The development and characterization of two types of chronic responses in irradiated mouse colon

The hypothesis to be tested is that there are two distinct types of chronic responses in irradiated normal tissues, each resulting from damage to different cell populations in the tissue. The first is a sequala of chronic epithelial depletion in which the tissue's integrity cannot be maintained, i.e. a "consequential" chronic response. The other response is due to cell loss in the connective tissue and/or vascular stroma, i.e. a "primary" chronic response. The purpose of this study was to test the hypothesis in the murine colon by first, establishing a model of each chronic response and then, by determining whether the responses differed in timing of expression, histology, and expression of specific collagen types. The model of late damage used was colonic obstructions/strictures induced by a single dose of 27 Gy ("consequential" response) and two equal doses of 14.75 Gy (t = 10 days) ("primary" response). "Consequential" lesions appeared as early as 5 weeks after 27 Gy and were characterized by a deep mucosal ulceration and a thickened fibrotic serosa containing excessive accumulations of collagen types I and III. Both types were commingled in the scar at the base of the ulcer. Fibroblasts were synthesizing pro-collagen types I and III mRNA 10 weeks prior to measurable increases in collagen. A significant decrease in the ratio of collagen types I:III was associated with the "consequential" response at 4-5 months post-irradiation. The "primary" response, on the other hand, did not appear until 40 weeks after the split dose even though the total dose delivered was approximately the same as that for the "consequential" response. The "primary" response was characterized with an intact mucosa and a thickened fibrotic submucosa which contained excessive amounts of only collagen type I. An increased number of fibroblasts were synthesizing pro-collagen type I mRNA nearly 25 weeks before collagen type I levels were increased. The "primary" response lesion had a significantly elevated collagen type I:III ratio at 10-13 months post-irradiation. These data show a clear difference between the two chronic response and suggest that not all chronic responses share a common pathogenesis, but depend on the cell population in the tissue that is damaged. ^

Contribution of activity and skin temperature to the risk of developing pressure ulcers in nursing facility residents

Purpose. The central concepts in pressure ulcer risk are exposure to external pressure caused by inactivity and tissue tolerance to pressure, a factor closely related to blood flow. Inactivity measures are effective in predicting pressure ulcer risk. The purpose of the study is to evaluate whether a physiological measure of skin blood flow improves pressure ulcer risk prediction. Skin temperature regularity and self-similarity, as proxy measures of blood flow, and not previously described, may be undefined pressure ulcer risk factors. The specific aims were to determine whether a sample of nursing facility residents at high risk of pressure ulcers classified using the Braden Scale for Pressure Sore Risk© differ from a sample of low risk residents according to (1) exposure to external pressure as measured by resident activity, (2) tissue tolerance to external pressure as measured by skin temperature, and (3) skin temperature fluctuations and recovery in response to a commonly occurring stressor, bathing and additionally whether (4) scores on the Braden Scale mobility subscale score are related to entropy and the spectral exponent. ^ Methods. A two group observational time series design was used to describe activity and skin temperature regularity and self-similarity, calculating entropy and the spectral exponent using detrended fluctuation analysis respectively. Twenty nursing facility residents wore activity and skin temperature monitors for one week. One bathing episode was observed as a commonly occurring stressor for skin temperature.^ Results. Skin temperature multiscale entropy (MSE), F(1, 17) = 5.55, p = .031, the skin temperature spectral exponent, F(1, 17) = 6.19, p = .023, and the activity mean MSE, F(1, 18) = 4.52, p = .048 differentiated the risk groups. The change in skin temperature entropy during bathing was significant, t(16) = 2.55, p = .021, (95% CI, .04-.40). Multiscale entropy for skin temperature was lowest in those who developed pressure ulcers, F(1, 18) = 35.14, p < .001.^ Conclusions. This study supports the tissue tolerance component of the Braden and Bergstrom conceptual framework and shows differences in skin temperature multiscale entropy between pressure ulcer risk categories, pressure ulcer outcome, and during a commonly occurring stressor. ^

Diagnosis of sexually transmitted infections in developing nations using syndromic management: Is it working?

