Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis.

Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical. Here, we address these challenges through a new approach combining advances in molecular and computational technologies. First, we develop statistical tools to select tissue-informative DNA methylation sites relevant to a disease process of interest. We then employ a capture protocol to select these sites and perform targeted methylation sequencing. Multi-modal information about the DNA methylation patterns are then utilized in machine learning algorithms trained to predict disease status and disease progression. We applied our method to two independent cohorts of ALS patients and controls (n=192). Overall, we found that the targeted sites accurately predicted ALS status and replicated between cohorts. Additionally, we identified epigenetic features associated with ALS phenotypes, including disease severity. These findings highlight the potential of cfDNA as a non-invasive biomarker for ALS.

Case report: Traumatic lingual hematoma.

We describe a case of traumatic lingual hematoma in a patient on dual antiplatelet therapy. After securing the airway, bilateral lingual artery embolization successfully halted expanding hematoma formation. Patient subsequently required tracheostomy for continued airway edema. Although patient course was wrought with postoperative complications, we review this case to illustrate how prompt hematoma evacuation and embolization can resolve significant vasovagal bradycardia and hypotension secondary to expansile lingual hematoma.

Evaluation of the perception of cultural competency assessment instrument for allied health students.

BACKGROUND: A growing effort is aimed at reducing health disparities influenced by culturally based misinterpretations between patients and health professionals. There are few validated instruments to assess students' self-efficacy of cultural understandings that are linked to pre and post testing of educational interventions. PURPOSE: To evaluate the psychometric properties of an instrument that measures perception of self-efficacy with respect to cultural competency in allied health students. METHODS: The Perception of Cultural Competency Assessment (POCCA) was developed and subsequently evaluated for reliability and validity in a convenience sample of 135 students of allied health programs. RESULTS: The POCCA demonstrated acceptable internal consistency (a = .92) and 2-week test-retest reliability of (R = .78). Four sub-scales were identified by factor analysis that accounted for 63% of total variance. The subscale a coefficients ranged from .61 to .89, and inter-item correlations varied from (R = .41-53). POCCA total scores following an educational intervention were significantly higher compared to pre-test values (p<.00001). DISCUSSION: While these findings provide support for POCCA, more refinement is warranted. The challenge remains to improve the test-retest reliability and to expand the sample to evaluate its effectiveness in a broader context.

Optimizing adherence to pharmaceutical care plans.

Adherence to pharmacotherapy is essential to optimal therapeutic outcomes. The pivotal role of the pharmacist in optimizing adherence encompasses many actions: assessing the adherence problem, identifying predisposing factors, providing comprehensive counseling, and recommending specific adherence strategies targeted to the patient's needs. Patients who have chronic conditions, physical or cognitive impairments, or cultural backgrounds outside the mainstream may have special needs that should be addressed in the adherence plan. Pharmaceutical care plans also should take into account the patient's age, stage of life, and literacy level. Although a wide range of adherence aids and strategies are available, the key to success is to tailor the intervention to the individual patient and, when necessary, to combine interventions to optimize adherence.

Esophageal perforations after anterior cervical surgery.

An esophageal perforation after anterior cervical surgery is an uncommon but well recognized complication. During the past 25 years, 44 patients have presented to Craig Hospital (Rocky Mountain Regional Spinal Injury Center) with esophageal perforations; this is the largest series reported to date. There were 34 patients whose esophageal injury was related to the operations performed for cervical fractures, of which 28 patients had plate and screw fixation. The most frequently occurring clinical symptoms were that of neck and throat pain, odynophagia, dysphagia, hoarseness, and aspiration. The most common clinical findings were an elevated temperature, localized induration and neck tenderness, crepitus or subcutaneous air in the neck and anterior chest wall, an unexplained tachycardia, and blood in the nasogastric tube. Imaging studies indicated an esophageal injury in only 32 (72.7%) patients. Twenty-two patients experienced cervical osteomyelitis or an abscess of the neck. Nonoperative treatment is fraught with a high mortality, and 42 patients required surgical repair of their esophageal injury. The length of hospital stay averaged 253 days. Successful management of esophageal perforations depends on the physicians' awareness of the causes, prompt recognition of the symptoms and clinical findings, and immediate institution of treatment.

Epithelioid hemangioendothelioma of soft tissue: report of a case with ultrastructural observations.

The ultrastructure of an epithelioid hemangioendothelioma arising in the soft tissues of the neck of an 18-year-old female is reported. Comparison with similar tumors in other sites from the authors' electron microscopy files indicates that diffuse nonspecific intermediate filaments, pinocytotic vesicles, intracytoplasmic lumens, and pericytic cells are frequent but variable features of this neoplasm.

