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Biomedical subjects

Matthew Q Bromer

Publications and source records attributed to Matthew Q Bromer.

9 recordsLinked to original sources

Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma.

BACKGROUND: The human polyomavirus JC virus (JCV) causes progressive multifocal leukoencephalopathy. Subclinical infection with JCV occurs in 85-90% of the population worldwide. The virus usually remains latent but can reactivate under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy. JCV is oncogenic in experimental animals and is associated with human brain tumors. JCV is found in normal mucosa of the gastrointestinal tract, and some colon carcinomas express the oncogenic JCV T-antigen protein. The objective of this study was to examine the presence of JCV DNA sequences and JCV protein expression in normal and malignant human esophageal tissues. METHODS: The authors examined the presence of JCV DNA sequences and protein expression in normal and malignant human esophageal tissues. Seventy well characterized biopsy specimens from patients with a spectrum of esophageal disorders were studied by immunohistochemistry, and 18 specimens were analyzed further by polymerase chain reaction amplification. RESULTS: JC viral DNA was isolated from 11 of 13 normal esophageal biopsy specimens (85%) and from 5 of 5 esophageal carcinomas (100%). Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and beta-catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser-capture microdissection verified the presence and specificity of JCV DNA sequences. beta-Catenin and p53 were colocalized with JCV T-antigen in the nuclei of neoplastic cells. CONCLUSIONS: The results provide evidence for infection of gastrointestinal tract cells by JCV and suggest a potential role of JCV in the development of upper digestive tract carcinomas.

Adult↗

Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis.

BACKGROUND: Botulinum toxin A injected into the pyloric sphincter has been reported in small case series to treat gastroparesis. This study reviews the use of this treatment in a large number of patients with gastroparesis. METHODS: Patients who underwent pyloric botulinum injection for treatment of gastroparesis were identified. Response was defined as improvement or resolution of the patient's major symptom and/or two minor symptoms for 4 weeks. RESULTS: Of 115 patients treated, 63 patients met the study criteria. There were 53 women, 10 men, mean age 42 years. Most patients (56%) had idiopathic gastroparesis. Twenty-seven of 63 (43%) patients experienced a symptomatic response to treatment. By stepwise logistic regression, male gender was associated with response to treatment (OR 3.27: 95% CI[1.31, 8.13], p = 0.01). Vomiting as a major symptom was associated with a lack of response (OR 0.16: 95% CI[0.04, 0.67], p = 0.01). Despite the association of male gender with response, the mean duration of response for those patients responding, with a minimum of 3 months' follow-up was 4.9 months (+/-2.7 months) for women and 3.5 months (+/-0.71 months) for men (p = 0.59). The corresponding medians and interquartile ranges (IQR) were 5 (IQR 3-6) for females and 3.5 (IQR 3-4) for males. CONCLUSIONS: Of the patients, 43% had a response to botulinum toxin treatment that lasted a mean of approximately 5 months. Male gender was associated with a response to this therapy; however, durability of response was unrelated to gender. Vomiting as a major symptom predicted no response.

Abdominal Pain↗

Screening for colorectal cancer--now and the near future.

When used appropriately, screening for colorectal cancer (CRC) can reduce disease-related morbidity and mortality. Current methods include fecal occult blood testing (FOBT), flexible sigmoidoscopy [FS], barium enema, and colonoscopy; all are cost-effective techniques. Unfortunately, offering an array of options has not increased screening utilization, which continues to lag behind that of other common cancers. Newer techniques, particularly virtual colonoscopy (VC) and stool DNA testing, may offer attractive alternatives for healthcare provider recommendation and patient use.

Barium Sulfate↗

Esophageal bacteria and Barrett's esophagus: a preliminary report.

