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Biomedical subjects

D Vernon

Publications and source records attributed to D Vernon.

18 recordsLinked to original sources

Viscoelasticity near the gel point: a molecular dynamics study.

We report on extensive molecular dynamics simulations on systems of soft spheres of functionality f, i.e., particles that are capable of bonding irreversibly with a maximum of f other particles. These bonds are randomly distributed throughout the system and imposed with probability p. At a critical concentration of bonds, p(c) approximately 0.2488 for f=6, a gel is formed and the shear viscosity eta diverges according to eta approximately (p(c)-p)(-s). We find s approximately 0.7 in agreement with some experiments and with a recent theoretical prediction based on Rouse dynamics of phantom chains. The diffusion constant decreases as the gel point is approached but does not display a well-defined power law.

Journal Article↗

Branching and annihilating Lévy flights.

We consider a system of particles undergoing the branching and annihilating reactions A-->(m+1)A and A+A-->Ø, with m even. The particles move via long-range Lévy flights, where the probability of moving a distance r decays as r(-d-sigma). We analyze this system of branching and annihilating Lévy flights using field theoretic renormalization group techniques close to the upper critical dimension d(c)=sigma with sigma<2. These results are then compared with Monte Carlo simulations in d=1. For sigma close to unity in d=1, the critical point for the transition from an absorbing to an active phase occurs at zero branching. However, for sigma bigger than about 3/2 in d=1, the critical branching rate moves away from zero with increasing sigma, and the transition lies in a different universality class, inaccessible to controlled perturbative expansions. We measure the exponents in both universality classes and examine their behavior as a function of sigma.

Journal Article↗

Accelerated evolution of functional plastid rRNA and elongation factor genes due to reduced protein synthetic load after the loss of photosynthesis in the chlorophyte alga Polytoma.

Polytoma obtusum and Polytoma uvella are members of a clade of nonphotosynthetic chlorophyte algae closely related to Chlamydomonas humicola and other photosynthetic members of the Chlamydomonadaceae. Descended from a nonphotosynthetic mutant, these obligate heterotrophs retain a plastid (leucoplast) with a functional protein synthetic system, and a plastid genome (lpDNA) with functional genes encoding proteins required for transcription and translation. Comparative studies of the evolution of genes in chloroplasts and leucoplasts can identify modes of selection acting on the plastid genome. Two plastid genes--rrn16, encoding the plastid small-subunit rRNA, and tufA, encoding elongation factor Tu--retain their functions in protein synthesis after the loss of photosynthesis in two nonphotosynthetic Polytoma clades but show a substantially accelerated rate of base substitution in the P. uvella clade. The accelerated evolution of tufA is due, at least partly, to relaxed codon bias favoring codons that can be read without wobble, mainly in three amino acids. Selection for these codons may be relaxed because leucoplasts are required to synthesize fewer protein molecules per unit time than are chloroplasts (reduced protein synthetic load) and thus require a lower rate of synthesis of elongation factor Tu. Relaxed selection due to a lower protein synthetic load is also a plausible explanation for the accelerated rate of evolution of rrn16, but the available data are insufficient to test the hypothesis for this gene. The tufA and rrn16 genes in Polytoma oviforme, the sole member of a second nonphotosynthetic clade, are also functional but show no sign of relaxed selection.

Algal Proteins↗

5-Aminolaevulinic acid methyl ester transport on amino acid carriers in a human colon adenocarcinoma cell line.

