Biomedical subjects
Publications and source records attributed to R Palmer.
When an elderly patient with Alzheimer's disease or other form of dementia exhibits agitated behavior, the caregiver often wants the physician to "do something"--i.e., give a neuroleptic drug. Yet, an individualized, rational approach to identify and treat the cause of the agitation is more effective. We present an algorithm that emphasizes environmental and behavioral therapy.
The patient centered "Acute Care of the Elderly Unit" is a multifaceted process of care that combines optimal geriatric nursing and medical care of elders within an interdisciplinary model. Although functional decline has been previously assumed to be an inevitable consequence of hospitalization, preliminary findings suggest that a patient centered multidisciplinary model of geriatric care prevents functional decline of hospitalized elders. In addition, the "low tech" interventions and cost savings outcomes suggests the feasibility of implementing this model of care in hospitals serving a variety of patient populations.
Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 microM, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs. ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANG I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P < 0.01); addition of cap decreased MAP to 95+/-3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101+/-129 to 370+/-158 pg/ml, P < 0.01; and ANG II = 22+/-40 to 466+/-49, P < 0.01); addition of cap further increased ANG I (1,790+/-158, P < 0.01) and decreased ANG II (33+/-49, P < 0.01). ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG I (8,269+/-502 and 6, 139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695). The finding of very high ANG I and ANG II levels in the ISF vs. intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces.
PURPOSE/OBJECTIVE: To evaluate the feasibility, response rates, and toxicity of a Phase II study using targeted supradose cisplatin and concurrent radiation therapy in unresectable Stage III-IV head and neck squamous cell carcinoma. METHODS AND MATERIALS: Sixty patients presenting between 6/93-9/94 were enrolled, 44 (73%) of whom had T4 and/or N2-N3 nodal disease. All patients were treated with rapid targeted superselective intraarterial infusions of cisplatin (150 mg/m2 weekly x 4) and simultaneous sodium thiosulfate intravenously (9 g/m2) for systemic neutralization of cisplatin. Concurrent (day 1) daily radiation therapy was delivered to the primary tumor and overt nodal disease to 66-74 Gy while the uninvolved lower neck received 50 Gy, at 2.0 Gy/fraction. RESULTS: Fifty-one (85%) patients completed the full RADPLAT protocol as planned. Fifty-seven of 60 patients were evaluable for response. Histological (n = 50) or clinical (n = 7) assessment of primary site revealed a complete response (CR) in 52 patients, partial response (PR) in 4, and stable disease (SD) in 1. Of the 40 patients presenting with nodal metastases, pathological (n = 31) or clinical (n = 6) assessment revealed a CR in 25, PR in 11, and SD in 1, while 3 were unevaluable. Overall, for both primary site and nodal disease, CR was attained in 44 (75%), PR in 12 (23%), and SD in 1 (2%) of the 57 evaluable patients. Only 2 (4%) of 57 evaluable patients have recurred above the clavicle, 1 in the primary site and 1 in the regional lymph nodes. Twelve patients (23%) have failed in distant sites. Grade III/VI toxicity has included gastrointestinal in 6, hematologic in 6, mucosal in 12, vascular in 4, and neurological in 4 patients. CONCLUSION: Concurrent radiation therapy and targeted supradose cisplatin (i.e., RADPLAT) can be safely delivered with high response rates and excellent loco-regional control in advanced Stage III/IV head and neck squamous cell carcinoma.
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In vitro umbilical cord blood B lymphocytes fail to form IgG and IgA secreting plasma cells when stimulated with Pokeweed mitogen. Since previous investigators have found percentages of B lymphocytes expressing surface IgG or surface IgA comparable to those seen in adults, this implies a defect in umbilical cord blood B-lymphocyte function. We have examined surface Ig expression on umbilical cord blood B lymphocytes by flow cytometry under conditions in which serum derived Ig are rigorously excluded. Under these conditions no B lymphocytes expressing surface IgG or IgA, which should serve as precursors for IgG and IgA secreting plasma cells, were observed. This finding was confirmed by comparing the ratio of mRNA levels for immunoglobulin gamma-chain to mu-chain in mononuclear cells by quantitative mRNA-based PCR. The ratio in umbilical cord mononuclear cells was 10-fold less than that seen in adult cells. The inability of newborn peripheral blood to form IgG and IgA plasma cells may result from an absence of appropriate precursor cells and not a defect in B lymphocyte maturation.
This is the second in a series of three articles addressing the intersection of interests in behavioral genetics and behavioral medicine. In this article, we use risk factors for cardiovascular disease as a prototypical trait for which behavioral genetic approaches provide powerful tools for understanding how risk factors, behavior, and health outcomes are related. The approach synthesizes a number of methods and areas of interest in an attempt to arrive at a comprehensive, whole-organism understanding of health-related risk factors and their response to behavioral interventions.
