The development of vaccination perspectives among chiropractic, naturopathic and medical students: a case study of professional enculturation.

An important influence on parents' decisions about pediatric vaccination (children under 6 years of age) is the attitude of their health care providers, including complementary and alternative medicine (CAM) providers. Very limited qualitative research exists, however, on how attitudes towards vaccination develop among healthcare professionals in-training. We explored perspective development among three groups of students: medical, chiropractic, and naturopathic. We conducted focus group sessions with participants from each year of study at three different healthcare training programs in Ontario, Canada. Semi-structured and open-ended questions were used to elicit dynamic interaction among participants and explore how they constructed their attitudes toward vaccination at the beginning and part way through their professional training. Analyses of verbatim transcripts of audiotaped interviews were conducted both inductively and deductively using questions structured by existing literature on learning, professional socialization and interprofessional relations. We found five major themes and each theme was illustrated with representative quotes. Numerous unexpected insights emerged within these themes, including students' general open-mindedness towards pediatric vaccination at the beginning of their training; the powerful influence of both formal education and informal socialization; uncritical acceptance of the vaccination views of senior or respected professionals; students' preference for multiple perspectives rather than one-sided, didactic instruction; the absence of explicit socio-cultural tensions among professions; and how divergences among professional students' perspectives result from differing emphases with respect to lifestyle, individual choice, public health and epidemiological factors-rather than disagreement concerning the biomedical evidence. This last finding implies that their different perspectives on pediatric vaccination may be complementary rather than irreconcilable. Our findings should be considered by developers of professional and interprofessional educational curricula and public health officials formulating policy on pediatric vaccination.

Three-dimensional computed tomography for determination of femoral anteversion in a cerebral palsy model.

BACKGROUND: Previous investigation has proven 3-dimensional (3D) computed tomography (CT) to be a poor method of assessing femoral anteversion in patients with cerebral palsy. However, new advancements in CT software yield the potential to improve upon those dated results. METHODS: CT was performed on 9 femoral models with varying amounts of anteversion (20 to 60 degrees) and varying neck-shaft angles (120 to 160 degrees). Each model was scanned in 2 holding devices. One holder placed the femur in an ideal position relative to the gantry. The other placed the femur in flexion, adduction, and internal rotation simulating a common lower extremity posture in cerebral palsy. Femoral anteversion was measured on 3D reconstructions by 4 observers on 2 separate occasions. Interobserver and intraobserver reliability, accuracy, and the effect of increasing neck-shaft angle of the measurements were examined and compared with previously published data using the same models. RESULTS: Pearson correlation coefficients between first and second measurements by the same examiner were all above 0.96 regardless of positioning of the femur in the gantry. The correlation coefficients among all examiners were 0.97 regardless of positioning of the femur in the gantry. Accuracy in measurements was comparable using 3D CT techniques with mean differences between the normal and cerebral palsy-positioned models of <3.6 degrees (SD, 3.1 to 3.3 degrees). Accuracy of the study's 3D CT technique in measuring femoral anteversion in cerebral palsy-positioned femurs was significantly more accurate than that of 2D CT (P<0.0001). CONCLUSIONS: Recent improvements in processing software and 3D reconstruction have made assessment of femoral anteversion with 3D CT accurate through the studied range of anteversion and neck-shaft angles. Using this technique, high intraobserver and interobserver reliability in the determination of femoral anteversion can be expected regardless of neck-shaft angle or postural deformity. LEVEL OF EVIDENCE: Level II.

Enhancing the Measure of Participation Burden in Protocol Design to Incorporate Logistics, Lifestyle, and Demographic Characteristics.

