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Biomedical subjects

P Gardner

Publications and source records attributed to P Gardner.

At least 109 records · Page 6Linked to original sources
PubMed1989

Triggering of T-lymphocytes via either T3-Ti or T11 surface structures opens a voltage-insensitive plasma membrane calcium-permeable channel: requirement for interleukin-2 gene function.

Stimulation of human T-lymphocytes via either the surface T3-Ti antigen-major histocompatibility complex receptor complex or the T11 molecule results in clonal proliferation through a calcium-dependent mechanism. To investigate this signal transduction, plasma membrane calcium-permeable channels were characterized in T-lymphocytes by means of whole cell or single channel patch-clamp recordings. Stimulation of T-lymphocytes via either structure results in opening of an identical set of voltage-insensitive plasma membrane Ca2+-permeable channels through the action of a diffusible second messenger. Previous work with excised inside-out patches suggests that inositol 1,4,5-trisphosphate is the activating second messenger of the voltage-insensitive T-cell Ca2+-permeable channel. Since there is a significant increase in phosphoinositide turnover after stimulation via either the T3-Ti or T11 pathway, it is suggested that triggering of either structure opens a common set of channels through this mechanism. Furthermore, currents flowing through Ca2+-permeable channels are apparently autoregulated, as inward conductance is abolished by elevation of Ca2+ concentration in the bathing solution. In particular, the steady-state rise in interleukin-2 (T-cell growth factor) mRNA is dependent on the rise of [Ca2+]i resulting from ion movement across this channel.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

An educational booklet diminishes anxiety in parents whose children receive total parenteral nutrition.

A major cause of anxiety in parents of hospitalized children is insufficient information about hospital procedures. In an effort to determine the extent to which parental anxiety could be diminished and knowledge and satisfaction enhanced in regard to total parenteral nutrition (TPN), we developed a booklet that describes the mechanics of TPN administration and related procedures. When informal discussions were held between parents and members of the nutritional support team during four alternating periods (every five to six months), parents of first-time recipients of TPN either did not receive the booklet (period 1, n = 20; period 3, n = 30) or received it (period 2, n = 23; period 4, n = 27). Within one week of TPN initiation, parents in both groups completed the Spielberger State-Trait anxiety scale, an attitude questionnaire, and a quiz on TPN. No differences between groups were found in ethnic background, socioeconomic status, severity of illness, age of children, or route of TPN administration. Predisposition to anxiety was also similar between the groups. In contrast, acute situational anxiety was significantly greater in the group with no booklet than in the booklet group. Parents in the no-booklet group demonstrated less comfort in the care of their children and less knowledge about TPN than did the booklet group. Written information provided to parents decreased their anxiety and increased satisfaction with patient care more successfully than did verbal communication. Such a booklet may reduce parentally induced anxiety in the child and facilitate parent-hospital staff interactions.

Anxiety↗
PubMed1989

Modulation of membrane K+ conductance in T-lymphocytes by substance P via a GTP-binding protein.

Modulation of the voltage-gated K+ conductance in T-lymphocytes by substance P was examined. Whole-cell recordings from JurkaT E6-1 human T-lymphocytes revealed two components of substance P action on the outward K+ current: (i) dose- and time-dependent reduction of current peak amplitude; and (ii) acceleration of the current inactivation rate. This action was blocked by substituting Cs+ for K+ in the recording pipette and by the substance P antagonist. [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P. As indicated by conductance-voltage relationship, the reduction in current peak amplitude as a result of substance P application was not due to a shift of the voltage dependence of the channel. Raising intracellular free calcium concentration from 2 to 200 nM reversed the reduction, induced by substance P, in current peak amplitude and disclosed an apparent desensitization towards the neuropeptide action. The treatment, however, did not reverse substance P-induced acceleration of the rate of current decay. Intracellular administration of hydrolysis-resistant guanosine triphosphate (to persistently activate GTP-binding protein) and guanosine diphosphate (to competitively inhibit GTP-binding proteins) analogues mimicked and inhibited substance P-induced reduction of K+ conductance, respectively. The data demonstrate a modulation of T-lymphocyte K+ channels by substance P and substantiate a possible role for GTP-binding proteins in this modulation.

Calcium↗
PubMed1989

The effects of vibratory acoustic stimulation on baseline fetal heart rate in term pregnancy.

