Search PubMed⌕ Search

Biomedical subjects

R A Jacobs

Publications and source records attributed to R A Jacobs.

At least 19 recordsLinked to original sources
PubMed2001

Experience-dependent visual cue integration based on consistencies between visual and haptic percepts.

We study the hypothesis that observers can use haptic percepts as a standard against which the relative reliabilities of visual cues can be judged, and that these reliabilities determine how observers combine depth information provided by these cues. Using a novel visuo-haptic virtual reality environment, subjects viewed and grasped virtual objects. In Experiment 1, subjects were trained under motion relevant conditions, during which haptic and visual motion cues were consistent whereas haptic and visual texture cues were uncorrelated, and texture relevant conditions, during which haptic and texture cues were consistent whereas haptic and motion cues were uncorrelated. Subjects relied more on the motion cue after motion relevant training than after texture relevant training, and more on the texture cue after texture relevant training than after motion relevant training. Experiment 2 studied whether or not subjects could adapt their visual cue combination strategies in a context-dependent manner based on context-dependent consistencies between haptic and visual cues. Subjects successfully learned two cue combination strategies in parallel, and correctly applied each strategy in its appropriate context. Experiment 3, which was similar to Experiment 1 except that it used a more naturalistic experimental task, yielded the same pattern of results as Experiment 1 indicating that the findings do not depend on the precise nature of the experimental task. Overall, the results suggest that observers can involuntarily compare visual and haptic percepts in order to evaluate the relative reliabilities of visual cues, and that these reliabilities determine how cues are combined during three-dimensional visual perception.

Cues↗
PubMed2001

Impact of an intravenous fluconazole restriction policy on patient outcomes.

OBJECTIVE: To evaluate both the economic and clinical impact of an intravenous fluconazole restriction policy in a university teaching hospital. METHODS: Intravenous fluconazole was restricted to patients unable to take oral medications due to significant nausea or to patients whose oral intake was restricted. A retrospective chart review and computerized record review was conducted in patients receiving intravenous or oral fluconazole from January 1 to June 30, 1997, and again from January 1 to June 30, 1998, after implementation of the policy. RESULTS: Six-month institutional expenditures for intravenous fluconazole decreased following policy implementation, from $81,900 to $45,400, an estimated annual institutional savings of $73,000. A 47% reduction in the number of patients treated with intravenous fluconazole was observed over the six-month period after policy implementation. During this time, the rate of successful clinical outcomes for documented or suspected disseminated Candida albicans infection or febrile neutropenia remained the same (66.6% prepolicy and 65.9% postpolicy; p = 0.95). Similarly, the number of deaths in patients receiving fluconazole remained unchanged (p = 0.31). CONCLUSIONS: A restriction policy for intravenous fluconazole results in significant cost savings, with no significant decrease in successful outcomes or change in mortality.

Administration, Oral↗
PubMed2000

Perceptual learning for a pattern discrimination task.

Our goal was to differentiate low and mid level perceptual learning. We used a complex grating discrimination task that required observers to combine information across wide ranges of spatial frequency and orientation. Stimuli were 'wicker'-like textures containing two orthogonal signal components of 3 and 9 c/deg. Observers discriminated a 15% spatial frequency shift in these components. Stimuli also contained four noise components, separated from the signal components by at least 45 degrees of orientation or approximately 2 octaves in spatial frequency. In Experiment 1 naive observers were trained for eight sessions with a four-alternative same-different forced choice judgment with feedback. Observers showed significant learning, thresholds dropped to approximately 1/3 of their original value. In Experiment 2 we found that observers showed far less learning when the noise components were not present. Experiment 3 found, unlike many other studies, almost complete transfer of learning across orientation. The results of Experiments 2 and 3 suggest that, unlike many other perceptual learning studies, most learning in Experiment 1 occurs at mid to high levels of processing rather than within low level analyzers tuned for spatial frequency and orientation. Experiment 4 found that performance was more severely impaired by spatial frequency shifts in noise components of the same spatial frequency or orientation as the signal components (though there was significant variability between observers). This suggests that after training observers based their responses on mechanisms tuned for selective regions of Fourier space. Experiment 5 examined transfer of learning from a same-sign task (the two signal components both increased/decreased in spatial frequency) to an opposite-sign task (signal components shifted in opposite directions in frequency space). Transfer of learning from same-sign to opposite-sign tasks and vice versa was complete suggesting that observers combined information from the two signal components independently.

