Sociocultural aspects of eating disorders.

Eating disorders, though recognized for centuries, are increasing in prevalence. The increase in rate is particularly remarkable over the last 30-40 years. The article considers how social function stems from biological function and evolution, and how biological function may hamper social development to the detriment of individuals. Social and cultural influences relevant to this change are examined, especially the changing position of women within society as a whole and the multiplication of conflicting roles which women find themselves balancing. Reference is made to the representation of women in the arts and media. Reference is also made to the role of those external agencies which have historically controlled populations (both men and women), such as religious bodies and governments, but which to some extent have been rejected. Evidence from in-depth studies of women with eating disorders and from transcultural studies are included to support the authors' ideas.


The treatment of bulimia nervosa.

Bulimia nervosa is a significant source of morbidity amongst young women. There has been a considerable body of work on its treatment since it was first described in 1979. Three treatments have shown particular promise: antidepressant drug treatment, cognitive behaviour therapy and exposure with response prevention. The research findings indicate that the approach of choice is cognitive behaviour therapy, with most patients benefiting significantly and the changes being well maintained. However, cognitive behaviour therapy is neither necessary nor sufficient for all patients with bulimia nervosa: some benefit from simpler interventions whilst others fail to respond. At present, too little is known about the factors that predict response to particular forms of treatment to allow the matching of patients with treatments.


Binge eating in the obese.

This review will first describe problems in the definition of the term binge eating, especially in the absence of purging (vomiting, laxative abuse). We highlight current approaches in the classification of obesity, and then provide an overview of the available literature on differences between obese binge eaters and obese non-binge eaters. Many studies indicate that binge eating is common among the female obese, with a frequency ranging from 23 to 46% among those seeking treatment for weight reduction. Despite differences in the definitions of binge eating and variability among the samples investigated, there is strong evidence that binge eaters represent a distinct subgroup among the obese. Binge eating obese exhibit significantly more eating and weight-related pathology, as well as more psychopathology compared to their non-binge eating obese counterparts.


NCLAN results and their application to the standard-setting process: protecting vegetation from surface ozone exposures. National Crop Loss Assessment Network.

The current form of the standard is not appropriate for protecting vegetation from O3 exposures. As an alternative to the current form of the standard, it has been suggested in the literature that a maximum cumulative 3-month SUM06 O3 exposure index be used as the form of a secondary standard to protect agricultural crops. However, applying this index may result in inconsistent protection for vegetation. It appears that cumulative indices will have to be combined with other parameters to accurately quantify the occurrence of high hourly average concentrations. This paper describes the characterization of the hourly O3 exposures in selected National Crop Loss Assessment Network (NCLAN) experiments and discusses the application of the results to the standard-setting process. Our results indicated that, in most cases, the NCLAN experimental data we analyzed appeared to support the observation that the repeated occurrences of hourly average O3 concentrations of 0.10 ppm and higher result in adverse effects on vegetation. For the NCLAN experiments, the characterized distributions reflected the ability of the high hourly average concentrations to affect crop yield reduction. Prior to suggesting a new form of the secondary standard, it will be important to carefully characterize the specific regimes responsible for affecting vegetation and identify the important components of those regimes responsible for the effects. By applying this approach, it should be possible to limit the occurrence of inconsistent results when applying a new form of the secondary standard.


Beta-cell expression of 65-kDa heat-shock protein mRNA is function- and age-dependent.

This study examined the expression of mRNA coding for the 65-kDa heat-shock protein (HSP) in rat islet cells of different functional states and different ages. In addition, beta cells and non-beta cells purified by fluorescence-activated cell sorting were studied. Total RNA from islet cells and insulin-producing RINm5F cells was isolated and analyzed by Northern blotting using a cDNA probe coding for the human homologue to the mycobacterial 65-kDa HSP, after which blots were quantified by densitometric scanning. Isolated beta cells were found to express 65-kDa HSP mRNA. The expression was increased in Lewis islet cells exposed to heat shock or high glucose concentration, four- and three-fold, respectively (p < 0.01). In isolated beta cells cultured at high glucose concentration a doubling in the content of 65-kDa HSP mRNA was seen compared with islets cultured at low glucose concentration (p < 0.05). In islets from Lewis rats fasted for 24 h, the content of 65-kDa HSP mRNA was 42% lower than in islets isolated from normally fed Lewis rats (p < 0.01). Both in BB rats and Wistar Furth rats the content of 65-kDa HSP mRNA was found to be higher in the 30- and the 60-day-old rats compared with the neonatal animals (p < 0.01). The expression of 65-kDa HSP mRNA was increased in RINm5F cells following heat shock, while no induction was seen after stimulation with glucose, TPA or IBMX. It is concluded that the 65-kDa heat-shock protein belongs to the family of inducible functional antigens in beta cells, which strengthens the interest in 65-kDa HSP as an antigen possibly involved in the initiation of autoimmune beta-cell destruction.


Growth patterns of pulmonary metastases and primary tumours from five murine fibrosarcoma cell clones.

The growth patterns, including the size, shape and regional preferences, of lung metastases from five murine fibrosarcoma cell clones were studied. Spontaneous metastases developed from tumours formed by subcutaneous inoculation of the cell clones. Lung colonies (experimental metastases) were established by i.v. injection of cells. The numbers of both spontaneously and experimentally formed subpleural lung metastases were counted through a stereomicroscope. The fraction of colonies that was located subpleurally was determined in histological sections of lungs. The growth kinetics of clonally derived primary tumours, and the number of spontaneous and experimental lung metastases, differed greatly between certain cell clones. The number of spontaneous lung metastases was correlated with the maximum size of primary tumours. No close correlation was observed between the size of the primary tumours and the size of experimental metastases. There were differences between the cell clones in the shape and regional preferences of their lung deposits. The subpleural colonies were generally larger than the intrapulmonary ones. Thus, both the regional distribution and the growth pattern of lung deposits differed between the clones.


Prevalence of antibodies against heat-stable antigens from Helicobacter pylori in patients with dyspeptic symptoms and normal persons.

Heat-stable antigens from Helicobacter pylori were investigated for the detection of serum IgG, IgA and IgM antibodies against H. pylori by an ELISA technique. Antibody titers against H. pylori were measured in 167 dyspeptic patients, of whom 96 were H. pylori positive confirmed by culture or microscopy, and in 482 controls (0-98 years). Increased IgG antibody titers were found significantly more often in dyspeptic patients with active chronic gastritis than in patients with normal morphology, as well as in H. pylori-positive patients as compared to H. pylori-negative patients, independent of the endoscopic findings. The heat-stable antigens were compared with acid glycine-extracted antigens and a high degree of concordance was found in the results obtained with the two antigen preparations. The differences in the IgA antibody titers against H. pylori between H. pylori-positive and H. pylori-negative dyspeptic patients were significant and may be useful to confirm a borderline IgG result. No differences were found in IgM antibody titer between H. pylori-positive and -negative patients. The greatest age-dependent increase in IgG and IgA antibody titers was found in children, and if a lower cut-off level is used for children than for adults, as has been proposed, the proportion of people with increased antibody titers against H. pylori would be almost constant from the age of between five and 10 years until the time between 61 and 80 years. Comparison of H. pylori IgG antibodies with IgG antibodies against Campylobacter jejuni and total antibodies against cytomegalovirus (CMV) showed a greater similarity between H. pylori and C. jejuni (R = 0.51) than between H. pylori and CMV (R = 0.22). This may possibly be caused by cross-reactions between H. pylori and C. jejuni. The H. pylori heat-stabile antigen seems not to be very different from other crude H. pylori antigens like acid glycine-extracted antigens, but purification and characterization of the antigens are needed to improve antibody assays.


Expression of epidermal growth factor receptor in human meningiomas and meningeal tissue.

The aim of this study was to examine meningeal tissue under normal, reactive, and neoplastic conditions for expression of epidermal growth factor receptor (EGFR) using an improved histochemical method, namely biotinylated epidermal growth factor. EGFR was found in all the examined meningiomas (12 benign and three anaplastic) and in neonatal rat meninges, whereas normal and injured adult human and rat meninges did not exhibit detectable EGFR. These observations indicate that EGFR is involved in the development of meningeal tissue. Further, EGFR is abnormally expressed in meningeal tumours, indicating a role of EGFR in the neoplastic process of these tumours. The regular expression of EGFR in human meningiomas suggests EGFR as a tumour marker for this tumour type.


Cancer-associated changes in glycosylation of fibronectin. Immunohistological localization of oncofetal fibronectin defined by monoclonal antibodies.

The extracellular matrix adhesion molecule fibronectin exhibits different isoforms derived by alternative splicing as well as recently demonstrated variation in O-glycosylation. Although fibronectin is widely distributed in normal tissues, the individual isoforms have been found to show restricted tissue distribution and association with malignancies. The monoclonal antibody FDC-6 defines a cancer-associated de novo glycosylation of a specific threonine residue in the C-terminal region of the fibronectin molecule termed oncofetal fibronectin. Here we report an immunohistological study of oral squamous cell carcinomas (n = 33), premalignant lesions (n = 15), and normal oral mucosa (n = 10) using the FDC-6 antibody. A selective expression of the oncofetal fibronectin epitope was demonstrated in close relation to the invading carcinoma, whereas no staining was observed in premalignant lesions without epithelial dysplasia, or in normal epithelium. Furthermore, we attempted to identify additional carbohydrate-related epitopes distinguishing fibronectin of human hepatoma cell line HUH-7 from plasma fibronectin. No novel epitopes were identified, as all generated monoclonal antibodies lacking reactivity with plasma fibronectin showed the same specificity as FDC-6. Previous studies have indicated that the de novo glycosylation is induced by a novel transferase activity only found in fetal and carcinoma cell lines, placenta and hepatoma tissues. Here we provide further evidence that a purified UDP-GalNAc:peptide N-acetylgalactosaminyltransferase from normal bovine thymus and human placentae is incapable of utilizing the hexapeptide VTHPGY as a substrate. The results demonstrate that oncofetal fibronectin is highly associated with malignancy, and appears to be induced by expression of a unique glycosyltransferase or modification of the specificity of the normally expressed transferase.


Vegetable oils instead of xylene in tissue processing.

