THE USE OF RADIOFREQUENCY NEUROABLATION IN THE TREATMENT OF OMALGIA IN PATIENTS WITH SHOULDER JOINT ARTHROSIS.

The aim of the study was to evaluate the effectiveness of radiofrequency denervation (neuroablation) of the suprascapular nerve in the treatment process of omalgia in patients with degenerative and dystrophic disorders of the shoulder joint. 31 patients (31 joints were researched) took the treatment and analyzed their data in the rehabilitation department of the State Institution "Institute of Traumatology and Orthopedics of the National Academy of Medical Sciences of Ukraine" from 2019 to 2021. X-ray assessment was performed to find out the stage of the disease according to the classification of M. Lequesne Kellgren and J. Lawrence. All patients had radiofrequency neuroablation of the suprascapular nerve. Patients were assessed before the RFN procedure, after 1, 3, 6, and 12 months after the procedure. Due to performed treatment, the average VAS score for pain was 7,65±1,23 cm. A decrease in pain level by 3 cm or more was considered reliable. 1 month after suprascapular nerve RFN we had a significant decrease in pain syndrome according to VAS in the group of patients within 3,87±1,06 cm (p<0,05); after 3 months a stable positive remained at the 3,1±1,42 cm; after 6 months began to gradually deteriorate to 5,52±1,24 cm and remained after 12 months at the 5,2±1,58 cm. Thus, the suprascapular nerve RFN procedure allows for maintaining a stable positive result for 6 months with subsequent deterioration. After 12 months abandoned the use of NSAIDs - 29,03% of patients and continued to additionally use NSAIDs for pain relief sometimes or constantly almost 64,52% of the group examined. The results of our studies complement those of Taverner et al., Eyigor et al., indicating a trend toward a decrease in pain and functional limitations among patients with omalgia after the RFN procedure, and the preservation of the effect during the follow-up year after the procedure. The suprascapular nerve RFN procedure makes it possible to reduce the level of pain syndrome and refuse the use of painkillers in patients with shoulder joint arthrosis in almost 30-40% of cases, and the effect of pain relief lasts from 6 to 12 months in most cases.

Lymphocyte transformation induced by autologous cells. V. Generation of immunologic memory and specificity during the autologous mixed lymphocyte reaction.

Lymphocyte proliferation in vitro may follow antigen recognition and serve as a correlate of cell-mediated immunity. Lymphocyte proliferation can also be simulated by nonimmune mechanisms as, for example, following culture with plant lectin, lipopolysaccharides, or staphylococcal protein A (1). The autologous mixed lymphocyte reaction (MLR) refers to the proliferation of T lymphocytes cultured with autologous mon-T lymphocytes (2,3). The purpose of this study was to determine whether lymphocyte proliferation in the autologous MLR results from immune or nonimmune mechanisms. We have shown that the autologous MLR has two classical attributes of an immune phenomenon: memory and specificity.

Immunological studies of aging. Decreased production of and response to T cell growth factor by lymphocytes from aged humans.

Human lymphocytes from elderly and young donors were cultured with phytohemagglutinin (PHA) or concanavalin A. Cultures from old donors produced less T cell growth factor (TCGF) and incorporated less tritiated thymidine (3H-Tdr) than did similar cultures from young donors in the presence of either mitogen. Furthermore, the response of lymphocytes from elderly donors to TCGF was impaired. Thus, PHA-activated T cells from aged donors showed no increase tritiated thymidine incorporation when incubated with exogenous human TCGF. In contrast, addition of exogenous human TCGF to PHA-activated peripheral blood leukocytes from younger individuals increased tritiated thymidine incorporation by 30-50%. The impaired response to TCGF was associated with decreased binding of TCGF by PHA-activated cells from old donors. TCGF production or responsiveness was not associated with the presence of "suppressor" activity in elderly T cell preparations. These studies suggest a possible molecular mechanism for the impaired proliferative response of elderly human T cells. These data lend support to the hypothesis that defects in the capacity to either produce or respond to TCGF may be a fundamental cause of immune deficiency.

Reduced expression and capacity of the striatal high-affinity choline transporter in hyperdopaminergic mice.