Fetal heart rate responses to vibratory acoustic stimulation have been studied in normal and complicated pregnancies. To determine the precise nature of these responses, we studied 50 normal term fetuses with 60 minutes of electronic antepartum fetal heart rate monitoring divided in two 30-minute segments separated by 3 seconds of vibratory acoustic stimulation. All tracings were analyzed by a programmed microcomputer. Comparison of grouped mean 30-minute values before and after vibratory acoustic stimulation showed significant increases in baseline fetal heart rate, fetal heart rate variation, frequency of accelerations exceeding 10 and 15 beats/min, duration of accelerations exceeding 15 beats/min, and frequency of decelerations after vibratory acoustic stimulation. Mean baseline fetal heart rate elevation greater than 10 beats/min occurred within 7.6 +/- 4.4 seconds in 42 of 50 fetuses and lasted for 596 +/- 531 seconds. Reactive tests increased from 35 (70%) to 47 (94%) after vibratory acoustic stimulation. Most healthy term fetuses exhibit fetal heart rate responses after differing in frequency or magnitude from spontaneous fetal heart rate changes. Vibratory acoustic stimulation may be a valid fetal assessment tool but cannot be considered the physiologic equivalent of nonstress testing.

Acoustic Stimulation↗
PubMed1989

The effects of acute alcohol intoxication on biophysical activities: a case report.

A computer-assisted biophysical assessment was performed in a woman with chronic alcoholism at 37 weeks' gestation. She was first seen in a state of acute alcohol intoxication (322 mg/dl). Although fetal breathing movement incidence was normal (30%), fetal tachypnea (67 breaths per minute) and decreased fetal body movements (0.11%) were seen. Because these findings differ from those previously reported with regard to normal pregnancies exposed to lower levels of alcohol, their implications are discussed.

Adult↗
PubMed1989

The structural biology of CD2.

The CD2 molecule is a 50-55KD transmembrane glycoprotein expressed on the vast majority of thymocytes and virtually all peripheral T lymphocytes. Its functions are two-fold: adhesion and activation. CD2 serves to facilitate conjugate formation between the T-lineage cell and its cognate partner via intermolecular interaction of CD2 and LFA-3 on the former and latter cells, respectively. Perturbation of the CD2 extracellular segment by certain combinations of anti-CD2 MAbs or LFA-3 and a single anti-CD2 MAb activate T-lineage function. These CD2-mediated activation events also synergize with signals mediated through the TCR to augment T-cell response. Based on microchemical analysis of immunoaffinity-purified human CD2 and cDNA and genomic cloning of mouse and human molecules, considerable structural information is now available. The mature surface human CD2 molecule consists of 327 amino acids: a 185 aa extracellular segment; a 25 aa hydrophobic transmembrane segment; and a 117 aa cytoplasmic domain rich in prolines and basic residues. The CD2 gene is comprised of five exons which span approximately 12 Kb on chromosome 1. A similar protein structure and gene exon organization is found for the mouse CD2 homologue. The CD2 adhesion domain is approximately 103 aa in length and is encoded by a single exon (exon 2). This domain is resistant to proteolysis, even though it lacks any intrachain disulfides and, like the entire extracellular segment protein expressed in a baculovirus system, binds to its cellular ligand, LFA-3. The latter occurs with a micromolar Kd. This relatively low affinity suggests that multivalent interactions among CD2 monomers on the T cells and individual LFA-3 structures on the cognate partner are important in enhancing the avidity of the T-cell interaction with its target or stimulator cell. The affinity of the CD2 extracellular segment for LFA-3 is not affected by truncations in the CD2 cytoplasmic domain, implying that ligand binding is not regulated by intracellular mechanisms. Given that CD2 mRNA expression and surface CD2 copy number are increased by more than one order of magnitude post-TCR stimulation, it is more likely that adhesion via CD2 is modulated by alteration in surface copy number. Analysis of early transduction events occurring via CD3-Ti (TCR) and CD2 including single channel Ca2+ patch-clamp recordings on living human T lymphocytes indicate a virtual identity of signals.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1989

Monitoring intrauterine pressure during active labor. A prospective comparison of two methods.