Increasing perceptions of disease vulnerability through imagery.

Increasing the cognitive availability of disease symptoms can increase perceptions of vulnerability to a fictitious disease. Research findings have also suggested that men and women respond differently to AIDS information; nevertheless, prior research has failed to examine the effects of imagery on both male and female perceptions of vulnerability to a real disease, such as AIDS. Undergraduates were presented with symptoms that were either hard to imagine or easy to imagine (labeled as related to either AIDS or hyposcenia-B) that the students then read or imagined. The results, which replicated prior research, indicated that imagining disease symptoms altered the students' perceived vulnerability to a fictitious disease. However, only imagery was significantly related to perceived vulnerability to AIDS, and gender interacted with this imagery process. Women expressed significant increases in perceived vulnerability when reading the disease symptoms, whereas men were more vulnerable when imagining the disease symptoms than they were when they read about the symptoms. The authors discuss the implications of their research for the integration of theory and experimentation in designing AIDS-intervention programs.

Correlation between presence of clonal rearrangements of immunoglobulin heavy chain genes and B-cell antigen expression in Hodgkin's disease.

Southern blot analysis of Hodgkin's disease (HD), although often compromised by the small number of abnormal cells present in the tissue, have tended to favor a B-cell derivation of the Hodgkin's and Reed-Sternberg (HRS) cells in cases of nodular sclerosis (NS) and mixed cellularity (MC) Hodgkin's disease. Eighteen frozen and 29 paraffin-embedded sections of lymph node specimens from 29 patients with pretreatment HD (22 NSHD and 7 MCHD) were studied by molecular analysis and immunohistochemistry to determine the phenotype of HRS cells. All cases were reviewed and showed typical morphology and CD45-, CD30+, CD15+, BLA.36+ HRS cells. In 11 of 29 (38%) cases, HRS cells were reactive with at least one B-cell marker (CD20, CD79a, MB2), 7 of 29 (24%) cases showed reactivity with the T-cell marker CD3, and 11 of 29 (38%) cases displayed a "null" phenotype. By using a polymerase chain reaction (PCR) and consensus primers for the V and J regions of the immunoglobulin heavy chain (IgH) gene, the authors were able to detect B-cell clonality in 9 of 18 (50%) frozen samples of HD analyzed. IgH gene rearrangement was present in 8 of 15 (53%) NSHD and in 1 of 3 (33%) MCHD. In five of nine (56%) of these cases, HRS cells were reactive with at least one B-cell marker, whereas one case expressed the T-cell marker CD3. The other three cases with IgH gene rearrangement showed a "null" immunophenotype. IgH gene analysis was negative in all remaining CD3+ cases and in two other cases that expressed B-cell markers by immunohistology. Southern blotting failed to detect rearrangement of the T-cell receptor beta-chain gene and immunoglobulin heavy and light genes in any of these cases. The results show that PCR represents a specific and sensitive technique for the detection of IgH gene rearrangements in cases of Hodgkin's disease. The results also suggest a lymphoid B-cell derivation of HRS cells in a high proportion of the cases.

Benign müllerian lymph node inclusions. An unusual case with implications for pathogenesis and review of the literature.

Endosalpingiosis with psammoma bodies within an intramammary lymph node presented as microcalcifications on mammography in the right breast of a 64-year-old woman. The radiographic differential diagnosis included primary breast carcinoma. The histologic differential diagnosis included metastatic papillary carcinoma, particularly of thyroid origin. To our knowledge, this is the first reported case of endosalpingiosis occurring above the diaphragm. The unusual location of these inclusions has relevant implications concerning their pathogenesis. Moreover, it is important for pathologists to be aware that endosalpingiosis may occur and mimic carcinoma at sites distant from the female pelvis.

Capacity of the store-regulator in maintaining iron balance.

There is evidence that iron stores alter iron absorption to meet body iron needs. In this study, quantitative aspects of this regulation of iron balance are examined. Two male subjects, one with low and one with average iron stores, were given additional dietary iron over 500 days. Changes in iron stores were monitored by plasma ferritin measurements, and the ferritin estimate of stores was validated at the end of the study by bleeding to the point of iron deficiency. The subject with low iron stores increased his ferritin by 39 micrograms/L or 0.8 mg/day, whereas the subject with average iron stores had no significant change. It is concluded that the mechanism by which stores regulate food iron absorption has a capacity of about 1 mg/day, sufficient to meet usual physiological needs, with the exception of pregnancy, as well as the ability to resist increase in stores above normal despite an iron rich diet.