In an effort to improve working conditions in the histopathologic laboratory, we have investigated whether less toxic substances may be substituted for the toxic organic solvent xylene currently in use. Xylene is used in the clearing as well as the deparaffinization process. We have tested whether the substitution of xylene by olive oil and coconut oil leads to any difference in the quality of the histologic sections. Two tissue blocks from each of 232 specimens sent for histopathologic evaluation were subjected to parallel processing in xylene and oil. The specimens represented a broad spectrum of tissue types. All sections were stained with hematoxylin-eosin to permit evaluation of histologic and cytologic details. Furthermore, a range of histochemical and immunohistochemical stainings were applied to a subgroup of tissue sections. The results showed qualitative differences between xylene-processed and oil-processed tissue in only a minority of cases. In no cases were the oil-processed samples considered less suitable for histologic diagnosis. In the histochemical and immunohistochemical stainings, no differences were registered. Although the long-term stability of oil-processed tissue remains to be clarified, we conclude that less toxic vegetable oil may probably be substituted for xylene without losing valuable diagnostic information.


Histological examination of the rabbit middle ear in secretory otitis media with and without a ventilation tube.

To study the time-related histopathological lesions in secretory otitis media as it develops into the chronic stage, including the influence of ventilation of the middle ear, we examined the middle ear mucosa in a rabbit model. The observation period was from two weeks until 18 months. The histological method applied included haematoxylin-eosin and Sirius red staining for morphometric quantification of the goblet cells, the thickness of the connective tissue layer, the area fractions of blood vessels, inflammatory cells, fibroblasts and collagen fibres. In conclusion, the middle ear mucosa in secretory otitis media exhibited inflammatory changes correlating with the duration of the disease. Ventilation of the middle ear in secretory otitis media did not improve the changes.


Estimation of the total number of mast cells in the human umbilical cord. A methodological study.

The aim of the present study was to estimate the total number of mast cells in the human umbilical cord. Using 50 microns-thick paraffin sections, made from a systematic random sample of umbilical cord, the total number of mast cells per cord was estimated using a combination of the optical disector and fractionated sampling. The mast cell of the human umbilical cord was found in Wharton's jelly, most frequently in close proximity to the three blood vessels. No consistent pattern of variation in mast cell numbers from the fetal end of the umbilical cord towards the placenta was seen. The total number of mast cells found in the umbilical cord was 5,200,000 (median), range 2,800,000-16,800,000 (n = 7), that is 156,000 mast cells per gram umbilical cord (median), range 48,000-267,000. Thus, the umbilical cord constitutes an adequate source of mast cells for further investigation of these cells in the newborn, e.g. for describing their functional and secretory characteristics and possible clinical relevance in relation to the development of allergic, inflammatory and immunological diseases in infancy and childhood.


Killing curve activity of ciprofloxacin is comparable to synergistic effect of beta-lactam-tobramycin combinations against Haemophilus species endocarditis strains.

Nine Haemophilus species strains, all beta-lactamase negative, isolated from patients with endocarditis were tested in killing curve experiments. Antibiotics used were penicillin, amoxicillin, aztreonam alone and in combination with tobramycin, as well as ciprofloxacin alone. Synergism between beta-lactams and tobramycin with reduction of colony counts to zero was seen after 24 h for H. influenzae, H. parainfluenzae and H. segnis strains. Ciprofloxacin was as effective as beta-lactam-tobramycin combinations. The H. aphrophilus strain was not killed as effectively as other strains by any of the antibiotics.


Quantitative estimation of diphtheria and tetanus toxoids. 6. Use of different antibody titration methods for evaluation of immunogenicity in animals during potency assay of diphtheria toxoid.

Two diphtheria toxoid preparations were compared in potency assays in guinea-pigs using different methods for evaluation of the responses to vaccination. The methods used were the direct skin challenge (Schick test) and ELISA and VERO cell titration of antibodies. The different evaluation methods resulted in the same relative potencies between the toxoids. It was observed that when first-vaccination sera were compared with a second-vaccination serum, the relative antibody concentration depended on whether ELISA or VERO cell titration was used.


Detoxification of diphtheria and tetanus toxin with formaldehyde. Detection of protein conjugates.

In a model system of purified diphtheria and tetanus toxins it was shown that conjugates between the two proteins are formed during detoxification with formaldehyde. Detoxification mixtures were fractionated by HPLC. Two protein conjugates with different molecular weights were detected and quantified by capture ELISA assay. In vivo the existence of the largest diphtheria-tetanus toxoid conjugate was demonstrated by its antibody response in mice vaccinated with a calcium phosphate adjuvated column fraction of detoxification mixture. To eliminate the risk of cross-linking foreign proteins to toxoids in an attempt to reduce the frequency of adverse reactions in vaccination programmes, it is preferable to purify toxins before treatment with formaldehyde.


Variation in the biological function of envelope protein epitopes of yellow fever vaccine viruses detected with monoclonal antibodies.

Three different virus strains (17D-204, 17DD and the French neurotropic vaccine) have been used as live attenuated yellow fever (YF) vaccines and are manufactured in different centres around the world. The envelope proteins of these vaccine viruses were examined and compared using mouse monoclonal antibodies (MAbs) in haemagglutination inhibition (HAI) and neutralization (N) tests. The epitopes eliciting HAI and/or N were found to vary depending on the virus examined. Such variation was also found between vaccine viruses of the same strain manufactured in different centres. These data were confirmed by the use of mouse polyclonal antisera. On the basis of the MAb results in HAI tests a dendrogram of the similarity coefficients between the viruses was constructed and showed that the viruses could be placed into three major groups. Thus, it is concluded that YF vaccines manufactured in different centres are antigenically distinct as recognized by the mouse immune system.


Potency assays for Anistreplase: comparison of the fibrin plate assay and a 96-well plate assay.

Several production lots of Anistreplase (Eminase) were assayed for potency by either two fibrin plate assays or a clot lysis assay performed in 96-well microtiter plates. The 96-well plate assay yielded comparable data to the fibrin plate assays and had the advantage of greater efficiency with respect to both time and reagents. As a result the newer method appears to be a suitable alternative to the fibrin plate assays for lot release of Anistreplase.


Application of the euglycaemic clamp technique to bioassay of insulin analogues.

The euglycaemic clamp method may offer a precise and clinically valid approach to assess the in vivo potency of new insulin analogues or derivatives relative to a human insulin standard. The proposed protocol was designed to overcome problems due to differences in pharmacokinetics between the test and standard preparations. An analogue of human insulin, GlyA21+ArgB27+ThrB30-NH2, which is absorbed very slowly after subcutaneous injection, and human insulin were compared in intravenous clamp experiments in pigs. Both insulins were infused for 4 h to achieve steady state glucose metabolism. The infusion rate ranged from 2.5-8 pmol min-1 kg-1. Parallel dose response curves were obtained with the mean glucose infusion rate from 180-240 min as the response and the logarithm of the insulin infusion rate as the dose. Standard bioassay analysis showed that the molar potency of the analogue relative to human insulin was 95.2% with a 95% confidence interval of 82.3-111.2%. To assess the clinical validity of the method a similar euglycaemic clamp study was carried out in human volunteers. The insulin infusion rates were 3 and 6 pmol min-1 kg-1, and the mean glucose infusion rate over the final 180-240 min period of the clamp was used as response. The statistical analysis showed, as in the pig clamp bioassay, no significant deviations from steady state or from the assumption of parallelism. The resulting molar potency of the analogue relative to human insulin was 85.5% with a 95% confidence interval of 49.5-128.4%. This was in agreement with the result of the pig clamp bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)


Safety aspects in the manufacturing of plasma-derived coagulation factor concentrates.

Plasma-derived coagulation factor concentrates, prepared using traditional manufacturing processes, have transmitted viral diseases, especially AIDS, hepatitis B and hepatitis C to patients. To date, more extensive selection of blood donors, improved screening procedures of each plasma donation for direct and indirect viral markers, and newly developed virucidal procedures, especially pasteurization and solvent-detergent, together with extraction technologies of plasma proteins based on high-resolution chromatographic separations, have diminished considerably the risks of transmitting these pathogenic agents. To ensure safety, each production process must be carefully validated, following a rigorous scientific approach to assess its ability to inactivate or eliminate viruses. In addition, Good Manufacturing Practices must avoid any variation from these validated viral inactivation processes and must eliminate risks of potential downstream contamination of purified plasma fractions following viral inactivation or elimination steps. Other side-effects associated with conventional low-purity preparations, such as acute haemolytic anemia due to contamination by isohaemagglutinins, or immunosuppression possibly due to an overload in fibrinogen and immunoglobulins, have not been reported following infusion of highly purified coagulation factor concentrates. Present state-of-the-art virus inactivation and protein-purification technologies have significantly improved the safety of plasma coagulation factor concentrates.


The construct of brain maturation in theories of child development.

Developmental psychologists have avoided using brain maturation as a primary construct in theories of child development for a variety of reasons during the past 40 years. However, during the last decade we have seen a return to considering brain growth as a useful element in theory construction. During the past few years, the frontal lobe has received increasing attention with respect to major developmental issues. In this Introduction, we review some of these historical and contemporary trends.


Attention deficit hyperactivity disorder and the frontal lobe syndrome.

The usefulness of frontal lobe (FL) dysfunction as a conceptual model for Attention Deficit Hyperactivity Disorder (ADHD) was investigated. Twenty-four ADHD and 24 normal control (NC) children were tested using two batteries of tasks. The first was sensitive to FL deficits in motor control and problem solving skills. The second consisted of memory tasks sensitive to temporal lobe dysfunction. ADHD children differed significantly from NCs on measures of FL function, but not on tests of temporal lobe functions. Where norms were available for normal children on the same FL tests, ADHDs performed like 6- to 7-year-olds, despite their mean age of 10 years and minimum age of 8 years. The differential performance of ADHDs on tasks sensitive to FL and temporal lobe dysfunction supports the hypothesis that ADHD deficits are analogous to FL dysfunction and demonstrates that the children's deficits do not reflect generalized cognitive impairment.


Anterior cerebral asymmetry and the nature of emotion.

