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Biomedical subjects

D B Smith

Publications and source records attributed to D B Smith.

At least 91 records · Page 5Linked to original sources
PubMed1996

Full-scale studies of factors related to coliform regrowth in drinking water.

An 18-month survey of 31 water systems in North America was conducted to determine the factors that contribute to the occurrence of coliform bacteria in drinking water. The survey included analysis of assimilable organic carbon (AOC), coliforms, disinfectant residuals, and operational parameters. Coliform bacteria were detected in 27.8% of the 2-week sampling periods and were associated with the following factors: filtration, temperature, disinfectant type and disinfectant level, AOC level, corrosion control, and operational characteristics. Four systems in the study that used unfiltered surface water accounted for 26.6% of the total number of bacterial samples collected but 64.3% (1,013 of 1,576) of the positive coliform samples. The occurrence of coliform bacteria was significantly higher when water temperatures were > 15 degrees C. For filtered systems that used free chlorine, 0.97% of 33,196 samples contained coliform bacteria, while 0.51% of 35,159 samples from chloraminated systems contained coliform bacteria. The average density of coliform bacteria was 35 times higher in free-chlorinated systems than in chloraminated water (0.60 CFU/100 ml for free-chlorinated water compared with 0.017 CFU/100 ml for chloraminated water). Systems that maintained dead-end free chlorine levels of < 0.2 mg/liter or monochloramine levels of < 0.5 mg/liter had substantially more coliform occurrences than systems that maintained higher disinfectant residuals. Free-chlorinated systems with AOC levels greater than 100 micrograms/liter had 82% more coliform-positive samples and 19 times higher coliform levels than free-chlorinated systems with average AOC levels less than 99 micrograms/liter. Systems that maintained a phosphate-based corrosion inhibitor and limited the amount of unlined cast iron pipe had fewer coliform bacteria. Several operational characteristics of the treatment process or the distribution system were also associated with increased rates of coliform occurrence. The study concludes that the occurrence of coliform bacteria within a distribution system is dependent upon a complex interaction of chemical, physical, operational, and engineering parameters. No one factor could account for all of the coliform occurrences, and one must consider all of the parameters described above in devising a solution to the regrowth problem.

Data Collection↗
PubMed1996

Interaction between T antigen and TEA domain of the factor TEF-1 derepresses simian virus 40 late promoter in vitro: identification of T-antigen domains important for transcription control.

The large tumor antigen (TAg) of simian virus 40 regulates transcription of the viral genes. The early promoter is repressed when TAg binds to the origin and DNA replication begins, whereas the late promoter is activated by TAg through both replication-dependent and -independent mechanisms. Previously it was shown that activation is diminished when a site in the viral enhancer to which the factor TEF-1 binds is disrupted. We show here that the NH2-terminal region of TAg binds to the TEA domain of TEF-1, a DNA binding domain also found in the Drosophila scalloped and the Saccharomyces cerevisiae TEC1 proteins. The interaction inhibits DNA binding by TEF-1 and activates transcription in vitro from a subset of naturally occurring late start sites. These sites are also activated by mutations in the DNA motifs to which TEF-1 binds. Therefore, TEF-1 appears to function as a repressor of late transcription, and its involvement in the early-to-late shift in viral transcription is discussed. The mutation of Ser-189 in TAg, which reduces transformation efficiency in certain assays, disrupts the interaction with TEF-1. Thus, TEF-1 might also regulate genes involved in growth control.

Animals↗
PubMed1996

Spasticity after stroke. Epidemiology and optimal treatment.

Spasticity following stroke reflects a spectrum of clinical problems including increased muscle tone, abnormal limb posture, excessive contraction of antagonist muscles and hyperactive cutaneous and tendon reflexes. The prevalence of stroke-related disability in stroke survivors is high, and spasticity may be a significant component of this. Management strategies include a multidisciplinary team approach utilising a variety of rehabilitation techniques. Although some interventions are well tolerated and fairly standardised, older adults may be particularly sensitive to drug treatment-related adverse effects. This article reviews some of the commonly employed interventions, such as oral medications, and some of the newer techniques, such as intrathecal baclofen infusion and botulinum toxin injections. The optimal management of spasticity following stroke in older adults requires careful goal setting and skilful combination of treatment modalities in order to produce the best outcome.

Cerebrovascular Disorders↗
PubMed1995

Innovations in acrylic bone cement and application equipment.

