Knowledge, attitudes and influencers of North American dog-owners surrounding antimicrobials and antimicrobial stewardship.

OBJECTIVES: To quantify the individual influences of antimicrobial cost, method of administration and drug importance in human medicine on dog-owner antimicrobial preference, and determine knowledge, attitudes and influencers of dog-owners surrounding antimicrobials and antimicrobial stewardship. MATERIALS AND METHODS: Data were collected through an online survey targeting three dog-owner participant groups. These consisted of individuals residing in: (1) Canada, (2) USA and (3) any country recruited through an educational social media site. USA and Canadian participants were financially compensated. Conjoint analysis was used to quantify the influence of antimicrobial cost, method of administration and drug importance in human medicine. Descriptive and analytical statistics were used for data evaluation. RESULTS: A total of 809 surveys were completed. Antimicrobial cost accounted for 47% of dog-owner preferences, followed by method of administration (31%) and drug importance in human medicine (22%). All groups preferred lower cost drugs that were administered once by injection. Participants were more likely to prefer drugs considered "very important" in human medicine, except for the social media participants, who preferred drugs that were "not at all important." Most respondents (86%) reported antimicrobial resistance as important in human medicine and 29% believed antimicrobial use in pets posed a risk for antimicrobial resistance in humans. Participants recruited through social media, and those in the highest education category, were significantly more likely to report antimicrobial use in pets as a risk to people. CLINICAL SIGNIFICANCE: Cost was the most important factor in dog-owner antimicrobial preferences. There is a need for dog-owner antimicrobial stewardship education.

Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease.

Primary antibody deficiencies require lifelong replacement therapy with immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both subcutaneous and intravenous routes of administering IgG can be effective and well tolerated. Treatment regimens can be individualized to provide optimal medical and quality-of-life outcomes in infants, children, adults and elderly people. Frequency, dose, route of administration, home or infusion-centre administration, and the use of self- or health-professional-administered infusion can be tailored to suit individual patient needs and circumstances. Patient education is needed to understand the disease and the importance of continuous therapy. Both the subcutaneous and intravenous routes have advantages and disadvantages, which should be considered in selecting each patient's treatment regimen. The subcutaneous route is attractive to many patients because of a reduced incidence of systemic adverse events, flexibility in scheduling and its comparative ease of administration, at home or in a clinic. Self-infusion regimens, however, require independence and self-reliance, good compliance on the part of the patient/parent and the confidence of the physician and the nurse. Intravenous administration in a clinic setting may be more appropriate in patients with reduced manual dexterity, reluctance to self-administer or a lack of self-reliance, and intravenous administration at home for those with good venous access who prefer less frequent treatments. Both therapy approaches have been demonstrated to provide protection from infections and improve health-related quality of life. Data supporting current options in IgG replacement are presented, and considerations in choosing between the two routes of therapy are discussed.

Efficacy and safety of a new immunoglobulin G product, Gammaplex(®), in primary immunodeficiency diseases.

This open-label multi-centre study evaluated a new intravenous immunoglobulin, Gammaplex®, in the treatment of 50 patients with primary immunodeficiency and significant hypogammglobulinaemia. Patients treated previously with other intravenous immunoglobulins received Gammaplex® on their same infusion schedule for 1 year; 22 were on a 21-day and 28 on a 28-day regimen (300-800 mg/kg/infusion). There were no serious, acute bacterial infections, whereas six subjects (12·0%) had at least one such infection in the 6 months before enrollment. Forty subjects (80·0%) had at least one non-serious infection; the median number of infective episodes per subject per year was 3·07. Antibiotics were taken by 38 subjects therapeutically and prophylactically by 16 at some time. Fewer than half (46·0%) missed any time off work or school because of infection or other illness. Trough immunoglobulin (Ig)G levels were above 6·00 g/l in all subjects at all assessments after 15 weeks with two exceptions. Overall, 21·2% of infusions were associated with an adverse event up to 72 h after infusion. The frequency of adverse events increased with infusion rate. Headache was the most common product-related adverse event (7·5% of 703 infusions). In conclusion, Gammaplex® is effective in primary immunodeficiency and is well tolerated.

Cyclic AMP causes differentiation and decreases the expression of neutral glycosphingolipids in cell cultures derived from a malignant glioma.

