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Biomedical subjects

J E Smith

Publications and source records attributed to J E Smith.

At least 91 records · Page 5Linked to original sources
PubMed2001

The community reinforcement approach to the treatment of substance use disorders.

Empirical support is presented for the Community Reinforcement Approach (CRA), a broad-spectrum cognitive-behavioral treatment for substance use disorders. At the core of CRA is the belief that an individual's environment can play a powerful role in encouraging or discouraging drinking and drug use. Consequently, it attempts to rearrange contingencies so that sober behavior is more rewarding than substance-abusing behavior. Originally tested in the early 1970s with a small sample of alcohol-dependent inpatients, it has repeatedly proven to be successful over the years with larger, diverse populations. Empirical backing is also presented for a new variant of CRA that works through family members to engage treatment-resistant individuals into substance abuse treatment.

Ambulatory Care↗
PubMed2001

Manoeuvres used to clear the airway during fibreoptic intubation.

Fibreoptic orotracheal endoscopy under general anaesthesia may be more difficult to perform if the upper airway cannot be fully cleared. We have studied the effectiveness of jaw thrust, lingual traction and the application of both manoeuvres simultaneously, in opening up the orolaryngeal airspace in 30 ASA group 1 or 2 patients aged between 16 and 70 yr undergoing elective general surgery requiring orotracheal intubation. Airway clearance was assessed fibreoptically at soft palate level by observing whether or not the uvula or soft palate was apposed to the base of the tongue, and at epiglottic level by observing whether or not the epiglottis was apposed to the posterior pharyngeal wall. Lingual traction with Duval's forceps cleared the tongue away from the uvula and soft palate significantly more times than did jaw thrust (P<0.05). Jaw thrust cleared the epiglottis away from the posterior pharyngeal wall more frequently than did lingual traction (P=0.052). Applying both jaw thrust and lingual traction simultaneously cleared the airway at both soft palate and epiglottic level in every patient. When used alone, jaw thrust and lingual traction fail to produce full airway clearance in a significant number of patients. Combined jaw thrust and lingual traction clears the airway more effectively but requires two assistants.

Adult↗
PubMed2001

The Drosophila daughterless gene autoregulates and is controlled by both positive and negative cis regulation.

As the only class I helix-loop-helix transcription factor in Drosophila, Daughterless (Da) has generally been regarded as a ubiquitously expressed binding partner for other developmentally regulated bHLH transcription factors. From analysis of a novel tissue-specific allele, da(lyh), we show that da expression is not constitutive, but is dynamically regulated. This transcriptional regulation includes somatic ovary-specific activation, autoregulation and negative regulation. Unexpectedly, the diverse functions of da may require that expression levels be tightly controlled in a cell and/or tissue-specific manner. Our analysis of da(lyh) identifies it as the first springer insertion that functions as an insulating element, with its disruptive activity mediated by the product of a fourth chromosome gene, Suppressor of lyh [Su(lyh)].

Alleles↗
PubMed2001

The effects of creatine supplementation on repeated upper- and lower-body Wingate performance.

Nineteen physically active men supplemented their diet with 20 g per day creatine monohydrate (Cr group) or placebo (PI group) for 6 days. Before and after supplementation, subjects performed 3 arm Wingates (AW1, AW2, and AW3) and 3 leg Wingates (LW1, LW2, and LW3) on consecutive days. Wingates were separated by 2 minutes each. Mean power (MP), peak power (PP), and percent decrease (%D) were compared between and within groups. MP did not change significantly for arms or legs. PP did not change significantly for legs. PP increased significantly in the Cr group (AW1) and for the P1 group (AW1 and AW3). MP and PP were not significantly different between groups. The %D increased significantly in the P1 group (AW1, AW3, and LW3). For the Cr group, %D decreased significantly (pre vs. post) and was significantly lower than for the P1 group (LW2-post). Results suggest that short-term Cr supplementation does not enhance MP and PP during repeated upper- and lower-body Wingate tests when not accompanied by an increase in body weight. However, changes in %D suggest possible ergogenic effects.

Adult↗
PubMed2000

Loss of cone molecular markers in rhodopsin-mutant human retinas with retinitis pigmentosa.

