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Biomedical subjects

R Curry

Publications and source records attributed to R Curry.

11 recordsLinked to original sources

Phase I human safety assessment of intrathecal neostigmine containing methyl- and propylparabens.

UNLABELLED: Intrathecal (i.t.) neostigmine produces analgesia in humans with acute experimental, postoperative, and chronic pain. The sole manufacturer of the preservative-free neostigmine solution used in the initial clinical studies no longer markets this preparation. Although solutions containing preservatives are generally avoided for i.t. injection, methyl- and propylparabens have not been demonstrated to be toxic. After preclinical toxicity screening in animals and Food and Drug Administration approval, 12 volunteers received i.t. neostigmine 10, 30, or 100 micrograms, containing these preservatives and glucose. This preparation produced dose-dependent analgesia, nausea, weakness, and sedation similar to the preservative-free preparation. I.t. neostigmine increased acetylcholine but not norepinephrine concentrations in cerebrospinal fluid. Although nitric oxide synthesis has been implicated in analgesia from i.t. neostigmine injection in animals, cerebrospinal fluid concentrations of nitrite as a measure of nitric oxide were not increased by i.t. neostigmine in these volunteers. These data support the investigational application of i.t. neostigmine containing methyl- and propylparabens in the concentrations studied. IMPLICATIONS: Because intrathecal injection of neostigmine may be a useful analgesic, we performed a Phase I tolerability and safety study of the commercially available neostigmine formulation in human volunteers and found no evidence of toxicity. These data are important to the clinical use of this new therapy.

Adult

Alfentanil, but not amitriptyline, reduces pain, hyperalgesia, and allodynia from intradermal injection of capsaicin in humans.

BACKGROUND: Intradermal injection of capsaicin produces brief pain followed by hyperalgesia and allodynia in humans, and the latter effects are mediated by spinal N-methyl-D-aspartate mechanisms. Amitriptyline recently was shown to antagonize N-methyl-D-aspartate receptors, and in this study, the authors sought to determine the effect of amitriptyline alone and with the opioid alfentanil on hyperalgesia and allodynia produced by intradermal injection of capsaicin. METHODS: Forty-six healthy volunteers in the general clinical research center received repeated intradermal injections of capsaicin (100 microg) alone or before and after systemic injection of 4 mg midazolam, 25 mg amitriptyline, alfentanil by computer-controlled infusion, or amitriptyline plus alfentanil. Acute pain and areas of mechanical hyperalgesia and allodynia were determined at specified intervals. Blood was obtained for alfentanil and amitriptyline assay. RESULTS: Capsaicin injection produced acute pain followed by hyperalgesia and allodynia. Alfentanil reduced these pain responses in a plasma-concentration-dependent manner, and reduction in hyperalgesia and allodynia correlated with reduction in acute pain. Amitriptyline alone had no effect and did not potentiate alfentanil. Alfentanil produced concentration-dependent nausea, an effect diminished by amitriptyline. DISCUSSION: These data correspond with previous studies in volunteers demonstrating reduction in hyperalgesia and allodynia after intradermal injection of capsaicin by systemically administered opioids, and they suggest that this reduction may be secondary to reduced nociceptive input by acute analgesia. These data do not support the use of acute systemic administration of amitriptyline for acute pain, hyperalgesia, and allodynia, although the roles of chronic treatment and spinal administration are being investigated.

Adult

Simultaneous better than sequential for brief presentations.

During perceptually intensive tasks such as reading, there is a bottleneck in the information transfer between the large number of alphanumeric characters available and the acquiring of these characters. This is due mainly to the limited number of characters that one can report at a glance (also known as the "magic number 7 +/- 2") [Psychol. Rev. 63, 81 (1956)]. To examine where in the perceptual pathway this bottleneck occurred, several investigators tested and compared performance with simultaneous and with sequential target presentations [J. Exp. Psychol. 79, 1 (1969); 93, 72 (1972); Percept. Psychophys. 14, 231 (1973)]. They found that performance was nearly equal in the two cases and concluded that the bottleneck must be due to the limitation of short-term memory. However, these studies were limited either by a long stimulus-onset asynchrony (SOA), or time interval between onsets of icon presentations, or by a lack of poststimulus masking. We report on experiments designed to overcome these limitations. We used shorter SOA's than did previous investigators, and we removed persistence effects by poststimulus masking. Our stimuli were presented either sequentially or simultaneously. For the sequential presentation a numeral ranging from 0 to 9 was displayed at any one of eight positions 1.5 deg from a central fixation cross. The appearance of the next numeral in another part of the display coincided with the masking of the previous numeral. This was done for trials of one to four numerals and SOA's of 16.7, 33.3, and 50.0 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Attention

Context effect of common objects on visual processing.

