Biomedical subjects

J C Reynolds

Publications and source records attributed to J C Reynolds.

At least 55 records · Page 3Linked to original sources

PubMed1997

Resting metabolic rate in African-American and Caucasian girls.

Recent studies have found a lower resting metabolic rate (RMR) in African-American (AA) women with obesity as compared with Caucasian (C) women with obesity. It is unknown if this difference in RMR is seen in prepubertal girls or in those of average body weight. Therefore, we studied RMR in 21 AA and 24 C girls, ages 7-10, who were well matched for age, weight, body mass index (BMI), and pubertal status. All had BMI between 15% and 85% for age and race, based on data from the First National Health and Nutrition Examination Survey. Fat free mass (FFM) was measured by dual-energy X-ray absorptiometry. RMR was measured with a Deltatrac indirect calorimeter under controlled conditions after the subjects underwent an overnight fast. The slopes of the regression equations were similar for both groups (p = 0.7). After adjustment for FEM, the AA girls had a significantly lower RMR than did the C girls (-92 +/- 32 kcal/d, p = 0.007 by analysis of covariance). This significance was maintained after exclusion of total body bone mineral content. These data suggest that normal-weight prepubertal AA girls may have reduced resting energy expenditure compared with C girls.

Adipose Tissue↗

PubMed1997

The changing role of radioiodine in the management of differentiated thyroid cancer.

This article discusses several aspects of the evaluation and management of differentiated thyroid carcinoma that are changing or may change in the near future. Although conventional treatment of this disease is highly effective, some modification may improve the welfare of patients and the overall results. Because the symptoms of hypothyroidism are vexing, there has been great interest in using recombinant human thyroid-stimulating hormone (rhTSH) to prepare patients for iodine 131 imaging. rhTSH has been about as effective as thyroid hormone withdrawal for diagnostic imaging so that approval for this use is expected. Another topic of interest is the administration of 131I therapy to patients whose serum thyroglobulin levels are abnormal but whose diagnostic 131I scans are negative. Because the 131I scans after therapy are often abnormal in these patients and a reduction of serum thyroglobulin can occur, this approach seems effective. The long-term impact of this therapy on recurrence and survival, however, is unknown. A third issue that is currently under review is the amount of 131I that should be used for diagnostic scanning. Although past opinion favored larger doses, "stunning" of thyroid remnant and tumor can occur with diagnostic 131I imaging. Substituting iodine 123 is an alternative for postthyroidectomy scanning, but when administered as 300 uCi it is less accurate than 131I for recurrent disease or distant metastases. Related to these issues, two other topics are reviewed: the use of other radiopharmaceuticals for imaging patients with thyroid cancer, and 131I dosimetry.

Cell Differentiation↗

PubMed1997

Extent of Barrett's metaplasia: a prospective study of the serial change in area of Barrett's measured by quantitative endoscopic imaging.

BACKGROUND: An accurate determination of the extent of Barrett's metaplasia is critical to the study of its natural history and response to therapy. Our hypothesis is that area calculations offer advantages over length estimates of Barrett's. METHODS: Changes in both measures and estimates of progression or regression between two endoscopies in 17 patients were compared. Area was calculated using a computer image analysis technique. RESULTS: Although there was no significant difference in length correlation versus area correlation between endoscopies (r = 0.90 vs 0.99), the mean change in absolute length (1.4 +/- 0.2 cm) was greater than the change in area (4.5 +/- 1.4 cm2, equivalent to a length of 0.67 +/- 0.2 cm, p = 0.001). The percent change in absolute length (26.9%) was greater than the change in area (16%, p = 0.001). Discordance of estimates of progression or regression between area and length was found in nine patients. The image technique detected no change in the area of squamous islands. CONCLUSIONS: Imaging analysis can precisely measure the extent of Barrett's including squamous islands. Area showed little change, whereas measures of length were more varied. Computer based image analysis provides a more precise estimate of interval change of Barrett's.

Adolescent↗

PubMed1997

Expression of p53, PCNA, and C-erbB-2 in Barrett's metaplasia and adenocarcinoma.

