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Biomedical subjects

Paul J Feustel

Publications and source records attributed to Paul J Feustel.

15 recordsLinked to original sources

Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat.

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and redox modulator. It has previously been reported to reduce infarct size in 7-day-old rat pups with an in vivo cerebral hypoxia/ischemia model (Jensen et al., 1994). In this study, we tested whether improvement is found in both behavioral measures of protection and by histological measures of infarcted tissue at 72 h after reversible middle cerebral artery occlusion (rMCAo) in adult rats. Two-hour rMCAo was induced in adult rats using the intraluminal suture technique. PQQ (10, 3, and 1 mg/kg) was given once by intravenous injection at the initiation, or 3 h after the initiation, of 2 h rMCAo. Neurobehavioral deficits were evaluated daily for 3 days followed by infarct volumes measurements by 2,3,5-triphenyltetrazolium chloride (TTC) staining. PQQ at 10 mg/kg infused at the initiation, or 3 h after the initiation, of rMCAo was effective in reducing cerebral infarct volumes measured 72 h later. At 3 h after ischemia, a dose of 3 mg/kg significantly reduced infarct volume compared to vehicle-treated animals, but 1 mg/kg was ineffective. Neurobehavioral scores were also significantly better in the PQQ-treated group compared to the vehicle controls when PQQ was given at 10 and 3 mg/kg, but not at 1 mg/kg. Thus, PQQ is neuroprotective when given as a single administration at least 3 h after initiation of rMCAo. These data indicate that PQQ may be a useful neuroprotectant in stroke therapy.

Animals↗

Behavioral and histological neuroprotection by tamoxifen after reversible focal cerebral ischemia.

We have previously shown that tamoxifen can reduce infarct sizes measured by 2,3,5,-triphenyltetrazolium chloride (TTC) staining at 72 h after 2 h of reversible middle cerebral artery occlusion (rMCAo) in rats. In this study, we tested whether improvement is found in both behavioral measures of protection and by histological measures of infarcted tissue at 7 and 14 days after 2 h rMCAo. Tamoxifen (10 mg/kg) was given once by intravenous injection 1 h after reperfusion, i.e. 3 h after initiation of rMCAo. Neurobehavioral deficits were evaluated daily for 1 week or 2 weeks followed by infarct volumes measurements by hematoxylin-eosin (HE) staining. Tamoxifen-treated rats had significantly improved neurobehavioral deficit scores when evaluated daily throughout the 1 week or 2 week periods and showed significantly reduced median infarct volumes measured after 1 week and 2 weeks. Median infarct values were 149 mm3 (interquartile range, IQR: 92 to 258) and 124 mm3 (IQR: 69 to 174) for the 1 and 2 week vehicle groups, respectively, compared with 5 mm3 (IQR: 3 to 16) and 4 mm3 (IQR: 0 to 48) for the comparable treated groups (both P < 0.05, Mann-Whitney test), giving a reduction of more than 90% in both cases. Thus, a single administration of tamoxifen given 3 h after initiation of rMCAo is extremely effective in producing long-term neuroprotection as assessed by neurobehavioral measures and histopathology in experimental stroke in rats. If these results are extrapolatable to human stroke, these data indicate that tamoxifen may be a useful neuroprotectant.

Animals↗

Efficacy and safety of repeated doses of botulinum toxin type B in type A resistant and responsive cervical dystonia.

Efficacy of botulinum toxin type B (BoNT B) for the treatment of type A-resistant (AR) and non-A-resistant (NAR) cervical dystonia (CD) has been demonstrated in several single injection studies. There is little data available on long-term therapy with repeated injection sessions and it is unknown if AR and NAR patients respond in a similar manner over time. To evaluate the long-term efficacy and safety of BoNT B in AR and NAR CD patients, we carried out a prospective, open-label study examining 10 repeated dosing sessions of BoNT B in 34 patients with CD (15 AR and 19 NAR). Dosing was started at 10,000 units and could be increased to 25,000. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and a patient global assessment at each baseline (injection) and Week 4 (peak effect) visit. Change in TWSTRS total was the primary efficacy end point. Data was analyzed using repeated-measures analysis of variance. BoNT B therapy resulted in an overall significant improvement of CD (P<0.001) and improvement was seen in all 10 individual sessions (2.5 years). The magnitude of response decayed over time (P<0.001). There was no difference between AR and NAR patients with regard to dose, treatment effect, or decay in response. The AR group perceived (patient global) treatment as being less effective (P=0.047). Dry mouth frequency decreased with each session despite increasing doses whereas flu-like syndrome and weakness increased. BoNT B therapy provides long-term benefit for CD patients but the magnitude of response diminishes over time. The cause of this decay is probably multifactorial. AR and NAR CD patients respond in a similar fashion.

