Migration of a Kirschner wire used in the fixation of a subcapital humeral fracture, causing cardiac tamponade: case report and review of literature.

Metallic pins and wires are frequently used for fixation of fractures and dislocations. Migration is one of the potential complications of such fixation methods. Usually, migration of the pins causes only minor complications, but if the device migrates to a vital cavity, serious damage and even death may ensue. The shoulder girdle is one of the areas in which pins and wires are mostly used, the humeral neck fractures being one of them. We report a case in which a Kirschner wire migrated from a subcapital humeral fracture site into the aorta and pericardium, causing sudden cardiac tamponade and death.

Direction dependent projection fields for the fast DRR generation for medical 2D/3D registration.

The fast generation of digitally reconstructed radiographs is a prerequisite for intensity-based registration approaches. For our approach, extensive pre-calculations are necessary that are saved in what we call a direction dependent projection field. The projection field approach reduces the complexity of the DRR calculation from O(n(3)) to O(n(2)). This paper develops the theoretical background and gives first examples of the application of projection fields for the 2D/3D registration of X-rays to CT data.

Roger A. Mann Award . The reliability of angular measurements in hallux valgus deformities. .

The purpose of this study was to determine the intraobserver and inter-observer reliability of physicians on a repetitive basis in making angular measurements of hallux valgus deformities. The hallux valgus angle, the 1-2 intermetatarsal angle, and the distal metatarsal articular angle and the assessment of congruency/subluxation of the first MTP joint were evaluated on a repetitive basis. Physicians were provided with a series of black and white photographs of radiographs with a hallux valgus deformity. Three different sets of photographs randomly ordered were sent at a minimum interval of six weeks to the participants. Participating physicians were extremely reliable in the measurement of the 1-2 metatarsal angle. 96.7% of the photographs were repeatedly measured within a range of 5 degrees or less. The angular measurements to determine the hallux valgus angle were slightly less reliable, but 86.2% of photos were repeatedly measured within a range of 5 degrees or less. In the measurement of the distal metatarsal articular angle, 58.9% of photographs were repeatedly measured within a range of 5 degrees or less. There was a wide range within physician evaluators who recognized very few congruent joints (2 of 21) and those who recognized several congruent joints (11 of 21). Most physicians appeared to be internally consistent in the assessment of MTP congruency; however, some photographs were much more difficult to assess than others. This study validates the reliability of the measurement of the hallux valgus and the 1-2 metatarsal angle. The interobserver reliability in the measurement of the distal metatarsal articular angle is questioned.

Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.

Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler.

Fenoterol hydrobromide delivered via HFA-MDI or CFC-MDI in patients with asthma: a safety and efficacy comparison.

The main objective of the study was to compare the long-term safety and tolerability of fenoterol hydrobromide delivered using a metered-dose inhaler formulated with the alternative propellant, hydrofluoroalkane 134a (HFA-MDI), with delivery using the currently available chlorofluorocarbon MDI (CFC-MDI; Berotec 100). A further objective was to compare the efficacy of fenoterol HFA-MDI with fenoterol CFC-MDI, using the pulmonary function parameters of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF). Following a 2-week run-in phase, a 12-week, double-blind parallel group comparison was undertaken in 290 patients randomized on a 2:1 basis to two puffs of 100 microg fenoterol four times a day (HFA-MDI=197 patients; CFC-MDI=93 patients). A total of 236 patients in this multi-centre study completed the trial as planned. The overall incidence of adverse events (AEs) was similar in both groups (29.9% of HFA-MDI patients and 28% of CFC-MDI patients). Reports of respiratory disorder AEs were also comparable (21.8% HFA-MDI; 22.6% CFCMDI). End of study laboratory tests, ECG, pulse, blood pressure and physical examination showed no significant differences from pre-study baselines in either group and both treatments appeared to be well tolerated. Pre-dose FEV1 measurements taken at the three clinic visits were constant and increase in FEV1 at 5 and 30 min post-dose demonstrated equivalent efficacy for the two formulations. No difference between the two groups was observed in PEF or in the use of rescue medication. We conclude from these findings that the long-term safety and efficacy profile of fenoterol HFA-MDI is comparable to that of the fenoterol CFC-MDI.

Respimat (a new soft mist inhaler) delivering fenoterol plus ipratropium bromide provides equivalent bronchodilation at half the cumulative dose compared with a conventional metered dose inhaler in asthmatic patients.