Sexually transmitted infections (STIs) are a major public health problem, and controlling their spread is a priority. According to the World Health Organization (WHO), there are 340 million new cases of treatable STIs among 15–49 year olds that occur yearly around the world (1). Infection with STIs can lead to several complications such as pelvic inflammatory disorder (PID), cervical cancer, infertility, ectopic pregnancy, and even death (1). Additionally, STIs and associated complications are among the top disease types for which healthcare is sought in developing nations (1), and according to the UNAIDS report, there is a strong connection between STIs and the sexual spread of HIV infection (2). In fact, it is estimated that the presence of an untreated STI can increase the likelihood of contracting and spreading HIV by a factor up to 10 (2). In addition, developing countries are poorer in resources and lack inexpensive and precise diagnostic laboratory tests for STIs, thereby exacerbating the problem. Thus, the WHO recommends syndromic management of STIs for delivering care where lab testing is scarce or unattainable (1). This approach utilizes the use of an easy to use algorithm to help healthcare workers recognize symptoms/signs so as to provide treatment for the likely cause of the syndrome. Furthermore, according to the WHO, syndromic management offers instant and legitimate treatment compared to clinical diagnosis, and that it is also more cost-effective for some syndromes over the use of laboratory testing (1). In addition, even though it has been shown that the vaginal discharge syndrome has low specificity for gonorrhea and Chlamydia and can lead to over treatment (1), this is the recommended way to manage STIs in developing nations. Thus, the purpose of this paper is to specifically address the following questions: is syndromic management working to lower the STI burden in developing nations? How effective is it, and should it still be recommended? To answer these questions, a systematic literature review was conducted to evaluate the current effectiveness of syndromic management in developing nations. This review examined published articles over the past 5 years that compared syndromic management to laboratory testing and had published sensitivity, specificity, and positive predicative value data. Focusing mainly on vaginal discharge, urethral discharge, and genital ulcer algorithms, it was seen that though syndromic management is more effective in diagnosing and treating urethral and genial ulcer syndromes in men, there still remains an urgent need to revise the WHO recommendations for managing STIs in developing nations. Current studies have continued to show decreased specificity, sensitivity and positive predicative values for the vaginal discharge syndrome, and high rates of asymptomatic infections and healthcare workers neglecting to follow guidelines limit the usefulness of syndromic management. Furthermore, though advocate d as cost-effective by the WHO, there is a cost incurred from treating uninfected people. Instead of improving this system, it is recommended that better and less expensive point of care and the development of rapid test diagnosis kits be the focus and method of diagnosis and treatment in developing nations for STI management. ^

Efforts of hospital system wound care teams to reduce hospital acquired pressure ulcers

New reimbursement policies developed by the Centers for Medicare and Medicaid Services (CMS) are revolutionizing the health care landscape in America. The policies focus on clinical quality and patient outcomes. As part of the new policies, certain hospital acquired conditions have been identified by Medicare as "reasonably preventable". Beginning October 1, 2008, Medicare will no longer reimburse hospitals for these conditions developed after admission, pressure ulcers are among the most common of these conditions.^ In this practice-based culminating experience the objective was to provide a practical account of the process of program development, implementation and evaluation in a public health setting. In order to decrease the incidence of pressure ulcers, the program development team of the hospital system developed a comprehensive pressure ulcer prevention program using a "bundled" approach. The pressure ulcer prevention bundle was based on research supported by the Institute for Healthcare Improvement, and addressed key areas of clinical vulnerability for pressure ulcer development. The bundle consisted of clinical processes, policies, forms, and resources designed to proactively identify patients at risk for pressure ulcer development. Each element of the bundle was evaluated to ensure ease of integration into the workflow of nurses and clinical ancillary staff. Continued monitoring of pressure ulcer incidence rates will provide statistical validation of the impact of the prevention bundle. ^

