Search PubMed⌕ Search

Biomedical subjects

D J Fisher

Publications and source records attributed to D J Fisher.

At least 19 recordsLinked to original sources
PubMed1995

Resurgence of rabies. A historical perspective on rabies in children.

Wildlife rabies in certain parts of the United States has been increasing. With greater urbanization, many areas have seen an influx of wild animals such as raccoons and foxes that are known wildlife reservoirs of rabies. Rabies encephalitis has been a fatal illness recognized by humans throughout history. The purpose of this review is to examine the history of rabies throughout the world to elucidate the evolution of popular and scientific knowledge of the disease in animals and humans. By examining this development from a pediatric perspective, we gain insight into the prevention and treatment protocols recommended for children today. Pediatricians need to include education about prevention and treatment of rabies exposures in their anticipatory guidance sessions with families.

Animals↗
PubMed1995

Recent insights into the regulation of cardiac Ca2+ flux during perinatal development and in cardiac failure.

Systolic and diastolic cardiac function improve during the transition from fetus to newborn to adult. This perinatal maturation is temporally correlated with and at least partially dependent on subcellular changes in the expression of several gene products that regulate cytosolic Ca2+ concentration. Expression of the Na(+)-Ca2+ exchanger of the sarcolemma is highest in the fetus, whereas expression of the sarcoplasmic reticulum Ca2+ pump and the voltage-dependent Ca2+ channel of the sarcolemma increase in conjunction with the perinatal maturation of cardiac function. Whereas cardiac relaxation in the normal mature heart depends primarily on the sarcoplasmic reticulum Ca2+ pump, relaxation in the fetal heart appears to be more dependent on transsarcolemmal Ca2+ flux. Like the fetal heart during prolonged relaxation, the failing human heart exhibits impaired relaxation and abnormal Ca2+ flux regulation. Although altered expression of several gene products has been demonstrated in the failing heart, the responsible factor(s) remains unknown.

Adult↗
PubMed1995

The effect of contrast dose, imaging time, and lesion size in the MR detection of intracerebral metastasis.

PURPOSE: To evaluate the effect of MR contrast dose versus delayed imaging time on the detection of metastatic brain lesions based on lesion size. METHODS: Contrast MR examinations with gadoteridol were obtained in 45 patients with brain metastases. The patients were divided into two groups: 16 received cumulative standard dose (0.1 mmol/kg) and 29 received cumulative triple dose (0.3 mmol/kg). Both groups were evaluated at two dose levels (lower dose and higher dose) with two separate injections. Each patient received an initial bolus injection of either 0.05 (cumulative standard dose) or 0.1 (cumulative triple dose) mmol/kg of gadoteridol to reach the lower-dose level and underwent imaging immediately and 10 and 20 minutes later. Thirty minutes after injection, an additional bolus injection of 0.05 (cumulative standard dose) or 0.2 (cumulative triple dose) mmol/kg was administered to reach the cumulative higher-dose level (cumulative standard dose, 0.1 mmol/kg; cumulative triple dose, 0.3 mmol). Images were acquired immediately. RESULTS: There was no difference in the detection rate for lesions larger than 10 mm among T2-weighted, lower-dose immediate and delayed, or immediate higher-dose images in both study groups. Lesions smaller than 10 mm had improved detection with delayed imaging in both study groups; however, the immediate higher-dose studies still had the highest detection rate. CONCLUSION: In the evaluation of small central nervous system metastases, either delayed imaging after the injection of standard contrast dose or higher contrast dose may improve their detection, and therefore affect clinical management. Higher contrast dose (cumulative triple dose) studies appear to be more effective than delayed imaging with standard dose.

Brain↗
PubMed1994

Granulocytic ehrlichiosis and meningitis in a dog.

