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Biomedical subjects

D L Stevens

Publications and source records attributed to D L Stevens.

At least 109 records · Page 6Linked to original sources
PubMed1992

Invasive group A streptococcus infections.

The late 1980s have witnessed the emergence of severe group A streptococcus (GAS) infection; shock, bacteremia, and acute respiratory distress syndrome are common features, and death has been associated with this infection in 30% of patients. Such infections have now been described in all parts of the United States, Europe, and Australia and have occurred predominantly in otherwise healthy adolescents and adults. The characteristic clinical and laboratory features of the streptococcal toxic shock syndrome include deep-seated infection associated with shock and multiorgan failure. Strains of GAS isolated from patients with invasive disease have been predominantly M types 1 and 3, which produce pyrogenic exotoxin A or B or both. In this report, the clinical and demographic features of streptococcal bacteremia, myositis, and necrotizing fasciitis will be presented and compared with those of streptococcal toxic shock syndrome. Current concepts of the pathogenesis of invasive streptococcal infection will also be presented in terms of the interaction between virulence factors of GAS and host defense mechanisms. Finally, new concepts for future treatment of serious streptococcal infections will be proposed.

Bacteremia↗
PubMed1992

Streptococcal toxic shock syndrome: synthesis of tumor necrosis factor and interleukin-1 by monocytes stimulated with pyrogenic exotoxin A and streptolysin O.

Previous studies have found that 80% of strains isolated from patients with the streptococcal toxic shock syndrome produce pyrogenic exotoxin A (SPEA) and 100% produced streptolysin O (SLO). To elucidate the cellular mechanisms contributing to shock, human monocytes were stimulated with SPEA (0.1-10 micrograms/10(6) monocytes) or SLO (0.2-2.5 hemolytic units/10(6) monocytes), and production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta was measured at 24, 48, and 72 h. SPEA and SLO were potent inducers of TNF alpha, with maximum production occurring at 72 h for SPEA and at 48 h for SLO (1067 and 687 pg/ml, respectively). In contrast, IL-1 beta production was greater for SLO than for SPEA (557 vs. 258 pg/ml). In addition, the effects of SPEA and SLO together were synergistic in terms of monocyte IL-1 beta production: SPEA, 193 pg/ml; SLO, 452 pg/ml; SPEA plus SLO, 799 pg/ml. These findings suggest TNF alpha and IL-1 beta are important candidates for mediating shock in severe streptococcal infections.

Bacterial Proteins↗
PubMed1992

Streptococcal pyrogenic exotoxin A and streptolysin O enhance polymorphonuclear leukocyte binding to gelatin matrixes.

Autopsy data from cases of streptococcal toxic shock demonstrate accumulation of polymorphonuclear leukocytes (PMNL) within lung and soft tissue microvasculature. Because of the increased prevalence of streptococcal pyrogenic exotoxin A (SPEA)-producing strains associated with streptococcal toxic shock syndrome, experiments were done to determine whether SPEA or streptolysin O (SLO, a thiol-activated cytolysin produced by all group A streptococci) could stimulate PMNL-dependent adherence mechanisms in vitro. SPEA (0.01-10 micrograms/5.5 x 10(6) PMNL) only modestly enhanced PMNL adherence over the entire range of concentrations tested. In contrast, SLO-induced PMNL binding was highly dose dependent (maximal binding, 55.1 +/- 1.6% at 0.5 hemolytic units/5.5 x 10(6) PMNL) and was mediated by CD11/CD18 adherence glycoprotein.

Antigens, CD↗
PubMed1992

Epidemiologic analysis of group A streptococcal serotypes associated with severe systemic infections, rheumatic fever, or uncomplicated pharyngitis.

