The social space of illness.
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Biomedical subjects
Publications and source records attributed to D Armstrong.
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OBJECTIVE: To study the pattern of transmission of tuberculosis (TB) among foreign-born persons living in New York City. DESIGN: A retrospective multicenter study comparing 158 foreign-born patients to 231 US-born patients diagnosed with TB between 1992 and 1994. The patients were stratified according to their Mycobacterium tuberculosis isolate DNA fingerprint patterns. RESULTS: Nineteen (16%) of 122 isolates from foreign-born TB patients and 75 (42%) of 180 isolates from US-born TB patients had DNA fingerprint patterns (cluster patterns) indicative of recent exogenous transmission (P < 0.001). All cluster pattern strains from foreign-born cases were identical to those found among US-born patients. The likelihood of infection with a cluster pattern strain among foreign-born persons increased with duration of residence in the US, and was significantly associated with being homeless (P < 0.05), or having multidrug-resistant TB (P = 0.00072). CONCLUSION: Although most (84%) cases of TB among foreign-born persons in New York City appear to result from reactivation of infections they acquired abroad, the ones who acquire new infections become infected with strains that are already circulating among the US-born TB patients in New York City, and they have risk factors similar to those faced by US-born tuberculosis patients.
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Numerous recent reports have detailed outbreaks of tuberculosis in hospitals and other congregate settings. The characteristics of such settings, including high concentrations of infectious patients and immunocompromised hosts, the potential for sustained daily contact for weeks and often months, and improper precautions taken for protection, make them well suited for tuberculosis transmission. However, community-based outbreaks, which are the source of much public concern, have not been reviewed since 1964, when 109 community outbreaks were examined. Since few of the characteristics of institutional settings are present in the community, the lessons learned may not be applicable to community-based outbreaks. Furthermore, recent studies with analysis by restriction fragment length polymorphisms have documented unexpectedly high rates of primary disease in certain urban communities, suggesting that our understanding of community-based transmission may be incomplete. We reviewed all reported community-based outbreaks of tuberculosis occurring in the last 30 years to assess the basis of our current understanding of community-based transmission. More than 70 outbreaks were identified, with schools being the most common site. In most, a delay in diagnosis, sustained contact with the index case, inadequate ventilation, or overcrowding was contributory. We conclude that community-based outbreaks of tuberculosis continue to occur and that well-established risks contribute to most outbreaks. Many outbreaks can be prevented or limited by attention to basic infection control principles.
OBJECTIVES: To explore general practitioners' reasons for recent changes in their prescribing behaviour. DESIGN: Qualitative analysis of semistructured interviews. SETTING: General practice in south east London. SUBJECTS: A heterogeneous sample of 18 general practitioners. RESULTS: Interviewees were able to identify between two and five specific changes that had occurred in their prescribing in the preceding six months. The most frequently mentioned changes related to fluoxetine, angiotensin converting enzyme inhibitors, and the antibiotic treatment of Helicobacter pylori. Three models of change were identified: an accumulation model, in which the volume and authority of evidence were important; a challenge model, in which behaviour change followed a dramatic or conflictual clinical event; and a continuity model, in which change took place against a background of willingness to change, modulated by other factors such as cost pressures and the comprehensible therapeutic action of a drug. Behaviour change was reinforced and sustained by experiences with individual patients. CONCLUSIONS: Multiple factors are involved in general practitioners' decisions to change their prescribing habits. Three models of change can be identified which have important implications for the design and evaluation of interventions aimed at behaviour change.
BACKGROUND: Increased production of reactive oxygen species (ROS) and lipid peroxidation may contribute to vascular complications in diabetes. to test whether DNA is also oxidatively damaged in diabetes, we measured 8-hydroxydeoxyguanosine (8-OHdG), an indicator of oxidative damage of DNA, in mononuclear cells. METHODS: For this laboratory-based study, 12 patients with insulin-dependent diabetes mellitus (IDDM) and 15 patients with non-insulin-dependent diabetes mellitus (NIDDM) were matched by age with ten healthy volunteers each. DNA was extracted from mononuclear cells from whole blood. 8-OHdG was assayed by high-pressure liquid chromatography, and ROS were assayed by chemiluminescence. FINDINGS: IDDM and NIDDM patients had significantly higher median concentrations (p , 0.001, U test) of 8-OHdG in their mononuclear cells than their corresponding controls (in fmol/micrograms DNA): 128.2 (interquartile range 96.0-223.2) and 95.2 (64.0-133.5) vs 28.2 (21.7-43.4) and 21.9 (18.0-24.4), respectively. ROS generation by mononuclear cells was also significantly greater (p < 0.01) in diabetic patients than in their controls (in mV): 238.0 (107.0-243.0) and 101.3 (66.0-134.0) vs 69.5 (49.8-91.9) and 56.0 (38.8-62.5), respectively. INTERPRETATION: IDDM and NIDDM patients showed greater oxidative damage to DNA, with increased generation of ROS, than controls. Such changes might contribute to accelerated aging and atherogenesis in diabetes and to the microangiopathic complications of the disease.
