Smart pills for gastrointestinal diagnostics and therapy.

Ingestible smart pills have the potential to be a powerful clinical tool in the diagnosis and treatment of gastrointestinal disease. Though examples of this technology, such as capsule endoscopy, have been successfully translated from the lab into clinically used products, there are still numerous challenges that need to be overcome. This review gives an overview of the research being done in the area of ingestible smart pills and reports on the technical challenges in this field.

Early constipation predicts faster dementia onset in Parkinson's disease.

Constipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson's Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n = 313, 67.3%), minor (n = 97, 20.9%) and major (n = 55, 11.8%). Clinical progression to all three outcomes was more rapid in those with more severe constipation at baseline (Kaplan-Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology.

Deep brain stimulation in ireland for Parkinson's disease and essential tremor.

Deep brain stimulation (DBS) is highly effective neurosurgery for idiopathic Parkinson's disease (IPD), essential tremor (ET) and primary dystonia. DBS involves stereotactic surgical implantation of a battery-operated stimulator into deep brain nuclei. Irish patients are referred abroad for DBS and have to travel repeatedly for pre and post-operative care resulting in stress, anxiety and hardship. Safe pre and post-operative care of these complex, ageing patients is compromised by the absence of a DBS service in Ireland. Moreover, both DBS surgery and the subsequent post-operative care abroad incurs substantial cost to the state. The Dublin Neurological Institute at the Mater Misericordiae University Hospital (DNI) is a non-profit institute for the care of patients with neurological diseases. The DNI developed, in collaboration with the Mater Private Hospital (MPH) and the Walton Centre, Liverpool, a DBS programme in 2008/2009. We performed DBS at the Mater Campus on three carefully selected patients from a cohort of movement disorder patients attending the DNI and continue to provide pre-operative assessment and post operative care for patients following DBS in Ireland and abroad.

Application of the Meckel's scan in a case of gastric corrosive injury.

This report describes a useful application of (99m)Tc-pertechnetate abdominal scintigraphy (Meckel's scan) in the assessment of gastric viability after corrosive injury. The Meckel's scan provided information about residual gastric mucosal function and prognosis in a less invasive manner than more usual methods.

How to test the safety of homemade antegrade colonic washout fluid?

Normal saline is commonly used for antegrade colonic washout enemas. The saline solution is usually made at home by adding measured quantities of common salt to tap water. The best method for the carers to check the concentration of salt in these homemade solutions has not been reported. Various concentrations of saline solutions were tested for specific gravity (SG) with an aquarium hygrometer and urine analysis sticks by two blinded independent observers. An aquarium hygrometer can read SG with an accuracy of 0.00046 for saline solutions made in tap water and 0.00051 for those made with sterile water. Urine analysis dipsticks sticks failed to achieve this accuracy. An aquarium hygrometer is a simple and reliable way to measure the SG of homemade saline solutions. Its use may avoid the problems associated with over- or under-concentration of salt in the antegrade enema solution.

Familial presacral masses: Screening pitfalls.

BACKGROUND/PURPOSE: Anterior sacral meningocele (ASM) and presacral teratoma (PT) are related malformations. Both can have familial occurrence. Surgical treatment of occult cases is essential. Hence, it is important to screen the asymptomatic relatives. Plain radiograph of the sacrum to look for any bony abnormalities is the usual accepted screening modality. The authors report ASM and PT in siblings (with positive family history) with no sacrococcygeal bony abnormality on imaging. Both the siblings had presacral mass on imaging. METHODS: The medical records of 2 siblings with ASM and PT were reviewed for the clinical presentation, diagnostic workup, and family history. RESULTS: One sibling was symptomatic, whereas the other was completely asymptomatic. A family history of sacral bony abnormalities and anterior meningoceles was present in father, 2 paternal cousins, paternal uncle, paternal aunt, paternal grandmother, and paternal grand uncle. CONCLUSIONS: These case reports suggest that imaging for screening for ASM and PT should be directed at identifying the presacral mass rather than sacral bony defect. Hence, computed tomography or magnetic resonance imaging looking for presacral mass rather than plain radiograph should be the screening modality. J Pediatr Surg 36:1841-1844.

Comparison of rheumatoid arthritis care costs in patients starting therapy with leflunomide versus etanercept.