PURPOSE: To examine the effect of rhodopsin mutations on cone photoreceptors in human retinas with retinitis pigmentosa (RP). METHODS: Four RP retinas with rhodopsin mutations and four normal retinas were examined by immunofluorescence with a battery of cell-specific antibodies against cone and rod cytoplasmic and outer segment membrane proteins. Areas of the retinas were studied that showed maximal preservation of photoreceptor structure. RESULTS: All four RP retinas showed loss of rods, ranging from mild (T-17-M), to more severe (P-23-H), to advanced degeneration (Q-64-ter and G-106-R). The majority of cones in the T-17-M and P-23-H retinas were cytologically normal but showed loss of immunoreactivity for the cytoplasmic proteins 7G6, calbindin, and X-arrestin. The cone outer segments (OS) remained positive for cone opsins and peripherin-2 (rds/peripherin). All remaining cones in the Q-64-ter and G-106-R retinas were degenerate, with short to absent OS, but had strong reactivity for these cytoplasmic and OS membrane markers. Cones in the maculas of the RP retinas were degenerate, with short to absent OS, but retained strong labeling for the cytoplasmic and OS proteins. CONCLUSIONS: Even before cones show cytologic changes in response to rod cell degeneration, they lose immunoreactivity for certain cytoplasmic proteins. These cones later show shortening and loss of OS, although their OS membrane proteins remain well labeled. Cones may down regulate expression of both cytoplasmic and outer segment membrane proteins in response to mutant rod cell dysfunction and/or cell death in human RP retinas. Such cytologic and immunocytochemical changes in the cones may presage death of these critical cells in the later stages of RP.

Aged↗
PubMed2000

The first positive: computing positive predictive value at the extremes.

Computing the positive predictive value (PPV) of a wellknown test for a relatively common disease is a straight-forward exercise. However, in the case of a new test for a rare disorder; the extreme numbers involved-the very low prevalence of the disorder and the lack of previous false-positive results--make it difficult to compute the PPV. As new genetic tests become available in the next decade, more and more clinicians will have to answer questions about PPVs in cases with extreme prevalence, sensitivity, and specificity. This paper presents some tools for thinking about these calculations. First, a standard PPV calculation with rough estimates of the prevalence, sensitivity, and specificity is reviewed. The "zero numerator" problem posed by not having seen any false-positive results is then discussed, and a Bayesian approach to this problem is described. The Bayesian approach requires specification of a prior distribution that describes the initial uncertainty about the false-positive rate. This prior distribution is updated as new evidence is obtained, and the updated expected false-positive rate is used to calculate PPVs. The Bayesian approach provides appropriate and defensible PPVs and can be used to estimate failure rates for other rare events as well.

Bayes Theorem↗
PubMed2000

Coherent rhythmic discharges in sympathetic nerves supplying thermoregulatory circulations in the rat.

1. In anaesthetised rats, activity recorded from sympathetic postganglionic neurones innervating the tail circulation has characteristic rhythmicity (0.4-1.2 Hz). At the population level this rhythmicity can be seen as a peak (T-peak) in autospectra of sympathetic activity recorded from ventral collector nerves (VCNs). 2. Here we investigated whether nerves supplying thermoregulatory circulations share common rhythmic discharges at T-peak frequency. Activity was recorded from nerve pairs consisting of left ventral collector nerve (LVCN) and one of the following: right ventral collector nerve (RVCN), left dorsal collector nerve (DCN), left saphenous nerve (SN) or left renal nerve (RN). 3. During central apnoea, T-peak frequencies in RVCN autospectra were similar to those of simultaneously recorded LVCN and these activities were coherent. Similar observations were made for nerve pairs involving LVCN-DCN and LVCN-SN. In contrast, autospectra of RN activity did not contain T-peaks. 4. In comparison to the peaks in autospectra of RN activity, when the frequency of rhythmic phrenic nerve activity was manipulated T-peaks in VCN, DCN and SN autospectra did not show obligatory 1:1 locking. 5. We conclude that T-peaks are a robust feature of autospectra of sympathetic discharges supplying thermoregulatory circulation but not those influencing the kidney. The high coherence demonstrated between the T-peak discharges is consistent with the view that common/coupled oscillators located within the CNS influence cutaneous vasoconstrictor sympathetic activity.

Animals↗
PubMed2000

Ventral pallidal extracellular fluid levels of dopamine, serotonin, gamma amino butyric acid, and glutamate during cocaine self-administration in rats.

