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Biomedical subjects

D R Wagner

Publications and source records attributed to D R Wagner.

At least 55 records · Page 3Linked to original sources

Core body temperature in narcoleptic and normal subjects living in temporal isolation.

The aim was to detect abnormalities in the circadian temperature rhythms of narcoleptic patients, as evidence of abnormal circadian pacemaker function. Six narcoleptic patients and nine normal controls lived in a time-isolation laboratory for 18-22 days. Rectal temperature was measured every minute and modeled by mean waveforms and cosine functions, which have complementary advantages. In this study, the two types of models gave similar results: The levels, periods, amplitudes, and phases of the circadian temperature rhythms of patients and controls did not significantly differ--evidence against an abnormality of circadian pacemaker function in narcolepsy. The increases of temperature that normally follow main sleep periods were smaller in narcoleptic subjects, and narcoleptic naps, which were involuntary, were heralded and accompanied by small decreases of mean temperature.

Aged↗

Influence of polyclonal immunoglobulins on the polymorphonuclear leukocyte response to lipopolysaccharide of Salmonella enteritidis as measured with luminol-enhanced chemiluminescence.

In gram-negative sepsis, the activation of polymorphonuclear leukocytes (PMN) by lipopolysaccharide (LPS) and the resulting production of superoxide and other oxygen radicals may be an important cause of tissue damage. A suppression of the PMN response to LPS stimulation would be therapeutically beneficial. The aim of this study was to determine whether different polyclonal immunoglobulins (Igs; 5S-Ig, 7S-Ig, and 19S-Ig) influence the PMN response to LPS of Salmonella enteritidis in vitro. The respiratory burst activity of PMN was measured with luminol-enhanced chemiluminescence. After addition of a 5S-Ig solution containing F(ab')2 fragments of IgG and a 19S-Ig solution containing 12% polyclonal IgM, luminol-enhanced chemiluminescence was reduced by 27% (P < 0.05) and 46% (P < 0.005), respectively. However, after addition of a 7S-Ig solution containing polyclonal IgG, luminol-enhanced chemiluminescence was increased fourfold (P < 0.05). The results suggest that the influence of polyclonal Igs on PMN response to LPS stimulation is dependent on the Ig class, F(ab')2 fragments of IgG and IgM leading to LPS neutralization and IgG leading to the production of potentially toxic oxygen radicals.

Humans↗

Existence and role of substrate cycling between AMP and adenosine in isolated rabbit cardiomyocytes under control conditions and in ATP depletion.

BACKGROUND: Adenosine, a physiological coronary vasodilator, has been proposed to regulate coronary circulation according to myocardial oxygen demand. In the present study, we investigated the mechanisms of adenosine formation and utilization in isolated rabbit cardiomyocytes and, in particular, the existence and the role of substrate cycling between AMP and adenosine in the regulation of its concentration. METHODS AND RESULTS: Rabbit cardiomyocytes were isolated by collagenase perfusion and incubated in HEPES-buffered Krebs-Henseleit solution at 37 degrees C, pH 7.4, in control conditions and in ATP depletion achieved by inhibiting glycolysis with 5 mmol/L iodoacetate. Under control conditions, adenosine accumulated at a rate of 4 pmol.min-1.10(-6) cells. The 13-fold elevation of adenosine accumulation induced by iodotubercidin (ITu), an inhibitor of adenosine kinase, proves that adenosine is normally recycled into AMP. This recycling involves 95% of the adenosine formed. In ATP depletion, adenosine accumulated at the rate of 335 pmol.min-1.10(-6) cells and was no longer rephosphorylated after 20 minutes, as shown by the absence of effect of ITu after this time interval. Moreover, adenosine was deaminated, as indicated by the twofold increase of its accumulation induced by deoxycoformycin (dCF), an inhibitor of adenosine deaminase. Both in control conditions and in ATP depletion, adenosine-dialdehyde, an inhibitor of S-adenosylhomocysteine (SAH) hydrolase, had no significant effect on adenosine formation, indicating that the transmethylation pathway is not an important source of adenosine in rabbit cardiomyocytes. CONCLUSIONS: The results indicate that recycling of adenosine into AMP is essential for the maintenance of low, nonvasodilatory concentrations of the nucleoside under control conditions and that interruption of recycling plays an important role in elevating adenosine during ATP depletion.

Adenine Nucleotides↗

Low-cost, office-based, screening colonoscopy.