BACKGROUND: Respimat, a possible alternative to the conventional metered dose inhaler (MDI), is a novel, reusable, propellant-free, multidose soft mist inhaler. Respimat slowly releases a metered dose of active substance as a soft mist with a high proportion of the dose in the fine particle fraction, leading to improved lung deposition following inhalation when compared with the conventional MDI. OBJECTIVES AND METHODS: The equipotent bronchodilating efficacy and safety of a combination of fenoterol hydrobromide and ipratropium bromide (F/I) in cumulative doses delivered by either Respimat or pressurised MDI was assessed in a randomised, controlled, double-blind (within device) 4-way crossover study. Forty-three patients with stable asthma (mean FEV(1) 62% predicted) responsive to F/I inhaled cumulatively 16 puffs on each of 4 test days (1 + 1 + 2 + 4 + 8 puffs at 50-min intervals) via Respimat delivering 50/20, 25/20 or 25/10 microg F/I per puff or via MDI delivering 50/20 microg F/I per puff. RESULTS: Cumulative doses of 400/160 and 400/320 microg F/I via Respimat produced bronchodilation (evaluated by average increase in FEV(1) 45-245 min after first inhalation) equivalent to that achieved with a cumulative 800/320 microg F/I via MDI (mean increase in FEV(1) above baseline 0.76, 0.73 and 0.71 litres, respectively). The tolerability of the F/I combination via Respimat was also comparable to that of twice the dose delivered via MDI. CONCLUSION: Therefore, a fenoterol hydrobromide/ipratropium bromide combination delivered by Respimat is as safe and effective as the MDI at half the cumulative dose, on acute administration to patients with asthma.

Hernia: is it a work-related condition?

BACKGROUND: Development of hernias among active workers is a major occupational problem, however, the work-relatedness of hernias has not been well investigated. It is a difficult question for occupational and primary care physicians who must often address whether a worker with an inguinal hernia should be restricted from work requiring lifting of heavy objects. METHODS: To evaluate the possible work-relatedness of inguinal hernias, a cross-sectional study was performed. The goal of the study was to determine hernia incidence according to occupation with the Annual Survey of Occupational Injuries and Illnesses from the Bureau of Labor Statistics in 1994. Hernia incidence rates (per 10,000 workers) for industry and occupation categories were calculated with the estimates of the number of hernias in males and the employed male workers from the Current Population Survey. Rate ratios (RR) of hernia incidence rates were calculated. RESULTS: In 1994, an estimated 30, 791 work-related hernias in males were reported by US private establishments. The occupation groups with the highest RR were laborers and handlers (RR, 2.47; 95% confidence interval (CI), 2.14-2.80), machine operators (RR, 2.13; 95% CI, 1.81-2.44), and mechanics and repairers (RR, 1.72; 95% CI, 1.43-2.00). CONCLUSIONS: Rate ratios for hernias vary considerably within industries and occupations, with the highest ratios found in industries and occupations involving manual labor. This provides support for the hypothesis that the hernias are work-related, especially in work involving strenuous, heavy manual labor. Am. J. Ind. Med. 36:638-644, 1999. Published 1999 Wiley-Liss, Inc.

Modification of the Mitchell osteotomy.

This technical modification of the Mitchell osteotomy facilitates the creation of the "step" in the distal fragment of the osteotomy and permits accurate alignment.

FK-binding protein is associated with the ryanodine receptor of skeletal muscle in vertebrate animals.

The ryanodine receptor/calcium release channel (RyR1) of sarcoplasmic reticulum from rabbit skeletal muscle terminal cisternae (TC) contains four tightly associated FK506-binding proteins (FKBP12). Dissociation and reconstitution studies have shown that RyR1 can be modulated by FKBP12, which helps to maintain the channel in the quiescent state. In this study, we found that the association of FKBP with RyR1 of skeletal muscle is common to each of the five classes of vertebrates. TC from skeletal muscle representing animals from different vertebrates, i.e. mammals (rabbit), birds (chicken), reptiles (turtle), fish (salmon and rainbow trout), and amphibians (frog), were isolated. For each, we find the following: 1) FKBP12 is localized to the TC (there are four FKBP binding sites/ryanodine receptor); 2) soluble FKBP exchanges with the bound form on RyR1 of TC; 3) release of FKBP from terminal cisternae by drug (FK590) treatment leads to a significant reduction in the net calcium loading rate, consistent with channel activation (the calcium loading rate is restored to the control value by reconstitution with FKBP12); and 4) RyR1 of skeletal muscle TC can bind to and exchange with either FKBP12 or FKBP12.6 (FKBP12.6 is the novel FKBP isoform found selectively associated with RyR2 of dog cardiac sarcoplasmic reticulum). We conclude that FKBP is an integral part of the RyR1 of skeletal muscle in each of the classes of vertebrate animals. The studies are consistent with a role for FKBP in skeletal muscle excitation-contraction coupling.

