PCP exposure for the Canadian general population: a multimedia analysis. Pentachlorophenol (PCP) is ubiquitous in the Canadian environment, as a result of the large quantities used in the wood preservation and wood protection industries. In the past decade, agricultural and wood protection applications of PCP in Canada have been sharply curtailed. A multimedia approach was used to update estimates of PCP exposure of the members of the general population in Canada, based on currently available information. A detailed review of PCP concentrations reported in air, water, foods, household dust, and soil was performed. PCP intake estimates for infants, toddlers, school-age children, and adults in Canada were calculated. Estimates were made for people with average intakes of air, water, foods, household dust, and soil, as well as for recreational anglers and aboriginal subsistence fishermen, who were expected to have higher intakes. The current estimated intake by all of these populations is well below the Acceptable Daily Intake (ADI) of 6 micrograms/kg bw/day. The average members of the general population have an estimated intake via all routes of 0.05 micrograms/kg bw/day; most exposure is calculated to occur via food (dairy products, grains and cereals and meats) and indoor air. Recreational anglers are estimated to be exposed to only marginally more PCP per day (roughly 2%) than the general population. In contrast, aboriginal subsistence fisherman, because of their very high consumption of fish and fish products, experience the highest exposure to PCP through food; their estimated intake of PCP is almost twice that of the general population.


Mammalian selenoproteins.

Mammalian selenoproteins. Selenium (Se) is an essential trace element for animals and humans. Its biological role was established following the discovery that Se is a structural component of the active center of the enzyme glutathione peroxidase (GSH-Px). During the last decade remarkable progress has been made in the recognition of the structure and function of several selenoproteins. Cellular GSH-Px was the first enzyme recognized as a selenoprotein. In it Se was found in the form of selenocysteine. The enzyme is a tetrameric protein and is composed of four apparently identical subunits each containing one gram atom of Se. Plasma GSH-Px also has a tetrameric form with identical subunits and with one atom of Se per subunit. It is, however, a glycosylated protein, and is distinct from cellular enzyme. Both enzymes catalyze the reduction of hydrogen peroxide and a variety of organic hydroperoxides by glutathione. A third GSH-Px, called phospholipid hydroperoxide glutathione peroxidase (PHGSH-Px), is a monomeric, membrane-associated enzyme containing one atom of Se per mole of protein. This enzyme destroys esterified lipid hydroperoxides. The fourth known mammalian selenoenzyme is a type I iodothyronine 5'-deiodinase that catalyzes the deiodination of L-thyroxine to the biologically active hormone 3,3',5-triiodothyronine. It is a monomeric enzyme and contains one atom of Se per mole of protein. Selenoprotein P, a fifth known selenoprotein, is a glycosylated, monomeric protein containing ten atoms of Se per molecule. The function of this protein is not known, but it may play a role in Se transport or be connected with a protective activity against free radicals. In all these selenoproteins the Se is incorporated into the protein molecule via the selenocysteinyl-tRNA which recognizes the specific UGA codons in mRNAs to insert selenocysteine into the primary structure of selenoproteins.


The effect of seafood consumption on the assessment of occupational exposure to arsenic by urinary arsenic speciation measurements. The determination of arsenite, arsenate, dimethylarsenic acid (DMA) and monomethylarsonic acid (MMA) in urine has been used for assessing occupational exposure to inorganic arsenic because these species were thought to be unaffected by dietary arsenic. However, this investigation reports how the consumption of certain types of seafood can lead to an increase in the amount of DMA excreted and hence an elevation in the urinary arsenic speciation total. Urine samples collected from volunteers between 4-20 hours after the ingestion of moderate-sized portions of mackerel, herring, crab or tuna, showed mean increases in the arsenic speciation totals of between 1.8 and 6.9 times compared with the levels in samples collected before the seafood was consumed. These findings have important implications in devising a biological monitoring strategy for workers exposed to inorganic arsenic.


Estimated distributions for total body surface area of men and women in the United States. For the U.S. population in the age range 18 to 74 years, we estimated distributions for total body surface area for men and women using Monte Carlo simulations based on estimated bivariate distributions for height and weight. Surface area is well fit by individual lognormal distributions for men and women. These distributions are appropriate for use in public health risk assessments. We also examined the effect of the correlation between height and weight on the surface area distributions.


Behaviour of 12 trace elements in serum of uremic patients on hemodiafiltration. The concentrations of the trace elements As, Au, Cd, Cs, Cu, Fe, Hg, Mo, Rb, Se and Zn were studied in the serum of 5 patients with end-stage renal failure who were undergoing treatment with hemodiafiltration. The concentrations of the following elements differ significantly from the reference values: As, Cd, Cu, Hg and Mo are higher, while Rb, Se, Zn and some of the Cs values are lower. The observed concentration deviations may be due to the uremic state and/or the dialysis process. To asses the contribution of the latter, the elements were determined in the substitution fluid and in the dialysate before and after blood contact and passage through the artificial kidney. Our findings suggest that the concentration abnormalities could be related to the substitution fluid for Cs, Rb, Se and Zn and to the dialysate for Mo and Rb.


Effects of measurement error on estimating biological half-life. Direct computation of the observed biological half-life of a toxic compound in a person can lead to an undefined estimate when subsequent concentration measurements are greater than or equal to previous measurements. The likelihood of such an occurrence depends upon the length of time between measurements and the variance (intra-subject biological and inter-sample analytical) associated with the measurements. If the compound is lipophilic the subject's percentage of body fat at the times of measurement can also affect this likelihood. We present formulas for computing a model-predicted half-life estimate and its variance; and we derive expressions for the effect of sample size, measurement error, time between measurements, and any relevant covariates on the variability in model-predicted half-life estimates. We also use statistical modeling to estimate the probability of obtaining an undefined half-life estimate and to compute the expected number of undefined half-life estimates for a sample from a study population. Finally, we illustrate our methods using data from a study of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure among 36 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam.


Cadmium intake with diet in Italy: a pilot study. Data on Cd sources in food are presented and the effects are discussed of the raised environmental level of Cd concentration in some foods. Information is also presented on normal dietary intakes of this element and how these intakes may be increased by environmental pollution or atypical dietary habits. With reference to the exposure risk, the FAO/WHO has established for adults a Provisional Tolerable Weekly Intake (PTWI) limit of 7 micrograms/kg B.W.. Therefore the evaluation of dietary Cd intake has become very important. The purpose of this work is the estimation of dietary intakes of Cd using data on the composition of an average Italian diet. Complete meals from a factory canteen were analyzed and calculations of weekly intake of Cd carried out. Mean dietary intake was 222 micrograms per week (range 137-326 micrograms per week) or 32 micrograms per day (range 19-46 micrograms per day), with the median intake being 198 micrograms per week or 28 micrograms per day. Analyses were performed by means of Zeeman Electrothermal Atomization Atomic Absorption Spectrometry (ETA-AAS). The results obtained, related to the average and representative food consumption of Italian people, show that the weekly intake is well within the PTWI, but the emission of Cd into the environment is continuing and attention must be paid to population groups at risk due to particular food habits.


Dose-response relationships of alimentary PtCl2 and PtCl4 in growing rats. In experiments with rats dose-response relationships of alimentary PtCl2 and PtCl4 were investigated. 2 x 81 animals weighing 35 g were randomly distributed among 9 treatment groups which were fed ad libitum with a synthetic diet containing various amounts of Pt during 4 weeks. Pt was added in the form of PtCl2 or PtCl4 in the amounts 0; 0.01; 0.05; 0.10; 0.50; 1.0; 5.0; 10 and 50 mg/kg diet. The Pt supplementation had no influence on life mass gain or food consumption. In the case of 50 mg/kg Pt in the form of PtCl4 the erythrocyte count and hematocrit were reduced by about 13% in comparison with the control group. Dependent on the Pt dose, the application of PtCl4 and PtCl2 induced Pt retention in nearly all tissues especially in kidney. The effects were greater with PtCl4 than with PtCl2. As a result of the higher Pt retention in the kidneys, the serum creatinine was increased for the higher doses of PtCl4.


Indoor concentration levels of selected pollutants and household characteristics. As part of a large health effect-related human exposure study conducted in the city of Zagreb, Republic of Croatia (Sega and Fugas, 1987), NO2, NH3, HCHO, and settled dust concentrations were measured during winter and summer periods in the kitchens and living rooms of 90 homes throughout the city. Characteristics of households and household members were recorded and correlated with the pollutant concentration levels. The results indicate that household characteristics may be useful for predicting human exposure to air pollutants.


Characterization of selenocysteine lyase in human tissues and its relationship to tissue selenium concentrations. The characterization of human selenocysteine lyase, an enzyme that specifically catalyzes the decomposition of L-selenocysteine to L-alanine and hydrogen selenide, is described. The enzyme is the first described that acts exclusively on a selenium compound. The enzyme from human tissues, analogous to that from pig tissues and bacteria, requires pyridoxal 5-phosphate as a cofactor. L-selenocysteine is the sole substrate with a Km = 0.50 mM. L-cysteine is a noncompetitive inhibitor of the enzyme with a Ki = 5.85 mM. The following amino acids and purines are inert: L-cysteine, selenocystamine, seleno-DL-methionine, 6-selenopurine, and 6-selenoguanosine. The enzyme was found in liver, kidney, heart, adrenal and muscle in decreasing order of specific activity. The enzyme activity in liver was found not to be related to tissue selenium concentration or glutathione peroxidase activity.