This article presents an overview of the author's recent electrophysiological studies of anterior cerebral asymmetries related to emotion and affective style. A theoretical account is provided of the role of the two hemispheres in emotional processing. This account assigns a major role in approach- and withdrawal-related behavior to the left and right frontal and anterior temporal regions of two hemispheres, respectively. Individual differences in approach- and withdrawal-related emotional reactivity and temperament are associated with stable differences in baseline measures of activation asymmetry in these anterior regions. Phasic state changes in emotion result in shifts in anterior activation asymmetry which are superimposed upon these stable baseline differences. Future directions for research in this area are discussed.


The role of frontal lobe functioning in the development of infant self-regulatory behavior.

In the last two decades, there has been tremendous growth in two fields of study related to human infant development: (1) the development of neural processes during the early postnatal years and (2) the development of self-regulatory behavior. In an attempt to stimulate research on the relation between early brain development and self-regulatory processes, several hypotheses pertaining to the role of frontal lobe functioning in the development of emotion regulation during infancy are proposed. The results of a study of the relation between frontal electroencephalographic (EEG) activity and emotional behavior of 21-month-old infants are reported. It was found that increases in frontal lobe activation were associated with increases in emotional arousal, while EEG activity recorded from the parietal region showed either a reciprocal pattern of activation or did not change as a function of level of emotional arousal. These results provide evidence for the specialized role of the frontal lobe in mediating emotional behavior during infancy.


Cyclic cortical reorganization during early childhood.

EEG coherence was computed from 8 left and 8 right intrahemispheric electrode pairs from 253 children ranging in mean age from 6 months to 7 years. The first derivative of mean coherence was computed in order to study growth spurts or rapid changes in mean coherence over the early childhood period. Growth spurts in EEG coherence were approximately 6 months to 1 year in duration and involved a cyclical process composed of a sequential lengthening of intracortical connections in the left hemisphere and a sequential contraction of intracortical connections in the right hemisphere. Each growth spurt cycle had a period of approximately 2 to 4 years and involved both a rostral-caudal expansion and contraction as well as a lateral-to-medial rotation. Data support the view that the functions of the left and right hemisphere are established early in human development through complementary developmental sequences and that these sequences appear to recapitulate differences in adult hemispheric function.


The role of the frontal lobes in the regulation of cognitive development.

Between the ages of 1.5 and 5 years, and again between the ages of 5 and 10 years, a sequence of changes takes place in children's behavior which indicates a fundamental reorganization of their attentional, executive, and self-reflexive processes. In the present article, these changes are summarized, and evidence is adduced to support the claims (1) that these changes are frontally mediated and (2) that the underlying mechanism that generates them is similar to the one that generates the changes in EEG coherence during the same time period. The psychological model that has been hypothesized to explain the cycles of cognitive development (Case, 1992) is then compared to the physiological model that has been proposed to explain cycles of EEG development (Thatcher, 1992). It is shown that the two models are complementary, both in the underlying developmental sequence that they postulate and in the recursive dynamic they propose for producing movement through this sequence. A number of implications and predictions are derived, which follow from the proposition that the two sets of changes are different manifestations of a common underlying process.


Developmental changes in the recognition and comprehension of facial expression: implications for frontal lobe function.

Children aged 6-15 years old and adults (over 18) were given three tests designed to test perception and comprehension of facial expression. In the first test subjects were given two composite symmetrical faces made from the left or right half of a normal face, the subjects' task being to indicate which composite more closely resembled the original face. In the second test the subjects matched a series of photographs from Life magazine with key photographs of one of six distinct emotions (sad, fear, happy, anger, disgust, surprise). In the third test the subjects chose a key photograph that was appropriate for the face of a faceless character in a cartoon. On the composite faces test the subjects in all groups exhibited a preference for the left visual field composite, implying that all age groups were processing the faces in a similar manner. The results of the other two tests showed that there was an improvement in the perception of facial expression between the ages of 6 and 8 years, little change until about 13 years, and then a second improvement to adult performance at about 14 years. The performance of the 8- to 13-year-old children was similar to that of adult patients with frontal lobe injuries, which could be taken as evidence that the regions of the frontal lobe involved in the performance of these tasks may not be mature until about 14 years of age.


Biological and psychological development of executive functions.

The purpose of this overview is to provide a background for understanding the relation between the biological maturation of the frontal lobes and the development of the psychological concept of executive functions. In the first section, an interactive hierarchical feedback model is presented as a heuristic way of conceptualizing the relationship of the frontal lobes and executive functions to other brain regions and abilities. The following two sections present a synopsis of research on biological maturation and the psychological development of executive functions.


Lateral versus frontal ERP predictors of reading skill.

Neuropsychological factors that could account for good versus poor reading skills include hemispheric asymmetry for language, signal processing efficiency, hemisphericity, and frontally based control of attention. Using event-related potential (ERP) measures of these constructs, we find that only hemisphericity accounts for individual differences in reading skill among our 15-year-old good readers, while the frontally generated Contingent Negative Variation attentional ERP accounts for reading skill differences among the poor readers. While good readers show expected hemispheric ERP asymmetries and poor readers do not, this group difference does not account for the variation in reading skill. These data suggest that below some crucial threshold, reading disability is predicted by frontal attentional skill, whereas above this threshold, good reading is better predicted by hemisphericity.


Management of congenital dacryocystocoele.

Congenital dacryocystocoele occurs when the nasolacrimal drainage apparatus in the newborn has concomitant blocks at the level of the junction of the common canaliculus with the lacrimal sac and at the distal end of the nasolacrimal duct. This results in a typical pink or blue swelling in the region of the medial canthus. Spontaneous resolution is common, although dacryocystitis may supervene. Treatment should be conservative unless dacryocystitis occurs, or intranasal extension coexists. A series of seven consecutive cases is presented and a management plan for the neonate with congenital dacryocystocoele is proposed.


The surgical management of congenital lacrimal fistulae.

Congenital lacrimal fistulae are developmental anomalies of the lacrimal apparatus that are usually symptomatic, frequently causing epiphora and occasionally causing fistulitis or dacryocystitis. They may be associated with other abnormalities of the lacrimal system or with systemic anomalies. Complete excision alone, or in combination with nasolacrimal intubation and/or dacryocystorhinostomy is recommended for treatment.


A clinicopathological study of loop recession in strabismus.

This communication reports the histological structure of loop recessions of extraocular muscles from seven patients. In all cases the loops formed pseudotendons in which the typical histological structure was well established by four months. Subsequently, moulding of these pseudotendons occurred with improved alignment of collagen and decrease in vascularity. By three and a half years after the operation the pseudotendon had acquired a very close resemblance to true tendon.


The role of botulinum toxin in third nerve palsy.

Isolated third nerve paresis is a rare diagnosis among patients presenting to the Botulinum Toxin Clinic at Moorfields Eye Hospital. Ten patients with this diagnosis are reviewed in this study. Head trauma is a common cause of third nerve palsy and is often severe enough to cause damage to fusion potential. If fusion is present and there is adequate adduction of the divergent eye, then botulinum toxin injection of the lateral rectus may induce long-term control of the ocular deviation. Three of the four patients who experienced long-term control of their ocular deviation following toxin injection shared these features. Toxin injected into the lateral rectus did not, however, reliably assess medial rectus function and therefore predict the outcome of horizontal squint surgery. Reasons for this are discussed.


Pterygium treatment with triethylene thiophosphoramide.

In this study 146 pterygia were excised from 116 patients. The eyes were treated with Thiotepa eyedrops over four weeks to discourage regrowth. All treatment was carried out by the one surgeon on consecutive patients. The relationship between pinguecula and pterygium is explored, and the pathogenesis of pterygium growth discussed.


Successful outcome following anastomosis of a severed trochlear nerve in the middle fossa.

Complete return of function has been obtained following neurosurgical repair of a trochlear nerve inadvertently divided during the clipping of a basilar tip aneurysm. To date this is the second case reported in the literature. The technique of repair and the method of recording the return of function is discussed.


Third nerve palsy due to cerebral artery aneurysm in a child.

We report a case of cerebral aneurysm in a seven-year-old girl who presented with subacutely progressive third nerve palsy. To our knowledge this is the youngest reported patient with this condition. Confusion with myasthenia gravis occurred because of improvement in the patient's ptosis after intravenous edrophonium chloride. Cerebral CT revealed a hyperdense mass that was characterised on cerebral angiography as an aneurysm of the posterior communicating artery. Another occult aneurysm of the posterior cerebral artery was found at surgery. This case demonstrates that third nerve palsy due to cerebral aneurysm may affect patients at a younger age than has previously been recognised. Therefore we suggest that even young children should have aneurysm excluded by cerebral CT and angiography if they present with acquired third nerve palsy involving the pupil. In addition this case highlights the false-positive results that may occur with the edrophonium chloride test for myasthenia gravis.


Present challenges in the global prevention of blindness.

Cataract is responsible for 50% of world blindness, with at present an estimated backlog of 13.5 million cases in need of surgery. Low-cost cataract surgery must be made more available in developing countries, making use of alternative approaches for outpatient surgery and optimal management of available resources. Trachoma control needs to be targeted at the worst affected areas in endemic countries, with more emphasis on behavioural, educational and community aspects of the disease. Vitamin A deficiency and xerophthalmia control are becoming matters of maternal and child health care, with early intervention during infancy in view of the mortality issue. There are good prospects for the prevention of blindness from onchocerciasis, through the availability of ivermectin, but large-scale distribution schemes are still needed in most of the African countries concerned. The early detection and management of open-angle glaucoma still poses a major problem in developing countries, and further development of appropriate technology is needed in this field. Another area where more efforts are needed is ocular trauma, which is commonly the cause of unilateral loss of vision. General preventive measures must be enforced and better training provided to health personnel to deal competently with such cases, in order to prevent late complications. Diabetes, finally, is on the increase in many developing countries, giving rise to problems in dealing effectively with the ensuing retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiological patterns of ocular trauma.

Ocular trauma is the cause of blindness in approximately half a million people worldwide, and many more have suffered partial loss of sight. Trauma is often the most important cause of unilateral loss of vision, particularly in developing countries. There is a cumulative risk of ocular trauma and visual loss during life, but the true incidence of accidents involving the eyes is not known. Males tend to have more eye trauma than females, and this is already apparent from childhood; lower socioeconomic classes are also more associated with ocular trauma. The setting for the occurrence of trauma is most commonly the workplace and, increasingly, road accidents. On the other hand, domestic accidents are probably under-reported. Of particular importance in some developing countries is the occurrence of superficial corneal trauma in agricultural work, often leading to rapidly progressing corneal ulceration and visual loss. The impact of ocular trauma, in terms of need for medical care, loss of income and cost of rehabilitation services when indicated, clearly makes the strengthening of preventive measures very worthwhile.