A new bone cement was developed with the purpose of reducing the adverse biological effects during cementation of implants. This bone cement is characterized by lower exotherm, low release of monomer, low residual content of monomer, and retained physical properties. The essential innovation was substitution of half of the methylmethacrylate (MMA) in the monomer with long chain, high molecular weight, less volatile, and less soluble methacrylates (n-decylmethacrylate, isobornyl-methacrylate), as well as alteration of the accelerator system to a mix of dihydroxypropyl-p-toluidine and N,N-dimethyl-p-toluidine. The powder contains butylmethacrylate-MMA copolymers. These measures lower the glass-transition temperature, and permit more complete mixing in an integrated package, mixing, and delivery system consisting of a vacuum packed, double chamber pouch. The porosity was reduced to about 2% and the largest voids measured 0.1 mm. The polymerization exotherm was reduced to 58 degrees C. The compressive strength was 82 MPa, the four-point bending strength 55 MPa, the flexural modulus 2.24 GPa, the tensile strength 32 MPa, and the shear strength 36 MPa. The fracture toughness was 0.89 MPa square root of cm. These mechanical properties together with the fatigue life were on level with manually mixed, conventional PMMA bone cements.

Biocompatible Materials↗
PubMed1995

Comparison of intravenous ketorolac and alfentanil as supplements to propofol anesthesia for diagnostic panendoscopy.

STUDY OBJECTIVE: To determine if ketorolac tromethamine is an acceptable alternative to alfentanil as a supplement to propofol for diagnostic panendoscopy. DESIGN: Randomized, double-blind study. SETTING: University medical center. PATIENTS: 40 patients scheduled for panendoscopy and laryngeal tissue biopsy. INTERVENTIONS: Patients were randomly assigned to receive either alfentanil 14.5 micrograms/kg or ketorolac 1.0 mg/kg in a double-blind fashion, 5 to 10 minutes before induction of general anesthesia. MEASUREMENTS AND MAIN RESULTS: Heart rate (HR) and noninvasive blood pressure (BP) were measured and recorded before and immediately after injection of the study drug, after laryngoscopy for the endotracheal tube placement, and after initiation of diagnostic panendoscopy. Bleeding in the operative field was rated by the endoscopist. Observation from discontinuation of the propofol infusion and nitrous oxide inhalation to eye opening, head lifting, and orientation to time and place was observed and recorded. The presence of stridor after extubation, and pulse oximeter-determined arterial blood oxyhemoglobin saturation immediately after extubation and 5 minutes later, were noted. In the recovery room, the ability to tolerate oral fluids, sit, stand, and walk were recorded. Supplementation with ketorolac provides faster recovery from anesthesia as evidenced by shorter time to eye opening, head lifting, and orientation to time and place. However, no intergroup differences were found in measured intraoperative variables (BP and HR following laryngoscopy, tracheal intubation, diagnostic panendoscopy, and tissue biopsy). Operative site bleeding was comparable in both groups. The variables reflecting street readiness and the incidence of nausea and vomiting were statistically comparable. CONCLUSION: Supplementation of propofol anesthesia with ketorolac is an efficacious alternative to supplementation with alfentanil. The faster recovery in the ketorolac group is explained by the mostly peripheral effect of this drug, whereas the slow decline in the alfentanil concentration at the effective site may be responsible for slower emergence from anesthesia.

Alfentanil↗
PubMed1995

Increasing and planned dose intensity of doxorubicin, cyclophosphamide and etoposide (ACE) by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) in the treatment of small cell lung cancer (SCLC). Medical Research Council Lung Cancer Working Party.

The aim of this Phase II study was to test the feasibility of intensifying standard chemotherapy in the treatment of small cell lung cancer (SCLC) by reducing the interval between cycles from 3 to 2 weeks by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) to shorten the duration of neutropenia following each cycle. Thirty-two patients with SCLC were prescribed six cycles of 2-weekly doxorubicin 50 mg/m2 and cyclophosphamide 1 g/m2 on day 1, and etoposide 120 mg/m2 i.v. on days 1, 2 and 3 (ACE), plus filgrastim in a fixed dose of 300 micrograms s.c. on days 4-14 of each cycle. Three patients died during the treatment period and a further nine had chemotherapy terminated before the sixth cycle, all nine because of toxicity. All 32 patients have been followed up for at least 21 months; 14 (44%) were alive at 12 months and the median survival period was 356 days. Of the 127 intervals between cycles of chemotherapy, 74 (58%) were of the prescribed 14 days, 18 (14%) of 15-20 days, 25 (20%) of 21 days, and 10 (8%) were longer. The results were best during the first four cycles, during which 71% of the 83 intervals were of 14 days and a further 10% were less than 21 days. The main reason for delay was haematological toxicity in 37 of the 53 instances. Symptoms of myelosuppression occurred in 23 patients, but at 14 days after a cycle of chemotherapy, all 127 available neutrophil granulocyte counts were normal. Twenty-one patients received blood transfusion and five platelet transfusion. The only adverse effects attributed to filgastrim were episodes of rash, throat swelling, anorexia and shivering, affecting one patient. We conclude that the policy of adding filgrastim allows the dose intensity of ACE chemotherapy to be increased by reducing the intervals between cycles. The findings reinforce those of a parallel study involving lenograstim.