RATIONALE: Dopamine innervation of the nucleus accumbens is thought to have a major role in the biological processes underlying cocaine self-administration. Recent data suggest that dopamine innervation of the ventral pallidum (VP) may also play an important role. OBJECTIVES: This experiment was initiated to assess extracellular fluid levels of dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), and glutamate (Glu) in the VP of rats self-administering cocaine using in vivo microdialysis. METHODS: Rats were implanted with intravenous jugular catheters and a microdialysis probe guide cannula into the VP and trained to self-administer (SA) three different doses of cocaine during each daily session. Other rats (yoked rats) were surgically prepared in identical fashion and received vehicle infusions during microdialysis sessions when the SA rat to whom they were yoked produced cocaine infusions. When stable baselines of self-administration were obtained, microdialysates were collected during two consecutive daily self-administration sessions. Neurotransmitter levels were measured using HPLC with electrochemical (DA and 5-HT) or fluorescence detection (GABA and Glu). RESULTS: In SA rats, extracellular fluid levels of DA [DA]e and 5-HT [5-HT]e were elevated throughout the session and levels of Glu [Glu]e showed small increases at a few isolated time points during the session. The increases in [DA]e and 15-HT]e were dose-dependent. Extracellular fluid levels of GABA [GABA]e were unchanged, as were levels of all four neurotransmitters in the yoked rats. CONCLUSIONS: These data support a potential role for DA and 5-HT innervations of the VP in intravenous cocaine self-administration.

Animals↗
PubMed2000

Strain and stage specific variation in Toxoplasma gondii antigens.

The antigenic profile of virulent (RH, ENT, Martin) and avirulent (RRA, DEG, ME49) Toxoplasma strains was compared directly by western blotting using a panel of immune mouse sera. Dominant antigens of approximate MR 30-33, 21 and 25 x 10(3) were common to tachyzoites of all strains, however, there were significant quantitative and qualitative differences in the antigen profiles, indicating a moderate degree of strain specific polymorphism in tachyzoite antigens. We found no specific association between antigenic variation and strain virulence. Comparison of tachyzoite and bradyzoite antigens from homologous strains (RRA, DEG, ME49) confirmed the existence of stage specific antigens and demonstrated a conserved antigen profile among bradyzoites.

Animals↗
PubMed2000

MEIS1 and HOXA7 genes in human acute myeloid leukemia.

Co-activation of Meisl with Hoxa7 or Hoxa9 homeobox genes by retroviral gene insertion has recently been reported to be leukemogenic in murine myeloid leukemia. In this study we determined their expression in human leukemia. Most human myeloid leukemia cell lines co-expressed MEIS1 with HOXA7 and HOXA9. Among patients with acute leukemia, 50% of AML patients expressed MEIS1, while the majority of ALL patients were negative. A total of 89.5% of patients expressing MEIS1 co-expressed HOXA7. In unadjusted models, poorer response to chemotherapy was associated with expression of HOXA7 regardless of MEIS1 status and older patients were more likely to express either gene.

Cell Line↗
PubMed2000

Histopathologic and immunocytochemical analysis of the retina and ocular tissues in Batten disease.

PURPOSE: To describe the pathophysiologic features of retinal degeneration in Batten disease (juvenile neuronal ceroid lipofuscinosis [JNCL]) caused by mutations in the CLN3 gene. STUDY DESIGN: Comparative human tissue study. MATERIALS: The retina and other ocular tissues of a 22-year-old man with JNCL were compared with the same tissues of a healthy 30-year-old man. DNA from whole blood and RNA from retina were used for genotype analysis. METHODS: The retinas, corneas, conjunctiva, and ciliary body were processed for histopathologic and immunofluorescence analysis. Genomic DNA was subjected to polymerase chain reaction (PCR) and nucleotide sequence analyses. Reverse transcriptase/PCR and sequence analysis were performed on retinal RNA. RESULTS: The JNCL donor was heterozygous for a approximately 1 kb deletion in CLN3, as found in most JNCL patients. The other allele had a single base pair deletion in exon 6 that resulted in a frame shift. Gross pathology of the JNCL retina resembled that in retinitis pigmentosa, including deposits of bone spicule pigment. Histopathologic studies revealed loss of neurons from all retinal layers. Immunofluorescence labeling with antibodies to rhodopsin, recoverin, and cone opsin demonstrated degenerate rods and cones with short outer segments in the far periphery. Autofluorescent lipopigment granules were prominent in ganglion cells and some cells of the inner nuclear layer, but not in the photoreceptors. The retinal pigment epithelium (RPE) had fewer lipofuscin granules than the control specimen. Increased numbers of lipofuscin granules were found in the epithelia of the ciliary body and conjunctiva, but not in the cornea of the JNCL eye. CONCLUSIONS: Immunofluorescence studies revealed degenerate rods and cones in the far periphery. Lipofuscin granules were decreased in the RPE, consistent with loss of photoreceptor outer segments. The novel finding that degenerate photoreceptors did not contain autofluorescent inclusions suggests that granule accumulation may not precede photoreceptor degeneration in JNCL. The presence of normal photoreceptor proteins in the degenerate rods and cones suggests that these cells may be capable of functional regeneration if a therapy for Batten disease is developed.