BACKGROUND: The management of pediatric oncology patients with fever and neutropenia assumes that all patients are at risk for bacteremia, and therefore generally involves hospitalization and broad-spectrum parenteral antibiotics for all patients. The determination of which patients are at low risk for having positive blood cultures and for developing complications related to bacteremia is of potential benefit. METHODS: The records of 161 pediatric patients with neoplastic disease hospitalized for 509 episodes of fever and neutropenia between January 1990 and June 1992 were retrospectively reviewed. Clinical features at initial presentation, clinical and microbiologic documentation of infection, and outcome were analyzed. RESULTS: The only presenting clinical features that correlated with an increased likelihood of having positive blood cultures were chills, hypotension, the requirement for fluid resuscitation (P < 0.001), or a diagnosis of leukemia or lymphoma (P < 0.041). Leukemia patients with relapse admitted for fever and neutropenia were no more likely to have positive blood cultures than those patients in remission. There were ten episodes of fever and neutropenia in which patients were transferred to the intensive care unit (ICU), and two sepsis related deaths. Nine episodes involving ICU management and both deaths were in patients who had persistent fever and an absolute neutrophil count (ANC) of less than 100 after 48 hours of hospitalization (n = 177). Patients with an ANC of less than 100 after 48 hours were twice as likely to have antibiotic changes, 15 times more likely to receive amphotericin B, and were hospitalized twice as long as patients with an ANC of 100 or higher after 48 hours. CONCLUSIONS: Children hospitalized for fever and neutropenia who have persistent fever and an ANC of less than 100 after 48 hours are at high risk for morbidity and are more likely to require antibiotic changes and antifungal therapy. Children who initially lack signs of sepsis, are afebrile, and have an ANC of 100 or higher after 48 hours are at low risk for complications and could be selectively discharged on antimicrobials after a 48-hour period of inpatient hospitalization.
The cellular and molecular mechanisms of IL-12-mediated anti-tumor activity have been examined. BALB/c mice bearing established s.c. RENCA or CT26 tumors that were treated daily with IL-12 showed essentially complete tumor regression while tumors in untreated animals grew progressively. Examination of inflammatory gene expression in tumor tissue from treated vs untreated mice revealed the selective expression of IFN-gamma and the IFN-gamma-inducible CXC chemokine IP-10. Immunohistologic analysis demonstrated that tumors from treated mice were heavily infiltrated with CD8+ T cells and Mac-1+ mononuclear cells. Tumor regression in IL-12-treated mice was associated with expression of the lytic effector molecules perforin and granzyme B. These findings support the hypothesis that the anti-tumor function of IL-12 treatment depends upon the induced expression of IFN-gamma by T cells and/or NK cells, the amplification of the immune response mediated by IFN-gamma-induced expression of chemoattractant cytokines, and the IL-12-dependent potentiation of the cytolytic effector function of recruited CD8+ T cells.
Coronary heart disease (CHD) deaths occurring outside of hospitals or in emergency rooms (OH/ER) have been used to estimate sudden CHD mortality. This study quantifies the potential impact of natural deaths coded to an unspecified cause on race differences in sudden CHD estimates, during 1980-1988. Death certificate data for OH/ER deaths in 40 U.S. states were used to create annual age-adjusted rates for sudden CHD and sudden CHD rates revised to include deaths with an unspecified cause (ICD9, 780-799). Revising the mortality rates to include unspecified deaths results in greater racial disparities for estimates of sudden CHD. In 1980, black-white race differences went from 89 to 128 and 103 to 121 (per 100,000) for men and women, respectively, with revision. Among blacks, revised sudden CHD mortality declined approximately 22%, during 1980-1988, compared to 10% for unrevised sudden CHD; with no observed effect of revision on percent declines among whites. Previous studies may have underestimated declines in racial disparities of sudden CHD, due to improved quality of OH/ER death certification among blacks. Improved access to routine and emergency medical care, through increased affordability and greater availability, may be important to address higher OH/ER CHD among blacks.