Oesophageal trauma in patients with spinal cord injury.

Oesophageal perforations associated with cervical fractures occur from a variety of injuries. Fractures of the cervical spine, blunt trauma and penetrating injuries such as gunshot wounds, knives and missiles, perforate the cervical oesophagus. This retrospective study consists of 24 patients with an oesophageal perforation and cervical fracture. Motor vehicle accidents were responsible for 54% of the oesophageal perforations. The other oesophageal injuries were related to anterior spine surgery, gunshot wounds and sports-related activities. The clinical features related to these injuries included the obvious signs of an oesophageal perforation as well as fever of unknown origin, leukocytosis and unexplained persistent tachycardia. A variety of techniques was used to establish the diagnosis. All the patients had treatment for the cervical fracture and 20 patients required surgical repair of the oesophagus. The most common oesophageal complications were stricture of the oesophagus (54%) and oesophageal diverticulum (10%). The other complications were atelectasis, pneumonia, tracheobronchitis, pulmonary embolism, cervical osteomyelitis, cervical abscess, mediastinitis, septicemia and cervical fistulae. These patients have a serious life-threatening illness that may be difficult to diagnose and treat.

Introducing total quality management.

Total quality management is a system that could pay dividends for National Health Service managers and employees but would require a change of culture, from one of crisis response to problems to one preventing them from happening in the first place. This article introduces the concept and describes the preconditions for its successful application.

Insertion and recovery of a new retrievable vena caval filter. Work in progress.

A new retrievable inferior vena cava (IVC) filter was tested in nine pigs. Insertion was through a 14 French sheath using both the femoral and jugular approaches. All insertions were successful, and there was a 100% postinsertion IVC patency rate (8/8 pigs at one week and 1/1 pig at one month). Addition of an apical hook to the filter design allowed transjugular retrieval of two filters at one week postinsertion. Three of nine filters migrated to the upper IVC. The filter's design allows paraxial blood flow despite trapped thrombus and inhibits filter tilting. In vitro, the filter captured 95% to 100% of 5 X 5 mm clots. If problems with migration can be solved, the new filter may provide effective short- and long-term prophylaxis against pulmonary embolism.

Histopathology and immunofluorescent immunoglobulins in asthmatics with aspirin idiosyncrasy.

Nearly 700 specimens of polyps and sinus tissues from 12 patients with asthma and aspirin idiosyncrasy were studied with histochemical and immunofluorescent immunoglobulin techniques. Hematoxylin-eosin, Giemsa, and Wright's stains were used for the histochemical analyses. Immunofluorescent antibodies for IgG, IgA, IgM, IgE, IgD, anti-C3, albumin, and fibrin were used. There was a uniform inflammatory reaction in all the tissues. A thick basement membrane and epithelial changes were also present. Immunofluorescent immunoglobulins were consistent in quantity and location in these tissues. IgG, IgA, and IgM were associated with inflammation. IgE was present in all the specimens, but this does not necessarily indicate a reagin-mediated reaction. Anti-C3 excluded the possibility of a hereditary absence of C1 esterase inhibitor.

Glottic and tracheal stenosis in spinal cord injured patients.

Between 1965 and 1985, 47 cases of glottic and/or tracheal stenosis were diagnosed at the Rocky Mountain Regional Spinal Cord Injury System. A retrospective review of medical records identified associated injuries, pulmonary and other medical complications in this patient population. Radiographic and endoscopic reviews utilised a grading system to classify the severity of stenosis. The clinical symptoms of stenosis were multiple, including dysphonia, aspiration, dysphagia, odynophagia, dyspnea and excessive secretions. The wide spectrum of treatment modalities included endoscopy with excision and/or dilation, general medical management, steroids, radiation therapy, intubation, stent insertion and surgical repair of the stenotic area. Outcome status was reviewed and suggestions provided for the early diagnosis and treatment of this potentially life-threatening condition.

Nasal polypectomy and sinus surgery in patients with asthma and aspirin idiosyncrasy.

This study attempted to determine whether or not nasal and sinus surgery had a beneficial or deleterious effect upon the asthma of patients with nasal polyps and aspirin idiosyncrasy. There were 205 patients in this study. A classification system was devised to provide a means of determining the severity of asthma before and after surgery. The data indicate that surgery does improve the patient's asthma for relatively long periods of time.