Submandibular gland transfer in the correction of dry eye.

Following rabbit experiments which showed that microvascular submandibular gland transfer could ameliorate the deleterious effects of lacrimal gland ablation, a clinical transfer of the submandibular salivary gland to the temple region was performed. The beneficial results from this initial operation have led to the procedure being used in a total of eight patients with 12 transfers. The procedure has led to increased moisture in the eye and decreased symptoms but the assessment of change in corneal function and pathology is difficult.


UV absorption complicates PCR decontamination.

UV irradiation is widely used to inactivate contaminating DNA in PCR. Highly UV-absorbent deoxyribonucleoside triphosphates in PCR mixtures reduce the efficiency of UV decontamination. Optimal decontamination may be achieved by irradiating the PCR mixture without the deoxyribonucleoside triphosphates.


A PCR-based method of identifying species-specific repeated DNAs.

A PCR-based method is described to facilitate the identification of DNA fragments that are highly repeated and species-specific. The precision of the technique was demonstrated by cloning a fragment that occurred in a high number of copies in the plant species Medicago granadensis but in a low number of copies in 17 other Medicago species and Melilotus officinalis. This method should greatly accelerate the isolation and cloning of short and long interspersed nuclear elements with species-specific distributions. Such clones should prove useful in studies of phylogenetic relationships in the identification of interspecific hybrids, as in situ chromosome markers and other applications.


Presence of single-stranded DNA in PCR products of slow electrophoretic mobility.

PCR products were characterized by electrophoresis, blotting and hybridization. In addition to the bands of expected size, bands of slower electrophoretic mobility were often detected. The slower bands completely disappeared when the PCR products were subjected to slow cooling, treated with S1 nuclease or run on an alkaline gel, whereas the bands of expected size were unaffected. The slower bands are therefore likely to contain single-stranded DNA.


Subcloning using simplified adaptor addition.

A simplified procedure for the addition of synthetic oligonucleotide adaptors to subclone DNA fragments with incompatible ends is presented. An organophosphate degradation gene on a PstI fragment was cloned into the HindIII site of the fungal vector pH1S. The opd gene specifies parathion hydrolase and was first isolated from a Flavobacterium sp. The gene was present in 12% of the plasmids recovered and was inserted in either direction with similar frequencies: 53% with the opd start codon distal to the single SalI site of pH1S and 47% in the other orientation. All enzymatic steps were carried out in a single microconcentrator eliminating DNA loss through manipulation and transfer. Normally, during adaptor or linker addition, a larger number of oligonucleotides are attached at each end of the insert DNA and must be removed before cloning. The need for enzymatic digestion to remove excess adaptors was avoided. Traditional methods have utilized phenol/chloroform extraction, ethanol precipitation, gel filtration chromatography, spermine precipitation, or preparative gel electrophoresis. Eliminating these steps resulted in a simpler, more reliable procedure.


A simple method for the preparation of single-stranded polydeoxynucleotides of desired length.

A method for the preparation of homogeneous, single-stranded polydeoxynucleotides of desired length up to 800 bases is described. The procedure entails 1) generation of double-stranded DNA of desired length by PCR using a pair of primers of which one is biotinylated and the other is either unlabeled or fluorescently labeled, 2) isolation of PCR products by agarose slab gel electrophoresis, 3) recovery of desired product by electroelution, 4) binding of the product to streptavidin-coated magnetic beads and is followed by 5) duplex denaturation and removal of the unbound single strand that is either unlabeled or fluorescently labeled. Final product characteristics were determined by capillary gel electrophoresis with fluorescence detection. Up to microgram quantities of homogeneous single-stranded DNA of a desired length were obtained. These can be used as single-stranded size standards in capillary gel electrophoresis experiments as well as in other techniques requiring such standards.


PCR-based analysis of the T-cell receptor V beta multigene family: experimental parameters affecting its validity.

The validity of semiquantitative, PCR-based analysis of gene expression within a multigene family, the human T-cell receptor (TCR) beta chain variable region family, was investigated. Primer comparability was addressed by grouping hybridization temperatures and limiting the size range of amplified fragments. Primers selected satisfied criteria for comprehensiveness, match to targets and discrimination of nontargets. Specificity was enhanced by maximizing mismatches with nontargets and using an elevated hybridization temperature. Reaction conditions are described that ensure specificity while maintaining sensitivity. Several results confirmed primer specificity. Limits on precision were documented: probable error was 3%-7% of mean value for target prevalences (% of all TCR mRNA represented by a particular V beta) in the 5%-40% range. Accuracy was limited by the nonlinear relationship between target prevalence and signal obtained. Because of this relationship, the effect of the observed limits of precision varied. Valid distinctions were possible between sufficiently separated prevalences, i.e., 0%-1%, 3%-5%, 10%, 30%, greater than 50%. Additional concerns addressed include: standardization of signals, coamplifiation and effects of primer artifacts, and the nature of the mRNA pool. Only when theoretical and practical limits in precision and accuracy are acknowledged can semiquantitative, PCR-based analysis be used with confidence to assess gene usage within a large, multigene family.


Heat-soaked PCR: an efficient method for DNA amplification with applications to forensic analysis.

Heat-soaked PCR (HS-PCR) is a method for enhancing amplification performed by heating the DNA sample at 94 degrees C in 90 microliters 1.1 x buffer for 30 min. A 10-microliters bolus of concentrated (10x) deoxynucleotides, Taq DNA polymerase and primers prepared without buffer is then added just prior to thermal cycling. We have investigated the application of this method in a variety of forensically important DNA samples and compared it with regular PCR (R-PCR). DNA samples extracted from bone, postmortem tissues, bloodstains and hair contained low concentrations of human DNA or were contaminated with either non- human DNA or hemoglobin degradation products. Optimal conditions for HS-PCR were determined for the 3' ApoB VNTR locus and applied to a centromeric repeat element and to a single-copy locus. HS-PCR consistently and reproducibly enhanced product yield and specificity over R-PCR at all three loci in the entire set of DNA samples. HS-PCR was also effective in overcoming the inhibitory effect of hemoglobin at concentrations that fully impeded R-PCR.


Analysis of mixed human/microbial DNA samples: a validation study of two PCR AMP-FLP typing methods.

The reliability of the PCR technique used to type two human variable number tandem repeats, that is, 3' to apolipoprotein B gene and locus D17S30, was examined using DNA samples of mixed human and microbial origin. Mixtures of human and microbial DNA were amplified, choosing microbes found commonly in the vagina. Total inhibition of human amplification and/or "drop-out" of the larger amplification fragment length polymorphism allele was observed at both loci in the presence of DNA from some vaginal micro-flora.


Improved efficiency in determining the titer of the Autographa californica baculovirus nonoccluded virus.

An economical and time-efficient method for titering the Autographa californica multiple-embedded nuclear polyhedrosis virus (AcMNPV) by the endpoint method is described. The method uses an electronic pipetting device to perform dilutions in the same 60-well microplate as is used for the assay, thus eliminating the need for test tubes or vials for making dilutions. Additionally, since small volumes are used for the dilutions, a substantial savings in medium is achieved. The effect of using three different lepidopteran cell lines in this assay for AcMNPV is also described. This test revealed that one line (the Trichoplusia ni IPLB-TN-R2 line) is at least 1.5 logs more sensitive to AcMNPV when using occlusion body formation as the measure of infection. The titer was about 6- to 12-fold higher in the IPLB-TN-R2 cell line than the other two lines when plaque assay procedures were used. The titer of a recombinant baculovirus with a bacterial beta-galactosidase gene was also measured in the three cell lines using X-gal as an indicator and showed the IPLB-TN-R2 line to be fourfold more sensitive to this virus.


Efficient purification of PCR products using ultrafiltration.

The use of disposable ultrafiltration devices for the purification of PCR-amplified DNA products from the other components of the reaction mixture is outlined. The advantages of using a 100,000 molecular weight cutoff membrane are discussed. The integrity of the membrane-purified DNA is checked by its successful use in sequencing, ligation and cloning procedures.


Eukaryotic cells grown on microcarrier beads offer a cost-efficient way to propagate Chlamydia trachomatis.

The use of microcarrier cell culture as a method for the in vitro propagation of the obligate intracellular bacterial parasite, Chlamydia trachomatis, is described. The microcarrier beads proved to be a more cost-effective means to propagate C. trachomatis than traditional tissue culture flasks or roller bottles without sacrificing yields or infectivity. In addition, microcarrier cell culture was found to be a much simpler technique to study the intracellular development of these bacteria.


Improved method for screening cDNA expression libraries for DNA-binding proteins.

The ability to successfully screen a lambda gt11 cDNA expression library for specific gene products that can bind to selected sequences of DNA depends on radioactive double-stranded DNA probes with high specific activity. We demonstrate here that probes labeled by the PCR are superior to probes made by the Klenow reaction. The use of these PCR-generated probes have facilitated our efforts to isolate recombinant phage containing putative DNA-binding gene products that recognized a 246-base pair transcriptional enhancer region of Rous sarcoma virus long terminal repeat.


Analysis of heat-denatured DNA using native agarose gel electrophoresis.

The use of native or neutral gels to resolve denatured DNA affords a rapid and convenient analytical method for assessing the consequences of a number of procedures employed in molecular biology research. We demonstrate that this method can be used to analyze transition melting temperature (Tm) and strand breakage in heat-denatured duplex DNA. This shows that some commonly recommended denaturation procedures can result in significant degradation of DNA and that reannealing or aggregation can occur when samples are concentrated or ionic conditions altered.


Multipurpose vectors for peptide expression on the M13 viral surface.

