A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis.

BACKGROUND: Thyroid dysgenesis is the most frequent cause of congenital hypothyroidism (CH), and its genetic basis is largely unknown. Hitherto, two mutations in the human thyroid transcription factor 2 (TTF-2) gene have been described in unrelated cases of CH with cleft palate, spiky hair, variable choanal atresia, and complete thyroid agenesis. Here, we describe a novel TTF-2 mutation in a female child resulting in syndromic CH in the absence of thyroid agenesis. RESULTS: The index case is homozygous for an arginine to cysteine mutation (R102C) of a highly conserved residue within the forkhead, DNA binding domain of TTF-2. Her consanguineous, heterozygous parents are unaffected, and the mutation was not detected in 100 control chromosomes. Consonant with its location, the R102C mutant TTF-2 protein showed loss of DNA binding and was transcriptionally inactive. CH in the proposita was associated with cleft palate, spiky hair, and bilateral choanal atresia. However, radiological studies showed the presence of thyroid tissue in a eutopic location. CONCLUSION: Our findings indicate that human thyroid development can occur despite loss of TTF-2 function and suggest that TTF-2 gene defects should also be considered in cases of syndromic CH without total athyreosis.

Elevated plasma adiponectin in humans with genetically defective insulin receptors.

CONTEXT: Adiponectin has been suggested to play a role in the etiopathogenesis of at least some forms of insulin resistance, in part based on a strong correlation between plasma levels of adiponectin and measures of insulin sensitivity. OBJECTIVE: The objective of the study was to establish whether this relationship is maintained at extreme levels of insulin resistance. DESIGN/SETTING: This was a cross-sectional study in a university teaching hospital of subjects recruited from the United Kingdom and the United States. PARTICIPANTS: Participants included 75 subjects with a range of syndromes of severe insulin resistance and 872 nondiabetic controls. OUTCOME MEASURES: Fasting plasma insulin, adiponectin, and leptin were measured. RESULTS: Unexpectedly, subjects with mutations in the insulin receptor, despite having the most severe degree of insulin resistance, had elevated plasma adiponectin [median 24.4 mg/liter; range 6.6-36.6 (normal adult range for body mass index 20 kg/m(2) = 3-19 mg/liter)], whereas all other subjects had low adiponectin levels (median 2.0 mg/liter; range 0.12-11.2). Plasma leptin in all but one subject with an insulin receptoropathy was low or undetectable [median 0.5 ng/ml; range 0-16: normal adult range for body mass index of < 25 kg/m(2) = 2.4-24.4 (female) and 0.4-8.3 ng/ml (male)]. CONCLUSIONS: We conclude that the relationship between plasma adiponectin and insulin sensitivity is complex and dependent on the precise etiology of defective insulin action and that the combination of high plasma adiponectin with low leptin may have clinical utility in patients with severe insulin resistance as a marker of the presence of a genetic defect in the insulin receptor.

Both Trevor and Ollier disease limited to one upper extremity.

A case is presented of a young boy in whom features of Trevor's dysplasia epiphysealis hemimelica and Ollier's enchondromatosis coexisted in a single extremity, the right upper. As Trevor disease consists of osteochondromas of epiphyses and their equivalents, such as carpal and tarsal bones, it is of interest that exostosis-like centers of the neck of radius and perhaps the proximal third metacarpal are present as well. Advanced maturation of selected centers was most marked at the right scaphoid. The child shows alignment abnormalities as a consequence of the varied lesions, including a varus of the right wrist. The coexistence of these varied osteochondromatous abnormalities in one extremity suggests a relationship in their etiologies.

Bronchial reactivity of healthy subjects: 18-20 h postexposure to ozone.