Malignant hyperthermia and neuromuscular disease. Malignant hyperthermia (MH) is a rare clinical syndrome characterized by hypermetabolism and triggered by specific anesthetic agents. The mechanism of this abnormal reaction is due to uncontrolled calcium flux in the skeletal muscles resulting in a variable clinical syndrome of muscle rigidity, respiratory and metabolic acidosis, and elevation of temperature. The specific genetic defect underlying this condition has not been identified in humans, though in susceptible swine a mutation of the gene for the ryanodine receptor, a large protein which comprises the calcium channel in the sarcoplasmic reticulum, has been identified recently. Inheritance in humans appears to be autosomal dominant with variable penetrance. Patients with MH rarely have physical or laboratory signs of muscle disease. However, scattered case reports and investigations of individuals with known myopathies and other muscle related problems, such as acute rhabdomyolysis or idiopathic persistently elevated creatine kinase, suggest a possible association of MH with a variety of neuromuscular diseases and stress syndromes. This association is very strong in the case of central core disease (CCD) where it is supported by clinical and laboratory evidence, including the proximity of the CCD gene to the ryanodine receptor gene on chromosome 19. A variety of other diseases have been implicated and can be classified as possibly associated (King-Denborough syndrome, Duchenne muscular dystrophy) or unlikely to be associated (myotonia congenita, sudden infant death syndrome, limb girdle dystrophy, neuroleptic malignant syndrome, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)


Cardiac transplantation in Becker muscular dystrophy. Becker muscular dystrophy is associated with abnormal cardiac features in about 75% of cases; up to one-third will develop ventricular dilatation leading to congestive cardiac failure. As this form of muscular dystrophy is relatively benign, failure to respond to medical treatment warrants assessment for cardiac transplantation.


Congenital myopathy associated with abnormal accumulation of desmin and dystrophin. We studied a 5-yr-old boy clinically presenting congenital myopathy. Muscle biopsy showed sarcoplasmic accumulation of desmin filaments leading to diagnosis of desmin storage myopathy. An immunohistochemical study of other cytoskeletal proteins (actin, alpha-actinin, vimentin and dystrophin) was performed. Desmin positive areas reacted strongly with anti-mid-rod and C-terminus dystrophin antibodies. Probed with the same antibodies by Western blot, desmin and dystrophin showed normal molecular size but densitometric analysis demonstrated a parallel increase of both proteins. Our results indicate that intrasarcoplasmic desmin storage is associated with an abnormal accumulation of dystrophin. Since no other cytoskeletal proteins are accumulated this finding seems to be specific and suggests a possible structural and functional association between these two proteins in striated muscle.


The dystrophin-related protein, utrophin, is expressed on the sarcolemma of regenerating human skeletal muscle fibres in dystrophies and inflammatory myopathies. Utrophin is the 400 kDa protein product of an autosomal homologue (DMDL) of the dystrophin gene. In normal skeletal muscle, utrophin is expressed in vascular smooth muscle, endothelium and nerves but not in mature muscle fibres except at the neuromuscular junction. We have examined the expression of utrophin in a wide range of human skeletal muscle diseases using monoclonal antibodies against three C-terminal epitopes. Utrophin is consistently expressed in all basophilic, regenerating fibres irrespective of the underlying disease or expression of dystrophin. It is also found in regenerating fibres from a normal volunteer. In Duchenne and Becker dystrophies, as well as in dermatomyositis, sarcolemmal staining for utrophin is also seen in larger fibres which are not obviously regenerating. These studies do not support the idea that utrophin occupies membrane attachment sites only when dystrophin is absent or reduced, but would be consistent with utrophin expression as part of an activated foetal programme during regeneration.


Myopathology and a mitochondrial DNA deletion in the Pearson marrow and pancreas syndrome. A patient with the Pearson marrow and pancreas syndrome is presented. She showed an anaemia with neutropenia and thrombopenia, failure to thrive, diarrhoea, disturbed glucose homeostasis and lactic acidosis. An exocrine pancreatic insufficiency was lacking. The disease followed a fatal course. Biochemical investigations of skeletal muscle revealed a disturbed mitochondrial energy metabolism, while many ultrastructural abnormal features were observed in the muscle tissue. Molecular genetic studies showed a de novo deletion in the mitochondrial DNA (mtDNA), different in size from the already published deletions and flanked by two 4 bp direct repeats, interspaced by 4-5 non-repeated nucleotides. mtDNA from 12 other tissues showed the same deletion in different percentages. No obvious relation between these percentages and tissue dysfunction was found. In spite of an open reading frame of 74 codons, only little transcription product of the genomic region resulting from the deletion was found.


Epidemiology of neuromuscular disorders in the under-20 population in Bologna Province, Italy. A retrospective epidemiological survey of the principal neuromuscular disorders was undertaken in the population under the age of 20 yr in Bologna city and province. The incidence of Duchenne muscular dystrophy (DMD) proved to be 25.8 x 10(-5), that is, comparable with the outcome of neonatal screening studies. The incidence of spinal muscular atrophy (SMA) was very high (11.2 x 10(-5), probably the result of our greater awareness and recognition of this disorder. The prevalence of neuromuscular disorders in the 0-19 yr population is 1.5 times that in the general population; that of DMD is 28 x 10(-5) vs 6.3 x 10(-5) and that of the SMA 6.5 x 10(-5) vs 1.2 x 10(-5). Our results indicate that neuromuscular disorders, particularly DMD and SMA I and II, have a much higher prevalence in the first two decades of life than is generally thought. Awareness of the higher prevalence of neuromuscular disorders among the under-20s is essential to the adequate planning of medical services.


Isokinetic muscle testing (IMT) in neuromuscular diseases. Preliminary report. Isokinetic muscle testing (IMT) allows precise and reliable measurement of the force produced by the skeletal muscle during exercise at constant velocity and accommodating resistance. This study reports on some clinical situations that illustrate the difference between manual muscle testing (MMT) and IMT in neuromuscular patients. IMT was performed by a special method (continuous passive motion plus gravity compensation) which allowed the measurement of very weak forces, such as in the four patients described in this study. It is important to note that for the same MMT grading the corresponding isokinetic force values were very different. Therefore there is an obvious correspondence between the isokinetic measurement of muscle strength and the morphological change in the muscle on the CT scan of the thigh, which did not show up on MMT. IMT could be extremely important for research into neuromuscular disorders, where the detection of even the tiniest variations in strength is relevant.


A chronic myopathy with coated vesicles and tubular masses. Two muscle biopsies from a 38-yr-old man with a lifelong mild chronic nonprogressive myopathy, showed accumulations of randomly oriented tubules of T-tubular origin, some of which had become greatly dilated and had accumulated osmiophilic material. The tubular masses lacked oxidative enzyme activity but during their evolution acquired esterase and acid phosphatase activity. Tubular areas appeared to break down and lead to intrusions of extracellular space into the center of fibers. Coated vesicles were numerous and often appeared to arise from the tubules. No abnormality could be detected on SDS PAGE electrophoresis of fractions from sucrose gradients.


Neonatal seizures and severe hypotonia in a male infant suffering from a defect in peroxisomal beta-oxidation. In this paper, we describe a baby male born to healthy non-consanguineous parents presenting at birth with hypotonia and seizures. Additional salient clinical features included the development of glaucoma, the absence of significant facial dysmorphism and the absence of liver enlargement or renal cysts. The patient died at the age of 3 months. At autopsy, liver fibrosis and kidney glomerulosclerosis were noted. Neuropathological findings included pachygyria of the olivary nuclei and cerebellar neuronal heterotopias. There was no evidence for a demyelinating process. Biochemically, the patient was found to have elevated plasma levels of very-long-chain fatty acids (VLCFA) and abnormal bile acid intermediates, whereas other indicators of peroxisomal function (plasmalogen biosynthesis and plasma pipecolic acid) were normal. Catalase staining of a liver biopsy specimen revealed peroxisomes to be present in normal numbers, although some were abnormally large. Trilamellar inclusions typical of a peroxisomal fatty acid oxidation defect were present in macrophages. Indeed, beta-oxidation of the very-long-chain fatty acid hexacosanoic acid (C26:0) was found to be strongly deficient. Fatty acyl-CoA oxidase activity in the patient's liver was normal, however. Furthermore immunocytochemical studies using antibodies against acyl-CoA oxidase, bifunctional protein and peroxisomal thiolase, revealed the normal localization of all three enzyme proteins within the peroxisomes. We suggest that our patient has a selective peroxisomal beta-oxidation defect, a recently identified heterogeneous group of early-onset peroxisomal disorders distinct from the Zellweger syndrome and other generalized peroxisomal disorders.


Immunoquantitation of carnitine palmitoyl transferase in skeletal muscle of 31 patients. We studied 31 patients suspected of having muscle carnitine palmitoyl transferase 2 (CPT2) deficiency. The catalytic activity of CPT2 was measured in muscle biopsies by the isotope exchange method and CPT2 immunoreactivity was quantitated by an enzyme-linked immunosorbent assay. Nine patients had normal enzyme activity and immunoreactivity. Eight patients had significant deficiencies in catalytic activity (> 3 S.D. below reference mean) of which six were also deficient in immunoreactivity. An additional nine patients were significantly deficient in immunoreactivity with normal catalytic activity and five patients had partial deficiencies in both. At least two categories of alterations in CPT may exist which lead to a deficiency based on the data presented: (1) a regulatory defect in CPT which only alters the enzyme active site; and (2) a structural defect due to altered synthesis, increased degradation, or changes in the immunoreactive site. It may prove to be of diagnostic importance to combine the analysis of enzyme activity and immunoreactivity in patients suspected of having a CPT deficiency and to further investigate the condition of partial CPT deficiency.


Parameters of human motor unit twitches obtained by intramuscular microstimulation. Intramuscular microstimulation of motor axons was used to study twitch responses of 209 motor units (MUs) in the first dorsal interosseus muscle (FDI) of 20 normal subjects. Twitch peak force (TF), maximum rate of rise of force (MRRF), contraction time (CT) and one-half relaxation time (HRT) were determined. The distributions of TF (mean 16.0 mN, median 10.3 mN) and MRRF (mean 0.88 N s-1, median 0.66 N s-1) were skewed to the right with the majority of the values lying in the lower ranges, whereas CT (mean 63 ms, median 62 ms) and HRT (mean 61 ms, median 58 ms) were approximately normally distributed. TF was significantly correlated with MRRF, but not with CT in contrast with studies of cat gastrocnemius muscle. TF values were similar to those obtained by spike-triggered averaging in the same muscle. The method proved to be reliable and appropriate for use in patients. Examples of MU twitch parameters from three patients with chronic partial denervation of the FDI are described.


Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy, with special reference to mental ability. We report the results of screening for molecular deletions in 164 boys with DMD and BMD and correlation of deletions with clinical features. A deletion was detected in 100 cases (61%) by Southern blot hybridization analysis with cDNA probes. Thirty-eight different deletions and two duplications were identified. All deletions except one (deletion of exons 48-53) found in males with DMD disrupted the translational reading frame of the gene; however, six deletions in boys with BMD were out of frame. The same deletion in different individuals was found to occur with or without mental impairment, and many different deletions were associated with mental retardation. We were able to ascertain a series of boys [from this study and a previous one (Hodgson S V, Hart K, Abbs S, et al. Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy. J Med Genet 1989; 26: 682-693)] without significant mental retardation who had deletions which, when combined, covered the whole region of the gene in which deletions are commonly found, and within which region individual deletions can be associated with mental retardation.