We sought to determine if an immunohistochemical panel of p53, PCNA, and c-erbB-2 was a useful biomarker of transformation in Barrett's metaplasia. P53, PCNA, and c-erbB-2 immunohistochemistry was performed on resected Barrett's specimens selected to show discrete grades of dysplasia and then on prospectively obtained biopsies. In resection specimens, p53 was positive in 36% with no dysplasia, in 30% with low-grade dysplasia, in 85% with high-grade dysplasia, and in 90% of adenocarcinomas. While an evaluation of proliferation throughout the specimen did not differ between groups, surface proliferation was significantly higher in high-grade dysplasia than in low-grade or no dysplasia. All high-grade dysplasia specimens were positive for at least one marker, compared to 44% with no or low-grade dysplasia. C-erbB-2 was only seen in 31% with high-grade dysplasia and in 10% of adenocarcinomas. Prospectively, the panel had a sensitivity of 100%, a specificity of 81% and an overall accuracy of 83% in identifying patients who developed high-grade dysplasia or cancer. Thus, overexpression of p53 occurs early in the malignant transformation of Barrett's and increases with histologic progression, and proliferation at the surface of Barrett's epithelium increases with progressive grades of dysplasia. An immunohistochemical panel of p53 and PCNA is a useful biomarker for Barrett's metaplasia.

Adenocarcinoma↗

PubMed1997

Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management.

BACKGROUND & AIMS: Recently [111In-DTPA-D-Phe1]-octreotide was approved for somatostatin receptor scintigraphy (SRS) of gastroenteropancreatic tumors. SRS and other tumor localization methods can be time consuming, expensive, and involve patient inconvenience. The role of SRS in comparison to other tumor localization modalities remains undefined because the relative effects of these methods on management have not been studied. The aim of this study was to determine whether SRS alters clinical management in Zollinger-Ellison syndrome. METHODS: One hundred twenty-two consecutive patients were studied prospectively. Each patient was assigned to one of five different clinical categories. Conventional imaging studies (ultrasonography, computerized tomography, magnetic resonance image, angiography, and bone scan) were performed, and the management was proposed. SRS was then performed. Clinical management was reassessed, and whether SRS altered management was determined based on six criteria. RESULTS: SRS was superior to any single imaging study. SRS altered management in 47% overall and in 22%-60% of patients in the five different clinical categories. Primary tumor localization and clarification of equivocal localization results from conventional studies were the principal reasons for altering management. SRS was equally useful in patients with or without metastatic liver disease. CONCLUSIONS: Because of the ability of SRS to alter clinical management combined with its superior sensitivity, high specificity, simplicity, and cost-effectiveness, SRS should be the initial imaging modality for patients with gastrinomas.

Adult↗

PubMed1997

Percent 131I uptake and post-therapy 131I scans: their role in the management of thyroid cancer.

This short review focuses on two questions commonly asked about 131I therapy of thyroid cancer. The first relates to radiation dosimetry. What percentage of 131I uptake is needed for effective therapy? Studies have shown that 131I uptake and therapeutic outcome may not be closely related. A more powerful relationship, however, occurs by using percent uptake per gram. A rearrangement of the basic dosimetry equation shows that for a specific level of radiation, percent uptake per gram and effective half-life are inversely related. Formulas developed from this relationship are useful in determining whether uptake is satisfactory but require estimates of effective half-life and tumor mass. The second question is whether post-therapy 131I scans are useful. Because the sensitivity of 131I scanning is related directly to the amount of radioactivity administered, imaging after therapy may show previously undetected lesions that not infrequently are distant metastases. Thus, information from post-therapy scans may 1) after therapy, 2) direct new diagnostic studies, 3) lead to formal dosimetry studies when maximal 131I doses are needed to treat distant metastases, and 4) be necessary to obtain when 131I therapy is administered to patients with elevated thyroglobulin and negative diagnostic scans. Should post-therapy scans always be performed? They are easy to perform and are clinically useful but may be inconvenient to patients and costly overall. At this time, however, there is not a simple paradigm for selecting patients who may forego these scans.

Half-Life↗

PubMed1997

Distinguishing small hepatic hemangiomas from vascular liver metastases in gastrinoma: use of a somatostatin-receptor scintigraphic agent.

PURPOSE: To compare somatostatin-receptor scintigraphy and conventional imaging modalities in the differentiation of small hepatic hemangiomas from small liver metastases in Zollinger-Ellison syndrome. MATERIALS AND METHODS: Twenty-nine patients had hypervascular liver lesions smaller than 2 cm that could have been either metastases or hemangiomas. Fourteen patients had metastases, 14 had hemangiomas, and one had both. Scintigraphy was compared with computed tomography (CT), magnetic resonance (MR) imaging, and angiography for the correct identification of the lesions. RESULTS: The hemangiomas and liver metastases both had a mean size of 1.3 cm. In the patients with hepatic hemangiomas, scintigraphy showed no lesions. CT, angiography, or MR imaging showed a lesion in 40%-93%. With metastases present, any liver lesion was detected in 93% with scintigraphy versus 20%-60% with another modality. Scintigraphy depicted liver metastases in 93% of patients, which was higher than the sensitivities of other modalities. The accuracy (96%) and positive (100%) and negative (93%) predictive values of scintigraphy for detecting liver metastases were superior to those of other modalities. There were 45 liver metastases and 31 hemangiomas; a per lesion analysis gave results similar to the per patient analysis results. CONCLUSION: In Zollinger-Ellison syndrome, somatostatin-receptor scintigraphy provides an excellent diagnostic tool to differentiate small hepatic hemangiomas from small liver metastases.