Adult↗
PubMed2000

Motor timing learned without motor training.

Improvements due to perceptual training are often specific to the trained task and do not generalize to similar perceptual tasks. Surprisingly, given this history of highly constrained, context-specific perceptual learning, we found that training on a perceptual task showed significant transfer to a motor task. This result provides evidence for a common neural architecture underlying analysis of sensory input and control of motor output, and suggests a potential role for perception in motor development and rehabilitation.

Adult↗
PubMed2000

Ceftriaxone therapy for staphylococcal osteomyelitis: a review.

Ceftriaxone, although less active than standard antistaphylococcal agents, is potentially useful in the treatment of osteomyelitis. Thirty-one patients with osteomyelitis due to Staphylococcus aureus were identified, 22 of whom were treated with ceftriaxone and 9 with other agents. Of those patients treated with ceftriaxone, 17 were cured; all treatment failures were associated with chronic osteomyelitis and continued presence of necrotic bone or infected hardware. It is concluded that ceftriaxone is effective in the ambulatory treatment of S. aureus osteomyelitis.

Adult↗
PubMed1999

Modeling the combination of motion, stereo, and vergence angle cues to visual depth.

Three models of visual cue combination were simulated: a weak fusion model, a modified weak model, and a strong model. Their relative strengths and weaknesses are evaluated on the basis of their performances on the tasks of judging the depth and shape of an ellipse. The models differ in the amount of interaction that they permit among the cues of stereo, motion, and vergence angle. Results suggest that the constrained nonlinear interaction of the modified weak model allows better performance than either the linear interaction of the weak model or the unconstrained nonlinear interaction of the strong model. Further examination of the modified weak model revealed that its weighting of motion and stereo cues was dependent on the task, the viewing distance, and, to a lesser degree, the noise model. Although the dependencies were sensible from a computational viewpoint, they were sometimes inconsistent with psychophysical experimental data. In a second set of experiments, the modified weak model was given contradictory motion and stereo information. One cue was informative in the sense that it indicated an ellipse, while the other cue indicated a flat surface. The modified weak model rapidly reweighted its use of stereo and motion cues as a function of each cue's informativeness. Overall, the simulation results suggest that relative to the weak and strong models, the modified weak fusion model is a good candidate model of the combination of motion, stereo, and vergence angle cues, although the results also highlight areas in which this model needs modification or further elaboration.

Computer Simulation↗
PubMed1999

Pineal nitric oxide synthase, but not heme oxygenase, mRNA is suppressed by continuous exposure to light.

We have previously shown that exposure of rats to constant light (LL) induced a decrease in NO synthase (NOS) activity in the pineal gland. We report here that the use of the sensitive technique of RT-PCR has demonstrated that mRNA for neuronal NOS is present in the pineal, and that it is photoneurally regulated. There was a marked decrease in pineal neuronal NOS mRNA levels in continuous light conditions, similar to the changes seen in NOS enzyme activity. Inducible NOS was not present in the pineal, and there was evidence that the photoregulatable form was not endothelial NOS. The mRNA for two isoforms of heme oxygenase, the enzyme responsible for the generation of the putative neuromodulator carbon monoxide, was also present in the pineal, but neither isoform was photoregulated. Using immunodetection, it was not possible to identify the presence of NOS protein, other than to a minimal extent, even though NOS activity was clearly present. NADPH-diaphorase staining and in situ hybridization were carried out in an attempt to identify the precise location of neuronal NOS message. A strong NADPH-diaphorase reaction was present in sympathetic nerve fibers of the pineal, but pinealocytes showed no or only very weak labelling. In situ hybridization was also unable to identify neuronal NOS message in pinealocytes. These data thus also suggest the possible presence of a pineal-specific NOS isoenzyme.

