ED staff's reporting of impaired drivers: understanding the issues, continuing the work.
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Biomedical subjects
Publications and source records attributed to S Shapiro.
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The spatial arrangements and associative behavior of Actinomyces naeslundii, Veillonella dispar, Fusobacterium nucleatum, Streptococcus sobrinus, and Streptococcus oralis strains in an in vitro model of supragingival plaque were determined. Using species-specific fluorescence-labeled antibodies in conjunction with confocal laser scanning microscopy, the volumes and distribution of the five strains were assessed during biofilm formation. The volume-derived cell numbers of each strain correlated well with respective culture data. Between 15 min and 64 h, populations of each strain increased in a manner reminiscent of batch growth. The microcolony morphologies of all members of the consortium and their distributions within the biofilm were characterized, as were interspecies associations. Biofilms formed 15 min after inoculation consisted principally of single nonaggregated cells. All five strains adhered strongly to the saliva-conditioned substratum, and therefore, coadhesion played no role during the initial phase of biofilm formation. This observation does not reflect the results of in vitro coaggregation of the five strains, which depended upon the nature of the suspension medium. While the possibility cannot be excluded that some interspecies associations observed at later stages of biofilm formation were initiated by coadhesion, increase in bacterial numbers appeared to be largely a growth phenomenon regulated by the prevailing cultivation conditions.
Variable-region-identical mouse immunoglobulin G1 (IgG1), IgG2b, and IgG2a monoclonal antibodies to the capsular polysaccharide of Cryptococcus neoformans prolong the lives of mice infected with this fungus, while IgG3 is either not protective or enhances infection. CD4+ T cells are required for IgG1-mediated protection, and CD8+ T cells are required for IgG3-mediated enhancement. Gamma interferon is required for both effects. These findings revealed that T cells and cytokines play a role in the modulation of cryptococcal infection by antibodies and suggested that it was important to more fully define the cytokine requirements of each of the antibody isotypes. We therefore investigated the efficacy of passively administered variable-region-identical IgG1, IgG2a, IgG2b, and IgG3 monoclonal antibodies against intravenous infection with C. neoformans in mice genetically deficient in interleukin-12 (IL-12), IL-6, IL-4, or IL-10, as well as in the parental C57BL/6J strain. The relative inherent susceptibilities of these mouse strains to C. neoformans were as follows: IL-12(-/-) > IL-6(-/-) > C57BL/6J approximately IL-4(-/-) >> IL-10(-/-). This is consistent with the notion that a Th1 response is necessary for natural immunity against cryptococcal infection. However, none of the IgG isotypes prolonged survival in IL-12(-/-), IL-6(-/-), or IL-4(-/-) mice, and all isotypes significantly enhanced infection in IL-10(-/-) mice. These results indicate that passive antibody-mediated protection against C. neoformans requires both Th1- and Th2-associated cytokines and reveal the complexity of the mechanisms through which antibodies modulate infection with this organism.
Deep inside each of us is a seed that holds our vision of truth, peace, and happiness. Our early childhood attachments, societal influences, and innate capacity determine how well that seed is nurtured and the deepest inner vision is set free. This article is about the ways that vision becomes clouded by attachment deficits, trauma, and subsequent symptoms. The deep inner wish to heal allows for transformation, and approaches like Eye Movement Desensitization and Reprocessing, and hypnotherapy can assist in creating a more rapid acceleration of trauma resolution and transformation of self.
The study of biofilm structure and function mandates the use of model systems for which a host of environmental variables can be rigorously controlled. We describe a model of supragingival plaque containing Actinomyces naeslundii, Veillonella dispar, Fusobacterium nucleatum, Streptococcus sobrinus, and Streptococcus oralis wherein cells are cultivated anaerobically in a saliva-based medium on hydroxyapatite discs coated with a salivary pellicle, with material and pieces of apparatus common to all microbiology laboratories. After 0.5 hr, 16.5 hrs, 40.5 hrs, and 64.5 hrs, the composition of adherent biofilms was analyzed by culture techniques, live/dead fluorescence staining, and confocal laser scanning microscopy. Repeated independent trials demonstrated the repeatability of biofilm formation after 40.5 hrs and 64.5 hrs. Brief exposures of biofilms to chlorhexidine or Triclosan produced losses in viability similar to those observed in vivo. This biofilm model should prove very useful for pre-clinical testing of prospective anti-plaque agents at clinically relevant concentrations.