Conventional recording of intrapartum uterine activity uses fluid-filled internal catheter systems requiring periodic maintenance. An intrauterine pressure catheter system, the INTRAN, uses an electronic pressure sensor and theoretically could obtain satisfactory uterine recordings with less maintenance. Simultaneous recordings with the INTRAN and standard fluid-filled systems were made in 40 third-trimester patients using comparably calibrated electronic monitoring systems. Comparisons of the recordings from each patient showed similar mean baseline uterine tone, contraction interval and duration. Mean peak uterine pressures were significantly higher with the INTRAN system (63 vs. 56 mm Hg). Coefficients of correlation for contraction interval, duration, peak intrauterine pressure and resting tone were .99, .87, .84 and .34, respectively. Both systems detected abnormal uterine activity equally well. Major technical failures were equally frequent with both systems; however, the fluid-filled catheters required more frequent readjustment.

Adolescent↗
PubMed1988

Single- vs double-lumen central venous catheters in pediatric oncology patients.

Double-lumen central venous catheters (CVCs) have been introduced recently for use in pediatric patients. The objective of our study was to determine if double-lumen CVC usage increased the possibility of infectious and mechanical complications compared with that of traditional single-lumen CVCs in a population at high risk for infection (oncology patients). Thirty pediatric patients (2.5 +/- 3.0 years old; mean +/- SD) who received single-lumen CVCs were compared with 31 patients (5.9 +/- 4.7 years old) who received double-lumen CVCs. The incidence of infectious complications was compared while controlling for potential confounding variables. Fifty-seven percent (17/30) of patients in the single-lumen group experienced bacteremia or cellulitis that required removal of six catheters compared with a rate of 52% (16/31) and nine catheter removals in the double-lumen group. Fewer manipulations occurred in the single-lumen group compared with the double-lumen group, but the incidence of mechanical complications tended to be greater. When managed carefully, double-lumen CVCs were not associated with a greater risk of infection than single-lumen CVCs.

Bacterial Infections↗
PubMed1988

Neutron therapy in cervical cancer: results of a phase III RTOG Study.

Between October 1976 and May 1984, 156 patients with locally advanced cervical cancer were entered into a Phase III trial with the participation of five institutions. Patients were randomly assigned to receive photons only (50 Gy in 25 fractions over 5 weeks plus intracavitary applications or external-beam boost) or mixed-beam radiotherapy (2 fractions a week of neutrons, 3 fractions a week of photons to a total RBE-adjusted dose of 50 Gy over 5 weeks plus intracavitary applications or external mixed-beam boost). Only patients with squamous carcinoma of FIGO Stages IIB, III, or IVA with negative para-aortic nodes on lymphangiogram were eligible. Ten patients were excluded from the analysis because of ineligibility or cancellation. Of the 146 patients analyzed, 80 were treated with mixed-beam radiotherapy and 66 with photons. Patients were grouped by stage and institution. The percentage of patients undergoing intracavitary applications was 50% on mixed beam and 75% on photons (p less than 0.01). Tumor clearance was 52% and 72% for mixed beam and photons, respectively (p less than 0.03). Local control at 2 years was 45% for mixed beam and 52% for photons. Median survivals were 1.9 years on mixed beam and 2.3 years on photons. Severe complications occurred in 19% and 11% in mixed beam and photons respectively (p less than 0.13). The inferior outcome with neutron therapy in this study may have resulted from the use of horizontal neutron beams of varying energy and penetration. A new randomized trial using high-energy hospital-based cyclotrons with gantry-mounted beam-delivery systems has recently been activated to evaluate more rigorously the role of fast-neutron therapy for advanced cervical cancer.

Adult↗
PubMed1988

Thoracic irradiation with or without levamisole (NSC #177023) in unresectable non-small cell carcinoma of the lung: a phase III randomized trial of the RTOG.