BACKGROUND: Growing interest in improving patient participation convenience and the feasible execution of clinical trials has increased demand for new approaches to leverage patient input in the protocol design process. METHODS: This study builds on prior work conducted by the Tufts Center for the Study of Drug Development in collaboration with ZS. A comprehensive participant burden algorithm based on protocol procedures, participation requirements and lifestyle preferences was developed and tested. Clinical trial preferences and perceptions from 3002 global patients were analyzed to inform and derive the algorithm. It was next tested against a convenience sample of 266 completed protocols. Descriptive statistics, significance tests, and regression analyses were performed. RESULTS: Mean participant burden scores were highly associated with, and predictive (p < 0.01) of, screen failure rates, overall clinical trial duration and the number of substantial protocol amendments; and predictive (p < 0.05) of protocol treatment duration. Of 11 subgroups assessed, those that most influenced the algorithm and drove higher overall burden scores included disease condition, caregiver reliance, race, prior experience as a clinical trial participant and participant age. Geographic area and participant sex showed only minimal influence. CONCLUSION: This study presents advancement and refinement in measuring participation burden that will assist drug development teams and protocol authors in retrospectively understanding clinical trial performance outcomes and in prospectively informing protocol design decisions.

Rosacea: a review of current topical, systemic and light-based therapies.

Rosacea is a common chronic inflammatory disorder of the facial skin characterized by periods of exacerbation, remission and possible progression. The principle subtypes include erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea and ocular rosacea. Although the pathogenesis is unknown, rosacea is largely recognized as an inflammatory disorder. Individual subtypes are likely a result of different pathogenic factors and respond best to different therapeutic regimens. The non-pharmacologic approach to therapy is adequate skin care, trigger avoidance and photoprotection; in addition, there are several topical, herbal, systemic and light based therapies available. Standard Food and Drug Administration (FDA) approved treatments include topical sodium sulfacetamide, metronidazole, and azelaic acid. Anti-inflammatory dose doxycycline, a controlled-release 40 mg formulation offers a non-antibiotic, anti-inflammatory treatment option. Combination of azelaic acid or topical metronidazole with anti-inflammatory doxycycline appears to have a synergistic effect. Oral isotretinoin may be effective for phymatous rosacea and treatment resistant rosacea. Light based therapies with pulsed dye laser and intense pulsed light are effective in treatment of erythema and telangiectasias. As our knowledge of rosacea and its therapeutic options expand, a multifaceted approach to treatment is warranted.

Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I.

Mutations in the human gene encoding cadherin23 (CDH23) cause Usher syndrome type 1D (USH1D) and nonsyndromic hearing loss. Individuals with Usher syndrome type I have profound congenital deafness, vestibular areflexia and usually begin to exhibit signs of RP in early adolescence. In the present study, we carried out the mutation analysis in all 69 exons of the CDH23 gene in 56 Usher type 1 probands already screened for mutations in MYO7A. A total of 18 of 56 subjects (32.1%) were observed to have one or two CDH23 variants that are presumed to be pathologic. Twenty one different pathologic genome variants were observed of which 15 were novel. Out of a total of 112 alleles, 31 (27.7%) were considered pathologic. Based on our results it is estimated that about 20% of patients with Usher syndrome type I have CDH23 mutations.

Pathophysiology of acute acid injury in rabbit esophageal epithelium.