BACKGROUND: Aerobic bacterial pathogens are recovered from 65 to 85% of patients with acute otitis media (AOM). Although Chlamydia pneumoniae is a common pathogen of pediatric pneumonia, it has rarely been cultured from children with chronic otitis media and its role in AOM is unknown. METHODS: We cultured for C. pneumoniae in tympanocentesis aspirates and nasopharyngeal swabs from 101 consecutive, otherwise healthy children with AOM or refractory AOM. A control group of 50 similarly aged, healthy children was evaluated for nasopharyngeal carriage of C. pneumoniae. Specimens were also evaluated by PCR for C. pneumoniae. RESULTS: C. pneumoniae was recovered by tympanocentesis in 8 (8%) of 101 children with AOM. Among the 8 children with C. pneumoniae-positive-AOM, 5 had C. pneumoniae detected by PCR in middle ear fluid, none had C. pneumoniae recovered by nasopharyngeal culture or PCR and 5 were younger than 16 months. C. pneumoniae was the sole pathogen isolated in 2 patients. Copathogens included beta-lactamase-positive positive Haemophilus influenzae (2), beta-lactamase positive Moraxella catarrhalis (1), penicillin-resistant Streptococcus pneumoniae (2) and penicillin-susceptible S. pneumoniae (1). C. pneumoniae was recovered from nasopharyngeal culture in 2 additional patients with C. pneumoniae-negative AOM and in none of 50 healthy control children, although 2 controls were positive by PCR from the nasopharynx. CONCLUSIONS: This is the first study to report the isolation of C. pneumoniae in middle ear fluid of children with AOM.
OBJECTIVE: To compare the hospital costs of caring for medical patients on a special unit designed to help older people maintain or achieve independence in self-care activities with the costs of usual care. DESIGN: A randomized controlled study. PARTICIPANTS: A total of 650 medical patients (mean age 80 years, 67% women, 41% nonwhite) assigned randomly to either the intervention unit (n = 326) or usual care (n = 324). MEASURES: The hospital's resource-based cost of caring for patients was determined from the hospital's cost-accounting system. The cost of the intervention program was estimated and included in the intervention patients' total hospital cost. RESULTS: The development and maintenance costs of the intervention added $38.43 per bed day to the intervention patients' hospital costs. As a result, the cost per day to the hospital was slightly higher in the intervention patients than in the control patients ($876 vs $847, P = .076). However, the average length of stay was shorter for intervention patients (7.5 vs 8.4 days, P = .449). As a result, the hospital's total cost to care for intervention patients was not greater than caring for usual-care patients ($6608 in intervention patients vs $7240 in control patients, P = .926). Sensitivity analysis demonstrated that the cost of the intervention program would need to be 220% greater than estimated before intervention patients would be more expensive then control patients. There were no examined subgroups of patients in whom care on the intervention unit was significantly more expensive than care on the usual-care unit. Ninety-day nursing home use was lower in intervention than control patients (24.1% vs 32.3%, P = .034). Ninety-day readmission rates (36.7% vs 41.1%, P = .283) and caregiver strain scores (3.3 vs. 2.7, P = .280) were similar. CONCLUSION: Caring for patients on an intervention ward designed to improve functional outcomes in older patients was not more expensive to the hospital than caring for patients on a usual-care ward even though the intervention ward required a commitment of hospital resources.
Both Williams syndrome and isolated supravalvular aortic stenosis (SVAS) are caused by mutations at the elastin locus. Deletion demonstrable by FISH is the hallmark of Williams syndrome, whereas the mutations reported so far in SVAS have been more subtle. FISH positive elastin hemizygosity has not been reported in isolated SVAS. This report records our experience of FISH for elastin deletion in isolated SVAS and specifically reports a patient with non-Williams related SVAS, positive for the elastin deletion by FISH.
Erythromycin inhibits mucus glycoconjugate secretion from airway cells in vitro and may increase mucus clearance in patients with asthma or diffuse panbronchiolitis. Because mucus hypersecretion is common in purulent rhinitis, we questioned whether clarithromycin would change the properties of nasal mucus from subjects without sinus disease and from patients with acute purulent rhinitis. Nasal secretions were collected before and after nasal methacholine challenge from 10 adults without nasal symptoms and without methacholine from 10 patients with purulent rhinitis. After 2 wk of oral clarithromycin (500 mg twice daily), secretions were again collected from both groups. Secretions were analyzed for viscoelasticity, cohesion, hydration, and ciliary and airflow (sneeze) transportability. Compared with secretions from healthy subjects, rhinitis secretions had decreased wettability (contact angle on Teflon 100 degrees versus 84.67 degrees; p = 0.001), increased cohesion (36.8 versus 24.3 mm; p = 0.003), decreased sneeze clearability (20.6 versus 32 mm; p = 0.04), and increased percent solids (4.61 versus 2.82%; p = 0.04). After clarithromycin, the rheology, hydration, cohesion, and transportability of the rhinitis secretions were similar to those of the postclarithromycin secretions from the healthy subjects. Secretion volume also decreased (500.1 versus 28.3 mg; p = 0.01), and mucociliary transportability increased by 30% (0.76 versus 0.99; p = 0.005). Although clarithromycin reduced mucus secretion in both rhinitis patients and normal subjects, it did not alter the secretory response to methacholine.
