Glyburide is Associated with Attenuated Vasogenic Edema in Stroke Patients

Background

Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known.

Methods

Using a case–control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the glyburide advantage in malignant edema and stroke-pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 (MMP-9) plasma level in large hemispheric stroke.

Results

We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level.

Conclusions

Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial.     

Implementation of amplitude-integrated electroencephalography in tertiary Canadian Neonatal Intensive Care Units—a longitudinal study

AimTo investigate the implementation of amplitude-integrated electroencephalography (aEEG) as bedside monitoring tool of cerebral function in tertiary Canadian Neonatal Intensive Care Units (NICU) over the past decade.MethodsLongitudinal study consisting of online surveys of neonatologists on the use of aEEG in 2009 and 2018.ResultsThe response rate to the survey was 72 of 149 (49%) in 2009 and 18 of 30 (60%) in 2018, respectively. aEEG has been implemented in almost all (2009: 62.5%; 2018: 94%) tertiary Canadian NICUs. Two-thirds (2009: 67%; 2018: 71%) of the respondents considered information from aEEG tracing helpful in clinical practice. The main indications for aEEG were term neonates with hypoxic ischemic encephalopathy (2009 and 2018: 76%) and seizure detection/surveillance (2009: 88%; 2018: 94%). Teaching on aEEG has been implemented for neonatologists (2018: 100%) and health care providers (2018: 50%) in tertiary Canadian NICUs but there is a lack of standardization of training. Use of aEEG in preterm neonates (2009: 37%, 2018: 33%) and application of aEEG in research (18% reported occasional use) is less common.ConclusionaEEG is well established in tertiary Canadian NICUs to monitor cerebral function and detect seizure activity. There is a need to develop formalized aEEG training programs and methods to assess competence. Further implementation of aEEG in preterm neonates and research is desirable.     

Effects of dexamethasone on selective lymphocyte subpopulations in hypercortisolemic patients with anorexia nervosa and with bulimia nervosa: Preliminary report

The studies reported here describe the effects of intravenous (IV) administration of the synthetic glucocorticoid dexamethasone (DEX) on certain neuroendocrine and immunological measures in hypercortisoiemic patients with anorexia nervosa (AN) and with bulimia nervosa (BN). The results demonstrate that failure to suppress cortisol levels after DEX administration in patients with AN is associated with failure to reduce the level of adrenocorticotropic hormone (ACTH), the ratio of CD4-to-CD8 lymphocytes, the percent and number of circulating CD4 lymphocytes, and the percent and number of virgin CD4 cells (CD4+CD45RA+). Administration of DEX to patients with BN suppressed plasma ACTH and cortisol levels, reduced the CD4/CD8 ratio and the percent and number of CD4 and of CD4 + CD45RA+ lymphocytes, and increased the percent and number of circulating CD8 lymphocytes. Administration of DEX failed to alter other immune measures in either patient population, including circulating populations of B and natural killer cells, the proliferative response to T-cell mitogen, and the number of glucocorticoid receptors in circulating lymphocytes.     

Multisystem Langerhans cell histiocytosis: Literature review and case report

Langerhans cell histiocytosis (LCH) refers to a group of diseases of unknown etiology, typically discovered in childhood, characterized by the accumulation of Langerhans cells (white blood cells with large cell nuclei that may contain cytoplasmic histiocytosis X bodies) involving one or more organ systems, including bones, lungs, pituitary gland, skin, lymph nodes, and liver. This disease is also known as histiocytosis X or eosinophilic granuloma. Pulmonary LCH is common (identified in 40% of LCH patients) and may be isolated to the lung or involve other organs. Although LCH is characterized by clonal cell proliferation, adult LCH is considered likely to represent the manifestation of an aberrant immune response to an unspecified antigenic stimulus rather than a manifestation of tumor proliferation. We report a very complicated clinical case of LCH, with multiple organ damage that received a variety of different diagnoses. An LCH diagnosis was confirmed based on postoperative spinal cord pathology results and immunohistochemistry examinations. This case report highlights the clinical, laboratory, and imaging signs observed in this case that should be noted to help doctors more quickly recognize, diagnose, and treat similar cases.     

