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Biomedical subjects

R S Fisher

Publications and source records attributed to R S Fisher.

At least 19 recordsLinked to original sources
PubMed2006

Regional gastric emptying abnormalities in functional dyspepsia and gastro-oesophageal reflux disease.

To characterize proximal and distal stomach emptying in functional dyspepsia (FD) and gastro-oesophageal reflux disease (GORD). Eighty-three patients underwent gastric emptying (GE) scintigraphy and symptom scoring for the evaluation of upper gastrointestinal symptoms and were divided into three groups: FD (n = 25), GORD (n = 20) and FD + GORD (n = 38). Total, proximal and distal gastric retention were determined scintigraphically and compared with normal controls. Delayed total GE was observed in each subgroup: FD (56%), GORD (45%) and FD + GORD (55%). Greater proximal gastric retention was observed after meal ingestion in GORD compared to FD. Greater distal gastric retention was observed in FD and FD + GORD but it was only mild in GORD. Nausea, vomiting, early satiety, distention and regurgitation were associated with proximal gastric retention whereas there was no symptom associated with distal gastric retention. Multiple regression demonstrated total gastric retention at 30 min and 1 h was positively correlated with regurgitation whereas early proximal gastric retention was positively correlated with regurgitation and negatively correlated with nausea. Selective abnormalities of proximal and distal stomach emptying were demonstrated in GORD and FD. GORD and FD symptoms were associated with proximal gastric retention suggesting that proximal stomach motor function may be important in the pathogenesis of symptoms associated with these disorders.

Adult↗
PubMed2005

The effect of rabeprazole on regional gastric acidity and the postprandial cardia/gastro-oesophageal junction acid layer in normal subjects: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Postprandial intragastric acidity is not uniform. Postprandial proximal gastric acid pockets have been described in the present study. AIM: To determine the effects of rabeprazole on regional intragastric acidity and proximal acid pockets. METHODS: Ten normal subjects underwent two 8-day oral dosing regimens with placebo or rabeprazole 20 mg each morning in a randomized, double-blind protocol. Oesophago-gastric pH monitoring was performed on days 1 and 8. RESULTS: Rabeprazole increased fasting and postprandial gastric pH to above 4 in each area of the stomach on days 1 and 8. With placebo, acid pockets were identified at the cardia/gastro-oesophageal junction in 62 and 50 of 150 pull-throughs on days 1 and 8, respectively. Acid pockets were detected postprandially 3.1 +/- 0.2-5.8 +/- 0.1 cm below the proximal border of the lower oesophageal sphincter with a mean pH drop from 4.6 +/- 0.1 to 1.5 +/- 0.1. Rabeprazole decreased the number of acid pockets to 30 and 27 on days 1 and 8, respectively. Rabeprazole also decreased their length and magnitude of the pH drop. CONCLUSIONS: Rabeprazole increased intragastric pH on day 1 and 8 and maintained an elevated pH during and after meals. Postprandial acid pockets, identified in the region of the cardia/gastro-oesophageal junction area postprandially, were decreased in number, length and magnitude by rabeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Gamma oscillation underlies hyperthermia-induced epileptiform-like spikes in immature rat hippocampal slices.

BACKGROUND: Recently a hyperthermic rat hippocampal slice model system has been used to investigate febrile seizure pathophysiology. Our previous data indicates that heating immature rat hippocampal slices from 34 to 41 degrees C in an interface chamber induced epileptiform-like population spikes accompanied by a spreading depression (SD). This may serve as an in vitro model of febrile seizures. RESULTS: In this study, we further investigate cellular mechanisms of hyperthermia-induced initial population spike activity. We hypothesized that GABA(A) receptor-mediated 30-100 Hz gamma oscillations underlie some aspects of the hyperthermic population spike activity. In 24 rat hippocampal slices, the hyperthermic population spike activity occurred at an average frequency of 45.9 +/- 14.9 Hz (Mean +/- SE, range = 21-79 Hz, n = 24), which does not differ significantly from the frequency of post-tetanic gamma oscillations (47.1 +/- 14.9 Hz, n = 34) in the same system. High intensity tetanic stimulation induces hippocampal neuronal discharges followed by a slow SD that has the magnitude and time course of the SD, which resembles hyperthermic responses. Both post-tetanic gamma oscillations and hyperthermic population spike activity can be blocked completely by a specific GABA(A) receptor blocker, bicuculline (5-20 microM). Bath-apply kynurenic acid (7 mM) blocks synaptic transmission, but fails to prevent hyperthermic population spikes, while intracellular diffusion of QX-314 (30 mM) abolishes spikes and produces a smooth depolarization in intracellular recording. CONCLUSION: These results suggest that the GABA(A) receptor-governed gamma oscillations underlie the hyperthermic population spike activity in immature hippocampal slices.

