Bupropion Hydrochloride.

Bupropion hydrochloride is a norepinephrine-dopamine disinhibitor (NDDI) approved for the treatment of depression and smoking cessation. Bupropion is a trimethylated monocyclic phenylaminoketone second-generation antidepressant, which differs structurally from most antidepressants, and resides in a novel mechanistic class that has no direct action on the serotonin system. Comprehensive chemical, physical, and spectroscopic profiles are presented. This analytical profile provides an extensive spectroscopic investigation utilizing mass spectrometry, one- and two-dimensional NMR, solid-state NMR, IR, NIR, Raman, UV, and X-ray diffraction. The profile also includes significant wet chemistry studies for pH, solubility, solution, and plasma stability. Both HPLC and UPLC methodology are presented for bupropion and its related impurities or major metabolites. The profile concludes with an overview of biological properties that includes toxicity, drug metabolism, and pharmacokinetics.

Testing for her2 in breast cancer: current pathology challenges faced in Canada.

This review is designed to highlight several key challenges in the diagnosis of human epidermal growth factor receptor 2 (her2)-positive breast cancer currently faced by pathologists in Canada: Pre-analysis issues affecting the accuracy of her2 testing in non-excision sample types: core-needle biopsies, effusion samples, fine-needle aspirates, and bone metastasesher2 testing of core-needle biopsies compared with surgical specimensCriteria for retesting her2 status upon disease recurrenceLiterature searches for each topic were carried out using the medline, Embase, International Pharmaceutical Abstracts, and biosis databases. In addition, the congress databases of the American Society of Clinical Oncology (2005-2011) and the San Antonio Breast Cancer Symposium (2007-2011) were searched for relevant abstracts.All authors are expert breast pathologists with extensive experience of her2 testing, and several participated in the development of Canadian her2 testing guidelines. For each topic, the authors present an evaluation of the current data available for the guidance of pathology practice, with recommendations for the optimization or improvement of her2 testing practice.

Updated recommendations from the Canadian National Consensus Meeting on HER2/neu testing in breast cancer.

Testing for HER2/neu in breast cancer at the time of primary diagnosis is now the standard of care. Accurate and standardized testing methods are of prime importance to ensure the proper classification of the patient's HER2/neu status. A meeting of pathologists from across Canada was convened to update the Canadian HER2/neu testing guidelines. This National HER2/neu Testing Committee reviewed the recently published American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) guidelines for HER2/neu testing in breast cancer. The updated Canadian HER2/neu testing guidelines are based primarily on the ASCO/CAP guidelines, with some modifications. It is anticipated that widespread adoption of these guidelines will further improve the accuracy of HER2/neu testing in Canada.

Surgical treatment of colonic ganglioneuromatosis in neurofibromatosis.

Gastrointestinal involvement in neurofibromatosis occurs in three forms: neurofibromatous tumours, visceral vasculopathy and ganglioneuromatosis. A case of colonic ganglioneuromatosis is reported and six similar cases from the literature are reviewed. The clinical and pathological features of this condition are summarized and guidelines for surgical therapy formulated. Subtotal colectomy is recommended for pseudo-obstructive symptoms refractory to medical management.

Multicentric gastric carcinoids complicating pernicious anemia. Origin from the metaplastic endocrine cell population.

We report three cases of multicentric carcinoid tumors of the stomach in patients with long-standing pernicious anemia and severe atrophic gastritis (type A). The tumor nodules arose in nonantral gastric mucosa showing marked intestinal metaplasia. Diffuse endocrine cell hyperplasia was present in both fundus and antrum. Antral G-cell hyperplasia was observed. A widely accepted pathogenesis of this syndrome suggests that the proliferating cell type is the argyrophilic, enterochromaffinlike cell native to the gastric body and fundus. Our findings conflict with this view, in that focal argentaffin staining was also present within tumor cells, as well as immunoreactivity for serotonin and substance P (more characteristic of small-intestinal enterochromaffin or Kulchitsky's cells and small-intestinal carcinoids). Findings in these cases at least suggest an alternative possibility: the tumors may derive from small-intestinal-type metaplastic endocrine cells within the atrophic mucosa, rather than the hypertrophic native endocrine cell population.

Brain hemorrhage associated with methanol poisoning.

We recently treated seven patients who were victims of accidental methanol intoxication. Five of the seven patients died within 72 h of hospital admission. The two survivors were discharged from the hospital without visual or neurologic impairment. Hemorrhagic necrosis of the brain was found on CT scan and at autopsy in two patients who died. This complication of methanol intoxication prompted us to review our experience with this poison since 1980. Of 45 methanol intoxication patients treated in our ICU, CT scan was performed in 21, and brain hemorrhage was documented in six, thereby giving an incidence of at least six of 45 or 13.5%. Although hemorrhagic and nonhemorrhagic putamenal necrosis has been described from methanol poisoning previously, we postulate that heparinization during hemodialysis may contribute to brain hemorrhage complicating methanol poisoning and recommend the use of artificial kidneys with albumin-primed biocompatible membranes so that heparin administration during hemodialysis can be minimized.

The osteoclast-type giant cell tumor of the pancreas.