Pulsed dye laser treatment of capillary malformations in infants at 2‐weekly versus 3‐monthly intervals,reducing the need for general anaesthesia

Capillary malformations (CM) cause significant psychosocial complications. Pulsed dye laser (PDL) treatment at 6–12‐weekly intervals under general anaesthesia (GA) commencing in infants at 6 months of age remains the standard of care in order to achieve maximal improvement prior to school age. The safety of repeated GA in children is controversial. Shortening the time between treatments increases the number that can be delivered prior to 6 months of age, thus reducing the number of subsequent treatments needed under GA. We investigated the safety and effectiveness of more frequent PDL treatment of CM in infancy via a pilot, prospective patient‐controlled study of 10 patients. Using 595 nm (Vbeam) PDL, the entire CM was treated initially, then half the CM randomly allocated to 2‐weekly and half to 3‐monthly intervals for two further treatments. Photographs of the CM taken 3 months after treatment completion were evaluated by an independent, blinded dermatologist. Nine infants completed the study. Three infants (33%) had more improvement on the 2‐weekly treated side and four (44%) had more improvement on the 3‐monthly treated side. Two patients (22%) showed no difference between sides. Treatments were well tolerated without complications. We conclude that 2‐weekly PDL treatments of CM in infants aged under 6 months is effective and well tolerated without adverse effects. Our preliminary data suggest a possible superior efficacy with 3‐monthly treatment intervals; however, larger studies are warranted for stronger evidence. More frequent non‐GA treatment of CM in infants should be further investigated to decrease the risk of repeated GA exposure in young children.     

A Study of the Growth Patterns of Breast Carcinoma Using 3D Reconstruction: A Pilot Study

Lumpectomy with microscopically clear margins is a safe and effective approach for surgical management of breast carcinoma. Margins are positive for tumor in 18–50% of lumpectomies, as it is not possible to accurately determine the shape or microscopic borders of a tumor preoperatively or intraoperatively. We examined the 3D microanatomy and growth patterns of common breast carcinoma subtypes to provide guidance for lumpectomy surgery. Prospective consent was obtained for the use of excess tissue from patients undergoing lumpectomy or mastectomy for breast carcinoma. Tissue blocks from nine breast carcinomas were serially sectioned. Hematoxylin and eosin‐stained slides at 100 μm intervals were scanned using a Nanozoomer (Hamamatsu, Japan) microscopic‐resolution scanner. Three‐dimensional reconstructions of tumors were created from scanned images using Reconstruct, open‐access software. Breast carcinoma subtypes demonstrated characteristic growth patterns within breast tissue, which may have implications for lumpectomy surgery. Invasive ductal carcinomas showed a spherical shape, with a spiculated surface representing tumor cells infiltrating into surrounding parenchyma. Ductal carcinoma in situ appeared to spread along the duct system, creating dilated, tortuous, tumor‐filled ducts. The invasive lobular carcinomas examined had a haphazard, linear, infiltrative growth pattern, different from the shape seen in ductal carcinomas. Our preliminary work suggests that invasive ductal and invasive lobular carcinomas appear to have distinct growth patterns in three dimensions and ductal carcinoma in situ appears to grow in a linear fashion along the duct network. The microanatomy studies described have the potential to guide refinements in breast lumpectomy technique.     

Attitudes toward Tuberculosis in Vietnamese Immigrants

OBJECTIVES: To explore Vietnamese immigrants' knowledge, attitudes, beliefs, and practices concerning tuberculosis (TB). METHODS: Three focus groups were conducted at community health centers in California as part of a nationwide research project on attitudes toward TB in Asians and Pacific Islanders. Vietnamese health workers mediated group discussions by asking 11 openended questions on the causes of TB, medical consequences of TB, TB treatment, and the impact of the disease on social relationships. The results of these groups were reviewed by a panel of Vietnamese health workers in Hawaii. RESULTS: The focus group participants attributed TB to malnutrition, stress, smoking, alcohol consumption, and hard labor. They expressed a belief in the extreme contagiousness of TB, that it can be spread through eating utensils or towels. Lung diseases and other organ complications were cited to be the chief problems of TB. The participants expressed belief that the use of Western medicine is more effective in treating TB than other form of treatment such as acupuncture or herbal medicines. A consequence of the extreme contagiousness of TB is social isolation, leading to mental anguish. CONCLUSIONS: An understanding of shared attitudes toward TB in Vietnamese may contribute to the treatment of patients with TB. Community education to rectify some common misconceptions may be of utility.