Biomedical subjects
Publications and source records attributed to J Hoffman.
A case report of adult type I Gaucher's disease is described, with profound terminal ileal haemorrhage in association with ileal lymphoid hyperplasia. Peroperative ileal endoscopy localized the segment involved allowing an appropriate resection and successful outcome for the patient.
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We studied the pharmacokinetics of methotrexate (MTX) in a 64-year-old man with rheumatoid arthritis. After 6 months of treatment, acute clinical complications arose, requiring emergency laparotomy and cholecystotomy. A biliary tube was inserted, and this allowed for direct analysis of the bile. The pharmacokinetics of 2 separate doses of MTX (orally and intravenously) were assessed (dosage 10 mg/m2). No substantive differences in the pharmacokinetics were found between pre- and post-cholecystotomy MTX treatment, including clearance rates, volumes of distribution, and terminal half-lives. The results, however, demonstrated a change in the bioavailability of the drug (decreasing from 84.7% to 38.9%). Based on extrapolations of the data, with assumed rates of bile flow, the findings also suggest that there is substantial biliary elimination of MTX (8.7-26.0%) and its principal 7-hydroxy metabolite (1.5-4.6%).
A new local anaesthetic, ropivacaine hydrochloride, was used in a concentration of 0.5 per cent in 32 patients receiving a subclavian perivascular block for upper extremity surgery. One group (n = 15) received 0.5 per cent ropivacaine without epinephrine and a second group (n = 17) received 0.5 per cent ropivacaine with epinephrine in a concentration of 1:200,000. Anaesthesia was achieved in 87 per cent of the patients in both groups in all of the C5 through T1 brachial plexus dermatomes. Motor block was profound with 100 per cent of patients in both groups developing paresis at both the shoulder and hand and 100 per cent developing paralysis at the shoulder. There was a rapid initial onset of sensory block (a mean of less than four minutes for analgesia) with a prolonged duration (a mean of greater than 13 hr of analgesia). The addition of epinephrine did not significantly affect the quality or onset of sensory or motor block. The duration of sensory block was reduced by epinephrine at T1 for analgesia and at C7, C8, and T1 for anaesthesia. The duration of sensory block in the remaining brachial plexus dermatomes as well as the duration of motor block was not effected by epinephrine. There was no evidence of cardiovascular or central nervous system toxicity in either group with a mean dose of 2.5-2.6 mg.kg-1 ropivacaine.
The purpose of this study was to determine the pharmacokinetic properties of the local anaesthetic ropivacaine used with or without epinephrine for brachial plexus block. Seventeen ASA physical status I or II adult patients undergoing elective orthopaedic surgery received a single injection of 33 ml ropivacaine for subclavian perivascular block and 5 ml to block the intercostobrachial nerve in the axilla. One group (n = 8) received 0.5 per cent ropivacaine without epinephrine (190 mg) and the other (n = 9) received 0.5 per cent ropivacaine with epinephrine 1:200,000 (190 mg). Plasma ropivacaine concentrations were measured from peripheral venous blood samples taken for 12 hr after drug administration. Ropivacaine base was determined in plasma using gas chromatography and a nitrogen-sensitive detector. The mean peak plasma concentration (Cmax) was 1.6 +/- 0.6 mg.L-1 and 1.3 +/- 0.4 mg.L-1 after administration of ropivacaine with and without epinephrine. The median time to peak plasma concentration (tmax) was 0.75 hr and 0.88 hr and the mean area under the plasma concentration curve AUC0-12h was 7.7 +/- 3.6 and 7.0 +/- 3.4 mg.l hr-1. The differences were not statistically significant. The terminal phase of the individual plasma concentration-time curves showed a varying and sometimes slow decline possibly indicating a sustained systemic uptake of ropivacaine from the brachial plexus. No central nervous system or cardiovascular symptoms attributed to systemic plasma concentrations of the drug were observed, with the dose (1.90-3.28 mg.kg-1) of ropivacaine used. It is concluded that the addition of epinephrine does not alter the pharmacokinetic properties of ropivacaine when used for subclavian perivascular brachial plexus block.
