that of the peptide alpha(S1)-CN(59-79) bound to calcium ions, revealing that the structurally significant secondary NH and alpha-chemical shifts were similar.

Traumatic brain injury/chronic pain syndrome: a case comparison study.

OBJECTIVE: To identify the pretreatment characteristics and progress in treatment and outcomes of chronic pain patients, with and without concomitant traumatic brain injury (TBI). DESIGN AND PATIENTS: Retrospective cohort study of 12 consecutive patients in a chronic pain treatment program who were discovered to have previously untreated brain injury and a cohort of 12 chronic pain patients from the same program matched for age and sex who did not have brain injury. SETTING: Interdisciplinary university-based outpatient rehabilitation medicine clinic. MAIN OUTCOME MEASURES: Length of time in treatment and vocational outcomes. RESULTS: A surprising number of patients referred for treatment of chronic pain were found to have history and symptoms indicative of previously untreated or undiagnosed mild traumatic brain injury (n = 21 of 65). Of these, 12 received therapy for both their brain injury and chronic pain. The 12 treated, dual diagnosed patients did not differ in terms of education, employment status, or marital status from the chronic pain patients. Those with TBI were more likely to have sustained an automobile injury and less likely to have a work-related injury. On admission, 25% of each group were working, and at discharge, that proportion reached 75% for each group. Those with TBI required significantly longer treatment (459 consecutive days) from intake to discharge compared with the control group (295 days). CONCLUSION: Patients who exhibit memory or concentration problems, who express confusion about their diagnosis, who were injured in an automobile accident, or who complain of pain in the head, neck, or arms should be questioned about the possibility of concurrent TBI. Most of these patients can achieve successful employment outcomes, however, the TBI group may require a longer treatment time.

Evaluation of bone thickness in the anterior hard palate relative to midsagittal orthodontic implants.

PURPOSE: The Straumann Orthosystem (Institut Straumann, Waldenburg, Switzerland) describes a technique that involves placement of titanium implants (4 or 6 mm long and 3.3 mm in diameter) into the midsagittal hard palate for orthodontic anchorage. The aim of this study was to determine the quantity of bone in the midline of the anterior hard palate, and specifically the thickness inferior to the incisive canal. MATERIALS AND METHODS: Twenty-five dry skulls were radiographed with a standardized cephalometric technique. The vertical thickness of the midsagittal palate was then measured to the nearest tenth of a millimeter. Next, gutta-percha was injected into the incisive canal, and the radiograph was repeated. The bone thicknesses were then measured from the inferior hard palate to the most Inferior part of the radiopaque canal. This is defined as the actual bone available for the implant without violating the canal. RESULTS: The measurements have shown that an average of 8.6 +/- 1.3 mm of bone is theoretically available for the implant. However, considering the canal (where only bone thickness inferior to it is utilized and measured), only 4.3 +/- 1.6 mm of bone exists. The canal itself averaged 2.5 +/- 0.6 mm in diameter. DISCUSSION: Prior studies have overestimated the amount of bone available for implants in the median hard palate. The main reason for this is that the incisive canal is not well visualized on cephalometric radiographs of live patients. CONCLUSION: This study supports the continued use of implants, as approximately 50% of skulls still had the requisite minimum 4 mm of bone inferior to the incisive canal for maximum osseointegration with the 4-mm implants. However, 6-mm implants should be used with caution.