Animals↗
PubMed1999

Optimal integration of texture and motion cues to depth.

We report the results of a depth-matching experiment in which subjects were asked to adjust the height of an ellipse until it matched the depth of a simulated cylinder defined by texture and motion cues. In one-third of the trials the shape of the cylinder was primarily given by motion information, in another one-third of the trials it was given by texture information, and on the remaining trials it was given by both sources of information. Two optimal cue combination models are described where optimality is defined in terms of Bayesian statistics. The parameter values of the models are set based on subjects' responses on trials when either the motion cue or the texture cue was informative. These models provide predictions of subjects' responses on trials when both cues were informative. The results indicate that one of the optimal models provides a good fit to the subjects' data, and the second model provides an exceptional fit. Because the predictions of the optimal models closely match the experimental data, we conclude that observers' cue-combination strategies are indeed optimal, at least under the conditions studied here.

Contrast Sensitivity↗
PubMed1999

Experience-dependent integration of texture and motion cues to depth.

Previous investigators have shown that observers' visual cue combination strategies are remarkably flexible in the sense that these strategies adapt on the basis of the estimated reliabilities of the visual cues. However, these researchers have not addressed how observers' acquire these estimated reliabilities. This article studies observers' abilities to learn cue combination strategies. Subjects made depth judgments about simulated cylinders whose shapes were indicated by motion and texture cues. Because the two cues could indicate different shapes, it was possible to design tasks in which one cue provided useful information for making depth judgments, whereas the other cue was irrelevant. The results of experiment 1 suggest that observers' cue combination strategies are adaptable as a function of training; subjects adjusted their cue combination rules to use a cue more heavily when the cue was informative on a task versus when the cue was irrelevant. Experiment 2 demonstrated that experience-dependent adaptation of cue combination rules is context-sensitive. On trials with presentations of short cylinders, one cue was informative, whereas on trials with presentations of tall cylinders, the other cue was informative. The results suggest that observers can learn multiple cue combination rules, and can learn to apply each rule in the appropriate context. Experiment 3 demonstrated a possible limitation on the context-sensitivity of adaptation of cue combination rules. One cue was informative on trials with presentations of cylinders at a left oblique orientation, whereas the other cue was informative on trials with presentations of cylinders at a right oblique orientation. The results indicate that observers did not learn to use different cue combination rules in different contexts under these circumstances. These results are consistent with the hypothesis that observers' visual systems are biased to learn to perceive in the same way views of bilaterally symmetric objects that differ solely by a symmetry transformation. Taken in conjunction with the results of Experiment 2, this means that the visual learning mechanism underlying cue combination adaptation is biased such that some sets of statistics are more easily learned than others.

Cues↗
PubMed1999

Expression and functional analysis of endothelial nitric oxide synthase (eNOS) in human placenta.

We have investigated the expression and localization of endothelium-derived nitric oxide synthase (eNOS) and the effect of eNOS on placental human chorionic gonadotrophin (HCG) release. eNOS mRNA was found to be expressed in all tissues, with its expression significantly (P<0.05) increased across gestation. Compared to normal term gestation, placentae from term pregnancies with fetal retardation, or maternal diabetes, but not with maternal hypertension, displayed significantly more (P<0.05) eNOS mRNA. By immunocytochemistry, we found staining for eNOS in both the cyto- and syncytiotrophoblasts of first trimester and a loss of cytotrophoblast eNOS staining in term placentae, while syncytiotrophoblasts at term were strongly eNOS positive. Additional staining was found in endothelium surrounding the vascular tree. HCG was found to colocalize with eNOS in trophoblasts, but not in endothelia. When placental explants were perifused, exposure to the NOS substrate, the NO donor, I-arginine and trinitroglycerol evoked a prompt, albeit transient, increase of HCG release. The NOS inhibitor delayed, but did not block arginine-induced HCG release. Thus, eNOS is expressed in the human placenta at increasing levels during gestation with further increases during some pathological conditions. A role for NO in the acute endocrine modulation of the placenta is suggested by the colocalization of eNOS with HCG in human trophoblasts and the prompt secretion of HCG in response to agents which increase NO concentrations.

