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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 289 records · Page 16Linked to original sources

Indirect computed tomography lymphography using iodinated nanoparticles to detect cancerous lymph nodes in a cutaneous melanoma model.

RATIONALE AND OBJECTIVES: To evaluate differences in contrast uptake in normal and cancerous lymph nodes on indirect computed tomography (CT) in swine, we conducted lymphographic examinations after subcutaneous injection of a lymphotropic iodinated nanoparticle suspension. METHODS: Perilesional subcutaneous contrast injections (2 ml per lesion) of a 15% wt/vol iodinated nanoparticle suspension were made in immature Sinclair miniature swine (n = 5) with cutaneous melanomas. Average attenuation, iodine concentration, node volume, and total iodine uptake were estimated on the CT scans for each opacified lymph node 24 hr after injection. Nodes were classified as normal or cancerous microscopically, and the percentage of tumor replacement was estimated in cancerous nodes. RESULTS: Average attenuation and iodine concentration were higher in normal nodes, and total iodine uptake was higher in cancerous nodes with greater than 25% replacement (p < .05). Architectural alterations in opacified cancerous nodes included medullary filling defects, expansile cortical lesions, and disruption of corticomedullary junctions. CONCLUSION: Quantitative and qualitative differences in iodinated nanoparticle enhancement characteristics are useful in distinguishing between normal and cancerous lymph nodes on indirect CT lymphography examinations.

Animals↗

Developmental regulation of transforming growth factor beta-mediated collagen synthesis in human intestinal muscle cells.

BACKGROUND & AIMS: The intestinal wall is formed by smooth muscle and the regulated deposition of specific collagen types. This study is the first to examine transforming growth factor beta (TGF-beta) in human fetal intestinal muscle. Studies localized TGF-beta within the muscularis propria, identified the cellular source, measured TGF-beta, and determined effects on collagen synthesis from 10 to 21 weeks of gestation. METHODS: Localization of TGF-beta within the intestinal wall and in cultured cells was determined immunohistochemically. TGF-beta was measured by the CCL-64 cell growth inhibition assay. Collagen production was assayed as the uptake of 3H-proline into collagenase-digestible protein. Collagen types were identified by polyacrylamide slab gel electrophoresis and quantitated by densitometry. Experiments were performed in TGF-beta (50-200 pg/mL) or anti-TGF-beta (50-200 micrograms/mL). RESULTS: TGF-beta 1 was localized in muscle cells of the muscularis propria and in culture. Muscle cells produced 340% more TGF-beta at 11 weeks of gestation than at 20 weeks. At 10 weeks of gestation, TGF-beta inhibited collagen production by 38%, but stimulated collagen synthesis by 70% at 21 weeks of gestation. TGF-beta altered the expression of individual collagen chains in an age-specific manner. CONCLUSIONS: Smooth muscle cells secrete TGF-beta during human fetal intestinal development. TGF-beta stimulates or inhibits the expression of specific collagen chains depending on gestational age.

Cell Division↗

Prevalence of anal human papillomavirus infection and anal cytologic abnormalities in HIV-seropositive women.

OBJECTIVE: To determine the prevalence of anal human papillomavirus (HPV) infections and anal cytologic abnormalities in HIV-seropositive and HIV-seronegative women. DESIGN: This cross-sectional study of a cohort of women with known HIV serostatus involved a standardized interview and a gynecologic examination, including a cytologic evaluation of the cervix and anus. Anal swabs were tested for HPV DNA using the Hybrid Capture assay. SETTING: Two HIV/AIDS clinics, a sexually transmitted disease clinic, a methadone clinic and women enrolled in a study of HIV heterosexual transmission in the greater New York City metropolitan area. PATIENTS: One hundred and two HIV-seropositive and 96 HIV-seronegative women were selected from an ongoing study of the gynecologic manifestations of HIV infection. MAIN OUTCOME MEASURES: Detection of anal HPV DNA and anal cytologic abnormalities. RESULTS: Anal cytologic abnormalities were detected in 27 (26%) of the 102 HIV-seropositive women and in six (7%) of 96 HIV-seronegative women. Five (5%) of the anal smears from the HIV-seropositive women and one (1%) from the HIV-seronegative women had low-grade anal intra-epithelial neoplasia. The remainder of the anal cytologic abnormalities were classified as mild squamous cytologic atypia. HPV DNA was detected in 30 (29%) of 102 HIV-seropositive and two (2%) of 96 HIV-seronegative women. Of the 33 patients with anal cytologic abnormalities, 19 (58%) had anal HPV DNA detected as compared to 13 (8%) of 160 women without cytologic abnormalities (P < 0.001). In a multivariate logistic regression analysis, HIV-seropositivity was found to be an independent risk factor for both anal HPV infection and anal cytologic abnormalities and the strength of the association was greater in women with lower CD4+ T-lymphocyte counts. CONCLUSION: The prevalence of both anal cytologic abnormalities and anal HPV infection are significantly increased in HIV-seropositive women.

