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Biomedical subjects

J Karp

Publications and source records attributed to J Karp.

16 recordsLinked to original sources

In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman primates.

[99mTc]TRODAT-1 was the first 99mTc-labeled imaging agent to show specific binding to dopamine transporters (DAT) in the striatum (STR) of human brain. Additionally, in vitro binding and autoradiographic experiments demonstrated that this tracer also binds to serotonin transporters (SERT) in the midbrain/hypothalamus (MB) area. In this study, [99mTc]TRODAT-1 was investigated as a potentially useful ligand to image SERT in the MB of living brain. A total of eight single-photon emission tomography (SPET) scans were performed in two baboons (Papio anubis) after intravenous (i.v.) injection of 740 MBq (20 mCi) of [99mTc]TRODAT-1 using a triple-head gamma camera equipped with ultra-high-resolution fan-beam collimators (scan time: 0-210 min). In four blocking studies, baboons were pretreated with (+)McN5652 (1 mg/kg, i.v.) or methylphenidate (1 mg/kg, i.v.) to specifically block SERT or DAT, respectively. After co-registration with magnetic resonance images of the same baboon, a region of interest analysis was performed using predefined templates to calculate specific uptake in the midbrain area and the striatum, with the cerebellum as the background region [(MB-CB)/CB, (STR-CB)/CB]. Additionally, two PET scans of the same baboons were performed after i.v. injections of 74-111 MBq (2-3 mCi) of [11C](+)McN5652 to identify the SERT sites. In [99mTc]TRODAT-1/SPET scans, the SERT sites in the MB region were clearly visualized. Semiquantitative analysis revealed a specific uptake in MB ([MB-CB]/CB) of 0.30+/-0.02, which was decreased to 0. 040+/-0.005 after pretreatment with nonradioactive (+)McN5652, a selective SERT ligand. Pretreatment with methylphenidate reduced the specific binding of [99mTc]TRODAT-1 to DAT sites [(STR-CB)/CB] from 2.45+/-0.13 to 0.32+/-0.04 without any effect on its binding to SERT sites [(MB-CB)/CB], which was confirmed by the co-registration of the [11C](+)McN5652/PET scans. This preliminary study suggests that specific binding of [99mTc]TRODAT-1 to SERT sites can be detected by in vivo SPET imaging despite the low target to background ratio. These findings provide impetus for further development of similar compounds with improved binding affinity and selectivity to SERT sites.

Adrenergic Uptake Inhibitors↗

Anxiety sensitivity and self-reported reasons for drug use.

Two studies examined the relationships between anxiety sensitivity (AS), drug use, and reasons for drug use. In Study 1, 229 university students (57% F) completed the Anxiety Sensitivity Index (ASI) and a drug use survey, assessing use of a variety of drugs within the last month, and coping reasons for drug use. Consistent with a modified tension-reduction hypothesis, ASI scores were positively correlated with the number of both anxiety- and depression-related reasons for drug use endorsed. In Study 2, 219 university students (74% F) completed the ASI and a drug use survey, assessing use of several drugs (e.g., alcohol, cigarettes, caffeine, and marijuana/hashish) within the last year, and primary reasons (coping, affiliative, or enhancement) for the use of each drug. Marijuana/hashish users reported lower ASI scores than non-users supporting a negative relation between AS and the use of cannabis. ASI scores were positively correlated with the use of alcohol primarily to cope, and negatively correlated with the use of alcohol primarily to affiliate, among both gender groups, and ASI scores were positively correlated with the use of nicotine primarily to cope among the females. Implications of these findings for understanding risk for abuse of stress-response-dampening drugs by high AS individuals are discussed.

Adaptation, Psychological↗

Carcinoma of the lung in HIV-positive patients: findings on chest radiographs and CT scans.