The objective of this study was to investigate if esophageal bacteria are associated with Barrett's esophagus (BE). This study was comprised of a retrospective (Part 1) and a subsequent prospective (Part 2) study. In Part 1, Gram stains were performed on esophageal biopsy specimens obtained in 47 patients. Bacteria were quantitated from 0 to 4. In Part 2, Gram stains and cultured bacterial counts of esophageal biopsies were obtained in 18 GERD patients (9 with BE and 9 without BE). Part 1 results were as follows. Bacteria were found in 37 of 47 esophageal biopsies. Quantitative bacterial stain scores for BE (2.5 +/- 0.2) were higher than for non-BE (1.5 +/- 0.3; P = 0.02). The quantitative bacterial stain scores correlated with increasing severity of dysplasia (r = 0.37, P = 0.028). In Part 2, bacteria were found in 8 of 18 esophageal biopsies by Gram stain (6 of 9 patients with BE vs. 2 of 9 non-BE). The distal esophageal bacterial stain scores in BE patients (1.6 +/- 0.5) were higher than in those without BE (0.4 +/- 0.3; P = 0.07). Patients on proton pump inhibitors tended to have higher bacterial stain scores (1.2 +/- 0.4) than patients who were not (0.7 +/- 0.3; P = 0.45). Bacterial colony counts were similar in patients with BE compared to those without BE. In conclusion, bacteria in esophageal biopsies were detected more often in BE than non-BE. Increasing bacterial stain scores were associated with metaplasia and increasing dysplasia. Esophageal bacteria, possibly related to stasis or gastric acid suppression therapy, may play a role in the pathogenesis of BE and dysplasia.

Adult↗

Acetaminophen hepatotoxicity.

Unlike the bulk of medications, described in this fascicle, that cause liver injury in humans, acetaminophen is a non-prescription drug that can be purchased in drug stores and supermarkets without a physician's involvement. Death or severe injury is far more likely to occur with its use than with all the other medications considered in this study. Whereas attempts to control the quantity of drug ingested have been made in the United Kingdom and elsewhere in Europe, no comparable moves have taken place in the United States. The Food and Drug Administration claims to have concerns about the situation, however, but has yet to make an effort to more closely regulate the marketing and distribution of the drug. It is to be hoped that this will not be the case by the time the next issue of Drug Hepatotoxicity is scheduled for this series.

Acetaminophen↗

Comparison of a salivary/sputum pepsin assay with 24-hour esophageal pH monitoring for detection of gastric reflux into the proximal esophagus, oropharynx, and lung.

The purpose of this study was to determine whether measurement of salivary/sputum pepsin could be used as a surrogate marker for detecting gastroesophageal reflux using 24-hr esophageal pH monitoring as the gold standard. Patients with gastroesophageal reflux symptoms underwent simultaneous 24-hr esophageal pH monitoring and collection of saliva and sputum samples for pepsin measurement using a recently developed assay. In all, 16 patients provided 19 positive (10.6%) and 161 negative pepsin assays. The mean pH values for the positive pepsin samples were lower then the negative samples at both the proximal [5.34 (95% CI, 4.94-5.75) vs 6.12 (95% CI, 6.03-6.20; P < 0.01)] and distal [4.97 (95% CI, 4.61-5.33) vs 6.03 (95% CI, 5.92-6.15; P < 0.01)] pH probes. Proximal esophageal reflux was not detected in patients who had a negative pepsin assay (N = 12); in contrast, proximal esophageal reflux was documented in three of four patients with a positive assay. In conclusion, detection of pepsin in the saliva and/or sputum may provide a noninvasive method to test for the proximal reflux of gastric contents.

Esophagoscopy↗

Predictors of recurrent specialized intestinal metaplasia after complete laser ablation.

OBJECTIVES: The aim of this study was to determine whether specialized intestinal metaplasia recurs after complete laser ablation and to evaluate the persistence of colon epithelial protein in esophageal mucosa after laser ablation as a predictor of recurrence. METHODS: A total of 31 patients with specialized intestinal metaplasia (Barrett's esophagus) underwent laser photoablation. Investigators without knowledge of treatment status evaluated serial hematoxylin and eosin-stained slides, Alcian blue-stained slides, and immunohistochemistry for the detection of colon epithelial protein (mAb Das-1). RESULTS: Endoscopic ablation of specialized intestinal epithelium was accomplished in 21 patients after 6.5 +/- 1.2 laser sessions. Complications included one perforation, one UGI bleed and one stricture. Of eight post-laser recurrences, seven were successfully re-ablated; one developed adenocarcinoma requiring esophageal resection. Cardia-type mucosa was present by biopsy at the time of complete ablation in all eight recurrent cases despite a normal endoscopic appearance. Colon epithelial protein was detected in all 31 patients before ablation, six of 21 completely ablated patients before they recurred and all eight recurrences. Only two of 15 patients, colon epithelial protein negative at the time of complete ablation, developed recurrent Barrett's esophagus. Thus, cardia-type mucosa and persistent colon epithelial protein staining after complete ablation of specialized intestinal epithelium were predictors of future recurrence (p < 0.001). CONCLUSIONS: Specialized intestinal epithelium was ablated by neodymium:yttrium-aluminum-garnet laser but recurred in eight of 21 (38%) of patients. Colon epithelial protein was present in all primary (31 of 31) and all recurrent (eight of eight) Barrett's esophagus. Recurrent specialized intestinal metaplasia may be deep to squamous epithelium. Replacement of specialized intestinal mucosa by cardia-type mucosa and persistence of colonic epithelial protein are predictors of recurrent specialized intestinal mucosa before its endoscopic or histological detection. Laser ablation of Barrett's epithelium is an investigational intervention that should be restricted to research protocols.