Cultures derived from a malignant glioma (U-87 MG) were treated with 3 mM dibutyryl cAMP. The treatment resulted in morphological differentiation of the cultures and a decrease in cell proliferation. Biochemically, dibutyryl cAMP treatment caused a general reduction in the concentration of neutral glycosphingolipids in the U-87 MG cells. The concentration of individual neutral glycosphingolipids in the untreated cells was 1.8- to 3.0-fold higher than in cells treated for 72 h with 3 mM dibutyryl cAMP. Cells were labeled with [3H]galactose to monitor synthesis of the neutral glycosphingolipids. Decreased synthesis was noted in cells treated with dibutyryl cAMP as compared with untreated cells as indicated by decreased uptake of [3H]galactose label. The ganglioside composition of the cells was essentially unchanged after dibutyryl cAMP treatment.

Effects of diethyldithiocarbamate on calmodulin in neuroblastoma cells.

Diethyldithiocarbamate (DDC) was used to treat the neuroblastoma cell line Neuro-2a. Cell injury caused by DDC affects the calcium-binding protein calmodulin (CaM) and alters copper homeostasis in these cells. Neuro-2a cells were treated with 1 x 10(-5) M DDC for 1 h and were harvested at various time points over a 24-h period. Light microscopy of control cells showed CaM deposited around the cell periphery and along the neuritic processes. Treated cells showed the same distribution until 3 h after treatment. Electron microscopy showed CaM deposited around the cell periphery and within the cytoplasm and nucleus of control cells. Treated cells showed a time-dependent localization of CaM in relation to cellular disorganization. Staining of electrophoretic transfers by ProtoGold showed that CaM was present in all control samples and treated samples through 6 h. Atomic absorption spectrophotometry showed no difference in calcium levels between control and treated samples, but copper levels were significantly elevated. This study indicated that degenerative changes induced by DDC altered calmodulin levels. These changes may have been caused by elevated copper content within the cells and subsequent cell injury.

Comparison of severity of illness indicators in an intensive care unit.

Meaningful comparison of patient outcomes requires an assessment of the severity of illness for the patients being compared. The more severe the underlying illness, the worse the expected outcome. We studied several severity of illness indicators derived from different methodologies in a medical intensive care unit. We compared the Acute Physiologic and Chronic Health Evaluation II, the accepted benchmark indicator for intensive care units, with one complex indicator, Computerized Severity Score, and three simpler indicators, Comorbidity, McCabe-Jackson, and American Society of Anesthesiologists. We found that all correlated well with a comorbidity index. We conclude that the Acute Physiologic and Chronic Health Evaluation II, the Computerized Severity Score, and the McCabe-Jackson scoring systems appear to be comparable predictors of comorbidity in a medical intensive care unit. Selection of a severity indicator will depend on the resources available and the intended uses.

SV-40 transformation: effect on GM2 ganglioside in cultured cell lines.

In previous work, we observed the presence of substantially elevated levels of GM2 after Simian Virus 40 (SV-40) transformation of human fetal brain cells. This elevated level of GM2 contrasted with the reports of many other investigators who had often observed decreased levels of GM2 and a simplification of ganglioside pattern in various non-neural rodent cell lines. In order to determine if the increase in GM2 in the transformed human brain cells would also be found in transformed rodent brain cells, we analyzed ganglioside changes after transformation in mouse brain cell lines and observed the increase in GM3 and low levels or lack of GM2 usually noted in rodent SV-40 transformed cell lines. In addition, we analyzed changes after SV-40 transformation in three human fibroblast lines and found that all three lines contained substantially elevated levels of GM2 after SV-40 transformation. As a result of this study, our earlier work on SV-40 transformed human brain cells, and occasional other reports of high levels of GM2 in human SV-40 transformed cell lines, elevated levels of GM2 may be considered a marker for SV-40 transformed human cells of both fibroblastic and neural origin.

Gangliosides in SV-40-transformed cells derived from Tay-Sachs disease fetal brain.

A human glial brain cell line derived from a Tay-Sachs disease fetal cerebellum was transformed with SV-40 virus in order to obtain a transformed brain cell line which reflected the characteristics of the disease. It was shown that the transformed TSD cell line maintained an elevated level of GM2 which was similar to that shown by the nontransformed precursor. In addition, the TSD transformed line lacked hexosaminidase A.

Fatal Portuguese man-o'-war (Physalia physalis) envenomation.

