The development of a novel Wellness Assessment Instrument and its use in the assessment of wellness status in patients with chronic obstructive pulmonary disease.

AIMS: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder that affects health outcomes on multiple levels including overall wellbeing. More specifically, factors such as spiritual wellbeing, and psychological, mental and motivational status which may be at least as important as others, have been rarely studied. This article reports the method of validating a new wellness assessment questionnaire and the status of several wellness domains in patients with COPD. METHODS: The study consisted of two phases: first, the development of a new Wellness Questionnaire with the help of focus groups; second, the validation and use of the questionnaire in a cohort of patients with COPD. For focus groups, healthy people ⩾45 years of age with no known comorbidity as well as people with a clinical diagnosis of COPD were invited to participate in the study. RESULTS: Thematic analysis of findings from focus groups and original cohort respondents highlighted some factors that appear to influence wellness status. Five domains were explored as potential markers of wellness in patients with COPD. Quantitative analysis with Spearman correlation demonstrated a significant correlation between Physical/Personal Wellness and other markers of COPD progression such as Global Initiative Obstructive Lung Disease (GOLD; 0.006), force expiratory volume in 1 s (FEV1%; 0.01), health-related quality of life (0.009), multidimensional BOD score and quartile (0.003 and 0.02). CONCLUSION: The findings suggest that a combination of personal, physical, emotional, mental and other psychological factors is responsible for negative COPD outcomes. While there is a need to validate this new wellness questionnaire in further research, it incorporates new markers of wellness that could benefit management of COPD.

Nardostachys jatamansi protects against liver damage induced by thioacetamide in rats.

Nardostachys jatamansi is a medically important herb of Indian origin used for centuries in Ayurvedic and Unani systems of medicine for the treatment of various ailments. In the present paper, a 50% ethanolic extract of the rhizomes of N. jatamansi is shown to possess hepatoprotective activity. Pretreatment of rats with the extract (800 mg/kg body wt, orally) for three consecutive days significantly ameliorated the liver damage in rats exposed to the hepatotoxic compound thioacetamide. Elevated levels of serum transaminases (aminotransferases) and alkaline phosphatase, observed in thioacetamide alone treated group of animals, were significantly lowered in N. jatamansi pretreated rats. Pretreatment of the animals with the extract also resulted in an increase in survival in rats intoxicated with LD90 dose of the hepatotoxic drug.

Sevoflurane for predicted difficult tracheal intubation.

Ten patients, predicted to pose a difficult intubation of the trachea, underwent inhalational induction of anaesthesia using sevoflurane. In all 10 cases the airway was secured successfully and the patient proceeded to have the planned operation. In six of the cases the anaesthetist experienced a problem during the induction but in no case did this present any real difficulties or lead to a critical incident. We feel that sevoflurane has a place for inhalational induction in this challenging group of patients.

Arachidonic and docosahexanoic acid content of bovine brain myelin: implications for the pathogenesis of multiple sclerosis.

Lipids were extracted from bovine brain myelin using a mixture of hexane and isopropanol (3:2). Myelin lipids were resolved, using Sep Pak chromatography, into four fractions: Fraction 1 contained neutral lipids, fraction 2, free fatty acids, fraction 3, ethanolamine phospholipids and fraction 4, choline phospholipids. Doscosahexanoic (DHA) and arachidonic (AA) acids in these fractions were measured by RPHPLC. Fraction 2 was analyzed directly, the other three fractions were subjected to alkaline hydrolysis before analysis for DHA and AA. DHA and AA were not found in fraction 1. Both DHA and AA were found in fractions 2 and 3. Only AA was consistently found in fraction 4. These results were confirmed by GC.

Age-related changes in lipid peroxidation and protective enzymes in the central nervous system.

Brain homogenates were used to measure in vitro formation of thiobarbituric acid reactive substances (TBARS) in 5 CNS regions of 3, 12 and 22 month old male Fischer 344 rats. Glutathione peroxidase, catalase and superoxide dismutase activity in 105,000 x g supernatants of these homogenates was also measured. Results indicated that in vitro TBARS formation declined with age in all 5 areas studied. Glutathione peroxidase, catalase and superoxide dismutase activity did not change with age. Regional differences in the activity of glutathione peroxidase and catalase were noted.

Hyperbaric oxygenation and erythrocyte antioxidant enzymes in multiple sclerosis patients.