To increase our understanding of the pathophysiology of reflux esophagitis, we sought the early sequence of changes in mucosal structure and function in acutely acid-damage rabbit esophagus. Using a perfused catheter technique esophageal potential difference (PD) profiles were obtained in anesthetized rabbits before, during, and after perfusion of the lower one-half of the esophagus with phosphate-buffered saline or 80 mM NaCl. When acid perfusion reduced the lower esophageal PD by 40-50% or 80-100% of the initial values, the esophagus was removed, sectioned, and the mucosa studied with light microscopy, transmission electron microscopy, and Ussing chamber technique for evaluation of sodium and mannitol transport. The earlier stage of acid damage (PD 40-50%) was associated with reduced mucosal resistance fom 2,180 +/- 199 to 673 +/- 157 ohm cm2 and increased passive transport of sodium (0.10 +/- 0.06 to 1.82 +/- 0.48 microeq/h.cm2) and mannitol (0.008 +/- 0.003 to 0.051 +/- 0.012 microM/h.cm2) (p less than 0.05). There was no significant change in shirt circuit current (0.35 +/- 0.05 to 0.35 +/- 0.04) or net sodium transport (0.32 +/- 0.06 to 0.37 +/- 0.12) at this stage, and the only morphologic finding was dilated intercellular spaces on electron microscopy. The later stage of acid damage (PD 80-100%) exhibited a further reduction in resistance to 299 +/- 65 ohm.cm2 (p less than 0.05), a finding now accompanied by a reduction in short circuit current (0.35 +/- 0.05 to 0.21 +/- 0.04 microeq/h.cm2) and complete inhibition of net sodium transport (0.32 +/- 0.06 to 0.01 +/- 0.13) (p less than 0.05). Morphologic studies at this time revealed cellular necrosis, edema, and vesicle formation in the stratum spinosum. Both gross mucosal changes and transmural necrosis were notably absent. When esophageal perfusion was performed with a combination of acid (80 mM HCl-80 mM NaCl) and pepsin (100 microgram/ml), the morphologic and physiologic findings were essentially the same as with acid alone; however, the time of perfusion to reach either the 50 or 100% reduction in PD was shortened. The findings in this model can be explained on an initial increase in cellular and/or paracellular permeability followed by inhibition of active sodium transport. The resulting loss of osmolar regulation leads to cell necrosis in the stratum spinosum.

Chronic hypertension and altered baroreflex responses in transgenic mice containing the human renin and human angiotensinogen genes.

We have generated a transgenic model consisting of both the human renin and human angiotensinogen genes to study further the role played by the renin-angiotensin system in regulating arterial pressure. Transgenic mice containing either gene alone were normotensive, whereas mice containing both genes were chronically hypertensive. Plasma renin activity and plasma angiotensin II levels were both markedly elevated in the double transgenic mice compared with either single transgenic or nontransgenic controls. The elevation in blood pressure caused by the human transgenes was independent of the genotype at the endogenous renin locus and was equal in mice homozygous for the Ren-1c allele or in mice containing one copy each of Ren-1c, Ren-1d, or Ren-2. Chronic overproduction of angiotensin II in the double transgenic mice resulted in a resetting of the baroreflex control of heart rate to a higher pressure without significantly changing the gain or sensitivity of the reflex. Moreover, this change was not due to the effects of elevated pressure itself since angiotensin-converting enzyme inhibition had minimal effects on the baroreflex in spontaneously hypertensive BPH-2 control mice, which exhibit non-renin-dependent hypertension. This double transgenic model should provide an excellent tool for further studies on the mechanisms of hypertension initiated by the renin-angiotensin system.

The prevalence of two 'commonly' encountered synthetic target fibres within a large urban environment.

A target fibre study was carried out to assess the random prevalence of two ostensibly commonly encountered synthetic fibre types; black acrylic and blue polyester. The study was performed in an environment which maximised the number of random contacts between textile garments in the population and specific surfaces, namely; seating relating to buses, public houses and cinemas found within a large urban conurbation. Surface debris tapings were collected from samples of bus seats (30), pub seats (54) and cinema seats (53). Using low power stereomicroscopy, a total of 114 and 68 fibres, superficially similar to the respective black acrylic and blue polyester target fibres, were recovered from these tapings. The full range of comparative microscopical and instrumental analysis used in operational forensic laboratories was performed on the recovered fibres. No matches were found with either of the target fibres. These findings are in accordance with similar studies which show that the probability of an 'adventitious' match with a particular fibre type/colour combination is extremely low. In addition, the findings demonstrate that the current techniques and instrumentation employed by operational forensic laboratories are fit for purpose. Importantly, the findings demonstrate that databases and surveys (e.g. fibre population studies) which do not consider the analytical/comparison processes, must not be used in isolation when evaluating fibre evidence at source level.

Conjugal loss and syndromal depression in a sample of elders aged 70 years or older.