We have developed a set of three cloning vectors for the expression of polypeptides on the surface of the M13 viral coat. The M13mp8 genome has been engineered for expression of foreign protein sequences near the NH2-terminus of the mature pIII protein, which is present in five copies on the outside of each M13 viral particle. All three of the vectors carry the same two useful restriction sites for directed cloning of inserts in the pIII coding region; in addition, one vector carries the bacterial gene conferring resistance to the antibiotic tetracycline, and another expresses the lacZ' polypeptide that allows functional complementation of beta-galactosidase activity within the host bacterial cell. All of these vectors propagate well in E. coli DH5 alpha F' cells and do not require helper phage. We demonstrate that a bacteriophage, expressing an eleven amino acid epitope (from human c-myc) at the NH2-terminus of pIII in one of our vectors, can be purified from a vast mixture of other M13 phage through panning techniques. In particular, we find that the c-myc-expressing viral particles can be easily recovered from phage mixtures with the biotinylated form of the monoclonal antibody, 9E10, and streptavidin-coated MagneSphere beads.


Microplate coagulation assays.

This report describes the development of microplate-based blood coagulation assays. The assays require a kinetic microplate reader to follow changes in absorbance at 405 nm caused by the coagulating plasma. Procedures for performing prothrombin time and activated partial thromboplastin time tests are described with intra- and inter-assay variability of a few percentage points. The prothrombin time of normal plasma was 64.5 +/- 3.6 s, and the activated partial thromboplastin time was 69.8 +/- 3.2 s. Clotting times were prolonged when normal plasma was mixed with plasmas deficient in particular coagulation factors, as expected. These assays take advantage of the microplate format (small sample size and multiple simultaneous assays) and can be customized for specific purposes, such as quantifying purified factor IX or assessing protein C activity in plasma.


Complete one-hour immunocytochemistry based on capillary action.

We describe a less than one-hour manual method for immunocytochemical analyses of B5 or formalin-fixed, paraffin-embedded tissue sections. The method employs capillary action to sequentially apply, incubate and remove liquid reagents from apposed pairs of up to 20 glass microscope slides and allows for simultaneous immunocytochemical analyses of as many as 10 different antigens. The method described here uses a) positively charged glass slides to rapidly immobilize tissue sections; b) rapid deparaffinization techniques; c) multipurpose reagents; d) ethanol-enriched buffer washes to improve capillary action and reduce nonspecific background; e) a single broad spectrum streptavidin-peroxidase or streptavidin-alkaline phosphatase detection system that identifies most primary monoclonal and polyclonal antibodies; and f) specific immunocytochemical signal amplification by cyclic chromogen enhancement.


Quantitation of targets for PCR by use of limiting dilution.

We describe a general method to quantitate the total number of initial targets present in a sample using limiting dilution, PCR and Poisson statistics. The DNA target for the PCR was the rearranged immunoglobulin heavy chain (IgH) gene derived from a leukemic clone that was quantitated against a background of excess rearranged IgH genes from normal lymphocytes. The PCR was optimized to provide an all-or-none end point at very low DNA target numbers. PCR amplification of the N-ras gene was used as an internal control to quantitate the number of potentially amplifiable genomes present in a sample and hence to measure the extent of DNA degradation. A two-stage PCR was necessary owing to competition between leukemic and non-leukemic templates. Study of eight leukemic samples showed that approximately two potentially amplifiable leukemic IgH targets could be detected in the presence of 160,000 competing non-leukemic genomes. The method presented quantitates the total number of initial DNA targets present in a sample, unlike most other quantitation methods that quantitate PCR products. It has wide application, because it is technically simple, does not require radioactivity, addresses the problem of excess competing targets and estimates the extent of DNA degradation in a sample.


Protecting researchers from instrument biohazards.

The prevention and control of biohazards arising from the use of laboratory instruments have become increasingly important in clinical and research applications. Centrifuges can be susceptible to contamination because of intense wear on primary containers (specimen tubes and bottles), worn O-ring container seals, or rotors and buckets lacking tight seals. A recent study by the Center for Applied Microbiology and Research, Porton Down, UK, has determined the biological safety of certain rotors in various speed ranges. This paper presents and discusses these findings.


Human amyloid precursor protein ameliorates behavioral deficit of flies deleted for Appl gene.

Drosophila amyloid precursor protein-like (Appl) gene encodes a protein product (APPL) similar to beta-amyloid precursor protein (APP) associated with Alzheimer's disease. To understand the in vivo function of APPL protein, we have generated flies deleted for the Appl gene. These flies are viable, fertile, and morphologically normal, yet they exhibit subtle behavioral deficits. We show that a fast phototaxis defect in Appl- flies is partially rescued by transgenes expressing the wild-type, but not a mutant, APPL protein. We further demonstrate a functional homology between APPL and APP, since transgenes expressing human APP show a similar level of rescue as transgenes expressing fly APPL.


Suppression of MAP2 in cultured cerebellar macroneurons inhibits minor neurite formation.

We show here that antisense MAP2 oligonucleotides inhibit neurite outgrowth in cultured cerebellar macroneurons. Unlike control neurons, which first extend a lamellipodial veil followed by a consolidation phase during which the cells extend minor neurites, MAP2-suppressed cells persist with lamellipodia and later become rounded. The induction of microtubules containing tyrosinated tubulin, which parallels neurite outgrowth in control neurons, was blocked under antisense conditions. The small but significant increase in acetylated microtubules was not affected. In contrast, the suppression of tau, which selectively blocks axonal elongation, completely prevented the increase of acetylated microtubules, but did not modify the induction of labile microtubules. These results suggest that MAP2 and tau have different functions: the initial establishment of neurites depends upon MAP2, whereas further neurite elongation depends upon tau and microtubule stabilization.


Cellular targets and trophic functions of neurotrophin-3 in the developing rat hippocampus.

The expression of the neurotrophins and trk receptors in the hippocampus has directed attention toward their roles in the development and maintenance of this region. We have examined the effects of the neurotrophins NT-3, BDNF, and NGF in cultures of developing rat hippocampal cells by two criteria: rapid induction of c-fos and neurotrophic responses. The selective induction of c-fos mRNA suggests the presence of functional receptors for NT-3 and BDNF, but not NGF, in embryonic hippocampal cultures. The NT-3-responsive cells were localized in pyramidal neurons of areas CA1 through CA3 and dentate granular and hilar cells of postnatal organotypic slices, as detected by c-Fos immunocytochemistry. In addition to immediate early responses, NT-3 caused a 10-fold increase in the number of cells expressing the neuronal antigen calbindin-D28k. This increase was dose dependent, with maximal stimulation at 10 ng/ml. In contrast, BDNF elicited small but significant calbindin responses. These results indicate biological responses to NT-3 in the CNS and suggest roles for for this neurotrophin during hippocampal neurogenesis.


Protein kinase C couples membrane excitation to acetylcholine receptor gene inactivation in chick skeletal muscle.

The signaling pathway connecting membrane depolarization and gene activity in skeletal muscle remains largely unknown. Using transcription elongation (run-on) analysis we have found that electrical stimulation of denervated chick skeletal muscle in vivo rapidly and selectively results in inactivation of acetylcholine receptor (AChR) subunit genes. We have studied the possible involvement of protein kinase C (PKC) in this response and have observed that electrical stimulation increases the activity of PKC in the nucleus by over two orders of magnitude within 10 min; phorbol esters, within minutes after intramuscular application, block AChR subunit genes in the absence of electrical activity; and the activity-triggered gene inactivation is blocked by the protein kinase inhibitor staurosporine or by enzyme depletion resulting from chronic pretreatment of muscle with phorbol esters. We conclude that PKC is an integral component of the pathway coupling membrane excitation and AChR gene control.


The alpha 5 gene product assembles with multiple acetylcholine receptor subunits to form distinctive receptor subtypes in brain.

The acetylcholine receptor (AChR) alpha 5 gene has been classified as a member of the AChR gene family based on sequence homology. Expression studies, however, have yet to identify a function for the alpha 5 gene product or even to demonstrate an interaction with known AChR subunits. We report here that the alpha 5 gene product is identical to the 49 kd protein previously found on immunoblots of AChRs purified from brain and ciliary ganglia. In brain the alpha 5 gene product is present both in alpha 3- and in alpha 4-based receptor subtypes, while in the ganglion it is found in an alpha 3-based receptor subtype concentrated in postsynaptic membrane. Immunoprecipitation experiments with subunit-specific monoclonal antibodies indicate that some native AChRs are likely to have at least three kinds of subunits, with two being of the alpha type. These findings support new views about the construction of AChRs in neurons.


An intrinsic neuronal defect operates in dystonia musculorum: a study of dt/dt<==>+/+ chimeras.

In the mouse mutant dystonia musculorum (dt), peripheral and central sensory axons develop focal swellings and degenerate. To identify the primary cellular target of the mutation, we have analyzed the spinal cords of dt/dt<==>+/+ aggregation chimeras. In these chimeras, characteristic swellings appeared only on the axons of mutant genotype neurons; the axons of wild-type neurons, identified by their expression of a transgene-encoded human neurofilament protein, were normal. This direct correlation of genotype and phenotype indicates that the dt mutation acts via a mechanism intrinsic to affected neurons. In addition, we show here that the dt mutation leads to a disorder of neurofilament processing in which phosphorylated neurofilament epitopes accumulate inappropriately in neuronal perikarya.


Dorsal root ganglion neurons expressing trk are selectively sensitive to NGF deprivation in utero.

In utero immune deprivation of the neurotrophic molecule nerve growth factor (NGF) results in the death of most, but not all, mammalian dorsal root ganglion (DRG) neurons. The recent identification of trk, trkB, and trkC as the putative high affinity receptors for NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively, has allowed an examination of whether their expression by DRG neurons correlates with differential sensitivity to immune deprivation of NGF. In situ hybridization demonstrates that virtually all neurons expressing trk are lost during in utero NGF deprivation. Most, if not all, neurons expressing trkB and trkC survive this treatment. In contrast, the low affinity NGF receptor, p75NGFR, is expressed in both NGF deprivation-resistant and -sensitive neurons. These experiments show that DRG neurons expressing trk require NGF for survival. Furthermore, at least some of the DRG neurons that do not require NGF express the high affinity receptor for another neurotrophin. Finally, these experiments provide evidence that trk, and not p75NGFR, is the primary effector of NGF action in vivo.


Patients' assessment of ambulatory anesthesia and surgery.

