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Biomedical subjects

S Howell

Publications and source records attributed to S Howell.

At least 37 records · Page 2Linked to original sources
PubMed2000

Endoscopic ultrasound guided biopsy of sub-carinal lymph nodes.

AIM/METHODS: Endoscopic ultrasound (EUS) guided biopsy is not widely available in the U.K., and sub-carinal nodes can be difficult to biopsy percutaneously. Tissue obtained from these nodes can influence patient management. We describe our initial experience with EUS guided transoesophageal biopsy of sub-carinal nodes using a Pentax FG-34 EUS probe and a 22 G Hancke-Villman or Echotip needle in 20 patients. RESULTS: Malignant cells were obtained from the nodes in 13 patients, and in another patient in whom the node biopsy was negative, small cell carcinoma cells were obtained from a lesion in the liver. There were no complications. CONCLUSIONS: Mediastinoscopy to obtain tissue, or the blind treatment of presumed malignancy was avoided in all the patients in whom a positive biopsy was obtained. In many of these patients, more conventional methods to obtain a tissue diagnosis had already failed. The problem solving capability of this safe, well-tolerated technique is discussed.Roberts, S. A. Clinical Radiology55, 832-836.

Adult↗
PubMed2000

Symptoms discriminate irritable bowel syndrome from organic gastrointestinal diseases and food allergy.

BACKGROUND: The value of specific gastrointestinal symptoms in discriminating irritable bowel syndrome (IBS) from organic disease has been documented. In contrast, there have been few attempts to identify symptoms that discriminate irritable bowel syndrome from food allergy, despite similarities in their respective symptom complexes. We aimed to investigate the value of symptoms in discriminating irritable bowel syndrome from organic disease and food allergy. METHODS: Subjects (n = 288) were recruited from consecutive patients presenting to the Internal Medicine, Gastroenterology and Allergy Units in Chieti. Patients completed the validated Bowel Disease Questionnaire (BDQ) prior to an independent diagnostic evaluation, which included endoscopy when appropriate. Food allergy was diagnosed using a 2-week elimination diet, followed by a placebo-controlled food challenge test, a skin prick test and serum RAST for specific IgE for suspected foods or additives. The results of the BDQ were not considered in formulating a diagnosis. In total, 99 patients were diagnosed with the IBS, 79 patients were diagnosed with organic disease and 22 patients were diagnosed with food allergy. A further 88 patients with extraintestinal allergies were included as a control group. RESULTS: Based on logistic regression analysis, six symptom items discriminated IBS from organic disease, while five symptoms discriminated patients with IBS from control subjects. A diagnosis of IBS compared to organic disease was positively associated with straining on defaecation (P=0.0001), diarrhoea (P=0.001) and abdominal bloating (P=0.01), but was negatively associated with pain in the upper abdomen (P=0.0004), reflux (P=0.0001) and appetite loss (P=0.004). A diagnosis of IBS compared to extraintestinal allergy was positively associated with pain relieved by bowel movement (P=0.0001), pain in the lower abdomen (P=0.0006), pain in both the upper and lower abdomen (P=0.003), frequent pain (P=0.001) and abdominal bloating (P=0.0009). In comparison between IBS and food allergy patients, a diagnosis of IBS was positively associated with pain in the lower abdomen (P=0.001), pain relieved by bowel movements (P=0.001), frequent pain (P=0.02) and abdominal bloating (P=0.03). CONCLUSION: Symptoms appear to be useful for discriminating IBS from organic gastrointestinal disease and food allergy.

Adolescent↗
PubMed1999

Methicillin-resistant Staphylococcus aureus infections in 11 dogs.

Methicillin-resistant Staphylococcus aureus infection was identified in 11 dogs. The infection was associated with surgical treatment especially orthopaedic surgery. Infection after traumatic wounding, and recurrent pyoderma was also seen. Oral antibiotic treatment improved or resolved the infection in nine of the 11 dogs, although the methicillin-resistant isolates were susceptible to relatively few antibiotics.