A 4-year-old male mixed-breed dog from the Sierra Nevada mountains in California was referred because of epistaxis and signs of cervical pain. Dermacentor variabilis ticks were found on the dog at the time of physical examination. Clinicopathologic abnormalities included nonregenerative anemia, thrombocytopenia, and rare intracytoplasmic morulae within circulating neutrophils. Abnormalities of the CSF included pleocytosis and intracytoplasmic morulae in approximately 9% of neutrophils. Serum antibody titers for Ehrlichia canis (40,960) and Rickettsia rickettsii (5,120) were high, and titer for E equi (40) was moderate. Treatment included administration of tetracycline, chloramphenicol, doxycycline, and prednisone. The dog had several relapses, but long-term remission was eventually achieved. Granulocytic ehrlichiosis has previously been associated with anemia, thrombocytopenia, and polyarthritis in dogs. This case suggests that granulocytic ehrlichiosis may be associated with meningitis and that the organisms that cause granulocytic ehrlichiosis may have the same vector as do the spotted fever-group rickettsiae.

Animals↗
PubMed1994

Delineation of gliomas with various doses of MR contrast material.

PURPOSE: To examine the effects of different gadolinium doses on the delineation of gliomas, particularly the demonstration of abnormal enhancement on T1-weighted images extending beyond the zone of apparent signal abnormality on corresponding T2-weighted images. METHODS: During phase II clinical trials of gadoteridol, 23 patients with pathologically proved gliomas were studied by MR with various doses of gadoteridol, ranging from 0.05 to 0.3 mmol/kg. RESULTS: All of the gliomas were readily detected by T2-weighted images. Twelve of 23 patients demonstrated enhancement on T1-weighted images extending beyond the zone of apparent signal abnormality demonstrated on T2-weighted images. These findings were seen in none of the six patients (0%) studied at 0.05 mmol/kg, one of five patients (20%) studied at 0.1 mmol/kg, four of five patients (80%) studied at 0.2 mmol/kg, and seven of seven patients (100%) studied at 0.3 mmol/kg. CONCLUSIONS: The detection of symptomatic gliomas does not require a contrast agent because they are generally large and readily demonstrated on T2-weighted images. However, the area of postcontrast enhancement of gliomas seems to be greater with higher doses of contrast agent. The cause of the abnormal enhancement extending beyond the zone of apparent signal abnormality on T2-weighted images seen in this limited study is unknown and probably represents tumor infiltration. The frequency of detection of such findings appears to be proportional to the dose of contrast material used.

Brain↗
PubMed1994

Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group.

OBJECTIVE: Prospective studies were conducted to test the hypothesis that infants unlikely to have serious bacterial infections (SBI) can be accurately identified by low risk criteria. METHODS: Febrile infants (rectal T > or = 38 degrees C) < or = 60 days of age were considered at low risk for SBI if they met the following criteria: 1) appear well; 2) were previously healthy; 3) have no focal infection; 4) have WBC count 5.0-15.0 x 10(9) cells/L (5000-15,000/mm3), band form count < or = 1.5 x 10(9) cells/L (< or = 1500/mm3), < or = 10 WBC per high power field on microscopic examination of spun urine sediment, and < or = 5 WBC per high power field on microscopic examination of a stool smear (if diarrhea). The recommended evaluation included the culture of specimens of blood, cerebrospinal fluid, and urine for bacteria. Outcomes were determined. The negative predictive values of the low risk criteria for SBI and bacteremia were calculated. RESULTS: Of 1057 eligible infants, 931 were well appearing, and, of these, 437 met the remaining low risk criteria. Five low risk infants had SBI including two infants with bacteremia. The negative predictive value of the low risk criteria was 98.9% (95% confidence interval, 97.2% to 99.6%) for SBI, and 99.5% (95% confidence interval, 98.2% to 99.9%) for bacteremia. CONCLUSIONS: These data confirm the ability of the low risk criteria to identify infants unlikely to have SBI. Infants who meet the low risk criteria can be carefully observed without administering antimicrobial agents.

Anti-Bacterial Agents↗
PubMed1994

Phase III multicenter trial of high-dose gadoteridol in MR evaluation of brain metastases.