A large inbred Palestinian family with two forms of muscular dystrophy. This paper reports the results of a clinical, genetic and histopathological study of 19 patients belonging to a large inbred Palestinian family living in Um-El-Fahem, a town located in Israel, which is solely inhabited by Arabs. Their custom of marrying only among relatives has kept the genetic homogeneity of the families intact. There were ten cases of congenital muscular dystrophy (CMD) and nine cases of adult limb-girdle muscular dystrophy (LGMD) belonging to two generations of the same family. Both forms showed autosomal recessive inheritance. The patients with congenital muscular dystrophy had generalized muscular weakness and hypotonia at birth without arthrogryposis or CNS involvement and then had a relatively benign evolution with stabilization of the clinical picture at different ages and variable degree of severity. Muscle biopsy showed a dystrophic pattern. The other nine patients presented with the picture of adult limb-girdle muscular dystrophy but with an unusual tendency to the stabilization of symptoms.


Severe periodic febrile myalgia in infancy due to carnitine palmitoyltransferase deficiency. A 7 1/2-yr-old girl suffered, since early infancy, severe recurrent myalgia during periodic attacks of fever, vomiting and pharyngitis. Neither myoglobinuria nor exercise-induced muscle pain was present. She was found to have carnitine palmitoyltransferase deficiency (CPTD) in leukocytes, fibroblasts and muscle. This case exemplifies the importance of looking for an associated metabolic etiology of recurrent febrile myalgia even in the absence of myoglobinuria.


Modulation of the immune response by transforming growth factor beta. For the past several years immunologists have been fascinated by a series of experiments showing that transforming growth factor beta (TGF beta) suppresses T- and B-lymphocyte growth as well as IgM and IgG production by B cells. Moreover, while exerting chemotactic activity on monocytes and inducing expression of interleukin-1 and interleukin-6 by these cells, TGF beta interferes with bacterially induced tumor necrosis factor alpha production, oxygen radical formation and the adhesiveness of granulocytes to endothelial cells. These mechanisms may provide the basis for the effect of TGF beta to prevent the microvascular changes associated with brain edema formation in bacterial meningitis. Given the potential of lymphocytes as well as macrophages to produce TGF beta 1, this cytokine may exert negative feedback signals on the immune response, provided the cytokine is processed from its latent form to the bioactive homodimer. Potent effects of TGF beta have been observed in experimental animals including the inhibition of the generation of virus-specific cytotoxic T cells and antiviral antibodies as well as the diminution of cellular infiltrates with decreased major histocompatibility complex class-II expression and CD8+ T cells in the tissue of virally infected animals. TGF beta may also be of importance in tumor immunology. By the production of bioactive TGF beta as detected in glioblastoma and acute T-cell leukemia, tumor cells may induce an immunodeficiency state and escape immune surveillance. In inflammation, monitoring of TGF beta in the tissue will bring light on the immune regulation in acute and chronic inflammatory diseases.


Immunoglobulin E and G4 antibodies to infective larvae in a Wuchereria bancrofti endemic population. IgE and IgG4 antibodies to infective larval antigen of W. bancrofti were measured by ELISA in filarial sera. IgE level was quite high in both infected and non-infected people living in filariae-endemic regions compared to people from non-endemic yet tropical regions. It was also demonstrated that IgE levels in amicrofilaraemic, normal children were lower compared to those of adults. Similarly IgG4 response in children was found to be reduced. The distribution of skin test (immediate hypersensitivity) reaction to larval antigen was not very extensive in people from endemic regions. Higher proportions of the normal population (39%) exhibited skin test reaction than either asymptomatic microfilaraemics or chronic patients (13% each). Specific IgG4 antibody was highly elevated in the sera of people with asymptomatic microfilaraemia. The rate of IgG4 seropositivity was 83% in microfilaraemic individuals compared to 20% in the normal population.


Presence of non-Fab IgE binding molecules in the intestinal nematode parasite of mice Heligmosomoides polygyrus. Unsuccessful attempts to identify serum parasite-specific immunoglobulin E (IgE) responses in mice following infections with the intestinal nematode parasite Heligmosomoides polygyrus prompted us to explore the possibility that IgE bound within the parasite antigen could account for the false-positive results observed. A live-worm ELISA was developed. Following incubation, irrelevant IgE monoclonal antibody to DNP, IgE present in normal mouse serum, as well as IgE in immune serum were independently identified within live adult worms in this H. polygyrus-modified ELISA. It was concluded that in addition to parasite-specific IgE binding to H. polygyrus, the parasite may attract both parasite-specific and non-parasite-specific IgE via non-Fab IgE-binding molecules.


Analysis of IgE-binding factors (sCD23) within newborn sera. Factors are discussed as potential diagnostic parameters of atopic disorders. The amounts of sCD23 in sera from newborn children (n = 4,329) were determined by radioimmunoassay with monoclonal antibodies specific for CD23. The sCD23 levels ranged between 0 and 81.5 ng/ml of CD23-specific mAb. Furthermore, the sera of newborns with more than 5 ng/ml (n = 45) were analyzed by SDS/PAGE and subsequent autoradiography using 125I-labeled IgE (PS). These experiments indicate that newborn sera with normal sCD23 amounts contain an IgE-binding activity with a molecular weight of 25 kD; this component was not observed within sera containing elevated amounts (> 5 ng/ml). In addition, a 60-kD IgE-binding component was detected within most of all newborn sera (76.4%). The data show that the IgE-binding pattern of newborn children and the pattern of adult donors are different. Our data suggest that the measurement of quantitative sCD23 amounts combined with the analysis of the molecular weight pattern of the IgE-binding factors might be a helpful diagnostic parameter with regard to IgE-associated diseases.


Effect of mast cell chymase on the morphology of thyroid cells in vitro. We studied the effect of mast cell chymase on the thyroid cells in culture. Rat serosal mast cells, similar functionally to connective tissue mast cells, were obtained after lavage of the peritoneal cavity and lyzed by freezing. The resulting lysate was used as crude enzyme preparation. Mast cell chymase was purified from the crude preparation by anion exchange chromatography. Crude and purified chymase incubated with thyroid cells induced cellular retraction, the appearance of long processes and gradual cell detachment from the substratum. The effect of the enzyme was not cytotoxic. The immunofluorescence studies of thyroid cells showed a decreased amount of polymerized actin and tubulin after incubation with chymase. Neutral protease inhibitor abolished the effect of crude and purified chymase on thyroid cell morphology. The above findings suggest that mast cell chymase may have a function in the control of cell morphology and cell-matrix interaction.


Molecular characterisation of group I allergen Eur m I from house dust mite Euroglyphus maynei. Using the polymerase chain reaction (PCR) we have amplified and cloned genomic DNA encoding the secreted group I allergen proteins from the house dust mite species Euroglyphus maynei, Dermatophagoides pteronyssinus and D. farinae. Affinity chromatography using a monoclonal antibody to the allergen Der p I was used to purify the group I protein from E. maynei. We present the deduced amino acid sequence of a new member of the group I house dust mite allergen family Eur m I. The three proteins show a high level of primary structure similarity: Eur m I and Der p I show 85% amino acid identity, and the three allergen amino acid sequences taken together show 78% identity. A potential N-glycosylation site and residues of the cysteine protease active site are also conserved between the three proteins.


Selective IgA deficiency and autoimmunity. Selective IgA deficiency is the most common primary immunodeficiency. Selective IgA deficiency, as most other immunodeficiencies, is frequently associated with autoimmune phenomena. In this article the authors critically review the literature concerning this association, and discuss the possible mechanisms leading to the increased frequency of autoimmune disorders in subjects with selective IgA deficiency.


Comparative immunoreactive profiles of Japanese and American patients with primary biliary cirrhosis against mitochondrial autoantigens. Primary biliary cirrhosis (PBC) has been described among various ethnic and racial populations in all parts of the world. However, the incidence and prevalence of PBC varies considerably in different geographic areas. It has the highest frequency in Northern Europe, is considerably lower in Japan and still lower in other parts of Asia. There has not hitherto been a detailed immunological profile of antimitochondrial antibodies according to geographic region. We have used recombinant or purified preparations from the 2-oxo-acid dehydrogenase enzyme complexes, the major mitochondrial autoantigens in PBC (PDC-E2, BCOADC-E2, OGDC, protein X and PDC-E1 alpha) to compare the reactivity of sera from either similarly staged sera from Japanese (n = 23) or American-Caucasian patients (n = 39) with PBC. In all cases, the first available sera following diagnosis was selected. Interestingly, only 65% of Japanese patients reacted by ELISA with PDC-E2 compared with more than 95% of the North American group. Moreover, the level of enzyme-inhibitory antibodies to PDC was lower in the Japanese. Our findings prompt the need for characterization of specific susceptibility genes and environmental factors in various parts of the world to clarify the etiology of PBC.


Analysis of autoantibodies among patients with primary and secondary uveitis: high incidence in patients with sarcoidosis. The sera of 122 patients with uveitis were examined for the presence of various antinuclear autoantibodies. Overall 21.3% of the patients had antibodies to ribonucleoprotein (RNP) and 18% to Ro (SSA). When subdividing the patients according to primary uveitis versus secondary uveitis, the autoantibodies were detected more frequently in the second group [anti-RNP 13.3 vs. 31.4%, anti-Ro (SSA) 11.8 vs. 27.7%, anti-Sm 10.3 vs. 24% and poly (G) 2.9 vs. 14.8%, respectively]. No differences could be asserted in autoantibody frequencies according to disease location within the uvea. Among uveitis patients afflicted with sarcoidosis a particular high incidence of autoantibodies was detected in comparison with all other subgroups of patients with uveitis. Although the presence of autoantibodies among patients with uveitis appears not to have a major diagnostic value, their assessment may aid to a better understanding of disease pathogenesis.