OBJECTIVES: Performing full colonoscopy at regular intervals and removing lesions at an early stage might significantly lower the incidence and mortality of colorectal cancer. Such a program must be inexpensive, safe, and time-efficient. METHODS: Screening colonoscopy was performed on 639 patients. For a normal examination, the physician's time is limited to giving the medication for conscious sedation, performing the colonoscopy, and completing a written report form. The total charge for a normal screening colonoscopy is $150. RESULTS: Adenomatous and/or hyperplastic polyps were detected in 218 patients (34.1%). One hundred sixty adenomatous and 134 hyperplastic polyps were removed. Forty-eight percent (48.1%) of the adenomatous and 21.6% of the hyperplastic polyps were above the sigmoid colon. Six adenocarcinomas were detected in five patients. One patient had a delayed bleeding episode requiring no transfusion or therapeutic intervention, and one patient had a "post-polypectomy syndrome" requiring no therapeutic intervention. The average physician time in the endoscopy room for normal examinations was 18 min. CONCLUSIONS: Screening colonoscopy can be safely performed in an office facility. Physician time with the patient should be limited to allow a low cost that compares favorably with screening costs for other malignancies. Long-term studies to assess the capability of screening colonoscopy to lower mortality from colorectal cancer should continue.

Adenocarcinoma↗

GM-CSF and G-CSF in Felty's syndrome.

The risk of infection is increased in patients with Felty's syndrome, neutropenia being one of the main reasons for the susceptibility to infection. We report the case of a 56-year-old patient with Felty's syndrome in whom successive therapy with GM-CSF, splenectomy, and G-CSF was tried because of recurrent severe infections. Therapy with GM-CSF and G-CSF resulted in improvement of neutropenia and in successful treatment of cutaneous and pulmonary infections.

Combined Modality Therapy↗

Effect of propranolol on portal vein hemodynamics: assessment by duplex sonography and indocyanine green clearance in healthy volunteers.

In the past decade several randomized trials have shown a beneficial effect of propranolol in cirrhotic patients. The effect of propranolol has been attributed to a reduction in portal vein pressure. So far the monitoring of portal vein hemodynamics following propranolol administration has been achieved mainly by hepatic vein catheterization. We studied the effect of propranolol on portal vein hemodynamics noninvasively in five healthy volunteers using duplex sonography and indocyanine green clearance. Measured by duplex sonography, blood flow was reduced by 28.6% in the portal vein (P < 0.05) and by 8.7% in the hepatic artery (NS) 60 min after oral administration of 80 mg propranolol. During this time total hepatic blood flow, measured by indocyanine green clearance, was reduced by 19.5% (P < 0.05). We conclude that both methods are useful for the study of portal vein hemodynamics during propranolol therapy, duplex sonography being more easily practicable.

Adult↗

Deposits of paraprotein in small vessels as a cause of skin ulcers in Waldenström's macroglobulinemia.

A 71-year-old man presented with epistaxis and large ulcers on arms and legs. A monoclonal IgM-kappa gammopathy and high levels of cryoglobulins were found. Histology of the affected skin showed deposits of paraprotein in the small vessels, causing luminal obstruction. This in turn caused ischemic skin lesions, which were successfully treated with cortisone (fluocortolone 100 mg/day every second day) and cyclophosphamide (100 mg/day).

Aged↗

Myoadenylate deaminase deficiency with severe rhabdomyolysis.

A 13-year-old Turkish girl was admitted because of recurrent episodes of muscle pain and weakness since the age of 5 years. As an outpatient she developed severe acute rhabdomyolysis (myoglobinuria and increased serum creatine kinase level of 19,000 units/l). The acute rhabdomyolysis and the preceding episodes of muscle pain and weakness had been induced by exercise. There was no increase in plasma ammonia level during ischaemic forearm exercise test and bicycle ergometry. Myoadenylate deaminase deficiency was proven both histochemically and biochemically. The girl was found to be homozygous for the C 34-T mutation of the AMPD1 gene causing primary myoadenylate deaminase deficiency in skeletal muscle. Both parents and her brother were heterozygous for that mutation. Myoadenylate deaminase deficiency has to be considered as a cause of severe rhabdomyolysis.

AMP Deaminase↗

Signal processors in duplex sonography: in vitro comparison between analog and digital methods.

Using a new flow-test phantom, which respects the acoustic properties of real blood as well as the proximal and distal impedances of body circulation, we assessed the performance of two duplex sonography signal processors on blood-flow measurements. With both the analog and the dynamic signal processor (Fast Fourier Transform), the correlation between duplex sonography and quantitative flow measurements was high (0.96-0.99) for different dynamic conditions (steady or pulsatile blood flow, varying heart rate, blood pressure, and hematocrit) and for different mechanical conditions (silicon tube or animal vessel). The real blood flow was overestimated by duplex sonography; the over-estimation was more pronounced with the analog processor (factor 1.87-4.20) than with the digital processor (factor 1.22-1.64, P < 0.05). Applied to the study of asymmetric stenoses, the digital processor was not superior to the analog processors described in the literature.

