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A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome.

OBJECTIVE: To describe a multigenerational family with transmission of an autosomal dominant disorder characterized by pyogenic arthritis, pyoderma gangrenosum, and severe cystic acne. MATERIAL AND METHODS: We present a detailed case report of a 39-year-old man with arthritic changes in several joints, pyoderma gangrenosum, and cystic acne. Several relatives from three generations of his family underwent clinical and genetic investigations. The findings in this kindred are reported. RESULTS: Ten affected family members in three generations manifested variable expression of a pauciarticular, nonaxial, destructive, corticosteroid-responsive arthritis that began in childhood; pyoderma gangrenosum; and severe cystic acne in adolescence and beyond. Other less commonly associated features included adult-onset insulin-dependent diabetes mellitus, proteinuria, abscess formation at the site of parenteral injections, and cytopenias attributable to sulfonamide medications. Laboratory evaluation was nondiagnostic. Genetic studies excluded linkage to the major histocompatibility locus. CONCLUSION: The acronym of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) is suggested for this newly recognized pleiotropic autosomal dominant disorder. The nature of the genetic alteration in PAPA syndrome is unknown.

Acne Vulgaris↗

Gallbladder and biliary tract candidiasis.

BACKGROUND: The clinical significance of Candida spp isolated from the gallbladder on the biliary tract is relatively unknown. METHODS: To provide this information, patients with Candida spp isolated from gallbladder and other biliary tract sources during a 10-year period were identified through the records of our clinical microbiology laboratory. Medical records were analyzed for biliary disease causes, culture data, treatment, and outcome. RESULTS: Twenty-seven patients were identified. Five of seven patients with cholecystitis were critically ill intensive care unit (ICU) patients in whom the mortality rate was 100%. Gallstone pancreatitis was found in four patients and was fatal in one patient with a pancreatic abscess and ongoing retroperitoneal sepsis. An external biliary shunt/endoprosthesis was placed in 16 patients to relieve biliary obstruction. Cholangitis was present in 14 patients, and most bile cultures contained Candida as part of a mixed flora. Only 3 of 27 patients had candidemia, and 22 of 27 patients were colonized with Candida at other sites. CONCLUSIONS: (1) The ICU patient with Candida cholecystitis has a grave prognosis. (2) Patients with Candida isolated from biliary stents placed for obstruction and cholangitis should be treated with both antifungal and broad spectrum antimicrobial agents. (3) Candidemia is not frequently seen in this setting.

Adult↗

Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease.

Granuloma annulare (GA) and necrobiosis lipoidica (NL) are generally considered to be idiopathic cutaneous palisading granulomatous dermatitides. There are sporadic reports of such lesions occurring in patients with coexistent systemic diseases other than diabetes mellitus. Having encountered 49 patients whose skin biopsies showed GA or NL lesions in the setting of extracutaneous disease, the authors set out to assess their clinical and histopathological findings to determine if any parameters were predictive of underlying systemic disease. Fifty-two skin biopsies from 49 patients having either GA or NL in whom there was a clinical history of an associated systemic disease were analyzed by light microscopy. The main systemic disease associations were rheumatologic, endocrine, hematologic, infectious, and inflammatory bowel diseases, ANCA positive vasculitic syndromes, and sarcoidosis. The clinical and histomorphological features were compared with those of a control group of patients whose skin biopsies showed GA or NL and in whom there was no history of extracutaneous disease. For the systemic disease group, patients were selected either retrospectively or prospectively from 160,000 cases accessioned in a 24-month period in the dermatopathology databases of Pathology Services, Inc (Cambridge, MA) and Central Medical Laboratories (Winnipeg, Canada). All systemic disease cases from the former service were analyzed blindly by the second author and from the latter service were analyzed blindly by the first author. Patients in the control group were obtained retrospectively from the Pathology Services Inc. database by the authors. The location of the lesions was atypical in 30 of 34 biopsies from systemic disease patients with a GA tissue reaction versus 10 of 22 biopsies of GA in the control group (P = .001). Six of 18 biopsies from patients with NL tissue reactions in the systemic disease group showed an atypical location, versus only 1 of 9 biopsies of NL from the control group (P = .19). The clinical diagnostic considerations were much broader in the systemic disease group versus the control group and included vasculitis, panniculitis, and connective tissue diseases including morphea in the former. In 22 of 34 GA biopsies and 16 of 18 NL biopsies from the systemic disease group, an active vasculopathy of leukocytoclastic, granulomatous, or thrombogenic subtypes was demonstrable. None of the GA or NL biopsies from the control group showed a similar active vasculopathy. An active vasculopathy was predictive of systemic disease in patients having either a GA-like or an NL-like tissue reaction (P < .001). Fifteen of 34 GA and 7 of 18 NL biopsies in the systemic diseases group showed extravascular neutrophilia in contrast to 3 of 22 GA (P = .02) biopsies and 2 of 9 NL (P = .33) biopsies in the control group. The finding of an active vasculopathy in a skin biopsy specimen showing a GA- or NL-like tissue reaction, particularly in the setting of an atypical clinical presentation both with respect to the location and appearance of lesions, should prompt consideration of an underlying systemic disease, as should extravascular neutrophilia in a skin biopsy showing a GA-like tissue reaction.