OBJECT: The authors have previously reported that the results of using cadaveric fibula and locking plate (CF/LP) fusion following anterior cervical discectomy (ACD) for cervical spondylotic radiculopathy and myelopathy are superior to those obtained using autologous iliac crest (AIC) grafts in the short term. The long-term results of using this construct are important in substantiating this improvement. The authors report on 246 consecutive patients (54% smokers) who underwent ACD with CF/LP fusion (175 with allogeneic bone matrix [ABM]) and compare them with 111 consecutive patients in whom AIC fusions (49% smokers) were performed by the same surgeons. METHODS: The study is a retrospective nonrandomized analysis, and chi-square statistics were used. Bone densitometric studies of AIC grafts and CF grafts were performed. A paired t-test was used for statistical analysis of the results. Disease in the group of patients undergoing CF/LP fusion included soft-disc herniation with radiculopathy in 14, soft-disc hemiation with myelopathy in seven, cervical spondylotic radiculopathy in 144, cervical spondylotic myelopathy in 75, AIC graft collapse pseudarthrosis in five, and ACD with no fusion collapse/kyphosis in one. Operations consisted of single-level CF/LP fusion in 142 patients and multilevel CF/LP fusion in 104. Perioperative complications in the CF/LP group included three cases of transient hoarseness. There were no transfusions, infections, neurological injuries, or deaths. The mean hospital length of stay was 1.2 days (28% outpatient and 66% 23-hour stay). The mean follow-up period was 60 months (range 12-94 months). Ten patients were lost to follow up after 1 year. Long-term complications included one traumatic plate fracture and one symptomatic pseudarthrosis with plate fracture. At 1 year and beyond, in 245 (99.6%) of 246 patients radiographically documented fusion with no motion at the fused level on flexion-extension films was demonstrated. There was no kyphosis, no symptomatic screw plate backout, and no CF/LP graft collapse (100% in the ABM group). In the 111 consecutive patients with AIC fusions, however, there was a 17% graft-related complication rate. There were significantly fewer graft-related complications in the CF/LP group (p < 0.001). There was no difference in neurological outcome for any of the groups. In the groups undergoing single-level ACD there was a significantly greater chance of complete relief of neck pain CF/LP fusion compared with those undergoing AIC fusion (p < 0.02). There was a significantly greater chance of AIC collapse with the passage of time compared with CF graft (p < 0.02). Time until return to work was shorter for the CF/LP group by 5 to 6 weeks (p < 0.02). There was a higher rate of radiographically documented pseudarthrosis in the AIC group (p < 0.006). The mean bone densitometry for the CF/LP group was 0.7 g/cm2, significantly greater than that of the AIC group, which was 0.2 g/cm2 (paired t-test p < 0.001). CONCLUSIONS: When fusion is necessary following ACD, the results of CF/LP fusion are significantly superior in the first 5 years after surgery compared with those for AIC fusions. It remains to be determined if demineralized ABM has a significant effect in enhancing fusion.
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(+)-Totarol, a diterpene extracted from Podocarpus totara, has been reported as a potent antioxidant and antibacterial agent. Although the molecular mechanism of action of this hydrophobic molecule remains unknown, recent work made in our laboratory strongly suggests that it could be lipid-mediated. Since (+)-totarol contains a phenolic ring, we have studied the intrinsic fluorescent properties of this molecule, i.e., quantum yield, lifetime, steady-state anisotropy and emission spectra, both in aqueous and in phospholipid phases, in order to obtain information on the interaction and location of (+)-totarol in biomembrane model systems. The phospholipid/water partition coefficient of (+)-totarol was found to be very high (K(p)=1.8x10(4)), suggesting that it incorporates very efficiently into membranes. In order to estimate the transverse location (degree of penetration) of the molecule in the fluid phase of DMPC model membranes, the spin labelled fatty acids 5-NS and 16-NS were used in differential quenching experiments. The results obtained show that (+)-totarol is located in the inner region of the membrane, far away from the phospholipid/water interface. Since (+)-totarol protects against oxidative stress, its interaction with an unsaturated fatty acid, trans-parinaric acid, was studied using fluorescence resonance energy transfer. No significant interactions were observed, molecules of trans-parinaric acid distributing themselves randomly amongst those of (+)-totarol in the phospholipid membrane.
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Adverse reactions are a potential concern for physicians when they prescribe or recommend drugs. Epidemiological principles, when combined with clinical judgment, can be of help in this situation, starting with an appreciation of the strengths and weaknesses of different sources of information on adverse reactions--clinical trials, case reports, and formal epidemiological studies. The latter studies generally provide the most comprehensive information on the risks of serious adverse drug reactions. An understanding of the different types of risk estimates, relative and absolute, is also needed--we stress the value of the absolute risk as the best measure of the impact of an adverse reaction. Rare serious reactions, although striking, have little impact on individual risk, whereas more common reactions, even with much lower fatality rates, are more likely to lead to adverse outcomes for patients. The importance of balancing risks and benefits, taking into account all the information about an individual patient's risk profile, is also highlighted.
