Ingestion of drugs by "parachuting": a unique drug delivery technique.

"Parachuting" is a technique of drug delivery where medications or illicit drugs are ingested by wrapping the drug of choice in a covering, which then will dissolve or unravel in the gastrointestinal tract, thereby releasing the drug for absorption. Parachuting of drugs can entail crushing of a pill prior to packaging to theoretically increase the surface area for absorption or may involve the packaging of a higher than usual dose of a drug in attempts to attain a sustained-release effect as the "parachute" dissolves or unravels. A case is presented in which a prescription drug abuser known to parachute his medications dies from obstruction of his airway by the inhaled packet. Risks of parachuting any drug would include overdose and fatal toxic effect from the drug itself and adverse effects from the packaging including bowel obstruction or perforation, or airway obstruction.

Appearance of chemical burns resulting from the washing of a deceased body with bleach.

The authors report on a case of postmortem washing of a body with bleach. An adult female victim was found nude in an alleyway with both hands removed in the City of Westminster, CO. Cause of death was attributed to severe blunt force trauma to the head. The victim had been dumped in the alleyway within 7 h of discovery. Evidence discovered at the crime scene and autopsy indicated that the murder and subsequent washing of the body with bleach occurred at a secondary location(s). The victim was wet to the touch, presenting a strong odor of bleach. Several "ribbon"-like burn patterns were observed on the victim's back and upper thighs. These burn marks were replicated by dowsing a deceased pig with an over-the-counter concentration of bleach.

Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis.

IMPORTANCE: Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV). OBJECTIVE: To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years. MAIN OUTCOMES AND MEASURES: Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS: Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR] = 2.86; 95% CI, 1.75-5.31; P < .001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR = 3.26; 95% CI, 2.03-5.98; P < .001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR = 2.43; 95% CI, 1.82-3.41; P < .001) and GCA-positive TAs (RR = 2.03; 95% CI, 1.52-2.86; P < .001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs. CONCLUSIONS AND RELEVANCE: In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis.

OBJECTIVE: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA). METHODS: Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen-positive slides were analyzed by PCR for VZV DNA. RESULTS: VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs (p < 0.0001, relative risk 9.67, 95% confidence interval 1.46, 63.69). Most GCA-positive TAs contained viral antigen in skip areas. VZV antigen was present mostly in adventitia, followed by media and intima. VZV antigen was found in 12/32 (38%) skeletal muscles adjacent to VZV antigen-positive TAs. Despite formalin fixation, VZV DNA was detected in 18/45 (40%) GCA-positive VZV antigen-positive TAs, in 6/10 (60%) VZV antigen-positive skeletal muscles, and in one VZV antigen-positive normal TA. Varicella-zoster virions were found in a GCA-positive TA. In sections adjacent to those containing VZV, GCA pathology was seen in 89% of GCA-positive TAs but in none of 18 adjacent sections from normal TAs. CONCLUSIONS: Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Sudden unexpected death in epilepsy: a retrospective study.

Patients with epilepsy have a mortality rate higher than that of the general population; sudden unexpected death represents a significant category of mortality in these patients. The precise frequency of occurrence of sudden unexpected death in epilepsy (SUDEP) is not well defined, with a range of 1 in 370 to 1100 in the general epileptic population. A major difficulty with incidence studies is the continued reluctance in using the term SUDEP as a cause of death, making reliance solely on death certificates inconsistent and incomplete. Knowledge about SUDEP remains limited, as no single common risk factor has yet been identified, although predisposing conditions have been suggested. The purpose of this study is to review the association between several clinical variables and SUDEP to elucidate risk factors. The characteristics of the 67 cases in this series correlate with published findings in previous studies. Attributes that may be used to define an at-risk group of epileptics include age less than 40 years, male gender, long history of seizure disorder, undermedication or poorly controlled seizure activity, and mental or physical stress. Education of physicians as to the existence of SUDEP and risk factors is imperative in improving patient education and reduction in mortality.

Epidermal growth factor receptor status in breast cancer metastases to the central nervous system. Comparison with HER-2/neu status.