A total of 285 patients with medically inoperable (RTOG Stage T1-2, N0-1) or unresectable (RTOG Stage T3, N0-1) non-small cell carcinoma of the lung were randomized by the Radiation Therapy Oncology Group (RTOG) to receive radiation therapy (6000 cGy total dose/6 weeks) plus levamisole (2.5 mg/kg twice weekly for 2 years or until tumor progression) or a placebo. One hundred twenty-nine evaluable patients were assigned to placebo and 131 to levamisole. This report is based on 260 (91%) eligible patients who started treatment and have adequate follow-up. Fifty percent of the patients in both treatment groups had Karnofsky scores of 90-100; 72% had squamous cell carcinoma, 12% adenocarcinoma, and 16% large cell undifferentiated carcinoma; 60% had RTOG Stage I or II primary tumors and 40% had Stage III (T3, N0-1) tumors. Complete regression of tumor was reported in 20% of the patients treated with levamisole and 36% of those receiving placebo. An additional 33% and 19%, respectively, had a partial response (trend test p = 0.08). Median survival was 9 months for patients treated with levamisole and 12 months for those on placebo (two-sided p less than 0.01); at 2 years, patients treated with levamisole had a 15% survival rate as compared to 24% in those receiving placebo. The cumulative proportion failing within the irradiated field with or without other sites of progression at 2 years was 30% in the levamisole group and 34% in the placebo patients. Median progression-free survival was 6 months for patients on levamisole and 7 months for those on placebo (overall two-sided p = 0.014); the estimated proportions progression-free at 2 years were 11% and 18%, respectively. The study showed no significant prolongation of survival, progression-free survival, or differences in patterns of failure in irradiated patients treated with levamisole compared with a placebo. Toxicity related to this immunoadjuvant was, in general, of moderate clinical importance. This study confirms a report by the Southeastern Cancer Study Group concluding that levamisole combined with definitive irradiation has no benefit in the treatment of unresectable non-small cell carcinoma of the lung.

Adenocarcinoma↗
PubMed1988

Dihydropyridine Bay K 8644 activates T lymphocyte calcium-permeable channels.

The effects of the dihydropyridine calcium channel agonist Bay K 8644 on indo-1-loaded Jurkat human leukemia T lymphocytes was assessed by flow cytometry. Bay K 8644 from 10(-9) to 10(-4) M caused a dose-dependent rise in the intracellular free Ca concentration, an effect that was not mimicked by the dihydropyridine Ca antagonist nifedipine. Single channel recordings by the extracellular patch-clamp technique indicated that Bay K 8644 activated an 8-pS, barium-permeable channel that opened as bursts of brief events. The channel appeared to be identical to the previously described voltage-insensitive, messenger-mediated, calcium-permeable channel involved in T cell activation. The predominant effect of Bay K 8644 on these channels was to increase the probability of channel reopening, apparently without a major effect on mean channel open-time. The results suggest that the dihydropyridine Ca agonist Bay K 8644 interacts with both voltage-gated and receptor-operated Ca channels and also suggest potential strategies for development of a new class of immunomodulatory drugs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Infections of mechanical cerebrospinal fluid shunts.

In the United States approximately 16,000 CSF shunt operations are performed annually in the treatment of patients with hydrocephalus. Despite a reduction in the incidence of ventricular shunt infections from previous rates of 15 to 30 percent to rates of 5 to 10 percent in recent years, shunt infections remain the most important complication of the treatment of hydrocephalus and contribute significantly to excess morbidity and mortality. Skin flora organisms such as S. epidermidis, S. aureus, and Proprionibacterium are the most common infecting organisms, and the clustering of approximately 70 percent of infections within the 2-month postoperative period strongly suggests that colonization during shunt placement is an important initiating event. In infections caused by S. epidermidis the production of a glycocalyx slime appears to be an important pathogenetic factor. Clinical manifestations of shunt infections are often non-specific, and fever is the only consistent finding. Therefore, a high index of suspicion and a low threshold for diagnostic evaluation are indicated. Needle aspiration of the shunt reservoir or tubing is the single most reliable diagnostic step and is a procedure remarkably free of complications. The most effective treatment regimen is removal of the infected shunt, treatment with effective systemic antibiotics, and replacement of a new shunt in a new site after evidence of CSF inflammation has subsided. Recent preliminary experience combining systemic antibiotics, local instillation of antibiotics into the shunt reservoir or tubing, and revision of the distal shunt appears to offer hope of an effective alternative therapy without total shunt removal. Comparison of this approach to the previous "gold standard" in a well-designed prospective study is a high priority. In addition, attempts to reduce bacterial colonization of shunts by development of new shunt materials and the evaluation of newer antibiotics such as the quinolones in the prophylaxis and/or therapy of shunt infections should be encouraged.

Anti-Bacterial Agents↗
PubMed1987

Correlation of radiotherapeutic parameters and treatment related morbidity in carcinoma of the prostate--analysis of RTOG study 75-06.