Animals↗
PubMed1999

Peri-operative silent myocardial ischaemia in patients undergoing lower limb joint replacement surgery: an indicator of postoperative morbidity or mortality?

One hundred and twenty-seven patients undergoing major lower limb joint replacement surgery were studied to determine the incidence of silent myocardial ischemia and to ascertain any link between pre-operative cardiac risk factors, silent myocardial ischaemia and postoperative morbidity. Patients underwent ambulatory ECG monitoring for 4 days (on the pre-operative night and for 3 days postoperatively). Postoperative cardiorespiratory symptomatology and morbidity was assessed by questionnaire at 3 months. Eighty-seven patients had risk factors for silent myocardial ischaemia; 42 patients (30 with risk factors) had peri-operative silent myocardial ischaemia. The median ischaemic loads (range) were 1.04 (0.32-13.31) min.h-1 pre-operatively and 5.53 (0.26-56.39), 6.69 (0.04-42.71) and 1.23 (0.1-53.74) min.h-1 on postoperative days 1-3, respectively. Risk factors did not predict the occurrence of silent myocardial ischaemia or an increased ischaemic load pre-operatively or overall postoperatively. New symptoms (chest pain, palpitations, breathlessness or fatigue) were associated with both silent myocardial ischaemia and ischaemic load (p < 0.05). Thus cardiac risk factors do not predict the occurrence of silent myocardial ischaemia or adverse outcome. Peri-operative silent myocardial ischaemia was associated with increased postoperative fatigue.

Aged↗
PubMed1999

Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene.

A large English family with autosomal dominant segregation of presenile dementia, ataxia and other neuropsychiatric features is described. Diagnoses of demyelinating disease, Alzheimer's disease, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome have been attributed to particular individuals at different times. An Irish family, likely to be part of the same kindred, is also described, in which diagnoses of multiple sclerosis, dementia, corticobasal degeneration and new variant CJD have been considered in affected individuals. Molecular genetic studies have enabled the classification of this disease at the molecular level as one of the group of inherited prion diseases, with the substitution of valine for alanine at codon 117 of the prion protein gene (PRNP). Only three other kindreds have been described world-wide with this mutation and only limited phenotypic information has been reported. Here we describe the phenotypic spectrum of inherited prion disease (PrPA117V). The diversity of phenotypic expression seen in this kindred emphasizes the logic of molecular classification of the inherited prion diseases rather than classification by specific clinicopathological syndrome. Indeed, inherited prion disease should be excluded by PRNP analysis in any individual presenting with atypical presenile dementia or neuropsychiatric features and ataxia, including suspected cases of new variant CJD.

Adult↗
PubMed1999

Targeting effect compartment or central compartment concentration of propofol: what predicts loss of consciousness?

BACKGROUND: An effect compartment has been postulated, and the ke0 has been quantified for several intravenous anesthetic drugs using electroencephalography (EEG) as the measure of effect. The authors wanted to validate that loss of responsiveness (LOR) was related to targeting an effect compartment concentration rather than a central compartment (plasma) concentration. METHODS: Twenty American Society of Anesthesiologists physical status I and II patients were randomized to receive propofol administered to a target central compartment or target effect compartment site concentration of 5.4 microg/ml propofol administered by a target-controlled infusion (TCI) using a previously validated set of pharmacokinetic parameters and a ke0 of 0.63 min(-1). Every 30 s for the first 5 min and every minute for the second 5 min the patients were asked to open their eyes. The time to LOR was measured by a blinded investigator. The authors also simulated the time to reach the desired target effect site concentration using varying ke0 values. RESULTS: The median time to LOR in the group targeted to a predicted plasma propofol concentration was 3.02 min and 1.23 min in the group targeted to a predicted effect compartment propofol concentration (P < 0.05). LOR to command in both groups occurred at a predicted median effect compartment concentration of 4.55 microg/ml. Simulations demonstrated that the time predicted to LOR targeting an effect site concentration of 5.4 microg/ml is markedly altered by the value chosen for the ke0. CONCLUSIONS: This study confirms the utility of the ke0 value to describe the effect compartment for propofol. The authors also illustrate the importance of selecting the correct ke0 value for the pharmacokinetic parameters used within the TCI system.