Animals↗

A predictive index for functional decline in hospitalized elderly medical patients.

OBJECTIVE: To prospectively develop and validate a predictive index to identify on admission elderly hospitalized medical patients at risk for functional decline. DESIGN: Two prospective cohort studies, in tandem. The predictive model developed in the initial cohort was subsequently validated in a separate cohort. SETTING: General medical wards of a university teaching hospital. PATIENTS: For the development cohort, 188 hospitalized general medical patients aged > or = 70 years. For the validation cohort, 142 comparable patients. MEASUREMENT AND MAIN RESULTS: The subjects and their nurses were interviewed twice weekly using standardized, validated instruments. Functional decline occurred among 51/188 (27%) patients in the development cohort. Four independent baseline risk factors (RFs) for functional decline were identified: decubitus ulcer (adjusted relative risk [RR] 2.7; 95% confidence interval [CI] 1.4, 5.2); cognitive impairment (RR 1.7; CI 0.9, 3.1); functional impairment (RR 1.8; CI 1.0, 3.3); and low social activity level (RR 2.4; CI 1.2, 5.1). A risk-stratification system was developed by adding the numbers of RFs. Rates of functional decline for the low- (0 RF), intermediate- (1-2 RFs), and high- (3-4 RFs) risk groups were 8%, 28%, and 63%, respectively (p < 0.0001). The corresponding rates in the validation cohort, of whom 34/142 (24%) developed functional decline, were 6%, 29%, and 83% (p < 0.0001). The rates of death or nursing home placement, clinical outcomes associated with functional decline in the hospital, were 6%, 19%, and 41% (p < 0.002) in the development cohort and 10%, 32%, and 67% (p < 0.001) in the validation cohort, respectively, for the three risk groups. CONCLUSIONS: Functional decline among hospitalized elderly patients is common, and a simple predictive model based on four risk factors can be used on admission to identify elderly persons at greatest risk.

Activities of Daily Living↗

A controlled trial of a nursing-centered intervention in hospitalized elderly medical patients: the Yale Geriatric Care Program.

OBJECTIVE: To test the effectiveness of a nursing-centered intervention to prevent functional decline among hospitalized elderly medical patients. DESIGN: Prospective cohort study with stratified and matched cohort analyses. SETTING: General medicine wards of a university teaching hospital. PATIENTS: Two hundred sixteen patients aged > or = 70 years (85 intervention and 131 control patients). INTERVENTION: The intervention included identification and surveillance of frail older patients, twice-weekly rounds of the Geriatric Care Team, and a nursing-centered educational program. MAIN OUTCOME MEASURE: Functional decline, defined as a net decline in five activities of daily living (ADLs). RESULTS: In stratified analyses, the intervention resulted in a beneficial effect with a relative risk of 0.82 (95% confidence interval [CI] 0.54 to 1.24) in patients (n = 106) with one of four geriatric target conditions at baseline (eg, delirium, functional impairment, incontinence, and pressure sores). The intervention had no effect in patients without target conditions at baseline (n = 110); thus, this subgroup was excluded from further analyses. When patients were matched on number of target conditions and risk for functional decline at baseline (n = 66), the intervention resulted in a significant beneficial effect, with a reduction in functional decline from 64% in controls to 41% in the intervention group, for a relative risk of 0.64 (95% CI, 0.43 to 0.96). The intervention group had significantly less decline in ADL score and in individual ADLs than control subjects. Specific interventions aimed at maximizing function, such as physical therapy, were received more often by intervention patients; however, the beneficial effects of the intervention were achieved without increasing per-day hospital costs. CONCLUSIONS: The intervention appears effective to decrease functional decline in targeted elderly hospitalized medical patients.

Activities of Daily Living↗

Predictors of formal home health care use in elderly patients after hospitalization.