Exposure of humans to ambient levels of ozone (O(3)) causes inflammatory changes within lung tissues. These changes have been reported for the "initial" (1- to 3-h) and "late" (18- to 20-h) postexposure periods. We hypothesized that at the late period, when protein and cellular markers of inflammation at the airway surface remain abnormal and the integrity of the epithelial barrier is compromised, bronchial reactivity would be increased. To test this, we measured airway responsiveness to cumulative doses of methacholine (MCh) aerosol in healthy subjects 19+/-1 h after a single exposure to O(3) (130 min at ambient levels between 120 and 240 parts/billion and alternate periods of rest and moderate exercise) or filtered air. Exposures were conducted at two temperatures: mild (22 degrees C) and moderate (30 degrees C). At the late period, bronchial reactivity to MCh increased, i.e., interpolated dose of MCh leading to a 50% fall in specific airway conductance (PC(50)) was less after O(3) than after filtered air. PC(50) for O(3) at 22 degrees C was 27 mg/ml (20% less than the PC(50) after filtered air), and for O(3) at 30 degrees C it was 19 mg/ml (70% less than the PC(50) after filtered air). The forced expiratory volume in 1 s (FEV(1)) at the late time point after O(3) was slightly but significantly reduced (2.3%) from the preexposure level. There was no relationship found between the functional changes observed early after exposure to O(3) and subsequent changes in bronchial reactivity or FEV(1) at the late time point. These results suggest that bronchial reactivity is significantly altered approximately 1 day after O(3); this injury may contribute to the respiratory morbidity that is observed 1-2 days after an episode of ambient air pollution.

Immunologic parameters of multiple chemical sensitivity.

Immunologic abnormalities have long been advanced as a potential mechanism for multiple chemical sensitivity (MCS). An immunologic mechanism is supported in part by the systemic nature of the symptoms reported, the complex interactions known to exist between the immune system and other systems, and limited experimental evidence. However, there are both theoretical grounds for doubting an immunologic mechanism in MCS and methodological constraints in many of the studies that have been conducted in humans. The authors discuss the structure and function of the immune system as it potentially applies to MCS, the uses and limitations of immunologic testing, and the evidence for immunologic theories of MCS. They describe recent work to validate some of the immunologic tests used in MCS and consider opportunities for further research.

Interventions for the primary prevention of work-related carpal tunnel syndrome.

OBJECTIVE: To evaluate interventions for the primary prevention of work-related carpal tunnel syndrome (CTS). SELECTION CRITERIA: Studies had to include an engineering, administrative, personal, or multiple component intervention applied to a working or working-age population. All study designs that included comparison data were considered. Outcome measures included the incidence, symptoms, or risk factors for CTS, or a work-related musculoskeletal disorder of the upper extremity that included CTS in the definition. RESULTS: Twenty-four studies met our inclusion criteria. Engineering interventions included alternative keyboards, computer mouse designs and wrist supports, keyboard support systems, and tool redesign. Personal interventions included ergonomics training, splint wearing, electromyographic biofeedback, and on-the-job exercise programs. Multiple component interventions (e.g., ergonomic programs) included workstation redesign, establishment of an ergonomics task force, job rotation, ergonomics training, and restricted duty provisions. Multiple component programs were associated with reduced incidence rates of CTS, but the results are inconclusive because they did not adequately control for potential confounders. Several engineering interventions positively influenced risk factors associated with CTS, but the evaluations did not measure disease incidence. None of the personal interventions alone was associated with significant changes in symptoms or risk factors. All of the studies had important methodologic limitations that may affect the validity of the results. CONCLUSIONS: While results from several studies suggest that multiple component ergonomics programs, alternative keyboard supports, and mouse and tool redesign may be beneficial, none of the studies conclusively demonstrates that the interventions would result in the primary prevention of carpal tunnel syndrome in a working population. Given the societal impact of CTS, the growing number of commercial remedies, and their lack of demonstrated effec- tiveness, the need for more rigorous and long-term evaluation of interventions is clear. Fund- ing for intervention research should prioritize randomized controlled trials that include: (1) adequate sample size, (2) adjustment for relevant confounding variables, (3) isolation of speci- fic program elements, and (4) measurement of long-term primary outcomes such as the inci- dence of CTS, and secondary outcomes such as employment status and cost.

