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Biomedical subjects

R Stevens

Publications and source records attributed to R Stevens.

At least 91 records · Page 5Linked to original sources

Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study.

BACKGROUND: Interleukin-2 is an important regulatory cytokine of the immune system, with potent effects on T cells, B cells, and natural killer cells. In vitro, interleukin-2 can induce the proliferation and differentiation of peripheral-blood mononuclear cells from patients infected with the human immunodeficiency virus (HIV). METHODS: We treated 25 HIV-infected patients with interleukin-2 administered as a continuous infusion at a dosage of 6 to 18 million IU per day for 5 days every 8 weeks during a period of 7 to 25 months. All patients also received at least one approved antiviral agent. Immunologic and virologic variables were monitored monthly. RESULTS: In 6 of 10 patients with base-line CD4 counts higher than 200 per cubic millimeter, interleukin-2 therapy was associated with at least a 50 percent increase in the number of CD4 cells. Changes ranged from -81 to +2211 cells per cubic millimeter. Interleukin-2 therapy resulted in a decline in the percentage of CD8 lymphocytes expressing HLA-DR and an increase in the percentage of CD4 lymphocytes that were positive for the p55 chain of the interleukin-2 receptor. Four patients had a transient but consistent increase in the plasma HIV RNA level at the end of each infusion. In the remaining 15 patients, who had CD4 counts of 200 or fewer cells per cubic millimeter, interleukin-2 therapy was associated with increased viral activation, few immunologic improvements, and substantial toxic effects. CONCLUSIONS: Intermittent courses of interleukin-2 can improve some of the immunologic abnormalities associated with HIV infection in patients with more than 200 CD4 cells per cubic millimeter.

Adult↗

Ability of bacterial endotoxin to diffuse through human dentin.

An in vitro system was developed to determine whether bacterial endotoxin is capable of diffusing through dentin without the use of filtration pressure. Cavities were prepared in five third molar teeth in order to produce a split chamber device consisting of occlusal and pulpal chambers with 0.5 mm of intervening dentin. Endotoxin was introduced into the occlusal chamber and the effluent in the pulpal chamber was sampled every 30 min for 5 h and at 24 h using the limulus lysate assay. In four specimens the initial appearance of endotoxin in the effluent ranged from 15 min to 4 1/2 h. In two specimens the concentration of endotoxin in the effluent leveled off in 4 1/2 and 5 h, respectively, whereas in another two the concentration continued to increase throughout the experiment. In one specimen no endotoxin was detected. The results indicate that endotoxin is capable of passing through 0.5 mm of dentin.

Aggregatibacter actinomycetemcomitans↗

Acrylamide in polyacrylamide gels can modify proteins during electrophoresis.

Many notable discoveries have resulted from the characterization or purification of compounds by electrophoresis. The results reported here show that when polyacrylamide gels are used as the support matrix for electrophoresis, proteins can be modified by reaction with unpolymerized monomers of acrylamide, forming covalent acrylamide adduction products. This was demonstrated by electrophoresis of human and rat hemoglobins and subsequent analysis by electrospray ionization mass spectrometry. The degree of covalent acrylamide binding can be appreciable. The degree of adduction is dependent upon the condition of the gel matrix, the amount of material applied, and the reactivity of the material under investigation.

Acrylamide↗

Effects of chronic systemic administration of 5-HT on food intake and body weight in rats.

The effects of chronic peripheral administration of 5-HT on food intake and body weight was investigated. In normal male Wistar rats, normal female Wistars, obese Zucker males, ovariectomised Wistar females, or normal Wistar males free fed a cafeteria diet, suppression of the creeping weight gain typical of control animals is observed. In females, this effect is not dependent on the local hormonal environment, because intact and ovariectomised females showed similar responses to treatment. One sex difference is that the weight suppressive effect in males is accompanied by an anorectic effect, whereas this anorectic effect is absent in females. Thus, although reduced food intake may partially explain the suppression of weight gain in males, in females it must be due to other, perhaps metabolic, effects. It is possible that these metabolic effects may also occur in males, suggesting one possible explanation of why the effect was typically larger in males than females.

Animals↗

Success rates in producing sympathetic blockade by paratracheal injection.