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BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.
Recent studies have suggested that progestogen-only contraceptives and combined estrogen/progestogen oral contraceptives (COCs) may increase the risk of breast cancer among women less than 35 years of age or among recent users. The authors conducted a case-control study, in which cases of breast cancer (n = 484) [corrected] and controls (n = 1,625) hospitalized for conditions unrelated to contraceptive use were interviewed from 1994 to 1997 in hospitals in greater Cape Town, South Africa. The women were aged 20-54 years, resided in a defined area around Cape Town, and were Black or of mixed racial descent. The relative risk for exposure to injectable progestogen contraceptives (IPCs), mostly depot medroxyprogesterone acetate, was 0.9 (95% confidence interval (CI) 0.7, 1.2). There were no consistent associations within categories of age or recency or duration of use. For exposure to COCs, the overall relative risk was 1.2 (95% CI 1.0, 1.5). Among women below age 35 years, the relative risk was 1.7 (95% CI 1.0, 3.0), and it was unrelated to the duration or recency of use. The findings suggest that IPCs do not increase the risk of breast cancer, and that COCs may increase the risk among women below age 35 years, although bias cannot be excluded.
STUDY DESIGN: An analysis of 44 cauda equina syndrome cases. OBJECTIVES: To determine the neurologic outcome of cauda equina syndrome cases, in light of the significant medical implications of this disorder. SUMMARY OF BACKGROUND DATA: Cauda equina syndrome from lumbar disc herniation accounts for up to 1% of all disc herniations. Most of the literature supports surgery within 24 hours as a means of improving the outcome. METHODS: A retrospective chi 2 analysis was performed of 44 patients surgically treated for lumbar disc herniation who initially sought treatment for cauda equina syndrome. RESULTS: In 20 patients, diagnosis was made and surgery performed within 48 hours of the cauda equina syndrome onset, including 18 patients (90%) who underwent surgery within 24 hours. In 24 patients, surgery was performed more than 48 hours after the onset of cauda equina syndrome, with a mean delay of 9 days, including 17 patients (71%) with a mean delay of 3.7 days. Causes for delay were patient-related in 4 cases (17%) and physician-related in 20 cases (83%). According to chi 2 analysis, a greater chance of persistent bladder/sphincter problem (P = 0.008), persistent severe motor deficit (P = 0.006), persistent pain (P = 0.025), and sexual dysfunction (P = 0.006) existed with delayed surgery. CONCLUSION: The data strongly support the management of cauda equina syndrome from lumbar disc herniation as a diagnostic and surgical emergency.
STUDY DESIGN: A randomized controlled trial comparing usual care with a program for the coordination of primary health care (CORE) for the treatment of subacute low-back pain patients. OBJECTIVES: To measure the effectiveness of the CORE program as a mean for implementing clinical practice guidelines for low-back pain in an urban community. SUMMARY OF BACKGROUND DATA: Clinical practice guidelines have been developed for primary care physicians and patients on the clinical management of low-back pain. The implementation of the guidelines in a large community is difficult with the multiplicity of medical and nonmedical back care providers and products. The CORE program was designed to make the guidelines fit in this complex environment. METHODS: One hundred ten workers compensated for low-back pain for 4 to 8 weeks in metropolitan Montreal were randomized in two groups: usual care (N = 56) and the CORE program (N = 54). Coordination of primary health care was performed by two primary care physicians and a nurse in liaison with the treating physicians, and included a complete examination, recommendations for the clinical management, and support to carry out the recommendations. All workers were followed for 6 months. Back pain and functional status were assessed at baseline, 3 months, and 6 months. RESULTS: In the 6-month follow-up, the CORE group returned to work 6.6 days (standard error = 8.9) quicker than the control group, a difference that was not statistically significant. However, the CORE group showed a sustained improvement in pain and functional status with two-fold differences at the end of the 6 months of follow-up. This represented nine points on the Oswestry scale (P = 0.02) and 12 points on the Quebec Back Pain Disability Scale (P = 0.01). The CORE group also used three times less specialized imaging tests of the spine at 3 months (P < 0.01) and exercised twice as much at 6 months (P < 0.05) than the controls. CONCLUSIONS: The therapeutic results for workers with low-back pain could be improved by implementing the clinical practice guidelines with primary care physicians in a large community, without delaying the return to work. The CORE intervention for back pain patients is highly relevant to primary care practice. It is simple in its application, flexible to accommodate physicians' and- patients' preferences in health care, and it is effective on patients' clinical outcome.