Adult↗

PubMed1997

Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with single-photon emission computerized tomography imaging.

High-flow interstitial infusion into the brain, which uses bulk fluid flow to achieve a relatively homogeneous drug distribution in the extracellular space of the brain, has the potential to perfuse large volumes of brain. The authors report reproducible long-term delivery of 111In-diethylenetriamine pentaacetic acid-apotransferrin (111In-DTPA-Tf) (molecular mass 81 kD) to Macaca mulatta brain and monitoring with single-photon emission computerized tomography (SPECT). The 111In-DTPA-Tf was infused at 1.9 microl/minute over 87 hours into the frontal portion of the centrum semiovale using a telemetry-controlled, fully implanted pump. On Days 1, 3, 4, 8, 11, and 15 after beginning the infusion, planar and SPECT scans of 111In-DTPA-Tf were obtained. Spread of protein in the brain ranged from 2 to 3 cm and infusion volumes ranged from 3.9 to 6.7 cm3. Perfusion of over one-third of the white matter of the infused hemisphere was achieved. From brain SPECT images of (99m)Tc-hexamethylpropyleneamine oxime, which was administered intravenously before each 111In scan, the authors also found that blood perfusion in the infused region was reduced by less than 5% relative to corresponding noninfused regions. Histological examination at 30 days revealed only mild gliosis limited to the area immediately surrounding the needle tract. These findings indicate that long-term interstitial brain infusion is effective for the delivery of drugs on a multicentimeter scale in the primate brain. The results also indicate that it should be possible to perfuse targeted regions of the brain for extended intervals to investigate the potential utility of neurotrophic factors, antitumor agents, and other materials for the treatment of central nervous system disorders.

Animals↗

PubMed1997

Etiology of Barrett's metaplasia and esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma in the United States is rising at an epidemic rate. Although the cause for this rapid rise is unclear, it is well established that nearly all cases of esophageal adenocarcinoma arise from a premalignant lesion of the esophagus, known as Barrett's esophagus. Although Barrett's esophagus is recognized as a precursor lesion, the etiology, prevalence, and malignant risk of this lesion remain unclear. The relatively short, two-decade time frame for the rise in esophageal adenocarcinoma incidence and the increase across populations is a strong argument for environmental factors as etiological agents, perhaps interacting with genetically determined characteristics that define personal susceptibility. Because of the strong link between Barrett's esophagus and esophageal adenocarcinoma and the link between Barrett's esophagus and gastroesophageal reflux disease, risk factors for gastroesophageal reflux disease have been the prime suspects offered as possible explanations for the rise in esophageal adenocarcinoma. A plethora of hypotheses have been advanced, implicating tobacco and alcohol consumption, changes in obesity and diet, and the changing pattern in use of medications that affect the upper gastrointestinal tract. The following text will review what is currently known about the epidemiology of Barrett's metaplasia, its risk for malignant transformation, and the proposed theories of etiogenesis.

Adenocarcinoma↗

PubMed1997

Glycophorin A as a biological dosimeter for radiation dose to the bone marrow from iodine-131.

The frequency of peripheral blood erythrocyte variants exhibiting allelic loss of glycophorin A (N/M antigen) has been used previously as a biological dosimeter to assess somatic mutations in bone marrow cells from external whole-body irradiation. The aim of the present study was to determine whether this marker could be used as a measure of bone marrow genotoxicity induced by 131I in the treatment of thyroid cancer. Flow cytometry of immunolabeled erythrocytes was performed to enumerate glycophorin A variants before and after eight therapy doses of 131I administered to five patients with differentiated thyroid carcinoma. Bone marrow radiation exposure from each dose was calculated from the integrated retention of 131I in the whole body and in the blood. In addition, the accumulated dose to the bone marrow received from earlier 131I therapy was calculated for each patient. Regression analysis was performed on the frequency of two glycophorin A variant cell types (N/O and N/N) as a function of accumulated dose to the bone marrow. Frequency of N/O variant cells showed a significant dose-related increase with a slope of 10.9 x 10(-6) per sievert. This dose effect is about one-half that previously observed after whole-body external irradiation at high dose rate. This decreased response could be explained by the low dose rate of the radiation to the bone marrow from 131I.