PURPOSE: To assess the efficacy and safety profile of high-dose (0.3 mmol/kg cumulative dose) gadoteridol in patients with suspected central nervous system metastatic disease. METHODS: We studied 67 patients using an incremental-dose technique. Patient monitoring included a medical history, physical examination, vital signs, and extensive laboratory tests within 24 hours before and after the MR examination. Precontrast T1- and T2-weighted spin-echo studies were performed, followed by intravenous injection of 0.1 mmol/kg of gadoteridol. T1-weighted images were acquired immediately after and at 10 and 20 minutes after injection. At 30 minutes an additional 0.2 mmol/kg of gadoteridol was administered (0.3-mmol/kg cumulative dose), and T1-weighted images were acquired. Cases demonstrating abnormal MR findings were assessed for efficacy by unblinded and blinded reviewers and were analyzed quantitatively. RESULTS: Three adverse effects in two patients were considered to be related to gadoteridol administration. No adverse effects were serious; all self-resolved. Forty-nine cases showed abnormal MR findings and were included in the efficacy analysis. A significantly greater number of lesions was seen on the high-dose as opposed to the standard-dose images. Blinded and unblinded readers identified 5 and 8 patients, respectively, with solitary lesions on standard-dose examination and multiple lesions on high-dose examination. Two patients who had normal standard-dose findings had lesions identified on high-dose studies. Quantitative analysis of 133 lesions in 45 patients demonstrated significant increases in lesion signal intensity on high-dose studies when compared with standard-dose studies. CONCLUSION: Gadoteridol can be safely administered up to a cumulative dose of 0.3 mmol/kg. High-dose contrast studies provide improved lesion detectability and additional diagnostic information over studies performed in the same patients with a 0.1-mmol/kg dose and aid in patient diagnosis and treatment. High-dose gadoteridol study may facilitate the care of patients with suspected central nervous system metastasis.

Adolescent↗
PubMed1994

Cost-effectiveness of high-dose MR contrast studies in the evaluation of brain metastases.

PURPOSE: To investigate the cost-effectiveness of high-dose MR contrast studies in the management of brain metastases. METHODS: During the phase III clinical trial of high-dose contrast studies (0.3 mmol/kg), 11 of 27 patients were judged by the reviewers to have potential treatment changes based on the additional information provided by the high-dose studies. We retrospectively evaluated how many of these 27 patients had actual treatment changes because of the results of the high-dose study. Using the fee schedule at our institution, the cost-effectiveness was analyzed based on the cost savings from treatment changes and the additional expense of implementing the high-dose studies. RESULTS: A total of 3 craniotomies ($22,800 each) and 2 aggressive courses of radiation therapy ($1122 each) were avoided in 4 patients because of the additional lesions detected by the high-dose studies. This resulted in a treatment cost savings of $70,644. The extra expense for implementing the high-dose study is $9126 for a single injection in all 27 patients, $9295 for 2 separate injections completed in 1 visit in the 11 patients, and $11,154 for 2 separate injections completed in 2 separate visits. The cost savings in management (diagnosis and treatment) therefore ranged from $59,490 to $61,518 for all patients and from $2203 to $2278 per patient. CONCLUSION: Based on our limited data, the high-dose study seems to impact positively on the cost-effectiveness in the management of brain metastases. However, because our study had limitations, our results need to be confirmed with a larger patient population and a more standardized treatment approach and fee schedule.

Adult↗
PubMed1992

Developmental regulation of the sarcoplasmic reticulum calcium pump in the rabbit heart.

Previous studies have demonstrated that myocardial function changes during mammalian perinatal development. The purpose of this study was to evaluate the subcellular basis underlying the slower relaxation in the developing heart by examining perinatal changes in sarcoplasmic reticulum (SR) function, and in SR Ca2+ pump protein and mRNA abundance. We measured Ca2+ uptake and ATPase rates in isolated fetal, newborn, and adult rabbit cardiac SR membranes. In fetal and adult SR membranes, we estimated the active Ca2+ pump protein content by measuring the steady state Ca(2+)-dependent phosphoenzyme content; the total Ca2+ pump protein content was estimated by Western analysis of the immunoreactive Ca2+ pumps. We isolated RNA from fetal and adult hearts and estimated the SR Ca2+ pump mRNA content by Northern analysis. Ca2+ uptake and ATPase rates were significantly lower in the fetal and newborn SR membranes compared with the adult. The contents of active and total Ca2+ pump protein and of Ca2+ pump mRNA were 52-63% lower in the fetus than in the adult. These results indicate that a great deal of the slower sarcoplasmic reticulum Ca2+ uptake and ATPase rates in the fetal rabbit heart can be related to lower Ca2+ pump mRNA and protein contents. It is evident that transcriptional and/or posttranscriptional regulation of the SR Ca2+ pump may form an important part of the subcellular basis of the perinatal change in mammalian cardiac relaxation.