Prevalence of Coxiella burnetii infections among North Dakota sheep producers.

A case of Q fever in a sheep producer was detected by a surveillance system in North Dakota in 1993, when Q fever was not reportable. This is the first officially documented case in the state. To estimate the prevalence of Coxiella burnetii infection and identify associated risk factors, we conducted a study covering the whole state. A total of 17 cases were identified among 496 sheep producers, their family members, and hired helpers. The number of sheep raised was a good predictor of C. burnetii infection. Lambing outdoors and frequent physical contacts with sheep during lambing were associated with a higher risk, but petting dogs was correlated with a lower risk. We conclude that C. burnetii infection is prevalent among sheep producers in North Dakota. As the result, Q fever became a reportable disease in North Dakota.

Collagenase 1 and collagenase 3 expression in a guinea pig model of osteoarthritis.

OBJECTIVE: To analyze the in vivo compartmental expression of collagenases 1 and 3 (MMP-1 and MMP-13) in the Hartley guinea pig model of spontaneously occurring osteoarthritis (OA) for the purpose of elucidating their roles in the pathogenesis of OA. METHODS: Competitive reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry quantification of messenger RNA (mRNA) and protein levels in medial and lateral tibial cartilage obtained from the knee joints of 2-month-old (no OA) and 12-month-old (OA) guinea pigs. RESULTS: The patterns of mRNA expression of collagenases 1 and 3 varied with the age of the animal and the compartment of the knee. We also found focal areas of collagenase 1 and collagenase 3 proteins localized to the extracellular matrix of OA lesion sites, coincident with three-quarter/one-quarter collagen cleavage. Collagenase 3 protein was also abundant throughout the medial tibial cartilage of 2-month-old animals. CONCLUSION: This represents the first description of bona fide collagenase 1 in a rodent species. Recent evidence, however, based on analysis of mitochondrial DNA homologies, suggests that the guinea pig is not a member of the order Rodentia and may be more closely allied with lagomorphs. This taxonomic controversy leaves open to question the issue of the expression of collagenase 1 in other rodents, such as mice and rats. The presence of active collagenases 1 and 3 at OA lesion sites is consistent with an important role of these enzymes in the cartilage degradation of OA in guinea pigs. The expression of collagenase 3 in medial tibial cartilage from 2-month-old guinea pigs may signify a role of this enzyme in cartilage remodeling with growth and development, or it may represent an early molecular manifestation of OA.

Association of occupational and non-occupational risk factors with the prevalence of self-reported carpal tunnel syndrome in a national survey of the working population.

To compare the association of occupational versus personal, nonoccupational risk factors with the prevalence of carpal tunnel syndrome (CTS), data from the 1988 National Health Interview Survey, Occupational Health Supplement, were analyzed. When both occupational factors (bending/twisting of the hands/wrists [B/T] and use of hand-held vibrating tools) and personal nonoccupational factors (gender, race, age, body mass index [BMI], smoking, education, and family income) were included in a multivariate logistic regression model, adjusted odds ratios (AORs) of these factors for reporting medically called CTS (MC-CTS) were: exposure to B/T, 5.5; exposure to vibration, 1.9; white race, 16.7; female gender, 2.3; BMI > or = 25, 2.0; history of cigarette smoking, 1.6; age > or = 40, 1.2; education > 12 years, 1.2; and annual family income > or = $20,000, 1.5. Although both occupational and nonoccupational factors are associated with reporting of CTS, repetitive bending/twisting of the hands/wrists and use of vibrating tools remain important risk factors for work-related carpal tunnel syndrome.

Gastrointestinal cancer mortality of workers in occupations with high asbestos exposures.

