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Biomedical subjects

R B Palmer

Publications and source records attributed to R B Palmer.

At least 19 recordsLinked to original sources
PubMed2000

Endotracheal lidocaine administration via an esophageal combitube.

The purpose of this study was to test the hypothesis that lidocaine is systemically absorbed after administration via a Combitube placed in the esophagus, and that therapeutically significant plasma lidocaine concentrations can be attained using this route with standard endotracheal doses (2.0 mg/kg). During general anesthesia, 27 elective surgical patients received 2.0 mg/kg lidocaine (diluted as necessary with 0.9% saline to a minimum total volume of 10 mL) via a Combitube (study group, n = 13) or an endotracheal tube (control group, n = 14). Venous blood samples were drawn for 3 h after lidocaine administration and plasma concentrations determined by gas chromatography using a nitrogen-phosphorus detector (NPD). Overall, average lidocaine concentrations were maximal after 5 min, reaching 0.8+/-0.7 and 1.7+/-0.7 microg/mL in the Combitube and endotracheal tube groups, respectively. Individual patient peak concentrations averaged 1.0+/-0.7 and 2.2+/-1.1 microg/mL in the same two groups, 19+/-16 and 10+/-15 min after lidocaine administration, respectively. No patients reported chest discomfort or dyspnea upon awakening, and no other side effects were noted. In support of the hypothesis, administration of lidocaine via an esophageal Combitube results in systemic drug uptake; however, at conventional endotracheal doses, plasma concentrations are subtherapeutic. It remains to be determined whether higher doses of lidocaine administered via an esophageal Combitube will result in therapeutic plasma concentrations.

Adolescent↗
PubMed2000

Transdermal kinetics of a mercurous chloride beauty cream: an in vitro human skin analysis.

BACKGROUND: Crema de Belleza-Manning is a popular mercurous chloride-containing beauty cream used to smooth and lighten the complexion and treat acne. Hundreds of people in the Southwestern US border states have been identified with elevated (>20 microg/L) urine mercury levels believed to be secondary to using this cream. The kinetic characteristics of percutaneous mercury absorption are incompletely defined. The objective of this study was to determine the transdermal kinetics of two formulations of mercurous chloride from a beauty cream in an in vitro human skin model. METHODS: A proprietary formulation and an aqueous formulation of the beauty cream were studied using modified Franz diffusion cells. Mercury content in the skin samples and the underlying diffusion buffer was determined using atomic absorption spectrophotometry. RESULTS: A rapid initial increase in mercury content both in the skin and the buffer was noted for both formulations. Mercury concentrations in the aqueous samples were significantly (p < 0.05) higher in both the skin and the diffusion buffer compared to parallel samples containing glycerol. CONCLUSIONS: Mercury was readily absorbed through the skin in this in vitro human skin model. The aqueous preparation had a markedly increased rate and extent of mercury absorption relative to the proprietary formulation.

Administration, Cutaneous↗
PubMed2000

Butoxyethanol ingestion with prolonged hyperchloremic metabolic acidosis treated with ethanol therapy.

BACKGROUND: Severe toxic ingestions of butoxyethanol (CAS No. 111-76-2) are rare despite the prevalence of this glycol ether in products such as glass and surface cleaners. Manifestations of acute butoxyethanol toxicity include metabolic acidosis, hemolysis, hepatorenal dysfunction, and coma, but vary widely in reported cases. Furthermore, the optimal therapeutic approach is not yet established. Much of the toxicity of butoxyethanol has been ascribed to its aldehyde and acid metabolites which are similar to those produced by oxidative metabolism of methanol and ethylene glycol. Although the roles of alcohol dehydrogenase inhibition with ethanol or fomepizole and hemodialysis are clear in the case of toxic ingestions of methanol and ethylene glycol, they remain poorly defined for butoxyethanol poisoning. CASE REPORT: We report the case of a 51-year-old female who ingested up to 8 ounces of Sanford Expo White Board Cleaner (butoxyethanol and isopropanol). She developed prolonged hyperchloremic metabolic acidosis and mental status depression and was treated with ethanol therapy but not hemodialysis. This patient recovered without apparent sequelae. The kinetics of butoxyethanol metabolism in this case are described and the potential therapeutic options are discussed.