Adolescent↗
PubMed1999

Does fear of serious disease predict consulting behaviour amongst patients with dyspepsia in general practice?

BACKGROUND: There have been relatively few studies of health care utilization amongst patients with upper gastrointestinal (GI) complaints. We postulated that health care utilization amongst patients with dyspepsia is primarily driven by fear of serious disease. METHOD: Consecutive patients presenting to primary care with dyspepsia were questioned about their health care utilization over a 12-month pre-consultation period. The patients completed a questionnaire which included validated measures of GI symptoms (including symptom frequency, duration and severity), and the shortened neuroticism scale of the Eysenck Personality Questionnaire. In total, 614 patients were recruited into the study, and 596 patients provided details of their health care utilization. Previous health care utilization was defined as one or more primary care visits for upper GI symptoms in the 12 months prior to the index visit; frequent health care utilization was defined as six or more visits over the same period. RESULTS: Previous health care utilization was reported by 80% of patients, while frequent health care utilization was reported by 26% of patients. Fear of serious illness and fear of cancer were univariately associated with previous and frequent health care utilization (both P = 0.001). However, the only independent predictors of previous health care utilization were frequent dyspepsia (odds ratio (OR) = 2.17), pain-related anxiety (OR = 2.08-4.66) and higher neuroticism scores (OR = 1.12); independent predictors of frequent health care utilization were frequent dyspepsia (OR = 3.25), pain-related anxiety (OR = 1.74-6.08), female gender (OR = 1.73) and being a non-drinker (OR = 1.72). Health care utilization was not independently associated with symptom severity or duration, or with patients' characteristics, such as age, marital status, ethnicity, smoking status or the use of non-steroidal antiinflammatory drugs. CONCLUSIONS: Consulting behaviour amongst patients with dyspepsia is driven in part by psychological factors and, in particular, by symptom-related anxiety as well as by the frequency of dyspepsia, but not primarily by fear of serious disease. Anxiety may help sustain health care utilization once the behaviour has been established.

Alcohol Drinking↗
PubMed1998

Role of the glycosyl-phosphatidylinositol anchor in the intracellular transport of a transmembrane protein in Madin-Darby canine kidney cells.

In order to compare the trafficking of proteins with different membrane anchors, we have constructed and expressed three different recombinant forms of neutral endopeptidase (NEP) in MDCK cells. The wild type form of NEP (WT-NEP) is attached to the plasma membrane by a single N-terminal membrane spanning domain, whereas the glycosylphosphatidylinositol-anchored form of the protein (GPI-NEP) contains a C-terminal GPI anchor. A double anchored form of NEP (DA-NEP) was also constructed, that contains both the original N-terminal membrane spanning domain and a C-terminal GPI anchor. We show here that WT-NEP, GPI-NEP and DA-NEP, which are all apically targeted in MDCK cells, behave differently when subjected to Triton X-100 solubilisation: despite the presence of the transmembrane anchor DA-NEP behaves as a GPI-anchored protein. This suggests that the GPI anchor of DA-NEP is dominant over the transmembrane anchor of the native protein to determine its pattern of solubility in Triton X-100.

Animals↗
PubMed1998

Structural and functional architecture of the yeast cell-cycle transcription factor swi6.

The structural and functional organisation of Swi6, a transcriptional regulator of the budding yeast cell cycle has been analysed by a combination of biochemical, biophysical and genetic methods. Limited proteolysis indicates the presence of a approximately 15 kDa N-terminal domain which is dispensable for Swi6 activity in vivo and which is separated from the rest of the molecule by an extended linker of at least 43 residues. Within the central region, a 141 residue segment that is capable of transcriptional activation encompasses a structural domain of approximately 85 residues. In turn, this is tightly associated with an adjacent 28 kDa domain containing at least four ankyrin-repeat (ANK) motifs. A second protease sensitive region connects the ANK domain to the remaining 30 kDa C-terminal portion of Swi6 which contains a second transcriptional activator and sequences required for heteromerisation with Swi4 or Mbp1. Transactivation by the activating regions of Swi6 is antagonised when either are combined with the central ankyrin repeat motifs. Hydrodynamic measurements indicate that an N-terminal 62 kDa fragment comprising the first three domains is monomeric in solution and exhibits an unusually high frictional coefficient consistent with the extended, multi-domain structure suggested by proteolytic analysis.

