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Biomedical subjects

M Schultz

Publications and source records attributed to M Schultz.

At least 19 recordsLinked to original sources

Global air pollution crossroads over the Mediterranean.

The Mediterranean Intensive Oxidant Study, performed in the summer of 2001, uncovered air pollution layers from the surface to an altitude of 15 kilometers. In the boundary layer, air pollution standards are exceeded throughout the region, caused by West and East European pollution from the north. Aerosol particles also reduce solar radiation penetration to the surface, which can suppress precipitation. In the middle troposphere, Asian and to a lesser extent North American pollution is transported from the west. Additional Asian pollution from the east, transported from the monsoon in the upper troposphere, crosses the Mediterranean tropopause, which pollutes the lower stratosphere at middle latitudes.

Aerosols↗

Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease.

BACKGROUND: Insomnia with predominant thalamic involvement and minor cortical and cerebellar pathologic changes is not characteristic of familial Creutzfeldt-Jakob disease (CJD) but is a hallmark of fatal familial insomnia. OBJECTIVE: To report a 53-year-old woman with intractable insomnia as her initial symptom of disease. METHODS: The authors characterized clinical, pathologic, and molecular features of the disease using EEG, polysomnography, neurohistology, Western blotting, protein sequencing, and prion protein (PrP) gene (PRNP) analysis. RESULTS: The patient developed dysgraphia, dysarthria, bulimia, myoclonus, memory loss, visual hallucinations, and opisthotonos, as well as pyramidal, extrapyramidal, and cerebellar signs. Polysomnographic studies showed an absence of stages 3 and 4, and REM. She died 8 months after onset. On neuropathologic examination, there was major thalamic involvement characterized by neuronal loss, spongiform changes, and prominent gliosis. The inferior olivary nuclei exhibited chromatolysis, neuronal loss, and gliosis. Spongiform changes were mild in the neocortex and not evident in the cerebellum. PrP immunopositivity was present in these areas as well as in the thalamus. PRNP analysis showed the haplotype E200K-129M. Western blot analysis showed the presence of proteinase K (PK)-resistant PrP (PrP(sc)) with the nonglycosylated isoform of approximately 21 kd, corresponding in size to that of type 1 PrP(sc). N-terminal protein sequencing demonstrated PK cleavage sites at glycine (G) 82 and G78, as previously reported in CJD with the E200K-129 M haplotype. CONCLUSIONS: Insomnia may be a prominent early symptom in cases of CJD linked to the E200K-129M haplotype in which the thalamus is severely affected.

Amino Acid Sequence↗

A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 2 of 2): economic results.

OBJECTIVE: Viscosupplementation with hylan G-F 20 has recently become registered for treatment of patients with osteoarthritis (OA) of the knee in most parts of the world. The cost effectiveness and cost utility of this new therapeutic modality were determined as part of a Canadian prospective, randomized, 1-year, open-label, multicentered trial. DESIGN: A total of 255 patients were randomized to 'Appropriate care with hylan G-F 20' (AC+H) or 'Appropriate care without hylan G-F 20' (AC). Costs (1999 Canadian dollars) were collected from the societal viewpoint and included all costs related to OA of the knee and OA in all joints. Patients completed a number of outcomes questionnaires including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Health Utilities Index Mark 3 (HUI3). Data were collected at clinic visits (baseline, 12 months) and by telephone (1, 2, 4, 6, 8, 10, and 12 months). RESULTS: The AC+H group over the year had higher costs ($2125-$1415=$710, P< 0.05), more patients improved (69%-40%=29%,P =0.0001), greater increases in HUI3 (0.13-0.03=0.10, P< 0.0001) and increased quality-adjusted life years (QALYs) (0.071, P< 0.05). The incremental cost-effectiveness ratio was $2505/patient improved. The incremental cost-utility ratio was $10000/QALY gained. Sensitivity analyses and a second cost perspective gave similar results. CONCLUSION: The cost-utility ratio is below the suggested Canadian adoption threshold. The results provide strong evidence for adoption of treatment with hylan G-F 20 in the patients and settings studied in the trial.