Acidosis↗
PubMed2000

Simultaneous determination of fenfluramine and phentermine in urine using gas chromatography mass spectrometry with pentafluoropropionic anhydride derivatization.

Fenfluramine and phentermine ('fen-phen') are stimulants used primarily for weight loss that have a causative association with serious health problems. Though voluntarily removed from the market by their manufacturers and the FDA in September of 1997, both drugs occasionally reappear in the clinical and forensic setting from individuals who retained old prescriptions, transported the drugs from foreign countries, or 'stockpiled' the medications immediately before their removal from the market. The authors describe an analytical method for simultaneous detection of fenfluramine, phentermine, and the internal standard, N-propylamphetamine, in urine using pentafluoropropionic anhydride derivatization. Detection using and mass spectrometry is described. Baseline resolution of the analytes was achieved in the presence of four other common sympathomimetic amines. The increased molecular weights, better peak profiles, and characteristic fragments containing portions of both derivatizing agent and parent compound aid in the unambiguous identification of these analytes.

Appetite Depressants↗
PubMed1999

Intraperitoneal erythropoietin in children on peritoneal dialysis: A study of pharmacokinetics and efficacy.

The pharmacokinetics and efficacy of intraperitoneal (IP) recombinant human erythropoietin (rHuEPO) were investigated in children undergoing chronic peritoneal dialysis. Eight children were administered a single dose of 100 U/kg of rHuEPO IP with 50 mL of dialysate into a dry peritoneal cavity after nighttime peritoneal dialysis. Serum erythropoietin (EPO) levels were measured at 0, 8, 12, and 24 hours. A mean peak EPO level of 187 mU/mL was obtained at 12 hours. The area under the curve was 5,818 mU/h/mL, and relative bioavailability was similar to that found using subcutaneous (SC) dosing. Nine children completed 11 to 12 weeks of IP rHuEPO therapy. The patients maintained a normal hematocrit (34% +/- 2.3%) with a mean final IP rHuEPO dosage that was not significantly greater than the mean previous SC dosage (IP, 290 +/- 194 U/kg/wk; SC, 279 +/- 126 U/kg/wk; P = not significant). There appeared to be a trend for a slightly increased risk for peritonitis compared with historical controls at our center (relative risk = 3.1; 95% confidence interval, 0.92 to 6.3). IP rHuEPO is effective in children undergoing continuous cycling peritoneal dialysis without requiring increased rHuEPO dosages, but the possibility of an increased risk for peritonitis will need to be further explored.

Adolescent↗
PubMed1999

Fatal brodifacoum rodenticide poisoning: autopsy and toxicologic findings.

This report details the pathologic and toxicologic findings in the case of a 15-year-old girl who deliberately and fatally ingested brodifacoum, a commonly used rodenticide. The mechanism of death, massive pulmonary hemorrhage, has not been previously reported. Brodifacoum was quantitated in liver, spleen, lung, brain, bile, vitreous humor, heart blood, and femoral blood using HPLC with fluorescence detection. The highest brodifacoum concentrations were detected in bile (4276 ng/mL) and femoral blood (3919 ng/mL). No brodifacoum was detected in brain or vitreous humor. A brodifacoum concentration of 50 ng/g was observed in frozen liver while formalin fixed liver exhibited a concentration of 820 ng/g. A very high blood:liver brodifacoum concentration ratio suggested acute poisoning but the historical and pathologic findings suggested a longer period of anticoagulation. Though most cases of brodifacoum poisoning in humans are non-fatal, this compound can be deadly because of its very long half-life. Forensic pathologists and toxicologists should suspect superwarfarin rodenticides when confronted with cases of unexplained bleeding. Anticoagulant poisoning can mimic fatal leukemia or infectious diseases such as bacterial sepsis, rickettsioses, plague, and leptospirosis. A thorough death scene investigation may provide clues that a person has ingested these substances.