Ankyrins↗
PubMed1998

Inhibition of calmodulin-activated smooth-muscle myosin light-chain kinase by calmodulin-binding peptides and fluorescent (phosphodiesterase-activating) calmodulin derivatives.

Aspects of the biochemistry of calmodulin have been addressed that bear on its cell biological role as a mediator of Ca2+ regulation. Calmodulin-binding peptides derived from the amino acid sequence of smooth-muscle myosin light-chain kinase (MLCK) were characterized as inhibitors of calmodulin activation of MLCK-catalyzed phosphorylation of the smooth-muscle regulatory light chain (MLC). MLCK activity was determined by measuring the rate of formation of one of the reaction products, ADP, in a coupled enzymatic assay by continuous fluorimetric monitoring of NADH removal in 100 microM CaCl2 at ionic strength 0.15 M, pH 7.0 and 21 degreesC. The Km value of calmodulin was 3.5 nM, a value 16-35-fold greater than the Kd value of calmodulin for MLCK [Török, K., and Trentham D. R. (1994) Biochemistry 33, 12807-12820]. The different Km and Kd values are most likely associated with the rate-limiting step in MLC phosphorylation being associated with product release from MLCK. The values of the inhibition constants, Ki, were the following: Ac-R-R-K-W-Q-K-T-G-H-A-V-R-A-I-G-R-L-CONH2 (Trp peptide), 8.6 (+/-1. 4 sd) pM; Y4-analogue of Trp peptide (Tyr peptide), 7.3 (+/-0.1) nM; and A-R-R-K-W-Q-K-T-G-H-A-V-R-A-I-G-R-L-S-S (RS20-like peptide), 0. 11-0.39 nM. The Ki values were consistent with kinetically determined Kd values of the peptides to calmodulin. Kinetic determination of Kd values required the use of a fluorescently labeled calmodulin, 2-chloro-(epsilon-amino-Lys75)-[6-(4-N, N-diethylamino-phenyl)-1,3,5-triazin-4-yl]-calmodulin (TA-calmodulin).1 Since, as here, Lys75 is a convenient labeling site on calmodulin for the introduction of fluorescent probes, the biological activity of the Lys-modified calmodulins was evaluated. TA-calmodulin and calmodulin selectively modified by 1-N, N-dimethylaminonaphthalene-5-sulfonyl chloride (dansyl-C1) at Lys75 (dansyl-calmodulin) were characterized as activators of cyclic AMP phosphodiesterase (PDE) and inhibitors of MLCK. The Km value for dansyl-calmodulin was equal to that of calmodulin, and that of TA-calmodulin was 3.5-fold greater. TA-calmodulin and Lys75-labeled dansyl-calmodulin thus distinguish between PDE and MLCK being agonists to the former and antagonists to the latter.

Amino Acid Sequence↗
PubMed1998

High-density immobilization of an antibody fragment to a carboxymethylated dextran-linked biosensor surface.

There are numerous chemical methods published that enable protein coupling to carboxymethyl (CM) dextran. Here we have taken traditional amine coupling using N-hydroxysuccinimide (NHS) and N'-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and coupled an antibody fragment (scFv) to CM dextran at a very high density. Using an upgraded BIAlite from Biacore AB, more than 7000 RU of scFv was coupled to a CM dextran biosensor chip. In addition, scanning electron microscopy was performed on CM dextran biosensor chips following amine coupling of 30 nm gold anti-IgG particles. This showed that amine coupling was uniform across the biosensor chip surface. Calculations show that 7620 RU of an scFv coupled to such a surface results in a mean distance between binding sites of 8.8 nm. This equates to a packing volume of approximately 20% of the available space occupied by the antibody fragment. Comparisons made with densities of covalently coupled IgG show that a greater number of antibody fragment molecules can be coupled per unit area. This is most likely due to the smaller size of an antibody fragment (scFv), which has a volume of less than 20% of an IgG molecule. The significance of these findings is discussed.

