Malignant hyperthermia, coexisting disorders, and enzymopathies: risks and management options.

Clinical episodes and abnormal laboratory tests compatible with a diagnosis of malignant hyperthermia have been observed in patients with a diversity of syndromes, enzymopathies, and coexisting disorders thereby raising the likelihood of causal associations and heightened perioperative risk in others carrying a shared diagnosis. In the present review, we survey available published series, case reports, and the results of contracture testing in patients identified by others to be potentially predisposed to malignant hyperthermia. For most conditions, evidence for a causal relationship with malignant hyperthermia susceptibility is weak.

Disseminated Cryptococcus neoformans: case report and review of the literature.

Cryptococcus neoformans is a yeastlike encapsulated basidiomycetous fungus that is able to cross the blood-brain barrier and cause meningitis in both immunocompetent and immunocompromised individuals. Cryptococcus neoformans has emerged as a major opportunistic pathogen because of the widespread use of immunosuppressive therapy. It causes most cryptococcal infections in humans, and disseminated infection can have cutaneous manifestations.

Perioperative genomic profiles using structure-specific oligonucleotide probes.

Objectives: Many complications in the perioperative interval are associated with genetic susceptibilities that may be unknown in advance of surgery and anesthesia, including drug toxicity and inefficacy, thrombosis, prolonged neuromuscular blockade, organ failure and sepsis. The aims of this study were to design and validate the first genetic testing platform and panel designed for use in perioperative care, to establish allele frequencies in a target population, and to determine the number of mutant alleles per patient undergoing surgery. DESIGN/SETTING/PARTICIPANTS AND METHODS: One hundred fifty patients at Marshfield Clinic, Marshfield, Wisconsin, 100 patients at the Medical College of Wisconsin Zablocki Veteran's Administration Medical Center, Milwaukee, Wisconsin, and 200 patients at the University of Wisconsin Hospitals and Clinics, Madison, Wisconsin undergoing surgery and anesthesia were tested for 48 polymorphisms in 22 genes including ABC, BChE, ACE, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, beta2AR, TPMT, F2, F5, F7, MTHFR, TNFalpha, TNFbeta, CCR5, ApoE, HBB, MYH7, ABO and Gender (PRKY, PFKFB1).

Expression of Pit-1 in nonsomatotrope cell lines induces human growth hormone locus control region histone modification and hGH-N transcription.

The POU domain transcription factor Pit-1 is expressed in somatotropes, lactotropes, and thyrotropes of the anterior pituitary. Pit-1 is essential for the establishment of these lineages during development and regulates the expression of genes encoding the peptide hormones secreted by each cell type, including the growth hormone gene expressed in somatotropes. In contrast to rodent growth hormone loci, the human growth hormone (hGH) locus is regulated by a distal locus control region (LCR), which is required in cis for the proper expression of the hGH gene cluster in transgenic mice.

Consensus statement: First International Workshop on Anesthetics and Alzheimer's disease.

In order to review the current status of the potential relationship between anesthesia and Alzheimer's disease, a group of scientists recently met in Philadelphia for a full day of presentations and discussions. This special article represents a consensus view on the possible link between Alzheimer's disease and anesthesia and the steps required to test this more definitively.

Attenuated P2X7 pore function as a risk factor for virus-induced loss of asthma control.

Rationale: Upper respiratory tract infection is a guideline accepted risk domain for the loss of asthma control. The ionotrophic nucleotide receptor P2X(7) regulates compartmentalized acute inflammation and the immune response to airway pathogens.

Objectives: We hypothesized that variability in P2X(7) function contributes to neutrophilic airway inflammation during a cold and thereby is linked to acute asthma.

The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines.

Background: Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate 3H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.

Evaluation of the sentinel immunized node for immune monitoring of cancer vaccines.

Background: We hypothesized that lymph nodes draining sites of cutaneous vaccination could be identified by sentinel node biopsy techniques, and that measuring T-cell response with lymphocytes obtained from these lymph nodes would provide a more sensitive measure of immunogenicity than would the same measurement made with peripheral blood lymphocytes (PBL).