More than 1100 group A streptococcal isolates collected in the United States (1988-1990) were examined to document an association of individual serotypes with specific clinical infections during the recent resurgence of group A infections and their sequelae. The most commonly isolated strains from patients with only uncomplicated streptococcal pharyngitis ("control" strains) were M serotypes 1, 2, 4, and 12. M1, M3, and M18 were statistically significantly more frequently isolated from patients with serious invasive infections and M3 and M18 from patients with rheumatic fever compared with the distribution of serotypes from the 866 control strains. An unexpected and important finding indicated that isolation rates of M1 streptococci varied geographically within the United States by year. The propensity for M1 streptococci to be statistically associated with severe systemic infections appeared unrelated to the M1 isolation rates from patients with only uncomplicated pharyngitis, thus offering additional support for the concept of strain-associated virulence rather than virulence broadly related to a given serotype.

Adult↗
PubMed1992

Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice.

The antinociceptive effects of various cannabinoids, alone and in combination with opiates, were evaluated in antinociceptive tests in mice. The cannabinoids tested produce marked antinociceptive effects after i.t. administration to mice. The rank order of potency for the drugs using the tail-flick test was levonantradol greater than CP-55,940 = CP-56,667 greater than 11-hydroxy-delta 9-THC greater than delta 9-THC greater than delta 8-THC; dextronantradol was inactive at a dose of 25 micrograms/mouse. Respective ED50 values in the tail-flick test were 0.4, 12.3, 4.2, 15, 45 and 72 micrograms/mouse. Although pretreatment with morphine somewhat enhanced the effects of delta 9-THC, pretreatment of the mice with naloxone (1 mg/kg s.c. or 1 micrograms/mouse i.t.) failed to block the antinociceptive effects of the cannabinoids, indicating that the cannabinoid-induced antinociception does not occur due to direct interaction with the opiate receptor. Pretreatment of mice with 3.13 micrograms/mouse and 6.25 micrograms/mouse of delta 9-THC shifted the ED50 of morphine to 0.15 and 0.05 micrograms/mouse, respectively (a 4-and a 12-fold shift). The shifts in the dose-response curve of the morphine were parallel. Naloxone administration (1 mg/kg s.c.) completely blocked the antinociceptive effects of the combination of 6.25 micrograms of delta 9-THC with morphine. The AD50 for naloxone blockade of the drug combination was 0.24 (0.06-0.94) mg/kg s.c. and the pA2 was 7.7 (6.7-8.9). The pA2 for naloxone blockade of the dimethylsulfoxide-morphine combination was 6.9 (5.7-8.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1992

A proposed mechanism of action for the antinociceptive effect of intrathecally administered calcium in the mouse.

Administration of i.t. calcium has been shown to produce effects which are opposite to those observed when calcium is injected into the brain. The purpose of this study was to elucidate the mechanism of the antinociceptive action of calcium (i.t.). Injection of calcium (i.t.) produced antinociceptive effects in the tail-flick and p-phenylquinone (PPQ) stretching tests. The ED50 value for calcium (i.t.) in the PPQ test was 4.8 (4.2-5.5) nmol per mouse vs. 344 (251-469) nmol per mouse for calcium (i.t.) in the tail-flick test. The antinociceptive effects of calcium (i.t.) were attenuated significantly in the tail-flick test by pretreatment with naloxone (i.t.) (AD50 value = 200 pmol/mouse) and ICI-174,864 (i.t.) (AD50 value = 20 nmol/mouse), but not by the kappa receptor-selective antagonist nor-BNI. The antinociceptive effects of calcium (i.t.) were attenuated significantly in the PPQ test by pretreatment with naloxone (i.t.) (AD50 value = 50 pmol/mouse) and norbinaltorphimine (i.t.) (AD50 value = 110 pmol/mouse), but not by the delta receptor-selective antagonists naltrindole and ICI-174, 864. Administration of calcium (i.t.) significantly enhanced the antinociceptive effects of mu [D-Ala2,N-Me-Phe4,Gly-ol]enkephalin, delta [D-Pen2,D-Pen5]enkephalin and kappa (U50,488H) opioid receptor-selective peptides. The injection of the dibutyryl derivative of cyclic AMP (i.t.), as well as forskolin (i.t.), blocked the antinociceptive effects of calcium (i.t.) (AD50 values = 39 nmol and 1.7 nmol/mouse, respectively). Injection of apamin (AD50 value = 2.9 pmol/mouse) and charybodotoxin (58 fmol/mouse), blockers of calcium-gated potassium channels, significantly blocked calcium (i.t.). The antinociceptive effects of calcium (i.t.) were also blocked by verapamil (30 and 60 nmol/mouse), theophylline (275 nmol/mouse) and substance P (7.4 nmol/mouse, i.t.). Thus, the data indicate that the mechanism underlying the antinociceptive effect of calcium (i.t.) involves mediation, at least in part, by opioid peptides, alterations in intraneuronal cyclic AMP and/or neuronal hyperpolarization, and decreased release of substance P. The administration of calcium (i.t.) may also enhance the release of adenosine as a significant factor in the antinociceptive effects of the calcium.