We present a case report of osteoclast-type giant cell tumor of the pancreas and review the literature concerning this rare neoplasm, the histogenesis of which is uncertain. Electron microscopic features have suggested stromal, histiocytic, and epithelial origins to different investigators. Analysis of the present case supports and epithelial origin, with positive immunocytochemical staining for carcinoembryonic antigen and for low molecular weight keratin in the mononuclear and in some osteoclastlike giant cells. These tumor cells did not stain for mesenchymal markers (lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S100 protein). Zymogen granules, desmosomes, and zonulae occludentes were identified ultrastructurally and further support an epithelial derivation.

Aspiration biopsy cytology of metastatic endometrial stromal sarcoma and extragenital mixed mesodermal tumor.

Aspiration biopsy from metastatic tumors in two cases of endometrial stromal sarcoma and one case of endometrial adenosarcoma revealed malignant endometrial stromal cells with ill-defined cytoplasm and round or oval hyperchromatic nuclei showing irregular chromatin clumping and conspicuous nucleoli. They were seen mainly in clusters. Aspirate from a metastatic tumor of a mixed mesodermal tumor arising from the omentum showed similar malignant endometrial stroma cells, irregular tight clusters of malignant glandular cells having scanty but well-defined cytoplasm and vesicular nuclei with conspicuous nucleoli, and fragments of atypical smooth muscle tissue. The diagnostic malignant endometrial stromal cells in those reported cases did not display any distinctive cellular features permitting their cytologic identification. They were difficult to differentiate from those of other types of sarcoma. In a clinical setting, with a known primary endometrial stromal sarcoma or mixed mesodermal tumor, however, a cytodiagnosis of its metastases may be suggested when malignant endometrial stromal-cell-like cells are seen in aspirated material, oviating an open-tissue biopsy.

Effect of prior influenza virus infections on susceptibility of AKR/J mice to respiratory challenge with Legionella pneumophila.

Influenza virus administered intranasally to AKR/J mice, followed 3 days later by Legionella pneumophila inoculated intranasally, caused significantly greater mortality than did either of the two agents administered alone. Viable concentrations of both bacteria and viruses dropped in sequentially infected animals, despite the ultimate fatal outcome. Viral concentrations, however, did not decrease as rapidly in sequentially infected as in singly infected mice. Histopathologic lesions were consistent with viral replication aided by elaboration of a bacterial toxin. This observation contrasts with the more commonly observed sequence in which the bacterium proliferates after the virus interferes with host defense. Cell-free preparations were found to have toxic activity.

Modifying effects of exercise on clinical course and biochemical response of the myocardium in influenza and tularemia in mice.

For a study of the interactions of strenuous physical exercise (daily swimming to exhaustion) and a viral as compared with a bacterial infection with regard to the clinical course and the biochemical response of the myocardium, influenza and tularemia of similar lethality were used in mice. In both infections, expected infection-induced catabolic alterations in the ventricular myocardium were evident 2 days before median lethality was achieved, with a more pronounced wasting in influenza than in tularemia. Exercise before inoculation (preconditioning) was beneficial in that the catabolic effects of both infections were limited and lethality in influenza was reduced. Thus, the myocardial protein-degrading effect of influenza did not occur with preconditioning, and oxidative tissue enzyme activities decreased less. In tularemia, cytochrome c oxidase activity was fully preserved with preconditioning, and activation of catalase was less pronounced. Exercise during ongoing infection counteracted the infection-induced decrease in the activities of glycolytic and oxidative enzymes in tularemia, but lethality and bacterial counts in the spleen were uninfluenced. Conversely, exhaustive exercise in influenza increased lethality and had no significant effect on cardiac enzymes. These exercise models caused no major alterations in activation of lysosomal enzymes (beta-glucuronidase and cathepsin D).

Influence of blue-green algae (cyanobacteria) on survival of Legionella pneumophila in aerosols.

The fluid in which blue-green algae (cyanobacteria) (Fischerella sp.) had been grown (algal extract) was investigated for its effect on aerosols of Legionella pneumophila. The bacteria were significantly more stable when suspended in algal extract than in the tryptose-saline solution employed in previously reported experiments. The stabilizing property of the extract disappeared after dialysis, suggesting that a relatively small molecule was involved. The relationship of this observation to the epidemiology of Legionnaires disease is discussed.

In vitro responses of guinea pig peritoneal macrophages to Legionella pneumophila.

Transmission and scanning electron microscopy were used to study the phagocytosis of virulent and avirulent strains of Legionella pneumophila. The interaction between L. pneumophila and peritoneal macrophages from normal guinea pigs or from animals that had survived infection was studied. The virulent strains survived and proliferated within the phagocyte after ingestion by either type of macrophage, whereas the avirulent strain of bacteria was killed by normal macrophages. Although the addition of immune serum enhanced phagocytosis, the outcome was the same as with normal serum.

Treatment of Klebsiella pneumoniae respiratory tract infection of squirrel monkeys with aerosol administration of kanamycin.