Animals↗
PubMed1992

The role of dicarboxylic anion transport in the slower Ca2+ uptake in fetal cardiac sarcoplasmic reticulum.

Sarcoplasmic reticulum- (SR-)mediated Ca2+ transport is slower in the fetal heart compared with the adult. Virtually all previous studies of cardiac SR Ca2+ transport were performed in the presence of oxalate, a dicarboxylic anion that is cotransported with Ca2+ in skeletal muscle SR. If anion transport is developmentally regulated in cardiac SR, this could explain, in part, the previously reported results. The purposes of this study were to establish the presence of an SR dicarboxylic anion transport process in the rabbit heart and to determine if the perinatal changes in SR Ca2+ transport occur in a dicarboxylic anion-dependent and/or independent manner. In isolated fetal and adult rabbit cardiac SR membranes, we measured Ca2+ ATPase rates and 45Ca2+ uptake in the presence of the dicarboxylic anions maleate and succinate compared with the zwitterionic buffer PIPES, to which cardiac SR is essentially impermeable. We also measured 14C-succinate uptake by fetal and adult SR membranes. Anion-independent Ca2+ ATPase activity and net 45Ca2+ uptake were significantly lower in the fetal SR membranes than in the adult. Maleate and succinate increased the Ca2+ ATPase rates in the fetal and adult SR, but the effect was significantly greater in the adult. Maleate and succinate stimulated earlier attainment of maximal net Ca2+ uptake in the fetal and adult SR, suggesting that these dicarboxylic anions stimulated the rate of Ca2+ accumulation. Maleate and succinate significantly increased the maximal net Ca2+ uptake in the adult SR, but not in the fetus. The percentage of stimulation of Ca2+ uptake by maleate and succinate was similar in the fetal and adult SR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The application of contrast agents in the evaluation of neoplasms of the central nervous system.

Magnetic resonance evaluation of central nervous system neoplasms has improved tremendously since the introduction of gadolinium-based contrast agents. The optimal application of these agents in clinical imaging, however, has not been well established. The article discusses the recent application of these agents to a number of intracranial neoplasms, including metastases, gliomas, pituitary adenomas, and acoustic neurinomas/cerebellopontine angle tumors.

Brain Neoplasms↗
PubMed1991

Inhibition of dicarboxylic anion transport by fluorescein isothiocyanate in skeletal sarcoplasmic reticulum.

It has been demonstrated previously that dicarboxylic anions are cotransported during ATP-dependent Ca2+ transport by skeletal muscle sarcoplasmic reticulum (SR) membranes, and that anion cotransport stimulates Ca2+ transport. In the current study, we present evidence that dicarboxylic anion cotransport and Ca2+ transport are kinetically distinct in SR, but both functions are mediated by the CaATPase protein. Preincubation of SR with 40 microM fluorescein isothiocyanate (FITC) (pH 7.0) inhibited essentially all of the Ca2+ ATPase activity, as well as active oxalate-supported and oxalate-independent 45Ca2+ accumulation. The addition of 1 mM beta, gamma-methyleneadenosine 5'-triphosphate (AMP-PCP) to the preincubation media fully protected the dicarboxylic anion-independent Ca2+ ATPase activity and the oxalate-independent active 45Ca2+ accumulation from the inhibitory effects of FITC; however, the ATP-associated [14C]oxalate accumulation, the oxalate-dependent 45Ca2+ accumulation, and the oxalate- and maleate-dependent stimulation of Ca2+ ATPase activity were not protected by AMP-PCP. Thus, the dicarboxylic anion accumulation and the stimulation of Ca2+ uptake by dicarboxylic anions could be functionally separated from the ATP-dependent, anion-independent Ca2+ translocation. FITC bound exclusively to the 100-kDa (CaATPase) and 92-kDa (phosphorylase) proteins in the SR membranes and to purified CaATPase in sodium dodecyl sulfate-polyacrylamide gel electrophoresis; 1 mM AMP-PCP inhibited 50-55% of the FITC fluorescence on the 100-kDa protein, but did not significantly alter fluorescence on the 92-kDa protein. Two-dimensional gel analysis demonstrated a single 100-kDa protein in longitudinal SR membranes. FITC appears to inhibit ATP-dependent Ca2+ transport, and dicarboxylic anion translocation through interaction at separate domains of the CaATPase protein.