Amino Acid Sequence↗
PubMed1991

Molecular analysis of pyrogenic exotoxins from Streptococcus pyogenes isolates associated with toxic shock-like syndrome.

Toxic shock-like syndrome (TSLS) is characterized by hypotension or shock, fever, multiorgan system involvement, and a concurrent group A streptococcal infection. We analyzed 34 streptococcal strains isolated from patients with clinically well-documented TSLS for their pyrogenic toxin profiles and M-protein types. Although strains of nine different M types were represented in the sample, 74% of the isolates were of either M type 1 or 3. It was determined that 53% produced streptococcal pyrogenic exotoxin type A under in vitro growth conditions and that 85% contained the gene encoding this toxin. These values are in contrast to the published value of 15% for the incidence of this gene in a sample of general group A streptococcal isolates. As has been found with all group A streptococci examined to date, regardless of disease association, 100% of TSLS-associated isolates contained the gene encoding pyrogenic exotoxin type B. This toxin was detectably produced by 59% of isolates. The gene encoding pyrogenic toxin type C was found in only 21% of isolates. We conclude that the pyrogenic exotoxin type A gene is associated with group A streptococcal strains isolated from patients with TSLS and may play a causative role in this illness. However, other factors are also likely to be important, since not all strains from patients with TSLS contained the A toxin gene.

Antigens, Bacterial↗
PubMed1990

Thickness measurements on V79-4 cells: a comparison between laser scanning confocal microscopy and electron microscopy.

A quantitative comparison has been carried out between laser scanning confocal microscopy on living cells and standard electron microscope methods on fixed samples. It was estimated from these measurements that there was about 10-20% reduction in thickness in fixed samples of monolayer V79-4 hamster cells. Precise information on the true thickness of living cells, as irradiated, is required for full interpretation of radiobiological data with poorly penetrating radiations, including ultrasoft X-rays. The confocal microscope allows rapid measurements on unperturbed living samples.

Animals↗
PubMed1990

Pulmonary carcinogenesis in rats given implants of shale oil in beeswax pellets.

Pellets of crude shale oil, neutral, basic, or polynuclear aromatic fractions of shale oil, or crude petroleum were implanted in the lungs of rats through a thoracotomy. The pellets had a beeswax-tricaprylin vehicle that allowed the slow release of material into the surrounding parenchyma. A dose-related incidence of lung cancer was observed with each of the materials studies. A greater risk for lung cancer was not demonstrated for crude shale oil compared to crude petroleum.

Animals↗
PubMed1989

Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A.