Action Potentials↗
PubMed2001

Rapid initiation of gabapentin: a randomized, controlled trial.

OBJECTIVE: To compare the tolerability of two different dose-initiation regimens of gabapentin for the adjunctive treatment of partial seizures. BACKGROUND: Patient compliance is a key feature of successful outpatient pharmacologic therapy for epilepsy, and one aspect of compliance is simplicity of initiation. By using a rapid titration rate, leading to a rapid therapeutic gabapentin dose, perhaps there could be an improvement with compliance. METHODS: Male or female patients, at least 12 years old, with a recent history of partial seizures with or without secondary generalization, were randomized to receive gabapentin (following a blinded placebo period of an undisclosed number of days) as either a Slow initiation (300 mg day 1, 600 mg day 2, then 900 mg/day) or a Rapid initiation (900 mg/day immediately following the placebo lead-in). RESULTS: Starting gabapentin therapy at an initial therapeutic dosage of 900 mg/day is well tolerated by patients with epilepsy and is as safe as initiating with a titration schedule over 3 days. Of the four most common adverse events (somnolence, dizziness, ataxia, fatigue), only one, dizziness, occurred more often in the nontitrated (Rapid initiation) group than in the titrated (Slow initiation) group. CONCLUSION: Initiation of gabapentin at 900 mg/day is as well tolerated as is a 3-day titration, except for a higher incidence of dizziness.

Acetates↗
PubMed2001

A pilot study of donepezil for memory problems in epilepsy.

We performed a pilot 3-month, open-label study of 5-10 mg donepezil, an anticholinesterase inhibitor, as treatment for memory problems in people with epilepsy. The Buschke Selective Reminding Test was administered at baseline and after 3 months of donepezil. In 18 completing patients, the total number of words recalled across learning trials was greater on donepezil (P = 0.4). No change was noted in attention, visual sequencing, mental flexibility, psychomotor speed, or reported quality-of-life scores. Mean 3-month seizure frequency at baseline was 2.70 ± 4.60, and during treatment, 3.06 ± 4.52 (P = 0.19, not significant). Two patients experienced increased tonic-clonic seizures. Side effects included diarrhea, stomach cramps, insomnia, depression, and blurred vision. Cholinergic medication is worthy of investigation as treatment for memory problems in people with epilepsy, but attention must be paid to possible exacerbation of seizures.

Journal Article↗
PubMed2001

Extending gastric emptying scintigraphy from two to four hours detects more patients with gastroparesis.

Gastric emptying scintigraphy (GES) is usually performed for up to 2 hr to measure the gastric emptying (GE) of solids. Symptomatic patients, however, may have borderline results at 2 hr, making it difficult to determine whether a gastric motor disorder is present. The aim of this study was to assess whether extending GES to 4 hr is useful in evaluating patients for gastroparesis and to correlate the results of GES with patient symptoms. We studied 129 patients undergoing GES at Temple University Hospital between July 1998 and March 1999. Solid-phase GE was measured at 0, 0.5, 1, 2, 3, and 4 hr after ingestion of a 99mTc sulfur colloid-labeled egg meal. Dyspeptic symptoms of upper abdominal discomfort, early satiety, postprandial abdominal bloating, nausea, vomiting, and anorexia were graded as none, mild, moderate and severe (0, 1, 2 and 3, respectively) with the sum representing a total symptom score. Of 129 patients, 86 had normal GE at 2 hr; 26 of the 86 normal scans at 2 hr were delayed at 3 hr. Six of the 60 scans normal at 2 and 3 hr were delayed at 4 hr. Of 43 patients with delayed GE at 2 hr, 39 were delayed at 3 hr and 35 were delayed at 4 hr. Overall, the percentage of patients with delayed GE increased from 33% at 2 hr only to 58% using the results of the 2-, 3-, and 4-hr scans (P < 0.05). There was a significantly greater symptom score in patients with delayed GE compared to patients with normal GE (8.4 +/- 0.5 vs 7.1 +/- 0.5; P < 0.05). Conclusion, prolonging GES after ingestion of a 99mTc-labeled egg meal from 2 to 4 hr increased the number of symptomatic patients found to have delayed GE. These results suggest that GES should be performed for up to 4 hrs when the 2-hr result is normal.

