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Biomedical subjects

R T Jones

Publications and source records attributed to R T Jones.

At least 55 records · Page 3Linked to original sources

Hemoglobin S/hemoglobin Osler: a case with 3 beta globin chains. DNA sequence (AAT) proves that Hb Osler is beta 145 Tyr-->Asn.

A 13-year-old African-American female with erythrocytosis and three different beta globins on electrophoresis beta A, beta S, and beta Osler, raised the possibility that one chromosome 11 might contain a duplicated beta globin gene, since there are normally only 2 beta globin genes. DNA sequence analysis showed GTG at codon 6 in exon 1, corresponding to Hb S and AAT at codon 145 in exon 3, indicating a substitution of Asn for Tyr. Thus, Hb Osler undergoes spontaneous post-translational deamidation, beta 145 Asn-->beta 145 Asp. Unmodified Hb Osler (Asn) co-migrates with Hb A on electrophoresis and co-elutes with Hb A on HPLC; therefore it has not been identified previously. All previous studies have incorrectly identified the mutation as being beta 145 (HC 2) Tyr-->Asp.

Adolescent↗

A controlled trial of fluoxetine in crack cocaine dependence.

This controlled study tested the efficacy of the selective serotonergic reuptake inhibitor fluoxetine in the out-patient treatment of primary crack cocaine dependence. Thirty-two subjects were randomly assigned, 16 in each group, to placebo or fluoxetine, 40 mg/day, in a double-blind controlled trial over a 12-week period. Outcome measures included quantitative urine benzoylecgonine concentration, self-reports of cocaine use and craving, and treatment retention. Subjects assigned to fluoxetine were retained in treatment significantly longer than those on placebo: a median of 11 weeks compared to 3 weeks (logrank test, P < 0.001). Because of the poor retention in the placebo group, between-groups comparisons of outcome were limited to the first 6 weeks of treatment. No differences in cocaine use or craving were found between the two groups over weeks 1 to 6. The significant improvement in retention associated with fluoxetine may support further study of this medication in the treatment of cocaine dependence.

Adult↗

Buprenorphine and naloxone interactions in opiate-dependent volunteers.

OBJECTIVE: Sublingual buprenorphine appears useful in the treatment of opiate dependence. A combination sublingual dose of buprenorphine and naloxone could have less potential for parenteral use by opiate-dependent individuals. To estimate the abuse potential of a combination formulation, we assessed the parenteral effects of a buprenorphine and naloxone combination in untreated heroin addicts. METHODS: Eight healthy, opiate-dependent daily users of heroin were given, under double-blind conditions on four separate occasions, either (1) 2 mg buprenorphine, (2) 2 mg naloxone, (3) 2 mg buprenorphine and 2 mg naloxone combined, or (4) placebo as a single intravenous infusion during a 30-second interval. Opiate agonist and antagonist physiologic and subjective effects were measured. Data were analyzed by analysis of variance. RESULTS: Buprenorphine increased opiate intoxication and relieved withdrawal. The buprenorphine and naloxone combination precipitated opiate withdrawal and was unpleasant and dysphoric in all subjects. Fifty percent of the subjects were unable to distinguish between naloxone alone and the combined medications during the first hour of testing. CONCLUSIONS: The buprenorphine and naloxone combination has a low abuse potential in opiate-dependent daily heroin users.

Adult↗

A prospective, controlled study showing that rubber gloves are the major contributor to latex aeroallergen levels in the operating room.

