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Biomedical subjects

W Rich

Publications and source records attributed to W Rich.

At least 19 recordsLinked to original sources
PubMed2005

Evidence of a pharmacogenomic response to interleukin-l receptor antagonist in rheumatoid arthritis.

Biological activity of the IL-1 system depends on the balance between two proinflammatory proteins (IL-1alpha and IL-1beta) and the related anti-inflammatory protein, the IL-1 receptor antagonist (IL-1Ra). The genes for these proteins lie within 430 kb on human chromosome 2. Based on a clinical trial of human recombinant IL-1ra in rheumatoid arthritis, we tested whether IL-1 genotype might be related to the likelihood of response to anti-IL-1 therapy. A positive response was defined as a reduction of at least 50% in the number of swollen joints by week 24, following treatment with either 150 mg/day IL-1ra or placebo. The response rate to treatment, independent of genotype, was 48% (44/91). A highly significant association was found between carriage of the rarer allele at IL1A(+4845) and response to treatment (P=0.0009; OR=4.85 (1.85,12.70)). The response rate in patients carrying this allele was 63.4% compared with 26.3% in noncarriers. A weaker association was found for IL1B(+3954) (P=0.02). There was a highly significant interaction between treatment (150 mg/day or placebo) and the composite genotype across IL1A(+4845) and IL1B(+3954) (P=7.6 x 10(-5)). No associations with IL-1 genotypes were found in patients receiving placebo. Thus, a significant pharmacogenomic effect was found in the treatment of RA patients with recombinant IL-1ra.

Alleles↗
PubMed2001

Comparison of methods of bag and mask ventilation for neonatal resuscitation.

BACKGROUND: There are a variety of manual bagging devices used for neonatal resuscitation. To our knowledge, there has been no comparison of the ability of different operators to utilize such devices for the delivery of predetermined inspiratory and end-expiratory pressures. In addition, the use of prolonged inflation may be of benefit for infants who require bag and mask ventilation, and there has been no evaluation of the ability of a variety of operators to reliably deliver such breaths using currently available equipment. METHODS: We utilized a neonatal manikin (Laerdal Armonk, NY) with a functional larynx and lungs, and a clear cushioned mask (Owens-BriGam, Morganton, NC). We studied a latex-free disposable anesthesia type bag (Model 5126 Vital Signs, Totawa, NJ), a Jackson-Rees (JR) type anesthesia bag (Model E191 Anesthesia Associates, San Marcos, CA) fitted with a Norman elbow and a flow-control tail-piece (Dupaco, Oceanside, CA), and the Neopuff (Fisher and Paykel, Auckland, New Zealand), an FDA approved mechanical device that is flow-controlled and pressure-limited, specifically designed to facilitate neonatal resuscitation. The ventilating pressures were continuously recorded throughout the process. We evaluated neonatal nurses, neonatal nurse practitioners, neonatal staff and fellows, pediatric residents and neonatal respiratory therapists. RESULTS: The peak inspiratory pressure (PIP) was significantly different between operators using either anesthesia bag, P<0.001. Similar results were found for positive end-expiratory pressure (PEEP) with a significant difference among the operator groups, P<0.001. All the differences in post hoc analysis were between the therapists and the other groups, P<0.05. Therapists produced significantly higher pressures than the other groups for both PIP and PEEP (P<0.001). The PIP was similar for all groups using the Neopuff device. The PIP and PEEP delivered by the Neopuff differed from the other two devices independent of the operators (P<0.05). On post hoc analysis, there was a significant difference between the disposable anesthesia bag and Neopuff for both PIP and PEEP for the therapists, whereas among the non-therapists, there was a difference in PIP with the JR device producing a greater PIP (26.6+/-3.8 cmH(2)O) compared with the Neopuff and disposable anesthesia bag (24.8+/-1.1 cmH(2)O, 24.8+/-4.3 cmH(2)O). The level of PEEP was significantly different among all three devices for the non-therapists (1.3+/-1.6 cmH(2)O, Disposable; 2.9+/-1.2 cmH(2)O, JR; 4.7+/-0.5 cmH(2)O, Neopuff; P<0.05). Only the therapists were able to consistently deliver PEEP with the anesthesia bags, whereas all operators could generate the target PEEP with the Neopuff (P<0.05). We compared the pressure delivered during the first second to the pressure delivered during the fifth second during prolonged 5-s inflations. The absolute differences between the first and fifth second for the Neopuff versus the anesthesia bags were significantly different with a median of 7.1 cmH(2)O for the anesthesia bags compared with 0.2 cmH(2)O for the Neopuff, P<0.001, reflecting the difficulty in obtaining and maintaining the target inflation pressures. CONCLUSIONS: Our experience suggests that the Neopuff, a purpose-built neonatal resuscitator ventilator, facilitates the delivery of the desired airway pressures while maximizing the operators ability to obtain and maintain a patent airway, and facilitates the delivery of prolonged inflations. Further research is required to determine the clinical benefit of end-expiratory pressure and prolonged inflations in neonatal resuscitation.