Behavioral and neuronal abnormalities observed in mice exhibiting a reduced expression of the dopamine transporter model important aspects of schizophrenia, addiction, and attentional disorders. As the consequences of a chronic hyperdopaminergic tone for striatal output regulation have remained poorly understood, the present experiments were designed to determine the status of striatal interneuronal cholinergic neurotransmission in dopamine transporter knockdown animals. The high-affinity choline transporter represents the rate-limiting step of acetylcholine synthesis and release. Compared with wild type mice, striatal high-affinity choline transporter expression in dopamine transporter knockdown mice was significantly decreased. As in vivo basal striatal acetylcholine release did not differ between the strains, reduced high-affinity choline transporter expression in dopamine transporter knockdown mice was not due to reduced basal cholinergic activity. Furthermore, the proportion of high-affinity choline transporters expressed in plasma membrane-enriched versus vesicular membrane-enriched fractions did not differ from wild type animals, suggesting that changes in intracellular high-affinity choline transporter trafficking were not associated with lower overall levels of striatal high-affinity choline transporters. Synaptosomal choline uptake assays indicated a reduced capacity of striatal high-affinity choline transporters in dopamine transporter knockdown mice, and thus the functional significance of the reduced level of high-affinity choline transporter expression. Likewise, in vivo measures of the capacity of striatal high-affinity choline transporters to clear increases in extracellular choline concentrations, using choline-sensitive microelectrodes, revealed a 37-41% reduction in hemicholinium-sensitive clearance of exogenous choline in dopamine transporter knockdown mice. Furthermore, clearance of potassium-evoked choline signals was reduced in dopamine transporter knockdown mice (1.63+/-0.15 microM/s) compared with wild type animals (2.29+/-0.21 microM/s). Dysregulated striatal cholinergic neurotransmission is hypothesized to disrupt the integration of thalamic and cortical information at spiny projection neurons and thus to contribute to abnormal striatal information processing in dopamine transporter knockdown mice.

Radioimmunotherapy of nude mice bearing a human interleukin 2 receptor alpha-expressing lymphoma utilizing the alpha-emitting radionuclide-conjugated monoclonal antibody 212Bi-anti-Tac.

The efficacy, specificity, and toxicity of bismuth (212Bi) alpha particle-mediated radioimmunotherapy was evaluated in nude mice bearing a murine lymphoma transfected with the human CD25 [human Tac; interleukin 2 receptor alpha (IL-2R alpha)] gene. The therapeutic agent used was the tumor-specific humanized monoclonal antibody anti-Tac conjugated to 212Bi. The human IL-2R alpha-expressing cell line was produced by transfecting the gene encoding human Tac into the murine plasmacytoma cell line SP2/0. The resulting cell line, SP2/Tac, expressed approximately 18,000 human IL-2R alpha molecules/cell. Following s.c. or i.p. injection of 2 x 10(6) SP2/Tac cells into nude mice, rapidly growing tumors developed in all animals after a mean of 10 and 13 days, respectively. The bifunctional chelate cyclohexyldiethylenetriaminepentaacetic acid was used to couple 212Bi to the humanized anti-Tac monoclonal antibody. This immunoconjugate was shown to be stable in vivo. Specifically, in pharmacokinetic studies in nude mice, the blood clearance patterns of i.v. administered 205/206Bi-anti-Tac and coinjected 125I-anti-Tac were comparable. The toxicity and therapeutic efficacy of 212Bi-anti-Tac were evaluated in nude mouse ascites or solid tumor models wherein SP2/Tac cells were administered either i.p. or s.c., respectively. The i.p. administration of 212Bi-anti-Tac, 3 days following i.p. tumor inoculation, led to a dose-dependent, significant prolongation of tumor-free survival. Doses of 150 or 200 microCi prevented tumor occurrence in 75% (95% confidence interval, 41-93%) of the animals. In the second model, i.v. treatment with 212Bi-anti-Tac 3 days following s.c. tumor inoculation also resulted in a prolongation of the period before tumor development. However, prevention of tumor occurrence decreased to 30% (95% confidence interval, 11-60%). In both the i.p. and s.c. tumor trials, 212Bi-anti-Tac was significantly more effective for i.p. (P2 = 0.0128 50/100 microCi 212Bi-anti-Tac versus 50/100 microCi Mik beta; P2 = 0.0142 150/200 microCi anti-Tac versus 150/200 microCi Mik beta) and for s.c. tumors (P2 = 0.0018 100 microCi anti-Tac versus 100 microCi Mik beta; P2 = 0.0042 200 microCi anti-Tac versus 200 microCi Mik beta 1) than the control antibody Mik beta 1 coupled to 212Bi at comparable dose levels. In contrast to the efficacy observed in the adjuvant setting, therapy of large, established s.c. SP-2/Tac-expressing tumors with i.v. administered 212Bi-anti-Tac (at doses up to 200 microCi/animal) failed to induce tumor regression.(ABSTRACT TRUNCATED AT 400 WORDS)

Nature of the bifunctional chelating agent used for radioimmunotherapy with yttrium-90 monoclonal antibodies: critical factors in determining in vivo survival and organ toxicity.