Evaluation of the biological significance of leukocyte infiltration of the thyroid in Graves' disease. Graves' goiter size and gland function may be affected by interferon-gamma influencing actions of the thyroid-stimulating antibody. Goiter weight (n = 20), lymphocytic infiltration and class II antigen expression were assessed. The largest goiters, strikingly, has least infiltration but, overall, the looked-for negative correlation between goiter size and lymphocyte infiltration did not materialize. This was presumably due, in part, to inhibiting antibodies in many (8/18) patients' sera. In addition, our data do not support a major pathogenetic role for class II antigen in Graves' disease.


Interferon-gamma production in atopic dermatitis: a role for prostaglandins? Peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) have a reduced capacity to produce interferon-gamma (IFN-gamma) in vitro, in response to phytohaemagglutinin (PHA) when compared to healthy non-atopic controls. This defect appears to correlate closely with the severity of AD at the time of sampling, with less IFN-gamma being produced by cells from patients with more severe disease. Enhanced production of IFN-gamma was observed as the patients clinical symptoms improved. In addition, IFN-gamma production could be increased by either pre-culturing the cells for 3 days prior to PHA stimulation or by addition of indomethacin to the culture medium. These observations suggest that the mechanism of reduced IFN-gamma production in AD is unlikely to be due to an intrinsic cellular defect. The possibility that prostaglandins mediate the suppressed production of IFN-gamma in AD was supported by demonstrating that exogenous prostaglandin E2 (PGE2) inhibited IFN-gamma production in PHA-stimulated PBMC. PGE2 at a physiological concentration (10(-9) M) was also shown to enhance interleukin 4 induction of IgE synthesis by PBMC cultures. Our data suggest that alterations in prostaglandin metabolism play a crucial role in the pathogenesis of AD by inhibiting the production of IFN-gamma.


Ultrastructural evidence for piecemeal and anaphylactic degranulation of human gut mucosal mast cells in vivo. One hundred and seventeen coded intestinal biopsies were examined by electron microscopy and evaluated for morphological evidence of mast cell and basophil secretion in situ. Sixty percent of the biopsies had evidence of secretion. Mast cell secretion was evident in control biopsies, many of which were obtained from uninvolved tissues of patients with inflammatory bowel disease. Biopsies of inflamed continent pouches from ulcerative colitis (UC) patients showed more mast cell secretion than noninflamed UC pouch biopsies. This evidence of mast cell secretion supports recent work that documents high constitutive levels of histamine in jejunal fluids of Crohn's disease patients and suggests a proinflammatory role for mast cells in inflammation associated with pouchitis.


Effect of inhaled platelet-activating factor on bronchial inflammation in atopic non-asthmatic subjects. We have investigated the effect of inhaled platelet-activating factor (PAF) on bronchial mucosal inflammation in 6 atopic non-asthmatic subjects in a double-blind, placebo-controlled, randomised and crossover study. On 2 study periods at least 4 weeks apart, fiberoptic bronchoscopy was performed 24 h after inhalation of either 200 micrograms PAF or methacholine (control) to obtain endobronchial biopsies. Immunocytochemistry using antibodies for trypase (AA1) and eosinophil cationic protein (EG2) was performed to enumerate mast cells and eosinophils, respectively, in the bronchial submucosa. Median values of AA1+ cells and EG2+ cells did not differ significantly after inhalation of PAF or control (23.8 vs. 39 and 6 vs. 8/mm2, respectively, PAF vs. control, non-significant). Our findings suggest that within 24 h of inhaling a bronchoconstrictor dose of PAF, this agonist does not induce bronchial hyperresponsiveness or mucosal inflammation in atopic non-asthmatic subjects. However, because of the small number of subjects studied, these preliminary data should be interpreted with caution.


Airway hyperresponsiveness is associated with inflammatory cell infiltration in allergic brown-Norway rats. The time course of the development of airway hyperresponsiveness (AHR) to inhaled acetylcholine (ACh) and the associated inflammatory cell recovery in bronchoalveolar lavage fluid (BAL) in actively sensitised Brown-Norway rats was studied following challenge with inhaled ovalbumin (OA). IgE for OA was detected in serum obtained from sensitised rats using passive cutaneous anaphylaxis, at titres of 1:10 to 1:30; none was detected in unsensitised animals. There was no significant change in either airway responsiveness to inhaled ACh or in BAL cell counts in rats challenged with saline over the 24 h. Following challenge with a 1% OA aerosol, airway responsiveness to inhaled ACh increased over the 24-hour period, maximal at 18-24 h (saline-challenged group mean -log PC200 1.95 +/- 0.07 M; OA-challenged group mean -log PC200 2.30 +/- 0.05 M; p < 0.01). The composition of the inflammatory cells in the BAL fluid after allergen inhalation varied over the 24-hour period, with an initial neutrophilia at 5-8 h (p < 0.01), followed at 18-24 h by an increase in lymphocytes (p < 0.01) and marked eosinophilia (p < 0.01). There was a significant correlation between airway responsiveness and eosinophil recovery at 5-8 h (p < 0.05), and at 18-24 h after allergen exposure (p < 0.05). At 18-24 h there was also a significant correlation between neutrophils and airway responsiveness (p < 0.05). There was no difference between baseline lung resistance in matched saline- or OA-challenged animals at each time point.(ABSTRACT TRUNCATED AT 250 WORDS)


Randomised controlled trial of effects of coordinating care for terminally ill cancer patients. To measure effects on terminally ill cancer patients and their families of coordinating the services available within the NHS and from local authorities and the voluntary sector. Randomised controlled trial. Inner London health district. Cancer patients were routinely notified from 1987 to 1990. 554 patients expected to survive less than one year entered the trial and were randomly allocated to a coordination or a control group. All patients received routinely available services. Coordination group patients received the assistance of two nurse coordinators, whose role was to ensure that patients received appropriate and well coordinated services, tailored to their individual needs and circumstances. Patients and carers were interviewed at home on entry to the trial and at intervals until death. Interviews after bereavement were also conducted. Outcome measures included the presence and severity of physical symptoms, psychiatric morbidity, use of and satisfaction with services, and carers' problems. Results from the baseline interview, the interview closest to death, and the interview after bereavement were analysed. Few differences between groups were significant. Coordination group patients were less likely to suffer from vomiting, were more likely to report effective treatment for it, and less likely to be concerned about having an itchy skin. Their carers were more likely to report that in the last week of life the patient had had a cough and had had effective treatment for constipation, and they were less likely to rate the patient's difficulty swallowing as severe or to report effective treatment for anxiety. Coordination group patients were more likely to have seen a chiropodist and their carers were more likely to contact a specialist nurse in a night time emergency. These carers were less likely to feel angry about the death of the patient. This coordinating service made little difference to patient or family outcomes, perhaps because the service did not have a budget with which it could obtain services or because the professional skills of the nurse-coordinators may have conflicted with the requirements of the coordinating role.


National survey of current arrangements for diversion from custody in England and Wales. To assess the extent and nature of psychiatric assessment schemes based at magistrates' courts in England and Wales for the early diversion of mentally disordered offenders from custody and to determine the response of the NHS to new initiatives concerning alternatives to custody for this group. Postal survey of the probation service, petty sessional divisions, mental health provider units, and district purchasing authorities in England and Wales. All chief probation officers (n = 55), clerks to the justices (n = 284), managers of mental health provider units (n = 190), and purchasers of mental health services (n = 190) in each of the district health authorities. Number of psychiatric assessment schemes, practical difficulties in their operation, extent of regular liaison with health and social services; current and future intentions to purchase or provide services for diversion from custody. Data were obtained from every magistrates' court. Forty eight psychiatric assessment schemes were identified with another 34 under development. Particular problems were lack of adequate transport arrangements, difficulties with hospital admissions, and overdependence on key people. There was little liaison between health, social services, and members of the criminal justice system. Twenty five of the 106 purchasers who responded had a policy dealing with diversion, and 39 had a scheme under development; 56 purchasers had no current or future plans about diversion. Sixty nine of the 150 providers who responded reported that diversion was included in their current or next business plan. Schemes to divert mentally disordered offenders from the criminal justice system are often hampered by lack of adequate transport arrangements, difficulties in hospital admissions, and overdependence on key people.


Prevalence of asthma in adults in Busselton, Western Australia. To estimate whether the prevalence of asthma in adults increased over a nine year interval. Serial cross sectional studies of the population with a protocol that included both subjective and objective measurements. Busselton, Western Australia. A random sample of 553 subjects aged 18-55 years in 1981, and of 1028 subjects aged 18-55 years in 1990. Respiratory symptoms measured by self administered questionnaire, bronchial responsiveness measured by bronchial challenge with histamine, and allergy measured by skin prick tests. Symptoms with increased prevalence were those with significant association with allergy in this population. Recent wheeze increased from 17.5% to 28.8% (p < 0.001) and diagnosed asthma increased from 9.0% to 16.3% (p < 0.001). The increase was greatest in subjects less than 30 years old. The prevalence of shortness of breath coming on at rest and of hay fever also increased significantly, but the prevalence of shortness of breath on exertion, chronic cough, bronchial hyperresponsiveness, current asthma (defined as recent wheeze plus bronchial hyperresponsiveness), and allergy did not increase. The severity of bronchial responsiveness did not change significantly in any symptom group. Young adults showed a significant increase in reporting of symptoms related to allergy but not in the prevalence of current asthma. The increase in symptoms may be due to increased awareness of asthma in this community, to changed treatment patterns, or to increased exposures to allergens.


Assessment of psychological care in general practice. To pilot a method of assessing psychological care by general practitioners. Prospective examination of psychological care given in general practice by using general health questionnaire with predetermined quantifiable and case specific indices of outcome established at the original consultation. Rural general practice in Clwyd, North Wales. 447 consecutive adult general practice attenders. Three month follow up consultation rates, one year retrospective consultation rates, continuity of care, changes in general health questionnaire scores at follow up, general satisfaction, and acceptability of outcome measures. The principal and trainee identified 72 patients with psychological problems, 46 of whom had new conditions. 133 patients scored over 6 on the 28 item general health questionnaire, 33 of whom were identified as new cases by the general practitioners. 62 patients were seen at follow up, including 23 patients identified by the questionnaire but not by the doctor. The doctors used diagnostic terms to describe the presenting condition in 38 cases. At three month follow up the general health questionnaire scores had fallen by more than 5 points in 22/39 patients identified and managed by doctors and 11/23 identified by the questionnaire. The agreed index of good outcome was almost or completely achieved by 20 of the 39 patients managed by doctors. Quantifiable methods of evaluating the quality of the structure, process, and outcome of psychological care can be achieved in general practice.