AIM: To determine whether misoprostol promotes the healing of non-steroidal anti-inflammatory drug-induced gastroduodenal lesions in a human experimental model. METHODS: Mucosal damage and healing of mucosal biopsy sites were assessed endoscopically in 10 healthy, Helicobacter pylori-negative volunteers with a normal initial endoscopy: they were enrolled in a double-blind, double-dummy, placebo-controlled cross-over study. They received 2-week courses of misoprostol (200 micrograms b.d.) or placebo; a water-soluble non-steroidal antiinflammatory drug diclofenac 50 mg t.d.s., was given during the second week of each dosage regimen after three endoscopic biopsies had been taken from each of the duodenum, antrum and corpus. RESULTS: The number of unhealed biopsy sites was not different after misoprostol or placebo, although the number of healed biopsy sites was greater in the corpus and duodenum than in the antrum. Misoprostol did not prevent the appearance of diclofenac-induced erosions and petechiae. Epigastric discomfort was related to the intake of diclofenac and was reduced by misoprostol. Bloating and flatulence occurred more frequently with misoprostol alone and with misoprostol plus diclofenac, than with placebo alone or placebo plus diclofenac. CONCLUSION: Misoprostol does not prevent new mucosal lesions induced by diclofenac in healthy volunteers and it does not accelerate the healing of the biopsy sites. Misoprostol decreases the frequency of diclofenac-induced epigastric discomfort, but it increases gas bloating and flatulence.
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BACKGROUND & AIMS: The study and management of reflux esophagitis require an endoscopic classification system founded on esophageal lesions that can be reproducibly identified. The aim of this study was to investigate interobserver agreement for the identification of endoscopic lesions typical of reflux esophagitis. METHODS: Paired comparisons of observers' descriptions were obtained. Seventeen endoscopists assessed 100 still images, and 42 endoscopists, including 13 endoscopists in training, assessed 23 endoscopic video recordings. In a third, ancillary study, using a simpler evaluation sheet, 219 gastroenterologists recorded their assessments of 20 still images. RESULTS: The agreement between endoscopists was similar for still images and video recordings. Agreement between experienced endoscopists was acceptable to good for recognition of minimal changes (erythema, friability, mucosal edema; kappa = 0.46 to kappa = 0.8), mucosal breaks (discretely, demarcated areas of slough or erythema; kappa = 0.84), and complications (ulceration, kappa = 0.92; stricturing, kappa = 0.80; columnar metaplasia, kappa = 0.81), although there was poor agreement when the circumferential extent and number of mucosal breaks were assessed. However, total circumferential extent of the mucosal break had a kappa value of 0.59. Agreement between inexperienced endoscopists was poor for recognition of minimal changes but was good for recognition of complications (kappa, 0.70-0.90). CONCLUSIONS: Endoscopists can identify mucosal breaks confined to a mucosal fold and lesions that extend throughout the esophageal circumference. Complications of reflux disease can be reproducibly recorded. Criteria for assessing the number of mucosal breaks and their radial extent must be defined more clearly, as must the features of minimal change esophagitis.