One factor that is critical to the potential effectiveness of radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. Stability in vivo depends on the condition that both the chelate linkage and radiolabeling procedures not alter antibody specificity and biodistribution. In addition, synthesis and selection of the chelating agent is critical for each radiometal in order to prevent inappropriate release of the radiometal in vivo. In the present study, we compare the in vivo stability of seven radioimmunoconjugates that use different polyaminocarboxylate chelating agents to complex yttrium-88 to the mouse anti-human interleukin-2 receptor monoclonal antibody, anti-Tac. Chelate linkage and radiolabeling procedures did not alter the immunospecificity of anti-Tac. In order to assess whether yttrium was inappropriately released from the chelate-coupled antibody in vivo, iodine-131-labeled and yttrium-88 chelate-coupled antibodies were simultaneously administered to the same animals to correlate the decline in yttrium and radioiodinated antibody activity. The four stable yttrium-88 chelate-coupled antibodies studied displayed similar iodine-131 and yttrium-88 activity, indicating minimal elution of yttrium-88 from the complex. In contrast, the unstable yttrium-88 chelate-coupled antibodies had serum yttrium-88 activities that declined much more rapidly than their iodine-131 activities, suggesting loss of the radiolabel yttrium-88 from the chelate. Furthermore, high rates of yttrium-88 elution correlated with deposition in bone. Four chelating agents emerged as promising immunotherapeutic reagents: isothiocyanate benzyl DTPA and its derivatives 1B3M, MX, and 1M3B. All four isothiocyanate agents showed prolonged yttrium-88 vascular survival which was essentially identical to that of their iodine-131 activity with only minimum accumulation (1.4-1.8%/g) of the yttrium-88 injected dose into bone. Thus, these four chelating agents were very stable in vivo and suitable for yttrium-monoclonal antibody radioimmunotherapy.

Reflex-mediated reduction in human cerebral blood volume.

Adrenergic nerves innervate the human cerebrovasculature, yet the functional role of neurogenic influences on cerebral hemodynamics remains speculative. In the current study, regional cerebrovascular responses to sympathoexcitatory reflexes were evaluated. In eight volunteers, contrast-enhanced computed tomography was performed at baseline, -40 mmHg lower body negative pressure (LBNP), and a cold pressor test (CPT). Cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF) were evaluated in cortical gray matter (GM), white matter (WM), and basal ganglia/thalamus (BGT) regions. Lower body negative pressure resulted in tachycardia and decreased central venous pressure while mean arterial pressure was maintained. Cold pressor test resulted in increased mean arterial pressure concomitant with tachycardia but no change in central venous pressure. Neither reflex altered end-tidal carbon dioxide. Cerebral blood volume was reduced in GM during both LBNP and CPT (P<0.05) but was unchanged in WM and BGT. Mean transit time was reduced in WM and GM during CPT (P<0.05). Cerebral blood flow was only modestly affected with either reflex (P<0.07). The combined reductions in GM CBV (approximately -25%) and MTT, both with and without any change in central venous pressure, with small CBF changes (approximately -11%), suggest that active venoconstriction contributed to the volume changes. These data demonstrate that CBV is reduced during engagement of sympathoexcitatory reflexes and that these cerebrovascular changes are heterogeneously distributed.

Tuberculosis surveillance among new immigrants in Montreal.