CONTEXT: The development of drug therapies (ZD1839) targeting epidermal growth factor receptor (EGFR) offers a pragmatic reason for exploring expression of EGFR in breast cancer, particularly metastatic breast cancer. There is a reported synergistic relationship between trastuzumab and ZD1839 therapy in patients with breast cancer. Although EGFR is the preferred dimerization partner for HER-2, it is unclear whether expression of these 2 interrelated receptors in a given patient with breast cancer would be parallel or mutually exclusive. OBJECTIVES: To assess EGFR status in primary breast carcinoma versus metastatic central nervous system (CNS) sites and to compare results with HER-2/neu status in the same tumor. DESIGN: Central nervous system metastases (n = 51) from 33 patients and corresponding primary breast cancer specimens, when available (n = 11), were immunohistochemically stained for EGFR using a monoclonal mouse anti-EGFR antibody (clone 31G7) that recognizes both the wild-type form and the 145-kd variant III form of EGFR. The sections were evaluated by visual and image analysis techniques, and results were compared to previously assessed HER-2/neu status. RESULTS: Epidermal growth factor receptor expression was found in CNS metastases from 39% of patients, with 82% concordance between the EGFR status of the primary breast and metastatic sites, and 92% concordance between the EGFR status among multiple CNS metastases in a given patient. Epidermal growth factor receptor and HER-2/neu status were concordant at the primary site in only 45% of patients. Additionally, EGFR and HER-2/neu status were concordant among multiple CNS metastases per individual case in only 45% of patients. CONCLUSION: Thirty-nine percent of patients with metastatic breast cancer express EGFR, with parallel expression between metastatic sites and the primary neoplasm in 82% of the cases. The discordance in 18% of the cases, however, suggests that anti-EGFR agents might not show equal efficacy against metastatic tumor deposits and the primary tumor within a given patient. An additional corollary for pathologists based on this nonhomogeneity of receptor expression is that both the primary breast and multiple metastatic tumor deposits may need to be individually assessed for EGFR status. In our study, most metastatic tumor deposits showed expression for either EGFR or HER-2/neu, and less often for both, implying that drug therapies could be individualized for patients based on test results for both receptors.

Leptin deficiency, not obesity, protects mice from Con A-induced hepatitis.

Leptin-deficient ob/ob mice are protected from Con A-induced hepatitis. However, it is unclear whether leptin deficiency or obesity itself is responsible for this protection. To address this question, wild-type (WT) obese mice with high serum leptin levels were generated by injection of gold thioglucose (WT GTG). Both Con A-injected WT and WT GTG mice developed hepatitis, whereas no hepatic damage was observed in ob/ob mice. Moreover, TNF-alpha and IFN-gamma levels as well as expression of the activation marker CD69 were elevated in liver mononuclear cells of WT and WT GTG mice, but not in ob/ob mice following administration of Con A. The liver of WT and WT GTG mice had the same percentage of NK T cells, a lymphocyte population involved in Con A-induced hepatitis. This population decreased equally in both WT and WT GTG mice after Con A injection. In contrast, the liver of ob/ob mice contained 50% less NK T cells compared to WT and WT GTG mice. Furthermore, no decrease in NK T cells was observed in Con A-injected ob/ob mice. We conclude that leptin-deficiency, not obesity, is responsible for protection from Con A-induced hepatitis.

Her-2/neu status in breast cancer metastases to the central nervous system.

CONTEXT: Breast cancer is lethal when it metastasizes; one frequent site for spread is the central nervous system (CNS). Approximately 15% to 30% of breast cancers overexpress the protein HER-2/neu at the primary site, but there are few data on whether metastases from these tumors overexpress HER-2/neu and might be responsive to the potentially toxic anti-HER-2/neu immunotherapy (trastuzumab [Herceptin]) used in patients with disseminated disease. OBJECTIVE: To assess CNS breast cancer metastases for HER-2/neu protein overexpression by immunohistochemistry and gene amplification by fluorescence in situ hybridization (FISH) and to compare the status in primary and metastatic sites in the same patient, whenever possible. DESIGN: Central nervous system breast cancer metastases (n = 53) from 33 patients and corresponding primary breast cancer specimens in a subset of these patients (n = 12) were retrospectively identified in surgical pathology and autopsy databases. Fluorescence in situ hybridization analysis using PathVysion probes for HER-2/neu and chromosome enumeration probe 17 (CEP 17) and immunohistochemistry using the c-Erb-B2 antibody (Dako A0485) were compared. Immunohistochemical sections were evaluated by both visual and image analysis techniques. RESULTS: Of 31 cases assessable by FISH, 26% showed gene amplification. One hundred percent concordance for HER-2/neu status was detected between the primary and CNS metastatic lesions in 10 of 10 patients analyzed by FISH; lesser concordance was noted in 12 cases compared by immunohistochemistry. In 9 patients with multiple CNS metastases, FISH showed concordance among different lesions within the same patient. CONCLUSIONS: When FISH is the detection method, CNS metastases accurately reflect the HER-2/neu status of the primary tumor. Central nervous system metastases from breast cancer received as surgical specimens can therefore be used to assess HER-2/neu status in patients in whom the primary tumor is unavailable for analysis.