OBJECTIVE: Cervical paratracheal local anesthetic injections (stellate ganglion blocks) are performed to determine the sympathetic contribution to painful and other conditions of the head, neck, and arm. A block is useful for diagnosis only if the desired physiological effect is confirmed, but the frequency with which sympathetic function is successfully blocked is unclear. The goal of this study is to examine the rates of achieving various endpoints of sympathetic interruption by these injections, using commonly available measures of sympathetic change. DESIGN: Retrospective review. SETTING: Training center. PATIENTS: One hundred unselected consecutive blocks in 40 patients. INTERVENTION: Paratracheal sympathetic block at sixth cervical level. OUTCOME MEASURES: Bilateral hand temperature, ophthalmic changes. RESULTS: Horner's syndrome was successfully produced in 84 blocks and the ipsilateral hand warmed by > or = 1.5 degrees C in 60 blocks. However, the contralateral hand also warmed in 31 blocks so that ipsilateral warming exceeded contralateral warming in only 27 blocks, with diminished success by this criterion when the hand was warm before the block. CONCLUSIONS: We conclude that (a) identifying a Horner's syndrome and ipsilateral warming are not by themselves adequate to confirm selective sympathetic blockade; (b) selective sympathetic blockade of the arm is confirmed only if the temperature increase of the blocked side exceeds that of the contralateral side; and (c) cervical paratracheal blocks frequently fail to produce evidence of sympathetic interruption to the arm. Pathophysiological inferences based on these blocks should be made with caution and only with adequate documentation of physiological evidence of sympathetic blockade.

Anesthesia, Local↗

The effects of gender and birth control pill use on spontaneous blink rates.

BACKGROUND: Two major reference works suggest that men and women blink spontaneously at different rates, but they disagree with regard to which gender blinks faster. METHODS: Spontaneous blink rates of 59 males and 86 females, 44 of whom were taking birth control (BC) pills, were measured for 5 consecutive minutes. Schirmer test results and tear break-up times (TBUTs) were also obtained. RESULTS: Females taking BC pills blinked at a mean rate of 19.6 times per minute, females not taking birth control pills blinked 14.9 times per minute, and males blinked 14.5 times per minute. There were very large differences between blink rates for individuals in each of the groups. No strong associations were found between spontaneous blink rates and a history of contact lens use, tear break-up time, Schirmer test results, temperature or humidity in the examination room, subject age, or menstrual cycle phase. CONCLUSIONS: The 32 percent increase in mean blink rate for females taking BC pills suggests that the pills affect at least one of the mechanisms that control spontaneous blinking, but it is unclear how they accomplish this.

Adult↗

Bone marrow transplantation for thalassaemia: experience of two British centres.

Bone marrow transplantation (BMT) was carried out on 38 patients with thalassaemia major over a period of 9 years; 30 were Asian. In all cases, the donor was an HLA-identical relative. The mean age at transplant was 6.4 years (range 0.5-20 years). Conditioning was busulphan and cyclophosphamide (CY). Cyclosporin (CsA) (n = 30), CsA + methotrexate (n = 6) or CsA + T cell depletion (n = 2) were used for prophylaxis against graft-versus-host disease (GVHD). Thirty-four patients successfully engrafted. Two patients required a second transplant and two achieved mixed chimerism, eventually rejecting their grafts. Nine patients (23.6) developed acute GVHD grade III-IV. Eleven patients (28.9) developed chronic GVHD. There were 11 deaths, 7 within the first 100 days post-BMT. Twenty-seven patients are alive from 156 to 3213 days post-BMT. The actuarial survival at 9 years post-BMT was 70%. The mortality is higher than in previously reported series; possible reasons for this are discussed.

Adolescent↗

The efficacy and safety of ondansetron in the prophylaxis of cancer-chemotherapy induced nausea and vomiting in children.

The management of chemotherapy induced emesis presents a major difficulty in the paediatric population. Ondansetron is a 5-HT3 antagonist and its antiemetic properties have been established in adults receiving chemotherapy. Experience in the treatment of children, however, is limited. There is no standard comparative antiemetic in paediatric practice, so this European, multi-centred study aimed to assess the clinical efficacy and safety of ondansetron in a large cohort of children receiving a range of emetogenic chemotherapy regimens for malignant disease. Two hundred patients were entered into the study, of whom 183 fulfilled entry criteria. Forty per cent (10/25) of patients receiving cisplatin, 68% (27/40) receiving ifosfamide and 70% (83/118) receiving other drugs had less than 3 emetic episodes (vomit or retch) during their worst 24 hours of chemotherapy. The number of days without vomiting or retching during and shortly after receiving chemotherapy was also related to the emetic potential of the agents in the regimen: cisplatin 82/182 (45%), ifosfamide 137/213 (64%) and other agents 430/566 (76%). The control of nausea appeared better than that of emesis in each of the sub-groups analysed. Ondansetron was safe, well tolerated and effective in the prevention of vomiting in children receiving a wide variety of chemotherapy regimens.

Antineoplastic Agents↗

Use of readily available data for identifying local health care needs and resources.