BACKGROUND: We undertook the present analyses to determine whether family history of colorectal cancer in a parent or sibling modifies the inverse association of nonsteroidal anti-inflammatory drug (NSAID) use with colorectal cancer risk. METHODS: We used data from two case-control studies of colorectal cancer. The hospital-based Case Control Surveillance Study included 1526 patients with primary colorectal cancer, 4192 cancer controls and 6036 noncancer controls. A population-based study conducted in Massachusetts enrolled 1201 incident cases of colorectal cancer and 1201 community controls. Data on NSAID use and risk factors for colorectal cancer were collected by interview. RESULTS: In both studies there was a reduction in the odds ratios among subjects who used NSAIDs regularly continuing into the previous year, regardless of family history. In the Case Control Surveillance data, the odds ratio was 0.4 (95% CI 0.2-0.9) among subjects with a family history and 0.5 (95% CI 0.4-0.7) among subjects without a family history. The comparable odds ratios in the Massachusetts data were 0.5 (95% CI 0.3-0.9) and 0.7 (95% CI 0.6-0.9). CONCLUSIONS: These data indicate that regular continuing NSAID use is associated with a reduced risk of colorectal cancer among persons with a family history of the disease, as well as those without such a history.
OBJECTIVES: An association of increased risk of ovarian cancer with use of antidepressants or benzodiazepine tranquilizers has been reported from a case-control study. We assessed the association between ovarian cancer risk and the use of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), phenothiazine antipsychotics, and benzodiazepines, in data from the Case-Control Surveillance Study. METHODS: From 1976 through 1998, data were collected from hospital patients in Boston, New York, Philadelphia, and Baltimore based on demographic factors, reproductive and medical history, and medication use. In the present analyses, cases of epithelial ovarian cancer (n = 748) were compared with cancer controls (n = 1496) and noncancer controls admitted for trauma and acute infection (n = 1496). We estimated Mantel-Haenszel odds ratios adjusted for age, study center, and year of interview. RESULTS: Odds ratios for regular use (at least 4 days/week for at least 1 month) were compatible with 1.0 for every drug class. For tricyclics and benzodiazepines the upper 95% confidence limits were less than 1.6. For phenothiazines the upper limit was 2.6 with cancer controls and 1.4 with noncancer controls. Only five cases used SSRIs, yielding unstable results. Odds ratios were not increased among women who had used any drug class for at least 5 years, nor among women who had first used them 10 or more years previously. CONCLUSIONS: These data do not support an association between regular use of any of the drugs under study with ovarian cancer risk.
OBJECTIVE: to compare patients with abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) with regard to risk factors for atherosclerosis, co-morbid conditions and inflammatory activity. PATIENTS AND METHODS: a total of 155 patients undergoing abdominal aortic surgery between January 1993 and October 1997: 82 (53%) had aneurysmal disease and 73 (47%) had occlusive disease. Principal risk factors were compared: age; gender; smoking; hypertension; hyperlipidaemia; diabetes mellitus; severe peripheral vascular disease (PVD) and ischaemic heart disease. Aortic wall tissue samples were obtained during surgery. A prospective blind analysis was performed for the presence of inflammatory cytokines TNF-alpha, IL-1 beta, IL-6 and TGF-beta. RESULTS: the average age of AAA patients was 74 years (50-88), while that of AOD patients was 61 years (43-82) (p<0.0001). Diabetes mellitus was found to be much more prevalent in the AOD group (p<0.001), while hypertension and severe PVD were more prevalent in the AAA group (p<0.001). No differences were found concerning any of the risk factors. Inflammatory cytokine activity: AAA tissue samples contained significantly higher mean TNF-alpha and IL-6 levels compared to the AOD samples (5.6+/-2.7 x 10 E-4 vs. 4.4+/-2.7 x 10 E-5 atmoles/microl (p=0. 01), and 0.6+/-0.4 vs. 0.01+/-0.006 atmoles/microl (p=0.02) respectively). No differences were found related to IL-1 beta and TGF-beta. CONCLUSIONS: (1) Patients with AAA have fewer atherosclerotic risk factors than do patients with AOD. (2) Patients with AAA and AOD have significantly different inflammatory activity. (3) The data supports the hypothesis that AAA and AOD are probably two different pathological entities.