In previous experiments on visual processing it was shown that correct identification of sequentially and simultaneously presented numerals declined as the presentation interval was decreased from 50.0 to 16.7 ms/numeral. To determine how performance was influenced in context, common everyday objects were used in place of the numerals. These objects were grouped into 36 different categories with 4 objects per category. An example of a category was fruit: apple, banana, pear, pineapple. For all experimental trials, objects (ranging in number from one to four) were presented randomly at four possible positions 1.5 degrees from a central fixation point. In a sequential trial, the objects were displayed in succession at different locations for a stimulus onset asynchrony (SOA) of either 16.7, 33.3, or 50.0 ms. The masking of a previous object coincided with the onset of the object that followed in the sequence. A simultaneous trial consisted of 2, 3, or 4 objects presented concurrently. For these trials, simultaneous masking occurred at SOA's of 16.7, 33.3, or 50.0 ms. For both experimental paradigms, one-half of the trials consisted of objects from the same category, and one-half from mixed categories. Results taken from four observers showed that performance for all three SOA's was consistently better when the objects were related as opposed to when the objects were not for both presentation protocols. This lent support to the theory that there was simultaneous interaction of top-down and bottom-up processes in visual processing. In addition, as was found in the numerals study, performance was better when the objects were presented simultaneously as opposed to sequentially.

Adult

Subcutaneous jugulofemoral bypass: a simple surgical option for palliation of superior vena cava obstruction.

BACKGROUND: Percutaneous placement of an intraluminal stent is usually a successful intervention for the disabling symptoms of Superior Vena Cava (SVC) obstruction. However, on occasion this may not be feasible and, as malignant disease is responsible for 90% of cases, the morbidity associated with median sternotomy or thoracotomy usually precludes surgical bypass. OBJECTIVE: To achieve good palliation of the symptoms of SVC obstruction by surgical bypass without performing sternotomy or thoracotomy. PATIENTS: Two patients with SVC obstruction secondary to lung cancer and a third after radiochemotherapy for malignant mediastinal teratoma. In all patients intraluminal stenting was considered but was not possible. METHODS: Jugulofemoral bypass was performed using long saphenous vein which was tunnelled subcutaneously from the femoral to the jugular vein. RESULTS: One patient required wound exploration for haemorrhage. Good palliation was achieved in all patients. One patient died 3 months post-operatively from lung cancer and the remaining two are alive without symptoms at 13 months and 6 weeks postoperatively. CONCLUSIONS: Though the majority of patients with SVC obstruction can be treated with non-surgical methods, subcutaneous jugulofemoral bypass may provide good palliation if these are not feasible.

Adult

Antibodies to and elevations of beta 2 microglobulin in the serum of ankylosing spondylitis patients.

Antibodies to beta 2 microglobulin are found in systemic lupus erythematosus patients and are important in the lymphocytotoxic reactions of sera from such patients. In this study, beta 2 microglobulin antibodies were measured with the use of an enzyme-linked immunosorbent assay with purified beta 2 microglobulin antigen and peroxidase-labeled anti-human IgG or IgM. IgG antibodies to beta 2 microglobulin were found in 68% of 22 patients with ankylosing spondylitis. This incidence was higher than the 5% in 80 controls (P less than 0.01) and similar to the 71% incidence found in 35 patients with systemic lupus erythematosus. Eleven (27%) of 41 patients with rheumatoid arthritis had elevated levels of antibodies to beta 2 microglobulin (P less than 0.01). The mean antibody levels expressed in enzyme units were 0.125 for patients with ankylosing spondylitis, 0.157 for those with systemic lupus erythematosus, 0.101 for those with rheumatoid arthritis, and 0.067 for controls. IgM anti-beta 2 microglobulin was not significantly different from controls. A competitive binding assay with enzyme-labeled beta 2 microglobulin was used to determine serum beta 2 microglobulin. These values were also found to be elevated in 48% of patients in all 3 disease categories (P less than 0.01). Beta 2 microglobulin antibodies and serum beta 2 microglobulin did not correlate with each other, renal diseases or antinuclear antibodies in patients with systemic lupus erythematosus, with rheumatoid factor or severity of articular disease in patients with rheumatoid arthritis, or with peripheral arthritis or iritis in those with ankylosing spondylitis. Although antibodies to beta 2 microglobulin might reflect a general disturbance of immune regulation in patients with systemic lupus erythematosus, their presence in those with ankylosing spondylitis, a disease closely associated with a specific HLA allotype and not usually associated with formation of autoantibody, suggests that they might play a role in the pathogenesis of the latter disease.

Adult

Rapid identification of human B-lymphocytes and monocytes with rhodamine-labeled Brucella melitensis.

The bacterium Brucella melitensis has been shown to bind selectively to human B-lymphocytes. The specificity of this binding can be exploited in a rapid technique for the determination of human B-lymphocytes and monocytes by use of rhodamine-labeled Brucella melitensis. This fluorescent labeled regent is simple to use and provides highly specific identification of human B-lymphocytes and monocytes, as demonstrated in a series of experiments characterizing known cellular markers on T- and B-lymphocytes, their separated cellular subpopulations and lymphoblastoid cell lines. The use of fluorescence conjugated bacteria greatly simplifies the application of this highly specific technique and makes its use more practical in routine screening for B-cell and monocyte populations.

Antigens

Rapid semi-quantitative isolation of beta-2-microglobulin from urine.

A rapid semi-quantitative purification of beta 2-microglobulin from transplant urine relies on a batch absorption using hydroxylapatite-cellulose. Stepwise elution is followed by Sephadex G-150 gel permeation chromatography. Using this methodology, it is possible to process quickly and conveniently many liters of urine at bench scale, with yields exceeding 95% and overall purity greater than 97% beta 2-microglobulin.

Absorption