Asbestos, which is a well-known risk factor for lung cancer and malignant mesothelioma, has also been suggested as a gastrointestinal (GI) carcinogen. This study was conducted to assess the relationship between high asbestos exposure occupations and the occurrence of G1 cancer. Death certificate data were analyzed from 4,943,566 decedents with information on occupation and industry from 28 states from 1979 through 1990. Elevated proportionate mortality ratios (PMRs) for mesothelioma were used to identify occupations potentially having many workers exposed to asbestos. All PMRs were age-adjusted and sex- and race-specific. The PMRs for GI cancers in white males were then calculated for these occupations after excluding mesothelioma, lung cancer, and non-malignant respiratory disease from all deaths. We identified 15,524 cases of GI cancer in the 12 occupations with elevated PMRs for mesothelioma. When these occupations were combined, the PMRs for esophageal, gastric, and colorectal cancer were significantly elevated at 108 (95% confidence interval = 107-110), 110 (106-113), and 109 (107-110), respectively. Esophageal cancer was elevated in sheet metal workers and mechanical workers. Gastric cancer was elevated in supervisors in production and managers. Colorectal cancer was elevated in mechanical and electrical and electronic engineers. However, high exposure occupations like insulation, construction painter supervisors, plumbers, furnace operators, and construction electricians showed no elevations of GI cancers. In conclusion, this death certificate study supports an association between asbestos exposure and some GI cancer, however the magnitude of this effect is very small.

Activation of T Cells by Autoantigen Immobilized by Specific Antibodies

A convenient microtiter-plate assay that uses immobilized antibody to capture specific antigens for presentation to T cells has been developed. Initial experiments used KLH as the antigen, immune antisera and draining lymph node cells from immunized NOD mice as the source of antibody and T cells, and spleen cells from naive NOD mice as the source of antigen-presenting cells (APCs). The resulting proliferation of the T cells was shown to be antibody- and antigen-specific, suggesting that the APCs had internalized and processed the captured antigen, presenting it to the T cells in the form of peptide/MHC complexes. The approach was also tested for an autoimmune disease as part of an effort to identify autoantigens responsible for the proliferation of T cells in the synovial fluid of rheumatoid arthritis patients. When immunoglobulin from autologous synovial fluid was captured on plates coated with anti-human immunoglobulin antibodies, the addition of HLA-DR4 peripheral blood mononuclear cells as APCs and synovial fluid-reactive HLA-DR4-restricted T-cell clones resulted in significant proliferation, indicating that the specific antigen in the crude synovial fluid was human immunoglobulin. This response was also shown to be antigen-specific and HLA-DR4-restricted. This assay format should permit the definition of autoantigens by capturing with antibodies to crude autoantigen extracts, followed by the addition of the appropriate APC and T-cell populations.

The insE open reading frame of IS1 is not required for formation of cointegrates.

The role of the insE open reading frame in transposition of IS1 was reexamined by using an insE nonsense mutation that does not alter the amino acid sequence of InsA inhibitor or InsAB transposase. The mutant was active in all strains tested, showing that insE is not essential for formation of cointegrates.

Expression patterns of laminin receptor splice variants alpha 6A beta 1 and alpha 6B beta 1 suggest different roles in mouse development.

The alpha 6 beta 1 integrin is a receptor for laminins and is present from early stages of mouse embryogenesis. In the present study we determined the temporal and spatial expression of the two cytoplasmic splice variants of the alpha 6 integrin subunit, alpha 6A and alpha 6B, in the early- and mid-gestation mouse postimplantation embryo using RT-PCR, in situ hybridization, and immunofluorescence. Our results show that alpha 6B is present in the embryo at all stages studied and is expressed before alpha 6A. alpha 6A expression begins in 8.5 day p.c. embryos and is initially exclusively localized to the developing heart. In 8.5 (and 9.5) day p.c. embryos alpha 6A mRNA and protein are present in a gradient in the myocardium of the heart tube from strongest expression in the sinus venosus and in the common atrial chamber to a weakening expression along the ventricle and bulbus cordis. In 10.5 day p.c. embryos this gradient is less evident and in 12.5 day p.c. embryos alpha 6A mRNA and protein are present in comparable amounts between atria and ventricles. Neither alpha 6A nor alpha 6B is present in endocardial cushion tissue. By day 12.5 p.c. alpha 6A expression is also present in the developing epidermis, dental primordia, lens, gonads, and in a few epithelia such as those of the digestive tract. alpha 6B expression is always much more widespread than alpha 6A expression. For example, only alpha 6B is present in the myotome of the somites of 9.5 day p.c. embryos, in the developing central and peripheral nervous systems, and in the nephrogenic system at all stages studied, except after the differentiation of the gonads when alpha 6A is also present. Furthermore, alpha 6B is the only splice variant present on endothelial cells. We also examined the distribution of the beta 4 integrin subunit to determine whether the alpha 6 beta 4 integrin was present during these stages of development. Beta 4 protein was absent in early postimplantation stages but was present in the epidermis and digestive tract of 12.5 day p.c. embryos. These results show a differential distribution of alpha 6A and alpha 6B during mouse development and thus strongly suggest a different function of these splice variants during embryogenesis. Our results point to a possible role for the alpha 6A beta 1 integrin in the development of the myocardium of the developing heart, but not in the migration of endocardial cushion cells, while alpha 6B beta 1 could be important in the developing nephrogenic and nervous systems.