Secondary analysis of effectivness of tinidazole-containing-quadruple eradication therapy in asymptomatic H. pylori infected children in El Paso

Helicobacter pylori infection is frequently acquired during childhood. This microorganism is known to cause gastritis, and duodenal ulcer in pediatric patients, however most children remain completely asymptomatic to the infection. Currently there is no consensus in favor of treatment of H. pylori infection in asymptomatic children. The firstline of treatment for this population is triple medication therapy including two antibacterial agents and one proton pump inhibitor for a 2 week duration course. Decreased eradication rate of less than 75% has been documented with the use of this first-line therapy but novel tinidazole-containing quadruple sequential therapies seem worth investigating. None of the previous studies on such therapy has been done in the United States of America. As part of an iron deficiency anemia study in asymptomatic H. pylori infected children of El Paso, Texas, we conducted a secondary data analysis of study data collected in this trial to assess the effectiveness of this tinidazole-containing sequential quadruple therapy compared to placebo on clearing the infection. Subjects were selected from a group of asymptomatic children identified through household visits to 11,365 randomly selected dwelling units. After obtaining parental consent and child assent a total of 1,821 children 3-10 years of age were screened and 235 were positive to a novel urine immunoglobulin class G antibodies test for H. pylori infection and confirmed as infected using a 13C urea breath test, using a hydrolysis urea rate >10 μg/min as cut-off value. Out of those, 119 study subjects had a complete physical exam and baseline blood work and were randomly allocated to four groups, two of which received active H. pylori eradication medication alone or in combination with iron, while the other two received iron only or placebo only. Follow up visits to their houses were done to assess compliance and occurrence of adverse events and at 45+ days post-treatment, a second urea breath test was performed to assess their infection status. The effectiveness was primarily assessed on intent to treat basis (i.e., according to their treatment allocation), and the proportion of those who cleared their infection using a cut-off value >10 μg/min of for urea hydrolysis rate, was the primary outcome. Also we conducted analysis on a per-protocol basis and according to the cytotoxin associated gene A product of the H. pylori infection status. Also we compared the rate of adverse events across the two arms. On intent-to-treat and per-protocol analyses, 44.3% and 52.9%, respectively, of the children receiving the novel quadruple sequential eradication cleared their infection compared to 12.2% and 15.4% in the arms receiving iron or placebo only, respectively. Such differences were statistically significant (p<0.001). The study medications were well accepted and safe. In conclusion, we found in this study population, of mostly asymptomatically H. pylori infected children, living in the US along the border with Mexico, that the quadruple sequential eradication therapy cleared the infection in only half of the children receiving this treatment. Research is needed to assess the antimicrobial susceptibility of the strains of H. pylori infecting this population to formulate more effective therapies. ^

Prevalence of gastro esophageal reflux disease following the Montreal Consensus and its association with Helicobacter pylori infection and obesity in a random sample of adults of Ciudad Juarez, Mexico, 2004.

Gastroesophageal reflux disease is a common condition affecting 25 to 40% of the population and causes significant morbidity in the U.S., accounting for at least 9 million office visits to physicians with estimated annual costs of $10 billion. Previous research has not clearly established whether infection with Helicobacter pylori, a known cause of peptic ulcer, atrophic gastritis and non cardia adenocarcinoma of the stomach, is associated with gastroesophageal reflux disease. This study is a secondary analysis of data collected in a cross-sectional study of a random sample of adult residents of Ciudad Juarez, Mexico, that was conducted in 2004 (Prevalence and Determinants of Chronic Atrophic Gastritis Study or CAG study, Dr. Victor M. Cardenas, Principal Investigator). In this study, the presence of gastroesophageal reflux disease was based on responses to the previously validated Spanish Language Dyspepsia Questionnaire. Responses to this questionnaire indicating the presence of gastroesophageal reflux symptoms and disease were compared with the presence of H. pylori infection as measured by culture, histology and rapid urease test, and with findings of upper endoscopy (i.e., hiatus hernia and erosive and atrophic esophagitis). The prevalence ratio was calculated using bivariate, stratified and multivariate negative binomial logistic regression analyses in order to assess the relation between active H. pylori infection and the prevalence of gastroesophageal reflux typical syndrome and disease, while controlling for known risk factors of gastroesophageal reflux disease such as obesity. In a random sample of 174 adults 48 (27.6%) of the study participants had typical reflux syndrome and only 5% (or 9/174) had gastroesophageal reflux disease per se according to the Montreal consensus, which defines reflux syndromes and disease based on whether the symptoms are perceived as troublesome by the subject. There was no association between H. pylori infection and typical reflux syndrome or gastroesophageal reflux disease. However, we found that in this Northern Mexican population, there was a moderate association (Prevalence Ratio=2.5; 95% CI=1.3, 4.7) between obesity (≥30 kg/m2) and typical reflux syndrome. Management and prevention of obesity will significantly curb the growing numbers of persons affected by gastroesophageal reflux symptoms and disease in Northern Mexico. ^