Public health in inner London.

Public health in inner London. One of Sir Bernard Tomlinson's aims in his inquiry into London's health services was to advise the secretary of state for health on the future balance of primary and secondary health care "taking account of the health needs of Londoners." Sir Bernard, however, also made it clear that "we have not seen it as part of our remit to carry out a comprehensive needs assessment for the whole of London," but concluded that the extremes of health need found in London were "unparalleled in the rest of England." Dr Jacobson highlights some of the major determinants of health inequality in inner London and assesses the extent to which the proposed solutions are likely to meet these needs.


Adapting antibodies for clinical use.

Adapting antibodies for clinical use. Techniques for antibody engineering are now overcoming the problems that have prevented monoclonal antibodies being used routinely in clinical practice. With chemical and genetic manipulation antibodies can be linked to bacterial toxins, enzymes, radionuclides, or cytotoxic drugs, allowing targeting of treatment. Antigen binding sites from antibodies raised in mice can be jointed with human IgG to reduce immunogenicity. In vitro gene amplification and genetic engineering of bacteriophage have produced large antibody gene libraries and facilitated large scale production of human monoclonal antibodies with high specificity. The trickle of monoclonal antibodies into clinical practice may soon become a flood.


Chromatin fiber loops protruded artificially from nuclei of rat ascites hepatoma cells. To determine the size and location of supranucleosomal fibers, the isolated and swollen nuclei from rat ascites hepatoma cells were broken mechanically by a homogenizer, and the broken nuclei were observed with an electron microscope, with and without treatment with detergent Joy. The observation of the broken nuclei treated with 0.06% Joy demonstrated that most, but not all the protruded chromatin, had a loop structure. Protrusion of chromatin from nuclear fragments was estimated to be about 0.77 microns in length. The conformation of protruded chromatin mainly consisted of supranucleosomal fiber, and a little of nucleosomal fiber. Electron microscopy also indicated that an anchorage of chromatin was nuclear lamina. Therefore, chromatin loop size of supranucleosomal fiber (solenoid) was about 1.54 microns in length, corresponding to nucleosomal fiber of about 9.24 microns in length.


[Optimization of gold immunolabeling techniques on ultrathin slides obtained from samples fixed with glutaraldehyde and osmium tetroxide and enclosed in epoxy resin]. An immunogold labeling technique was carried out on plants infected with CMV, fixed with glutaraldehyde and osmium tetroxide and embedded in araldite CY 212. The effect of the type of support-film used, the resin and manipulations of the grids during immunogold steps, were studied and are discussed. The antigenic activity of virus was restored by treating the sections with sodium metaperiodate. The very high non-specific reactions observed with the support-film or with the resin were eliminated by adding powdered skimmed milk or non-purified albumin into the buffers. Purified bovine serum albumin (grade V) or chicken albumin (grade III to V) were inefficient in reducing this non-specific background.


Electron microscopical demonstration of alkaline phosphatase activity with the cerium-based method in citrate-containing medium at pH 9.3 and the influence of glutaraldehyde fixation. A cerium-based incubation medium, developed for the light microscopical demonstration of alkaline phosphatase activity, was tried out for the electron microscopical demonstration of this enzyme in kidney and heart muscle of the rat. The medium is very stable and the pH is in the optimum range of the enzyme. The medium consists of 14 mM CeCl3, 11 mM Na-citrate, 4 mM MgCl2, 10 mM p-nitrophenyl phosphate, 0.18 M glycine/NaOH buffer, pH 9.3. Other concentrations of cerium and citrate were tried out as well but 14 mM CeCl3, and 11 mM Na-citrate gave the best results with a small amount of non-specific reaction product in the nucleus that can be largely avoided by postincubation rinsing in cerium-containing buffer. In the kidney reaction product was only present along the microvilli of the proximal tubular epithelial cells. In the glomerulus no reaction product could be found whereas light microscopical cryotome sections contained activity in the glomerulus. Replacement of glutaraldehyde by formaldehyde fixatives resulted in reaction product in glomerular and tubular basement membranes, on podocyte plasma membranes and in tubular basal infoldings. In glutaraldehyde-fixed heart muscle, reaction product was present in the basement membranes and on lateral plasma membranes of endothelial cells of blood capillaries.


Murine lymphocytes exhibit heterogeneity in their proliferative responsiveness to calcium ionophore. The calcium ionophore, A23187, when used alone was found to induce proliferation of murine T cells, at concentrations of 0.5-1 mM. This response required the presence of syngeneic splenic adherant cells (SAC) as a source of accessory cells. Interestingly, only CD4+ T cells but not CD8+ T cells or B cells responded to the calcium ionophore by proliferation. The inability of CD8+ T cells or B cells to respond was not related to decreased elevation in the intracellular ionized calcium [Ca2+]i concentration induced by the ionophore, because activated CD4+ T, CD8+ T and B cells all exhibited similar elevation in [Ca2+]i. The inability of CD8+ T cells to respond to calcium ionophore was probably due to insufficient production of autocrine growth factors, such as IL-2, inasmuch as the addition of exogenous IL-2 could completely restore the CD8+ T cell responsiveness. Also, exogenous rIL-1 could partially restore purified T cell response to calcium ionophore, whereas, rIL-6 failed to do so. IL-2, but not IL-4, acted as an autocrine growth factor for T cells responding to the calcium ionophore in the presence of SAC, since, antibodies against IL-2 or IL-2 receptor (IL-2R) but not against IL-4, could inhibit the T cell proliferation. Furthermore, exogenous rIL-2 but not rIL-4 supported the proliferation of T cells to calcium ionophore in the absence of accessory cells. Our results suggest that murine lymphocytes exhibit heterogeneity in their proliferative responsiveness to calcium ionophore and that this may not depend on the early activation signal such as the elevation in [Ca2+]i) induced by the ionophore but may depend on subsequent signals which regulate endogenous growth factor production.


Functional analysis of a CArG-like promoter element in cardiac myosin light chain 2 gene. We have examined the functional properties of a putative regulatory sequence, CCAAAAGTGG, (element A) in chicken cardiac myosin light chain 2 (MLC2) gene promoter by deletion/substitution mutagenesis and transcriptional analysis of RNA by S1 nuclease mapping. The results indicate that the element A sequence, which resembles the evolutionarily conserved A/T-rich CArG box, plays a role in defining the transcription initiation site in MLC2 gene. This is accomplished via repression of a potential transcription initiation at site -40 and promoting the initiation at +1. One of the two other dA-dT-rich sequences (element C), located proximal to initiation site (+1), serves as the basal promoter while the distal A/T rich element B participates in tissue specific transcription of the gene.


Modification of RBC properties by an autoantibody. Binding to RBC senescent antigen. It has been reported that natural antibodies alter aging RBCs, so increasing their vulnerability for removal from the blood stream. Results presented indicate that binding of anti-Gal, a natural antibody, to erythrocytes increases RBC rigidity in terms of microviscosity and deformability. Removal of RBCs from circulation could, at least in part, depend on these alterations.


Changes in plasma membrane protein composition during early development of the frog Rana ridibunda. Plasma membranes of fully-grown oocytes and early developmental stage embryos of Rana ridibunda were isolated by differential and density gradient centrifugation; they were purified 18-fold as indicated by 5'-nucleotidase. The plasma membrane protein pattern of five different developmental stages was studied by two-dimensional polyacrylamide gel electrophoresis. More than 60 protein species could be detected by silver staining. Most of them are largely conserved during development. The rest either show precise stage specificity or exhibit stronger staining intensity at particular stages. The number of proteins specific for each stage is small, neurula being exempted. The changes observed in the plasma membrane profile during development are mostly prominent in a group of proteins with similar molecular weights (40-45 kDa) but with different pI values. The differences observed in the plasma membrane patterns are discussed in relation to the significance of each stage during development.


Purification and characterization of semicarbazide-sensitive amine oxidase from porcine aorta. We purified semicarbazide-sensitive amine oxidase (SSAO) from porcine aorta by sequential DEAE-Sephacel, DEAE-Sephadex and Affi-gel-Con A chromatography. The analysis of this protein under denaturing conditions exhibited two protein bands migrating at 110-107 kDa. Under non-denaturing conditions only a single protein band was observed. By isoelectric focusing pI of SSAO was estimated to be 5.5. The apparent Km and Vmax of porcine SSAO for oxidation of benzylamine were 4.5 microM and 200 nmol/hr/mg protein, respectively. Porcine SSAO was inhibited both by semicarbazide and phenelzine while deprenyl or clorgyline were without any effect on enzyme activity. IC50 for inhibition of semicarbazide and phenelzine was 0.015 microM and 1 nmol, respectively.


Cold shock response of yeast cells: induction of a 33 kDa protein and protection against freezing injury. Cold shock (10 degrees C) treatment to Saccharomyces cerevisiae cells normally grown at 30 degrees C resulted in splitting of vacuoles and retarded membrane fluidity as detected by phase contrast microscopy and in vivo nuclear magnetic resonance (NMR) studies, respectively. The treatment was found to impart protection against subsequent freezing as studied by cell viability and colony forming efficiency. We have earlier reported similar protection and retarded membrane fluidity as a result of heat shock treatment to these cells (Obuchi et al., 1990). This suggests that cold shock and heat shock treatments to yeast cells evoke some analogous responses. However, biochemically a new 33 kDa protein (CSP 33) was detected upon cold shock treatment which is distinct from heat shock induced family of proteins (Kaul et al., 1992). We present here the first report of this kind and its practical implications for protection against freezing.