Adult↗

Computed tomographic observations on subcutaneous fat: implications for liposuction.

The anatomy of the abdominal subcutaneous tissues is discussed in the light of data obtained in 20 female patients examined on a modern computed tomographic system. We have shown that the superficial fascia, which separates the superficial and deep layers of subcutaneous fat, forms a continuous circumferential fascial plane. This superficial fascia, contrary to previous reports, does not appear to merge with the deep fascial plane around the external oblique muscle. The fat in the deep subcutaneous layer, bounded by the superficial fascia, is the target for liposuction techniques. The CT data have shown that about 50 percent of subcutaneous fat resides within this deep layer.

Adipose Tissue↗

Pacemaker patient-triggered event recording: accuracy, utility, and cost for the pacemaker follow-up clinic.

Many pacemaker patients have vague symptoms following implantation. It is often difficult for the physician to ascertain if they are cardiac in origin. A new pacemaker feature has been introduced, Patient-Triggered Event Records (PTER), to help the physician with this diagnosis. The PTER is a continuously running event record which stores the cardiac rhythm and rate. Brief application of a magnet will transfer the record into the device's memory. The data recorded will be the 97 events prior to the magnet application and the 30 events following magnet removal. The exact state of pacing (atrial and ventricular sensing/pacing, or premature ventricular events) and the rate of the ventricular events will be graphically displayed by the programmer for all 127 events. Thus, the exact pacer and cardiac rhythm can be determined during the period of the symptomatic episode. A total of three PTER's can be stored within the device. If a fourth is recorded, it will replace the oldest record. Three pacemakers with the PTER feature were tested in vitro with five different simulated cardiac rhythms. A beat-by-beat comparison between the PTER and the 15 simulated test rhythms revealed a 100% accurate documentation by PTER. Sixteen pacemaker patients which have the PTER feature were monitored using a King of Hearts for a total of 43 symptomatic events. The PTER records produced clinically relevant information 98% of the time while the King of Hearts produced clinically relevant information 81% of the time. A comparison of costs of the two different methods of monitoring these patients, was $2,432 versus $4,480 for the PTER and loop event monitor respectively. The PTER is an accurate, lower cost method for monitoring and diagnosing symptomatic pacemaker patients. The PTER can be used as the first diagnostic tool in troubleshooting patients with paroxysmal symptoms in the pacemaker clinic population.

Adult↗

Safe performance of magnetic resonance imaging on five patients with permanent cardiac pacemakers.

UNLABELLED: Five patients with permanent cardiac pacemakers (Pacesetter models 261, 285, 2016, 2020, 2022) underwent magnetic resonance imaging (MRI). Only one patient (underlying rhythm asystole) was pacemaker dependent. A variety of pacing configurations (single and dual chamber; unipolar and bipolar; sensor and nonsensor driven) were scanned. A thorough evaluation of each pacing system was performed before and after scanning including determination of pacing and sensing thresholds. During MRI the patient was monitored using either ECG, pulse oximetry, or direct voice contact. In four patients heavy dressings were applied over the pacemaker pocket site. Patients were asked to report any symptoms experienced during MRI. RESULTS: The four nonpacemaker dependent patients remained in sinus rhythm throughout the MRI. During and after the MRI all pacemakers continued to function normally except for one transient pause of approximately 2 seconds (noted by pulse oximeter) toward the end of the scan. This occurred in a pacemaker dependent patient with a unipolar dual chamber device programmed DOO. No patient experienced any torque or heat sensation. CONCLUSION: When appropriate strategies are used our experience suggests that MRI may be performed, when necessary, with an acceptable risk-benefit ratio to the patient. It is unclear whether the isolated pause that was observed was due to the effect of the MRI, an artifact with the monitoring system, or oversensing by the pacemaker. Appropriate patient selection, close monitoring during the scan, and follow-up after MRI are of paramount importance. Further study is necessary to refine the appropriate strategies that could be used to consistently perform MRI safely in a selected pacemaker population.