Adult↗

Non-O157 Vero cytotoxin producing Escherichia coli: aetiological agents of diarrhoea in children in Dunedin, New Zealand.

Strains of Escherichia coli that produce Vero cytotoxin (VTEC) commonly cause diarrhoea, haemorrhagic colitis and haemolytic-uraemic syndrome in many northern hemisphere countries. In these countries, serotype O157:H7/H-predominates and has caused large food-borne outbreaks of infection. In contrast, few cases of infection with this serotype have been reported in New Zealand. Over a 3-month period, 484 stool specimens submitted to medical laboratories in Dunedin were screened for E. coli O157:H7/H-using sorbitol MacConkey agar, Y1 and Vero cell assays. Where possible, Vero cytotoxin production was confirmed by an ELISA test. Specimens from children aged 12 years or less were additionally screened for non-O157 VTEC. In the specimens of the children tested, O157:H7/H-VTEC was not isolated, but VTEC belonging to other serogroups were isolated from the children. Of interest was the detection of other species of Enterobacteriaceae, which produced a cytopathic effect on Vero cells. This study confirms the low incidence of infection with O157:H7/H- VTEC in New Zealand and suggests that non-O157 VTEC is a more important cause of diarrhoeal disease.

Animals↗

A descriptive study of blood exposure incidents among healthcare workers in a university hospital in Sweden.

In an attempt to document blood exposure incidents and compliance with recommended serological investigations, universal precautions and incident reporting routines, data was collected from occupational injury reports during a two-year period. In addition, a sample of healthcare workers (HCWs) answered a questionnaire about blood tests and work routines. In a third part of the study some HCWs were asked about the type and actual frequency of incidents, together with the number of reported incidents during the two-year study period. Of a total of 473 reported occupational blood exposures, the majority came from nurses and the minority from physicians. Most reported incidents occurred on hospital wards. The most common incidents were needlestick injuries, and 35% occurred when the needle was recapped. Medical laboratory technicians (MLT) reported significantly more mucocutaneous incidents than other professionals (P < 0.01). In 10% of the incidents, the patient had a known blood-borne infection. Serological investigations post-exposure varied among professional groups, and 35% were not tested. No seroconversion was shown in the HCWs tested. In the third part of the study, respondents recalled 1180 incidents, although only 9% of these had been reported. The majority occurred in operating theatres, and in connection with anaesthesia. There was a significant difference (P < 0.001) between the different professional groups with regard to the frequency of incident reporting. Physicians reported only 3% and MLTs 36% of the incidents. Eighty-one percent believed that the accident could have been avoided. Despite knowledge of universal precautions, professionals continue to behave in a risky manner, which can result in blood exposure incidents.

Adolescent↗

The impact of diagnosis-related groups on the cost of hospitalization for end-stage renal disease patients at Rhode Island Hospital from 1987 to 1990.