A fatal case of Physalia physalis (Portuguese man-o'-war) envenomation occurred on the Florida Atlantic coast in 1987. Despite appropriate beachside first aid, the patient was conscious only several minutes before having primary respiratory arrest and, later, cardiovascular collapse that resulted in death. Discharged nematocysts were still visible on the injured stratum corneum five days after envenomation. Additional treatment maneuvers suggested by this case include testing the tentacle fragments found on the victim's skin before their removal to ensure that nematocyst firing has been counteracted. We document the first human fatality caused by P physalis envenomation.

Induction of lymphomas and fibrosarcomas in nude mice after implantation of simian virus 40-transformed human meningioma.

Human cells transformed by Simian virus 40 (SV40) usually show little or no tumor formation after implantation in nude mice. In long-term studies, however, we have observed that 127 to 366 days after subcutaneous injection of SV40-transformed human meningioma cells (KJ-M2-T) into nude mice (Nu/Cox), 6 of 15 animals developed lymphomas or fibrosarcomas, usually at the site of inoculation. The induced tumors were of murine origin and were positive for SV40-T antigen. Chromosome analysis and G11 staining revealed no evidence of hybridization between human and mouse cells. No spontaneous shedding of SV40 was noted with KJ-M2-T cells in vitro; however, SV40 could be rescued after fusion of KJ-M2-T with BS-C-1 monkey kidney cells, but not with L929 mouse fibroblasts. A parallel study using SV40-transformed human fetal brain cells failed to induce tumors in nude mice despite the demonstration that infectious SV40 could also be rescued from this line after fusion with BS-C-1 but not with L-929. Subcutaneous injection of 5 X 10(3) TCID's of SV40 (strain J436) into nude mice resulted in the induction of fibrosarcomas at the injection site in 6 of 15 mice after 273 to 396 days. The induction of malignant lymphomas after implantation of SV40 transformed cells contrasted with the development of fibrosarcomas after injection of free virus. This study suggests that after subcutaneous implantation into nude mice, some SV40-transformed human tumor cell lines can serve as vectors for transmitting SV40 to murine cells causing transformation and tumor development in the host animal.

Further investigation of the association between gastroesophageal reflux and bronchoconstriction.

A double-blind modification of the intraesophageal acid perfusion challenge (Bernstein procedure) was performed in asthmatic subjects with and without gastroesophageal reflux, nonasthmatic subjects with reflux, and normal subjects. Conventional spirometric functions and total respiratory resistance (Rrs) were measured prior to and after the infusion. There were no changes in pulmonary functions except in the asthmatic subjects who had had a positive acid challenge. The greatest changes occurred in Rrs, which increased significantly with reflux symptoms (p less than 0.01) and decreased toward baseline (p less than 0.05) when these symptoms were relieved with antacids. The response was even greater in asthmatic subjects who associated reflux symptoms with attacks of asthma. These results support previous findings that acid reflux symptoms could cause a bronchoconstrictive response in certain asthmatic patients.

The effect of theophylline on the lower esophageal sphincter pressure.

The effects of theophylline on lower esophageal sphincter pressure (LESP) were studied on four normal volunteers and six asthmatics with symptoms of gastroesophageal reflux (GER). Manometric evaluations of LESP were obtained before and after an intravenous dose of aminophylline. All subjects had therapeutic theophylline levels at the time of the second measurement of LESP and a significant decrease in LESP occurred in normal and asthmatic volunteers.

Assessment of a technique for scintigraphic monitoring of pulmonary aspiration of gastric contents in asthmatics with gastroesophageal reflux.

Ten asthmatics with gastroesophageal reflux had scintigraphic evaluation of gastropulmonary aspiration. Five mCi of Tc99m sulfur colloid diluted in 50 ml of isotonic saline were administered by nasogastric tube at bed time and the lungs were imaged the following morning. Imaging in 20 studies yielded no evidence of gastropulmonary aspiration. Scintigraphic evaluation has previously been reported to demonstrate gastropulmonary aspiration in some patients with gastroesophageal reflux and pulmonary disease. This study indicates that the technique may lack adequate sensitivity or that gastropulmonary aspiration in asthmatics with gastroesophageal reflux occurs in only a small subgroup of these patients or at infrequent intervals and is difficult to detect.

Gastroesophageal reflux and asthma: a possible reflex mechanism.

Fifteen asthmatic patients with gastroesophageal reflux underwent an intraesophageal acid provocation test. Pulmonary function measurements demonstrated increased flow resistance when reflux symptoms occurred. After relief of symptoms, these changes tended to rapidly reverse. The technique employed and the prompt reversal of pulmonary functions suggest reflex mechanisms may be producing the observed bronchoconstriction.