OBJECTIVE: The goal of this study was to describe the association between conjugal loss and both syndromal depression and depressive symptoms in a prospective cohort study of people aged 70 years or older. METHOD: A measure of syndromal depression, the shortform Composite International Diagnostic Interview (CIDI), and a revised version of the Center for Epidemiologic Studies--Depression Scale (CES-D Scale) were administered to a group of 5,449 elders in a longitudinal cohort study. The authors compared the rates of syndromal depression (CIDI diagnosis) and depressive symptoms (six CES-D Scale symptoms) in married participants and those who lost spouses between the first and second waves of assessment. RESULTS: The rate of syndromal depression in the newly bereaved was nearly nine times as high as the rate for married individuals, and the rate of depressive symptoms was nearly four times as high. The percentage of the bereaved respondents who had scores above threshold on the revised CES-D Scale was higher for those interviewed up to 2 years after loss of a spouse than for married respondents. Age, sex, prior psychiatric history, and the expectedness of the death did not differ between depressed and nondepressed newly bereaved subjects. CONCLUSIONS: Recent bereavement is a significant risk factor for syndromal depression in the elderly. Some widows and widowers experienced high levels of depressive symptoms up to 2 years after the loss of their spouses. Neither demographic variables nor variables concerning the nature of the spouse's death predicted bereavement-related depression.

Delayed complications from fine-needle biopsies of solid masses of the abdomen.

A prospective study was conducted from 1977 through 1983, to determine the incidence of complications, particularly bleeding, after fine needle biopsy for suspected malignancy of the abdomen and pelvis. Hematocrits before and after the biopsy procedure, medical record follow-up, and review by a coagulation specialist were used to identify bleeders. We performed 395 biopsies on 360 patients. Thirteen percent of the patients had bothersome pain either during or after the biopsy. Hematocrit drops of 3% or more were found in 51 (12.7%) of the patients; nine were determined to be a direct result of the biopsy procedure. Our results and review of the literature suggest that there are complications, including delayed bleeding, yet few are life threatening. We caution, however, that adequate follow-up to identify bleeders is very important in patients having fine-needle biopsies of solid masses of the abdomen.

Cytologic criteria for the diagnosis of pancreatic carcinoma.

Fine-needle aspiration and endoscopic aspiration of pancreatic cells permit the diagnosis of pancreatic carcinoma and avoid the complications and morbidity of pancreatic biopsy. In this study, the accuracy of fine-needle and endoscopic aspiration were compared, and cytologic criteria for pancreatic carcinoma were sought. Pancreatic cytologic preparations from 79 patients, including 39 fine-needle aspirates and 48 endoscopic aspirates, were retrospective reviewed. When compared with definitive tissue diagnosis or clinical course, fine-needle aspiration had a sensitivity for pancreatic carcinoma of 79%. Endoscopic aspiration of pancreatic secretions had a sensitivity of only 33%. There was a single falsely suspicious fine-needle aspirate, but there were no false positive diagnoses when using either collection technic. Seventeen cytologic features were examined to determine cytologic criteria of malignancy. The presence of disoriented or crowded cells in three-dimensional groups, and extreme nuclear enlargement combined with nuclear contour irregularity were the best criteria for pancreatic malignancy.

"Walk in to Work Out": a randomised controlled trial of a self help intervention to promote active commuting.

STUDY OBJECTIVE: To determine if a self help intervention, delivered via written interactive materials (the "Walk in to Work Out" pack), could increase active commuting behaviour (walking and cycling). DESIGN: Randomised controlled trial. The intervention group received the "Walk in to Work Out" pack, which contained written interactive materials based on the transtheoretical model of behaviour change, local information about distances and routes, and safety information. The control group received the pack six months later. Focus groups were also conducted after six months. SETTING: Three workplaces in the city of Glasgow, Scotland, UK. PARTICIPANTS: 295 employees who had been identified as thinking about, or doing some irregular, walking or cycling to work. MAIN RESULTS: The intervention group was almost twice as likely to increase walking to work as the control group at six months (odds ratio of 1.93, 95% confidence intervals 1.06 to 3.52). The intervention was not successful at increasing cycling. There were no distance travelled to work, gender, or age influences on the results. Twenty five per cent (95% confidence intervals 17% to 32%) of the intervention group, who received the pack at baseline, were regularly actively commuting at the 12 month follow up. CONCLUSION: The "Walk in to Work Out" pack was successful in increasing walking but not cycling. The environment for cycling must be improved before cycling will become a popular option.