Adolescent↗
PubMed2001

Ischemic colitis during treatment with alosetron.

Irritable bowel syndrome (IBS) is one of the most common entities observed by both primary care physicians and gastroenterologists. Alosetron is a potent and selective serotonin antagonist that recently became the first Food and Drug Administration-approved agent for diarrhea-predominant IBS. However, since approval, significant side effects have been noted with the use of alosetron including severe constipation, fecal impaction, and ischemic colitis. We describe a case of ischemic colitis in a male patient with IBS who was briefly treated with alosetron. Clinical, endoscopic, and pathologic features of the focal colitis strongly suggested ischemia. Symptoms correlated temporally with alosetron use, and symptoms abated with discontinuation of the drug. Endoscopic and pathologic resolution of the colitis were documented.

Carbolines↗
PubMed2001

Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington's disease transgenic mice.

We examined passive and active membrane properties and synaptic responses of medium-sized spiny striatal neurons in brain slices from presymptomatic (approximately 40 days of age) and symptomatic (approximately 90 days of age) R6/2 transgenics, a mouse model of Huntington's disease (HD) and their age-matched wild-type (WT) controls. This transgenic expresses exon 1 of the human HD gene with approximately 150 CAG repeats and displays a progressive behavioral phenotype associated with numerous neuronal alterations. Intracellular recordings were obtained using standard techniques from R6/2 and age-matched WT mice. Few electrophysiological changes occurred in striatal neurons from presymptomatic R6/2 mice. The changes in this age group were increased neuronal input resistance and lower stimulus intensity to evoke action potentials (rheobase). Symptomatic R6/2 mice exhibited numerous electrophysiological alterations, including depolarized resting membrane potentials, increased input resistances, decreased membrane time constants, and alterations in action potentials. Increased stimulus intensities were required to evoke excitatory postsynaptic potentials (EPSPs) in neurons from symptomatic R6/2 transgenics. These EPSPs had slower rise times and did not decay back to baseline by 45 ms, suggesting a more prominent component mediated by activation of N-methyl-D-aspartate receptors. Neurons from both pre- and symptomatic R6/2 mice exhibited reduced paired-pulse facilitation. Data from biocytin-filled or Golgi-impregnated neurons demonstrated decreased dendritic spine densities, smaller diameters of dendritic shafts, and smaller dendritic fields in symptomatic R6/2 mice. Taken together, these findings indicate that passive and active membrane and synaptic properties of medium-sized spiny neurons are altered in the R6/2 transgenic. These physiological and morphological alterations will affect communication in the basal ganglia circuitry. Furthermore, they suggest areas to target for pharmacotherapies to alleviate and reduce the symptoms of HD.

Action Potentials↗
PubMed2001

Diagnostic modalities for achalasia.

Diagnostic evaluation for achalasia in patients with dysphagia begins with barium esophagography to evaluate for an anatomic lesion of the esophagus or the gastric fundus. Most of the patients with achalasia can be detected with an initial radiologic approach. Esophageal manometry, however, remains the gold standard for the diagnosis of achalasia and is important for patients for whom a correct diagnosis is uncertain or essential. The article reviews these and other diagnostic tests that may be used in evaluating patients suspected of having achalasia.

Barium Sulfate↗
PubMed2000

The postictal state: a neglected entity in the management of epilepsy.

Some of the disability deriving from epilepsy derives from the postictal state (PS). The PS may be complicated by impaired cognition, headache, injuries, or secondary medical conditions. Postictal depression is common, postictal psychosis relatively rare, but both add to the morbidity of seizures. The mechanisms of the PS are poorly understood. Alteration of cerebral blood flow both results from and contributes to the PS. Many neurotransmitters or neuromodulators are involved in the physiology of the PS. Response to glutamate may partially desensitize after a seizure. Endogenous opiates and adenosine serve as natural antiepileptic medications in some circumstances. Nitric oxide has numerous effects on brain excitability, and may be particularly important in regulating postictal cerebral blood flow. Just as the pathophysiology of seizures is complicated, so is that of the PS multifactorial. As a practical issue, it would be very useful to have medications that reduce the morbidity of the PS.

Journal Article↗
PubMed2000

The impact of epilepsy from the patient's perspective I. Descriptions and subjective perceptions.