Botulinum Toxins, Type A↗

Successful thyroid tissue ablation as defined by a negative whole-body scan or an undetectable thyroglobulin: a comparative study.

BACKGROUND: Successful thyroid tissue ablation of patients with well-differentiated thyroid cancer can be defined by a negative whole-body scan (WBS) and/or an undetectable thyroglobulin (Tg). Variables associated with success are poorly understood. Tg measurement, although more sensitive than WBS, has not been firmly established as the sole monitoring method. In a previous study, we retrospectively evaluated the variables associated with scintigraphic success. Ablation dose (AD) was the only variable associated with success (odds ratio (OR): 1.96 per 1.85 GBq increment; 95% confidence interval (CI)=1.11-3.46). OBJECTIVES: (1) To determine if the variables associated with success are the same using Tg. (2) To determine whether Tg measurement can become the sole method for assessing ablation success. METHODS: We performed the analysis using a Tg level <2 ng.ml-1 as a criterion for completed ablation. Data were available from 109 patients. RESULTS: Univariate analysis showed an effect of stage (OR=0.05; 95% CI=0.01-0.23) and female sex (OR=2.8; 95% CI=1.14-6.89). Multivariate analysis demonstrated only stage to be a significant predictor of success. Ablation was successful by both methods in 62/109 patients and it failed by both in 10/109. There were 21 WBS- Tg+ and 16 WBS+ Tg- patients. CONCLUSIONS: Investigation of the variables associated with successful ablation yields different results depending on the definition of success. There was a significant incidence of WBS+ Tg- cases after initial ablation. Until it is firmly established that such patients have a benign course both monitoring methods should be used.

Adult↗

Increasing the radiochemical purity of 99mTc sestamibi commercial preparations results in improved sensitivity of dual-phase planar parathyroid scintigraphy.

BACKGROUND: Poor results for dual-phase parathyroid scintigraphy have recently prompted increased use of dual-tracer imaging. We noticed that seminal studies used higher radiochemical purity than provided by current commercial preparations meeting US Pharmacopea (USP) specifications (90% of technetium bound to sestamibi). We surmised that the presence of unbound Tc (non-MIBI tracer) might hamper dual-phase detection that is dependent on rapid wash-out of technetium from thyroid tissue. PURPOSE: To test the hypothesis that reducing non-MIBI tracer will enhance thyroid wash-out and improve sensitivity of dual-phase imaging. METHODS: Starting in April 2003 we decreased the technetium to sestamibi ratio. This resulted in a significant decrease of non-MIBI tracer from 8.1+/-2.2% (SD) (group 1, n = 42) to 3.5+/-1.1% (group 2, n = 47) (P < 0.05 t-test). We performed a retrospective review of 89 patients with primary hyperparathyroidism who underwent imaging and subsequent surgery. The pathological findings served as the 'gold standard'. RESULTS: Scanning detected 21/39 diseased glands (sensitivity=54%) in group 1 patients. In group 2 imaging detected 38/45 diseased glands (sensitivity = 84%). An improvement in sensitivity (P < 0.01) was achieved by modifying the radiopharmaceutical preparation. CONCLUSIONS: Elevated levels of non-MIBI tracer in Tc-MIBI commercial preparations result in persistent thyroid background activity that may interfere with detection of parathyroid pathology. Achieving a higher degree of radiochemical purity (at least 95% bound, 5% impurities) than required by USP may be needed for optimal results. The large variation in sensitivity reported in the literature may be related in part to non-uniform radiopharmaceutical preparation.

Adult↗

Volume-regulated anion channels are the predominant contributors to release of excitatory amino acids in the ischemic cortical penumbra.