BACKGROUND: Avirulent pathogens elicit a battery of plant defenses, often accompanied by collapse of the challenged cells. In soybean cells, sustained accumulation of H2O2 from an oxidative burst cues localized host cell death. Such hypersensitive cell death appears to be an active process, but little is known about the mechanisms underlying cellular collapse. RESULTS: We show that H2O2 stimulates a rapid influx of Ca2+ into soybean cells, which activates a physiological cell death program resulting in the generation of large (approximately 50 kb) DNA fragments and cell corpse morphology--including cell shrinkage, plasma membrane blebbing and nuclear condensation--characteristic of apoptosis. In contrast, H2O2 induction of the cellular protectant gene glutathione S-transferase is Ca(2+)-independent. Apoptosis in soybean cells and leaf tissue was induced by avirulent Pseudomonas syringae pv. glycinea but was not observed at comparable stages of the compatible interaction with the isogenic virulent strain, which fails to elicit a hypersensitive response. Apoptosis was also observed at the onset of the hypersensitive response in Arabidopsis leaves inoculated with avirulent P. syringae pv. tomato and in tobacco cells treated with the fungal peptide cryptogein, which is involved in the induction of non-host resistance to Phytophthora cryptogea. CONCLUSIONS: These observations establish a signal function for Ca2+ downstream of the oxidative burst in the activation of a physiological cell death program in soybean cells that is similar to apoptosis in animals. That the characteristic cell corpse morphology is also induced in Arabidopsis and tobacco by different avirulence signals suggests that apoptosis may prove to be a common, but not necessarily ubiquitous, feature of incompatible plant-pathogen interactions. Emerging similarities between facets of hypersensitive disease resistance and the mammalian native immune system indicate that apoptosis is a widespread defence mechanism in eukaryotes.
OBJECTIVE: To pilot a targeted chemoradiation protocol for patients with advanced carcinoma of the larynx and pharynx that would circumvent upper aerodigestive tract dysfunction related to major oncologic surgery. DESIGN: Weekly intra-arterial infusions of supradose cisplatin (150 mg/m2 per week x 4) rapidly delivered to the tumor bulk, simultaneous intravenous sodium thiosulfate for systemic drug neutralization, and conventional external-beam irradiation (1.80-2.00 Gy per fraction x 35) were used. Between February 1991 and April 1994, 42 patients were treated who would otherwise have required a major resection of the tongue base, pharyngeal wall, or larynx. MAIN OUTCOME MEASURES: Tumor response, toxic effects, disease control above the clavicle, preservation of the larynx, maintenance of oral nutrition, and overall and disease-related 2-year survival. RESULTS: Three complications were related to the weekly transfemoral superselective intra-arterial procedures performed 160 times. Grade 3 to 4 chemotoxic effects were infrequent, occurring in 9 (5.5%) of 160 cycles, and only 1 patient required a radiotherapy break because of severe mucositis. A complete response in the primary site was obtained in 36 (86%) of 42 patients, 2 of whom had residual disease in the neck. Median follow-up was 13 months (range, 3-46 months). To date, there have been 5 recurrences: 2 regional and 3 distant. The 2-year overall and disease-related survival was 64% and 76%, respectively. The rate of disease control above the clavicle at 2 years was 86%. CONCLUSIONS: We believe this chemoradiation protocol represents an effective management scheme for patients with advanced head and neck cancer while minimizing dysfunction and possibly improving survival.
To assess the cardiac response of elderly adults, three sedentary men and six women (M = 68 years) with no known cardiovascular disease had their cardiac responses to activities done in a laboratory setting (walking, climbing stairs, carrying bags, shuffleboard); normal daily activities and aerobic walking (pace at 60% of the age-adjusted heart rate) were assessed by a 24-hour holter monitor. Supraventricular and ventricular ectopies were common during the 24 hours of monitoring, but none occurred during any of the activities. Bradycardia occurred at night, along with some supraventricular and ventricular ectopy, none clinically significant. Heart rate increased as the intensity of the activity increased (e.g., 68/ minute for carrying 5 pounds of groceries to 90/ minute during aerobic walking). When prescribing exercise or activity limitations, the chronotropic effects of usual daily activities must be considered in counseling sedentary, apparently healthy older adults.