OBJECTIVE: Several recent clinical studies have described an association between HIV seropositivity and lung cancer. The purpose of this study was to describe the spectrum of imaging findings in HIV-positive patients who had proved carcinoma of the lung. In particular, we attempted to define the role of CT in diagnosing HIV-associated lung cancer. MATERIALS AND METHODS: The study population consisted of 23 HIV-positive patients from two institutions who had lung cancer diagnosed between 1989 and 1993. All patients had both chest radiographs and CT scans. The group included 19 men and four women with a mean age of 42 years. The diagnosis of lung cancer was confirmed by bronchoscopy in eight patients, by pleural fluid aspiration or pleural biopsy in seven, by percutaneous needle biopsy of a lung lesion in three, by biopsy of an extrathoracic site in four, and by thoracotomy in one. Two thoracic radiologists retrospectively evaluated the chest radiographs and CT scans to identify parenchymal masses, lymphadenopathy, pleural disease, chest wall or mediastinal invasion, and metastatic lesions. RESULTS: Fifteen (65%) of the 23 patients had a central or peripheral mass or nodule. Eight (35%) had extensive pleural disease, either as an isolated finding or in combination with other abnormalities. CT scans showed the malignant lesion underlying the extensive pleural disease in all but one case. All patients with extensive pleural disease had adenocarcinoma. No patient in the study was considered a candidate for resection on the basis of clinical and radiologic evaluation. CONCLUSION: Lung cancer in HIV-positive patients manifested most often on chest radiographs as a central or peripheral mass or nodule. Extensive pleural disease in the absence of an apparent primary lesion was the second most common major manifestation. Lung cancer therefore merits serious consideration in the differential diagnosis of extensive pleural disease in HIV-positive patients. CT was most useful in evaluating malignant lesions associated with extensive pleural disease.

Adenocarcinoma↗

Lung cancer in patients with immunodeficiency syndrome.

We report adenocarcinoma of the lung in seven patients with human immunodeficiency virus (HIV) infection. We compared age, clinical findings and survival data with a sex-matched control group of HIV-negative patients with adenocarcinoma of the lung. Median age of HIV-infected patients with lung cancer was lower than in control patients with lung cancer. The HIV-infected patients had more systemic symptoms and abnormal physical findings than control subjects. Both groups had smoking histories. Laboratory data were similar but control subjects had lower blood oxygen tensions than did HIV patients; HIV patients had more abnormalities on chest roentgenograms and computed tomography scans than did control subjects. All HIV-infected patients were stage IV. Median survival was 4 weeks. For control patients, 50 percent had stage IV disease; median survival was 25.5 weeks. Thus, patients with HIV infection develop lung cancer at a younger age than sex-matched control subjects and undergo a more fulminant course with shortened survivals.

Acquired Immunodeficiency Syndrome↗

Bone densitometry observations of osteopetrosis in response to bone marrow transplantation.

Spinal bone density was measured in eight patients with osteopetrosis to assess the natural history of the disease and to monitor the response to therapy. Quantitative computed tomographic scans of the lumbar vertebra were obtained in seven patients, and dual photon absorptiometric scans were obtained when the technique became available. Six children were afflicted with the infantile malignant recessive condition and two with the less severe dominant condition. In all cases, bone densitometry values ranged from four to five times higher than the mean for normal age and gender-matched controls. In four children with recessive osteopetrosis, quantitative computed tomographic and dual photon absorptiometric scans showed an excellent correlation (R = 0.93) between the methods. Quantitative computed tomographic values ranged from 597 to 730 mg/cm3 (mean = 655 mg/cm3) in children with osteopetrorickets and from 901 to 1000 mg/cm3 (mean = 980 mg/cm3) in the same children when the rickets was cured. In two children treated with bone marrow transplantation, bone densitometry values returned to normal within three years. Bone densitometry provides a safe and noninvasive method for observing the natural history and therapeutic response of the osteopetrotic syndromes.

Absorptiometry, Photon↗

Blood lead, calcium status, and behavior in preschool children.

To determine if calcium status is associated with blood lead levels and behavior, 64 black urban children aged 18 to 47 months were studied. Twenty-seven controls (blood lead levels, less than 1.45 mumol/L) were compared with 37 cases (blood lead levels, greater than or equal to 1.45 mumol/L) with respect to four calcium measures (calcium intake, serum calcium level, 1,25-dihydroxyvitamin D level, and bone densitometric findings) and three behavioral scores. Levels of 25-hydroxyvitamin D provided a measure of vitamin D sufficiency. As expected, blood lead level was associated with pica scores. However, none of the calcium measures differed between cases and controls. Controlling for four confounders (season, pica score, maternal education, and sex), yielded no significant differences between the two groups in the mean values of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D level. There was no interaction between blood lead level and the four covariates. No relationship could be demonstrated between calcium status and the pica scores.