BACKGROUND: Although protocols have been published for reducing natural rubber latex exposure in medical environments, there are no objective data documenting their effectiveness. OBJECTIVE: We prospectively studied the impact of a single intervention, substitution of low-allergen-containing latex gloves for high-allergen-containing latex gloves, on latex aeroallergen levels in a single operating room (OR). METHODS: We sampled OR air on 52 consecutive days, including 33 surgery days and 19 nonsurgery days. On each surgery day all personnel wore either high-allergen gloves (n = 18 days) or low-allergen gloves (n = 15 days). Latex aeroallergen levels (in nanograms per cubic meter) and extractable latex glove allergen contents (in allergen units per milliliter) were measured by inhibition immunoassays. An on-site study monitor recorded the number of gloves used, the total time spent by all patients in the OR each day (OR time), and the total time of all procedures for each day (operating procedure time). RESULTS: Latex aeroallergen levels during low-allergen glove use days (mean, 1.1 ng/m3; median, 0.9 ng/m3; range, 0.1 to 3.5 ng/m3) were significantly lower than on high-allergen glove use days (mean, 13.7 ng/m3; median, 7.7 ng/m3; range, 2.2 to 56.4 ng/m3) (p < 0.001) but not significantly different from that on nonsurgery days (mean, 0.6 ng/m3; median, 0.3 ng/m3; range, 0.1 to 3.6 ng/m3). Latex aeroallergen levels were strongly correlated with the total number of gloves used on designated high-allergen glove days (r = 0.66, p = 0.003). There was no appreciable day-to-day carryover of latex aeroallergen. CONCLUSIONS: The substitution of low-allergen-containing latex gloves for high-allergen-containing latex gloves can reduce levels of latex aeroallergen by more than 10-fold in an OR environment.

Air Pollutants, Occupational↗

Monospecific allergy to swordfish.

BACKGROUND: Fish allergy is a relatively common and potentially fatal condition. Most fish allergic subjects are allergic to multiple fish species. We encountered a patient clinically allergic only to swordfish. OBJECTIVE: To characterize the in vivo and in vitro IgE antibody responsiveness of this patient solely allergic to swordfish. METHODS: Prick skin tests, as well as immunoassay and protein immunoblotting for IgE antibody were performed using commercial fish extracts and fresh swordfish. A more typical multiple fish-allergic subject and a subject not allergic to food were also studied for comparison. RESULTS: The multiple fish-allergic subject demonstrated IgE antibody to a 13-kD protein in all fish tested (probably Gad c 1 and its analogues in other fish). The swordfish-allergic subject did not recognize this 13-kD band but did demonstrate IgE directed against a 25-kD band only in swordfish. The negative control showed no IgE binding to either the 13 or 25 kD bands. CONCLUSIONS: It is possible to be allergic to a single fish species, such as swordfish, and such monospecific allergy may be due to the presence of species-specific allergens, in this case a 25-kD allergen in swordfish.

Adult↗

A medical-center-wide, multidisciplinary approach to the problem of natural rubber latex allergy.

Latex is a common cause of occupational allergy in health care workers; latex-sensitized patients are at increased risk of allergic reactions in medical environments. Skin test reagents and latex-specific immunoglobulin E immunoassays were established for diagnosis of latex allergy. Inhibition immunoassays were developed for measuring latex aeroallergens and latex allergens in rubber products. A registry of latex-sensitive employees was established. High-allergen gloves were removed from the medical center inventory; latex aeroallergen levels subsequently declined. Despite an increasing number of gloves used annually, expenditures for gloves in 1994 were lower than in previous years. Latex-sensitive individuals can be identified using skin tests or immunoassays. Latex aeroallergen levels in medical environments can be reduced substantially at lower cost by using powder-free rubber gloves with lower allergen content.

Air Pollutants, Occupational↗

Immediate effects of intravenous cocaine on the thoracic aorta and coronary arteries. A transesophageal echocardiographic study.

UNLABELLED: STUDY OBJECTIVES AND DESIGN: Arterial vasoconstriction is thought to play a role in the etiology of cocaine-induced cardiovascular complications, but little is known about the immediate effects of cocaine on the thoracic aorta and coronary arteries. To examine these effects, we used transesophageal echocardiography to examine the thoracic aorta and coronary arteries before and immediately after intravenous (i.v.) cocaine (1.2 mg/kg) in 15 subjects. MEASUREMENTS AND RESULTS: Immediately after cocaine infusion, average heart rate, systolic BP, and double product were increased compared with baseline (22%, 15%, 35%, respectively). There was no significant change in the diameters of the ascending aorta (27.5 vs 27.1 mm; p = 0.85), the descending aorta (19.8 vs 20.4 mm; p = 0.62), or the left main coronary artery (4.3 vs 4.7 mm; p = 0.15). However, there was a trend for an increase in coronary blood flow immediately after cocaine (226 vs 309 mL/min; p = 0.10). CONCLUSIONS: We conclude that in the 15 subjects studied, there was no evidence of thoracic aorta of coronary artery vasoconstriction immediately after i.v. cocaine. Instead, we found that the diameters of the thoracic aorta and the left main coronary artery were unchanged, and that there was a trend for augmentation of coronary artery blood flow.