Aged↗

A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results.

OBJECTIVE: First, to assess the clinical effectiveness of hylan G-F 20 in an appropriate care treatment regimen (as defined by the American College of Rheumatology (ACR) 1995 guidelines) as measured by validated disease-specific outcomes and health-related quality of life endpoints for patients with osteoarthritis (OA) of the knee. Second, to utilize the measures of effectiveness and costs in an economic evaluation (see accompanying manuscript). DESIGN: A total of 255 patients with OA of the knee were enrolled by rheumatologists or orthopedic surgeons into a prospective, randomized, open-label, 1-year, multi-centred trial, conducted in Canada. Patients were randomized to 'Appropriate care with hylan G-F 20' (AC+H) or 'Appropriate care without hylan G-F 20' (AC). Data were collected at clinic visits (baseline, 12 months) and by telephone (1, 2, 4, 6, 8, 10, and 12 months). RESULTS: The AC+H group was superior to the AC group for all primary (% reduction in mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale: 38% vs 13%,P =0.0001) and secondary effectiveness outcome measures. These differences were all statistically significant and exceeded the 20% difference between groups set a priori by the investigators as the minimum clinically important difference. Health-related quality of life improvements in the AC+H group were statistically superior for the WOMAC pain, stiffness and physical function (all P< 0.0001), the SF-36 aggregate physical component (P< 0.0001) and the Health Utilities Index Mark 3 (HUI3) overall health utility score (P< 0.0001). Safety (adverse events and patient global assessments of side effects) differences favoured the AC+H group. CONCLUSION: The data presented here indicate that the provision to patients with knee OA of viscosupplementation with hylan G-F 20 within an appropriate care treatment regimen provides benefits in the knee, overall health and health related quality of life at reduced levels of co-therapy and systemic adverse reactions.

Aged↗

Nature and extent of gastric lesions in symptomatic Chilean children with Helicobacter pylori-associated gastritis.

UNLABELLED: Chile has one of the highest rates of gastric cancer in the world and most children and adolescents in the country are colonized by Helicobacter pylori. This study assessed the nature and extent of the gastric lesions in 73 consecutive patients aged 5-17 y, referred for upper gastrointestinal endoscopy. Their H. pylori-associated gastric pathology was characterized and these data were compared with their sociodemographic status. Endoscopic assessment was normal in 43 patients while in 30 there was a variety of mucosal lesions. Sixty patients (83%) had histological chronic gastritis of the antrum and in 45 (63%) the lesions also involved the gastric corpus; 90% of patients with chronic gastritis were colonized by H. pylori. Although most of these patients had epithelial erosions and dedifferentiation of the pit epithelium, atrophy and metaplasia were not found. Patients' socioeconomic status was inversely correlated with their rate of colonization by H. pylori (p < 0.005), the frequency of gastric lesions on endoscopy (p < 0.01) and the frequency of involvement of antral and corpus mucosa by chronic gastritis (p < 0.002). This latter feature was positively correlated with age (p < 0.001). CONCLUSION: This study shows a high frequency of extensive lesions of H. pylori-associated chronic gastritis in young Chilean patients. This histological picture is consistent with the hypothesis of a H. pylori-associated progressive gastric pathology which may represent a major factor in the high local rate of gastric cancer.

Adolescent↗

Treatment of chronic renal allograft rejection in rats with a low-molecular-weight heparin (reviparin).