Bone Marrow↗

PubMed1997

bcl-2 protein expression in gastric remnant mucosa and gastric cancer 15 or more years after partial gastrectomy.

Partial gastrectomy is a risk factor for subsequent gastric cancer. The genetic alterations associated with malignant transformation, however, are poorly understood. Ninety-eight biopsies from 22 patients with benign gastric mucosa (BGM) at least 15 years after gastrectomy and resected specimens from 13 patients with postgastrectomy stump cancer (GC), were evaluated for immunohistochemical expression of bcl-2 oncogenic protein and correlated with the presence of dysplasia and subtypes of intestinal metaplasia (IM), categorized using high-iron diamine-alcian blue and alcian blue-periodic acid-Schiff stains. In BGM patients, 91% had chronic gastritis with atrophy, 18% showed complete (Type I) IM, 36% showed incomplete (Type II) IM, and 45% Type III IM. Twelve biopsy specimens from nine BGM patients showed mild-to-moderate dysplasia. Increased bcl-2 expression was present in 27% of BGM patients, with a significant association with increasing grade of IM: 20% in specimens with Type I IM, 30% with Type II, and 40% with Type III (P = .01). bcl-2 overexpression was more often present in the area of the anastomosis than in the body or fundus (P = .06). Of GC patients, 15% had Type II IM and 85% Type III IM. Moderate-to-severe dysplasia was present in adjacent benign mucosa in 46%. bcl-2 was present in 54% of GCs, and increased expression was detected in the adjacent benign mucosa in 60%. bcl-2 expression did not correlate with the presence or degree of dysplasia in either BGM or GC patients. bcl-2 protein is frequently expressed in GC. Increased expression is observed in mucosa adjacent to tumor and, to a lesser extent, in biopsy specimens of BGM, often associated with Type III IM. These findings suggest a possible role for the bcl-2 proto-oncogene in malignant progression.

Adult↗

PubMed1996

Effect of celiac ganglionectomy on tachykinin innervation, receptor distribution and intestinal responses in the rat.

Substance P (SP) is an important neurotransmitter in the control of intestinal motility and is found in both the enteric and sympathetic nervous systems. This study examined the effect of celiac ganglionectomy on (1) mechanical properties of the circular muscles of the duodenum, ileum and proximal colon, (2) circular muscle responses to SP and neurokinin A. (3) distribution of substance P-like immunoreactive nerves, and (4) the distribution of neurokinin 1 and neurokinin 2 receptors. Celiac ganglionectomy resulted in an effective sympathectomy as evidenced by a marked decrease in norepinephrine content and tyrosine hydroxylase staining in the duodenum, ileum and proximal colon. The in vitro length/tension characteristics of the circular muscle of the duodenum, ileum and colon were unchanged after ganglionectomy. In all regions of the gut studied, substance P and neurokinin A caused dose-dependent contractions that were unaltered by celiac ganglionectomy. Immunohistochemistry revealed moderate substance P-like immunoreactive fibers in the myenteric plexus, submucosal plexus and circular muscle of the ileum, while in the colon, substance P-like immunoreactivity was intense in the myenteric plexus, and moderate in the circular muscle. In vitro autoradiography showed minimal binding of SP (NK1 receptor) or neurokinin A (NK2 receptor) in the ileum and significantly greater binding in the circular muscle layer of the colon. Celiac ganglionectomy did not affect substance P-like immunoreactivity, or NK1 or NK2 receptor binding. A greater contractile response to neurokinins was seen in the colon than in the duodenum or ileum, which paralleled the receptor density. The studies demonstrate that surgical celiac ganglionectomy, unlike chemical sympathectomy, does not affect the substance P innervation, receptor density or physiological responses of the intestine. The greater contractile response of the colon than the ileum parallels the greater receptor density rather than the peptide content as determined by immunhistochemistry.

Animals↗

PubMed1996

Morphologic, histologic, and molecular similarities between adenocarcinomas arising in the gastric stump and the intact stomach.