Concentration of sialic acid in alloxan diabetic rat islets of Langerhans. A microanalytical procedure for the determination of total and surface sialic acid concentrations was employed to establish their changes in relation to the length of alloxan diabetes in rat islets of Langerhans. 14 and 60 days after alloxan administration (65 mg/kg), the number of Langerhans islets was significantly decreased (p < 0.001) compared to the control. According to their size, the distribution of islets displayed no significant difference in diabetic and control animals 14 days after alloxan administration, while after 60 days no large islets (dia > or = 128 microns) were found in diabetic animals. The surface sialic acid was significantly increased in the small islets (p < 0.001), whereas no change was found in the large islets 14 days after alloxan administration. After 60 days, the surface sialic acid of both small and large islets was significantly decreased (p < 0.001). These results demonstrate that chronic beta-cell destruction induces a decrease in the sialic acid content in the pancreatic islet cells, suggesting that sialic acid might play a role in insulin secretory regulation regarding chronic effects of alloxan beta-cytotoxicity.


Synthesis and secretion of glycosaminoglycans and proteins in human normal and otosclerotic bone cells. Some biosynthetic activities of normal and otosclerotic temporal bone cultures have been studied. Bone cells were cultured for 24 hrs. in medium containing 3H-glucosamine, 35SO4 or 3H-proline. Labelled glycosaminoglycans (GAG) and proteins were precipitated from cells and media. In otosclerotic bone cells there was an evident reduction in the synthesis and secretion of radiolabelled macromolecules. The inhibitory effect was always greater in the extracellular than in the intracellular compartment. Some glycosidases were also studied. Otosclerosis decreased the activity of all enzymes examined, indicating that the lower GAG synthesis and secretion in otosclerotic bone cells were not due to an increased degradation.


Flow visualization analysis in a model of artery-graft anastomosis. Flow characteristics near the end-to-end anastomosis of vascular graft were studied in model tubes by flow visualization techniques. Artery and vascular graft were modelled by an elastic tube fabricated from an elastomeric polymer and a rigid plastic tube, respectively. Anastomotic models were made by connecting these two tubes, which had compliance mismatch at their anastomoses. These model tubes were installed into a mock circulatory loop and flow was visualized using hydrogen bubbles and aluminum powder as the tracer. Flow disturbances including flow separation and eddies were observed near the modelled distal anastomosis (graft-to-artery anastomosis). Peak values of the wall shear rate were high in the proximal anastomotic area (artery-to-graft anastomosis) and low in the distal region. These phenomena were enhanced in the models with increased compliance mismatch. The local abnormal flow observed in the anastomotic zone might cause thrombus formation and subintimal hyperplasia. To improve the patency in small-calibered arterial grafts, it is important to match their compliance to that of natural arteries.


Chemical characterization of a potassium hydroxyapatite prepared by soaking in potassium chloride and carbonate solutions. A potassium-doped synthetic apatite was prepared by soaking hydroxyapatite in potassium carbonate and potassium chloride solutions. The hydroxyapatite was prepared by firing slip cast ceramic bodies in vacuum at 1100 degrees C. The conical ceramic samples and a crushed material of this were soaked in carbonate and chloride solutions for 2, 4, 6, and 8 weeks. Potassium, calcium, and phosphate were determined by direct current plasma emission spectroscopy. The carbonate content was determined by thermogravimetric analysis and chloride titrimetrically. After 2 weeks, one potassium ion substituted one calcium ion when soaked in a carbonate solution. When soaked in the chloride solution substitution occurred to the same extent. At phosphate sites the substitution of phosphate for carbonate occurred at one sixth of the sites after 2 weeks. Chloride incorporated one half of the OH-sites after 2 weeks. After 4 weeks about one chloride ion was found in the apatite, and after 6 weeks one and a half of the OH-sites were occupied by chloride ions.


Analysis of primary bone formation in porous alumina: a fluorescence and scanning electron microscopic study of marrow cell induced osteogenesis. Porous alumina ceramics alone and combined with rat marrow cells were implanted subcutaneously in the back of syngeneic Fischer rats. Fluorochrome-labeling was performed post operatively and the ceramics were harvested 6 and 8 weeks after implantation. Undecalcified sections of the implants were observed under fluorescence microscopy and the de novo bone-ceramic interfacial areas were analyzed by a scanning electron microscope equipped with an electron probe microanalyzer. Alumina ceramics alone did not show any bone formation, while all marrow cell loaded ceramics showed new bone formation 6 and 8 weeks after implantation. Bone formation was first observed in the center of the pores and proceeded in a centrifugal direction, leading to contact with the ceramic. These results suggest that bone marrow cells have inherent osteogenic capacity and in the pore region of alumina ceramics progression of the osteogenesis causes the dissipation of intervening fibrous tissue between the de novo bone and alumina ceramic surface.


Interleukin-1 alpha: regulation of cellular proliferation and collagen synthesis in cultured human osteoblast-like cells. In this work the authors studied the effects of interleukin-1 alpha on metabolic activities of human osteoblast-like cells in vitro. The bone nature of the cells was established by assaying for specific bone protein, the osteonectin, and the parathormone receptor, an osteoblast marker. Administration of interleukin-1 alpha to cultured osteoblasts produce an increase in cellular proliferation as suggested by 3H-thymidine incorporation and cell growth studies. Interleukin-1 alpha also affected collagen synthesis confirming its potential role on bone-formation and resorption processes.


Partially purified bacteriocin kills malignant cells by apoptosis: programmed cell death. Bacterial proteins, partially purified bacteriocin (PPB), were investigated for their selective killing of malignant cells. It is shown here that upon PPB-cell interaction DNA fragmentation starts within one hour and peaks at 6 hrs. This process requires an on-going cellular metabolism. It is prevented by both actinomycin D, a DNA dependent RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor. We show here that the DNA fragmentation is triggered by PPB-cell membrane-receptor interaction which signals the activation of endogenous cellular endonucleases rather than actually penetrating the cell and interacting directly with the DNA, or serving as a nuclease itself. Thus, it is suggested that the cell death initiated by the lethal bacterial proteins, PPB, is a programmed, step-wise cell death involving apoptosis.


The effect of protease inhibitors, leupeptin and E64d, on differentiation of C2C12 myoblasts in tissue culture. Intracellular calcium levels play an important role in myofibril disintegration and regeneration of muscle fibers. Earlier studies have shown that the calcium activated protease, calpain, is involved in the removal of Z-discs from myofibrils of striated muscle and the tripeptide-aldehyde, leupeptin, which is an inhibitor of calpain, inhibits this activity. In the present communication, we demonstrate that leupeptin and another calpain inhibitor, E64d, inhibit the fusion of mouse skeletal muscle C2C12 myoblasts to form multinucleated myotubes in tissue culture.


Physical and biological characteristics of the main biomaterials used in pelvic surgery. Our study compared mechanical and biological properties of four materials classically used in surgery: polyethylene terephtalate (Mersilene), polypropylene (Marlex), polytetrafluoroethylene (Teflon) and expanded one (Gore-Tex) and polyaramide (Kevlar). No deterioration for polytetrafluoroethylene and polypropylene under irradiation was observed when materials were treated by physical means. Mechanical tests showed that all these materials could bear more than 50 N. Such a high tensile strength is never reached in visceral physiology. Results of graft elongation during tensile strength test shows two classes: a first one that includes high elongation grafts (Gore-Tex and Marlex) and a second one that includes low elongation grafts (Mersilene and Kevlar). As these materials have many potential uses in surgery, we have performed cytotoxicity tests. Material extracts were obtained under standardized conditions, and we have looked at a potentially toxic effect of substances eventually leached from the materials towards cells cultured in vitro. None of the material extracts listed above were cytotoxic except for untreated Kevlar. Toxicity disappeared when Kevlar was treated with methanol. As suspected, untreated Kevlar contains toxic additives introduced during the manufacture of this textile. Thus, in spite of good mechanical properties, Kevlar should not be used in pelvic surgery on account of its lower bicompatibility. These results shows that the choice of the grafts by surgeons must be relevant in a given application.


Induction of conjunctival epithelial alterations by contact lens wearing. A prospective study. In a prospective clinical study, contact lenses were applied to 14 wearers of glasses with clinically and cytologically normal conjunctiva. The alterations of conjunctival cytology after the start of contact lens wearing were recorded with the technique of impression cytology over a period of 6 months. Within the first few weeks after application of the contact lenses, the patients developed a rapidly increasing alteration of cell size and nuclear morphology. Enlargement of the cell diameter with flattening of the cell body was seen together with numerous different nuclear alterations, in particular snakes (condensations of the nuclear chromatin into a sticklike or snakelike shape, centrally arranged in the nucleus). After this very rapid onset, the alterations increased more slowly towards a possible saturation point (and it seemed that the ultimate changes might possibly not be reached within the investigated period). At about 3-6 months, the patients reached a degree of cytological alteration which was seen in long-time contact lens wearers in our previous study and before this, except for the lack of keratinization, only observed in diseases of the ocular surface. There was a distinct squamous metaplasia of major parts of the conjunctival epithelium which normally is columnar and a decrease of goblet cell density. Squamous metaplasia and nuclear alterations increased with the length of time which had elapsed since the application of contact lenses and with extending the daily wearing time but were always restricted to the contact lens excursion zone on the eye and disappeared after contact lens omission, as seen before. Even patients with major cytological alterations remained free of symptoms, and the conjunctiva was still clinically normal.


NMR study of seed hydration: the role of the seed anatomical structures in water uptake of soaked cowpeas. A NMR method based on the analysis of the transverse magnetization decay curve of water protons, was employed to study the hydration process of commercial cowpeas. In order to investigate the role of the different anatomical parts of the seeds, hilum and micropyle, or alternatively seed coat, were inhibited by a water resistant epoxy resin. The kinetic constant for the hydration of the different sets of beans was measured.


Simplified microsurgical method of therapy for recurrent corneal erosion. Recurrent corneal erosion can develop after superficial trauma and can prove unresponsive to traditional forms of conservative treatment. Over the past 5 years, we have treated 17 unilateral cases with our own surgical technique. The following method was applied for treatment: under an operating microscope the separated corneal epithelium was excised with microforceps and Vannas microscissors. After this, the underlying hypertrophic basement membrane was peeled off Bowman's membrane with a foreign body needle and excised at the rim with Vannas microscissors. The site of hyalin-like formation adhering on the area of Bowman's membrane was next carefully scraped with the foreign body needle. Following this procedure, a dressing lens was fitted to the eye. In 2 cases recurrences occurred, but the healing process was successful in these cases after treatment. With this simplified microsurgical procedure, the recurrent corneal erosion was curable. Through the application of dressing lenses, the danger of recurrence was eliminated, and the healing process was considerably shortened.