This study surveyed the perceptions about and subjective experience of 1023 people with epilepsy in two community-based samples: one from a national postal survey; the other callers to the Epilepsy Foundation. Response to a mail survey was 49%. In comparison with US Census Bureau norms, respondents had received less education, were less likely to be employed or married, and came from lower income households. Complex partial seizures were the most prevalent seizure type, but a convulsion had occurred in 61%. Fifty percent of respondents reported incomplete control of their seizure disorder, although 25% of these had a seizure in the prior year. Thirteen percent had a longest inter-seizure interval of a year or greater, 37% of 3 months, 22% of 1 month, 10% of 1 week and 4% of 1 day. Respondents listed uncertainty and fear of having a seizure as the worst thing about having epilepsy. Lifestyle, school, driving, and employment limits were also listed as major problems. When asked to rank a list of potential problems, cognitive impairment was ranked highest. These data indicate that ongoing medical and psychosocial problems continue for those with epilepsy in the view of those questioned and their families, even in a sample where the majority report good control of their epilepsy.

Adolescent↗
PubMed2000

The impact of epilepsy from the patient's perspective II: views about therapy and health care.

A national survey of 1023 people with epilepsy in the US assessed their attitudes about their therapies. Subjects were drawn from responders to a previous national survey of US households or from those who phoned the Epilepsy Foundation. Overall response rate was 49%. Approximately 90% of the respondents were taking medications for their epilepsy. Only 56% were on monotherapy, while 26% were taking two, 6% three, and 2% four medications. Only 68% of respondents were very satisfied with their current seizure medications. When asked to rank five areas of importance regarding their seizure medication, the rank order (highest to lowest) was seizure control, fewer side effects, convenient dosing regimens and cost. Adverse medication events were listed in descending rank order as problems with cognition, energy level, school performance, childbearing, coordination, and sexual function. Inter-individual differences in side effects of concern were listed, suggesting medication choices should be individualized according to potential side effects. Twenty percent of 920 respondents adjusted their medications on their own, by adjusting amount (62%), dosing schedule (31%), or both (3%). Eighty percent of respondents were satisfied with their medical care systems. In this group, 82% had health insurance that covered epilepsy. The large majority (94%) of respondents had seen a neurologist. Subjects expressed dissatisfaction about time limits and lack of accessible information about epilepsy. People with epilepsy are generally satisfied with efforts to treat their disorder, but adverse events are of concern. Many patients requested more information about epilepsy.

Adolescent↗
PubMed2000

An automated drug delivery system for focal epilepsy.

Previous studies have demonstrated the ability to stop seizures in animal models with injection of antiepileptic medication directly onto the seizure focus. The present experiments describe automated detection and focal therapy for seizures in the laboratory setting. Focal seizures were created in Sprague-Dawley rats using bicuculline, a GABA antagonist. Computerized detection of seizures was linked to a programmable infusion pump to deliver either diazepam (DZP) or pH-balanced vehicle (VEH) directly onto the seizure focus. Mean numbers of seizures following initial delivery of drug were 2.9+/-1.45 for the VEH-treated group and 0.2+/-0.42 for the DZP-treated group (P<0.0001, Student's t-test, nonpaired, one-tailed). In another series of experiments, early injection of DZP shortened seizure duration. Three DZP-treated animals died. This model provides proof-in-principle for the development of a clinically applicable treatment for intractable partial epilepsy. Such therapy might avoid some of the problems inherent to systemic administration of antiepileptic drugs.

Animals↗
PubMed2000

Does fasting serum gastrin predict gastric acid suppression in patients on proton-pump inhibitors?

Proton pump inhibitors (PPIs) block gastric acid secretion and may increase serum gastrin concentration. The aim of this study was to determine whether fasting serum gastrin concentration predicts gastric acid suppression in patients on PPI therapy. Ambulatory pH monitoring with one pH probe in the distal esophagus and a second probe in the stomach was performed in patients with persistent symptoms of GERD despite PPI treatment. Upon completion of pH monitoring, blood was drawn for measurement of fasting serum gastrin concentration. In all, 51 patients were studied: 26 on PPIs, 1 on H2-receptor antagonists, and 24 off acid suppression. Fasting serum gastrin correlated inversely with percent time of gastric pH < 4 for all patients (r = -0.553; P<0.001) and for the subgroup of 26 patients on PPIs (r = -0.435; P = 0.027). In patients on PPIs, an elevated gastrin (> or =100 pg/ml) was associated with gastric pH < 4 for 25+/-7% of the time compared to 54+/-5% when the gastrin was normal (P = 0.004). Therapeutic gastric acid suppression (gastric pH < 4 for <50% of time) was present in 6 of 7 (86%) patients with an elevated fasting serum gastrin, compared with only 8 of 19 (42%) patients with a normal serum gastrin (P<0.05). In conclusion, there is a significant inverse correlation between the fasting serum gastrin concentration and gastric acid profile in patients with GERD. An elevated fasting serum gastrin concentration while on PPI therapy suggests that gastric acid secretion is adequately suppressed.