Chemical hazards in radiology.

A variety of chemicals are used in medical imaging as developer and fixer ingredients, germicides, and cleaning agents. Glutaraldehyde, a potent sensitizer, may cause occupational skin and respiratory diseases in exposed individuals. Poor ventilation, unsafe practices, and lack of hazard recognition may contribute to occupational asthma and other respiratory disease in susceptible medical imaging personnel. Failure to respond effectively to initial health complaints and reduce exposure levels can have serious consequences for affected employees. It is therefore important for occupational safety and health professionals to alert health facility managers to potential dangers and to recommend effective intervention strategies. When problems are identified, a multidisciplinary team approach is the best method for evaluating and controlling hazards. This team should include industrial hygienists, safety staff, occupational medicine physicians, mechanical and ventilation engineers, personnel specialists, and medical imaging staff. A thorough hazard assessment, medical diagnosis, and administrative personnel actions are critical to effective problem identification and correction. In the case of chemical sensitization, removal of the affected employee may be necessary. By working with designers and equipment installers to monitor compliance with appropriate codes and manufacturers' specifications, hazards can be prevented. We present additional operations, ventilation, and design improvements to reduce chemical exposures to radiology employees.

The "circle sign": a new sonographic sign of pneumatosis intestinalis - clinical, pathologic and experimental findings.

BACKGROUND: Pneumatosis intestinalis (PI) represents gas in the bowel wall. The appearance of PI using high-resolution ultrasound (HRUS) has not been well described. OBJECTIVE: The purpose of this report is to describe a new ultrasound sign of pneumatosis seen in three patients. This sign, called the "circle sign", is indicative of bubbles of gas within the circumference of the bowel, producing an appearance of a continuous echogenic ring on ultrasound. Further studies of the sonographic characteristics of pneumatosis were performed with an in vitro model. MATERIALS AND METHODS: HRUS was performed prospectively in three patients demonstrating extensive PI radiographically. The appearance of the gas was characterized and the behavior of the intramural bubbles was studied when the bowel was compressed with the ultrasound transducer. Either CT scan or pathologic correlation was obtained in all patients. Experimental models of PI using air injected into the wall of sausage casing were developed. RESULTS: The presence of echogenic gas bubbles within the circumference of the wall of the bowel seen with HRUS was shown to represent pneumatosis intestinalis at histologic examination or by CT scanning in the three study patients. In vitro studies confirmed the clinical impression that the use of compression is helpful in distinguishing intramural from intraluminal air. CONCLUSION: The presence of echogenic gas bubbles in the wall of the bowel, often seen as a circle within the circumference of the bowel, may be helpful in diagnosing PI on ultrasound using HRUS.

Vertex hemangioma mimicking an encephalocele.

Most extracranial masses detected prenatally by use of ultrasonography are either encephaloceles or meningoceles. This article describes an extracranial mass detected prenatally that was initially thought to be an encephalocele, but was subsequently found to be a large hemangioma.

Evaluating occupational health and safety programs in the public sector.

BACKGROUND: Two case studies are presented of public sector occupational health and safety (OHS) program evaluations, one of an occupational medicine and safety program (OMSP), one of an employee assistance and wellness program (EAWP). METHODS: Both audits involved interviews with key personnel, review of written documentation and physical resources, chart audits, and surveys of the programs' stakeholders. RESULTS: Key findings of the OMSP evaluation were that the various functions were substantially hampered by the absence of an integrated information system. Mechanisms for effective coordination, communication, and feedback were also lacking. The EAWP audit concluded that it provided a valuable and needed service. The mission, staff, facilities, and services offered were in line with the needs of the served community. DISCUSSION: Differences between private and public sector OHS program evaluation include programmatic and environmental factors such as resource availability, organizational structure, and accountability. Similarities include trends in both sectors forcing programs to justify themselves in terms of economic benefits to their respective organizations.