The transport mechanisms of 5-aminolevulinic acid methyl ester (5-ALA-ME) have been studied in a human adenocarcinoma cell line (WiDr) by means of 14[C]-labeled 5-ALA-ME. The transport was found to be partly Na+ dependent, while the extracellular Cl- concentration did not affect the uptake. The transport of 5-ALA-ME into WiDr cells was dependent on the incubation temperature and was found to be completely blocked by the inhibitors of energy metabolism, 2-deoxyglucose and sodium azide. WiDr cells were treated with 10 mM of 14 different amino acids and the substrate specificity of the 5-ALA-ME transporter(s) was analyzed by treating the cells with 23 microM or 1 mM 14[C]-labeled 5-ALA-ME. The transport of 5-ALA-ME was found to be inhibited to the highest extent, i.e. about 60%, by the nonpolar amino acids L-alanine, L-methionine, L-tryptophan and glycine. The uptake of 5-ALA-ME followed an exponential decay with increasing concentration of glycine, reaching a maximum inhibition of uptake of 5-ALA-ME of 55%. Sarcosine, a specific inhibitor of system Gly, did not significantly inhibit 5-ALA-ME transport. In contrast to transport of 5-ALA, 5-ALA-ME does not seem to be taken up by system BETA transporters. In conclusion, the cellular uptake of 5-ALA-ME into WiDr cells seems to be due to active transport mechanisms, involving transporters of nonpolar amino acids.

Adenocarcinoma↗

5-Aminolevulinic acid photosensitization of dysplastic Barrett's esophagus: a pharmacokinetic study.

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) may have a role in the treatment of dysplastic Barrett's esophagus. Before ALA-induced PDT can be used clinically, optimum treatment parameters must be established. In this study of 35 patients, the issues of drug dosage, time interval between drug and light delivery and side effects of oral ALA administration are addressed. Spectrofluorometric analysis of tissue samples demonstrates that oral ALA administration induces porphyrin accumulation in esophageal tissues, with maximum levels at 4-6 h. High-performance liquid chromatography confirms the identity of this porphyrin as PpIX, and fluorescence microscopy analysis demonstrates that it preferentially accumulates in the esophageal mucosa, rather than in the underlying stroma. Side effects of ALA administration included malaise, headache, photosensitivity, alopecia, transient derangement of liver function, nausea and vomiting. Fewer side effects and less hepatic toxicity was seen with 30 mg/kg than 50 mg/kg ALA. In conclusion, oral ALA administration induces preferential PpIX accumulation in the esophageal mucosa, with peak PpIX fluorescence noted at 4 h and minimal systemic toxicity at a dose of 30 mg/kg.

Aminolevulinic Acid↗

High-frequency jet ventilation in the pediatric intensive care unit.

Scientific data and anecdote on the utility of HFJV in children remain divergent. There seems to be some evidence that ventilation and oxygenation in critically ill patients can sometimes be achieved at lower peak airway pressures and tidal volumes. There is also growing consensus that HFJV may be a superior ventilatory technique for patients with air leak syndrome. However, conclusive evidence of the effect of this technology on overall survival, length of ventilation, or even resource consumption remains illusive. Until such time, a general recommendation for the use of HFJV in pediatric patients is not possible.

Adolescent↗

Endogenous porphyrin distribution induced by 5-aminolaevulinic acid in the tissue layers of the gastrointestinal tract.

The accumulation of endogenous porphyrins in rats following systemic administration of 5-aminolaevulinic acid (ALA) has been examined to assess the photosensitization characteristics of this technique for photodynamic therapy (PDT) and chemical extraction assays with fluorescence and absorbance detection of the porphyrin content have been carried out. We compared the results obtained using quantitative microfluorimetry on normal gastric and colonic tissues in rats at 0.5, 1, 2, 4 and 6 h and chemically induced duodenal tumours 2 and 4.5 h after intravenous administration of ALA at a dose of 200 mg kg-1. With chemical extraction followed by high performance liquid chromatography analysis, protoporphyrin IX (PpIX) was found to be the predominant porphyrin present, reaching peak levels of several microgrammes per gramme at 2-4 h in each type of tissue; a small amount of coproporphyrin was detected at 0.5 and 2 h in normal gastric mucosa and duodenal tumour respectively. Both the extraction assay and quantitative microfluorimetry showed that the porphyrin fluorescence builds up rapidly in the mucosal layers of the colon and stomach, reaching a maximum at 2 h, whereas lower fluorescence levels were found with a slower rate of accumulation in the corresponding muscularis layers. A significant PpIX content was found in the duodenal tumour, with a maximum of 7.1 micrograms g-1 4.5 h after ALA administration. We conclude that systemic administration of ALA can induce effective tissue sensitization with protoporphyrin IX and appears to be a promising technique for PDT.