Green tobacco sickness: occupational nicotine poisoning in tobacco workers.

In this study the authors describe the investigation of a 1992 outbreak of green tobacco sickness, a form of nicotine poisoning from dermal exposure, among 47 tobacco workers in a five-county region of central and south-central Kentucky. Cases were identified through medical record searches at participating hospitals, as well as from reports submitted to the Occupational Health Nurses in Agricultural Communities program. A case-control study was undertaken to assess risk factors for green tobacco sickness. In a 20-min telephone interview, 40 cases and 83 controls responded to questions contained in a questionnaire. In 1992, 47 persons (3 were under age 16 y) in the study region sought medical treatment for green tobacco sickness. Twelve persons were hospitalized and 2 required intensive-care treatment. The crude incidence in 1992 was 10.0/1,000 tobacco workers. In 1993, 66 cases (7 were under age 16 y) of green tobacco sickness were identified in the study region (i.e., annual incidence of 14.0/1,000). A case-control study demonstrated that ill workers were younger, and were more likely to have worked in wet conditions, compared with workers who were not ill. Green tobacco sickness is a common problem among tobacco workers that may be prevented by avoiding work in wet tobacco or by use of protective clothing. Children younger than 16 y of age represented 9% of the green tobacco sickness cases in 1992 and 1993. Current occupational safety and health laws do not address protection of tobacco workers with respect to green tobacco sickness.

Expression of TGF-beta s and their receptors during implantation and organogenesis of the mouse embryo.

The spatial and temporal expression of the transforming growth factor beta (TGF-beta) receptors type III, type II, and two types I (ALK-5 and Tsk 7L) and their ligands TGF-beta 1 and TGF-beta 2 in postimplantation mouse development were examined using the reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. With RT-PCR, expression of the signaling TGF-beta receptors (types II and ALK-5) was shown to be absent in isolated germ layers of 6.0-7.5 days postcoitum (dpc) embryos, whereas the type III receptor and Tsk 7L were differentially expressed at these stages. In contrast, all TGF-beta receptor types were expressed at these stages in the pregnant uterus and decidua. TGF-beta 1 and TGF-beta 2 transcripts were detected before gastrulation at 6.5 dpc only in the visceral embryonic endoderm, whereas during gastrulation, at 7.5 dpc TGF-beta 1 and TGF-beta 2 mRNA was detected in all three germ layers. In situ hybridization and immunohistochemistry of the expression of the TGF-beta type II receptor confirmed the data obtained by RT-PCR. Furthermore, the type II receptor was detected in the extraembryonic ectoderm of 7.5 dpc embryos. In the embryo proper, TGF-beta type II receptor expression was detected only later in differentiating tissues and developing organs, but not in the brain and neural tube. Since the expression of the type II receptor may essentially determine whether a cell is able to respond to TGF-beta, the results are consistent with the view that TGF-beta s might be implicated in embryo implantation and organogenesis, but are not involved in gastrulation of the embryo.

A biomechanical analysis of prophylactic fixation for pathological fractures of the distal third of the humerus.

Twenty-four matched pairs of fresh-frozen humeri from human cadavera were divided randomly into four groups, in order to determine the most biomechanically desirable construct for the prophylactic fixation of impending fractures of the distal third of the humerus. Group I comprised intact humeri and matched humeri in which a 50 per cent lateral, semicylindrical cortical defect of the distal third had been created, resulting in a reproducible model of an impending fracture due to a lytic defect involving 50 per cent cortical disruption at the distal end of the humeral medullary canal. In Group II, such a lateral defect was created in both the right and the left, matched humeri. Group III was composed of humeri in which the defect had been fixed prophylactically with a single plate and the contralateral humeri, which had been treated with double-plating. Group IV comprised specimens in which the defect had been fixed with double-plating as well as those fixed with Rush rods. The fixation of each specimen in Groups III and IV was supplemented with bone cement. Each specimen was tested in torsion to failure, and the resulting peak torque, torsional stiffness, and total energy absorbed were analyzed for each group. The Group-I specimens that had a defect had a significantly lower (p < 0.05) peak torque, torsional stiffness, and total energy absorbed than the intact specimens; all of the specimens with a defect failed at the defect, and all of the intact specimens failed proximally. In Group II, there was a high side-to-side association with respect to peak torque, torsional stiffness, and total energy absorbed.(ABSTRACT TRUNCATED AT 250 WORDS)