Magnetic resonance imaging of Takayasu's aortitis in an infant.

A fusiform aneurysm involving the ascending aorta and aortic arch in an 8-month-old infant was imaged with magnetic resonance. Histologic studies of the excised aneurysm indicated Takayasu's arteritis. Takayasu's arteritis has rarely been reported in infants, and involvement of the ascending aorta and aortic arch is an unusual finding in this age group.

Noninvasive botryoid extension of Wilms' tumor into the bladder.

We present the previously unreported CT appearance of a Wilms' tumor which extended down the ureter and protruded into the bladder as a botryoid mass. The tumor apparently arose from an intralobar nephrogenic rest and demonstrated local invasion into renal sinus vessels and papillae. There was no tumor invasion into the wall of the ureter or bladder, and therefore, the extension into the ureter and bladder did not upstage the tumor. This report adds to the list of differential diagnoses of a botryoid bladder mass in a child and demonstrates yet another unusual manifestation of Wilms' tumor.

Colon carcinoma discovered in an adolescent during inguinal hernia repair.

Colon carcinoma is an unusual tumor during childhood. The authors report a case of metastatic colonic adenocarcinoma diagnosed in a 14-year-old boy during inguinal hernia repair. To the authors' knowledge, this is the first reported case of this rare disease presenting as an inguinal hernia.

Outcome studies in industry: cost-effectiveness of cumulative trauma disorder prevention.

Cost-effectiveness analysis (CEA) is a method for choosing between alternative strategies to achieve a specified outcome in an environment of limited resources. This paper discusses the use of CEA in evaluating prevention strategies in industrial settings, using cumulative trauma disorder (CTD) prevention programs as an example. Methodologic issues in designing studies of cost-effectiveness for preventive interventions are discussed. A decision analysis model of a CTD prevention program is described as a means of studying the program's cost-effectiveness. The relationship between CEA and outcomes research, and the strengths and limitations of CEA in evaluating occupational health prevention programs is considered.

Clinical evaluation of 58 organolead manufacturing workers.

Fifty-eight workers were evaluated at a university-based occupational health clinic for potential health effects related to organic and inorganic lead exposures. The clinical evaluation included a history, physical, and laboratory examination, and in a subset of workers, neurobehavioral tests and nerve conduction studies. Workers reported symptoms that predominantly involved the central and peripheral nervous systems. Findings for which no alternative medical explanations could be found included neurobehavioral abnormalities (18 of 39 workers) and sensorimotor polyneuropathies (11 of 31 workers). The clinical presentation and evaluation of workers exposed to organic lead are discussed.

Detection of bone lesions in Langerhans cell histiocytosis: complementary roles of scintigraphy and conventional radiography.

PURPOSE: This research was undertaken to determine the relative sensitivity of scintigraphic and radiographic bone survey examinations in detecting bone lesions in various regions of the skeleton in patients with a histopathologic diagnosis of Langerhans cell histiocytosis (LCH). PATIENTS AND METHODS: Radionuclide skeletal scintigraphy (RNSS) and x-ray skeletal surveys (XRSS) of 42 children with a histopathologic diagnosis of LCH were evaluated retrospectively. RESULTS: Of the 191 lesions detected in 42 patients, 36 (19%) were missed on RNSS and 55 (29%) were missed on XRSS. Most of the missed lesions on RNSS were in the skull (26 of 36). XRSS also missed 13 skull lesions seen on RNSS. Most of the lesions missed on XRSS were in the ribs (20 of 30 rib lesions), whereas RNSS identified 29 of them. XRSS also missed 13 of 38 lesions in the spine and pelvis, while RNSS demonstrated all of them. Both modalities showed comparable sensitivity in the extremities. CONCLUSION: RNSS has a greater value in detecting sites of bone involvement with LCH than reported previously. RNSS is more sensitive than XRSS in detecting histiocytic lesions in the ribs, spine and pelvis and less sensitive in identifying lesions in the skull.