The introduction of diagnosis-related groups (DRGs) for the reimbursement of hospital costs in the Medicare population made no provisions to identify end-stage renal disease (ESRD) patients. To assess the impact of the DRGs on ESRD patients, we prospectively evaluated all hospitalizations (901) at the Rhode Island Hospital from July 1987 through April 1990 among a chronic hemodialysis population of 587 patients. The complied data on length of hospital stay, cost per day, and total cost were compared with the accepted allowances as defined by the DRG codes assigned to the admissions. The mean values and comparisons were length of stay, 10.2 +/- 21 days (ESRD) versus 9.7 +/- 3.6 days (DRGs), P = 0.44; cost per day, $1,240 +/- $685 (ESRD) versus $671 +/- $897 (DRGs), P = 0.0001; and total cost, $9,660 +/- $17,170 (ESRD) versus $6,815 +/- $8,872 (DRGs), P = 0.0001, a difference of $2,275 per admission. The increase in daily, and thus total, costs was primarily due to the use of supplies, medications, laboratory procedures, and transfusion services. It appears from our data that the DRGs do not adequately reflect the cost of caring for ESRD patients with the same DRGs as non-ESRD patients because of increased demand for ancillary services. If these observations are confirmed, a reevaluation of the DRG process as it relates to ESRD patients is warranted.

Diagnosis-Related Groups↗

Combination of boron neutron capture therapy and external beam radiotherapy for brain tumors.

PURPOSE: Boron neutron capture therapy (BNCT) has been used clinically as a single modality treatment for high-grade gliomas and melanomas metastatic to the brain. The purpose of the present study was to determine whether its efficacy could be enhanced by an X-ray boost administered after BNCT. Two brain tumor models were used, the F98 glioma as a model for primary brain tumors and the MRA 27 human melanoma as a model for metastatic brain tumors. METHODS AND MATERIALS: For biodistribution studies, either 10(5) F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats or 10(6) MRA 27 melanoma cells were implanted intracerebrally into National Institutes of Health (NIH)-rnu nude rats. Biodistribution studies were performed 11-13 days after implantation of the F98 glioma and 20-24 days after implantation of the MRA 27 melanoma. Animals bearing the F98 glioma received a combination of two boron-containing drugs, sodium borocaptate at a dose of 30 mg/kg and boron phenylalanine (BPA) at a dose of 250 mg/kg. MRA 27 melanoma-bearing rats received BPA (500 mg/kg) containing an equivalent amount of 10B (27 mg B/kg). The drugs were administered by either intracarotid or i.v. injection. RESULTS: The tumor boron concentration after intracarotid injection was approximately 50% greater in the F98 glioma and MRA 27 melanoma after intracarotid injection (20.8 and 36.8 microg/g, respectively) compared with i.v. injection (11.2 and 19.5 microg/g, respectively). BNCT was carried out at the Brookhaven National Laboratory Medical Research Reactor approximately 14 days after tumor implantation of either the F98 glioma or the MRA 27 melanoma. Approximately 7-10 days after BNCT, subsets of animals were irradiated with 6-MV photons, produced by a linear accelerator at a total dose of 15 Gy, delivered in 5-Gy daily fractions. F98 glioma-bearing rats that received intracarotid or i.v. sodium borocaptate plus BPA, followed 2.5 h later by BNCT and 7-10 days later by X-rays, had similar mean survival times (61 days and 53 days, respectively, p = 0.25), and the non X-irradiated, BNCT-treated animals had a mean survival time of 52 and 40 days, respectively, for intracarotid vs. i.v. injection; the latter was equivalent to that of the irradiated animals. The corresponding survival time for MRA 27 melanoma-bearing rats that received intracarotid or i.v. BPA, followed by BNCT and then X-irradiation, was 75 and 82 days, respectively (p = 0.5), 54 days without X-irradiation (p = 0.0002), 37 days for X-irradiation alone, and 24 days for untreated controls. In contrast to the data obtained with the F98 glioma, MRA 27 melanoma-bearing rats that received i.v. BPA, followed by BNCT, had a highly significant difference in mean survival time compared with the irradiated controls (54 vs. 37 days, p = 0.008). CONCLUSION: Our data are the first to suggest that a significant therapeutic gain may be obtained when BNCT is combined with an X-ray boost. Additional experimental studies are required to determine the optimal combination of X-radiation and neutron doses and whether it is more advantageous to administer the photon boost before or after BNCT.

Animals↗

Boron neutron capture therapy of brain tumors: enhanced survival following intracarotid injection of sodium borocaptate with or without blood-brain barrier disruption.