Light microscopic radioautographic study on the DNA synthesis of prenatal and postnatal aging mouse retina after labelled thymidine injection. The DNA synthesis of mouse retina from the 19th prenatal day through 12 months postnatal has been studied by light microscopic radioautography after the injection of tritiated thymidine. A peak of the labeling index after incorporation of tritiated thymidine was found at fetal day 19. The labelled cells decreased gradually with the developing of the eye from the first postnatal day and were completely disappeared in two weeks after birth. The data also indicated obvious regional differences of the incorporation of tritiated thymidine during the periods of the retina development. The labeling index was the greatest in the anterior region compared to the equator region and the posterior region in the same group of age. The average number of the silver grains in labelled nucleus lead to a decrease with the development of the retina after birth, but there was no significant regional differences found in the same group of age. The data shown from this study suggest that the cell differentiation in mouse retina proceed from posterior to anterior region.


The significance of brown coloration with regard to lens nuclear hardness in the case of extracapsular lens extraction. Prior to extracapsular cataract extraction, it is useful to have an indication of the nuclear hardness by means of slit-lamp microscopy. Using a fine conical probe and a miniature dynamometer, the resistance to penetration (hardness) of different colored lenses and different forms of 'senile' cataract was measured exactly. In cataracts with gray, brown, or black nucleus and sometimes a clear cortex or deep supranuclear, subcapsular or intumescent cortical opacities, distinct hardening of the nucleus was found, which reached values 3-4 times higher than in clear lenses of 80 year olds. Increasing pathological brown or black coloration of the lens nucleus is related to maximum hardness; on the other hand, maximum hardening was not restricted to brown or black coloration. In some cases we only found brownish or grayish coloration in the lens nucleus that had reached maximum hardness. We found the consistency of clear nuclei of deep supranuclear and subcapsular cortical cataracts to be the same values as those of clear lenses with clear nuclei of the same age.


Low-dose methotrexate treatment in noninfectious uveitis resistant to corticosteroids. A total of 14 patients (10 women and 4 men) ranging in age from 18 to 56 years who presented with active chronic noninfectious uveitis were treated with low-dose methotrexate (MTX). All patients had failed to respond to previous systemic corticosteroid therapy. MTX therapy was initiated in 8 patients at a dose of 40 mg given intravenously once weekly for 4 weeks followed by 15 mg/week given orally; 6 subjects were started on the oral regimen of 15 mg/week. During a follow-up period of 3-24 months, intraocular inflammation improved in all subjects under immunosuppressive therapy with MTX. A concomitant improvement in visual acuity was observed in 11 patients. Side effects included slight elevations in transaminases in 4 patients, transient mucositis in 1 case, partial alopecia in 2 subjects, and nausea in 3 patients. Our initial results suggest that low-dose MTX therapy may be considered as a therapeutic modality in noninfectious, steroid-refractory uveitis.


Quantitative duplex and color Doppler ultrasound in the follow-up of beta-irradiated (106Ru/106Rh) choroidal melanomas. A prospective study. The tumor response to radiotherapy depends highly on the local oxygen concentration, which is governed by the tumor's microcirculatory network. The aim of this prospective study was to quantitate the neovascular blood flow in human choroidal melanomas prior to 106Ru/106Rh irradiation and during a 1-year follow-up period. Pulsatile blood flow was elicited by means of duplex and color Doppler ultrasound in 54 of a total of 55 untreated melanomas with a mean peak systolic frequency of 1.0 kHz (range 0.3-2.7 kHz). The neovascular blood flow decreased significantly 4 and 6 months after beta-irradiation. No intrinsic tumor vascularity was detected 8 and 12 months after treatment. In 3 patients, a rising peak systolic frequency occurred following radiotherapy in advance of recurrent tumor growth. Results indicate that the noninvasive quantitation of neovascular blood flow in irradiated choroidal melanomas by pulsed Doppler ultrasound offers a new diagnostic modality for assessing tumor recurrence.


Argon laser trabeculoplasty: long-term follow-up of at least 5 years. This retrospective study evaluates the long-term follow-up of 331 eyes of 219 patients treated with argon laser trabeculoplasty (ALT). A total of 258 eyes were included with a follow-up of at least 5 years. Success was defined as an intraocular pressure of under 22 mm Hg with a stable visual field and optic nerve head. Overall, 22% (58/258) were regulated after 5 years (glaucoma chronicum simplex 26%, pigment dispersion glaucoma 31%, pseudoexfoliation glaucoma 19%, angle-closure glaucoma 14%, secondary glaucoma 7%). Filtration surgery was performed in 13% (33/258) mainly (73%) in the first 3 years after ALT. Repeat ALT was done in 43% of the eyes, and 60% of these eyes with repeat ALT underwent filtration surgery in the first year. With repeat ALT the overall success rate increased to 38%. High initial intraocular pressure and the stage of glaucoma documented by the visual field loss correlated with the failure of ALT. These results indicate that ALT and re-ALT were effective in glaucomatous eyes, yet there was a substantial diminishing effect as time progressed. Therefore, close follow-up on ALT-treated patients is necessary.


Effects of endothelin and calcium channel blockers on membrane voltage and intracellular calcium in cultured bovine trabecular meshwork cells. The membrane voltage was measured in cultured bovine trabecular meshwork cells. External barium (Ba2+; 10 mM) evoked repetitive overshooting action potentials which were reversibly inhibited by 10(-6) M nifedipine but insensitive to tetrodotoxin (10(-5) M). In contrast, no action potentials could be induced in bovine corneal endothelial cells. The vasoactive peptide endothelin (10(-9)-10(-6) M) induced dose-dependent depolarizations. The intracellular calcium concentration measured by the fura-2 method increased after endothelin application. An initial peak was followed by a sustained plateau. The effect of endothelin on the membrane potential and intracellular calcium value is typical for smooth muscle cells showing a contractile response to the peptide. Recent studies have shown the contractility of bovine trabecular meshwork. We conclude that calcium-channel antagonists and endothelin may alter the aqueous humour outflow through the trabecular meshwork.


Quantitative measurement of aqueous flare and aqueous "cells" in eyes with diabetic retinopathy. In order to evaluate the applicability of the laser flare-cell meter to diabetic oculopathy, we measured aqueous flare and aqueous "cells" in 84 diabetic eyes of 84 patients and 50 normal control eyes of 50 age-matched subjects. Using fluorescein angiography, diabetic retinopathy was divided into background retinopathy (11 eyes), preproliferative retinopathy (38 eyes), and proliferative retinopathy (35 eyes). In diabetic eyes, the occurrence of both aqueous flare (0.73 +/- 0.39 mg/ml human albumin equivalent) and aqueous cells (mean 2.96, range 0-35.7 cells/0.075 mm3) was significantly greater than in the normal control group (flare 0.14 +/- 0.06 mg/ml, cells 0.39, range 0-2 cells/0.075 mm3, P < 0.0001 and P < 0.0002, respectively). The flare values also showed differences between the diabetic subgroups, with flare values being higher in more advanced stages of diabetic retinopathy. No significant correlation could be found between the flare values and the kind of diabetic therapy, the duration of the diabetes, and the number of or the time interval since previous retinal laser coagulations. A flare value of more than 0.5 mg/ml was found to represent probably a "critical value" indicating a tendency towards preproliferative and or proliferative changes. The laser flare-cell meter is a valuable instrument for noninvasive, quantitative assessment of alterations of the blood-aqueous barrier in diabetes. The increase of flare values seems to parallel the progression of diabetic retinopathy.


Proliferative activity and immunohistochemical cell differentiation in human epiretinal membranes. Epiretinal membranes are a complex tissue mainly formed by the proliferation of retinal pigment epithelial cells, macrophages, glial cells, and fibroblasts. The proliferative contribution of these cells in regard of the formation of an epiretinal membrane is not yet clear. We determined the cellular proliferative activity by the use of the monoclonal antibody Ki-67 in 46 epiretinal membranes of proliferative vitreoretinopathy (PVR), PVR recurrences after intraocular silicone oil tamponade, proliferative diabetic retinopathy, and macular pucker. The proliferative activity of each membrane was indicated by the proliferative index (PI), which is the ratio of the actively proliferating Ki-67-positive cells and the total cell number in a cross-section of the membrane. The PI of each membrane was combined with the expression pattern of cell type associated antigens like cytokeratin for epithelial-like cells, KiM7 for macrophages, and glial fibrillary acidic protein for glial cells. Such a membrane typing revealed distinct interindividual differences, but no strict correlation with the underlying disease process. Our findings support the idea of an individual "fingerprint-like" membrane typing at the time of surgery combining the information about the antigen expression pattern of the participating cells and their functional proliferative state. Individual membrane typing for each patient might become clinically significant as soon as the dominating cells for tissue proliferation become key targets for specific pharmacological interventions.


Lymphocytes, macrophages and HLA-DR expression in vitreal and epiretinal membranes of proliferative vitreoretinopathy. An immunohistochemical study. Proliferative vitreoretinopathy (PVR) as a severe complication of retinal detachment and also the main cause of failure in its treatments is not yet completely understood. In the present study, we examined 16 PVR epiretinal membrane specimens removed during vitrectomy from 16 patients with complicated rhegmatogenous retinal detachment by immunostaining of cryosections. We looked for the presence of lymphocytes and detected helper/inducer T lymphocytes (CD4+), suppressor/cytotoxic T lymphocytes (CD8+), B lymphocytes (CD22+), macrophages (CD68+), and HLA-DR expression. The results showed that 6 out of 16 specimens reacted positively with monoclonal antibody against the helper/inducer T cell subset (38%), 5 out of 16 reacted positively with a suppressor/cytotoxic T cell-specific monoclonal antibody (31%), 7 out of 16 reacted with B cell-specific monoclonal antibody (44%), and 14 out of 16 were positive for macrophages and HLA-DR (88%). Nevertheless, we think that the invasion of macrophages and lymphocytes into the membranes is not the cause for the pathogenesis, but a secondary event that might further complicate the course of the disease.