This double-blind, randomized study was designed to compare the effectiveness of intravenous regional sympatholysis using guanethidine, reserpine and normal saline. Twenty-one patients with reflex sympathetic dystrophy of an upper or lower extremity were enrolled and received intravenous regional blockade (IVRB) with one of the three medications. There was significant pain relief in all three groups at 30 min. There were no significant differences among the three groups in the degree of pain relief, the number of patients obtaining pain relief in the 30 min after the block, or the number of patients reporting more than 50% pain relief for more than 24 hr. The saline group's high rate of pain relief could be partially due to a mechanism of tourniquet-induced analgesia.
Nine patients with metastatic cancer who had pain refractory to traditional treatments received a subarachnoid injection of salmon calcitonin. Eight of the nine patients reported pain relief after subarachnoid injection varying from 1 hr to 5 days. Four of the responding patients subsequently received an epidural injection of salmon calcitonin, and two of these patients reported pain relief. Although many patients experienced pain relief, nausea and vomiting appeared to be a significant side effect, occurring in seven out of nine patients.
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Moloney murine sarcoma virus (MoMuSV349) is produced by MuSV349 cells in at least eight-fold excess over the replication-competent helper virus. Less than 48-hours-old Balb/c mice inoculated intraperitoneally with supernatant from MuSV349 cells containing approximately 10(4) MuSV349 infectious units developed clinical symptoms, including severe generalized wasting, 15 to 20 days after inoculation. These infected mice became moribund 35 to 45 days after inoculation. Gross examination of the bodies revealed the presence of cutaneous and subcutaneous 0.2-cm to 1.5-cm macules, plaques, or nodules located predominantly on the ventral abdomen and legs. Nodules also were found in the spleen, liver, ovaries, testes, meninges, nerves, and skin. The nodules were semisoft, cystic, or solid and some expressed variable amounts of blood. Histologic examination of the macules, plaques, and nodules showed spindlelike cells intermingled with tortous, jagged vascular channels lined by plump and normal endothelial cells and unlined slitlike spaces filled with erythrocytes. These angiomatous lesions were infiltrated extensively with neutrophils, lymphocytes, macrophages, and some plasma cells. In some cases the lesions also included foci of densely packed eosinophils. These angiomatous lesions are clearly distinguishable from the fibrosarcomas induced by the myeloproliferative sarcoma virus (MPSV), and resemble the sarcomas induced in mice by Gz-MSV and Balb MSV, the sarcomas induced in rats by MPSV and Ha-MSV, and the acute generalized form of Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS) in humans. Electron microscopy also revealed the presence of numerous extracellular type C virions and virions budding from the plasma membrane of endothelial and spindlelike cells. Erythrophagocytosis by the endothelial and spindlelike cells was demonstrated by light and electron microscopy. The widely disseminated lesions appear to have developed simultaneously as a consequence of viremia rather than metastasis.
Addition of glucose (5-20 mM) to rat adipocytes provoked dose-related increases in diacylglycerol, without increasing production of [3H]inositol phosphates. Cytosolic protein kinase C enzyme activity and immunoreactivity decreased within 1-5 min of 5 mM glucose addition, and further over 20 min. Membrane protein kinase C increased stoichiometrically during the first 5 min and then decreased. Higher concentrations (10 and 20 mM) of glucose provoked greater and more rapid decreases of cytosolic and membrane protein kinase C. Our findings suggest that glucose stimulates diacylglycerol production by providing substrate for phosphatidic acid synthesis de novo, and this is associated with translocative activation of protein kinase C.
