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Biomedical subjects

R Curry

Publications and source records attributed to R Curry.

18 recordsLinked to original sources
PubMed2001

Development of drug resistance in patients receiving combinations of zidovudine, didanosine and nevirapine.

OBJECTIVE: To evaluate the development of phenotypic and genotypic resistance to zidovudine, didanosine and nevirapine as a function of the virologic response to therapy in a group of drug-naive individuals receiving various combinations of these agents. DESIGN: All patients were enrolled in a double-blind controlled randomized trial (the INCAS study) and were selected for detailed resistance studies based on specimen availability and virologic response. METHODS: Within the three study groups (zidovudine/nevirapine, zidovudine/didanosine or zidovudine/nevirapine/didanosine), 16, 19 and 24 patients, respectively, had evaluable baseline isolates and remained in the study > 24 weeks. Phenotypic resistance to all three drugs was evaluated using the VIRCO recombinant virus assay. Genotypic sequencing was done on selected specimens from patients receiving zidovudine/nevirapine/didanosine. RESULTS: After 24 weeks, all available isolates taken from patients receiving nevirapine were resistant to this agent, while 18/21 (86%) patients receiving triple therapy carried such isolates at 30--60 weeks. At 24 weeks, zidovudine resistance developed in 4/40 isolates but was more frequent after 30--60 weeks, especially in patients on two drugs. The degree of zidovudine resistance (rise in concentration required for 50% inhibition) appeared lower in the triple therapy group compared with zidovudine/didanosine (P = 0.0004). All nevirapine-resistant isolates that were sequenced carried at least one mutation associated with resistance, most often K103N and/or Y181C. CONCLUSION: The use of highly active drug therapies may be associated with a beneficial effect on the development of antiretroviral drug resistance. The characteristics of virologic suppression that must be maintained to avoid resistance are currently being studied in hypothesis-driven clinical trials.

Anti-HIV Agents↗
PubMed2000

Family dynamics, parental-fetal attachment and infant temperament.

Family dynamics, parental-fetal attachment and infant temperament The purpose of this longitudinal study of families having their first or second baby was to explore relationships among family dynamics, paternal- and maternal-fetal attachment, and infant temperament. Data were collected from 156 women and 62 of their partners during the third trimester of pregnancy. One year later, when the infant was 8-9 months old, 75 of the women and 30 of their partners participated. In a hierarchical multiple regression analysis, after controlling for demographic variables, mutuality in the family was associated with greater maternal- and paternal-fetal attachment. Family dynamics were stable across the transition to parenthood except for an increase in role conflict reported by mothers. Sensitivity to specific family experiences by clinicians can provide assistance to families during these periods.

Adult↗
PubMed2000

Mutations in the WRN gene in mice accelerate mortality in a p53-null background.

Werner's syndrome (WS) is a human disease with manifestations resembling premature aging. The gene defective in WS, WRN, encodes a DNA helicase. Here, we describe the generation of mice bearing a mutation that eliminates expression of the C terminus of the helicase domain of the WRN protein. Mutant mice are born at the expected Mendelian frequency and do not show any overt histological signs of accelerated senescence. These mice are capable of living beyond 2 years of age. Cells from these animals do not show elevated susceptibility to the genotoxins camptothecin or 4-NQO. However, mutant fibroblasts senesce approximately one passage earlier than controls. Importantly, WRN(-/-);p53(-/-) mice show an increased mortality rate relative to WRN(+/-);p53(-/-) animals. We consider possible models for the synergy between p53 and WRN mutations for the determination of life span.

4-Nitroquinoline-1-oxide↗
PubMed1999

Spinal versus epidural anesthesia for cesarean section in severely preeclamptic patients: a retrospective survey.

BACKGROUND: Selection of spinal anesthesia for severely preeclamptic patients requiring cesarean section is controversial. Significant maternal hypotension is believed to be more likely with spinal compared with epidural anesthesia. The purpose of this study was to assess, in a large retrospective clinical series, the blood pressure effects of spinal and epidural anesthesia in severely preeclamptic patients requiring cesarean section. METHODS: The computerized medical records database was reviewed for all preeclamptic patients having cesarean section between January 1, 1989 and December 31, 1996. All nonlaboring severely preeclamptic patients receiving either spinal or epidural anesthesia for cesarean section were included for analysis. The lowest recorded blood pressures were compared for the 20-min period before induction of regional anesthesia, the period from induction of regional anesthesia to delivery, and the period from delivery to the end of operation. RESULTS: Study groups included 103 women receiving spinal anesthesia and 35 receiving epidural anesthesia. Changes in the lowest mean blood pressure were similar after epidural or spinal anesthesia. Intraoperative ephedrine use was similar for both groups. Intraoperative crystalloid administration was statistically greater for patients receiving spinal versus epidural anesthesia (1780 +/- 838 vs. 1359 +/- 674 ml, respectively). Neonatal Apgar scores and incidence of maternal intensive care unit admission or postoperative pulmonary edema were also similar. CONCLUSION: Although we cannot exclude the possibility that the spinal and epidural anesthesia groups were dissimilar, the magnitudes of maternal blood pressure declines were similar after spinal or epidural anesthesia in this series of severely preeclamptic patients receiving cesarean section. Maternal and fetal outcomes also were similar.

Adult↗
PubMed1998

Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers.

UNLABELLED: Clonidine is approved for intraspinal administration in the treatment of neuropathic cancer pain. Some studies have suggested an analgesic effect after systemic clonidine administration. The purpose of this study was to compare the analgesic effects of intrathecal and IV clonidine with acute noxious stimulation and with hyperalgesia from intradermal capsaicin injection in volunteers. Sixteen healthy volunteers received intradermal injections of capsaicin (100 microg) before and after the IV or intrathecal injection of clonidine 50 or 150 microg in a randomized, double-blind manner. Pain and areas of mechanical hyperalgesia and allodynia were determined at specified intervals. In addition, pain to noxious heat stimulation was determined. The capsaicin injection produced pain, followed by hyperalgesia and allodynia. The intrathecal, but not IV, injection of 150 microg of clonidine reduced capsaicin-induced pain and area of hyperalgesia. Intrathecal clonidine (150 microg) reduced pain to heat stimulation, whereas IV clonidine did not. The groups did not differ in hemodynamic or sedative effects from clonidine. These data support the value of intraspinal administration of clonidine for the treatment of acute pain and of pain states associated with hyperalgesia. Similarly, they suggest that analgesia from the systemic administration of this alpha2-adrenergic agonist, if any, is weak in doses that produce sedation and reduce blood pressure. IMPLICATIONS: To the extent that the experimental pain conditions used in this study reflect those in patients with acute and chronic pain, these data support the spinal rather than IV injection of clonidine for analgesia.

Adrenergic alpha-Agonists↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1982

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↗
PubMed1981

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↗
PubMed1981

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↗