OBJECTIVE: To identify differences in rheumatoid arthritis (RA) care costs and utilization among patients receiving therapy with leflunomide (LEF) or etanercept (ETA). STUDY DESIGN: A retrospective cohort analysis of patients diagnosed with RA and starting treatment with LEF or ETA. METHODS: Patients diagnosed with RA and receiving newly prescribed LEF or ETA in 1998 were identified from a database containing patient-level medical and pharmaceutical claims. Patients were subsequently observed for 6 months. RA-related treatment charges during the observation period were compared between cohorts. RESULTS: A total of 527 LEF- and 281 ETA-treated patients were identified. The 2 cohorts were comparable with respect to demographics, comorbid conditions, and concomitant medication use, although LEF recipients were, on average, older than ETA recipients (mean age 52.97 versus 48.43 years; P < .0001). ETA recipients had higher mean 6-month postdiagnosis charges than LEF recipients ($7722.01 +/- $5285.20 versus $3301.84 +/- $4054.75; P < .0001). This difference was primarily related to differences in RA-related pharmacy charges ($5877.78 +/- $2237.68 versus $1877.23 +/- $1258.05; P < .0001). CONCLUSIONS: Compared with charges in the ETA group, RA care costs in the LEF group were significantly lower during the 6 months after the initiation of therapy. The difference in mean total RA-related charges was attributable mainly to the difference in RA-related pharmacy charges.

The costs of nonsedating antihistamine therapy for allergic rhinitis in managed care: an updated analysis.

OBJECTIVE: To update a prior study evaluating the use and costs of new-generation antihistamines for the treatment of allergic rhinitis in a managed care population. STUDY DESIGN: A retrospective database review of rhinitis-related medical and pharmacy-related claims during a treatment period of 12 months. METHODS: Patients who had been diagnosed as having allergic rhinitis and had at least 1 prescription claim were identified from a database containing patient-level medical and pharmaceutical claims. The treatment patterns for patients meeting study criteria were documented for a 12-month period to describe how nonsedating antihistamines are being used in allergic rhinitis, and to assess the associated costs of various medications. Subanalyses of patients categorized by comorbidity status were also performed. RESULTS: A total of 105,696 patients were included in this updated analysis, covering calendar year 1999. Nonsedating antihistamines were used by 68% of the sample, with loratadine and fexofenadine being the most commonly prescribed agents. The mean annual rhinitis-specific charge for fexofenadine-treated patients was $409 (standard deviation [SD] 727), which was significantly lower compared with charges for loratadine-treated patients, $424 (SD 740), P = .0144, or cetirizine-treated patients, $444 (SD 625), P < .0001. This trend was also observed in comparisons of patient subgroups. CONCLUSIONS: Consistent with our prior study, loratadine and cetirizine were generally associated with significantly higher treatment charges than fexofenadine. This result was observed across different stratifications of patients, including those with comorbid respiratory illness, concomitant use of nasal steroids, and asthma and/or sinusitis. These results provide further useful insights into the differential costs associated with the use of nonsedating antihistamines for allergic rhinitis treatment.

Noncervicofacial atypical mycobacterial lymphadenitis in childhood.

BACKGROUND/PURPOSE: Atypical mycobacterial (AM) lymphadenitis is common in children but rarely occurs outside the cervicofacial region. The authors report their experience in the diagnosis and management of noncervicofacial AM lymphadenitis. METHODS: A retrospective review was conducted of cases diagnosed at our institution between January 1976 and December 1999, based on positive culture of atypical mycobacteria or consistent histology with supportive skin testing. RESULTS: Thirty-seven patients were identified over the 23-year review period. The median age was 4.3 years (range, 8 months to 13 years and 5 months), with 19 boys and 17 girls. The median duration of symptoms was 4 weeks, and the most commonly affected sites were the inguinal region (n = 17), axilla (n = 8), and lower limb (n = 6). Preceding local trauma was described in 10 patients and a viral illness in 4. Laboratory culture for atypical mycobacteria was positive in 22, and skin testing suggestive in 21 and equivocal in 2. Treatment was by excision in 28 and drainage with or without curettage in 9. At a median follow-up of 19.7 months, disease had recurred in 4 patients, none of whom had been treated initially by excision. CONCLUSIONS: Atypical mycobacterial infection is an uncommon cause of noncervicofacial lymphadenitis in children. It typically presents with a 4-week history of painless regional lymphadenopathy that may follow penetrating trauma. If untreated, the overlying skin becomes involved with a violaceous discoloration, and ulceration may occur. Definitive treatment involves complete surgical excision, preferably before suppuration extending beyond the involved lymph nodes.

A descriptive analysis of the use and cost of new-generation antihistamines in the treatment of allergic rhinitis: a retrospective database analysis.