To obtain patients' assessments of ambulatory anesthesia and surgery using a return-mail questionnaire postcard. Return-mail questionnaire given to consecutive ambulatory surgery patients. Adult ambulatory surgery unit of a university hospital. The questionnaire was given to 3,722 patients. Responses were returned by 1,511 patients (41%). Among the respondents, 95% had gynecologic procedures and 5% had general surgical procedures. Eighty-six percent of respondents reported at least one minor sequela persisting after discharge. Laparoscopy patients experienced significantly more aches, drowsiness, dizziness, sore throat, nausea, and vomiting. For all patients, sequelae lasted 1 day for 59% of all patients, 2 days for 28%, and 3 or more days for 14%. Different sequelae had different durations. Thirty-eight percent of respondents were able to return to their usual activities the day after surgery; the remainder required 3.2 +/- 2.0 additional days. The main reasons for delayed recovery included general malaise (57%) and surgical discomfort (38%). Assessing their overall satisfaction, 97% would choose day surgery again. Return-mail questionnaires can be used for patient follow-up after ambulatory surgery, with limitations characteristic of unselected-patient methods. Patients' assessments of their anesthesia and surgery can identify common sequelae that ambulatory patients should realistically expect to experience.


Intraoperative autologous blood salvage with cardiac surgery: an analysis of five years' experience in more than 3,000 patients.

To analyze intraoperative autologous salvage of shed mediastinal blood and subsequent transfusion in cardiac surgery. Retrospective statistical analysis. University hospital. Three thousand twenty two patients undergoing cardiac surgery from 1984 to 1988. A review of anesthesia and transfusion records of all patients who underwent intraoperative salvage of shed blood and autologous transfusion using the Sorenson Receptal Auto Transfusion System (ATS) with saline wash prior to reinfusion in cardiac surgery. The salvaged blood volume ranged from 36 to 2,795 ml, with a mean of 321 +/- 222 ml (SD). Eighteen percent of patients did not receive any homologous blood products during their hospitalization. Patients who received only salvaged autologous transfusion were younger, had higher preoperative hemoglobin and hematocrit values, had a larger body surface area, and had shorter surgeries compared with patients who received only homologous blood or both autologous and homologous blood. More blood products were given to patients who received salvaged autologous blood compared with those who did not. Patients who underwent normovolemic hemodilution prior to extracorporeal circulation with subsequent reinfusion received significantly fewer blood products. Ten preoperative and four intraoperative variables significantly influenced the salvaged volume. Previous cardiac surgery was the most significant preoperative variable, and repair of ventricular septal defect produced by myocardial ischemia was the most significant intraoperative variable. Considering the average salvaged volume and its current autologous transfusion-related expense, autologous blood salvage is potentially an economic benefit. Perioperative blood conservation requires a considerable commitment from surgeons, anesthesiologists, perfusionists, and intensive care physicians to be effective.


Three balanced anesthetic techniques for neuroanesthesia: infusion of thiopental sodium with sufentanil or fentanyl compared with inhalation of isoflurane.

To compare emergence from anesthesia and the hemodynamic and respiratory depressant effects of thiopental sodium infusion plus sufentanil or fentanyl with those of isoflurane as the primary component of a balanced technique for neuroanesthesia. Randomized, double-blind, prospective study. University hospital and its affiliated Veterans Affairs Medical Center. Thirty patients undergoing elective craniotomy for aneurysm or tumor. Thiopental with infusion of sufentanil 0.1 microgram/kg/hr, thiopental with infusion of fentanyl 1 microgram/kg/hr, or inhalation of 0.25% to 2% isoflurane as the major component of a balanced anesthesia technique that included nitrous oxide (N2O) and vecuronium (potency ratio of sufentanil to fentanyl, 10:1). Intraoperative stress response (as indicated by intraoperative hypertension) was said to be the percentage of time the patient required administration of an antihypertensive drug, measuring from the first dose of thiopental to discontinuation of N2O at the end of the procedure, excluding any period of induced hypotension. Rapidity of emergence was measured by the number of minutes from discontinuation of N2O to first opening of the eyes on command. Adequacy of spontaneous ventilation was evaluated by determining partial pressure of arterial carbon dioxide 1, 2, and 3 hours after discontinuation of N2O. Extent of vasoactive drug administration for control of intraoperative hypertension (as determined by the clinicians caring for the patients) was described by minutes of vasodilator infusion and milligrams of propranolol or labetalol administered. The frequency of postoperative hypertension was defined as the number of patients in each group who required medication for postoperative hypertension. No significant differences in variables were found for thiopental/sufentanil, thiopental/fentanyl, or isoflurane when these drugs were used with N2O and vecuronium. Any one of these balanced anesthetic techniques appears appropriate for craniotomy.


Elderly patients recover more rapidly from desflurane than from isoflurane anesthesia.

To compare the hemodynamic, emergence, and recovery characteristics of desflurane-nitrous oxide (N2O) anesthesia with those of isoflurane-N2O anesthesia in elderly patients. Randomized study. Main operating room of a major U.S. teaching hospital. Thirty-four ASA physical status II and III patients aged 65 or older undergoing surgical procedures of greater than 1 hour duration. Group 1 (17 patients) received desflurane in 60% N2O for their surgical procedure. Group 2 (17 patients) received isoflurane in 60% N2O. Thiamylal 2 mg/kg administered intravenously (IV) induced anesthesia, and succinylcholine 1.5 mg/kg i.v. facilitated intubation. Muscle relaxation was maintained with vecuronium. Titration of the anesthetics maintained hemodynamics to within 20% of the patients' preinduction values. Measurement of hemodynamics occurred every 2 minutes prior to skin incision and every 5 minutes thereafter. The times for discontinuation of inhaled anesthetics to eye opening, hand grip on command, and recall of name and date of birth were measured in a standardized fashion for both groups. The time to discharge from the postanesthesia care unit (PACU) was determined by a blinded PACU nurse using standard published criteria. The two groups did not differ with respect to demographics, hemodynamic stability, and times to eye opening (5 +/- 3 minutes for desflurane vs. 8 +/- 4 minutes for isoflurane), hand grip on command (9 +/- 4 minutes vs. 12 +/- 1 minutes), and recall of name and date of birth (13 +/- 8 minutes vs. 12 +/- 7 minutes). The median duration of PACU stay was significantly shorter (p < 0.03) in the desflurane group (80 minutes) compared to the isoflurane group (128 minutes). Desflurane may benefit elderly patients by providing a more rapid recovery from anesthesia, leading to a shorter PACU stay.


Attenuation of hypertensive response to tracheal intubation with nitroglycerin.

To evaluate the efficacy and safety of intravenous (IV) nitroglycerin in attenuating the hypertensive response to laryngoscopy and intubation as a new application of the drug. Controlled, randomized, double-blind study. University hospital. Thirty normotensive patients (ASA physical status I) undergoing elective surgery were divided into three groups of ten patients each. Anesthesia was induced with thiopental sodium 5 mg/kg i.v., and tracheal intubation was facilitated with vecuronium 0.2 mg/kg i.v. During anesthesia, ventilation was assisted or controlled with 1% enflurane and 50% nitrous oxide in oxygen. Either 1.5 micrograms/kg of nitroglycerin, 2.5 micrograms/kg of nitroglycerin, or saline (control) was administered IV simultaneously with the start of laryngoscopy (lasting 30 seconds), which was attempted 2 minutes after administration of thiopental sodium and vecuronium. Patients receiving saline showed a significant increase in mean arterial pressure and rate-pressure product associated with tracheal intubation. These increases following tracheal intubation were significantly reduced in nitroglycerin-treated patients compared with those in the control group (p < 0.05). A single, rapid IV dose of nitroglycerin is a simple, practical, effective, and safe method to attenuate the hypertensive response to laryngoscopy and tracheal intubation.


Butorphanol for the relief of shivering associated with extradural anesthesia in parturients.

To assess the efficacy of butorphanol for the relief of shivering following the epidural administration of 2% lidocaine. Randomized, double-blind study. Labor and delivery department of a university-affiliated hospital inpatient facility. Sixty-one healthy labor patients. Patients who had sustained shivering associated with lidocaine epidural anesthesia were given normal saline or butorphanol 1 mg. Patients were observed for 20 minutes following the administration of a study solution. Shivering ceased within a mean time of 12.9 +/- 3.8 minutes in approximately 81% of the patients who received epidural butorphanol (p < 0.01), while 3% of the patients in the placebo group had no shivering following the administration of epidural saline. No sedation or changes in fetal heart rate were associated with epidural butorphanol. Epidural butorphanol is effective in the treatment of postepidural shivering associated with epidural lidocaine. Epidural agonist opioids have been reported to be efficacious in the management of postepidural shivering. This study demonstrated that a partial agonist opioid also is effective in the treatment of postepidural shivering.


Blind oral intubation: the development and efficacy of a new approach.

To develop an approach to blind oral intubation. With the aid of a fiberoptic laryngoscope and stylet within an endotracheal tube, a video camera, a monitor, and a recorder to correlate the effects of various manipulations of the airway on access to the trachea, a suitable approach was devised. We then evaluated its efficacy. Randomized, prospective comparison of regimens. Inpatient surgery at a university-affiliated teaching hospital. One hundred adult patients with no known abnormalities of the upper airway by history or on physical examination, scheduled to undergo elective surgery, and without evidence of major cardiac disease or need for a rapid-sequence induction of anesthesia. Fifty patients in each of two groups were given fentanyl 5 micrograms/kg intravenously (IV), followed 2 minutes later by thiopental sodium 5 mg/kg and succinylcholine 2 mg/kg. Patients in Group 1 (the controls) were orally intubated via direct laryngoscopy using a Macintosh #3 blade. Patients in Group 2 (the experimentals) were intubated orally with the approach developed without the use of a laryngoscope. Intubations were deemed successful if they were performed within 1 minute after the mouth was opened. All the patients in Group 1 were successfully intubated within 1 minute, while 49 of the 50 patients in Group 2 were successfully intubated within 1 minute. Blind oral tracheal intubation can be successfully performed in a safe and effective manner after appropriate teaching of the technique.


Lidocaine inhalation attenuates the circulatory response to laryngoscopy and endotracheal intubation.