Cells, Cultured↗
PubMed1999

Expression of menin gene mRNA in pituitary tumours.

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant inherited disorder characterised by the combined occurrence of parathyroid, endocrine pancreas and anterior pituitary tumours. The gene responsible for MEN 1, the menin gene, a putative tumour-suppressor gene located on human chromosome 11q13, has been cloned. To investigate the role of the menin gene in sporadic anterior pituitary tumorigenesis, its mRNA was assessed in a group of pituitary tumours. METHODS: Menin gene expression, along with glyceraldehyde phosphate dehydrogenase (GAPDH) gene expression, has been studied in a group of normal pituitaries and in 23 pituitary tumours not associated with the MEN 1 syndrome. The pituitary tumours included 4 prolactinomas, 11 growth-hormone-secreting tumours and 8 non-functional tumours. Total RNA was extracted from the normal pituitaries and tumours, and cDNA was synthesised with standard reverse transcriptase methods. Duplex polymerase chain reaction (PCR) was standardised in order to quantify the expression of the menin gene using intron-spanning primers across exons 9 and 10 in relation to the 'house-keeping' gene GAPDH. The PCR products were separated on agarose gel and densitometric analysis of the bands allowed semi-quantification. RESULTS: There was no evidence for a change in menin gene expression in any of the pituitary tumours when compared with normal pituitaries. CONCLUSIONS: These studies complement previous work on mutational analysis, and do not suggest a major role for the menin suppressor gene in sporadic pituitary tumorigenesis.

DNA Primers↗
PubMed1999

Prevention of adverse events in hospitalized patients using an antimicrobial review program.

OBJECTIVE: To evaluate whether an antimicrobial review system is associated with a reduction in antimicrobial-associated adverse events. DESIGN: All antimicrobial medication orders for patients hospitalized over a two-year period were evaluated. High-level interventions intended to prevent adverse antimicrobial events were collated. Based on literature estimates of adverse antimicrobial events, potential reduction of high-level adverse antimicrobial events was estimated. SETTING: Department of Clinical Pharmacy and Division of Infectious Diseases at a tertiary care teaching hospital. RESULTS: A total of 452 interventions were classified as "high-level." The incidence of preventable adverse antimicrobial events requiring intervention was 16 per 1000 antimicrobial orders. The incidence of high-level errors necessitating intervention was 4.4 per 1000 antimicrobial orders. An estimated 125 to 198 high-level adverse events were avoided. CONCLUSION: An antimicrobial review program has the potential to reduce significant adverse events in hospitalized patients.

Anti-Bacterial Agents↗
PubMed1998

Acute and subacute effects of endotoxin on hypothalamic gaseous neuromodulators.

Although two-way communication between the hypothalamus and the immune system in now well established, particularly for the hypothalamo-pituitary-adrenal axis, the role of the gaseous neurotransmitters nitric oxide (NO) and carbon monoxide (CO) is much less well understood in terms of hypothalamic function. These agents are an important part of the peripheral inflammatory response; and their synthetic enzymes, NO synthase (NOS) and heme oxygenase (HO), respectively, have been localized to the hypothalamic PVN and SON. The induced generation of both NO and CO leads to the suppression of CRH and vasopressin, the major stimulators of the HPA. Thus, the addition of hemin to hypothalamic explants is maximally active at 1 microM in attenuating the release of CRH and vasopressin, and this dose is also most effective in generating biliverdin and associated CO. CO generation is also able to stimulate cyclooxygenase to produce prostaglandin E2, an established intermediary in the cytokine-stimulated activation of the HPA. Finally, inducible NOS mRNA is specifically induced in the hypothalalmus in response to endotoxin, in parallel to interleukin-1. These data provide increasing evidence in favor of NO and CO as counterregulatory agents in the HPA response to immune activation.