OBJECTIVE: This retrospective database analysis was conducted to evaluate the use and cost of new-generation antihistamines (i.e., those that are nonsedating) in the treatment of allergic rhinitis in a managed care population. STUDY DESIGN: The study is a retrospective database review of medical and pharmacy-related claims linked by episodes of care. METHODS: Patients who had been diagnosed as having allergic rhinitis and had at least 1 prescription claim were identified from a database containing patient-level medical and pharmacy-related claims. The treatment patterns of patients with allergic rhinitis who met the study criteria were documented for a 12-month period in which the use of nonsedating antihistamines was described and the associated costs of various medications were assessed. Subanalyses of patients categorized by comorbidity status were also performed. RESULTS: A total of 202,426 patients participated in the study. Nonsedating antihistamines were used by 71% of the patients; the most commonly prescribed drugs were loratadine and fexofenadine. The mean annual charges per patient for the treatment of allergic rhinitis in the study population were $465.21 (standard deviation [SD], 548). The greatest departmental cost was that of pharmacy-related charges (mean, $236.02; SD, 233); the next highest cost was that of outpatient charges (mean, $216.31; SD, 396). Comparisons of departmental charges indicated the use of loratadine was associated with significantly higher treatment costs than that of fexofenadine in a number of patient subgroups. CONCLUSION: In this analysis, loratadine was associated with significantly higher treatment charges than was fexofenadine. This result was observed consistently across different stratifications of patients, including the presence of comorbid respiratory infection, concomitant use of nasal steroids, and the presence of asthma and/or sinusitis. These results provided useful insights into the differential costs associated with the use of nonsedating antihistamines in the treatment of rhinitis.

Adverse outcome of congenital diaphragmatic hernia is determined by diaphragmatic agenesis, not by antenatal diagnosis.

BACKGROUND/PURPOSE: The authors studied their congenital diaphragmatic hernia (CDH) cases retrospectively to ascertain if classical CDH and diaphragmatic agenesis (DA) have separate clinical manifestations, whether antenatally diagnosed cases behave differently from those not diagnosed antenatally, and if antenatal diagnosis before 25 weeks carries a worse prognosis. METHODS: The authors performed a retrospective review of 23 infants with CDH treated at their institution between January 1996 and March 1999. The patients were divided into 3 groups that were analyzed: DA and classical CDH, antenatally diagnosed and nonantenatally diagnosed, and antenatally diagnosed before 25 weeks and after 25 weeks. RESULTS: There were 8 cases of DA and 11 cases of classical CDH. Four infants died without operation and could not be classified. Neonates with DA had significantly longer mean duration of preoperative stabilization compared with classical CDH (5.25+/-2.76 days v 1.36+/-1.0 days) and postoperative mechanical ventilatory support (15.7+/-3.0 days v 4.9+/-3.0 days). Fifty percent of DA patients died; all classical CDH patients survived. Twelve cases were diagnosed antenatally, 6 before 25 weeks' gestation. Antenatally diagnosed cases had no statistically significant difference in mortality rates from those not diagnosed antenatally; 50% of those diagnosed before 25 weeks survived. CONCLUSIONS: DA cases require more preoperative preparation and postoperative ventilation and have a bad prognosis compared with classical CDH. Antenatal diagnosis of CDH does not convey a different prognosis. Fifty percent of CDH patients with antenatal diagnosis before 25 weeks survive.

Analysis of the RET proto-oncogene in sporadic parathyroid adenomas.

Missense germline mutations of the RET proto-oncogene have recently been identified in the hereditary cancer syndromes MEN2A, MEN2B, and FMTC, all characterized by medullary carcinoma, but also including phaeochromocytoma in MEN2A and MEN2B and parathyroid disease in MEN2A. In addition, somatic RET proto-oncogene mutations have been identified in a subset of sporadic medullary carcinomas and phaeochromocytomas. This study investigated the possibility that RET plays a role in sporadic parathyroid neoplasia. Firstly, normal and neoplastic parathyroid tissues were screened for expression of the RET proto-oncogene, using an RT-PCR approach on autopsy material. Secondly, 20 archival parathyroid adenomas were screened for somatic mutations in the transmembrane region of RET, the region associated with germline mutations in MEN2A and hence parathyroid disease, using a PCR-solid phase direct sequencing approach. RET expression was identified in all the parathyroid tissues analysed. However, no mutations were identified in any of the 20 adenomas, suggesting either that other mechanisms of RET activation occur, such as translocation, or that RET plays a more minor role in the growth control of the parathyroid cells than in C cells or phaeochromocytes.

RET activation in adult and childhood papillary thyroid carcinoma using a reverse transcriptase-n-polymerase chain reaction approach on archival-nested material.