4-Hydroxycoumarins↗
PubMed1998

Endotracheal flumazenil: a new route of administration for benzodiazepine antagonism.

The purpose of this study was to determine if flumazenil is absorbed from broncho-pulmonary tissue after intratracheal administration and whether therapeutically significant plasma concentrations can be obtained. Six elective surgical patients received a dose of 1.0 mg flumazenil in 10 mL saline intratracheally during general anesthesia. Blood samples were drawn for 6 hours after administration and plasma concentrations were determined by gas chromatography-mass spectrometry (GC-MS). An average peak plasma flumazenil concentration of 65.9 +/- 43.1 ng/mL was attained within 1 minute after administration. No patients reported chest discomfort or dyspnea upon awakening and there were no other side effects noted. Administration of flumazenil via an endotracheal tube results in rapid attainment of therapeutic blood levels.

Absorption↗
PubMed1997

(E)- and (Z)-7-arylidenenaltrexones: synthesis and opioid receptor radioligand displacement assays.

The E-isomer of 7-benzylidenenaltrexone (BNTX, la) was reported by Portoghese as a highly selective delta-opioid antagonist. The corresponding Z-isomer 1b was not readily available through direct aldol condensation of naltrexone (6) with benzaldehyde. Using the photochemical methods employed by Lewis to isomerize cinnamamides, we have obtained Z-isomer 1b in good yield from E-isomer 1a. A series of (E)- and (Z)-7-arylidenenaltrexone derivatives was prepared to study the effect of larger arylidene groups on opioid receptor affinity in this series. By aldol condensation of naltrexone (6) with benzaldehyde, 1-naphthaldehyde, 2-naphthaldehyde, 4-phenylbenzaldehyde, and 9-anthracaldehyde, the (E)-arylidenes were readily obtained. Photochemical isomerization afforded the corresponding Z-isomers. These compounds were evaluated via opioid receptor radioligand displacement assays. In these assays, the Z-isomers generally had higher affinity and were more delta-selective than the corresponding E-isomers. The (Z)-7-(1-naphthylidene)naltrexone (3b) showed the greatest selectivity (delta:mu ratio of 15) and highest affinity delta-binding (Ki = 0.7 nM). PM3 semiempirical geometry optimizations suggest a significant role for the orientation of the arylidene substituent in the binding affinity and delta-receptor selectivity. This work demonstrates that larger groups may be incorporated into the arylidene portion of the molecule with opioid receptor affinity being retained.

Animals↗
PubMed1994

Spinal electrical stimulation for intractable angina--long-term clinical outcome and safety.

Spinal cord electrical stimulation is an alternative therapy for patients with chronic pain syndromes including angina. Although it has been shown to produce symptomatic relief and reduce ischaemia, doubts remain about its long-term safety. We report here for the first time the results of a follow-up study over a period of 62 months, mean 45 months (range 21-62), of 23 patients who had stimulator units implanted for intractable angina unresponsive to standard therapy. Symptomatic improvement was good and persisted in the majority with a mean (SD) change of NYHA grade from 3.1 (0.8) pre-operatively to 2.0 (0.9) (P < 0.01) immediately after operation and 2.1 (1.07) at the latest follow-up. GTN consumption fell markedly. Mean (SEM) treadmill exercise time increased from 407 (45) s with the stimulator off to 499 (46) s with the stimulator on (P < 0.01). Forty-eight hour ST segment monitoring in those with bipolar leads showed a reduction of total number and duration of ischaemic episodes. There were three deaths, none of which were sudden or unexplained and this mortality rate is acceptable for such a group of patients. Two patients had a myocardial infarction, which was associated with typical pain and not masked by the treatment. Complications related to earlier lead designs were frequent. This study confirms that spinal electrical stimulation is an effective and safe form of alternative therapy for the occasional patient whose angina is unresponsive to standard therapies.