This study assessed the efficacy, safety, and technical feasibility of inducing bone formation in an animal model of maxillary sinus floor augmentation using recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated on an absorbable collagen sponge (ACS). Bilateral antral maxillary sinus floor elevation procedures were surgically performed in six adult female Alpine-Saanen goats. Bone formation in response to the implant was evaluated using sequential radiographs, computerized tomography, and gross pathologic and histologic analysis performed at necropsy. Computerized tomographic scans documented nonosseous radiopacity in both sinuses postimplantation. Sinuses implanted with the rhBMP-2/ACS subsequently demonstrated increasing radiopacity local to the implant site, while radiopacity of the negative control sinuses remained unchanged or decreased. The results demonstrated the ability of an rhBMP-2/ACS implant to induce substantive new bone formation within the maxillary sinus of goats without adverse sequelae. The rhBMP-2/ACS composite implant may represent an acceptable alternative to traditional bone grafts and bone substitutes for maxillary sinus floor augmentation procedures in humans.
A screening program for cystic fibrosis (CF) heterozygotes was conducted in a large HMO prenatal population, to evaluate the level of interest among eligible patients, the effectiveness of prescreening education, attitudes toward the screening process, psychological effects, and utilization of prenatal diagnosis and its outcomes. The heterozygote identification rate and frequency of specific CFTR mutations were also assessed. Identified carriers were offered genetic counseling and testing of male partners. Prenatal diagnosis was offered if both parents were identified as carriers. A total of 5,161 women underwent carrier testing; 947 others completed survey instruments only. The acceptance rate of screening was high (78%), and pretest education by videotape was generally effective. Adverse psychological effects were not reported. Participants generally found screening to be desirable and useful. Screening identified 142 female heterozygotes, 109 couples in which the male partner was not a carrier, and 7 high-risk couples. The incidence of R117H mutations was much higher than expected. The number of identified carriers was much lower in Hispanics than in Caucasians. We conclude that large-scale prenatal screening for CF heterozygotes in the absence of a family history of CF is an acceptable method for identifying couples at risk for affected fetuses. Sufficient pretest education can be accomplished efficiently, test insensitivity is well accepted, adverse psychological events are not observed, and general patient satisfaction is high.
Although the use of physical restraint has declined in nursing homes, the practice remains widespread in hospitals. The use of physical restraint in hospitals was reviewed to identify the current clinical, legal, and ethical issues and the implications for policy and further research. Clinicians use physical restraints to prevent patient falls, to forestall disruption of therapy, or to control disruptive behavior, but they vary in how they determine to institute these restraints. The evidence to support the reasons for their determinations is not compelling. Fear of litigation remains a powerful motivator. The ethical dilemma of autonomy versus beneficence has not been resolved satisfactorily for patients in this setting. The lack of large-scale studies in any of these areas makes it difficult for policy makers to determine whether it is necessary to address hospital physical restraint practices through additional regulation.
OBJECTIVE: To characterize an urban street youth population, their self-reported rates of drug use, and their involvement in behaviors that put them at risk for infection with the human immunodeficiency virus. DESIGN: A brief structured interview was administered to 409 youths who had been living on the streets for 2 or more consecutive months, or who were fully integrated into the "street economy." SETTING: Thirty percent of the sample were recruited from community-based service sites and 70% were recruited from street locations and at natural hangouts. PARTICIPANTS: Youths were aged 12 to 23 years; 74% were male, 48% were ethnic minorities, 72% were homeless, 14% were gang affiliated, 20% were involved in drug dealing, 43% were engaged in survival sex (ie, the exchange of a sexual favor for money, food, a place to stay, clothes, and/or drugs), and 40% were homosexual or bisexual. RESULTS: Seventy percent of the youths were sexually active, with an average of 11.7 sexual partners (past 30 days). Youths with multiple sexual partners were more likely to have had a previous sexually transmitted disease (P < .01), to use drugs during sex (P < .001), and to be involved in survival sex (P < .001). Marijuana (55%), methamphetamine (62%), and crack (38%) were the drugs of choice, with 30% of the sample reporting injecting drug use (58% of this subset reported injecting drug use within the past 30 days). Substance-abusing youth were 3.6 times more likely to use drugs during sex, 2.2 times more likely to engage in survival sex, and 2.5 times more likely to have been diagnosed as having a sexually transmitted disease. CONCLUSIONS: High-risk sexual and drug use behaviors were prevalent and interrelated in this urban street youth sample. This suggests the need for new and innovative educational promotions and prevention interventions targeted to this population.