Analysis of Variance↗
PubMed2001

Randomized, prospective study of low-dose versus high-dose inhaled nitric oxide in the neonate with hypoxic respiratory failure.

OBJECTIVE: There is little information on the response to very low doses of inhaled nitric oxide (iNO) in hypoxic near-term infants. The potential toxicities of iNO are dose related; thus, the ability to use lower doses safely and effectively may be advantageous. We hypothesized that there is no difference in the acute improvement in oxygenation between treatment with inhaled nitric oxide at 1 to 2 parts per million (ppm) or 10 to 20 ppm. METHODS: We randomized near-term and term infants with hypoxic respiratory failure with oxygenation indices (OIs) of >/=10 and PaO(2) <100 on 2 separate blood gases taken at least 30 minutes apart. Infants with congenital diaphragmatic hernia were excluded. After parental consent was obtained, patients were randomized to receive a starting nitric oxide (iNO) dose of either 1 to 2 ppm (low-dose group, n = 15) or 10 to 20 ppm (high-dose group, n = 21). The response to iNO was assessed according to the increase in arterial PaO(2) and decrease in OI 30 to 60 minutes after exposure to the initial starting concentration. A response of <10% increase on PaO(2) and a <10% decrease in OI resulted in a doubling of iNO within the dose range protocol (1, 2, 4, and 8 ppm for the low-dose group; 10, 20, 40, and 80 ppm for the high-dose group). RESULTS: Thirty minutes after the study gas was initiated, PaO(2) increased significantly overall in the low-dose (90.7 +/- 41 torr to 166.8 +/- 95.6 torr) and high-dose (76.2 +/- 32.7 torr to 198.7 +/- 142.8 torr) groups; the maximal increase was seen in the infants who initially were treated with 10 ppm. The OI also decreased significantly overall and also was significant in the high-dose group (21.0 +/- 13.7 to 11.4 +/- 10.4; low-dose: 18.3 +/- 7.1 to 13.2 +/- 12.3). There was a nonsignificant fall of PaCO(2) with iNO treatment (low dose 35 +/- 7.3 to 30 +/- 8.5 torr vs high dose 35.2 +/- 9.9 to 32.4 +/- 10.7 torr). A sustained response (ie, maintaining a PaO(2) and OI gain greater than 20% for the duration of the study gas administration) was greater in the high-dose group (53.3% vs 30.0%). In addition, dose increases were required more often in the low-dose group than in the high-dose group (80.0% vs 57.1%). Among patients who did not respond to the initial iNO dose, 100.0% and 83.3% responded at higher doses of iNO for the low- and high-dose groups, respectively. There were no differences for death, need for extracorporeal membrane oxygenation, or other outcomes between the groups. CONCLUSIONS: We did not find any significant difference in response to low- versus high-dose iNO. An initial exposure to low-dose iNO does not compromise the response to higher doses if required and may result in less toxicity.

Administration, Inhalation↗
PubMed2000

Video recording as a means of evaluating neonatal resuscitation performance.

