Quantitative measurement of nasal production of nitric oxide in awake humans

The aim of this study was to determine, quantitatively, the production of nitric oxide (NO) in the nose and nasopharynx. Subjects were instructed to perform a Valsalva manoeuvre with their mouth open as gas was aspirated from a closely fitting nasal CPAP mask by a chemiluminescence analyser (Sievers 270B, Sievers Instrument Corp. Boulder, Colorado, U.S.A.). Room air was free to flow in through the mouth and out through the nose and hence to the analyser. The manoeuvre was continued until a smooth plateau of at least 20 seconds in duration was achieved on a chart recorder. The mean plateau concentrations were 176 (+/- 39.6) parts per billion (ppb) for males and 135.8 (+/- 24.4) ppb for females. The mean male production of NO was 15.8 nanomol/min which was significantly different from that of females of 12.5 nanomol/min (Mann-Whitney U Test; P < 0.01). By measuring the concentration of NO in gas aspirated from the nose during Valsalva manoeuvre, we excluded the respiratory tract below the glottis from our sampling and as such results represent the portion of NO produced in the nose and nasopharynx. These findings suggest that nasally produced NO is produced in sufficient quantities to act as a continuous pulmonary vasodilator, being inspired preferentially into areas of greatest ventilation, thus perhaps acting to continually match ventilation to perfusion.     

Coronary artery fistula as a complication of percutaneous transluminal coronary angioplasty

The aim of this study was to assess the quality of storage of tetanus vaccine in accident and emergency (A&E) departments and also of the awareness of Department of Health guidelines. A postal questionnaire was sent to 50 randomly selected major A&E departments in the British Isles, enquiring about awareness of Department of Health guidelines (Department of Health, 1990). Forty (80%) A&E departments responded. Only 14 were aware of the Department of Health guidelines and in only 18 was there a member of staff taking responsibility for vaccine storage. The study found that safe storage of vaccine, and therefore guarantee of efficacy, is not occurring in the majority of A&E departments. Unnoticed failure of refrigerators could be exposing patients to the risk of tetanus infection.     

Combined effect of gamma radiation and heating on the destruction of Listeria monocytogenes and Salmonella typhimurium in cook-chill roast beef and gravy

The effect of heating alone (60, 65 or 70 degrees C), heating after irradiation (0.8 kGy) and heating after irradiation and storage for 14 days at 2-3 degrees C on the destruction of Listeria monocytogenes and Salmonella typhimurium in artifically inoculated minced cook-chill roast beef and gravy was investigated. Inoculated minced roast beef samples (5 g) were heated in Stomacher bags completely immersed in a water bath at each of the test temperatures. Survivors were enumerated and D and z values were determined for each of the pathogens. Observed thermal D values for two strains of L. monocytogenes at 60, 65 and 70 degrees C in the absence of pre-irradiation were 90.0-97.5 s, 34.0-53.0 s and 22.4-28.0 s, respectively, whereas thermal D values after pre-irradiation were 44.0-46.4 s, 15.3-16.8 s and 5.5-7.8 s at 60, 65 and 70 degrees C, respectively. This reduction in D values provides evidence for radiation-induced heat-sensitisation in L. monocytogenes. There was some evidence of heat-sensitisation of S. typhimurium at 60 degrees C, but not at either 65 or 70 degrees C. The z value also decreased as a consequence of pre-irradiation to a dose of 0.8 kGy (11.0-12.7 degrees C). The radiation-induced heat-sensitivity in L. monocytogenes was found to persist for up to 2 weeks storage at 2-3 degrees C prior to heating. As cook-chill products are intended to be reheated prior to consumption the results of the present study suggest that any L. monocytogenes present in a cook-chill product would be more easily killed during reheating if it were to be treated with a low dose of gamma radiation during manufacture.     

Self-reported illness from chemical odors in young adults without clinical syndromes or occupational exposures

The present survey of young adult college students investigated the prevalence of self-reported illness from the smell of the five following common environmental chemicals (cacosmia): (1) pesticide, (2) automobile exhaust, (3) paint, (4) new carpet, and (5) perfume. Sixty-six percent of 643 students reported feeling ill from one or more of the five chemicals; 15% identified the smell of at least four chemicals as making them ill. Ratings of illness from pesticide correlated weakly but significantly with ratings for the largest number of individual symptoms (9 of 11); daytime tiredness and daytime grogginess both correlated at high levels of significance with illness ratings (on a 5-point scale) for four of the five chemicals. The most cacosmic group (CS) included significantly more women (79%) than the noncacosmic group (NS) (49%); women overall were more cacosmic than men (p < .001), even with the significant covariate of depression. Ratings of cacosmia correlated only weakly with scores for depression (r = 0.16), anxiety (r = 0.08), and trait shyness (r = 0.18) in the total sample. On stepwise multiple regression with cacosmia score as the dependent measure, shyness accounted for 5.8% of the variance, while depression, anxiety, sense of mastery, and repression did not enter the equation. Histories of physician-diagnosed hay fever, but not asthma, were more frequent in the CS (16%) than in the NS group (5%). Without the confounds of chronic illness or specific treatment programs, these data are similar to patterns described clinically for a subset of patients with multiple chemical sensitivities (MCS), including previous data on increased nasal resistance in MCS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and economic analysis of allogeneic peripheral blood progenitor cell transplants: a Canadian perspective