Aged↗
PubMed1995

Variation of the hepatitis C virus 5' non-coding region: implications for secondary structure, virus detection and typing. The International HCV Collaborative Study Group.

Variation in the 5' non-coding region (5'NCR) of hepatitis C virus (HCV) was investigated in detail by comparing 314 5'NCR sequences of viruses of genotypes 1 to 6. Evidence was obtained for the existence of associations between particular 5'NCR sequence motifs and virus types and subtypes. No recombination was observed between the 5'NCR and coding regions of different genotypes, implying that the sequence of subgenomic regions such as the 5'NCR can be used to deduce virus genotype. The distribution of polymorphic sites within the 5'NCR is used to propose improved oligonucleotide primers for virus detection and quantification that would be equally efficient in detecting RNA of different virus genotypes. The accuracy of two different genotyping methods (RFLP and the line probe assay) based on analysis of sequence polymorphisms in the 5'NCR is predicted from the sequences surveyed to be 97% and 83% respectively for types 1 to 6, with higher accuracies for distinguishing between subtypes 1a/1b, 2a/2b or 3a/3b. Several sites of genotype-specific polymorphism were covariant and maintained the base pairings required for a secondary structure model of the 5'NCR. Other sites of variation suggest minor modifications to this model and have implications for the probable functions of the 5'NCR.

Base Composition↗
PubMed1995

Human antibody response to Plasmodium falciparum merozoite surface protein 2 is serogroup specific and predominantly of the immunoglobulin G3 subclass.

MSP2 is a merozoite surface protein of Plasmodium falciparum and, as such, is a potential component of a malaria vaccine. In this study, we have used a panel of recombinant MSP2 antigens in enzyme-linked immunosorbent assays to investigate the recognition of MSP2 by antibodies from malaria-immune human serum. These recombinant antigens include full-length proteins of serogroups A and B and fragments representing the conserved, group-specific, or repeat regions of each serogroup. Ninety-five percent of the serum samples tested contained MSP2-specific antibodies: 81% of serum samples tested responded to serogroup A, and 86% responded to serogroup B. The antibody response is directed almost exclusively towards dimorphic and polymorphic regions of MSP2; the conserved regions are rarely recognized, and antibodies to serogroups A and B do not cross-react. Interestingly, the antibody response is predominately of the cytophilic and complement-fixing subclass immunoglobulin G3.

Amino Acid Sequence↗
PubMed1995

Acute hepatitis C infection after sexual exposure.

A case is described of a woman with acute hepatitis C infection whose partner had chronic hepatitis C infection and where heterosexual contact was the only major risk factor. Infection of both partners was confirmed serologically and by the finding of virus RNA by reverse transcription and polymerase chain reaction amplification. Nucleotide sequence analysis of the NS5 region (RNA polymerase) was used to show that both partners were infected with virus of the same genotype (1a). The nucleotide sequence of virus RNA found in the female patient is closest to variants cocirculating in the male contact, consistent with transmission having occurred between the two.

Acute Disease↗
PubMed1995

Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.

Animals↗
PubMed1995

The uninsured consumer and hospital choice: an assessment of emergency department utilization.

The term "choice" has played an important role in the ongoing debate over health care reform in the United States. One of the major assumptions underlying reform efforts is that affordability drives consumers' choice of health care providers, particularly for the uninsured. In the state of Maryland, the issue of affordability is addressed by an "all-payor" system. In such a scenario, where enhanced choice opportunities are available for the uninsured, such consumers seem to be making choices which lead to the use of hospitals other than those which would be predicted based upon convenience or closeness of location alone.

Community Participation↗
PubMed1995

Hepatitis C virus variants and the role of genotyping.

Hepatitis C virus demonstrates considerable divergence in nucleotide sequence. This variation may affect virus detection, disease outcome, and the effectiveness of interferon treatment. For example, infection with genotype 1 is associated with a lower response rate to interferon treatment. Hepatitis C virus can be classified into six distinct types, comprising at least 74 different subtypes. Both types and subtypes are subject to geographical differences in distribution, presumably reflecting the epidemiological history of the virus. However, because this history may be blurred by migration and by commerce in blood products between regions, screening and typing assays must recognize both the major indigenous and more exotic virus genotypes. Little information exists about the role of virus sequence variation in screening for hepatitis C virus antibodies, but there is some evidence that the reactivity of current serological screening assays for hepatitis C virus is genotype dependent. In the future, screening assays may need to include antigens specific for different virus types or may need to be designed with regard to the particular types found in a certain area. Antigenic variation may also mean that an effective vaccine needs to be multivalent to protect against all genotypes present in a given region. There are several polymerase chain reaction-based methods of distinguishing between hepatitis C virus variants. These methods must be continually updated, however, as new sequence variants are discovered. Alternative genotyping assays are based on the host's serological response to virus infection, but these cannot distinguish between virus subtypes and are unsuitable for immunocompromised patients. As more countries are sampled, it is likely that more genotypes will be identified and this may help elucidate the origins of hepatitis C virus. Detailed epidemiological studies may delineate past and current routes of transmission.