Adult↗

Allosteric transition intermediates modelled by crosslinked haemoglobins.

The structural end-points of haemoglobin's transition from its low-oxygen-affinity (T) to high-oxygen-affinity (R) state, have been well established by X-ray crystallography, but short-lived intermediates have proved less amenable to X-ray studies. Here we use chemical crosslinking to fix these intermediates for structural characterization. We describe the X-ray structures of three haemoglobins, alpha 2 beta 1S82 beta, alpha 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, which were crosslinked between the amino groups of residues beta Val1 and beta Lys82 by 3,3'-stilbenedicarboxylic acid (S) or trimesic acid (Tm) while in the deoxy state, and saturated with carbon monoxide before crystallization. alpha 2 beta 1S82 beta, which has almost normal oxygen affinity, is completely in the R-state conformation; however, alpha 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, both of which have low oxygen affinity, have been prevented from completing their transition into the R state and display many features of a transitional intermediate. These haemoglobins therefore represent a snapshot of the nascent R state.

Allosteric Regulation↗

Gas chromatographic determination of methamphetamine and its metabolite amphetamine in human plasma and urine following conversion to N-propyl derivatives.

A gas chromatographic method for the simultaneous determination of methamphetamine and its metabolite amphetamine in human plasma and urine is described. The method utilizes reductive alkylation with propionaldehyde and sodium borohydride to produce N-propyl derivatives, which have excellent chromatographic properties. Structural analogs of the analytes, p-methylmethamphetamine and p-methylamphetamine, are used as internal standards. The method has good precision and accuracy for concentrations ranging from less than 10 ng/ml to 5000 ng/ml and has been used to measure plasma concentrations as part of a pharmacokinetic/pharmacodynamic study of methamphetamine in humans.

Aldehydes↗

Major histocompatibility complex class II+B7-1+ tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice.

Mice carrying large established major histocompatibility complex (MHC) class 1+ sarcoma tumors can be successfully treated by immunization with genetically engineered sarcoma cells transfected with syngeneic MHC class II plus B7-1 genes. This approach is significantly more effective than previously described strategies using cytokine- or B7-transduced tumor cells which are only effective against smaller tumor loads, and which cannot mediate regression of longer-term established tumors. The most efficient tumor rejection occurs if both the class II and B7-1 molecules are coexpressed on the same tumor cell. Immunity induced by immunization with class II+B7-1(+)-transfected sarcoma cells involves CD4+ and CD8+ T cells, suggesting that the increased effectiveness of the transfectants is due to their ability to activate both of these T cell populations.

Animals↗

Left ventricular morphologic features and function in nonhospitalized cocaine users: a quantitative two-dimensional echocardiographic study.

To determine whether left ventricular (LV) hypertrophy or dysfunction is present in nonhospitalized cocaine users, we performed quantitative two-dimensional echocardiography in 20 intravenous cocaine users and 20 age- and sex-matched controls. Cocaine users were normotensive, had begun taking cocaine an average of 14 years earlier, and had used cocaine an average of 8 times/mo during the preceding year. There were no significant differences between cocaine users and control subjects for LV mass index (79 vs 74 gm/m2, respectively), mean wall thickness (0.95 vs 0.91 cm), end-diastolic volume index (55 vs 56 ml/m2), end-systolic volume index (17 vs 19 ml/m2), or ejection fraction (70 vs 66%; p > or = 0.09 for all comparisons). Moreover, none of the cocaine users or control subjects had significant regional wall motion abnormalities, and none of the subjects or controls had ejection fractions < 55%. Thus we found little evidence that significant LV hypertrophy or dysfunction is present in nonhospitalized cocaine users. From these results we speculate that cocaine-associated LV hypertrophy and dysfunction may be restricted to certain high-risk groups of chronic cocaine users.