Biocompatibility of silicone oil and high-density liquids. An immunologic study. Silicone oil and high-density liquids can be useful tools in the treatment of complicated retinal detachments. To test whether these substances induce specific and/or unspecific inflammatory responses, we performed immunoassays on 60 rats of two different inbred strains. After sensitization, each rat was injected in the right foot pad with either silicone oil, fluorosilicone oil, perfluorooctane, or perfluoropolyether. Depending on the inbred strain, the volume of the foot pads increased up to the fifth day, indicating an injection-induced inflammatory reaction. Histopathological examination of rats injected with silicone oil showed infiltration by mononuclear cells and occasional giant cells. In rats receiving fluorosilicone oil, additional eosinophilic reactions were observed. The most pronounced reactions occurred after injection of the two perfluorocarbons, which induced a greater number of giant cells and a slight granulomatous reaction. The degree of tissue response was independent of the type of sensitization; the majority of the draining popliteal lymph nodes showed no enlargement. Our findings demonstrate that all substances tested induced inflammatory though unspecific responses.


Depth position of spontaneous venous pulsations in ocular hypertensives and control-group discs. Spontaneous venous pulsation can be observed at the site of entry of retinal veins into the physiological cup of the optic disc. Although it has been speculated that spontaneous vessel pulsation is related to primary open-angle glaucoma, no evaluation has been done on the depth position of such a pulsation inside the cup and its relationship to the intraocular pressure. Using laser scanning tomography, we measured the depth position of the maximal spontaneous vessel pulsation inside the optic cup in 24 discs of 24 patients, including 15 ocular hypertensives and 9 controls. The two groups did not differ significantly in age or refraction. The depth position of the maximal venous collapse, however, showed a significant difference between the two groups (p < 0.005), the mean value being 301 +/- 95 microns beyond the first retinal vessel reflection in the control-group eyes and 507 +/- 193 microns in the ocular hypertensive discs. The location of the depth position of the maximal venous collapse within the excavation could be a parameter that indicates the individual pressure tolerance of the ocular tissues.


Hearing loss among nursing home residents: perceptions and realities. Audiometric examinations were conducted on a random sample of 104 elderly Massachusetts' nursing home residents. The testing revealed that the majority of the participants were hearing impaired. The participants, however, consistently reported satisfaction with their hearing ability and no related hearing problems. Qualitative observations of communication among the participants, staff, and visitors documented that the elderly were negatively affected by their hearing loss. Recommendations are made to improve the quality of care for residents with hearing impairment in the nursing home setting.


The parent expectations survey: a measure of perceived self-efficacy. Self-efficacy in early parenting is the confidence that a mother has in her ability to meet the demands of the role of new parent. The Parent Expectations Survey (PES) was developed to measure perceptions of self-efficacy in early parenting. This article traces the development and psychometric testing of the PES. The PES was tested on 82 primiparas at 1 and 3 months postpartum. It demonstrated internal consistency reliability and concurrent validity. Those mothers who had higher self-efficacy early in the transition to parenthood had greater confidence in parenting and less stress 1 year after delivery, thus establishing the predictive validity of the instrument. The PES, both easy to use and to score, may be used by clinicians during the perinatal period to ascertain a mother's early perceptions of self-efficacy in parenting. For those mothers with low self-efficacy, interventions to empower them in that new role may then follow.


Women's views of the preterm labor experience. This study used a naturalistic approach to describe the childbearing woman's views of her preterm labor and delivery experience. Specifically, the aim was to identify how women describe, interpret, and manage preterm labor and subsequent preterm or term delivery. The views of 20 women who were hospitalized for preterm labor (before 37 weeks) were documented with semistructured, tape-recorded, in-depth interviews during their hospitalization for preterm labor and after delivery. Qualitative data analysis focused on the process of becoming a preterm labor patient and on living with a diagnosis of preterm labor. Women either waited for a period of time before seeking care or sought care immediately for the symptoms they were experiencing. Women interpreted the experience by identifying causes of preterm labor and by worrying about the outcome for the baby. Managing preterm labor required extensive, moderate, or limited changes in their lives. Women who delivered at term appeared to have more tangible help than those who delivered preterm. A better understanding of women's preterm labor experiences will provide clues to nurses on how to improve the care they provide.


The impact of critical injury as described by a spouse: a retrospective case study. This descriptive study explored the initial experience of critical injury from a spouse's perspective. A case study was used to examine the Lazarus stress and coping paradigm. The subject was 43-year-old Caucasian woman, with three young children. Semistructured interviews were conducted 1 month following critical injury. Analysis of data confirmed the cognitive, behavioral, and emotional coping processes as suggested by Lazarus. From the spouse's description, three distinct phases of the critical care experience also emerged: notification, arrival at the hospital, and waiting periods. Cognitive, behavioral, and emotional coping processes were clustered according to the spouse's distinct phases of this experience. A 3 x 3 matrix provides a description of the coping processes during the initial critical care period and offers direction for nursing interventions.


Body image measurement in overweight females. This article details two studies of the reliability and validity of three instruments to measure body image and suggestions for their use in interventions for weight control programs. Weight control programs often fail because there is no attempt to modify clients' negative body images; hence clients may regain weight to match incorrect images. Short, easily administered instruments, such as the Nash Body Image Scale, the Body Image Photo Technique, and the Body Shape Questionnaire used in these studies, are needed to evaluate clients' progress in weight control programs. Subjects were 120 women who were either satisfied or dissatisfied with their body image and weight. All subjects completed body image measures at the outset of the study and 43 subjects completed measures again to determine trait stability of body image at 1 year. Cronbach's alpha estimates provided evidence of reliability, with internal consistency coefficients ranging from .83 to .96. Validity of the measures was supported by significant correlations with scores on the Physical subscale of the Tennessee Self-Concept Scale (r = .60 to .63) as well as by significant differences on the three measures between normal-weight and overweight groups (Nash: F = 28.03, p = .001; Photo: F = 11.58, p = .001). Body image was found to be stable over the 1-year period on the Nash Body Image Scale and the Body Image Photo Technique. These instruments can provide valuable information and potential intervention content for practitioners and researchers alike. The three body image instruments discussed were found to have sufficient reliability and validity to warrant their use in practice and research.


Challenging commonly held beliefs about obesity. The task of nurses is to diagnose and treat human responses to illness and the threats of illness. The challenge is in finding the correct diagnosis and selecting the appropriate treatment. To do this appropriately, nurses need to separate health and illness from life-style; to discover whether or not life-style changes are really called for in treating illness or threats of illness or if nurses are uncomfortable with life-styles that are different from their own and expect all people to have a life-style similar to theirs. To intervene appropriately, nurses need to know whether they are working to help others return to their life-style preference or are forcing patients to chose the nurses' life-style preference. The case of the obese and the search for the successful dieter exemplifies the health care system's need to have individuals follow an exercise and eating program to lead them to thinness (a cultural value) whether or not they value thinness. Are health professionals forcing patients to conform to the professionals' life-style rather than assisting them to a healthier state within their own?


Improving elders' continence state.

Improving elders' continence state. A 6-month study was conducted to assess the effects that noninvasive self-managed interventions on 12 remediable risk factors had on elder's urinary continence status. Each remediable risk factor was linked with a criterion meeting normal and if not normal, one or more interventions. Continence history assessments were conducted monthly on 31 elders (M age = 67.65 years). After the first assessment, elders were identified as continent, incontinent or at risk for loss of continence. At the end of the 6 months, 9 of the 11 incontinent elders moved to the at-risk group and the other 2 remained incontinent, and 12 of the 20 at-risk elders became continent. Both the elders who were initially at risk and those who were incontinent had a statistically significant reduction in the number of remediable risk factors reported at the end of the study period. The assessments and interventions are useful.


Current understanding of malignant hyperthermia: genesis, prevention, and treatment. Malignant hyperthermia (MH) is an uncommon and potentially fatal pharmacogenetic complication of anesthesia. It is commonly triggered by administration of halothane and succinylcholine. The treatment of choice is to administer dantrolene sodium while simultaneously discontinuing the triggering agent. The continued treatment of the patient will reflect the hypermetabolic state. Anesthesia can be safely administered to MH-susceptible patients. Nontriggering agents are used, and meticulous monitoring of the patient is performed. All anesthesia providers should be familiar with MH.


Thermoregulation in the neonate and the consequences of hypothermia. The anesthesia provider plays a major role in the maintenance of a homeothermic state in the neonate undergoing a surgical procedure. It is essential for the anesthesia provider to be knowledgeable about the principles of thermal regulation in the neonate and the potential consequences that can occur as a result of thermal instability.


Post-traumatic stress disorders and European war veterans. After tracing the history of PTSD as a diagnosis and exemplifying its use among non-European war veteran groups, this review article documents the size and characteristics of European war veteran populations and the known psychological, social and medical sequelae of war experience since 1918. Models of psychopathology vary markedly over time and between countries. Treatment practices owe more to sociopolitical and military expediency than systematic assessment of European veterans' needs and treatment outcomes. PTSD has not yet attained the pivotal status it enjoys in studies of American war veterans. Reasons for this are offered along with a proposal that recent European studies rightly highlight a broad spectrum of post-war adjustment difficulties in which PTSD emerges as a process phenomenon with implications for prognosis and future care planning.


Patterns of service for the long-term mentally ill in Europe. Mental health services are organized and financed in very different ways across Europe; nevertheless there are a number of common trends and issues. In this paper we deal with some of those issues which influence the quality of services to those with long-term and severe mental health problems and disabilities. The most obvious trend has been the rundown of psychiatric beds particularly in the large mental hospitals and this in its turn has given rise to the problem of providing alternative services. Throughout Europe people are striving, with mixed success, to establish new services that are community orientated, provide reasonable levels of clinical care with some continuity and coordination, and ensure that the individuals served have appropriate accommodation and day-time activities. While there are some excellent services, there are even more services throughout Europe struggling to solve common problems. We have tried to draw some lessons from their efforts.


Clinical psychology training in Europe.

Clinical psychology training in Europe. Clinical psychology training in the United Kingdom (UK) and in the remainder of Europe differs in several respects; in particular, the latter allows for greater variability and clinical specialization with much more training taking place postqualification than in the UK; differences in content and in the balance between the supply of, and demand for, clinical psychologists also exist. These differences reflect employment arrangements and, to a lesser extent, the structure of higher education and legal regulation. Various current and predicted changes in health-care systems and in the legal and educational context will probably lead to training in the UK and elsewhere in Europe becoming more similar in the years after 1992.