Contraindications↗

Short-course intravenous antibiotics with oral quinolone prophylaxis in the treatment of neutropenic fever in autologous bone marrow or peripheral blood progenitor cell transplant recipients.

The effectiveness of short-course intravenous antibiotics concurrent with prophylactic oral ciprofloxacin in the treatment of neutropenic fever was studied in 81 patients undergoing autologous bone marrow or peripheral blood progenitor cell transplantation (ABMT or PBPCT). During the neutropenic period following ABMT or PBPCT, 10/81 (12%) patients did not require treatment with intravenous antibiotics. Seventy-one patients required antibiotics. Forty-seven of the 71 (66%) responded to 72 h treatment with gentamicin, azlocillin or ceftazidime, and vancomycin. Thirty-three of the 47 (70%) responders had a complete resolution of their fever with no further recurrence. Fourteen of the 47 responders developed a second fever between 2 and 25 days after stopping first-line antibiotics. Eleven of the 14 patients responded to a second course of intravenous antibiotics. Twenty-four of the 71 patients did not respond to intravenous antibiotics and were treated with intravenous amphotericin and the intravenous antibacterial agents were discontinued. Eighteen of the 24 patients responded to amphotericin. The 6 patients who had persistent fever resolved their temperature when their neutrophil count recovered. There were no deaths due to infection during the study. Short-duration intravenous antibiotics in conjuction with oral ciprofloxacin prophylaxis are a safe and effective treatment for neutropenic fever.

Adolescent↗

Phase II study of topotecan in patients with extensive-stage small-cell carcinoma of the lung: an Eastern Cooperative Oncology Group Trial.

PURPOSE: To determine the response rate and survival of chemotherapy-naive patients with extensive-stage small-cell lung cancer (SCLC) treated with topotecan, and to determine the relationship of topotecan pharmacokinetics with response and toxicity. PATIENTS AND METHODS: Forty-eight patients with previously untreated, extensive-stage SCLC received 2.0 mg/m2 of topotecan daily for 5 days. The first 13 patients were treated without colony-stimulating factor (CSF) support; the next 35 patients received 5 micrograms/kg of granulocyte-colony-stimulating factor (G-CSF) for 10 to 14 days starting on day 6. Cycles were repeated every 3 weeks for a maximum of four cycles. Patients who had a partial response to topotecan after four cycles, stable disease after two cycles, or progressive disease at any time received salvage chemotherapy with cisplatin and etoposide. Topotecan pharmacokinetics were measured using a four-point sampling scheme. RESULTS: Of 48 patients, none had a complete response and 19 had a partial response, for an objective response rate of 39% (95% confidence interval [CI], 25.2% to 53.0%). The median response duration was 4.8 months (95% CI, 3.0 to 7.3). After a median follow-up duration of 18.2 months, the overall median survival time was 10.0 months (95% CI, 8.2 to 12.7); the 1-year survival rate was 39% (95% CI, 25.2% to 53.0%). Eight of 34 patients (24%) who received salvage chemotherapy responded. Four of 17 patients who did not respond to first-line therapy with topotecan responded to cisplatin and etoposide. The most common toxicity was hematologic. Ninety-two percent of patients treated without G-CSF developed grade 3 or 4 neutropenia, compared with 29% who received G-CSF. However, the incidence of neutropenic fevers was similar between the two groups (8% and 11%, respectively), and one patient in each group died of neutropenic fevers. There were no differences in objective tumor response, duration of response, time to treatment failure, or survival between the 13 patients who entered the study before G-CSF administration was mandated and the 35 patients who entered after and received G-CSF. There was poor correlation between the WBC count and absolute neutrophil counts (ANCs) and both the area under the curve (AUC) and maximum concentration++ (Cmx) of total topotecan in plasma. There was no correlation between the tumor response and either AUC or Cmx of total topotecan. CONCLUSION: The activity of topotecan in extensive-stage SCLC noted in this study warrants further investigation of this agent in phase III clinical trials.