Adult↗

Methamphetamine and ethanol interactions in humans.

OBJECTIVE: Methamphetamine and ethanol are commonly used together. We examined the effects of intravenous methamphetamine (30 mg), oral ethanol (1 gm/kg), and the combination of methamphetamine (30 mg) and ethanol (1 gm/kg). METHODS: Eight methamphetamine and ethanol users were studied in a double-blind, double-placebo, within-subject, balanced Latin-square design. Ethanol was administered in six drinks over 30 minutes. Methamphetamine was injected 60 minutes after the first drink was begun. Cardiovascular, subjective, and neuropsychologic effects of the drug combinations were measured for 6 hours. Methamphetamine and amphetamine in plasma and urine were measured by capillary gas chromatography for 48 hours. Data were analyzed by repeated-measures ANOVA. RESULTS: Compared with methamphetamine alone, the combination increased heart rate but decreased systolic blood pressure. The net cardiovascular effect was an increase in rate pressure product, an index of cardiac work and myocardial oxygen consumption. The combination diminished the subjective effects of ethanol while not affecting the subjective effects of methamphetamine. Methamphetamine pharmacokinetics were not altered by the concurrent administration of ethanol, with the exception of lowering the apparent volume of distribution at steady state for methamphetamine. CONCLUSIONS: As a potent sympathomimetic drug with alpha-agonist-like effects, methamphetamine increased systolic blood pressure, with minimal change in heart rate. The concurrent administration of methamphetamine and ethanol increased cardiac work, which could produce more adverse cardiovascular effects than either drug taken alone. The increased perceived global intoxication may explain the popularity of this drug combination.

Administration, Oral↗

Quantitative image analysis of p53 protein accumulation in keratoacanthomas.

Keratoacanthomas are benign skin tumors that grow rapidly but eventually regress. They occur most commonly in sun-exposed skin and are histologically remarkably similar to squamous cancers. Since mutations of the p53 tumor suppressor gene are found frequently in cutaneous squamous cell carcinomas, we hypothesized that p53 mutations might contribute to the development of keratoacanthomas. To address this question, we did p53 immunohistochemistry with a polyclonal rabbit antiserum, CM-1, that binds both mutant and wild-type p53 proteins. Although wild-type p53 protein degrades rapidly and is generally undetected by immunohistochemistry, mutant p53 protein has a longer half-life and accumulates to detectable levels. We tested 26 formalin-fixed keratoacanthomas and 4 normal skin biopsies. Positive nuclear staining was detected in 20 of 26 (77%) of the keratoacanthomas and in none of the normal skin samples. Nuclear staining occurred in the outermost layer of the neoplasms and not in the keratin-filled central cores. Since nuclear p53 protein within a cutaneous squamous cell carcinoma usually correlates with missense mutation, these data suggest that p53 mutations contribute to the development of this benign neoplasm. The histologic similarity to squamous cell carcinoma and the accumulation of p53 protein suggest progression toward malignancy, but the invariable regression of these tumors suggests an arrest at some point in multistage carcinogenesis. If this model is correct, then genetic analysis of keratoacanthomas may provide clues to the later stages of squamous carcinogenesis including local invasion and metastasis.

Animals↗

An epidemic of occupational allergy to latex involving health care workers.