BACKGROUND AND PURPOSE: Release of excitatory amino acids (EAA) is considered a cause of neuronal damage in ischemia. We investigated the sources and mechanisms of EAA release using microdialysis in regions of incomplete ischemia where perfusion was reduced by 50% to 80%, by applying inhibitors of volume-regulated anion channels (VRACs) and the GLT-1 glutamate transporter. METHODS: Reversible middle cerebral artery occlusion (rMCAo) was induced in anesthetized rats using the intraluminal suture technique. Microdialysate concentrations of glutamate, aspartate, and taurine were measured before, during 2 hours of rMCAo, and for 2 hours after rMCAo. Vehicle, dihydrokainate (DHK, 1 mmol/L), a GLT-1 inhibitor, or tamoxifen (50 micromol/L), a VRAC inhibitor, were administered continuously via the dialysis probes starting one hour prior to ischemia. RESULTS: During incomplete ischemia, dialysate glutamate levels averaged 1.74+/-0.31 micromol/L (SEM) in the control group (n=8), 2.08+/-0.33 micromol/L in the DHK group (n=7), and were significantly lower at 0.88+/-0.30 micromol/L in the tamoxifen group (n=9; P<0.05). As perfusion returned toward baseline levels, EAA levels declined in the vehicle and tamoxifen-treated animals but they remained elevated in the DHK-treated animals. CONCLUSIONS: In contrast to previous results in severely ischemic regions, DHK did not reduce EAA release in less severely ischemic brain, suggesting a diminished role for transporter reversal in these areas. These findings also support the hypothesis that in regions of incomplete ischemia, release of EAAs via VRACs may play a larger role than reversal of the GLT-1 transporter.

Amino Acid Transport System X-AG↗

The age dependent relationship between facial fractures and skull fractures.

OBJECTIVE: To provide clinical evidence to support the age dependent relationship between facial fractures and skull fractures. DESIGN: Retrospective chart review of all children and adults admitted with combined facial fractures and skull fractures and skull fractures alone between January 1991 and November 1997. SETTING: The Albany Medical Center Hospital, a tertiary level-one trauma center. PATIENTS: Two hundred and one children, ages 1 month to 17 years, with skull fractures (frontal, parietal, or temporal), and 41 children with concurrent facial fractures were included in this study. One hundred and thirty-nine adults, ages 18-90 years, with skull fractures, and 70 adults with concurrent facial fractures were also studied. OUTCOME MEASURES: The gender, age, skull fracture, facial fracture, Glasgow coma score (GCS), mechanism of injury, and outcome of all patients admitted with frontal, parietal, or temporal fractures with or without facial fractures. RESULTS: There are a significantly greater (P < 0.001) number of facial fractures associated with skull fractures among adults as compared to children. Moreover, there is an exponential rise in facial fractures associated with skull fractures between infancy and adolescence. The GCS of children with combined facial and skull fractures is significantly lower than in those with skull fractures only (P < 0.001). CONCLUSION: The spectrum of craniofacial injuries is related to the specific developmental stage of the craniofacial skeleton. This is demonstrated by the variable pattern of combined facial and skull fractures observed clinically in children and adults.

Accidents, Traffic↗

Early carotid endarterectomy after acute stroke.

PURPOSE: Carotid endarterectomy (CEA) after acute stroke is generally delayed 6 to 8 weeks because of fear of stroke progression. This delay can result in an interval stroke rate of 9% to 15%. We analyzed our results with CEA performed within 1 to 4 weeks of stroke. METHODS: Records for all patients undergoing CEA after stroke between 1980 and 2001 were analyzed. Perioperative evaluation included carotid duplex scanning or angiography, and head computed tomography or magnetic resonance imaging. All patients with nonworsening neurologic status, additional brain territory at risk for recurrent stroke, and severe ipsilateral carotid stenosis underwent CEA. Patients were grouped according to time of CEA after stroke: group 1, first week; group 2, second week; group 3, third week; group 4, fourth week. Statistical analysis was performed with the chi(2) test, logistic regression, and analysis of variance. RESULTS: Two hundred twenty-eight patients underwent CEA within 1 to 4 weeks of stroke. Perioperative permanent neurologic deficits occurred in 2.8% of patients in group 1 (72 procedures), 3.4% of patients in group 2 (59 procedures), 3.4% of patients in group 3 (29 procedures), and 2.6% of patients in group 4 (78 procedures). There was no relationship between location or size of preoperative infarct and time of surgery. Only preoperative infarct size correlated with probability of neurologic deficit after CEA (P <.05). CONCLUSION: Incidence of postoperative stroke exacerbation is similar at all intervals. The results are within acceptable limits for treatment of symptomatic carotid stenosis. CEA may be performed within 1 month of stroke with similar results at all intervals during this period.