There is concern that group A streptococci, which have caused less serious infections in developed countries in recent decades, may be acquiring greater virulence. We describe 20 patients from the Rocky Mountain region who had group A streptococcal infections from 1986 to 1988 that were remarkable for the severity of local tissue destruction and life-threatening systemic toxicity. Among the 20 patients (median age, 36), necrotizing fasciitis with or without myositis was the most common soft-tissue infection (55 percent). Nineteen patients (95 percent) had shock, 16 (80 percent) had renal impairment, and 11 (55 percent) had acute respiratory distress syndrome. The mortality rate was 30 percent. All patients but 1 had positive tissue cultures for Streptococcus pyogenes; 12 had positive blood cultures. Most of the patients had no underlying disease; 2 used intravenous drugs. Strains of group A beta-hemolytic streptococci isolated from 10 patients were not of a single M or T type; however, 8 of the 10 strains produced pyrogenic exotoxin A (scarlet fever toxin A, a classic erythrogenic toxin), which has rarely been observed in recent years. From our study of this cluster of severe streptococcal infections with a toxic shock-like syndrome, we conclude that in our region, more virulent group A streptococci have reappeared that produce the pyrogenic toxin A associated with scarlet fever.

Adult↗
PubMed1989

The regulation of platelet-activating factor production in endothelial cells. The role of calcium and protein kinase C.

Endothelial cells (EC) synthesize platelet-activating factor (PAF) when stimulated with agonists that bind to cell-surface receptors. We examined events that link receptor binding to synthesis of PAF by EC. Bovine EC stimulated with agonists that interact with specific cell-surface receptors accumulated PAF only in the presence of extracellular calcium. Hormonal stimulation of EC resulted in Ca2+ entry characteristic of that seen with receptor-operated calcium channels; Indo-1 measurements demonstrated that this inward flux of Ca2+ caused prolonged elevated levels of intracellular Ca2+. EC were exposed to melittin or theta toxin from Clostridium perfringens (pore-forming peptides that increase the permeability of the plasma membrane for small molecules) resulting in an inward flux of Ca2+ and accumulation of PAF. Ca2+ appears to be regulatory for PAF production at the level of phospholipase A2-mediated production of the PAF precursor 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine, as Ca2+ was required for the stimulated hydrolysis of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine. PAF accumulation in EC is also regulated by protein kinase C. Pretreatment of EC with phorbol esters that activate protein kinase C or with dioctanoylglycerol, followed by stimulation, resulted in a 2-fold increase in stimulated PAF production. The regulatory effect of protein kinase C also appears to be at a phospholipase A2-mediated hydrolysis of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine.

Adenine Nucleotides↗
PubMed1989

A case study of the Tenwek hospital community health programme in Kenya.

Tenwek mission hospital, situated in the west-central highlands of Kenya, initiated a community health programme in 1984. This paper describes the major features of the programme and assesses the impact on a number of health and family planning practices after 3 years of implementation. Comparison of the results in the programme areas with the baseline survey and with control areas show significant changes in several indicators. It is concluded that Tenwek hospital demonstrated the impact a hospital can have on health of communities by effectively moving into community-based health care.

Community Health Services↗
PubMed1989

Neurology in Gloucestershire: the clinical workload of an English neurologist.

Attempts to determine the ideal number of consultant neurologists that will be required in the United Kingdom in the future are hampered by a lack of information on a variety of topics, one of which concerns the workload of the average neurologist at the present time. This paper attempts to correct this deficiency by examining the clinical workload of a single handed neurologist practising in the south west of England. Diagnostic information is given on the 3020 new patients seen during 1984-1986 and is compared with similar data on 836 new patients seen in 1975. The pattern of diagnoses on these patients varies little from year to year, indicating a constancy of referral habit of those who seek neurological advice. However, the referral rates for different conditions do not correspond with what would be expected from epidemiological data, for when the incidence of particular conditions in the neurology clinic is compared with the calculated incidence in the community, very wide variations are noted. The implications of these data are discussed and it is suggested that further studies should be performed before detailed predictions are made on how many neurologists will be needed in this country in the future.

Cross-Sectional Studies↗