Methods: ELISpot analysis was used to determine the magnitude of vaccine-specific T-cell response in the sentinel immunized nodes (SIN), random lymph nodes, and peripheral blood lymphocytes (PBL) obtained from patients enrolled in clinical trials of experimental melanoma vaccines.

Results: The SIN biopsy was successful in 97% of cases and morbidity was very low.

Treatment of ovarian cancer cell lines with 5-aza-2'-deoxycytidine upregulates the expression of cancer-testis antigens and class I major histocompatibility complex-encoded molecules.

Purpose: To test the hypothesis that decrease in DNA methylation will increase the expression of cancer-testis antigens (CTA) and class I major histocompatibility complex (MHC)-encoded molecules by ovarian cancer cells, and thus increase the ability of these cells to be recognized by antigen-reactive CD8(+) T cells.

Methods: Human ovarian cancer cell lines were cultured in the presence or absence of varying concentrations of the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC) for 3-7 days. The expression levels of 12 CTA genes were measured using the polymerase chain reaction.

A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells.

We characterize a sonic hedgehog (Shh) signaling domain restricted to the adventitial layer of artery wall that supports resident Sca1-positive vascular progenitor cells (AdvSca1). Using patched-1 (Ptc1(lacZ)) and patched-2 (Ptc2(lacZ)) reporter mice, adventitial Shh signaling activity was first detected at embryonic day (E) 15.5, reached the highest levels between postnatal day 1 (P1) and P10, was diminished in adult vessels, and colocalized with a circumferential ring of Shh protein deposited between the media and adventitia.

A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer.

Nine participants with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who were human leukocyte antigen (HLA)-A1, HLA-A2, or HLA-A3, were eligible to enroll in a phase 1 study designed to assess the safety and immunogenicity of a peptide-based vaccine. Participants received 5 class I major histocompatibility complex-restricted synthetic peptides derived from multiple ovarian cancer-associated proteins plus a class II major histocompatibility complex-restricted synthetic helper peptide derived from tetanus toxoid protein. The vaccines were administered with granulocyte macrophage-colony stimulating factor in Montanide ISA-51 adjuvant over a 7-week period.

Effect of nitrous oxide on neurologic and neuropsychological function after intracranial aneurysm surgery.

Background: Laboratory studies suggest that nitrous oxide augments brain injury after ischemia or hypoxia. The authors examined the relation between nitrous oxide use and outcomes using data from the Intraoperative Hypothermia for Aneurysm Surgery Trial.

Methods: The Intraoperative Hypothermia for Aneurysm Surgery Trial was a prospective randomized study of the impact of intraoperative hypothermia (temperature = 33 degrees C) versus normothermia (temperature = 36.

Correlates of problematic eating behaviors in less acculturated Latinas.

We examined whether body weight, depression, and body dissatisfaction could predict problematic eating behaviors in a community sample of less acculturated adult Latina women. Three hundred and forty-nine Latina women ages 20-40 were classified as non-overeater (n=244), eating disorder not otherwise specified-binge eating disorder features (EDNOS-BED) (n=65), or eating disorder not otherwise specified-bulimia nervosa features (EDNOS-BN) (n=40). Participants completed measures of problematic eating behaviors, depression, and body image.

The TAG family of cancer/testis antigens is widely expressed in a variety of malignancies and gives rise to HLA-A2-restricted epitopes.

The TAG-1, TAG-2a, TAG-2b, and TAG-2c cancer/testis genes, known to be expressed in an unusually high percentage of melanoma cell lines, are shown here to be expressed in a variety of tumor lines of diverse histologic type, including cancers of the brain, breast, colon, lung, ovary, pharynx, and tongue. The genes are also expressed in fresh, uncultured melanoma, and ovarian cancer cells. Epitope prediction algorithms were used to identify potential HLA-A1, HLA-A2, HLA-A3, HLA-B7, and HLA-B8 epitopes, and these potential epitopes were tested for their ability to stimulate a peptide-specific cytotoxic T lymphocyte response using lymphocytes from healthy donors.