A cohort study of occupational asbestos-exposure related neoplasms in Texas Gulf Coast area

A cohort study was conducted in Texas and Louisiana Gulf Coast area on individual workers who have been exposed to asbestos for 15 years or more. Most of these workers were employed in petrochemical industries. Of the 15,742 subjects initially selected for the cohort study, 3,258 had positive chest X-ray findings believed to be related to prolonged asbestos exposure. These subjects were further investigated. Their work out included detailed medical and occupational history, laboratory tests and spirometry. One thousand eight-hundred and three cases with positive chest X-ray findings whose data files were considered complete at the end of May 1986 were analyzed and their findings included in this report.^ The prevalence of lung cancer and cancer of the following sights: skin, stomach, oropharyngeal, pancreas and kidneys were significantly increased when compared to data from Connecticut Tumor Registry. The prevalence of other chronic conditions such as hypertension, emphysema, heart disease and peptic ulcer was also significantly high when compared to data for the U.S. and general population furnished by the National Center for Health Statistics (NCHS). In most instances the occurrence of cancer and the chronic ailment previously mentioned appeared to follow 15-25 years of exposure to asbestos. ^

William Osler: Original Papers 1881-1897

Part 1: 1881-1888 On Some Points in the Etiology and Pathology of Ulcerative Endocarditis, 1881 On Certain Parasites in the Blood of the Frog, 1883 The Third Corpuscle of the Blood, 1883 On the Use of Arsenic in Certain Forms of Anaemia, 1886 Antifebrin, 1887 Case of Arterio-Venous Aneurism of the Axillary Artery and Vein of Fourteen Year's Duration, 1887 Typhilitis and Appendicitis, 1888 Part 2: 1889-1892 Annual Address - License to Practice 1889 Case of Syphiloma of the Cord of the Cauda Equina-Death From Diffuse Central Myelitis, 1889 On a Case of Simple Idiopathic Muscular Atrophy, Involving the Face and the Scapulo-Humeral Muscles, 1889 Note on Intra-Thoracic Growths Developing from the Thyroid Gland, 1889 On the Value of Laveran's Organisms in the Diagnosis of Malaria, 1889 On the Form of Convulsive Tic Associated with Corprolalia, Etc., 1890 A Case of Sensory Aphasia Word-blindness with Hemianopsia, 1891 Rudolf Virchow: The Man and the Student, 1891 The Healing of Tuberculosis, 1892 The Cold-Bath Treatment of Typhoid Fever, 1892 Part 3: 1893 Remarks on the Varieties of Chronic Chorea, and a Report Upon Two Families of the Hereditary Form, With One Autopsy, 1893 Note on Arsenical Neuritis Following the use of Fowler's Solution, 1893 Note on a Remarkable House Epidemic of Typhoid Fever, 1893 Cases of Sub-Phrenic Abscess, 1893 On Sporadic Cretinism in America, 1893 Notes on Tuberculosis in Children, 1893 Part 4: 1849-1895 Parotitis in Pneumonia, Case of Pericarditis Treated by Incision and Drainage, 1894 The Army Surgeon, 1894 Introductory Remarks to Course of Clinical Demonstrations on Typhoid Fever, 1894 Cancer of the Stomach with Very Rapid Course, 1895 Case of Sporadic Cretinism (Infantile Myxcedema) Treated Successfully with Thyroid Extract, 1895 Visible Contractile Tumour of the Pylorus Following Ulcer of the Stomach, 1895 On the Association of Enormous Heart Hypertrophy, Chronic Proliferative Peritonitis, and Recurring Ascites, with Adherent Pericardium, 1895 Teaching and Thinking the Two Functions of a Medical School, 1895 The Practical Value of Laveran's Discoveries, 1895 Part 5 1896 Addison's Disease, 1896 On Six Cases of Addison's Disease, 1896 Hemiplegia in Typhoid Fever Thomas Dover (of Dover's Powder) Physician and Buccaneer, 1896 John Keats The Apothecary Poet, 1896 On The Classification of the Tics or Habit Movements, 1896 The Cerebral Complication of Raynaud's Disease, 1896 Part 6: 1897 On Certain Features in the Prognosis of Pneumonia, 1897 Clinical Lecture on Mitral Stenosis - Sudden Death - Ball Thrombus in the Left Auricle, 1897 The Diagnosis of Malarial Fever, 1897 The Functions of a State Faculty (President's Address), 1897 A Clinical Lecture on The Ball-Valve Gall-Stone in the Common Duct, 1897 Pneumonia (Review of Cases studied), 1897 Internal Medicine as a Vocation, 1897 Back Notes