Eating disorders. Guide to medical evaluation and complications.

Eating disorders lead to numerous physical complaints with signs and symptoms affecting nearly every organ system of the body. We review the presentation of a patient with eating disorder to the primary care giver or general psychiatrist, focusing on the physical manifestations of the underlying illness. Specific complications related to laboratory findings, the gastrointestinal tract, and the endocrine system are reviewed. Algorithms for medical evaluation of these patients are also presented.

Platelet volume is not increased in essential hypertension.

Platelet size, a determinant of platelet function, is a newly emerging risk factor for atherothrombosis. Platelet volume has previously been shown, using less than ideal methodology, to be increased in essential hypertension. Mean platelet volume was measured in 38 patients with essential hypertension and 38 paired normotensive control subjects matched for age and sex. Platelet volume, median (interquartile ranges) 7.7 (7.2-8.5) fl vs. 7.8 (7.5-8.4) fl (2P = 0.40), platelet count 242 (220-288) x 10(9)/l vs. 243 (215-292) x 10(9)/l (2P = 0.68) and platelet mass 1.91 (1.67-2.18) ml/l vs. 1.84 (1.70-2.23) ml/l (2P = 0.90) were similar in the hypertensive patients (supine BP: SBP 168 (153-178) mmHg, DBP 103 (98-110) mmHg) and control subjects (SBP 126 (112-138) mmHg, DBP 78 (74-82) mmHg). Serum lipids and plasma glucose and creatinine concentrations were not different between the groups. Mean BP did not correlate with platelet volume (rs = -0.100, 2P = 0.39) or platelet count (rs = 0.111, 2P = 0.34). These data suggest that platelet volume is not altered in essential hypertension.

The mercury sphygmomanometer should be abandoned before it is proscribed.

Both in clinical practice and medical research, blood pressure is still largely measured by auscultation using a mercury sphygmomanometer. Blood pressure is the most important predictor of life expectancy. Treatment of high blood pressure reduces strokes, heart attack and heart failure. Accurate measurement is therefore essential. At a large London teaching hospital, just under 500 mercury sphygmomanometers and their associated cuffs were examined. More than half had serious problems that would have rendered them inaccurate in measuring blood pressure. At the same time, assessment of the technical knowledge needed to measure blood pressure by the ausculatory technique was also carried out amongst medical and nursing staff. This showed a considerable level of ignorance. These results inevitably lead to inaccurate measurement of blood pressure with serious consequences. In addition mercury is a non-degradable pollutant, eventually accumulating on the sea bed. The use of mercury in sphygmomanometers is already in the process of being eliminated in Scandinavia and Holland and other countries are likely to follow. Our results suggest that mercury sphygmomanometers are not adequately maintained and require expertise that is not available for accurate measurement of blood pressure. Their use should be dispensed with on these grounds before a ban for other and, perhaps less justifiable reasons. Validated automatic devices, which are less liable to measurement and observer error should be used instead. At the same time a concerted effort is needed to instruct health care professionals on the importance of more accurate measurement of blood pressure. Journal of Human Hypertension (2000) 14, 31-36.

Double-blind comparison between nifedipine and amlodipine for the treatment of essential hypertension.