PURPOSE: Sodium borocaptate (Na2B12H11SH or BSH) has been used clinically for boron neutron capture therapy (BNCT) of patients with primary brain tumors. The purpose of the present study was to determine if tumor uptake of BSH and efficacy of BNCT could be enhanced in F98 glioma-bearing rats by intracarotid (i.c.) injection of the compound with or without blood-brain barrier disruption (BBB-D). METHODS AND MATERIALS: For biodistribution studies 100,000 F98 glioma cells were implanted stereotactically into the brains of Fischer rats, and 12 days later BBB-D was carried out by i.c. infusion of 25% mannitol, followed immediately thereafter by i.c. injection of BSH (30 mg B/kg body weight). Animals were killed 1, 2.5, and 5 h later, and their brains were removed for boron determination. For BNCT experiments, which were initiated 14 days after intracerebral implantation of 1000 F98 cells, BSH (30 mg B/kg b.wt. was administered intravenously (i.v.) without BBB-D, or i.c. with or without BBB-D. The animals were irradiated 2.5 h later with a collimated beam of thermal neutrons at the Brookhaven National Laboratory Medical Research Reactor. RESULTS: The mean tumor boron concentration after i.c. injection with BBB-D was 48.6 +/- 17.2 microg/g at 2.5 h compared with 30.8 +/- 12.2 microg/g after i.c. injection without BBB-D and 12.9 +/- 4.2 microg/g after i.v. injection. The best composite tumor to normal tissue ratios were observed at 2.5 h after BBB-D, at which time the tumor:blood (T:B1) ratio was 5.0, and the tumor: brain (T:Br) ratio was 12.3, compared to 1.1 and 4.6, respectively, in i.v. injected rats. The mean survival time for untreated control rats was 24 +/- 3 days, 29 +/- 4 days for irradiated controls, 33 +/- 6 days for those receiving i.v. injection of BSH, 40 +/- 8 days for rats receiving i.c. BSH without BBB-D, and 52 +/- 13 days for BBB-D followed by BNCT (p = 0.003 vs. i.v. injected BSH). CONCLUSIONS: Intracarotid administration of BSH with or without BBB-D significantly increased tumor uptake of BSH and enhanced survival of F98 glioma-bearing rats following BNCT. BBB-D may be a useful way to enhance the delivery of both low and high molecular weight boron compounds to brain tumors. Further studies are in progress to assess this approach with other boron delivery agents.

Animals↗

Training costs and investment payback of implementing molecular diagnostics for identification of vancomycin resistant enterococci in a clinical microbiology laboratory.

Molecular diagnostics may be a more efficient method to manage resources; but most Microbiology laboratories have not introduced them into routine use due to the specialized training required. Using vancomycin resistant enterococci (VRE) screening during a comparison of a multiplex PCR (MPCR) and conventional biochemical testing (CBT) we studied 3 objectives: 1) to develop a molecular diagnostics in-house training program, 2) to assess the training program outcomes for competency and confidence, and 3) to determine laboratory payback. A training program for 14 technologists using multiple adult learning methods was implemented. Methods to minimize technical errors were introduced and included: use of a calibrated loop to deliver sample; prealiquotting reagents; increasing volume of specimen; addition of gel loading dye directly into reaction tubes; and establishment of an equivocal zone. In our laboratory MPCR costs $7.06 less than CBT, therefore the payback period for training and implementation would be approximately 3 years.

Cost-Benefit Analysis↗

Antimicrobial resistance and serotypes of Shigella isolates in Kigali, Rwanda (1983 to 1993): increasing frequency of multiple resistance.