The influence of antibacterial susceptibility and pharmacodynamics on the therapeutic response of infection

This prospective cohort study estimated how antibacterial resistance affected the time until clinical response. Relative rates of improvement and cure were estimated by proportional-hazards regression for 391 patients with culture-confirmed bacterial keratitis who had the ciprofloxacin minimal inhibitory concentration (MIC) measured of the principal corneal isolate and who were treated with ciprofloxacin 0.3% solution or ointment. After adjusting for age and hypopyon status and stratifying by ulcer size, clinic, and ciprofloxacin formulation, the summary rate of clinical improvement with ciprofloxacin therapy was reduced by 42% (95% confidence limits [CL], 3%, 65%) among patients whose corneal isolate's ciprofloxacin MIC exceeded 1.0 μg/mL compared to those with more sensitive isolates. The summary rate of resolution to improvement and cure was reduced by 36% (95% CL, 11%, 53%) among corneal infections having a higher ciprofloxacin MIC. Rate ratios were modified by the size of the presenting corneal ulceration; for ulcer diameters of 4 mm or less and of more than 4 mm, improvement rate ratios were 0.56 (95% CL, 0.31, 1.02) and 0.65 (95% CL, 0.23, 1.80), respectively; resolution rate ratios were 0.63 (95% CL, 0.44, 0.91) and 0.67 (95% CL, 0.32, 1.39), respectively. Sensitivity analysis showed that the summary improvement rate ratio could be maximally overestimated by 24% (95% CL, −29%, 114%) because of informative censoring or by 33% (95% CL, −21%, 126%) from loss to follow up. Based on reported corneal pharmacokinetics of topical ciprofloxacin, the probability of clinical improvement was 90% or more if the ratio of the achievable corneal ciprofloxacin concentration to the corneal isolate's ciprofloxacin MIC was above 8 or the ratio of the area under the 24-hour corneal concentration curve to the ciprofloxacin MIC was greater than 151. This study suggests that corneal infections by bacteria having a higher ciprofloxacin MIC respond more slowly to ciprofloxacin treatment than those with a lower MIC. While the rate of clinical resolution is affected by patient age and clinical severity, antimicrobial susceptibility testing of corneal cultures can indicate the relative effectiveness of antibacterial therapy. A pharmacodynamic approach to treating bacterial keratitis offers the prospect of optimal antimicrobial selection and modification. ^