IgE-mediated sensitivity to natural rubber latex is being recognized more frequently among health care workers. Between January 1990 and June 1993, we evaluated 342 consecutive Mayo Medical Center employees who reported symptoms suggestive of latex allergy. All were interviewed and underwent puncture skin testing with extracts of rubber gloves. In some cases, latex-specific IgE antibodies were measured by immunoassay. One hundred four of the 342 employees evaluated (30%) were latex-allergic. Risk factors for sensitization included frequent use of disposable gloves, presence of prior atopic disease, and prior or current hand dermatitis. The peak onset of symptoms occurred in late 1989 and early 1990 and did not correlate with a peak in glove usage at our medical center, which continued to rise. Most sensitized employees (78%) reported contact urticaria from rubber gloves, and over two thirds also experienced allergic rhinitis, conjunctivitis, or asthma when working in areas where large numbers of gloves were being used. Sixteen episodes of rubber-induced anaphylaxis were documented in 12 employees; six episodes occurred after latex skin testing and were easily reversed with appropriate therapy. Our findings substantiate a local epidemic of latex allergy among medical center employees. Epidemiologic studies are needed to assess the effects of various interventions to reduce occupational exposure to latex allergens. Although prick skin testing with concentrated latex glove extracts presents some risk of systemic reaction, pending availability of commercial diagnostic extracts, such testing is generally safe when performed by skilled laboratory personnel. Skin testing is warranted to investigate health care workers suspected of being latex-sensitive.

Anaphylaxis↗

Anaphylaxis induced by the carboxymethylcellulose component of injectable triamcinolone acetonide suspension (Kenalog).

BACKGROUND: Allergic reactions to various corticosteroids are rare but have been reported previously. OBJECTIVE: We wished to determine the etiology of an anaphylactic reaction in a patient who had received intracutaneous Kenalog (triamcinolone acetonide). METHODS: Skin testing and serologic testing for allergen-specific IgE antibodies was performed for triamcinolone acetonide, its individual components, and three other corticosteroid preparations in both the patient and six other nonallergic persons. RESULTS: The patient had positive skin tests to only the carboxymethylcellulose component of triamcinolone acetonide. He had negative skin test reactions to three other steroid preparations which did not contain carboxymethylcellulose. Specific IgE antibodies to carboxymethylcellulose were also elevated by immunoassay and immunoblotting. Control patients had negative skin tests to triamcinolone acetonide, its components, and three other corticosteroid preparations, and their sera lacked significant specific IgE antibodies to these materials. CONCLUSIONS: Our results indicate that the triamcinolone acetonide component responsible for the patient's reaction was the suspending agent carboxymethylcellulose. We urge physicians to consider component testing when patients experience allergic-type reactions to drugs.

Adult↗

Oral allergy syndrome successfully treated with pollen immunotherapy.

BACKGROUND: Some patients with allergic rhinitis have oral allergic reactions to fresh fruits and vegetables. This phenomenon has been termed "oral allergy syndrome" and is proposed to be due to cross-reacting allergens in the foods and pollens. METHODS: We report a patient with allergic rhinitis and oral allergy syndrome treated with pollen immunotherapy. Prior to immunotherapy, eating any fresh fruit or vegetable caused immediate itching and swelling of his tongue and throat. Prick skin test titration with pollens and foods was performed before and after 13 months of immunotherapy. Specific IgE immunoassay was performed with the same extracts on serum obtained before and after 7 and 13 months of immunotherapy. IgE immunoblots were performed on the same extracts separated by polyacrylamide gel electrophoresis using sera from the same time periods. RESULTS: After 1 year on immunotherapy, the patient's allergic rhinitis symptoms resolved, and he was able to eat fresh fruits and vegetables without reaction. Skin testing and specific IgE immunoassay demonstrated a marked reduction in sensitivity to not only the pollens but the foods as well. Immunoblots revealed that the intensity of IgE binding to most components of the extracts, some common to pollens and foods, declined during immunotherapy. CONCLUSIONS: These results support the notion that oral allergy syndrome is due to cross-reacting allergens in foods and pollens and may be amenable to treatment with pollen immunotherapy.

Adult↗

Psychosocial correlates of fire disaster among children and adolescents.

This study examined the extent of children's and adolescents' psychosocial maladjustment associated with a natural disaster, namely, wildfire. The course of psychopathology was assessed six weeks after a major wildfire destroyed 420 homes. Victims' functioning relative to a comparison group from the same community, matched for age, gender, socioeconomic status, and fire insurance was examined. The major goal of this study was to assess systematically the short-term mental health consequences of a wildfire disaster among children and adolescents. This goal was achieved through the use of standardized assessment procedures. The results of this study add useful information to the literature concerning the impact of disaster among children and adolescents and provide a methodological framework for future efforts in this area.

Adolescent↗