SETTING: Foreign-born persons account for over 60% of Canadian tuberculosis (TB) incidence; immigrants with TB-related lung scarring ('inactive TB') are at particularly high risk, and represent an important target for preventive efforts. OBJECTIVE: To document the performance of the immigrant surveillance programme for inactive TB in Montreal. DESIGN: All immigrants arriving with inactive TB are referred by the public health department to the Montreal Chest Institute. We prospectively recorded clinical and radiographic data for those evaluated in 1999 and 2000. We examined physicians' adherence to Canadian guidelines. We also evaluated concordance of chest radiographic interpretation. RESULTS: Of 1444 immigrants notified, 792 (55%) were sent referral letters. Most of the others lacked valid addresses. Of the 654 (45%) who were examined, 322 (22%) were diagnosed with untreated latent TB, 215 (15%) were recommended therapy, and 156 (11%) completed it. Of 388 potential candidates for treatment of latent TB, 274 (71%) underwent tuberculin tests. Treatment decisions followed guidelines for 87% of patients with full testing. Agreement between clinicians and chest radiologists as to TB-related radiographic abnormalities was frequent (K 0.63). Six 'high volume' clinicians performed better than others with respect to management and radiographic interpretation. CONCLUSION: Centralised post-immigration surveillance requires more accurate referrals, and more consistent provider performance.

Alpha-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized anti-CD33 antibodies: pharmacokinetics, bioactivity, toxicity and chemistry.

UNLABELLED: The alpha-particle-emitting radionuclides have several physical characteristics that make them attractive candidates for radioimmunotherapy: (a) high linear energy transfer; (b) short path lengths (50-80 microm); and (c) limited ability of cells to repair damage to DNA. This article describes the pharmacokinetic, bioactivity, toxicity and chemical characteristics of alpha-particle-emitting, 213Bi and 212Bi radiometal conjugated HuM195 (anti-CD33) constructs. Conjugation of HuM195 to SCN-CHX-A-DTPA resulted in the attachment of up to 10 chelating ligand molecules per antibody. RESULTS: Radiolabeling efficiency of the CHX-A-DTPA-HuM195 construct with 213Bi was 78%+/-10% (n = 46) after 10 min at specific activities of up to 1110 MBq/mg. The immunoreactivity of the 213Bi-labeled CHX-A-DTPA-HuM195 construct was 84%+/-10% (n = 28) and was independent of the specific activity. The bismuth-labeled CHX-A-DTPA-HuM195 construct was rapidly internalized into the cell in a time-dependent manner ranging from 50% at 1 h to 65% at 24 h. 205Bi/206Bi-labeled constructs were stable for at least 2 d in vitro in the presence of human serum at 37 degrees C. After injection into mice, there was no uptake or loss of bismuth to mouse tissues, which do not express CD33, or to the kidney, which has avidity for free bismuth. Mice injected intraperitoneally with doses of (213Bi)CHX-A-DTPA-HuM1 95 ranging from 18.5 to 740 MBq/kg showed no toxicity, but at 2590 MBq/kg, two of the three mice died within 2 wk and a third mouse showed significant reductions in white blood cell counts. Mice injected intravenously with doses of (213Bi)CHX-A-DTPA-HuM195 up to 370 MBq/kg exhibited little toxicity, but 666 MBq/kg was above the MTD for mice. Leukemia cell killing in vitro with bismuth-labeled HuM1 95 showed dose- and specific activity-dependent killing of CD33+ HL60 cells; approximately 50% killing was observed when two bismuth atoms (50 fM radiolabeled antibody) were initially bound onto the target cell surface. CONCLUSION: Alpha-emitting antibodies are among the most potent cytotoxic agents known, yet are specific and appear safe in vivo. The physical and biochemical characteristics of the 213Bi isotope and its generation, as well as the biochemistry of the 213Bi-labeled CHX-A-DTPA-HuM195 construct, make it possible to use the constructs safely and feasibly in humans at therapeutic levels.

Lymphocyte proliferation induced by autologous cells. XV. Relationships between the human autologous mixed lymphocyte reaction stimulated by non-T and activated T cells.

The human (T:T act) AMLR was characterized in its relationship to the (T:Non-T) AMLR and its validity as a nonxenogeneic antigen induced response was extended. Human T cell lines, established from responding T cells in an autologous mixed lymphocyte reaction (MLR), were maintained in medium containing human serum and interleukin-2 (IL-2). These cells stimulated 3H-thymidine incorporation by autologous T cells and by autologous unfractionated blood mononuclear cells. Freshly activated T cells isolated from an autologous MLR stimulated autologous T cells to a lesser extent could be enhanced by adding IL-2. Twenty-five to 50% of T cells stimulated by activated T cells express the T8 determinant. In contrast, we have previously shown that less than 10% of T cells activated after 6 days in culture with non-T cells express the T8 determinant. The number of T8 bearing cells were increased significantly after 10 days in culture with non-T cells. This suggested that two types of reactions, the (T:Non-T) and (T:T act) AMLR, might occur in sequence when T cells and autologous non-T cells are cocultured: first, the activation of T4 cells by non-T cells, then by the activation of T8 cells by activated T4 cells. Finally, activated T cells can stimulate unfractionated autologous mononuclear cells without prior exposure to sheep erythrocytes or fetal calf serum.