OBJECTIVE: To determine the compliance to Neonatal Resuscitation Program (NRP) guidelines in our institution, by the use of videotaped newborn resuscitations. BACKGROUND: NRP is the standard of care for newborn resuscitation. The application of NRP guidelines and resuscitation skills in actual clinical settings is undocumented. DESIGN/METHODS: A video recorder, mounted to the radiant warmer in the main obstetrical operating room, was used to record all high-risk resuscitations. All members of the resuscitation team were NRP-certified. The videotapes were reviewed within 14 days of the resuscitation and then erased. This ongoing review was approved as a quality assurance (QA) project ensuring confidentiality under California law. The first 100 resuscitations were evaluated to assess NRP compliance. Each step in the resuscitation (positioning, oxygen delivery, ventilation, chest compressions, intubation, and medication) was graded. A score was devised, with 2 points being awarded for every correct decision and proper procedure, 1 point for delayed interventions or inadequate technique, and zero points for indicated procedures that were omitted or for interventions that were not indicated. The total points were divided by the total possible points for that patient. The scores for the first 25 resuscitations (group 1) and the last 25 resuscitations (group 2) were compared. RESULTS: Fifty-four percent of the 100 resuscitations had deviations from the NRP guidelines. Ten percent received overly aggressive stimulation and 22% had poor suction technique. Of the 78 infants given oxygen, this decision was considered incorrect in 15% and the delivery technique was poor in 10% of the infants given oxygen. Of those requiring mask ventilation (n = 18), 24% had poor chest expansion, 11% used an incorrect rate, and 17% had inadequate reevaluation. Twelve infants were intubated; only 7 were successfully intubated on the first attempt and only 4 were intubated in <20 seconds. The longest intubation attempt was 50 seconds. Naloxone was given to 2 patients. One was breathing spontaneously with a heart rate >100. Resuscitations receiving a perfect evaluation score were more likely to occur in infants needing less intervention. The level of resuscitation required for groups 1 and 2 were statistically similar. There was no difference in resuscitation scores between the 2 groups. Only the inappropriate use of deep suctioning improved, with 8 of 25 events in group 1, and 0 of 25 in group 2. CONCLUSIONS: We have found a significant number of deviations from the NRP guidelines. Video recording of actual clinical practice is a useful QA tool for monitoring the conduct of newborn resuscitation. We are now conducting repeat video assessments of individual NRP providers to determine whether there is improved performance.

California↗
PubMed1998

Thoracoabdominal motion in newborns during ventilation delivered by endotracheal tube or nasal prongs.

Preterm infants have asynchronous thoracoabdominal motion (TAM) secondary to a highly compliant chest wall and different lung mechanics compared to term infants. We compared TAM during continuous positive airway pressure (CPAP) administered through an endotracheal tube (ETT-CPAP) or nasal prongs (nasal-CPAP), and during synchronized intermittent mandatory ventilation administered by nasal prongs (nasal-SIMV) in 14 preterm newborn infants. Asynchrony of TAM was quantified by measuring relative motion of chest wall and abdomen with strain gauges and calculating phase angles (theta). Phase angles were lower during nasal-SIMV compared to nasal-CPAP or ETT-CPAP (P < 0.05), and lower during nasal-CPAP compared to ETT-CPAP (P < 0.05). The reduced TAM asynchrony during nasal-SIMV and nasal-CPAP may be due to elimination of resistance of the ETT and/or effective stabilization of the chest wall. These data suggest that nasal-SIMV may be an effective mode of respiratory support for preterm infants requiring minimal ventilatory support.

Abdomen↗
PubMed1998

Effects of different gain settings during assisted mechanical ventilation using respiratory unloading in rabbits.

Compared with conventional modes of patient-initiated mechanical ventilation, respiratory mechanical unloading aims at improving the match between ventilator pressure profiles and the specific derangements in lung mechanics. This may reduce lung barotrauma. The ventilator pressure increases either in proportion to the volume or to the flow of spontaneous breathing (elastic or resistive unloading), thereby selectively decreasing elastic or resistive work of breathing. The clinician sets a gain of increase in pressure per unit of volume or flow. In an attempt to develop criteria for selecting an appropriate gain, we investigated the effects of unloading using increasing gains that either partially compensated or overcompensated lung elastance or resistance. We studied spontaneously breathing, anesthetized, and tracheotomized rabbits. Compared with continuous positive airway pressure, respiratory unloading decreased the electromyographic activity of the diaphragm and increased minute ventilation in normal (n = 5) and surfactant-depleted (n = 6) animals when the gain was partially compensating. Fluctuations in systemic blood pressure associated with breathing decreased. The end-expiratory lung volume remained unchanged. Overcompensation of lung elastic recoil during elastic unloading with an excessive gain caused large tidal volumes associated with a cyclic decrease in blood pressure. Overcompensation of resistance induced oscillations. Complete inhibition of spontaneous breathing occurred with a further increase in gain. We conclude that respiratory unloading with an appropriate gain enhances the effect of diaphragmatic muscle activity on ventilation. A stable breathing pattern ensues whenever a regular spontaneous effort is present. However, excessive gain causes large tidal volumes during elastic unloading or oscillations during resistive unloading.