Treatment related morbidity, recorded in patients entered onto a RTOG phase III study (testing the value of periaortic irradiation in locally advanced carcinoma of the prostate), has been correlated with radiotherapeutic parameters to identify and quantify the relationship with treatment volumes, doses, and techniques. Between 1976 and 1983 a total of 526 analyzable cases were entered onto the study. The study design entailed randomization to either pelvic irradiation followed by a prostate boost or pelvic and periaortic irradiation followed by a prostate boost. Periaortic irradiation was not associated with a significantly increased incidence of bowel injuries manifested by diarrhea. No correlation between the total dose to the regional lymphatics (ranging from 4400 to 5100 cGy) and the incidence of bowel and bladder injuries could be established. Doses to the prostate in excess of 7000 cGy have not resulted in a significantly increased incidence of bladder injuries, but have been associated with a significant increase in the incidence of bowel injuries manifested by diarrhea. The techniques of pelvic irradiation did not seem to significantly influence the incidence of bowel or bladder complications. The technique of delivery of the prostatic boost did seem to influence the incidence of bowel injuries. This refers to the lateral boost technique and the perineal boost technique which have been associated with a higher incidence of diarrhea. All of the conclusions based on this analysis are applicable only to treatment volumes and dose ranges used in this study and to conventional fractionation of 180 to 200 cGy per day.

Cystitis↗
PubMed1986

Use of serum prolactin in rats as a determinant in detecting endophyte infected tall fescue seed.

The purpose of this study was to examine the effects of endophyte (Acremonium coenophialium) toxic tall fescue seed on serum prolactin, daily feed intake, and average daily weight gain in male rats. Thirty Sprague-Dawley male rats (218 g) were randomly assigned to treatments of (I) rat chow (50%) plus an endophyte-free tall fescue seed (50%), (II) same as I only restricted feed intake as III, (III) rat chow (50%) plus endophyte infected tall fescue seed (50%) and (IV) rat chow (50%) plus endophyte infected tall fescue seed (25%) plus endophyte free tall fescue seed (25%). Dry matter intake and average daily gain were lower (P less than .05) for rats fed treatment II and III than for those fed treatment I and IV, with treatment IV being lower (P less than .05) than treatment I. Body weights on days 4, 11 and 21 followed the same trend with the rats fed treatment I having higher weights at each weigh period than those on treatments II, III and IV; and those fed treatment IV having higher weights at each period than those on treatment II and III. Baseline concentrations of serum prolactin were similar among treatments. Serum prolactin concentrations were lower (P less than .05) in rats fed treatment III and IV than in those fed treatment II, and those fed treatment I were not different from all others on day 4. On day 11, rats fed treatment I, III and IV had lower (P less than .05) serum prolactin concentrations than those fed treatment II.(ABSTRACT TRUNCATED AT 250 WORDS)

Acremonium↗
PubMed1985

Infections of central nervous system shunts.

Approximately 1 out of every 10 ventricular shunts for hydrocephalus will become infected. This represents a three- to fivefold increase in infection rate compared with other neurosurgical procedures. Most often, the infection results from colonization of the shunt device by normally nonpathogenic skin flora at the time of surgery. Properties of the foreign body itself may contribute to this increased risk of infection, and most infections are clinically apparent within the first 6 months following surgery. Meticulous surgical technique remains one of the most important variables in reducing shunt infection while the role of prophylactic antibiotics is still unclear. When a shunt infection is suspected, percutaneous needle aspiration of the shunt reservoir is most always diagnostic. Fluid specimens should be sent for Gram smear, culture, and susceptibility testing. Appropriate systemic antibiotics should be started. In most instances, the infected patient should be treated by external ventricular drainage and intraventricular antibiotics until the CSF is sterilized. The drain should then be removed and a new shunt placed. Immediate removal of the infected shunt with simultaneous replacement by a new shunt in a different location also has a high cure rate but carries an increased risk of subsequent infection. With few exceptions, antibiotic therapy alone or partial shunt revision will be unsuccessful, and these therapies carry increased morbidity and mortality rates due to prolonged shunt infection. Despite the frequency of shunt surgery and its high rate of infection, a well-organized investigational approach to this problem has been lacking. Both laboratory and clinical investigation needs to explore new shunting techniques, biomaterials, the role of antibiotics, and microbial factors involving host defenses and the shunt apparatus itself.

Anti-Bacterial Agents↗