BACKGROUND: Low-molecular-weight heparin (LMWH) has been shown to prolong survival of rat cardiac allografts independently from immunosuppressive treatment. Furthermore, long-term treatment reduces the development of chronic graft vascular disease after experimental heart transplantation. The aim of the present study was to determine whether treatment with the LMWH reviparin has a beneficial effect on chronic rejection in a rat renal allograft model. METHODS: Kidneys of Fisher (F344) rats were transplanted into unilaterally nephrectomized Lewis (LEW) recipients. LEW-->LEW isografts served as controls. Animals were treated with cyclosporine (5 mg/kg/d) for the first 10 days. Nephrectomy of the remaining kidney was performed after 10 days. Allografted animals were treated either with reviparin (2 mg/kg/d subcutaneously) for 24 weeks (Allo-24), from week 12 to 24 (Allo-12), or with vehicle for 24 weeks. Proteinuria was determined at regular intervals. Kidneys were harvested after 24 weeks for histomorphological and immunohistochemical evaluation. RESULTS: No major bleeding complications were observed in reviparin-treated animals. Proteinuria was significantly reduced in allografted animals both by early as well as by late-onset treatment with reviparin. Transplant glomerulopathy was diminished in Allo-24 and in Allo-12 groups compared to vehicle-treated animals, whereas tubulointerstitial inflammation was influenced only in animals immediately treated with reviparin. Immunohistochemical studies demonstrated a marked reduction of renal monocyte and T-cell infiltration as well as expression of MHC II by treatment with reviparin. CONCLUSIONS: Treatment with the LMWH reviparin significantly improved chronic renal allograft rejection in the F344-to-LEW rat model, both after early and late start of therapy. Although the exact mechanisms of this beneficial effect remain unclear, our data offer a potential new therapeutical approach for prevention of chronic allograft nephropathy.

Animals↗

Paleohistopathology of bone: a new approach to the study of ancient diseases.

Light microscopy, particularly the use of polarized light, has such a high value for the differential diagnosis of dry bones that it can no longer be neglected. Alterations caused intra vitam by disease or other living conditions can clearly be differentiated by this technique from changes due to postmortem reactions (e.g., pseudopathology). As a reliable diagnosis is the basis not only of the study of case reports but also of the etiology and epidemiology of diseases in ancient populations, paleopathologists would be well-advised to employ histological analysis for their research, to avoid false diagnoses. The necessary basis for such research is the knowledge of the general histology, histogenesis, and growth as well as pathophysiology of bone. Some new techniques which facilitate the practical use of microscopic analysis, such as the preparation of thin-ground sections from undecalcified bone samples and nonrehydrated mummified soft tissues, are described. Selected examples of mechanisms of pathological bone changes, particularly the determination of vestiges of diseases in macerated bones by microscopy, are presented. Emphasis is placed on the differential diagnoses of proliferative reactions (e.g., periosteal processes of long bones and the skull). In this context, the importance of meningeal reactions on the endocranial lamina of the skull for morbidity and mortality in ancient populations is demonstrated. Furthermore, porotic hyperostosis of the skull vault and the orbital roof, i.e., the cribra cranii externa and cribra orbitalia, is discussed. Selected examples of the etiology and epidemiology of ancient diseases are presented (e.g., anemia, scurvy, rickets, and meningeal diseases), and ideas on living conditions and their implications for the origin and the spread of disease are given to establish a better understanding of deficiency and infectious diseases in the past.

Autolysis↗

Treatment costs for glioblastoma multiforme in Nova Scotia.

BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and malignant brain tumor in adults. The median survival in patients harboring this neoplasm is 12 months irrespective of any form of therapy. Health care costs of illnesses with high mortality rates, such as GBM, are of particular interest in times of constrained health care resources. No information regarding costs for the treatment of patients with GBM is available in Canada. The aim of this study was to conduct an analysis of the costs of treatment of GBM in Nova Scotia. METHODS: Patients with histologically proven GBM during a three year period (1996-1998) in Nova Scotia were included in the study. Analysis was based on hospital costs supplemented by data on additional medical services received following discharge for the primary intervention. RESULTS: The mean cost of medical care per patient from the time of diagnosis to death was $17,149. The highest costs were related to hospitalization with ward costs alone accounting for 48% of all costs. Radiotherapy costs were 25%, surgery costs were 16% and chemotherapy costs were 7% of all costs. Costs for diagnostic procedures were 6% of the total costs. CONCLUSION: Our data reflect the costs and practice pattern in the treatment of GBM in Nova Scotia and may be of value as an initial attempt to analyze costs of treatment of GBM in Canada.

Adult↗

Disrupted B-lymphocyte development and survival in interleukin-2-deficient mice.