Erythrocyte glutathione peroxidase, catalase, and superoxide dismutase activities were measured in 18 patients with clinically definite MS, and results compared with those from neurological controls. These studies indicated that glutathione peroxidase activity in erythrocytes of MS patients was not different from that of the neurological controls. However, superoxide dismutase was lower in the MS patients compared to neurological controls. The effect of hyperbaric oxygenation on these erythrocyte enzymes in MS patient's was also investigated. Exposure of MS patients to 2 ata with either 10% O2 or 100% O2 had no effect on glutathione peroxidase activity. Comparison of each individual MS patient's pre- and post-treatment superoxide dismutase values indicated a significant increase after 100% O2. Similar examination of each individual's catalase activity indicated an increase after exposure to both 10% O2 and 100% O2 at 2 ata. These data suggest that erythrocyte enzyme response to oxygen stress does not involve changes in activity of all the antioxidant enzymes. Instead, only specific enzymes appear to be affected by HBO.

Glutathione peroxidase activity in surgical and autopsied human brains.

Glutathione peroxidase (GSHPx) activity was assayed in normal cerebral gray and white matter samples obtained from frontal, temporal, occipital and parietal lobes during surgical approach to an underlying lesion, and also in normal autopsied human frontal gray and white matter. GSHPx was assayed by a 2 step enzyme reaction which was monitored by following the oxidation of NADPH at 340 nm. It was found that all the brain samples studied contained GSHPx activity. Parietal lobe appeared to have the lowest GSHPx activity compared to temporal, occipital or frontal lobes. Mean enzyme activity in autopsied samples was comparable to that in surgical material. However, considerable loss of activity was observed after 10 years of tissue storage at -80 degrees C.

Biochemical studies on brains of young and old inbred (BC3F1) mice.

Brains of 9 BC3F1 mice, 5 aged 6 months (young group) and 4 aged 29 months (old group), were studied. Basic protein (BP) content as determined by radioimmunoassay was significantly (0.05 less than p less than 0.02) increased in the old mouse group with a mean value of 6.2 mg BP/g dry weight as compared to the young group wiith a mean value of 4.6 mg BP/g dry weight. Phenol-formic acid-water disc gel electrophoresis of whole brain homogenates showed increased density of the basic protein low-molecular-weight component in the aged mouse as compared to the young. Water content, total protein content and 2',3'-cyclic nucleotide 3'-phosphodiesterase specific activity were unchanged with increasing age.

Biochemical and immunological studies with human optic and olfactory tracts.

Clinical and pathological studies have revealed that in multiple sclerosis (MS) the involvement of the optic tracts is much more frequent than that of the olfactory tracts. To investigate the possible reasons for this difference in involvement of these two adjacent structures, both containing a central type myelin, we have studied optic and olfactory tracts obtained at autopsy from 7 adult males ranging in age from 54 to 64 years. White matter from the frontal poles of the same individuals was used for reference. These tissues were compared with respect to the relative content of a) water, b) soluble proteins, c) 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity, and d) immunologically precipitable basic protein (BP). Homogenates from these tissues were further compared by disc gel electrophoresis in two systems; phenolformic acid-water and SDS-urea gels. Results indicate that while the optic tracts and the frontal pole white matter were similar with respect to their water, total protein content and BP content, the optic tracts had lower CNP activity than the frontal poles. The olfactory tracts contained more water and less BP and the CNP activity of these structures was lower than that of the frontal pole white matter. Assuming the CNP activity and the BP content are true measures of the total myelin content of a given tissue, it appears that olfactory tracts have smaller amounts of myelin. On the other hand, the optic tracts contain only half as much CNP-activity with a disproportionately greater amount of BP. The possible significance of these findings is discussed.

Electrophoretic and morphologic studies on normal human white matter obtained at surgery with special reference to its basic protein component.

Histologically confirmed normal pieces of human white matter removed during surgical approach to underlying pathology were studied by acrylamide disc gel electrophoresis and electron microscopy. A basic electrophoretic pattern of the white matter homogenates from three separate patients is described. Aliquots of white matter from two of these patients were incubated at 4 degrees C and 23 degrees C for intervals up to 18 hours, then homogenized and electrophoresed to detect any degradative changes in the basic protein band. Results of these studies indicated that the basic protein band of freshly obtained normal human white matter was unaffected by incubation at 23 degrees C for as long as 18 hours. Electron microscopic examination of white matter that was incubated for 2 hours at room temperature prior to fixation, showed sporadic areas of lamellar separation, a finding similar to but not as extensive as that described earlier in white matter obtained at autopsy that was performed 8 hours post-mortem. These findings 1) confirm earlier observations made on autopsy material, 2) are compatible with location of basic protein along the cytoplasmic surface of myelin lamellae, and 3) further emphasize the remarkable resistance of basic protein in situ to autolytic degradation.

Qualitative and quantitative studies on human myelin basic protein in situ with respect to time interval between death and autopsy.