Animals↗
PubMed1998

Lipid formulations of amphotericin B: clinical efficacy and toxicities.

Commercially available lipid formulations of amphotericin B (Abelcet, Amphotec, and AmBisome) represent a significant advance in drug delivery technology. Differences in biochemical, pharmacokinetic, and pharmacodynamic properties among the lipid products have been shown in in vitro and in vivo models. Clinical experience with these products has been primarily in patients either refractory to or intolerant of conventional amphotericin B deoxycholate (AmBd). None of the lipid-based products demonstrates superior efficacy when prospectively compared with AmBd in the treatment of documented infections. When used for the empirical treatment of febrile neutropenia, AmBisome significantly reduced the incidence of proven emergent fungal infections but did not improve short-term survival rates, in comparison with AmBd. Acute infusion-related adverse events vary, whereas nephrotoxicity is reduced with all three lipid formulations. Until superior efficacy is clearly shown (for documented infections) or pharmacoeconomic analyses document the value of these drugs, use of such expensive agents should be highly restricted to those who are intolerant of or refractory to AmBd.

Amphotericin B↗
PubMed1998

Endotoxin induces interleukin-1beta and nitric oxide synthase mRNA in rat hypothalamus and pituitary.

The gases nitric oxide (NO) and carbon monoxide (CO) may be involved in hypothalamo-pituitary-adrenal axis (HPA) modulation. In the brain, NO is synthesized by two forms of NO synthase (NOS), a constitutive neuronal form (nNOS) and an inducible form (iNOS). There are also a constitutive heme oxygenase (HO2) and an inducible form (HO1) which generate CO. We have therefore investigated the effect of peripheral lipopolysaccharide (LPS) administration on the gene expression of these enzymes along with interleukin-1beta (IL-1beta) gene expression in the hypothalamus, pituitary and liver. Male Wistar rats (200-250 g body weight) were injected intraperitoneally with endotoxin (Escherichia coli, 055 B5) dissolved in sterile normal saline [250 microg/kg first group, 2.5 mg/kg (second group) and 6.25 mg/kg (third group)] in a final volume of 0.5 ml, or saline alone in the control group. The first and the second groups were studied 1, 3, 8 and 24 h after LPS (n = 4 per group); the third group was studied at 3 h. Total RNA was extracted from the hypothalamus, pituitary and liver, and cDNA was made using standard reverse transcriptase methods. Duplex polymerase chain reaction (PCR) was standardised in order to quantify the expression of a specific gene in relation to the 'house-keeping' gene beta-actin. The specific genes studied were iNOS, nNOS, HO1, HO2 and IL-1beta. The PCR products were separated on agarose gel and densitometric analysis of the bands allowed semi-quantification. In the second group, iNOS and IL-1beta were induced in hypothalamus, pituitary and liver, showing a peak at 3 h (p < 0.001), returning to baseline levels at 24 h. Neuronal NOS was not expressed in the liver under basal conditions or after LPS; in the hypothalamus and pituitary, nNOS was expressed basally but there was no change after LPS. In the first group, iNOS and IL-1beta were again induced in all three tissues studied, but with a delayed time course compared to the second and third groups; the peak change for IL-1beta occurred at 8 h (p < 0.05), again returning to baseline levels at 24 h. The peak for iNOS occurred at 24 h. HO1 and HO2 were expressed in all three tissues under basal conditions; HO1 was increased at 1 h in the liver in the second group, and at 3 h in the pituitary in the third group. There was no change in either HO1 or HO2 in the hypothalamus at any dose at any time point. We conclude that IL-1beta and iNOS are induced in rat hypothalamus and pituitary following various doses of endotoxin. We speculate that while IL-1beta may mediate stimulation of the HPA by endotoxin, NO generation may be involved in the counter-regulation of this response.

Animals↗
PubMed1998

Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors.