Acute Disease↗

Is elevated creatinine level a contraindication to endovascular aneurysm repair?

PURPOSE: It is widely believed that chronic renal insufficiency (CRI) greatly increases the risk associated with endovascular abdominal aortic aneurysm repair (EVAR) and is a relative contraindication to the procedure and to the use of intra-arterial contrast agents (IACA). We reviewed a 5-year EVAR experience to determine whether the procedure and use of IACA have an important deleterious effect on renal function in patients with and without pre-existing CRI. METHODS: Endovascular aneurysm repair (EVAR) was performed in 200 patients with a variety of endografts, with intra-arterial contrast agents. The patients were retrospectively assigned to three groups on the basis of preoperative serum creatinine concentration (Cr): group 1 (n = 108), Cr less than 1.5 mg/dL (normal range); group 2 (n = 65), Cr 1.5 to 2.0 mg/dL; group 3 (n = 27), Cr 2.1 to 3.5 mg/dL. No patients had undergone hemodialysis. In groups 2 and 3, patients received hydration perioperatively, and received mannitol intraoperatively; no nephrotoxic drugs were administered during the procedure, other than nonionic contrast agent (Omnipaque 350). RESULTS: The incidence of postoperative complications between the three study groups was not statistically different. In group 1 a transient increase in serum Cr (>30% over baseline and >1.4 mg/dL) was noted in three patients (2.7%), two of whom (1.9%) required temporary hemodialysis and one (0.9%) who died of renal failure. In group 2 a transient increase in serum Cr was noted in two patients (3.1%); both patients (3.1%) required temporary hemodialysis, and one patient (1.5%) died of renal failure. In group 3 a transient increase in serum Cr was noted in two patients (7.4%); one patient (3.7%) required temporary hemodialysis, and one patient (3.7%) died of renal failure. Perioperative hypotension significantly increased the risk for elevated serum Cr and death (P <.05), and larger contrast volume was associated with an increase in serum Cr (P <.05) during the postoperative period. CONCLUSIONS: EVAR with intra-arterial contrast agents can be accomplished in patients with chronic renal insufficiency who do not require dialysis, with limited and acceptable morbidity and mortality, similar to that observed with open aneurysm repair. Contrary to other reports in which perioperative precautions were not used, our study shows that with EVAR the risk for worsening renal failure, dialysis, and death is only slightly, and not significantly, greater in patients with preoperative chronic renal insufficiency compared with patients with normal renal function. Perioperative hypotension and increased contrast volume are significant risk factors for postoperative increase in serum Cr and death. With appropriate precautions such as averting perioperative hypotension and limiting the volume of nonionic contrast agents, elevated Cr need not be a contraindication to EVAR with intra-arterial contrast agents.

Aged↗

Inhibition of release of taurine and excitatory amino acids in ischemia and neuroprotection.

Volume regulated anion channels (VRAC) have been extensively studied in purified single cell systems like cell cultures where they can be activated by cell swelling. This provides a convenient way of analyzing mechanisms and will likely lead to the holy grails of the field, namely the nature or natures of the volume sensor and the nature or natures of VRACs. Important reasons for such an understanding are that these channels are ubiquitous and have important physiological functions which under pathological conditions convert to deleterious effects. Here we summarize data showing the involvement of VRACs in ischemia-induced release of excitatory amino acids (EAAs) in a rat model of global ischemia. Using microdialysis studies we found that reversal of the astrocytic glutamate transporter and VRACs contribute about equally to the large initial release of EAAs and together account for around 80% of the total release. We used the very potent VRAC blocker, tamoxifen, to see if such inhibition of EAA release via VRACs led to significant neuroprotection. Treatment in the focal rat MCA occlusion model led to around 80% reduction in infarct size with an effective post initiation of ischemia therapeutic window of three hours. However, the common problem of other effects for even the most potent inhibitors pertains here, as tamoxifen has other, potentially neuroprotective, effects. Thus it inhibits nitrotyrosine formation, likely due to its inhibition of nNOS and reduction of peroxynitrite formation. Although tamoxifen cannot therefore be used as a test of the "VRAC-excitotxicity" hypothesis it may prove successful for translation of basic stroke research to the clinic because of its multiple targets.