The therapeutic efficacy of IM-administered kanamycin was compared with the efficacy of aerosol-administered kanamycin in Klebsiella pneumoniae-infected squirrel monkeys. Differences in mortality or morbidity were not seen with equivalent dosages of antibiotic ranging from 15 to 6.9 mg/kg of body weight/day. Seemingly, the IM route of kanamycin administration was as effective as the aerosol route for therapy.

Dose-response of guinea pigs experimentally infected with aerosols of Legionella pneumophila.

Experiments were carried out to determine the infectivity, clinical course of disease, and lethality of aerosols of Legionella pneumophila for guinea pigs. The median infectious dose was less than 129 organisms; the 50% lethal dose was 1.4 x 10(5) organisms. In addition, the intraperitoneal 50% lethal dose was 3.0 x 10(6) cells, a value indicating that the organisms were less virulent by the intraperitoneal route than by aerosol. Nonfatal disease always included fever and weight loss. These signs were accompanied by sporadic bacteremia and dyspnea. Leukocyte counts were uninformative. In general, the severity of fever and extent of serologic (microagglutination titer) response were dose-related. The guinea pig may be used as a model for Legionnaires' disease, but the only dependable clinical criteria of infection after airborne challenge are weight loss, fever, and seroconversion.

Protection against Klebsiella pneumoniae respiratory tract infection of mice and squirrel monkeys given kanamycin by aerosol and injection.

The methods of aerosol administration of kanamycin and IM injection of the antibiotic were compared for their protection of mice and squirrel monkeys against Klebsiella pneumoniae respiratory tract infection. Mice exposed to LD90 of K pneumoniae at 0.5, 4, 24, 48 and 72 hours after they were treated with aerosol of kanamycin (27 mg/kg of body weight) were significantly better protected at all exposure times than were mice given the antibiotic (450 mg/kg) by IM injection. Squirrel monkeys given the aerosol at dose level of 11.25 mg/kg were completely protected against K pneumoniae exposure at 6 and 24 hours, whereas only one of eight monkeys treated with the same dose given IM survived the exposure at 6 hours and none survived at 24 hours. Antibiotic clearance curves indicated that kanamycin remained in the lungs at higher concentrations and for longer periods after aerosol treatment than after IM treatment.

Nonhuman primate model for the study of respiratory Klebsiella pneumoniae infection.

Squirrel monkeys were inoculated by the intratracheal inoculation of 700 Klebsiella pneumoniae organisms and developed lobar pneumonia in about 24 h. Characteristic clinical findings were fever, anorexia, and coughing. Laboratory findings included leukocytosis or leukopenia (with the latter more prominent in ultimately fatal infections), bacteremia, and shedding of bacteria into the pharynx. Infected monkeys showed increased plasma lysozyme activity as well as increased plasma ceruloplasmin, haptoglobin and alpha1-antitrypsin. The mortality rate was 60%, and the mean time of death was 50.5 h. Pathologically, the disease spread by means of Kohn's pores and other pathways that generally did not involve airways as a means of dissemination until about 30 h. Squirrel monkeys seem to be better models for human respiratory K. pneumoniae infection than rats or mice.

Relationship of method of administration to respiratory virulence of Klebsiella pneumoniae for mice and squirrel monkeys.

Klebsiella pneumoniae given by aerosol was significantly less virulent in mice and monkeys than when given by intranasal (mice) or intratracheal (monkeys) instillation.

Activity of amantadine, rimantadine, and ribavirin against swine influenza in mice and squirrel monkeys.

Amantadine, rimantadine, and ribavirin given orally, either prophylactically or therapeutically, reduced mortality and increased the survival time of 3-week-old mice infected with the type A/New Jersey/8/76 (swine) strain of influenza virus. In addition, amantadine and rimantadine, administered therapeutically, increased the rate of virus clearance from lungs of infected mice. Administration of amantadine either before or after virus challenge ameliorated the illness in squirrel monkeys; when administered therapeutically, it appeared to eliminate virus shedding from infected monkeys within hours after therapy was initiated.

Evaluation of commercially prepared vaccines for experimentally induced type A/New Jersey/8/76 influenza virus infections in mice and squirrel monkeys.

Mice and squirrel monkeys were vaccinated and subsequently challenged at selected times to evaluate the immunoprophylactic value of vaccines against influenza virus type A/New Jersey/76. Mice were challenged with virulent, homologous virus either 17 or 60 days after vaccination with 80 chick cell-agglutinating (CCA) units of whole-virus vaccine. Vaccinated mice showed minimal lesions and virus in lung tissue and had lower lung weights than unvaccinated controls. These mice had titers of hemagglutination-inhibiting (HAI) antibody in serum of greater than 1:400, but only traces of antibody were found in lung washes. Vaccinated squirrel monkeys had significantly less illness than unvaccinated controls when challenged with virulent virus 30 days after intramuscular immunization with 200 CCA units of whole virus or 400 CCA units of split virus given either once or twice (at 30-day intervals). Equal protection was observed in all monkeys despite the absence of serum HAI antibody in some monkeys after vaccination. Anamnestic reactions were observed only in monkeys vaccinated with whole virus. The possible roles of various immune factors and antibody to neuraminidase are discussed.