Bone Density↗

Magnetic resonance imaging of experimental demyelinating lesions.

An animal model of central nervous system demyelination was created by injecting rat internal capsules with lysophosphatidylcholine (LPC). The resulting chemically induced demyelinating lesions were readily visible in T1-weighted spin-echo, T2 weighted spin-echo, and inversion-recovery magnetic resonance imaging (MRI) sequences. Changes in lesions were followed over 8 weeks and correlated with histopathology. Histologically, lesions were characterized initially by an acute, inflammatory phase with edema and blood-brain barrier breakdown, followed by macrophage-mediated removal of myelin debris and finally by remyelination after 3 to 4 weeks. MRI can differentiate lesion stages in the LPC model and may be useful in investigating mechanistic aspects of the demyelinating process. In addition the well-localized lesions may be amenable to study by techniques of volume-localized NMR spectroscopy.

Animals↗

Bone mineral content in black pre-schoolers: normative data using single photon absorptiometry.

Fifty-nine children aged 18 to 47 months with normal and elevated blood lead levels had bone mineral density (BMD in gm/cm2) and bone mineral content (BMC in gm/cm) measured using the technique of single photon absorptiometry of the radius shaft. No normative data are available for black children of this age group. Moderate elevations of blood lead were not found to influence bone mineralization. The BMC of the study children was significantly higher than the published values for white children of the same age. We found no statistical difference between the bone mineral density of males and females in this age group.

Absorptiometry, Photon↗

Single photon absorptiometry imaging as a screening method for diminished dual photon density measures.

Scanning of the new 5-mm distal-radius site and the mid-radius (33% site) was performed using single photon absorptiometry (SPA) and of the L2-L4 region of the spine using dual photon absorptiometry (DPA) in a group of healthy women (age range 36-66 yr) in order to develop parameters to enable SPA to be used to screen for low DPA measures. The study data were analyzed as follows: 1. Women were classified as either 'intact' or 'post pelvic surgery' and the data for the two groups were separated. 2. Each SPA measurement was scrutinized and the one which produced the lowest score (% young normal [YN]) was entered for data analysis and graphing. The application of these two analytical discriminators represents a new approach in the biomedical literature. The findings were as follows: 1. When women were separated according to whether they were intact or had undergone pelvic surgery, the threshold value for screening using radius measures among intact women was set at 80% YN. 2. The necessary threshold value for the pelvic-surgery group needed to be set higher, at 93% YN. 3. If either the distal density or the mid-shaft density was below its threshold level, DPA was indicated. 4. At these threshold levels, no women with diminished spinal density (less than 83% YN) were omitted from screening procedure. We conclude that by refining our evaluation of each healthy woman according to her pelvic physiology status (intact or post-surgery) and considering whether either of the two SPA measures is below the threshold value, we will be able to screen for diminished DPA density and thereby eliminate a significant number of expensive but uninformative DPA readings.

Adult↗

Norfloxacin for prevention of bacterial infections in granulocytopenic patients.

The efficacy and safety of norfloxacin were compared with those of placebo, vancomycin-polymyxin, and trimethoprim-sulfamethoxazole (TMP/SMX) for prophylaxis of bacterial infections in granulocytopenic patients. The study results showed that norfloxacin treatment, which was well tolerated and not associated with any serious systemic adverse effects, prevented acquisition of gram-negative bacillary organisms. Fewer norfloxacin-treated patients (38 of 108 patients, or 35 percent) experienced microbiologically documented infections compared with patients receiving placebo (27 of 40 patients, or 68 percent), vancomycin-polymyxin (16 of 30 patients, or 53 percent), or TMP/SMX (14 of 28 patients, or 50 percent). Gram-negative bacteremia developed in five of 108 norfloxacin-treated patients (5 percent), compared with 17 of 40 placebo-treated patients (43 percent), five of 30 treated with vancomycin-polymyxin (17 percent), and one of 28 patients treated with TMP/SMX (4 percent). The incidence of gram-positive bacteremia was similar in all study groups and was not affected by norfloxacin or any other oral prophylactic antibiotics. These results suggest that norfloxacin is both safe and effective for the prevention of serious gram-negative bacillary infections in granulocytopenic patients. More effective prophylaxis of gram-positive bacterial infections, however, is needed.

Adolescent↗