Synthetic GH secretagogues (GHSs; GH-releasing peptides and their nonpeptide mimetics) stimulate GH release, activate the hypothalamo-pituitary-adrenal axis, and release PRL in vivo. Patients with acromegaly show an exuberant GH response to GHSs, whereas patients with pituitary-dependent ACTH-secreting tumors show an exaggerated rise in ACTH and cortisol. We, therefore, studied the presence of GHS receptor (GHS-R) messenger ribonucleic acid (RNA) in 38 human pituitary tumors of different cell types, 3 ectopic ACTH-secreting tumors, a pancreatic gastrinoma, 3 insulinomas, and a non-secreting thymic carcinoid as well as in 7 normal pituitary glands. Certain pituitary tumors were also studied by in vitro cell culture with measurement of secreted GH, ACTH, PRL, FSH, LH, alpha-subunit, and TSH. RNA was extracted from tissue samples and, after RT, a duplex PCR reaction with primers for the GHS-R gene and for the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase was performed, allowing semiquantitation of GHS-R expression. All the somatotroph adenomas (n = 8) showed a 2-10 times higher expression of the GHS-R gene compared to normal pituitaries. Higher than normal expression was shown in 5 of 18 tumors from patients with ACTH-secreting pituitary adenomas and in 1 of 3 ectopic ACTH-secreting carcinoid tumors. Two of the pituitary ACTH-secreting adenoma samples showed completely absent expression of the GHS-R, 8 showed expression similar to that of normal pituitary tissue, and 3 of the corticotroph adenoma tissue samples and 2 ectopic ACTH-secreting tumors showed a very low level of expression. One of 4 prolactinoma samples showed a high level of expression, 1 showed expression similar to that of normal pituitary, and 2 samples showed a very low level of expression. Nonfunctioning pituitary adenoma samples showed either absent or very low level expression of the GHS-R. The pancreatic gastrinoma sample showed expression similar to that of normal pituitary tissue, whereas 3 insulinomas showed low level expression of the GHS-R gene; a nonsecreting thymic carcinoid tumor showed no detectable expression. In summary, although GHS-R messenger RNA is abundant in human somatotroph adenomas, it is also present in other pituitary adenomas, particularly ACTH-secreting tumors. These findings may explain the in vivo responses to GHSs in patients harboring such tumors. It also appears from our study that GHS-R may be expressed in other neuroendocrine tumors.

Acromegaly↗
PubMed1997

Induction of nitric oxide synthase and interleukin-1beta, but not heme oxygenase, messenger RNA in rat brain following peripheral administration of endotoxin.

Previous studies have suggested that both nitric oxide (NO) and carbon monoxide (CO) are important modulators of the inflammatory response, while more recent data have implicated both gases as regulators of hypothalamic neuroendocrine function, particularly the hypothalamo-pituitary-adrenal axis. We have, therefore, investigated the modulation of the transcripts for the synthetic enzymes for both NO and CO following the intraperitoneal administration of lipopolysaccharide, serotype B5 055, over the course of 24 h. The mRNA for type I or neuronal nitric oxide synthase (nNOS), and type II or inducible (iNOS), and heme oxygenase1 ('inducible') and heme oxygenase2 ('constitutive'), were reverse transcribed to cDNA, amplified by the polymerase chain reaction, and then quantified using a co-amplified internal standard, beta-actin. This allowed for assessment of relative changes in transcript concentration. In addition, these were compared to changes in expression of the cytokine, IL-1beta. Finally, absolute levels of the synthetic enzyme transcripts were assessed by means of co-amplification in the presence of varying amounts of mutant templates in a competitive PCR reaction. Our data revealed rapid induction of IL-1beta, iNOS and HO1 in the liver, returning to baseline at 24 h. In the hypothalamus, all transcripts were present under basal conditions, but only IL-1beta and iNOS were induced by the LPS. We conclude that hypothalamic IL-1beta and iNOS can be induced by a non-lethal dose of endotoxin, and are, thus, in a position to mediate certain of the neuroendocrine consequences to inflammatory stress.

Animals↗