Allogeneic peripheral blood progenitor cell (PBPC) transplants are an alternative to BMT, although G-CSF mobilization dose, timing of pheresis and risk of GVHD are not well defined. We compared harvest characteristics, donor and recipient outcomes and costs of two PBPC transplant strategies with historical controls who received BMT. Twenty donors mobilized with four daily s.c. G-CSF doses (5 microg/kg/day) (group 1) and 20 mobilized with 10 microg/kg/day G-CSF (group 2) were compared with 20 BM controls (group 3). G-CSF and phereses were well tolerated. Four of 40 PBPC donors required femoral catheter placement. At least 2.5 x 10(6) CD34+/kg recipient weight were collected with two phereses in 19/20 donors (group 1) and 18/20 donors (group 2). Time to neutrophil (18 vs 20 vs 22 days, P = 0.02) and platelet (21 vs 24 vs 27 days, P = 0.005) engraftment was shorter in the PBPC groups (group 2 vs group 1 vs group 3) but secondary engraftment outcomes were not different. The incidence of grade 2-4 aGVHD was higher in the low-dose G-CSF group (group 1) but there was no difference in cGVHD, 100-day or 1-year survival. The mean PBPC transplant cost (group 1) at first hospital discharge was less than BM (group 3) ($34,643 vs $37,354) but the mean overall cost for both groups was similar at 100 days ($46,334 vs $46,083). Allogeneic PBPC transplant with short course, low-dose G-CSF mobilization is safe, feasible and cost equivalent to allogeneic BMT.     

Activation status and function of the VLA-4 (alpha4beta1) integrin expressed on human melanoma cell lines

A highly sensitive microspectrophotometer was developed to measure spectral changes of oxyhemoglobin (oxy Hb) in single red blood cells (RBC) incubated with stimulated macrophages as a model of nitric oxide (NO) dependent cytotoxicity. Our microspectrophotometer, using a modified acousto-optic tunable filter (AOTF) and a 2-dimensional CCD array, allows fast spectrophotometric data acquisition. Human RBC treated with various concentrations of NO showed spectral changes due to the conversion of oxy Hb to methemoglobin (met Hb), in which the change in absorption differences at alpha (557 590 nm) and beta (542-525 nm) bands showed a linear relationship with the concentration of NO up to 100 microM. In contrast to highly diffusible NO, nitrite ions (NO2-) seem to enter RBC very slowly, resulting in negligible formation of met Hb in the presence of 5 mM glucose even during a prolonged incubation period. RBC were incubated with murine macrophages with and without lipopolysaccharide (LPS) in the presence of glucose for 24 and 40 h and subjected to the microspectrophotometric assay. The RBC incubated with LPS-stimulated macrophages showed significant changes in the spectrum due to NO-dependent conversion of oxy Hb to met Hb, which corresponded to the spectral changes of RBC treated with a several times higher concentration of NO than that in the culture medium. The trapping efficiency was calculated from the amounts of the NO released from macrophages and of the met Hb formed in the RBC, which gave a high efficiency (43%). The results suggest that RBC trap NO directly by cell cell interaction with macrophages. This spectrophotometric system is available for use with just a few drops of samples to study NO-specific cytotoxicity as a model of RBC without the use of any chemical reagent, in parallel with microscopic observations on changes of the cellular morphology under physiological conditions, such as membrane damage leading to hemolysis, adherence, and phagocytosis.     

Tear hyperosmolarity in renal dialysis patients asymptomatic for dry eye

Plasma levels of IGF-I, IGFBP-I and IGFBP-3 were measured before and during treatment with tamoxifen up to 19+ months in 34 post-menopausal patients with advanced breast cancer. In 28 patients, pro-IGF-IIE (IGF-IIE) levels were determined and IGFBP-3 was evaluated by immunoblot in 27 patients. Tamoxifen suppressed plasma levels of IGF-I by a mean value of 25.5%-37.7% at different times. This effect was fully developed after 1-2 months of treatment. IGF-IIE was decreased by a mean value of 7.7-23.2% at different time intervals during treatment with tamoxifen, but this effect was significant after long-term treatment (19 months +) only. Plasma IGFBP-I increased by a mean value varying between 48.6% and 190.1%. Tamoxifen had no significant effect on total IGFBP-3 levels. However, patients responding to treatment had a 28% reduction in fragmentation of IGFBP-3, while patients with progressive disease had a 36% increase in fragmentation. The difference between responders and non-responders was highly significant. These findings confirm and extend previous observations regarding the effects of treatment with tamoxifen on IGF-I and IGFBP-I. The finding that patients responding to tamoxifen achieve a reduction in the ratio of fragmented to intact IGFBP-3, while patients progressing on therapy experience an increase in the IGFBP-3 fragmentation ratio, suggest that the tumor burden influences IGFBP-3 protease activity in breast- cancer patients.