To evaluate the effect of lidocaine inhalation on the circulatory response to direct laryngoscopy and endotracheal intubation. Prospective, randomized study. Operating theater at a public hospital. Eighty patients (ASA physical status I and II ages 25 to 45 years) scheduled for major abdominal surgery. In the first stage, 40 patients were randomly assigned to receive inhalation of either lidocaine 40 mg or a 0.9% solution of sodium chloride (placebo). In the second stage, the next 20 consecutive patients received inhalation of lidocaine 120 mg, and another 20 consecutive patients received intravenous (IV) lidocaine 1 mg/kg. Mean arterial pressure rose significantly in the i.v. lidocaine group (21.2 mmHg; p < 0.05), the saline inhalation group (29.2 mmHg; p < 0.05), and the lidocaine 40 mg inhalation group (22.9 mmHg; p < 0.05), but not in the lidocaine 120 mg inhalation group (10.1 mmHg). The heart rate (HR) response to intubation with lidocaine inhalation was dose dependent. In the saline inhalation group, HR increased by 15.6 beats per minute (bpm) (p < 0.05); in the lidocaine 40 mg inhalation group, HR increased by 9.1 bpm (p < 0.05); and in the lidocaine 120 mg inhalation group, HR increased by only 3.1 bpm. Inhalation of lidocaine 120 mg prior to induction of anesthesia is an effective, safe, and convenient method to attenuate the circulatory response to laryngoscopy and endotracheal intubation.


Are automated anesthesia records better?

To determine whether data recorded by an information management system is significantly different from that recorded manually. A comparison was made between 13 handwritten and 13 computer-generated anesthesia records by calculating the frequency with which recorded variables were outside predetermined acceptable ranges. Five physiologic variables [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), end-tidal partial pressure of carbon dioxide (PETCO2), and oxygen saturation by pulse oximeter (SpO2)] were compared during the initial 1 1/2 hours of operation. Surgical suite at a university-affiliated hospital. Thirteen adult patients scheduled for operations that required general anesthesia for longer than 1 1/2 hours. In addition to the traditional handwritten anesthesia records, an information management system (ARKIVE Patient Management System, DIATEK, San Diego, CA) was used to collect data from each case. No significant differences were found between the methods in the frequency of elevated SBP, elevated DBP, and tachycardia. However, the manual records showed low SBP, DBP, and HR with a significantly lower frequency (2%, 11%, 1%, respectively) than the automated records (6%, 26%, 5%, respectively; p < 0.01). The automated PETCO2 readings were higher than the upper limit (40 mmHg) with a higher frequency (18%) than the manual records (3%; p < 0.01). On the automated records, SpO2 was noted to be 90% or less on two occasions, but significant desaturation was noted only once on the manual charts. Observer bias, missed readings, and errors of memory, which affect manual anesthetic records, may cause significant inaccuracy and may be avoided by using automated records generated by information management systems.


Use of the Augustine stylet anticipating difficult tracheal intubation in Treacher-Collins syndrome.

Treacher-Collins syndrome is a familial and congenital condition often associated with a difficult airway. Although the condition is rare, the anesthesia care provider may encounter it on occasion. This report describes a patient with Treacher-Collins syndrome scheduled to undergo facial reconstruction (fore-head plasty, brow lift, and rhinoplasty) as the sixth of multiple operations. A nasotracheal intubation using the stylet component of a recently introduced airway device, the Augustine Guide, was successfully performed. This is believed to be the first reported use of this method using the Augustine stylet.


Thoracoabdominal aortic aneurysm repair in a 15-month-old child.

This case report describes a young child with a thoracoabdominal aortic aneurysm, a very rare condition in pediatrics. The anesthetic management for resection of the aneurysm and repair of the aorta are presented, and special considerations for pediatric patients are discussed.


Low back pain following epidural blood patch.

A patient underwent outpatient knee arthroscopy with spinal anesthesia administered at the patient's request. The patient was discharged after a 3-hour recovery period. Three days later, the patient returned because of a headache that had begun the evening after surgery and progressively worsened. Treatment with caffeine and hydration for presumed postdural puncture headache resulted in relief for approximately 1 hour. An epidural blood patch was then performed and relieved symptoms for 3 hours until backache began and worsened over the next 7 hours. Computed axial tomography showed epidural air. After symptomatic treatment and observation overnight, the patient was released, and follow-up by telephone was planned. For 2 days, symptoms persisted. Therapy with aspirin 600 mg 4 times daily resulted in acute and significant relief. The backache resolved after 1 week. A review of the literature on backache following epidural blood patch is presented.


Anesthesia for pediatric laparoscopic cholecystectomy.

We report the general anesthetic events and clinical concerns encountered with a laparoscopic cholecystectomy in a 19-month-old toddler. Carbon dioxide was insufflated to create a pneumoperitoneum, with resulting intra-abdominal pressures ranging from 5 to 11 mmHg. The end-tidal partial pressure of carbon dioxide (PETCO2) rose as high as 48 mmHg (a 10 mmHg increase from baseline), requiring a 68% increase in minute ventilation to achieve preinsufflation values. Careful monitoring of ventilation, PETCO2, and intra-abdominal pressure are recommended for optimal anesthetic management of the pediatric laparoscopic cholecystectomy patient.


The rational pharmacology of digoxin.

Although digoxin remains one of the most widely prescribed drugs in the United States, potential pharmacodynamic and pharmacokinetic interactions between this compound and other drugs, diseases, and events commonly encountered in the perioperative period remain largely unappreciated. Furthermore, the therapeutic benefit of discontinuing or initiating digoxin treatment preoperatively remains unclear. We present a basic review of current knowledge regarding digoxin pharmacology and examine those concepts from the perspective of clinical anesthesiologists.


An antibody with specificity for surfactant protein C precursors: identification of pro-SP-C in rat lung.

Surfactant protein C (SP-C) is a lung-specific, hydrophobic peptide found in organic extracts of pulmonary surfactant. Alveolar SP-C (3.5 kD) is produced from proteolytic cleavage of a larger precursor molecule (pro-SP-C; 21 kD). While SP-C is synthesized by type II cells, the pathways for processing and secretion have remained elusive due, in part, to the lack of monospecific antibodies against SP-C or its precursors. This report describes production and characterization of a new antibody directed against pro-SP-C epitopes. Polyclonal antisera (anti-CPRO-SP-C) was prepared using a synthetic peptide corresponding to a portion of rat SP-C cDNA sequence (Ile26-Ser72). This contained amino acids 3-35 of mature SP-C plus additional C-terminal residues (His59-Ser72). On Western blots, anti-CPRO-SP-C competitively reacted to CPRO-SP-C but not to mature SP-C. Immunoblots of in vitro synthesized pro-SP-C confirmed that the antisera also recognized native protein. Immunocytochemistry with anti-CPRO-SP-C demonstrated staining for pro-SP-C peptides in isolated type II cells as well as in alveolar epithelial cells of rat lung sections. Pro-SP-C preferentially co-localized to cells that stained positive for Maclura pomifera antigen. Anti-CPRO-SP-C staining was not observed in lung interstitium, pulmonary vasculature, or several control tissues (brain, heart, and liver were negative). Western blotting of subcellular fractions demonstrated pro-SP-C peptides in plasma membrane (20 kD) and microsomal (20 and 21 kD) fractions with a 16 kD peptide present in lamellar bodies. No pro-SP-C peptides were detected in purified surfactant. These results demonstrate the use of a synthetic peptide to generate specific antiserum against more hydrophilic domains of pro-SP-C sequences and confirm that SP-C propeptides are unique to the lung.


Pathways of fibrin turnover of human pleural mesothelial cells in vitro.

The mesothelium contains both procoagulant and fibrinolytic activities. An imbalance between these activities could account for the abnormal fibrin turnover and pleural fibrin deposition that is characteristic of pleural inflammation. Procoagulant activity of human pleural mesothelial cells (HPMC) is in part due to tissue factor, and the prothrombinase complex can also assemble at the HPMC surface. HPMC express tissue plasminogen activator (tPA) but no detectable fibrinolytic activity in a fibrin plate assay. Inhibition of HPMC fibrinolytic activity is due, in part, to elaboration of plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) as well as antiplasmins. Synthesis of PAI-1 and PAI-2 is inhibited by actinomycin D and cyclohexamide. HPMC PAI-1 is increased by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), as is tPA release, while PAI-1 mRNA is unchanged and tPA mRNA is increased. PAI-2 release is induced by TNF-alpha and TGF-beta. Because they are a rich source of PAI-1 and PAI-2, HPMC may contribute to the high levels of these inhibitors in pleural exudates. Stimulation of HPMC by TNF-alpha or TGF-beta in vitro did not alter HPMC procoagulant activity nor the balance of elevated PAI and antiplasmins relative to PA, changes that collectively favor formation and persistence of pericellular fibrin.


Murine hypersensitivity pneumonitis: production and importance of colony-stimulating factors in the course of a lung inflammatory reaction.

The release of colony-stimulating factors (CSFs) and their contribution to the inflammatory response in the lungs of mice exposed by the intranasal route to the actinomycete Faeni rectivirgula (150 micrograms/day, 3 days/wk), an important thermophilic actinomycete that determines farmer's lung in humans, was examined. Bronchoalveolar lavages (BAL) and lung homogenates of normal mice or saline-instilled mice contained undetectable levels (less than 0.5 U/ml) of the cytokines interleukin-3 (IL-3), colony-stimulating factor-1 (CSF-1), and granulocyte/macrophage colony-stimulating factor (GM-CSF). Mice instilled with F. rectivirgula developed a CSF cytokine response early (24 h) after the instillation that increased and plateaued 2 wk later, and stayed high thereafter. Similarly, lung homogenates of F. rectivirgula-challenged mice contained significant levels of all three CSFs from 24 h after treatment until termination of the experiment. The offending agent itself, F. rectivirgula, was found to directly induce the secretion of IL-3 and GM-CSF from isolated mouse BAL cells and mouse splenocytes, at doses ranging from 1 to 100 micrograms/ml. This was not due to contaminating endotoxin, as inclusion of polymyxin B did not modify this release. Instillation of antibodies against the CSFs in mice challenged with F. rectivirgula did not modify the increase in BAL cell number determined by the challenge (11-fold increase in BAL cell number in F. rectivirgula-instilled mice at 3 wk, whether given anti-CSFs or not). Moreover, direct intratracheal infusion of CSFs (5,000 U of IL-3/CSF-1/GM-CSF) every week did not change the cellular response seen in challenged mice.(ABSTRACT TRUNCATED AT 250 WORDS)


Luminal purinergic regulatory mechanisms of tracheal ciliary beat frequency.