Interleukin-2-deficient (IL-2-/-) mice develop a spontaneous, progressive, CD4+ T-cell-mediated colitis with an age-related decrease in the number of B lymphocytes. The aim of this study was to determine the mechanisms of B-cell loss in IL-2-/- mice. Serum immunoglobulin G1 (IgG1) levels in 8-week-old IL-2-/- mice were above normal but then decreased dramatically with advancing age. Between 8 and 11 weeks of age, the number of B-cell progenitors (B220+ IgM-) in the bone marrow of IL-2-/- mice was less than half of those in IL-2+/+ littermates. By 22 weeks of age, very few progenitor cells remained in the bone marrow of most mice, and spleens were almost devoid of B cells. Likewise, B1 cells were not present in the peritoneal cavity of aged IL-2-/- mice. Flow cytometry analysis of B-cell differentiation in the bone marrow suggested a progressive loss of B cells from the most mature to the least mature stages, which was not dependent on IL-2 receptor-alpha (IL-2Ralpha) expression. B cells transferred from normal animals had similar survival rates in IL-2-/- and wild-type mice. We conclude that conventional B cells in older IL-2-/- mice are lost by attrition owing to a derangement in B-cell development. Because B1 cells are less dependent on the bone marrow, a separate mechanism for their loss is suggested.

Animals↗

Nosocomial infection among immunosuppressed patients in the intensive care unit.

Advances in technology and development of multidrug-resistant antibiotics have increased the number of immunosuppressed patients in need of crisis care and the incidence of nosocomial infection in the nation's hospitals. Nosocomial infections are proving particularly difficult to prevent in intensive care units (ICUs), where special care must be taken to avoid transmission of any infection. The authors present an overview of this problem in the ICU, outlining basic measures to be taken in preventing nosocomial infections and ensuring the safety of the patients.

Cross Infection↗

Proinflammatory cytokine expression in gastric tissue from children with Helicobacter pylori-associated gastritis.

BACKGROUND: Helicobacter pyloriinfection of the gastric mucosa in humans is usually acquired early in life. The chronic inflammation that ensues involves the increased production of inflammatory cytokines. Published data on production of these mediators by gastric mucosa of H. pylori-infected children are few. METHODS: Seventy-nine children, aged 5 to 18 years, referred for upper gastrointestinal endoscopy to four separate hospitals in Chile, were studied. The concentrations of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor alpha were measured in homogenates of gastric mucosal biopsy specimens. Cytokine expression was confirmed by reverse transcription polymerase chain reaction. These data were correlated with the patients' clinical, histologic and sociodemographic status. RESULTS: Patient rate of colonization by H. pylori was inversely correlated with socioeconomic status (P < 0.005) and positively correlated with age (P < 0.0025). In gastric mucosa, concentrations of IL-1beta, IL-8, and tumor necrosis factor alpha were all significantly higher in H. pylori-positive patients than in H. pylori-negative patients and in patients who had histologic gastritis than in those with normal gastric mucosa. In patients with peptic ulcer disease, only IL-1beta and IL-8 concentrations were significantly elevated when compared with those of patients without ulcers. Interleukin-6 concentrations were comparable among the different groups analyzed. CONCLUSIONS: This study suggests that increased gastric mucosal production of the proinflammatory cytokines IL-1beta and IL-8 is probably involved in H. pylori-associated gastric damage in children and may be crucial in determining the different clinical outcomes.

Adolescent↗

Different subsets of enteric bacteria induce and perpetuate experimental colitis in rats and mice.

Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycin-imipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation.

Animals↗

Are the strategic stars aligned for your corporate brand?