Aminolevulinic Acid↗

Biodistribution of a methylene blue derivative in tumor and normal tissues of rats.

By using a chemical extraction procedure and confocal laser scanning fluorescence microscopy we have investigated the kinetic patterns of uptake and biolocalization of a methylene blue derivative (MBD) in tumors and various normal tissues of Wistar rats bearing fibrosarcoma (Leeds ovarian tumor) after intravenous injection of MBD (10 mg kg-1 body weight). Similar kinetics of accumulation and elimination of MBD fluorescence were found in tumor tissue and surrounding normal skin and muscle tissues. However, the tumor:skin and tumor:muscle ratios of the MBD fluorescence intensity were found to be 9 and 4, respectively, 4 h after intravenous injection, indicating selective uptake of MBD by the tumor tissue. MBD was localized on the walls of all the vessels and extensively in the area of neoplastic cellular and tumorigenic fibrous components in the tumor tissue. Interestingly, no MBD fluorescence could be detected in the metastatic neoplastic cells in the remote lymph nodes. In the skin, MBD was mainly distributed in the keratinized epithelium of the epidermis, hair follicles and their accessories, while little was found both in the epidermis and dermis. In most other tissues, the maximal fluorescence intensity of MBD was found 1-4 h after injection, after which it decreased dramatically to almost undetectable levels 120 h postinjection. Strong fluorescence of MBD was seen in the tracheal mucosal epithelium, while little fluorescence was noted in the transitional epithelium of bladder. The kinetics of biolocalization of MBD in some other tissues (liver, spleen, kidney, brain, muscle, lung, heart) were also studied.

Animals↗

Comparison of midazolam with propofol for sedation in outpatient bronchoscopy.

We have compared sedation for fibreoptic bronchoscopy provided by incremental doses of midazolam with that provided by a computer-controlled infusion of propofol. These two methods were compared in terms of operator and patient acceptability, anxiolysis, effects on systolic arterial pressure and oxygen saturation. Tests were made also of memory and motor reactions, before and 60 min after the end of the procedure. Acceptability to operators and patients was high in both groups. There were no significant differences between the groups in systemic arterial pressure or anxiolysis. Oxygen saturation decreased in both groups (propofol group median 83% (range 69-95%); midazolam group median 86% (range 77-95%)) (ns). The median recovery time was 5 min (range 5-10 min) in the propofol group and 10 min (range 5-40 min) in the midazolam group (P < 0.01). Memory and motor reaction times 60 min after the end of the procedure did not differ from baseline in the propofol group, but were significantly impaired in the midazolam group.

Adult↗

A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection.

BACKGROUND: Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. METHODS: We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. RESULTS: Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA: The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95 percent confidence interval, 4.6 to 26; attributable risk, 52 percent). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae. CONCLUSIONS: Cervical intraepithelial neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18.

Adolescent↗

Role of flexible bronchoscopy and bronchoalveolar lavage in the diagnosis of pediatric acquired immunodeficiency syndrome-related pulmonary disease.

Flexible fiberoptic bronchoscopy with bronchoalveolar lavage was performed in 16 pediatric patients with the acquired immunodeficiency syndrome (AIDS) and deterioration in pulmonary function suggestive of opportunistic infection. In 62% of the patients Pneumocystis carinii was identified. Culture results showed a pure growth of Pseudomonas aeruginosa for one patient in addition to the Pneumocystis carinii. Bronchoscopy with lavage was well tolerated, with few complications even among patients with significant tachypnea and hypoxia. Because of its relative safety and effectiveness, this procedure should be considered the first invasive measurement used for evaluation of parenchymal lung disease in this population of patients.