BACKGROUND: Patients with gastric remnants resulting from partial resections have an increased risk for carcinoma. It is unclear whether adenocarcinoma arising in the gastric stump (GSca) differs from intact stomach carcinoma (Gca). The goal of this study was to examine the pathologic and molecular features of GSca and compare them with Gca. METHODS: Adjacent nonmalignant areas and tumors from 14 patients who were 19-55 years postgastrectomy (mean, 32.1 years) were compared with 14 Gca by pathologic and molecular analysis. Formalin fixed, paraffin embedded specimens were immunohistochemically stained for p53 followed by topographic genotyping. Exons 5-8 were amplified by the polymerase chain reaction and directly sequenced. RESULTS: No differences were noted between the two groups regarding gender, types of metaplasia, dysplasia, morphology, or histologic tumor type. However, a higher incidence of cystic dilatation and foveolar hyperplasia were present in GSca. p53 gene point mutations occurred in 5 of 14 (35.7%) GSca patients. GSca p53 mutations included missense point mutations (G:A transitions in four patients and G:C transversion in one patient) with allelic loss. In four of the five patients with p53 mutations, the same mutation was also observed in the adjacent area. p53 point mutations were present in 4 of 14 Gca (28.6%), in exons 5, 6, and 8. In one case, the same mutation was also detected in the adjacent nonmalignant mucosa. CONCLUSIONS: Similarities in clinical, pathologic, and molecular features between GSca and Gca suggest the possibility that they share similar mechanisms of carcinogenesis. p53 gene alterations in premalignant areas may denote a possible early role of this gene in gastric carcinoma.

Adenocarcinoma↗

PubMed1996

Challenges in the treatment of colonic motility disorders.

The pathophysiology and treatment of colonic motility disorders are reviewed. Colonic dysfunction is a common reason for patients to seek medical care, although patients' perceptions may not reflect abnormal function. Abnormalities in colonic function can result from a primary disorder of the large intestine or from metabolic, neurologic, collagen vascular, neoplastic, or infectious diseases. Irritable bowel syndrome, a common disorder of colonic motility, can be caused by alterations in colonic neuromuscular functions, afferent neural function, or psychosocial factors. Colonic dysmotility can also result from malabsorption of carbohydrates. The most severe form of altered colonic motility is acute colonic pseudo-obstruction. Diagnostic studies should be limited to tests appropriate for the patient's symptoms and apparent severity of disease. Most motility disorders are functional disorders and do not result in abnormal studies. Pharmacotherapy should be directed by objective measures, the most useful of which are measurement of whole gut transit time and quantification of the water content of stools. Treatment should be determined by the nature of the disorder and the symptoms involved. For constipation, treatment should begin with changes in diet, fluid and fiber intake, and concurrent medications. Irritant laxatives can have damaging effects and should not be used habitually; however, polyethylene glycol-based purgatives can be helpful. Newer prokinetic agents, such as cisapride, have been shown to promote colonic motility. For selected patients with intractable constipation, surgery has a good success rate. For patients with functional diarrhea, opioid analogues can increase fluid absorption and delay transit.

Colon↗

PubMed1996

Influence of pathophysiology, severity, and cost on the medical management of gastroesophageal reflux disease.

This article summarizes the pathophysiology of gastroesophageal reflux disease (GERD) and the wide spectrum in disease and symptom severity as they influence the selection of cost-effective treatment strategies. The vast majority of patients with GERD have mild symptoms, no gross endoscopic evidence of esophagitis, and little risk of developing complications. More than 85% of patients with GERD symptoms have uncomplicated disease. Diffuse ulcerations or complications (grade III or IV esophagitis) occur in only 3.5% of patients < 65 years of age. However, some patients with GERD can develop severe complications, including esophageal obstruction, significant blood loss, and, in rare circumstances, perforation. Furthermore, adenocarcinoma of the esophagus, which is increasing in incidence faster than any other cancer, is caused by GERD. Although severe ulcerations are uncommon in young patients, they occur in 20-30% of patients over age 65. Patients with ulcerative esophagitis are not only more prone to develop complications, they are also more resistant to treatment. Cost-effective medical management of GERD must take into account the wide spectrum of symptom and disease severity. Therapy consists of both nonpharmacologic treatment and the appropriate use of medications from several classes of drugs, either alone or in combination. Traditionally, prokinetic agents or histamine receptor antagonists have been used as primary therapy; proton-pump inhibitors are reserved for more resistant cases. The rationale for this and for alternative approaches is discussed.

Aged↗

PubMed1996

Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study.