Animals↗
PubMed1997

Peroperative microbial contamination of anterior chamber aspirates during extracapsular cataract extraction and phacoemulsification.

BACKGROUND: The normal conjunctival flora is one of the main sources of intraocular contamination during cataract surgery. The theory that the positive anterior chamber (AC) pressure during phacoemulsification (phaco), and the smaller wound utilised, might reduce the rate of contamination was studied. METHODS: The peroperative AC aspirates of 210 consecutive patients undergoing cataract surgery were assessed. In group 1, 100 patients underwent a standard extracapsular cataract extraction (ECCE). In group 2, 110 patients underwent phacoemulsification of the crystal-line lens through a scleral tunnel. AC aspirates from the Simcoe irrigation/aspiration cannula (group 1) and phaco probe (group 2) were collected and microbiological studies performed after direct and enrichment cultures. RESULTS: There were 29 (29%) positives in the ECCE group compared with 22 (20%) positive cultures from AC aspirates in the phaco group. Coagulase negative staphylococcus (CNS) was the commonest contaminant in both groups. CONCLUSION: Although there was a higher rate of AC contamination during ECCE, the difference was not statistically significant (p > 0.10, chi 2 = 2.31).

Anterior Chamber↗
PubMed1992

Radioprotection of mice by recombinant rat stem cell factor.

Treatment with recombinant rat stem cell factor (rSCF) protects mice from the lethal effects of irradiation. Mice treated with a single dose of rSCF prior to irradiation of up to 1150 rads [given as a split dose (1 rad = 0.01 Gy)] resulted in > 80% long-term survival, whereas a single injection given after the last dose of irradiation was not radioprotective. The combination of pre- and posttreatment (-20 h, -2 h, and +4 h) with rSCF resulted in 100% survival of otherwise lethally irradiated mice. Using this optimum schedule of rSCF administration, a radioprotective factor of 1.3-1.35 was achieved. The major cause of death in the control animals was massive bacteremia consisting of enteric organisms. The rSCF-treated animals had a much lower frequency of septicemia, due primarily to a rapid hematopoietic recovery of bone marrow function not evident in control animals.

Animals↗
PubMed1982

Advantages and disadvantages of different methods of senile cataract surgery.

Intra and extra capsular cataract surgery are discussed with regard to advantages and problems. Particular consideration is given to modern microsurgical extracapsular technique. Analysis of corneal complications, cystoid macular oedema and retinal detachment suggest that the present evidence does not justify a change to extracapsular technique, other than to give support to a posterior chamber intraocular lens. It is pointed out that for many surgeons, such a change of technique may cause more problems than it prevents.

Aged↗
PubMed1980

Determination of organic acids in biological fluids by ion chromatography: plasma lactate and pyruvate and urinary vanillylmandelic acid.

We describe the general aspects of ion chromatography and how on-line counted ion-exchange techniques can be utilized to determine pyruvic and lactic acids in plasma and vanillymandelic acid in urine. Pyruvate and lactate are extracted from deproteinized plasma by use of an ion-exclusion resin. After elution from the resin, the plasma extract is chromatographed on an anion-exchange column, with 0.66 mmol/L sodium bicarbonate as the mobile phase. The effluent is detected with an electrical conductivity cell. Vanillylmandelic acid is extracted from diluted urine by use of an anion-exchange resin. After elution from resin, the urine extract is chromatographed on an ion-exclusion column, followed by electrochemical detection. We evaluated the procedures for precision, linearity, analytical recovery, intefering substances, and correlation with an established procedure. the combination of a preliminary resin extraction, an ion chromatographic separation, and a conductivity or electrochemical detector results in rapid, specific methods that can be adapted for use in the clinical laboratory. Preliminary data for other organic acids are presented.

Carboxylic Acids↗