Normal human frontal lobe white matter obtained at autopsy was used to determine the extent of in situ post-mortem degradation of myelin basic protein (BP). Effects of the following two factors were studied: 1) time interval between death and autopsy, and 2) freezing and thawing the tissue. Quantitative extraction of BP from the autopsy material showed only minimal loss of BP that could be attributed to the time interval between death and autopsy (up to 48 h). The purified BP from these samples was electrophoresed on acrylamide gels at pH 4.3 and it was found that the electrophoretic patterns were comparable to zero hour bovine BP samples. The BP obtained from the autopsy samples was found to be encephalitogenic in guinea pigs. When tested against rabbit anti-human-BP serum, the purified BP preparations gave a single arc in immunoprecipitin test. BP extracted and purified from tissue that was frozen once and processed before it could thaw showed yields, encephalitogenic activity and acrylamide disc gel electrophoretic patterns that were similar to those of BP from tissue that was never frozen. However, frozen tissue that was thawed and then incubated for 8 h at room temperature before processing yielded only 13-25% of the total extractable protein. This BP also was encephalitogenic and showed acrylamide banding pattern that was similar to BP from tissue that was never frozen. Samples of white matter were examined by electron microscope. Unfrozen autopsy material showed some separation of myelin lamellae. Myelin in sections of frozen and thawed white matter showed separation as well as disruption of the lamellae. Samples that were frozen, thawed and then incubated at room temperature for 8 h showed sporadic loss of dense line material in addition to lamellar separation and disruption. The results a) show that BP is quite resistant to autolytic changes and b) are consistent with the location of BP along the cytoplasmic surface of the myelin membrane.

Olfaction in multiple sclerosis. With a note on the discrepancy between optic and olfactory involvement.

Serial binary dilutions of amyl acetate and nitrobenzene were used in a double-blind test to determine olfactory acuity of 40 multiple sclerosis (MS) patients. Similar determinations were made on 24 age- and sex-matched controls. Results of repeated measurements on 18 patients indicated that the methodology was reliably reproducible. When mean olfactory threshold on MS patients was compared with that of the controls no differences could be found. Among the MS patients, olfactory threshold did not vary with the presence or absence of optic involvement and correlated poorly with the degree of disability. These results are in disagreement with those of WENDER and SZMEJA who reported olfactory dysfunction in 18 out of 52 MS patients. Our findings are compatible with the observations of ZIMMERMAN and NETSKY who failed to find any plaques in olfactory tracts of MS brains. The significance of this disparity between involvement of optic and olfactory systems, both of which contain central myelin, is discussed. Available biochemical evidence suggests that, as postulated by LUMSDEN, sparing of olfactory tracts may in part be related to the relatively lower basic protein content of these structures.

Circulating IgE, allergy and multiple sclerosis. Serum levels of IgE, other immunoglobulins and complement (C's) in patients with multiple sclerosis in exacerbation and other neurologic diseases.

Serum levels of IgE, other immunoglobulins and C'3 were measured in 36 MS patients, and the results compared with those of 40 age- and sex-matched patients hospitalized on Neurology Service. Diagnoses among controls included cerebral infarction, cervical spondylosis, nonmigrainous headache, seizure disorders and peripheral neuropathy. Six patients in the MS group and seven in the non-MS group had a past history of allergy to food, drugs, dust or other substances. IgE levels were measured by double-antibody radioimmunoassay. Other immunoglobulins (G, M, D and A) and C'3 were quantitated by Mancini's method. Results indicate that the median IgE and C'3 levels of MS patients were slightly lower than those for non-MS subjects. Concentrations of other immunoglobulins were similar for the two groups. CSF samples from 12 MS and five non-MS patients were studied and none of these contained measureable (greater than 7.5 U/ml) IgE. In view of: 1) recent reports describing mast cells in MS plaques, 2) the suggested role of biogenic amines in the pathogenesis of demyelinating diseases, and 3) because IgE exists in free and cell bound state, it is suggested that tissue surveys of MS plaques for IgE deposits similar to those seen in glomeruli in nephrotic syndromes may provide a clue to the pathogenesis of MS.

Decreased myelin basic protein content of the aged human brain.

Myelin basic protein was extracted from frontal lobe white matter obtained at autopsy from seven individuals ranging in age from 72 to 78 years. Qualitative and quantitative comparisons were made between basic protein from this group and that extracted from another group of individuals ranging in age from 45 to 65 years. The basic protein content of the older brains was considerably lower than that of the younger brains. Qualitative studies that included assay for encephalitogenic activity, disk gel electrophoresis at pH 4.3, and immunoprecipitation did not reveal any difference in the basic protein derived from the two age groups. Possible factors that may help explain the decreased basic protein content of the aged brain are discussed.