Animals↗

Recurrence risk in infants with urinary tract infections and a negative radiographic evaluation.

PURPOSE: Infants with urinary tract infections (UTI) and no abnormality on radiological evaluation are usually discharged from urological followup but the natural history of these children is unknown. We evaluate the rate of and potential risk factors for UTI recurrence in this specific population. MATERIALS AND METHODS: We reviewed retrospectively charts of children evaluated for first UTI before age 6 months between January 1996 and February 2001. Only patients with a normal ultrasound and voiding cystourethrogram were included in this study. A telephone questionnaire was administered to the parents, which inquired about the UTI, duration of breast-feeding, type of formula, family history of UTI, neurological problems, history of constipation or recurrent fevers, as well as social status. Chi-square test was performed for statistical analysis. RESULTS: We identified 264 children with UTIs, of whom 119 (45%) had a negative ultrasound and voiding cystourethrogram. Followup was available on 68 girls (81%) and 16 boys (19%) of the 119 children (71%). Of the 84 children 16 (19%) had recurrent UTI. Mean followup was 4.4 years (range 1.9 to 7.0). No factors had a statistically significant correlation for UTI recurrence. The p value for gender and history of undiagnosed fevers was 0.077 and 0.082, respectively. CONCLUSIONS: About 20% of children will have recurrent UTIs despite negative radiological evaluation. Although not statistically significant, there was a trend for an increased risk in girls and those with recurrent febrile illnesses. History of daytime dryness and/or constipation was not predictive of recurrent UTIs in our series.

Child↗

Neuroprotective activity of tamoxifen in permanent focal ischemia.

OBJECT: The authors have previously shown that tamoxifen is effective in protecting brain tissue from ischemic injury in a rat model of reversible focal ischemia. In this study the authors tested whether similar protective effects are found in a rat model of permanent focal ischemia (permanent middle cerebral artery [MCA] occlusion). METHODS: Tamoxifen (20 mg/kg) was given either before or at 1, 3, or 6 hours after permanent MCA occlusion in rats, with sustaining doses given every 12 hours thereafter. The median infarct volume measured after 72 hours was 113 mm3 for the vehicle (dimethyl sulfoxide) groups, compared with 31 mm3 for pretreatment, and 14, 27, and 98 mm3 for treatment beginning at 1, 3, and 6 hours, respectively, after permanent MCA occlusion. The infarct reductions in the pretreated and 1- and 3-hour post-MCA occlusion treatment groups were statistically significant (p < 0.05). At 3 hours after permanent MCA occlusion, tamoxifen also significantly reduced the infarct size at a lower dose of 5 mg/kg but not at 1 mg/kg; the same sustaining doses of 5 and 1 mg/kg were given every 12 hours. CONCLUSIONS: Tamoxifen is as effective in a permanent model of focal ischemia as it is in the reversible model, and the therapeutic window of 3 hours after initiation of ischemia is identical. This effectiveness is likely due to several properties of the drug, including its known ability to cross the blood-brain barrier. Because tamoxifen has been administered safely in humans for treatment of gliomas at similarly high doses to those used in this study, it may be clinically useful as a treatment for ischemic stroke.

Animals↗

Factors affecting profitability for craniotomy.