Health departments everywhere are struggling to balance shrinking resources against increasing requests for services. According to the Institute of Medicine report, The Future of Public Health, one of the barriers to solving public health problems is "... disjointed decision-making without necessary data and knowledge ..." (p. 107). Leadership of the Middle Tennessee Region of the Tennessee Department of Health have addressed this issue by developing a practical, usable data base from which to consider the needs and resources of the region.

Data Collection↗

Maximizing the utilization and impact of medical educational software by designing for local area network (LAN) implementation.

The design, development and implementation of medical education software often occurs without sufficient consideration of the potential benefits that can be realized by making the software network aware. These benefits can be considerable and can greatly enhance the utilization and potential impact of the software. This article details how multiple aspects of the IMMEX problem solving project have benefited from taking maximum advantage of LAN resources.

California↗

Sources of genotoxicity and cancer risk in ambient air.

Products of incomplete combustion are identified as a major source of carcinogenic risk in urban areas, especially those from small non-industrial sources. The major ubiquitous emission sources outdoors in populated areas are residential home heating and motor vehicles. Indoors the major combustion source is environmental tobacco smoke. Polycyclic organic matter adsorbed onto the particles emitted from incomplete combustion are estimated to make the largest contribution to human genotoxic and cancer risk. Mutagenic emission factors combined with dispersion modelling indicated that automobiles and heating sources were major sources of mutagens. Ambient air studies to apportion the sources of mutagens in non-industrial areas confirmed this prediction. To apportion and estimate the cancer risk of ambient organic matter from particles in vivo animal tumour data, receptor modelling and human exposure data were combined. Tumourigenicity studies of the source apportioned ambient organic matter provided the relative tumour potencies of two ambient samples of different source composition. The human cancer unit risks were developed based on the comparative potency method using tumour data from these ambient samples. Residential wood combustion accounted for 75% of the exposure to particle associated organics, but only 20% of the estimated cancer risk. The remaining 80% of the risk appears to be associated with the mobile source component and atmospheric transformation products from these source emissions.

Air Pollutants↗

Blood spot screening and confirmatory tests for syphilis antibody.

We developed a blood spot test for syphilis antibody using enzyme-linked immunosorbent assay (ELISA) technology. Dried blood was eluted by buffered saline or, for a supplementary confirmatory test, by treponemal-antibody test diluent. Eluates were diluted in an absorption buffer (Calypte Biomedical, Berkeley, Calif.) and added to plate wells coated with cardiolipin antigen (ADI Diagnostics, Toronto, Ontario, Canada). The wells were washed and treated sequentially with an immunoglobulin G conjugate, buffer washes, and enzyme substrate. Substrate conversion was measured photometrically, and specimen reactivity was determined by reference to nonreactive controls. The optimum test protocol was established by tests of serum and plasma. The serum ELISA specificity with normal specimens was 98.9%. The sensitivity with sera from patients with undefined syphilis was 97.4%, that with sera from patients with documented primary and secondary disease was 100%, and that with sera from patients with early and late latent disease was 95.7%. The specificity of the spot test with donor blood was 94.2%, and its specificity with newborn blood was 94.9%. The sensitivity with 25 spots spiked with reactive sera was 96%. The seroprevalence rates for parturient women in one hospital were 6.01% according to spot tests of sera from 599 newborns and 6.81% according to Rapid Plasma Reagin tests of 499 maternal serum specimens. Seventy percent of infants born to 50 seropositive women were reactive by either the newborn spot or the Rapid Plasma Reagin serum test. The results show that blood spots may be used in seroprevalence or serodiagnostic studies, especially to identify women who are infected or to identify possible cases of congenital infection. The test provides for studies of children and adults when routine venipuncture and serum handling and storage are problematic.

Antibodies, Bacterial↗

Identification of an early-growth-response gene encoding a novel putative protein kinase.

Early-growth-response genes, also known as immediate-early genes, play important roles in regulating cell proliferation. We have identified a new type of early-growth-response gene product, a 77,811-Da putative serine/threonine kinase, which is highly inducible by serum and phorbol ester. mRNA encoding this putative kinase is markedly elevated within 1 h after treatment with mitogen, and this induction is synergistically increased by cycloheximide. Dexamethasone blocks serum induction of the kinase mRNA, as does transformation by v-Ki-ras. The kinase mRNA was detected in mouse brain, lung, and heart. This new putative kinase, which we term Snk, for serum-inducible kinase, showed similarity in its proposed catalytic domain to many other protein kinases; however, no other kinase showed enough sequence similarity with Snk to suggest the existence of a common function. Hence, Snk represents a new type of protein kinase involved in the early mitogenic response whose activity is transcriptionally and posttranscriptionally regulated.

3T3 Cells↗