Nifedipine is an effective compound for the treatment of hypertension. However, even as a tablet formulation it is relatively short acting requiring two or three times daily administration. Amlodipine is a long-acting calcium antagonist and effectively lowers BP in patients with essential hypertension. In the present study we compared the BP-lowering effect of nifedipine and amlodipine in patients with essential hypertension. Thirteen patients were studied. They had been on nifedipine tablets for at least four weeks and DBP had been consistently > 95 mmHg. After a further month run-in on nifedipine they entered a randomised double-blind crossover study of one month' treatment with either nifedipine tablet (20 mg twice daily) or amlodipine (5 mg once daily). BP was measured 12 and 2 hours after the last dose of nifedipine and 24 and 2 hours after the last dose of amlodipine. There was a significant peak/trough effect while on nifedipine tablets, the BP being significantly higher at 12 hours than at 2 hours after the last dose (155.2/90.9 +/- 4.6/1.7 vs. 136.1/84.8 +/- 4.3/1.7 mmHg; P < 0.001/P < 0.005). There was no overall difference in BP between nifedipine and amlodipine treatment when BPs were taken at the respective troughs (i.e. 12 hours and 24 hours). If anything, amlodipine tended to be slightly more effective at least on supine SBP (155.2/90.9 +/- 4.6/1.7 vs. 147.6/89.1 +2- 4.3/1.8 mmHg; P < 0.05, NS). In conclusion, amlodipine given once daily is at least as effective as nifedipine tablets given twice daily in patients with essential hypertension.

Solution stability of ciclosidomine.

The stability of N-cyclohexanecarbonyl-3-(4-morpholino)-sydnone imine hydrochloride (ciclosidomine) in solution was studied as a function of pH, temperature, ionic strength, and buffer species. The rate of hydrolysis in the absence of light was found to be apparent first order in drug and general acid- and base-catalyzed reactions. The pH rate profile at an ionic strength of 0.1 M at 60 degrees C had a minimum value near pH 6. Change in ionic strength in the range of 0.05 to 0.2 M did not affect the rate of degradation at pH 7 (carbonate buffer) or pH 2 (phosphate buffer) at 60 degrees C. Similar degradation rates were noticed in air or nitrogen in the dark at pH 3, 5, and 6. However, degradation in light was very rapid in either case at pH 3, 5, and 6, and, therefore, the protection of solutions from light was required during all studies. The time for 10% loss of drug in solution at pH 6 in dilute phosphate or citrate buffer at an ionic strength of 0.154 M was projected to be 9 months at 20 degrees C and 2.6 months at 30 degrees C.

Enhancement of ampicillin partition behavior.

Several ion-pair or adduct forming additives tha" enhanced ampicillin partition behavior were identified and evaluated. At pH 3, picric acid and trichloroacetic acid increased the ampicillin aqueous-octanol partition coefficient 250 and 30 times, respectively. At pH 7, quaternary compounds gave the most significant increases in the partition coefficient. Values for an aqueous pH 7 chloroform system increased from zero in the absence of additives to 2.28, 1.86, 1.82, and 1.70 for equimolar amounts of benzalkonium, tetraheptylammonium, benzethonium, and cetalkonium chlorides, respectively. Extraction of ampicillin from aqueous pH 7 solution was possible by adding a quaternary agent in an equimolar amount. However, extraction of ampicillin from plasma required large molar excesses. Tetraheptylammonium chloride was added at a molar concentration 10(3) times greater than that of the ampicillin. Plasma samples spiked at the 3-microgram/ml level gave 93% recovery (CV 6.7%, n = 16) when extracted three times. The extracts were quantitated by TLC.

Congenital insulinoma (nesidioblastoma): ultrastructural evidence for histogenesis from pancreatic ductal epithelium.

An insulinoma removed from a neonate with proved hyperinsulinemia was examined with the electron microscope. The tumor was composed of pancreatic ductal epithelium and beta cells in direct contact and in lobular units. The pattern of the tumor, the morphologic evidence of beta cell-type activity in ductal cells, and the similarity of the arrangement of tumor cells to that observed in islet regeneration after subtotal pancreatectomy in the rat indicate that this tumor originated from ductal epithelium.

Fibroblastic tumor of the urinary bladder after cyclophosphamide therapy.

An unusual fibroblastic tumor occurred in a teenage boy following treatment with cyclophosphamide for Hodgkin's disease. To our knowledge, only one other similar case has been reported. The cellular and structural composition of the tumor resembles that of cyclophosphamide-induced cystitis and therefore suggests a relationship between the two lesions.