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Combination chemotherapy for primitive neuroectodermal and other malignant brain tumours.

The toxicity and efficacy of a chemotherapy schedule comprising vincristine and cyclophosphamide, alternating with carboplatin and etoposide, has been assessed in a group of 15 patients with medulloblastoma, supratentorial primitive neuroectodermal tumours (PNET) or other malignant brain tumours. The patients comprised four adults and 11 children. Chemotherapy was given for palliation of recurrent disease (six patients), as an adjuvant to radiotherapy and surgery in five poor prognosis patients, or to delay the need for radiotherapy in four children aged 2 years or less. The treatment was generally well tolerated, with the principal toxicity being myelo-suppression. Among the ten assessable patients, there were six complete responders and one partial, an overall response rate of 70%. Three patients had progressive disease. Responses, although associated with good symptomatic improvement, were short lived, with two patients relapsing while still receiving chemotherapy. Three of four very young children relapsed within 7 months of completing chemotherapy and then received radiotherapy. It is concluded that this schedule merits further evaluation and comparison with more protracted and toxic schedules.

Adolescent↗
PubMed1994

Identification of genotypes of hepatitis C virus by sequence comparisons in the core, E1 and NS-5 regions.

Isolates of hepatitis C virus (HCV) show considerable nucleotide sequence variability throughout the genome. Comparisons of complete genome sequences have been used as the basis of classification of HCV into a number of genotypes that show 67 to 77% sequence similarity. In order to investigate whether sequence relationships between genotypes are equivalent in different regions of the genome, we have carried out formal sequence analysis of variants in the 5' non-coding region (5'NCR) and in the genes encoding the core protein, an envelope protein (E1) and a non-structural protein (NS-5). In the E1 region, variants grouped into a series of six major genotypes and a series of subtypes that could be matched to the phylogenetic groupings previously observed for the NS-5 region. Furthermore, core and E1 sequences showed three non-overlapping ranges of sequence similarity corresponding to those between different genotypes, subtypes and isolates previously described in NS-5. Each major genotype could also be reliably identified by sequence comparisons in the well conserved 5'NCR, although many subtypes, such as 1a/1b, 2a/2c and some of those of type 4, could not be reliably distinguished from each other in this region. These data indicate that subgenomic regions such as E1 and NS-5 contain sufficient phylogenetic information for the identification of each of the 11 or 12 known types and subtypes of HCV. No evidence was found for variants of HCV that had sequences of one genotype in the 5'NCR but of a different one in the E1 or NS-5 region. This suggests that recombination between different HCV types is rare or non-existent and does not currently pose a problem in the use of subgenomic regions in classification.

Base Sequence↗
PubMed1994

Differentiation of distribution systems, source water, and clinical coliforms by DNA analysis.

During a 2-week period, Enterobacter cloacae was isolated from throughout the water distribution system in New Haven County, Connecticut. There was no forewarning of this event and no apparent reasons for it. Several epidemiologic and public health questions required rapid answers. Were these E. cloacae isolates the result of treatment failure and breakthrough or was regrowth occurring within the system? Did the E. cloacae isolates represent a health threat and were they causing infection? Pulsed-field gel electrophoresis utilizing whole-cell DNA digestion with restriction endonuclease SpeI permitted the rapid generation of specific information to answer these questions. Gel bands were stained with ethidium bromide and photographed with UV illumination. Homogeneity among isolates was confirmed by repeat digestion with XbaI. From each of the water distribution isolates, a single pattern of restriction endonuclease fragments was generated, indicating that only one clone of E. cloacae was in the distribution system. There was no homogeneity between source and distribution water E. cloacae isolates. Moreover, E. cloacae clinical isolates from patients from New Haven area hospitals showed no identity with E. cloacae isolated from the distribution system. Therefore, pulsed-field gel electrophoresis DNA analysis demonstrated that the E. cloacae from the distribution system was the result of a regrowth bloom within the system and not the result of treatment failure and that this clone was not causing a public health risk.

Bacterial Typing Techniques↗