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OBJECTIVE: To determine the duration of stool shedding and incidence of clinical infection among pediatric oncology patients colonized with vancomycin-resistant Enterococcus faecium (VRE) in our institution. METHODS: Stool cultures were obtained from all patients admitted from May 15 to August 2, 1994. Patients were followed for evidence of clinical VRE infection and surveillance stool results through August 15, 1995. Genetic relatedness of stool-clinical isolate pairs and serial stool samples was evaluated using pulsed field gel electrophoresis. RESULTS: Twenty-three (32%) of 73 screened patients were colonized with VRE. Eight (35%) of the colonized patients cleared VRE from stool; 10 (43%) were persistent carriers, excreting organisms for 19 to 331 days (median, 112 days); and 5 patients had an insufficient number of stools to determine length of carriage. Persistent carriers had a median of 6 hospital readmissions; 8 of 10 were positive at first or second readmission Clinical VRE infection developed in 6 of 73 patients (annual incidence, 8.2%). Clinical cases had more days of neutropenia between colonization and infection than colonized patients during a comparable follow-up (49 vs. 16 days, P = 0.04). Five of 6 stool-clinical isolate pairs were identical by pulsed field gel electrophoresis. Serial stools from 6 of 7 patients (collected 20 to 343 days apart) were identical by pulsed field gel electrophoresis. CONCLUSION: Persistent gastrointestinal colonization with VRE is common among pediatric oncology patients. Carriage of the same VRE clone for up to 1 year was demonstrated. In the majority of cases invasive and colonizing isolates were identical by DNA fingerprinting techniques, suggesting that the colonizing VRE was the source of infection. Intermittent excretion of organisms in stool makes vigilant tracking and immediate isolation of such patients crucial to control efforts. Prolonged neutropenia may increase the risk of developing clinical infection among VRE-colonized patients.
This study evaluated the presence of extradural dead space following a monobloc or facial bipartition osteotomy and examined its natural history and relationship to postoperative infection and the presence of a ventriculoperitoneal shunt at the time of osteotomy in a consecutive series of patients with craniofacial dysostosis, frontonasal dysplasia, midline cranio-orbital clefts, and orbital hypertelorism. Only patients followed for at least 1 year were included in the study (range 1.3 to 5.5 years). The 23 patients studied were divided into three groups: 10 patients (mean age 9 years) underwent a monobloc osteotomy with advancement, 7 (mean age 8 years) a facial bipartition osteotomy with advancement, and 6 (mean age 7 years) a facial bipartition osteotomy without advancement. Standard craniofacial computed tomographic (CT) scans were obtained for each patient early after surgery (within 2 weeks in 13 patients and at 6 to 8 weeks in 10 patients) and again 1 year after surgery in every case. The extradural dead space was measured from a reproducible axial CT scan slice for each patient at each postoperative interval. An initial dead space was documented in the retrofrontal region of the anterior cranial fossa when the reconstruction incorporated forward projection of the osteotomy parts. This space was found to be obliterated by the expanded brain by 6 to 8 weeks in the patients examined by CT scan slice for each patient at each postoperative in all patients. Perioperative complications also were documented. The presence of a ventriculoperitoneal shunt at the time of osteotomy (7 of 23 patients) did not increase the risk of complications or alter the pattern of dead space closure after operation. Two patients developed infectious complications that were managed without long-term consequences.
We investigated lymphatic drainage pathways of the central nervous system in conscious sheep and quantified the clearance of a cerebrospinal fluid (CSF) tracer into lymph and blood. In the first group of studies, 125I-HSA was injected into the lateral ventricles of the brain or into lumbar CSF and after 6 h, various lymph nodes and tissues were excised and counted for radioactivity. Multiple lymphatic drainage pathways of cranial CSF existed in the head and neck region defined by elevated 125I-HSA in the retropharyngeal/cervical, thymic, pre-auricular and submandibular nodes. Implicated in spinal CSF drainage were mainly the lumbar and intercostal nodes. In a second group of experiments, multiple cervical vessels and the thoracic duct were cannulated and lymph diverted from the animals. Transport of tracer through arachnoid villi was taken from recoveries in venous blood. Following intraventricular administration, the 6 h recoveries of 125I-HSA in the lymph (sum of cervical and thoracic duct) and blood were 8.2% +/- 3.0 and 12.5% +/- 4.5 respectively and at 22 h, 25.1% +/- 6.9 and 20.8% +/- 4.1 respectively. When 125I-HSA was injected into lumbar CSF, the 6 h recoveries of tracer in thoracic duct and blood were 11.6% +/- 2.7 and 16.3% +/- 3.7 respectively. Total lymph and blood recoveries were not significantly different in any experiment. We conclude that the clearance of 125I-HSA from the CSF is almost equally distributed between lymphatic and arachnoid villi pathways.
Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.
Mycobacterium genavense, a recently reported cause of a wasting illness in patients with AIDS, was isolated from a cervical lymph mode from a dog with severe hind limb weakness and from trachael tissue from a parrot with acute onset respiratory distress. Physicians caring for immunocompromised patients should consider birds and dogs potential sources of M. genavense infection and submit appropriate specimens for culture.