Adenosine Triphosphate↗
PubMed1991

Correlation between Korotkoff's sounds and ultrasonics of the brachial artery in healthy and normotensive subjects.

The clinical measurement of blood pressure is generally obtained by auscultation for Korotkoff's sounds over the brachial artery using a sphygmomanometer and cuff. Real-time two dimensional ultrasound and Doppler techniques were used to study the brachial artery movements and blood flow patterns during these pressure measurements. Simultaneous recordings of Korotkoff's sounds were obtained. A strong correlation in time was demonstrated between Korotkoff's five phases, brachial artery wall movements and specific blood flow patterns. The evidence largely supports what to date has been speculation as to the origin of Korotkoff's sounds in that Korotkoff's phases 1 and 3 appear to be produced by vigorous arterial wall motion and phase 5 by cessation of this movement. Phase 2 is produced by blood flow disturbance. Furthermore, the lack of correlation between phase 4 and any specific vascular event may go some way to explaining why in clinical practice phase 5 readings are now preferred for diastolic pressure.

Adult↗
PubMed1991

Specific T-cell response to a Pneumocystis carinii surface glycoprotein (gp120) after immunization and natural infection.

T cells have been shown to be important in recovery from Pneumocystis carinii pneumonitis, although no specific antigen of P. carinii has been defined as containing T-cell epitopes. P. carinii has an abundant mannosylated surface glycoprotein of approximately 120 kDa (gp120) which induces a prominent host antibody response in experimental animals after exposure to P. carinii in the environment or after recovery from P. carinii pneumonitis. P. carinii gp120 was purified from infected lungs by lectin affinity chromatography. Standard in vitro lymphocyte stimulation assays using purified gp120 and control normal lung preparations were performed on isolated T cells obtained from BALB/c mice after immunization with P. carinii-infected crude lung homogenates or lectin-purified gp120. Lymphocytes from reconstituted severe combined immunodeficient mice which had recovered from naturally acquired P. carinii pneumonitis were also tested. A specific T-cell response was elicited by gp120 after immunization with P. carinii gp120 and after recovery from P. carinii pneumonitis. In addition, the mice developed a strong antibody response to gp120 as ascertained by Western blot (immunoblot). These data suggest that gp120 may be important in the recognition of P. carinii by T cells.

Animals↗
PubMed1991

MR evaluation of CNS tumors: dose comparison study with gadopentetate dimeglumine and gadoteridol.

In phase II and III trials of gadoteridol (Gd-HP-D03A), a new nonionic, low-osmolar contrast agent, 40 patients with intracranial neoplasms underwent magnetic resonance (MR) imaging with experimental doses of 0.05-0.3 mmol/kg. Fifteen patients also underwent contrast studies with the standard dose (0.1 mmol/kg) of gadopentetate dimeglumine. Both gadopentetate dimeglumine and gadoteridol appear to have a similar effect when given in equal doses (0.1 mmol/kg, n = 5). Lesion enhancement and delineation were better at higher experimental doses (0.2 or 0.3 mmol/kg, n = 7) and worse at a lower experimental dose (0.05 mmol/kg, n = 3). Quantitative analysis of 10 lesions examined with identical imaging protocols revealed a directly proportional relationship (r = .975) between lesion contrast ratio and dose over a range of 0.05-0.3 mmol/kg. Phantom experiments support the clinical results. Improved enhancement, detection, and delineation of central nervous system (CNS) neoplasms resulting from increased injected doses of gadoteridol have the potential to be clinically significant and may justify the possibly higher cost of increased contrast material dosage. Lower doses may not be adequate for the evaluation of most CNS tumors.

Adult↗