The serotype distribution and susceptibility to nine antibiotics was determined for 2491 Shigella isolates cultured in the medical laboratory of the Centre Hospitalier de Kigali, Rwanda, during 1983 to 1993. Overall, Shigella flexneri was the most frequent species, ranking before Shigella sonnei, Shigella boydii, and Shigella dysenteriae. However, the relative frequency of the different Shigella spp. showed an important variability over time. S flexneri increased from 40% in 1983 to 68% of the isolates in 1993 whereas S. dysenteriae Type 1 decreased gradually from 30 to 0.5% of the isolates in 1992. After the outbreak of severe civil unrest, which caused the displacement of many people to the capital, a new epidemic of dysentery started in the Kigali area and S. dysenteriae Type 1 accounted again for 24% of the isolates in 1993. In 1983, resistance to tetracycline, streptomycin, and sulfonamides was common among the endemic Shigella spp. Resistance to chloramphenicol was observed in 17% (30/182) of the isolates. Only 10% were resistant to ampicillin and an equal proportion to trimethoprim, whereas 5% of the isolates showed resistance to both products. By 1993, 66% (195/295) of the isolates were resistant to chloramphenicol (for comparison with 1983, p < 0.001), 70% (207/295) to ampicillin (p < 0.001), 67% to trimethoprim (p < 0.001), and 58% had combined resistance to the latter two drugs (p < 0.001). Resistance patterns differed strongly by species, S. flexneri being more frequently resistant than S. sonnei. In 1983, all S. dysenteriae Type 1 isolates were resistant to ampicillin, chloramphenicol, tetracycline, and sulfonamides. Trimethoprim resistance increased from 31% (25/80) in 1983 to 96% (26/27) of the isolates in 1986 (p < 0.001). After the introduction of nalidixic acid as an alternative for trimethoprim-sulfamethoxazole, trimethoprim resistance decreased to 87%, during 1987 to 1992, and subsequently to 68% of the isolates in 1993. However, 20% of the isolates became resistant to nalidixic acid in 1993. Ampicillin and trimethoprim-sulfamethoxazole are no longer useful for the empirical treatment of shigellosis in Rwanda.

Anti-Bacterial Agents↗

Quantitative determination of dibekacin using radioimmunoassay, substrate-labelled fluorescent immunoassay and rate nephelometric inhibition immunoassay for tobramycin.

Radioimmunoassay, rate nephelometric inhibition immunoassay and substrate-labelled fluorescent immunoassay were employed for the quantitative determination of dibekacin in serum. The cross-reactivity of the antibody provided with each assay allowed the use of tobramycin assay procedures for measuring dibekacin concentrations. With radioimmunoassay and nephelometric immunoassay, a dibekacin calibration curve was required, whereas fluorescent immunoassay was directly suitable for dibekacin assay, with cross-reactivity of nearly 100%. This allows the purchase of one assay kit for testing two antibiotics and thus reduces the cost to medical laboratories.

Cross Reactions↗

Biodegradation of orthodontic appliances. Part II. Changes in the blood level of nickel.

The purpose of this study is to determine whether orthodontic patients accumulate measurable concentrations of nickel in their blood during their initial course of orthodontic therapy. Blood samples were collected at three different time periods: before the placement of orthodontic appliances, 2 months after their placement, and 4 to 5 months after their placement. The study involved 31 subjects, 18 females and 13 males, who had malocclusions that required the use of a fully banded and bonded edgewise appliance. The age of the subjects in the study ranged between 12 and 38 years. The blood samples were frozen and shipped to a commercial medical laboratory for analysis by atomic absorption spectrophotometry. The three blood samples for each patient were analyzed in succession on the same day to eliminate equipment variance that could occur if blood samples were analyzed on separate days. A total of 93 blood samples were sent for analysis. From the findings in this study the following can be concluded: (1) Patients with fully banded and bonded orthodontic appliances did not show either a significant or consistent increase in nickel blood levels during the first 4 to 5 months of orthodontic therapy. (2) Orthodontic therapy using appliances made of alloys containing nickel-titanium did not result in a significant or consistent increase in the blood levels of nickel. The results obtained from both parts of this investigation indicate that orthodontic appliances used, in their "as-received" condition, corrode in the oral environment releasing both nickel and chromium, in amounts significantly below the average dietary intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A client/server system for Internet access to biomedical text/image databanks.