Fasting↗
PubMed2000

Early initiation of post-PEG feeding: do published recommendations affect clinical practice?

Since its introduction in 1980, percutaneous endoscopic gastrostomy (PEG) has become the procedure of choice for long-term enteral feeding in patients who are unable to take adequate oral nutrition. Traditionally, gastroenterologists have waited for 24 hr after PEG tube placement before initiating feedings. However, recently published data have described the safety and efficacy of initiating PEG tube feedings as early as 3 hr after PEG tube placement. The objectives of this study were to determine how many hours after PEG tube placement practicing gastroenterologists initiate feedings and to determine whether they were aware of the pertinent literature. A four-page questionnaire was mailed to 35 practicing gastroenterologists, and the data gathered were analyzed using the SAS statistical package. A majority (81.5%) were aware of articles published in the last six years regarding the safety and efficacy of early initiation of feeding after PEG; of interest, however, only 10.7% were initiating feedings less than 3 hr after PEG tube placement. In conclusion, there exists a discrepancy between published recommendations and clinical practice regarding early initiation of feedings after PEG tube placement in this group of gastroenterologists who were surveyed.

Adult↗
PubMed2000

The potential for vigabatrin-induced intramyelinic edema in humans.

PURPOSE: Vigabatrin (Sabril, Hoechst Marion Roussel) is an antiepilepsy drug (AED) presently marketed in 64 countries for the treatment of partial and secondarily generalized seizures. Vigabatrin (VGB) is marketed in a subset of these countries for the treatment of infantile spasms. Clinical experience in humans has shown that VGB provides effective seizure control with a wide margin of safety. However, animal toxicity studies raised concern when prolonged administration of VGB was shown to induce intramyelinic edema (IME) in some laboratory animal species. METHODS: Animal and human data were reviewed with respect to the potential for VGB-induced IME. Surveillance of patients receiving VGB in clinical trials or by prescription has been conducted for >15 years to identify patients developing clinical abnormalities that might be IME related. RESULTS: The histologic lesions of VGB-induced IME in animals are reliably reproduced and correlate with changes in multimodality evoked potentials (EPs) and magnetic resonance imaging (MRI). Numerous studies of the effects of VGB on EP and MRI in epilepsy patients have demonstrated no clear-cut IME-related changes in these modalities. Additionally, autopsy and surgical brain samples from VGB-treated patients have been scrutinized for potential IME histopathology. In an estimated 350,000 patient-years of VGB exposure (approximately 175,000 patients exposed for 2 years at an average dose of 2 g/day), no definite case of VGB-induced IME has been identified. CONCLUSIONS: Comprehensive review of a variety of sources of data failed to identify any definite case of IME in humans treated with VGB.

Animals↗
PubMed2000

Role of flexible endoscopy in the evaluation of possible esophageal trauma after penetrating injuries.

OBJECTIVE: In urban medical centers, penetrating injuries of the chest, neck, and head are frequently encountered due to the use of firearms and sharp weapons. Successful management of esophageal injury requires a high index of suspicion and prompt diagnosis. The role of flexible endoscopy, a readily available modality, has not been studied extensively in the management of potential esophageal injuries due to trauma. METHODS: A retrospective chart review of 55 patients who underwent emergent flexible endoscopy for the evaluation of suspected penetrating esophageal injuries was performed to determine if endoscopy was safe and if it yielded information that altered patient management. RESULTS: Flexible endoscopy was performed safely in all patients. It yielded a sensitivity of 100%, specificity of 92.4%, a negative predictive value of 100%, and a positive predictive value of 33.3% for detecting an esophageal injury. Although positive findings (prevalence, 3.6%) are infrequent, no esophageal injuries were missed. Endoscopy altered patient management in 38 (69.1%) patients. CONCLUSIONS: Emergent flexible endoscopic examination of the esophagus is a safe and useful diagnostic tool in the early evaluation of penetrating injuries. Flexible endoscopy resulted in four negative surgical explorations, which was deemed acceptable by the Trauma Service, as the consequences of a missed esophageal injury is likely to be devastating.

Adolescent↗