In recent years, companies have increasingly seen the benefits of creating a corporate brand. Rather than spend marketing dollars on branding individual products, giants like Disney and Microsoft promote a single umbrella image that casts one glow over all their products. A company must align three interdependent elements--call them strategic stars--to create a strong corporate brand: vision, culture, and image. Aligning the stars takes concentrated managerial skill and will, the authors say, because each element is driven by a different constituency: management, employees, or stakeholders. To effectively build a corporate brand, executives must identify where their strategic stars fall out of line. The authors offer a series of diagnostic questions designed to reveal misalignments in corporate vision, culture, and image. The first set of questions looks for gaps between vision and culture; for example, when management establishes a vision that is too ambitious for the organization to implement. The second set addresses culture and image, uncovering possible gaps between the attitudes of employees and the perceptions of the outside world. The last set of questions explores the vision-image gap--is management taking the company in a direction that its stake-holders support? The authors discuss the benefits of a corporate brand, such as reducing marketing costs and building a sense of community among customers. But they also point to cases in which a corporate brand doesn't make sense--for instance, if you are a product incubator, if you've recently experienced M&A activity, or if you are expecting fallout from risky ventures.

Commerce↗

From a dry bone to a genetic portrait: a case study of sickle cell anemia.

The potential and reliability of DNA analysis for the identification of human remains are demonstrated by the study of a recent bone sample, which represented a documented case of sickle cell anemia. beta-globin gene sequences obtained from the specimen revealed homozygosity for the sickle cell mutation, proving the authenticity of the retrieved residual DNA. Further investigation of mitochondrial and Y chromosome DNA polymorphic markers indicated that this sample came from a male of maternal West African (possibly Yoruban) and paternal Bantu lineages. The medical record, which became available after the DNA analyses had been completed, revealed that it belonged to a Jamaican black male. These findings are consistent with this individual being a descendent of Africans brought to Jamaica during the trans-Atlantic slave trade. This study exemplifies how a "reverse population genetics" approach can be applied to reconstruct a genetic profile from a bone specimen of an unknown individual.

Africa↗

Probiotics and inflammatory bowel diseases.

The pathogenesis of inflammatory bowel diseases remains elusive. However, the resident luminal bacteria seem to be an important factor in their development and chronicity. There is evidence to suggest that inflammatory bowel diseases may represent an aggressive immunological response to the resident luminal flora, rather than an alteration in the normal flora. In prior research, probiotic bacteria were effective in managing certain acute diarrheal diseases, and investigators reported that certain Lactobacilli strains seem to have protective immunomodulating and bowel flora manipulating properties. We report the results of recent studies with probiotics in animal models, in which promising effects for the treatment of chronic inflammatory bowel disease, pouchitis, and ulcerative colitis were observed. Future research may clarify a precise role for probiotic bacteria in managing chronic inflammatory bowel diseases.

Animals↗

The effectiveness of 10% chlorhexidine varnish treatment on dental caries incidence in adults with dry mouth.

OBJECTIVES: This study compared a 10% chlorhexidine varnish treatment with placebo and sham treatments for preventing dental caries in adult patients with xerostomia (dry mouth). DESIGN: The study was a multicentred, randomized, parallel group, double blind, placebo-controlled clinical trial. SETTING: All examinations and procedures were performed at Tuft's University, Boston, MA, the University of British Columbia, Vancouver, BC or the University of Western Ontario, London, ON. SUBJECTS: Subjects were adults with recent or current dental caries experience, high salivary levels of cariogenic microorganisms and low salivary flow rates. RESULTS: 236 subjects completed at least one post-treatment examination. There were 697 new carious lesions diagnosed, 446 (64%) located on coronal surfaces and 251 (36%) located on root surfaces. The mean attack rate was 0.23 surfaces/100 surfaces at risk. A treatment difference observed between the Active and Placebo groups was statistically significant for root caries increment (p = .02) and total caries increment (p = .03). A treatment difference observed between the Active and Sham groups was not statistically significant for coronal, root or total caries increment. Analysis of variance of treatment group differences was performed using mutans streptococci counts, salivary flow rates, age, sex, caries prevalence, medications, time to first event and early withdrawal as co-variables. These factors did not meaningfully alter the findings. CONCLUSIONS: The difference between the 10% chlorhexidine varnish and placebo treatments is considered to be highly clinically significant for root caries increment (41% reduction) and for total caries increment (25% reduction) but only for coronal caries increment (14%).

Aged↗