Adult↗
PubMed2000

Learning fibreoptic endoscopy. Nasotracheal or orotracheal intubations first?

We have studied the extent to which learning fibreoptic nasotracheal endoscopy first helped anaesthetists to learn fibreoptic orotracheal endoscopy later, and vice versa. After preliminary training on a bronchial tree model, 30 anaesthetic trainees were randomly allocated to the nasal first/oral second group, who performed 10 nasal intubations followed by 10 oral intubations, or the oral first/nasal second group, who performed 10 oral intubations followed by 10 nasal intubations, in anaesthetised, ASA group I or II patients undergoing elective oral or general surgery. Each type of endoscopy was taught in a standard manner, with the aid of an endoscopic video-camera system, under the supervision of experienced instructors. Performing nasal endoscopy second (average 70.8 s) took significantly less time than performing it first (average 84.4 s) and performing oral endoscopy second (average 35.2 s) took significantly less time than performing it first (average 48.5 s). The mean (SD) total endoscopy time for all the endoscopies (both nasal and oral) in the nasal first/oral second group [1196 (162) s] was not significantly different from that for all the endoscopies in the oral first/nasal second group [1193 (188) s]. Because there is no advantage or disadvantage to be gained in starting to learn either type of endoscopy first, graduated training programmes can be planned according to the availability of suitable patients for fibreoptic intubation, without instructors needing to consider whether trainees make better progress if they learn one technique before the other.

Adult↗
PubMed2000

Relation of serum retinol to acute phase proteins and malarial morbidity in Papua New Guinea children.

BACKGROUND: Acute phase proteins (APPs) are associated with malaria-induced hyporetinemia (serum retinol <0.70 micromol/L); however, the degree of the association is not well documented. OBJECTIVE: The association between malaria-induced hyporetinemia and APPs was assessed. DESIGN: In a cross-sectional study, 90 children with serum retinol concentrations from <0.35 to >1.05 micromol/L were selected from children in a clinical trial of vitamin A supplementation. Serum was collected before treatment allocation. Retinol binding protein (RBP) concentrations were determined by radioimmunoassays, and transthyretin, alpha(1)-acid glycoprotein (AGP), alpha(1)-antichymotrypsin, C-reactive protein (CRP), haptoglobin, and albumin concentrations by radial immunodiffusion assays. RESULTS: Children in the subsample had high rates of splenomegaly and Plasmodium-positive blood-smear slides (P < 0.01); AGP (Pearson's r = -0.40, P < 0.001) and CRP (r = -0.21, P = 0.04) were inversely correlated with retinol. The negative APPs RBP, transthyretin, and albumin were positively and significantly associated with retinol. All APPs, except alpha(1)-antichymotrypsin, were significantly correlated with splenomegaly. Of the positive APPs, AGP correlated with CRP (r = 0.37, P < 0.001), indicating chronic inflammation. In a stepwise regression analysis, 73% of retinol's variability was explained by RBP and transthyretin. The model predicted that a 1-SD increase in RBP or transthyretin increases retinol by approximately 0.38 or 0.47 micromol/L, respectively, whereas an equivalent increase in AGP decreases retinol by 0.12 micromol/L. CONCLUSIONS: The RBP-transthyretin transport complex of retinol is not altered by inflammation. Positive APPs are useful markers of type and severity of inflammation; however, except for AGP, it is unlikely that they can correct for malaria-induced hyporetinemia.

Acute-Phase Proteins↗