Vasopressin potentiation of the melatonin synthetic pathway via specific V1a receptors in the rat pineal gland.

The pineal gland releases the "time-keeping' hormone melatonin following a rhythmic sympathetic input which translates light information. The aim of this work was to study the role and mechanism of action of the central vasopressinergic input on pineal cAMP-dependent melatonin synthesis in the rat. The pineal was found to display vasopressin receptors of the V1a subtype, as the V1a antagonist [125I]HO-LVA bound in a saturable manner to pineal membranes with a high affinity (kd = 10 pM) and a maximal binding capacity (B(max)) of 13 fmol/mg protein. Vasopressin was able to displace [125I]HO-LVA binding in a dose-dependent manner (k(i) = 1.9 nM). Vasopressin had no effect on the basal cAMP level and melatonin secretion in cultured rat pinealocytes. However, it clearly and dose-dependently (EC50 = 7 nM) potentiated by 2-3 times cAMP accumulation and by 1.5-2.5 times melatonin secretion induced by moderate noradrenergic stimulation. On strongly stimulated pinealocytes, however, vasopressin could potentiate cAMP accumulation, but not melatonin secretion. The potentiatory effect of vasopressin was inhibited in the presence of the V1a antagonist. These results indicate that vasopressin is a potent modulator of rat pineal synthetic activity.

Hypothalamic neuropeptide Y content and mRNA expression in weanling rats subjected to dietary manipulations during fetal and neonatal life.

Hypothalamic neuropeptide Y (NPY) is present very early during the fetal life and is rapidly functional in the regulation of feeding behavior after birth. In the present experiment, we tried to determine the influence that the diet type ingested by dams during gestation and lactation would have on the growth and hypothalamic and pancreatic peptides of their progeny immediately after weaning. The dams were fed on either a high-carbohydrate (HC), a high-fat (HF) or a control diet ad libitum. At 3 days of age, the HC pups weighed significantly more than the two other groups (P < 0.02 vs. C and P < 0.002 vs. HF). At weaning, the HF rats were significantly lighter than the two other groups (P < 0.001). Food intake was significantly lower in the HF rats than in the two other groups 3 days (P < 0.002) and 5 days after weaning (P < 0.02). Plasma glucose of the HF rats was significantly lower than that of the control rats (P < 0.05) and of the HC rats (P < 0.01). Immunoreactive insulin in the HF rats was also significantly lower than that in the control rats (-53%; P < 0.001) and in the HC rats (-47%; P < 0.001). NPY content and mRNA expression in the arcuate nucleus were not significantly different between the three groups. NPY concentration only varied in the ventromedian nucleus. In the control rats, it was significantly lower than that of the HC rats (-35%; P < 0.01) and that of the HF rats (-32%; P < 0.002). These data demonstrated that the regulatory mechanisms of feeding behavior in offspring are completely and differentially modified by the macronutrient content of the diets ingested by their mother. Both peripheral and central mediators were strongly implicated. These modifications could have long-term repercussions on body weight and composition.

Dietary composition during fetal and neonatal life affects neuropeptide Y functioning in adult offspring.

The aim of this study was to examine the impact of maternal diet during the gestation and lactation periods on the neuropeptide Y (NPY) system in adult offspring. Male Long-Evans rats were obtained from dams fed either on a well-balanced diet (C), a high carbohydrate diet (HC) or a high-fat diet (HF) and fed themselves on the well-balanced diet for their whole life. At 6 months of age, their feeding response to various doses of NPY injected in the lateral brain ventricle was measured in one group and NPY concentrations in microdissected nuclei of the hypothalamic were measured in a second group. The HF rats were lighter than the two other groups (P<0.001). The control rats showed a typical dose-dependent feeding response to NPY. The HC rats showed a continuous increase in the response, starting at the intermediate dose (1.0 microg) only while the HF rats had a maximal response at the lowest dose (0.5 microg). The HF rats ate twice as much as the HC rats at the lowest dose tested 1 h after injection (4.4+/-0.6 vs. 2.7+/-0.4 g; P<0.05), showing therefore the greatest sensitivity to NPY. This change in the sensitivity was not related to hypothalamic NPY concentration as it was not modified in the arcuate and paraventricular nuclei. The diet imposed on the mother could have long-lasting effects on body weight regulation of the offsprings and alter the NPY system likely through modifications at the receptor level.