Adult↗

The effect of physical therapy on respiratory complications following cardiac valve surgery.

STUDY OBJECTIVE: To determine whether higher personnel intensive chest physical therapy can prevent the atelectasis that routinely follows cardiac valve surgery. DESIGN: Randomized, controlled trial. SETTING: Tertiary care hospital. PATIENTS: Seventy-eight patients undergoing elective cardiac valve surgery between October 1991 and April 1993 were enrolled. INTERVENTIONS: Patients were randomized in an unmasked fashion to receive early mobilization and sustained maximal inflations (lower-intensity treatment) or to receive early mobilization, sustained maximal inflations, and single-handed percussions (higher-intensity treatment.) MEASUREMENTS AND RESULTS: Clinical efficacy was determined by extent of atelectasis, length of ICU stay, total length of hospital stay, and personnel costs. The extent of postoperative atelectasis was similar in both groups on the fifth postoperative day. Postoperative values of FVC and FEV1 were reduced to a similar extent in both groups. Hospital stays and ICU stays were similar regardless of treatment. Physical therapy costs were highest in the higher-intensity therapy group. CONCLUSIONS: Postoperative respiratory dysfunction is common but does not usually cause significant morbidity or prolong hospital stay. The routine prescription of high-intensity physical therapy does not improve patient outcomes but does add significantly to patient costs.

Aged↗

Employee age and perceptions of work in self-managing and traditional work groups.

Self-managing work groups are a form of work design in which employees take responsibility for the group's tasks and have discretion over decisions which impact group performance. To explore the impact of age and work teams on job attitudes, data from 477 employees suggested that self-managed work group members differed from traditional job holders regarding perceived general job satisfaction, perceived control by supervisors, as well as a number of specific dimensions of the work environment. Moreover, while there was evidence of an age effect on attitudes toward supervisory control, there was no joint effect of age by work design on job attitudes, i.e., one's perceived general job satisfaction. Older employees who were members of self-managed work groups were however, more impacted by this form of work design in reporting more positive perceptions of their access to information essential to the performance of their work. These findings suggest that an "older" work force should not be considered a barrier to implementing a work teams approach to job design.

Adult↗

In vitro competitive inhibition of plasma cholinesterase by cocaine: normal and variant genotypes.

OBJECTIVE: To determine the inhibitory constant, Ki, of cocaine for a number of the different genetic variants of human plasma cholinesterase. DESIGN: In vitro analysis of plasma cholinesterase activity in the presence of cocaine as a competitive inhibitor. METHODS: Six normal (UU) control sera and seven sera with the following plasma cholinesterase genotypes were assayed: AA, UA, AS, UF, US, AF and SS. Plasma cholinesterase activity was determined in the samples by colorimetric measurement of propionylthiocholine metabolism over a range of concentrations. Competitive activities were then determined in the presence of varying concentrations of cocaine. Double reciprocal plots (1/v vs 1/S) were used to calculate Km and Vmax for propionylthiocholine, and Ki for cocaine for each genotype. RESULTS: The variant forms of the plasma cholinesterase had high cocaine Ki values--all were approximately ten times greater than the Ki for normal plasma cholinesterase. CONCLUSIONS: Since the inhibitory constant is an indirect measure of an enzyme's affinity for a competing substrate, a high Ki for cocaine at recreational or therapeutic concentrations would translate into a longer in vivo half-life. Our results support the growing evidence that low plasma cholinesterase activity predisposes to cocaine toxicity.

Cholinesterase Inhibitors↗

Medical examination of the internationally adopted child: screening for infectious diseases and developmental delay.

Because of the number of internationally adopted children with undiagnosed disease, a defined set of screening tests for medical evaluation is now recommended. By and large, these tests are directed toward infectious diseases that are more common abroad than in the United States. In this article, the authors examine various aspects of screening and highlight tests that are useful in children from specified areas. They also review developmental issues that are of prime importance to these children and their new families.