Subtrochanteric valgus osteotomy for chronically dislocated, painful spastic hips. Surgical technique.

Background: Many treatments have been proposed for a painful chronically dislocated hip in a child with spasticity who is unable to walk. The valgus subtrochanteric femoral osteotomy was originally described as a treatment for a missed congenital hip dislocation in a young adult who was able to walk. The purpose of this study was to investigate the outcomes of a modified Hass subtrochanteric valgus osteotomy for the treatment of symptomatic chronic hip dislocations in patients with spasticity due to neuromuscular disorders.

N-desmethylclozapine an M1 receptor agonist enhances nitric oxide's cardiac vagal facilitation in the isolated innervated rat right atrium.

We have previously determined that neuronal nitric oxide (NO) may partly mediate its established cholinergic effect via activation of muscarinic type 1 (M1) receptors located at the preganglionic/postganglionic synapse. In this series of experiments we set out to confirm this finding using an M1 agonist. Experiments were carried out on the isolated vagally innervated right atrium in the presence of atenolol (4 microM).

Gastric bezoar after lung transplantation in non-cystic fibrosis patients and review of the literature.

Gastric bezoars have been associated with solid-organ transplantation. In this report we describe the occurrence of gastric bezoars in two patients who underwent sequential single-lung transplantation for severe chronic obstructive pulmonary disease, and analyze the possible pathophysiologic mechanisms responsible.

Immunological profiling of a panel of human ovarian cancer cell lines.

Purpose: The efficient identification of peptide antigens recognized by ovarian cancer-specific cytotoxic T lymphocytes (CTL) requires the use of well-characterized ovarian cancer cell lines. To develop such a panel of cell lines, 11 ovarian cancer cell lines were characterized for the expression of class I and class II major histocompatibility complex (MHC)-encoded molecules, 15 tumor antigens, and immunosuppressive cytokines [transforming growth factor beta (TGF-beta) and IL-10].

Methods: Class I MHC gene expression was determined by polymerase chain reaction (PCR), and class I and class II MHC protein expression was determined by flow cytometry.

Subtrochanteric valgus osteotomy for chronically dislocated, painful spastic hips.

Background: Many treatments have been proposed for a painful chronically dislocated hip in a child with spasticity who is unable to walk. The valgus subtrochanteric femoral osteotomy was originally described as a treatment for a missed congenital hip dislocation in a young adult who was able to walk. The purpose of this study was to investigate the outcomes of a modified Hass subtrochanteric valgus osteotomy for the treatment of symptomatic chronic hip dislocations in patients with spasticity due to neuromuscular disorders.

The safety of single-physician procedural sedation in the emergency department.

Background: Previous research has shown the safety of procedural sedation in the emergency department in university settings involving multiple emergency physicians.

Objective: To examine sedation in the emergency department conducted by a single emergency physician with monitoring by the emergency nurse.

Methods: The Procedural Sedation in the Community Emergency Department Registry is a prospective observational database of procedural sedation cases directed by the emergency physicians.

Adoptive transfer of vaccine-induced peripheral blood mononuclear cells to patients with metastatic melanoma following lymphodepletion.

Cancer vaccines can induce the in vivo generation of tumor Ag-specific T cells in patients with metastatic melanoma yet seldom elicit objective clinical responses. Alternatively, adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in 50% of lymphodepleted patients, but are logistically and technically difficult to generate. In this study, we evaluated the capability of vaccine-induced PBMC to mediate tumor regression after transfer to patients receiving the same chemotherapy-induced lymphodepletion used for TIL transfer therapy.

Lamin B1 duplications cause autosomal dominant leukodystrophy.

Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurological disorder characterized by symmetrical widespread myelin loss in the central nervous system, with a phenotype similar to chronic progressive multiple sclerosis. In this study, we identify a genomic duplication that causes ADLD. Affected individuals carry an extra copy of the gene for the nuclear laminar protein lamin B1, resulting in increased gene dosage in brain tissue from individuals with ADLD.