OBJECT: The authors studied factors influencing hospital profitability after craniotomy in patients who underwent craniotomy coded as diagnosis-related group (DRG) 1 (17 years of age with nontraumatic disease without complication) and who met their hospital's craniotomy pathway criteria and had a hospital length of stay 4 days or less during a 20-month period. METHODS: Data in all patients meeting these criteria (76 cases) were collected and collated from various hospital databases. Twenty-one cases were profitable and 55 were not. Variables traditionally influencing cost of care, such as surgeon, procedure, length of operation, and pharmacy use had no significant effect on whether a patient was profitable. The most important influence on profitability was the individual payor. Cases in which care was reimbursed under the prospective payment system based on DRGs were nearly always profitable whereas those covered by per diem plans were nearly always nonprofitable. CONCLUSIONS: 1) Hospital information systems should be customized to deliver consolidated data for timely analysis of cost of care for individual patients. This information may be useful in negotiating profitable contracts. 2) A clinical pathway was successful in reducing the difference in cost of care between profitable and nonprofitable postcraniotomy cases. 3) In today's health care environment both cost containment and revenue assume importance in determining profitability.

Adolescent↗

The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia.

Recently, several small studies have indicated that quetiapine may be useful in the treatment of drug-induced psychosis in patients with PD. However, there have been questions related to atypical antipsychotic therapy and patient selection and how that may affect response and tolerability, especially worsening of the motor symptoms of PD. In particular, the presence or absence of dementia seems to be important. The aim of this study was to evaluate the effect of quetiapine on psychosis and motor symptoms in PD patients with and without dementia. A retrospective record review of patient responses to quetiapine was conducted. Response of psychosis was assessed through patient and caregiver interviews. Motor symptom change in relation to this therapy was assessed by patient and caregiver interviews and completion of the motor portion of the Unified Parkinson's Disease Rating Scale (UPDRSm). Analysis was performed by comparing psychosis and motor feature measures from before and after therapy for the group as a whole and for demented and nondemented subgroups, using nonparametric tests and Fisher's exact test. Forty-three consecutively treated PD patients were evaluated. The mean dose of quetiapine was 54 mg per day and the duration of therapy was 10 months. Eighty-one percent of patients demonstrated partial or complete amelioration of psychosis. Five patients (13%) experienced a worsening of PD motor symptoms, which was corroborated by changes seen in UPDRSm. When the group was examined as a whole, no significant change in UPDRSm score was noted. When demented (n = 20) and nondemented (n = 19) patients were compared, improvement in psychosis occurred in similar numbers of patients, but a significant difference in the numbers of patients who experienced a worsening of motor symptoms was seen (P < 0.02, Fisher's exact test). All five patients who complained of motor worsening were in the demented group. UPDRSm score after therapy tended to be worse in the demented group (P = 0.55, Mann-Whitney U test). There was no significant change in the levodopa dose. Approximately 80% of patients chose to continue therapy. We conclude that quetiapine is effective in improving psychosis in approximately 80% of PD patients both with and without dementia. Patients with dementia seem to have a higher propensity for worsening of motor symptoms.

Aged↗

Intracranial endoscopy.

The authors' intention is to reduce the invasiveness of intracranial procedures while avoiding traumatization of brain tissue, to decrease the risk of neurological and mental deficits. Intracranial endoscopy is a minimally invasive technique that provides rapid access to the target via small burr holes without the need for brain retraction. Craniotomy as well as microsurgical brain splitting and dissection can often be avoided. Furthermore, because obstructed cerebrospinal fluid pathways can be physiologically restored, the need for shunt placement is eliminated. The ventricular system and subarachnoid spaces provide ideal conditions for the use of an endoscope. Therefore, a variety of disorders, such as hydrocephalus, small intraventricular lesions, and arachnoid and parenchymal cysts can be effectively treated using endoscopic techniques. With the aid of special instruments, laser fibers, and bipolar diathermy, even highly vascularized lesions such as cavernomas may be treated. Moreover, during standard microsurgical procedures, the endoscopic view may provide valuable additional information ("looking around a corner") about the individual anatomy that is not visible with the microscope. In transsphenoidal pituitary surgery, transseptal dissection can be avoided if an endonasal approach is taken. In the depth of the intrasellar space, the extent of tumor removal can be more accurately controlled, especially in larger tumors with para- and suprasellar growth. The combined use of endoscopes and computerized neuronavigation systems increases the accuracy of the approach and provides real-time control of the endoscope tip position and approach trajectory. In the future, the indications for neuroendoscopy will certainly expand with improved technical equipment.

Journal Article↗