Adoption↗

Pilot study of vinorelbine (navelbine) and paclitaxel in patients with refractory non-small cell lung cancer.

Eighteen patients with metastatic non-small cell lung cancer were treated with a combination of intravenous vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) 25 mg/m2 on days 1 and 8 and intravenous paclitaxel 175 mg/m2 on day 2 every 3 weeks. All patients were given granulocyte colony-stimulating factor 5 micrograms/kg/d subcutaneously on days 3 through 7 and 9 through 17 or until the absolute neutrophil count reached 10 x 10(9)/L or higher. One patient was enrolled in this study too recently to be assessed. The mean age of the remaining 17 patients was 59 years (age range, 33 to 75 years); all but one patient had refractory disease, mostly to cisplatin-containing regimens. Four patients were ineligible (two because of poor performance status and two because of previous exposure to vinblastine). Three partial responses were observed, with durations of 46, 64, and 140+ days. Four patients had stable disease and four had progressive disease. The most common side effect was neutropenia (five grade 4 and one grade 3); two patients died of leukopenic sepsis in the first cycle. Peripheral neuropathy was also common (four grade 1 and one grade 2 sensory neuropathy). Other toxic effects were anemia and nausea and vomiting. The median survival was 153 days in all patients and 179 days in eligible patients. The preliminary results in this ongoing study of combination vinorelbine and paclitaxel as second-line therapy for metastatic non-small cell lung cancer are promising, and using this regimen as first-line therapy is warranted.

Adult↗

Expression cloning of a human brain neuropeptide Y Y2 receptor.

The 36-amino acid peptide, neuropeptide Y (NPY), is a member of a peptide family that includes the endocrine peptides, peptide YY (PYY), and pancreatic polypeptide (PP). NPY receptors have been broadly subdivided into postsynaptic Y1 receptors and presynaptic Y2 receptors based on the preference of Pro34-substituted analogues for the Y1 receptors and carboxyl-terminal fragments for the Y2. A Y1 receptor has been cloned, and this receptor appears to mediate several effects of NPY, including vasoconstriction and anxiolysis in animal models. We report the cloning of a human brain Y2 receptor from a human brain library. Pools of clones were transiently expressed in COS-1 cells, and 125I-PYY binding pools were identified by autoradiography. After a single positive pool was detected in the original screening, a single clone was isolated by four rounds of sequential enrichment. The clone encoded a 381-amino acid protein of the heptahelix (seven TM) type. Amino acid identity of this receptor with the Y1 receptor was 31% overall with 40% identity in the TM regions. Comparison with the human PP1 receptor indicated 33% overall amino acid identity with 42% identity in the TM regions. Pharmacologically, the receptor exhibited high affinity for NPY, PYY, and carboxyl-terminal fragments of NPY and PYY. In addition, Pro34-substituted analogues had very low affinity. With the use of Northern blot analysis, high levels of Y2 mRNA were detected in a variety of brain regions with little expression in peripheral tissues. Thus, the receptor protein has the pharmacological properties and distribution of the human Y2 receptor.

Amino Acid Sequence↗

Evaluation of the biomaterial-interface of screw threads in patients having clinical pain.

Fixation devices are normally anchored and stabilized with the use of metallic screws. Under normal circumstances, the patient has no adverse response to the fixation device. However, there are some patients that experience a significant amount of pain and the hardware needs to removed. Removal of the hardware, alleviates the pain. The tissues adjacent to the implanted devices were harvested and analyzed histochemically for cellular detail and immunochemically for the presence of PGE2. These tissues were compared with tissues retrieved from nonpainful stable fixation devices that were removed when they no longer were needed for stabilization. The results showed radiographically the presence of osteolysis in the area of the screw thread in patients with clinical pain. Also, histologically there was a presence of synovial-like granuloma tissue possibly produced by the micromotion of the loosened screw. When the tissues were analysed qualitatively by ELISA for PGE2 they had a statistically significant amount in comparison with tissue retrieved from patients with no clinical pain. The presence of PGE2 in the tissues suggest that this inflammatory mediator is produced in tissues adjacent to unstable devices and may mediate the osteolysis associated with the late implant failure and clinical pain.

Biocompatible Materials↗