The effects of excitotoxic lesions of the pedunculopontine tegmental nucleus on conditioned place preference to 4%, 12% and 20% sucrose solutions.

A number of studies have suggested that the pedunculopontine tegmental nucleus (PPTg) may play a role in reward-related behaviour. The present study was intended to investigate this further using conditioned place preference. In conditioned place preference paradigms the amount of time spent in a preferred environment is proportional to the value of the reinforcement present, until a maximum is reached. In the present experiments we aimed to determine whether this relationship was affected by lesions of the PPTg by examining the formation of a conditioned place preference to either 4%, 12% or 20% sucrose solutions in food-deprived PPTg lesioned rats. The conditioned place preference apparatus had two compartments different in colour, smell and floor texture. During conditioning, rats were restricted to one compartment or the other, one of which was paired with sucrose. This was carried out during 30 min sessions, alternating conditioned or nonconditioned trials for 14 days. On the test day, rats were given access to both compartments through a connecting chamber, and were scored for side preference over 15 min. Both PPTg and sham lesioned rats showed a conditioned place preference to 12% and 20% sucrose, but no place preference was formed by either group to 4% sucrose. There was no significant difference between the groups in the place preference shown. Consumption of 4% sucrose was not affected by excitotoxic lesions of the PPTg, but PPTg lesioned rats consumed significantly more 12% and 20% sucrose than sham controls. This suggests that perception of reward value, as judged by CPP formation, is unchanged by excitotoxic lesions of the PPTg. The increased consumption of 12% and 20% sucrose shown by rats bearing such lesions is therefore not likely to be a product of altered reward perception.

Evaluation of dithiol chelating agents as potential adjuvants for anti-IL-2 receptor lead or bismuth alpha radioimmunotherapy.

The dithiol chelating agents 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for use as potential adjuvants to reduce or prevent radiotoxicity in anti-interleukin-2 receptor (IL-2R) Lead-212 or Bismuth-212 alpha-radioimmunotherapy. DMPS was less toxic than DMSA to tumor cell lines in culture. No adverse effects on the ability of an anti-IL-2R monoclonal antibody (MAb) to bind to its specific antigen were detected using DMPS or DMSA at concentrations up to 600 ug/mL in 10% or 100% mouse serum. After a 5-day oral administration of chelating agent, neither acute nor chronic toxicities on blood hematology, blood chemistry or organ weights were observed for treated mice. DMPS and DMSA were effective in accelerating whole body clearance of the gamma-emitting tracer Bismuth-206. Both chelates significantly reduced femur uptake of tracer when compared to nontreated control mice. However, only DMPS prevented early (2 h postinjection) renal accumulation. These studies support the use of DMPS as a potential adjuvant chelation therapy in Lead-212 or Bismuth-212 radioimmunotherapy protocols.

An absorptiometry method for the determination of arterial blood concentration of injected iodinated contrast agent.

A single photon absorptiometry method to measure the arterial concentration of injected iodinated contrast agent was developed. A prototype absorptiometry unit was built which consists of either a square or circular cross section acrylic (polymethylmethacrylate) cuvette connected to an arterial catheter at one end and a paristaltic pump at the other via PE60 surgical tubing. At opposing ends of the length of the cuvette were a 0.4 GBq 125I source and a scintillation crystal/photomultiplier tube assembly. This assembly was connected to a single-channel analyser (SCA)/scaler unit to count the transmitted photons through the cuvette. The scaler was interfaced to an IBM PC and counts accumulated in preset time intervals were transmitted to the computer via a serial interface. Experiments were performed to calibrate the unit for measurement of blood concentration of contrast agent (Isovue 300) and to determine the dispersion characteristics of the unit. Deconvolution was used to correct the measured concentration waveform for the dispersion introduced by passage through the lead-in tubing and the cuvette. The precision of concentration measurements was determined to be between 5 and 10% using computer simulations and theoretical calculations. The method was used successfully in a number of patient and animal studies to measure the contrast concentration in blood following intravenous injection of contrast agent.