Acquired Immunodeficiency Syndrome↗

The response of a rodent fibrosarcoma to superficial/interstitial photochemotherapy, chemotherapy or radiotherapy.

Growth and dose-response curves were established for a subcutaneously implanted isogenic fibrosarcoma in BD9 rats after treatment with photochemotherapy (PCT), using Photofrin II or polyhaematoporphyrin with superficial or interstitial 630 nm light, cyclophosphamide or gamma-irradiation. Tumour response to PCT increased with dose up to 200 J.cm-2 for superficial light or 200 J for interstitial light but no further response occurred after higher light doses. The maximum response after interstitial treatment was significantly greater than after superficial treatment where only a small margin of normal tissue was treated. The incidence of necrosis in the overlying skin was significantly less after interstitial than superficial light suggesting a better therapeutic ratio after interstitial than superficial PCT. Tumour response increased with the diameter of the treatment field after superficial light supporting the possibility of a tumour bed effect associated with PCT. The largest tumour that could be effectively treated with a single optical fibre was 12 mm. The dose-response curves for interstitial PCT and cyclophosphamide were similar but ionizing irradiation produced increasing tumour response throughout the range of doses used (5 to 30 Gy) and the maximum response was greater after radiotherapy than after PCT or chemotherapy suggesting that in this tumour model interstitial PCT is as effective as cyclophosphamide but less effective than radiotherapy.

Animals↗

Neurone specific enolase (NSE) in small cell lung cancer: a tumour marker of prognostic significance?

Pretreatment serum levels of neurone specific enolase (NSE) were measured in patients with small cell lung cancer (SCLC). Median values were significantly higher in patients with extensive compared with limited stage disease (48 ng ml-1 v. 17 ng ml-1: P less than 0.001). Serial NSE levels paralleled the clinical response to treatment. In 37 patients with limited SCLC, receiving identical chemotherapy, the pretreatment NSE level was of prognostic significance: with an approximate reduction in median survival of 10% for each 5 ng ml-1 incremental rise in NSE (P = 0.004).

Biomarkers, Tumor↗

The epidemiology of pediatric air medical transports in Utah.

OBJECTIVE: To describe the air-transported patients treated at Primary Children's Medical Center (PCMC), the sole pediatric tertiary care center in Utah and a referral center in the intermountain region. This study describes the patients who utilized the air medical transport system, the medical services provided in the prehospital setting, and the corresponding charges for transport and treatment. METHODS: Participants were air-transported patients aged 17 years and less who were treated at PCMC during the calendar years 1991-1992. The study population excluded patients who were transported to other medical facilities, and newborns. Data were abstracted retrospectively from the patients' medical and transport records. Data collected included demographic information, patient diagnoses, and treatments performed during transport. Financial data were supplied by the hospital. RESULTS: During the study period, 874 pediatric patients met the participant criteria. Helicopter and fixed-wing transports comprised 561 and 313, respectively, from nine states in the mountain and western regions. The majority (313, 56%) of the patients transported by helicopter were trauma patients, while the majority (195, 62%) of fixed-wing transports were for illness-related conditions. Scene transports accounted for 120 (21%) of helicopter transports. Children with special health care needs accounted for 171 (20%) of all transports. CONCLUSIONS: Injury severity scores indicate that, overall, air-transported patients were more severely injured than comparable ground-transported patients. However, it is apparent that some patients who were air-transported could have been transported by ground ambulance without detriment. medical services.

Adolescent↗

The health of traveller-Gypsies.

Travellers are not a healthy group. They experience widespread prejudice and discrimination from the settled population. In the sphere of health care, they have poor access to services. This article reviews the prevalent health care needs of this group from the perspective of client factors and service factors.

Attitude to Health↗