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The pharmacokinetics and bioavailability of low-dose methotrexate (MTX) (10 mg/m2) were evaluated in 41 subjects who had definite or classical rheumatoid arthritis as defined by the American Rheumatism Association criteria. Subjects received 10 mg/m2 (to the nearest 2.5 mg) of MTX in a single oral dose and a single intravenous (iv) dose one week apart. Serum concentrations for this low-dose regimen were monitored using a radiochemical ligand binding assay. The results indicate the MTX is cleared from the plasma at a rate of 84.6 mL/min/m2. The terminal half-life was approximately 6 h. The volumes of distribution at steady state and for the central compartment were 22.2 and 13.5 L/m2, respectively. The mean residence time in the body, in the systemic circulation, and in the periphery were estimated to be 4.7, 3.0, and 1.7 h, respectively, with a peripheral single-pass mean transit time of 6.0 h and an intrinsic mean residence time in the periphery of 7.9 h. The mean absorption time was 1.2 h and the oral bioavailability was 0.70. The ratio of synovial fluid concentration to serum concentration 4 and 24 h after a dose was found to be approximately 1.0, indicating that at least within that time range serum and synovial fluid concentrations are approximately equal. Because of conflicting results and insufficient data from previous high-dose pharmacokinetic studies, it is difficult to say whether or not low-dose MTX pharmacokinetics differs from those of high-dose MTX.
This study compared the use of phenol and cryogenic blocks for neurolysis in 28 patients. Patients were assigned randomly to receive peripheral nerve blocks with either phenol or cryoanalgesia. Significantly more patients in the phenol group received 20% or greater relief at 2, 12, and 24 wk than patients in the cryogenic group. Only 27% of patients received significant relief, however, indicating that neurolytic blocks were not particularly effective even though local anesthetic blocks produced significant but temporary pain relief.
Following anaesthesia with enflurane, some patients receiving isoniazid have increased serum concentrations of fluoride ion, presumably because of induction of an isozyme of cytochrome P450 which is responsible for enflurane biodegradation. In rats, isoniazid and ethanol enhance metabolism of enflurane and also induce a form of cytochrome P450 which is homologous with a form of rabbit liver cytochrome P450 known as 3a. Isoniazid, ethanol and imidazole increase the concentration of cytochrome P450 3a in hepatic microsomes. We have pretreated rabbits with imidazole, the most potent of the three inducers of isozyme 3a, to determine if the hepatic microsomal metabolism of enflurane is enhanced and if purified isozyme 3a catalyses the oxidation of enflurane. Imidazole produced a 250% increase in the hepatic microsomal metabolism of enflurane, sevoflurane, methoxyflurane and the control substrate, aniline. Polyclonal antibodies to cytochrome P450 3a inhibited 90% of enflurane metabolism, but only 40% of methoxyflurane biotransformation in the microsomes from imidazole-pretreated rabbits. Thus isozyme 3a or a structurally similar cytochrome P450 seemed to catalyse almost all microsomal metabolism of enflurane. In addition, purified cytochrome P450 3a catalysed the metabolism of enflurane, sevoflurane and methoxyflurane, and the oxidation of these anaesthetics by cytochrome P450 3a was stimulated four-fold by cytochrome b5, a protein which serves as an alternate source of electrons for some cytochrome P450 reactions.
The cold pressor test elicits an emotional/motivational pain experience from the immersion of a limb in cold water. It has been widely used to evaluate (experimental and chronic) pain. However, normative models for quantification and comparison for pain tolerance have not previously been established. This study developed a normative mathematical model for pain tolerance using the cold pressor test with over 600 subjects. Norms for age, sex, and ethnic group were calculated. In addition, chronic pain patients were compared with pain-free patients to determine normative differences in response. The results indicate that at any given age Anglo-Saxon males have the longest tolerance time followed by non-Anglo-Saxon males, Anglo-Saxon females, and finally non-Anglo-Saxon females. There is a consistent decrease in tolerance time as the male age increases and minimal change in tolerance time as the female age increases. Chronic pain patients exhibited the same type of pain response pattern as healthy volunteers when corrected for age, sex, and ethnocultural subgroup.