Activation of the RET tyrosine kinase domain occurs in a proportion of thyroid papillary carcinomas. Three chromosomal rearrangements have been described, of which PTC1 is the commonest. Wide differences (2.5-25%) in frequency of PTC1 in different populations have been reported; it is not clear whether these are due to environmental factors, racial differences or technical reasons. We have developed a simple and rapid reverse transcriptase nested polymerase chain reaction (RT-nPCR) method enabling the detection of gene expression from single 5 microns sections of formalin-fixed paraffin wax-embedded archival material. We have applied this approach to detect expression of the RET tyrosine kinase domain, allowing identification of RET activation resulting from any rearrangement, whether characterised or not, or from overexpression. A retrospective study was performed on 22 adult and 21 childhood papillary carcinomas. Thirteen of 22 (59%) adult and 10 of 21 (48%) childhood carcinomas showed evidence of RET activation, demonstrating a major role for the RET oncogene in UK thyroid papillary carcinogenesis. This study also shows a similar frequency of RET activation in both children and adults. The use of a technique that allows reliable amplification of RNA from archival material, using primers chosen in different exons so that amplified products are readily distinguished from genomic DNA, will allow correlation of translocations and chromosomal rearrangements with a variety of specific tumour types.

Alcohol attributable fractions for trauma in South Africa.

The misuse and abuse of alcohol is widespread in South African society and is likely to have a large impact on the economy. A major burden is borne by the hospital care system, in particular the cost of alcohol-related trauma. The purpose of this study was to estimate the cost of alcohol misuse in terms of fatal and non-fatal trauma. The design of the study was a cross-sectional survey of key informants. Each key informant was mailed a list of 11 trauma categories found to be linked to alcohol in both the local and international literature. They were asked to make an estimate of the alcohol attributable fraction (AAF) for each trauma category, based on their clinical experience and knowledge of empirical research. The median estimates for each trauma category showed that alcohol misuse could be linked to a substantial amount of mortality and morbidity, particularly with respect to motor vehicle trauma and interpersonal violence. These AAF estimates were supported by the findings of other empirical research conducted in South Africa, as well as by the literature on mortality data in the U.S.A. This suggests that there is potential for a vast amount of injuries and deaths to be eliminated if alcohol misuse could be controlled or eliminated.

Immature Ixodes scapularis (Acari: Ixodidae) parasitizing lizards from the southeastern U.S.A.

Preserved museum specimens of 13 lizard and 3 snake species common in the southeastern U.S.A. were examined for immature Ixodes scapularis Say ticks. Five Eumeces and 4 Ophisaurus lizard species yielded an infestation prevalence of 17.8% for species of Eumeces and 29.0% for species of Ophisaurus. Mean intensity of larvae and nymphs was 7.1 and 2.7, respectively, for species of Eumeces, and 6.3 and 1.4, respectively, for species of Ophisaurus. Collection dates of the lizards ranged from January through December, but most were collected from March through October. The maximum number of immatures found on a single specimen was 193 larvae and 11 nymphs on a specimen of Eumeces and 75 larvae and 7 nymphs on a specimen of Ophisaurus. For species of Eumeces, 75.2% of all nymphs observed were attached in the shoulder area. Larvae were most abundant on the rear legs (53.3%), followed by the front legs (26.3%) and shoulders (12.9%). Larvae and nymphs on species of Ophisaurus were found almost exclusively in the lateral groove area (84.0% and 94.4%, respectively). Three other lizard species (Anolis carolinensis, Sceloporus undulatus, Scincella lateralis) had only a few ticks or none. A fourth species, Cnemidophorus sexlineatus, hosted a total of 3 larvae on 3 specimens (infestation prevalence, 10.7%). Three snake species (Diadophis punctatus, Virginia striatula, Crotalus adamanteus) had none.

Isolation and transmission of the Lyme disease spirochete from the southeastern United States.

The isolation of the Lyme disease spirochete (Borrelia burgdorferi) from the southeastern United States is reported. Three isolates, two from cotton mice (Peromyscus gossypinus) and one from the black-legged tick (Ixodes scapularis), were recovered from Sapelo Island, Georgia, in July and September 1991. The spirochetes were characterized by indirect fluorescent antibody assay using a battery of five monoclonal antibodies, by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of whole cell lysates, and by the polymerase chain reaction (PCR) assay using primers for three DNA target sequences found in B. burgdorferi reference strain B-31. Transmission experiments indicate that the three Georgia isolates can infect experimentally inoculated hamsters and mice. Tick transmission of one of the isolates has been attempted so far; I. scapularis transmitted isolate SI-1 from hamsters to mice, but the lone-star tick, Amblyomma americanum, did not.