Animals↗
PubMed1998

The Trp64Arg mutation of the beta3-adrenergic receptor is associated with hyperglycemia and current body mass index in Jamaican women.

The Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR) has been linked to earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, abdominal obesity, and an increased capacity to gain weight in some European and Japanese populations. We studied the prevalence of the mutation and its association with NIDDM and obesity in our population, in which both rates are high, especially in women. The frequency of the homozygous mutation was 1.53%, and of the Arg allele, 10.5%. Rates were similar in men and women. Significantly higher body mass index (BMI), weight, hip circumference, and fasting and postchallenge 2-hour blood glucose concentrations were associated with the presence of the Arg allele in women but not in men. The association with weight and hip measurements and with hyperglycemia was present only in women aged less than 55 years. In multivariate analysis, the mutation was associated with the BMI and sex in a model that also included age. The variation in fasting and 2-hour blood glucose levels was predicted by beta3-AR, gender, age, and BMI. These results suggest that the presence of the mutation contributes to obesity and hyperglycemia in our female population.

Adult↗
PubMed1998

Gonadal damage from chemotherapy and radiotherapy.

Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men and women. Alkylating agents such as cyclophosphamide and procarbazine are the most common agents implicated. The vast majority of men receiving procarbazine-containing regimens for the treatment of lymphomas become permanently infertile. Cisplatin-based chemotherapy for testicular cancer results in temporary azoospermia in most men, with a recovery of spermatogenesis in about 50% after 2 years and in 80% after 5 years. There is also evidence of Leydig cell impairment in a proportion of these men, although the clinical significance of this is not clear. The germinal epithelium is very sensitive to radiation-induced damage, with changes to spermatogonia occurring following as little as 0.1 Gy and permanent infertility after fractionated doses of 2 Gy and above. Cytotoxic-induced premature ovarian failure is age- and drug-dependent and ensues in approximately half of women treated with procarbazine-containing chemotherapy for lymphomas. High-dose chemotherapy, total body irradiation, and irradiation at an ovarian dose above 6 Gy usually result in permanent ovarian failure. The course of ovarian function after chemotherapy is variable, and late recovery occurs in some patients. Several methods of preserving gonadal function during potentially sterilizing treatment have been considered. Currently, sperm banking remains the only proven method in men, although hormonal manipulation to enhance the recovery of spermatogenesis and cryopreservation of testicular germ cells are possibilities for the future. Transposition of the ovaries to allow better shielding during radiotherapy is of use in some women, and the prospect of cryopreservation and reimplantation of ovarian tissue is promising.

Antineoplastic Agents↗
PubMed1998

An evaluation of whole blood testing for Helicobacter pylori in general practice.

BACKGROUND: Rapid whole blood tests for Helicobacter pylori infection were developed to assist in the management of patients with dyspepsia in general practice. However, they have not been extensively tested in this setting. AIM: To investigate the test characteristics of the BM-Test (Helisal Quick Test) when used in general practice. METHOD: One hundred and ten dyspeptic patients attending local general practitioners were recruited into the study. The BM-Test was administered by the general practitioner at the screening visit according to standard instructions supplied with the test kit. The patient was then referred to Nepean or Mornington Peninsula Hospitals for further assessment. including a 14C-urea breath test. The test kit was forwarded to the appropriate hospital centre for an independent, blinded reading. The sensitivity and specificity of the BM-Test were evaluated against the results of the 14C-UBT. RESULTS: Based on general practitioner readings, the BM-Test had a sensitivity of 59.3% and a specificity of 90.2%. The positive and negative predictive values were 87.5% and 65.7%, respectively. When based on independent readings, sensitivity rose to 71.2% and specificity fell to 88.2%. The BM-Test was more sensitive for older patients than for younger patients when based on both the general practitioner and independent readings. CONCLUSION: The BM-Test performs below the generally recommended sensitivity and specificity of 90% required for clinical practice.