OBJECTIVE: To prospectively study the incidence of and risk factors for home health care (HHC) use in a cohort of elderly medical and surgical patients discharged from acute care. Although HHC is commonly received by patients in this group, its predictors have not been well studied. DESIGN: Prospective cohort study. SETTING: Medical and surgical wards at a university teaching hospital, followed by 23 Medicare-certified HHC agencies in the study catchment area. PATIENTS: 226 medical and surgical patients aged 70 years and older immediately after discharge from acute care. MEASUREMENTS: HHC initiated within 14 days after hospital discharge, measured by direct review of HHC agency records. RESULTS: The incidence of HHC initiated within 2 weeks post-discharge was 75/226 (34%). The median duration of service was 30 days (range 3-483) with a median of 3 visits per week. Four independent predictors of HHC were identified through multivariate analysis: educational level < or = 12 years (relative risk (RR) 3.3; 95% confidence interval (CI) 1.6 to 6.6); less accessible social support (RR, 1.7; CI 0.9 to 3.1); impairment in at least one instrumental activity of daily living (RR, 1.9; CI, 1.0, 3.4); and prior HHC use (RR, 2.1; CI, 1.2 to 3.6). Risk strata were created by adding one point for each risk factor present: with 0-1 risk factors, 8% used HHC; with two risk factors, 28%; with three risk factors, 45%, with four risk factors, 76%. This trend was statistically significant (P < 0.001). CONCLUSIONS: HHC use is common among elderly patients after discharge from acute care. A simple predictive model based on four risk factors can be used on admission to predict HHC use. This model may be useful for discharge planning and health care utilization planning for the elderly population.

Activities of Daily Living↗

Erythromelalgia unmasked during norephedrine therapy: a case report.

A thirty-eight-year-old woman presented with typical signs of erythromelalgia: burning, redness, and warm congestion of the extremities. These symptoms occurred after cessation of obesity drug therapy with norephedrine (250 mg/day) continuously over six years. The condition was refractory to treatment with acetylsalicylic acid. It is suggested that erythromelalgia in this case was unmasked by the vasoactive properties of norephedrine. Continuous drug therapy with norephedrine may have led to adaptive adrenergic subsensitivity of vascular smooth muscles. The pathomechanism of primary erythromelalgia is still unknown. Their observations suggest that an enhanced vasodilatation due to an abnormal adrenergic sensitivity may play an important role in the pathogenesis of primary erythromelalgia.

Adult↗

Age-related differences in recovery from simulated jet lag.

Six healthy young men and eight early middle-aged men were isolated from environmental time cues for 15 days. For the first 6-7 days (one or two nights adaptation, four nights baseline), their sleep and meals were scheduled to approximate their habitual patterns. Their daily routines were then shifted 6 hours earlier by terminating the sixth or seventh sleep episode 6 hours early. The new schedules were followed for the next 8 or 9 days. Important age-related differences in adjustment to this single 6-hour schedule shift were found. For the first 4-day interval after the shift, middle-aged subjects had larger increases of waking time during the sleep period and earlier termination of sleep than young subjects. They also reported larger decreases in alertness and well-being and larger increases in sleepiness, weariness and effort required to perform daily functions. The rate of adjustment of the circadian core temperature rhythm to the new schedule did not differ between groups. These results suggest that the symptoms reported by the middle-aged subjects may be due mainly to difficulty maintaining sleep at early times of the circadian day. The compensatory response to sleep deprivation may also be less robust in middle-aged individuals traveling eastbound.

Adolescent↗

Cognitive and motor performance of narcoleptic and normal subjects living in temporal isolation.

Six unmedicated narcoleptic subjects and nine normal controls lived in a temporal isolation laboratory for 18-22 days. They were permitted to "free-run" for the last 9-13 days. Brief cognitive and motor performance tests were repeated on average six times per subjective day. They consisted of serial search, complex verbal reasoning tasks and manual dexterity of each hand. Only minor differences in performance were found between the narcoleptic subjects and controls. Narcoleptic subjects showed mild impairment of accuracy on the search task that could be explained by occasional lapses and an afternoon dip in performance. Narcoleptic subjects also tended to perform some tasks more slowly, but the group differences were not significant. Neither speed nor accuracy of performance of narcoleptic subjects decreased over the course of the experiment. By one standard of performance, therefore, all or nearly all of the sleep need of these subjects was met by the sleep they obtained in the laboratory. That amount, in turn, did not exceed the total sleep obtained by the normal controls. Significant time-of-day effects were found in narcoleptic subjects for speed of verbal reasoning (progressive slowing over the course of the day), manual dexterity (fluctuations in speeds) and accuracy of serial search (afternoon dip). These variations in performance could not be attributed to changes in core body temperature or to occurrences of naps or meals.

Adult↗

Combined parenteral and enteral nutrition in severe trauma.

Early enteral feeding is increasingly advocated for the nutrition support of severely stressed patients. The successful use of this modality in critical illness is often limited by the patient's condition, the availability of access for feeding, and the patient's tolerance of the enteral formula. Factors such as abdominal injury or constraints on fluid volume also complicate nutrition support in this setting. Attention to a secure and well-maintained small bowel access tube and appropriate formula selection allow safe tube feeding in these patients. This case report describes the clinical course of a patient with severe chest and abdominal trauma who received enteral nutrition despite a large, open abdominal wound.

Adult↗