Internet access to mixed text/image databanks is finding application in the medical world. An example is a database of medical X-rays and associated data consisting of demographic, socioeconomic, physician's exam, medical laboratory and other information collected as part of a nationwide health survey conducted by the government. Another example is a collection of digitized cryosection images, CT and MR taken of cadavers as part of the National Library of Medicine's Visible Human Project. In both cases, the challenge is to provide access to both the image and the associated text for a wide end user community to create atlases, conduct epidemiological studies, to develop image-specific algorithms for compression, enhancement and other types of image processing, among many other applications. The databanks mentioned above are being created in prototype form. This paper describes the prototype system developed for the archiving of the data and the client software to enable a broad range of end users to access the archive, retrieve text and image data, display the data and manipulate the images. System design considerations include; data organization in a relational database management system with object-oriented extensions; a hierarchical organization of the image data by different resolution levels for different user classes; client design based on common hardware and software platforms incorporating SQL search capability, X Window, Motif and TAE (a development environment supporting rapid prototyping and management of graphic-oriented user interfaces); potential to include ultra high resolution display monitors as a user option; intuitive user interface paradigm for building complex queries; and contrast enhancement, magnification and mensuration tools for better viewing by the user.

Anatomy, Cross-Sectional↗

Dietary treatments of obesity.

Numerous dietary treatments that purport to promote something unique for stimulating weight loss have been published. These treatments include fad diets, diets formulated by various commercial slimming clubs, very-low-energy diets (VLCD) and conventional diets. Fad diets may possibly reduce some weight short-term; however, there is no scientific basis to their long-term use. Commercial slimming clubs may be suitable for some individuals but they need to be properly assessed professionally. There are specific guidelines for the use of VLCD, which are only appropriate for short-term use. There is scientific evidence to suggest that conventional diets can produce both short- and long-term weight loss. A successful weight-loss programme depends on a multidisciplinary team approach. Management strategies should be devised for addressing issues such as goals, monitoring, follow-up, relapse and evaluation. Initial assessments should include medical, laboratory and anthropometric data, fitness level and dietary and behavioural attitudes. These results will form the basis of the treatment plan. Frequent visits to the clinic are fundamental in promoting continuing weight loss during the long-term maintenance stage of treatment. The visits should be made worthwhile for the patient. Realistic and attainable goals for diet, exercise and behaviour modification should be made. The diet should have a novel approach and be tailored to the needs of the patient. It should be adequate nutritionally, low in energy and fat. The overall aim should be to promote lifelong changes in lifestyle, improvement in quality of life and health risks.

Anthropometry↗

Commercial watercress as an emerging source of fascioliasis in Northern France in 2002: results from an outbreak investigation.

In April 2002, five cases of fascioliasis were diagnosed in Tourcoing. A case-finding and a case-control study were carried out to identify the source of the outbreak and take appropriate control measures. Eighteen cases were identified through the medical laboratories carrying out serology for fascioliasis. Fourteen cases and 23 controls, identified by the physicians of the cases, were interviewed on symptoms of the disease and their consumption of uncooked plants. Cases were more likely than controls to have eaten commercialized raw watercress (OR 86.7, P < 0.001) and 13 (93%) of the cases reported its consumption. A single producer common to all cases was identified. The inspection of his watercress beds showed a lack of protection against Lymnaea truncatula. This outbreak of fascioliasis due to commercialized watercress indicates that actual sanitary regulations do not allow for the efficient prevention of infestation of watercress production in France.

Adult↗

Nanoliter viscometer for analyzing blood plasma and other liquid samples.

We have developed a microfabricated nanoliter capillary viscometer that quickly, easily, and inexpensively measures the viscosity of liquids. The measurement of viscosity is based on capillary pressure-driven flow inside microfluidic channels (depth approximately 30 microm and width approximately 300 microm). Accurate and precise viscosity measurements can be made in less than 100 s while using only 600 nL of liquid sample. The silicon-glass hybrid device (18 mm by 15 mm) contains on-chip components that measure the driving capillary pressure difference and the relevant geometrical parameters; these components make the nanoliter viscometer completely self-calibrating, robust, and easy to use. Several different microfabricated viscometers were tested using solutions with viscosities ranging from 1 to 5 cP, a range relevant to biological fluids (urine, blood, blood plasma, etc.). Blood plasma samples collected from patients with the symptoms of hyperviscosity syndrome were tested on the nanoliter capillary viscometer to an accuracy of 3%. Such self-calibrating nanoliter viscometers may have widespread applications in chemical, biological, and medical laboratories as well as in personal health care.

Blood Viscosity↗