Ketorolac vs meperidine for the management of pain in the emergency department.

OBJECTIVE: To compare the pain relief, sedation, and common side effect profiles of ketorolac tromethamine and meperidine for the management of acute pain in the emergency department (ED). METHODS: A prospective, double-blind, randomized clinical trial was conducted over a 12-month period using consecutive adult patients presenting to a university teaching hospital ED (annual census: 32,000), who required IM analgesia for acute pain. Adult patients with acute pain of various etiologies were randomly assigned to receive a single fixed IM dose of ketorolac (60 mg) or meperidine (100 mg). RESULTS: Ninety-three patients were enrolled in the study; 46 were randomized to meperidine and 47 to ketorolac. Using a visual analog scale, there was no difference in pain relief between the ketorolac and meperidine groups even after adjusting for baseline pain level. Ketorolac caused significantly (p < 0.005) less sedation than did meperidine at one hour. Rescue analgesia was required for seven of the 46 (15.2%) patients receiving meperidine and five of the 47 (10.6%) patients receiving ketorolac (p = NS). Seventeen of 45 (38%) patients receiving meperidine experienced side effects compared with eight of the 47 (17%) patients receiving ketorolac (p = 0.0452). CONCLUSIONS: When used to treat patients who had acute pain states, 60 mg of IM ketorolac produced analgesia similar to that produced by 100 mg of IM meperidine; however, the ketorolac produced fewer subjective side effects and less sedation than did the meperidine.

The threat of funding cuts for graduate medical education: survey of decision makers.

OBJECTIVE: To assess the potential actions of medical school deans, graduate medical education (GME) committee chairs, and hospital chief executive officers (CEOs) regarding future funding reductions for residency training. Specifically, institutions with emergency medicine (EM) residencies were surveyed to see whether EM training was disproportionally at risk for reductions. METHODS: An anonymous 2-page survey was used. Ninety-eight EM residency programs were identified using the American Medical Association Graduate Medical Education Directory 1994-95. Seventy deans, 102 GME chairs, and 97 hospital CEOs were identified. The survey posed a hypothetical 25% forced reduction in residency positions and asked the decision makers for their responses. Options included: 1) proportional reductions of training positions from all residencies, 2) proportional reductions in either primary care or specialty residency positions, or 3) reduction or elimination of specific training programs. The survey asked for a first and second choice of residencies to be reduced or eliminated from an alphabetical list of 17. The survey elicited explanations for each program reduction. RESULTS: 200 (74%) of 269 surveys were returned. Eighty-four responders selected specific residencies to be reduced or eliminated. EM was selected 8 times, making EM the seventh most vulnerable residency to be targeted for reductions. The decision makers who selected proportional reductions chose to reduce across all residencies 32 times, among only the specialty residencies 129 times, and among only the primary care residencies 3 times. CONCLUSIONS: In the setting of anticipated residency cuts, favored proportional reductions in specialty residencies would likely affect EM training. However, most GME decision makers with an existing EM residency program do not consider the EM residency a top choice to be reduced or eliminated.

Cell receptor assays.

There are four general assay methods used to quantify a drug/biologic in a preparation, including: (1) in vivo bioassays; (2) in vitro bioassays; (3) immunoassays; and (4) receptor assays. The cell receptor assay is used to evaluate the first step in the molecular action of the drug biologic, its interaction with a specific cellular receptor. Subsequently, the drug biologic must initiate other events, such as internalisation, signal transduction, and/or alterations of one or more cellular constituents in order to elicit its biological effect. Major factors to consider in cell receptor assay development include: (1) establishment of a reference standard preparation; (2) labelling; purifying and characterisation of the biologic drug; (3) cell receptor source; (4) methodology, e.g. separation of bound and free, and other factors affecting accuracy and reproducibility; (5) ligand specificity; and (6) correlation with bioactivity. It should be emphasised that cell receptor binding cannot be assumed to correlate with biological activity because of the requirement that subsequent steps must take place prior to achieving the final response. Chemically altered drugs biologics may bind to a specific cell receptor without eliciting a biological activity. Thus, utilisation of a cell receptor assay requires careful evaluation at both the chemical and biological levels prior to its acceptance as a measure of potency.