Adult↗
PubMed1998

Improving the specific gravity adjustment method for assessing urinary concentrations of toxic substances.

Changes in urinary flow induce changes in urinary concentrations of toxic substances. The authors modified the conventional specific gravity adjustment method for measuring urinary concentration of toxic substances to compensate for the dilution effects from varying degrees of hydration. The conventional specific gravity adjustment method is a special case to the more general method proposed in this article. The conventional method generally does not correct the urinary concentration to the mean specific gravity of urine. It requires the assumption that a change in urine flow preserves the relative ratio between the mass of the xenobiotic and the mass of total dissolved solids. The derivation of the modified specific gravity adjustment method shows that a change in urine flow does not necessarily preserve this ratio. An experimental slope between urinary flow and urinary specific gravity was linear on a log scale. A ratio was formed between the experimental slope and Araki's "b" slopes for various substances to predict changes in urine concentrations due to changes in the specific gravity of a spot sample. Since excretion rates typically vary for different substances with changes in urinary flow, an appropriately weighted exponential adjustment factor is required for each substance to normalize its concentration to the standard specific gravity of urine.

Adult↗
PubMed1998

Intranasal midazolam for premedication of children undergoing day-case anaesthesia: comparison of two delivery systems with assessment of intra-observer variability.

Midazolam is often used for paediatric premedication. We have compared two methods of administering midazolam intranasally in 44 surgical day-case children allocated randomly to receive midazolam 0.2 mg kg-1 as drops or midazolam 0.1 mg kg-1 from an intranasal spray device. Behaviour was recorded on a four-point scale by the parent, nurse and anaesthetist. Coefficients were obtained representing the change in behaviour score. There was no significant difference in method of administration (coefficient 0.13, P = 0.39). Children were significantly more distressed at the time of premedication and at the time of venous cannulation (coefficients 1.31 and 0.70) than at baseline. There was no significant difference in the assessments between observers. Midazolam by either method was equally effective but acceptability of the premedication was poor in both groups. Intranasal midazolam cannot be recommended as a method for routine premedication of young children.

Administration, Intranasal↗
PubMed1998

The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the Bispectral Index.

UNLABELLED: The Bispectral Index (BIS) correlates well with the level of consciousness with single anesthetic drugs. We studied the effect of the interaction of propofol with alfentanil on propofol concentration and BIS associated with 50% probability of loss of consciousness and lack of recall (Cp50 and BIS50, respectively). We studied 40 consenting volunteers at two institutions who were randomly assigned to receive stepped increases of propofol (10 subjects at each site), propofol plus alfentanil 50 ng/mL (10 subjects at Emory site), or propofol plus alfentanil 100 ng/mL (10 subjects at Duke site) by using a target-controlled infusion device. Measures of sedation, BIS, deltaBIS (absolute change of BIS after a painful stimulus), memory, and drug concentration were obtained at each target drug concentration. The relation among BIS, measured drug concentration, sedation score, and presence or absence of recall was determined by linear and logistic regression for different drug regimens, and the prediction probability (Pk) was calculated. The addition of alfentanil in increasing doses did not significantly affect the BIS50 and propofol Cp50 values for loss of consciousness and lack of recall. DeltaBIS was significantly decreased by both an increase in the concentration of propofol and the presence of alfentanil. The Pk for BIS was >0.93 with all drug regimens, better than those of the target and measured propofol concentrations. We conclude that BIS correlated well with the hypnotic component of anesthesia independent of the presence of an opioid. Moreover, the level of consciousness, and, therefore, the BIS index, is affected by a painful stimulus, and this response is ablated either by opioids or increasing propofol concentration. IMPLICATIONS: In volunteers, the sedation and changes in memory function produced by propofol correlated well with changes in the Bispectral Index. This relationship was not altered by the addition of an analgesic (alfentanil). However, in moderately sedated patients who received a painful stimulus, the Bispectral Index increased, but this response was blocked by the analgesic or increasing propofol concentrations.

Adult↗