To investigate the modulation of tracheal ciliary beat frequency (CBFt) by purine nucleotides and nucleosides acting on luminal receptors, aerosolized ATP, GTP, AMP-PNP, GMP-PNP, adenosine, and guanosine were each administered separately to the tracheal lumen in eucapnically ventilated, barbiturate-anesthetized beagles. Four studies were conducted in each of seven dogs from a cohort of eight dogs. The CBFt responses were measured on the right lateral surface of the mid-trachea using heterodyne mode correlation analysis laser light scattering. Aerosolized 10(-6) M and 10(-5) M ATP stimulated CBFt from the baseline of 5.9 +/- 1.4 Hz to maxima of 12.1 +/- 1.4 Hz and 13.3 +/- 1.6 Hz, respectively, while the same corresponding ATP-analogue (AMP-PNP) concentrations stimulated baseline CBFt to maxima of 12.7 +/- 4.1 Hz and 18.1 +/- 2.1 Hz, respectively. Similarly, 10(-6) M and 10(-5) M GTP stimulated baseline CBFt to maxima of 14.8 +/- 1.1 Hz and 12.8 +/- 4.6 Hz, respectively. The corresponding GTP-analogue (GMP-PNP) concentrations stimulated CBFt to maxima of 14.5 +/- 2.1 Hz and 18.8 +/- 4.4 Hz, respectively. Prior delivery of 10(-5) M adenosine reduced all these nucleotide-induced stimulatory responses. Prior delivery of 10(-5) guanosine partially reduced the GTP- and the GMP-PNP-induced stimulatory responses. These data demonstrate that nucleotides and nucleosides modulate CBFt through specific P2 and P1 purinergic receptors on the luminal surface, thus providing a direct mechanism within the airways to enhance the transport of mucus.


Endotoxin induces the expression of macrophage inflammatory protein 1 alpha mRNA by rat alveolar and bone marrow-derived macrophages.

Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a newly described cytokine that is present in large amounts in the culture supernatant of an endotoxin-stimulated murine macrophage-like cell line (RAW 264.7). There is increasing information that suggests that this cytokine mediates acute neutrophilic inflammation, although the mechanism of mediation is unknown. Data examining the production and regulation of MIP-1 alpha by primary rat macrophages are lacking, and MIP-1 alpha has not been studied previously in an animal model of endotoxin-induced neutrophilic alveolitis. In this study, we performed Northern analysis of steady-state rat MIP-1 alpha mRNA using an oligonucleotide probe complementary to amino acids 4-13 of murine MIP-1 alpha. Our data demonstrate that rat alveolar and bone marrow-derived macrophages can be induced by in vitro endotoxin treatment to express a 1.1-kb MIP-1 alpha mRNA. Expression of the mRNA could be elicited by treatment with 0.1 to 10.0 micrograms/ml of endotoxin in vitro with peak steady-state levels detectable up to 9 h after adding endotoxin to the media. Alveolar macrophages recovered by whole lung lavage from endotoxin-treated rats expressed increased amounts of the mRNA homologous to MIP-1 alpha mRNA when treated in vitro with endotoxin. We also found that rat neutrophils could be induced by endotoxin in vitro to express the MIP-1 alpha mRNA. We were able to identify MIP-1 alpha in culture supernatant from endotoxin-stimulated rat alveolar and bone marrow-derived macrophages by immunoprecipitation with a specific goat anti-murine MIP-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)


The influence of intravenous Albunex injections on pulmonary arterial pressure, gas exchange, and left ventricular peak intensity.

Contrast ultrasonography may be used to assess regional tissue perfusion. The purpose of this study was to evaluate the safety and efficacy of a new, commercially prepared ultrasound contrast agent (Albunex) in dogs. The injections were administered from peripheral intravenous (IV), right atrial (RA), and pulmonary artery (PA) sites. Acute pulmonary hemodynamic and gas exchange effects of low-dose (0.5, 1.0, 2.0 ml) Phase I injections, and high-dose (2.0, 5.0, 10, 20 ml) Phase II injections of Albunex were evaluated in nine dogs. Immediately before and after each injection, pulmonary artery pressure (PAP) and oxygen tension (PO2) were determined. In addition, left ventricular cavity opacification was assessed visually and by videodensitometric off-line analysis. Visual assessment was performed by four blinded observers who graded on a scale of 0 to 3 (0 = no contrast enhancement of the left ventricular (LV) cavity; 1 = weak or suboptimal contrast enhancement; 2 = optimal or excellent contrast enhancement; and 3 = attenuation of the ultrasound signal following a contrast injection). Peak pixel intensity was also determined with videodensitometric analysis. Results showed that significant changes in PAP or PO2 were not noted after Albunex injections, regardless of injection site or dose range. The average change in PAP after Albunex injection was 1.0 mm Hg +/- 1.2 mm Hg (NS), and the average change in PO2 after Albunex injections was 6.2 mm Hg +/- 6.7 mm Hg (NS). The left ventricular cavity peak pixel intensity was dependent on both injection site (PA = RA > IV) and dose range (2.0 = 1.0 > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)


Sensitivity of contrast ultrasound in the detection of atrial septal defect with predominant left-to-right shunting.

Ultrasound contrast techniques are used widely as a screening test for intracardiac shunt. We performed a retrospective analysis of contrast echocardiograms in 29 consecutive patients with atrial septal defect (excluding Eisenmenger's) proved by cardiac catheterization. A positive (right-to-left atrial) ultrasound contrast effect was seen in 25 patients in whom catheterization pulmonary-to-systemic flow rate (Qp/Qs) was 2.2 +/- 0.9 (SD). Four patients had false-negative contrast echocardiography results; their Qp/Qs was 2.9 +/- 0.4 (p = 0.07). The percent left-to-right shunt was higher in the group with false-negative contrast echocardiographic results (65% +/- 4% vs 47% +/- 21%) (p = 0.05). Shunts with Qp/Qs < or = 2.0 had a sensitivity of 100%, whereas those with Qp/Qs > or = 2.1 had a sensitivity of 73%. In the four false-negative contrast echocardiographic results, three had findings of an atrial septal defect by pulsed Doppler, color Doppler, or both. Thus the presence of a large left-to-right shunt may decrease the sensitivity of the ultrasound contrast technique for the detection of an atrial septal defect. Contrast ultrasonography should be used in conjunction with Doppler and two-dimensional echocardiography criteria for diagnosis of atrial septal defect.


Value of transesophageal color Doppler echocardiography for detection of different types of atrial septal defect in adults.

In 121 adults, the value of transthoracic and transesophageal color Doppler echocardiography for detection of different types of atrial septal defect (ASD) or of partial anomalous pulmonary venous return was analyzed. The 121 patients had a total of 129 defects with left-to-right atrial shunting (including eight patients with two types of defects). All of six cases with primum-type ASD were diagnosed correctly by both echocardiographic methods. Ninety-seven patients showed a secundum-type ASD during transesophageal echocardiography: by transthoracic echocardiography, only eight (20%) of the 40 small defects (diameter < 5 mm) were detected as compared with 15 (83%) of the 18 defects with a diameter of 5 to 10 mm and all 39 defects with a diameter > 10 mm. A sinus venosus--type ASD was evident by transesophageal echocardiography in 11 patients, of which only one (9%) was demonstrated by the transthoracic approach. Partial anomalous pulmonary venous return was seen by transesophageal echocardiography in 13 patients but missed in two other patients in whom anomalous pulmonary venous return was subsequently identified by surgery (both with anomalous return of the upper right pulmonary vein into the superior vena cava). By use of the transthoracic technique, partial anomalous venous return was detected in only two cases, both of which had "scimitar syndrome." Compared with transthoracic echocardiography, the transesophageal approach is clearly superior in the detection of small secundum-type ASD, sinus venosus--type ASD, and partial anomalous pulmonary venous return.


Computerized measurement of Doppler flow velocity waveforms: validation of a new system.

Manual measurement of Doppler flow velocity waveforms is time-consuming and carries unavoidable and significant intraobserver and interobserver variability. Those drawbacks limit the routine use of Doppler-derived indexes of systolic and diastolic function. This report describes a system that performs automatically all relevant measurements currently obtained from mitral, tricuspid, aortic, and pulmonary waveforms. One hundred and sixty waveforms, obtained from patients whose ages ranged from a 19-week fetus to a 21-year-old adult, were measured both manually and automatically. High correlations were found for all types of measurement: r = 0.993 for velocity measurements, r = 0.995 for time interval measurements, r = 0.881 for acceleration measurements, r = 0.867 for pressure half-time measurements, and r = 0.993 for flow integral measurements. When compared with manual measurements, automatized measurements displayed significantly lower intraobserver and interobserver variabilities for all types of measurements. Finally, the automatized measurement system cuts the time spent by a factor of more than five. Such a system of computerized measurements of Doppler flow velocity waveforms should become increasingly valuable as both a clinical and a research tool.


Restrictive left ventricular diastolic filling identifies patients with heart failure after acute myocardial infarction.

Left ventricular diastolic filling was characterized by transmitral pulsed-wave Doppler velocities in 62 patients with acute myocardial infarction, and diastolic filling variables were correlated with the presence of clinical heart failure. At the time of admission, 47 patients were free of heart failure and 15 patients were in Killip class II to IV. In the latter group of patients with heart failure, peak velocity of late filling wave caused by atrial contraction (A) was lower (0.48 versus 0.59 m/sec, p < 0.05), ratio of peak velocity of early rapid filling wave to peak velocity of late filling wave caused by atrial contraction (E/A) was higher (1.5 versus 1.1, p < 0.01), and deceleration time (136 versus 196 msec, p = 0.0001) was shorter when compared with the patients not in heart failure after acute myocardial infarction. Multivariate analysis showed that the deceleration time was a powerful independent predictor of presence of heart failure after controlling for systolic functional variables. Therefore, diastolic filling variables can complement systolic functional variables in the identification of the patients with postinfarction left ventricular failure.