Adult↗

Simultaneous measurement of gastric emptying with a simple muffin meal using [13C]octanoate breath test and scintigraphy in normal subjects and patients with dyspeptic symptoms.

The objective of this study was to determine how the [13C]octanoate breath test (OBT) using a muffin meal correlates with gastric emptying scintigraphy (GES) in normal subjects and patients with dyspeptic symptoms. Ten normal subjects and 23 patients with dyspeptic symptoms underwent simultaneous GES and [13C]OBT. After an overnight fast, a muffin labeled with [99mTc]-sulfur colloid and [13C]octanoate was ingested along with water labeled with [111In]DTPA. Breath samples and scintigraphic images were obtained at baseline and at regular postprandial intervals over 6 hr. In the normal subjects, the mean GES 71/2 of solids and liquids were 64 +/- 17 and 55 +/- 27 minutes, respectively. The calculated OBT T1/2 using the 6-hr breath collection was 138 +/- 15 min and correlated with T1/2 for solids by GES (r = 0.664; P = 0.051), but did not correlate with T1/2 for liquids by GES (r = 0.13; P = 0.738). In dyspeptic patients, the T1/2 for GES was 87 +/- 53 min and 81 +/- 70 min for solids and liquids, respectively. The mean OBT T1/2 was 155 +/- 57 min and correlated with GES T1/2 for solids (r = 0.86; P < 0.001) and GES T1/2 for liquids (r = 0.73; P < 0.001). Delayed gastric emptying (GE) of the muffin meal was identified by scintigraphy in seven patients. The sensitivity and specificity for OBT identifying delayed GE were 86% and 94%. Use of the initial truncated 4-hr OBT results also revealed a significant correlation between OBT and GES T1/2 for solids (r = 0.86; P < 0.001) with sensitivity and specificity for detecting delayed GE of 86% and 94%, respectively. In addition, a linear regression model was able to reduce the number of collection points to four, while maintaining the same sensitivity and specificity. In conclusion, the OBT for GE, using an easily prepared muffin meal, significantly correlates with GES for solids. This muffin-based OBT is a sensitive and specific method to detect delayed GE in dyspeptic patients.

Adolescent↗

Treatment of idiopathic gastroparesis with injection of botulinum toxin into the pyloric sphincter muscle.

OBJECTIVES: We aimed to determine if botulinum toxin injection into the pyloric sphincter improves gastric emptying and reduces symptoms in patients with idiopathic gastroparesis. METHODS: Patients with idiopathic gastroparesis not responding to prokinetic therapy underwent botulinum toxin (80-100 U, 20 U/ml) injection into the pyloric sphincter. Gastric emptying scintigraphy was performed before and 4 wk after treatment. Total symptom scores were obtained from the sum of eight upper GI symptoms graded on a scale from 0 (none) to 4 (extreme). RESULTS: Ten patients were entered into the study. The mean percentage of solid gastric retention at 4 h improved from 27+/-6% (normal < 10%) before botulinum toxin injection into the pylorus to 14+/-4% (p = 0.038) 4 wk after treatment. The symptom score decreased from 15.3+/-1.7 at baseline to 9.0+/-1.9 (p = 0.006) at 4 wk, a 38+/-9% decrease. Improvement in symptoms tended to correlate with improved gastric emptying of solids (r = 0.565, p 0.086). CONCLUSIONS: This initial pilot study suggests that botulinum toxin injection into the pylorus in patients with idiopathic gastroparesis improves both gastric emptying and symptoms.

Adult↗