Angina Pectoris↗
PubMed1992

Epidural spinal electrical stimulation for severe angina: a study of its effects on symptoms, exercise tolerance and degree of ischaemia.

The effectiveness of epidural spinal electrical stimulation has been studied in 14 patients with severe intractable angina unresponsive to standard therapies including bypass grafting. After implantation of the neurostimulator units the patients were assessed by a symptom questionnaire, treadmill exercise testing and right atrial pacing. There was a significant improvement of symptoms and GTN consumption fell markedly. With the neurostimulator on, exercise duration increased from a mean (CI) of 414 (153) to 478 (149) s, and total ST segment depression was less both at maximum exercise (7.1 (4.5) vs 5.6 (4.2) mm) and at 90% of the maximum control heart rate (3.5 (3.7) vs 2.6 (4.3) mm), with similar rate-pressure product at maximum exercise. With right atrial pacing the maximum heart rate reached before onset of angina was increased (143 (14) to 150 (7) b.min-1) and total ST segment depression was less at all heart rates. Benefit has persisted in some patients for over 2 years without any apparent adverse sequelae. Epidural spinal electrical stimulation is, therefore, an alternative therapy for some patients with intractable angina which has not responded to standard therapies.

Angina Pectoris↗
PubMed1990

4-Isoxazolyl-1,4-dihydropyridines: biological, theoretical, and structural studies.

Biological activity was determined for a series of seven isoxazolyldihydropyridines (IDHPs). The highest biological activity was observed for 5-alkyl-3-phenyl-IDHP (1), for which the O-endo conformation at the ring juncture between the heterocyclic rings is known in the solid state. The 3,5-dialkyl-IDHPs were intermediate in overall activity. A theoretical study of rotation about this ring juncture was performed to estimate the relative energy and barrier to rotation for the different conformers as a function of both the ring juncture between the heterocyclic rings and the esters in the 3- and 5-position of the dihydropyridine. Molecular mechanics predicts the minimum energy conformer to be O-exo-ap,ap, while quantum mechanical calculations predict O-exo-sp,sp as the minimum-energy conformer. Both methods indicate that the barrier to rotation about the heterocyclic ring juncture should be relative low, but both methods appear to overestimate the difficulty of ester rotation. A single-crystal X-ray diffractometry study of the (3,5-dimethylisoxazolyl)dihydropyridine 2 was carried out, and shows the O-endo ring juncture and sp,sp ester conformation. 2D NOESY NMR spectroscopy indicates the presence of both conformations about the ring juncture, at room temperature, as evidenced by correlations for both alkyl groups on the isoxazole with the C-2 methyl on the DHP moiety. The ap ester conformer was also evidenced by NOESY, indicating that ester interconversion must take place.

Animals↗
PubMed1980

Relationships between psychological measurements and cerebral organic changes in Alzheimer's disease.

Twenty-two patients were carefully defined as having progressive dementia without other known cause and not complicated by clinical or laboratory evidence of multiinfarct dementia. Their degree of dementia measured by the ESD correlated highly with EEG disturbance (r=-0.79). The LPRS correlated 0.73 with ventricular enlargement. Although the EEG and CT scan only correlated significantly with each other in advanced cases, a combined index of EEG and CT Scan change, (Physical Measures Index) achieved a correlation of 0.93 with a combined index of psychological change (Psychological Measures Index). The results indicate the possiblity of using physical and psychological measures to monitor quantitative change in Alzheimer's Disease, the EEG contributing more initially and the CT scan more in the most advanced cases.

Alzheimer Disease↗