OBJECTIVE: To compare the sensitivity of somatostatin receptor scintigraphy done using [111In-DTPA-DPhe1]octreotide with that of other imaging methods in the localization of gastrinomas in patients with the Zollinger-Ellison syndrome. DESIGN: Prospective study. SETTING: Referral-based clinical research center. PATIENTS: 80 consecutive patients with the Zollinger-Ellison syndrome. INTERVENTIONS: Conventional tumor localization studies (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], selective angiography, and bone scanning) and somatostatin receptor scintigraphy done using [111In-DTPA-DPhe1]octreotide with single-photon emission CT imaging at 4 and 24 hours. Patients with possible liver metastases had biopsies done for confirmation, and 15 patients had exploratory laparotomies done to assess primary tumor localization. RESULTS: Extrahepatic gastrinomas or liver metastases were identified by ultrasonography in 19% of patients, by CT in 38% of patients, by MRI in 45% of patients, by angiography in 40% of patients, and by somatostatin receptor scintigraphy in 70% of patients. Somatostatin receptor scintigraphy was as sensitive as the other tests combined (59%), and when the results of all other tests were added to the somatostatin receptor scintigraphy results, tumors were localized in 75% of patients. Among patients with a possible primary tumor, the results of ultrasonography were positive in 9%, the results of CT were positive in 31%, the results of MRI were positive in 30%, the results of angiography were positive in 28%, and the results of somatostatin receptor scintigraphy were positive in 58%. Somatostatin receptor scintigraphy was as sensitive as all of the other imaging studies combined; when the results of scintigraphy were added to the results of the other studies, possible primary tumors were identified in 68% of patients. In 24 patients who had histologically proven metastatic liver disease, sensitivities for the detection of any metastatic liver lesions were 46% for ultrasonography, 42% for CT, 71% for MRI, 62% for angiography, and 92% for somatostatin receptor scintigraphy. Somatostatin receptor scintigraphy was significantly better than all of the conventional imaging methods in the identification of gastrinomas later found at surgery (P = 0.004), but it still missed 20% of gastrinomas. CONCLUSIONS: Somatostatin receptor scintigraphy is the single most sensitive method for imaging either primary or metastatic liver lesions in patients with the Zollinger-Ellison syndrome. Because of its sensitivity, simplicity, and cost-effectiveness, it should be the first imaging method used in these patients. For patients with negative results on somatostatin receptor scintigraphy, guidelines about the use of other imaging studies are proposed.

Adolescent↗

PubMed1996

Comparative p53 mutational analysis of multiple primary cancers of the upper aerodigestive tract.

BACKGROUND: Tumors arising in the upper aerodigestive tract (UAT) are often associated with predisposing factors that place the patient at risk for development of multiple synchronous or metachronous tumors. The aim of this study was to evaluate p53 as a susceptibility gene in UAT malignancy. METHODS: Seventeen patients with 41 separate primary tumors involving esophagus (n = 15), larynx (n = 14), pharynx (n = 6), lung (n = 2), mouth (n = 2), and tongue (n = 2) were analyzed for the presence and specific genotype of p53 point mutation. Immunohistochemical staining of p53 and topographic genotyping consisting of polymerase chain reaction amplification and direct sequencing of p53 exons to 5 to 8 were performed. RESULTS: Eleven tumors were metachronous (6 months to 11 years), and 11 were synchronous. We found p53 point mutations in 19 (46.3%) of 41 tumors in exons 8 (n = 11), 7 (n = 4), 5 (n = 3), and 6 (n = 1). Tumors possessed either wild-type p53 or a single type of point mutation. Metastases displayed the identical genotype of its primary tumor in all cases. Most importantly, p53 genotype was found to be completely discordant between separate primary tumors for the same patient. CONCLUSIONS: Complete discordance in p53 genotype between separate primary UAT cancers strongly indicates that p53 is not functioning as a susceptibility gene in this setting.

Adult↗

PubMed1996

Gastrointestinal manifestations of scleroderma.

The gastrointestinal tract is commonly involved in SSc. The esophagus is the most frequently affected, followed by the anorectal region, the small bowel, stomach, and colon. Smooth muscle atrophy and to a lesser degree fibrosis is the underlying defect responsible for the resulting abnormalities. These smooth muscle alterations have a significant impact on gastrointestinal motility, which results in secondary disorders of GER, pseudo-obstruction, bacterial overgrowth, and disordered bowel functions. The clinical presentation for these conditions ranges from asymptomatic to life-threatening. Thus, gastrointestinal evaluation and treatment of these conditions is an important aspect in the management of patients with SSc.

Colonic Diseases↗