Management of reflux esophageal disease.

Although frequent or prolonged exposure of the esophageal mucosa to gastric contents results in epithelial damage, it is also becoming clear that the pathophysiology of reflux esophageal disease may be multifactorial. The severity of this disease may relate to the frequency of reflux episodes, certainly to the duration of mucosal exposure to refluxed material, and probably to as yet unquantified factors of mucosal resistance and the specific noxiousness of refluxed gastroduodenal and pancreatic secretions. The phenomenon of esophageal clearance is a critical determinant in preservation of mucosal integrity, and a disturbance in this function may lead to severe signs and symptoms of reflux esophageal disease. A detailed analysis of the specific pathophysiologic abnormalities in individual patients may permit more "tailored" therapeutic approaches and more favorable results.

Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation.

PURPOSE: To evaluate the soft tissue and bone tolerance of radiation therapy (RT) in patients undergoing radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. METHODS AND MATERIALS: From 1990 to 1994, 47 patients with primary or recurrent oral cavity or oropharyngeal carcinomas were treated with radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Eleven patients received no RT (no RT), 10 patients received RT greater than 10 months from the time of surgery (remote RT), and 26 patients received RT within 12 weeks of surgery (perioperative RT). The radiation dose to the reconstructed mandible ranged from 45 to 75 Gy (median 63 Gy). The effect of the titanium plate on the radiation dose was measured using film dosimetry and soft tissue and bone-equivalent materials. The median follow-up was 17 months (range: 3-50 months). RESULTS: Late complications included four patients with osteomyelitis or necrosis, two plate exposures requiring flap revision, one chronic infection, two cases of chronic pain, two fistulae, and one case of trismus and malocclusion. The crude incidence of late complications by treatment was: (a) no RT: 3 of 11 patients (27%); (b) remote RT: 2 of 10 patients (20%); and (c) perioperative RT: 9 of 26 patients (35%). One patient in the no-RT group lost the plate due to chronic pain. Five patients in the perioperative RT group also had plate loss, four due to osteomyelitis and/or necrosis, and one due to pain related to a recurrent tumor. No patients in the remote RT group had plate loss. The actuarial prosthesis preservation rate at 2 years was 88% for the no RT, 100% for the remote RT, and 57% for the perioperative RT groups (p = 0.05). Phantom dose measurements showed that for parallel opposed 6 MV photon beams, there was no significant increase in the dose proximal or distal to the plate in either a soft tissue- or bone-equivalent phantom. CONCLUSIONS: The impact of radiation therapy on plate preservation after mandibular reconstructive surgery using a titanium plate may be dependent on the timing of RT relative to surgery. Significantly more mandibular reconstruction plates were lost when the involved mandible received RT in the perioperative period than when RT was delivered beyond 10 months from surgery or when no RT was given. The use of alloplastic implants such as titanium plates in conjunction with myocutaneous flap coverage for mandibular reconstruction is attractive because it allows immediate reconstruction of the defect and promotes a good functional and cosmetic result; however, administration of perioperative RT may result in a higher plate failure rate.

Experience with omeprazole in erosive oesophagitis.

Omeprazole is a potent, highly specific, and clinically efficacious anti-secretory agent. Current clinical data suggest that omeprazole could be a useful drug in the short-term treatment of patients with severe erosive oesophagitis resistant to standard H2-receptor antagonist therapy. The magnitude of omeprazole's eventual role in the treatment of acid secretory-related disorders will depend on the results of its expanded postmarketing clinical experience and upon resolution of concerns regarding potential adverse effects associated with long-term administration.

Comparison of calcium channel blocking agents and an anticholinergic agent on oesophageal function.

The effects of oral doses of three calcium blockers and an anticholinergic drug on oesophageal function were compared. Nifedipine (20 mg) and hyoscyamine (0.25 mg) significantly reduced lower oesophageal sphincter (LES) pressure and oesophageal contractile pressure. Verapamil (120 mg) and diltiazem (60 mg) had no significant effect on any of the oesophageal variables measured. Oesophageal transit time and oesophageal contractile duration were not affected significantly by any of the agents. Only hyoscyamine significantly prolonged acid clearance time. The combination of nifedipine and hyoscyamine was no more effective in decreasing LES pressure or oesophageal contractile pressure than either agent alone. Either nifedipine or hyoscyamine would appear to be potentially effective for the treatment of oesophago-spastic and other hypertensive motor disorders, but hyoscyamine may lead to prolongation of acid clearance from the oesophagus.

Effect of enprostil on the gastroduodenal mucosa of healthy volunteers.

Enprostil is a synthetic dehydro-prostaglandin E2 with gastroduodenal ulcer-healing and mucosal-protective properties. One hundred and three healthy volunteers were randomized to receive capsules of enprostil 35 micrograms b.d. (the clinically recommended dose), enprostil 70 micrograms b.d., or placebo b.d. All underwent endoscopic assessment of the gastroduodenal mucosa, scored using a 0-4 scale, at baseline and on Days 3, 7, 14, 21 and 28 of dosing. Mean and median maximum scores demonstrated a dose response, and the mean maximum scores were statistically significantly higher for both enprostil groups on each endoscopy day when compared with placebo. The majority of enprostil-treated subjects had petechial haemorrhages. The proportion of volunteers with small white-based mucosal breaks (erosions) was significantly higher for the fundus in the enprostil 70-microgram group on Days 21 and 28 when compared with placebo, but there were no significant differences between treatment groups for any area on the other study days. The 70-microgram dose was associated with significantly more gastrointestinal adverse events than the 35-microgram dose, which was similar to placebo. There were no significant differences between groups for large white-based mucosal breaks (ulcers). We conclude that oral enprostil produced gastric mucosal petechial haemorrhages, primarily in the fundus of the stomach. Gastric mucosal petechial haemorrhages are probably without clinical significance because they are very common in the general population (10-15%) and do not progress to erosions and ulcers.

Dose--response effect of famotidine on patterns of gastro-oesophageal reflux.

The present study attempts to assess the alteration in patterns of gastro-oesophageal reflux as assessed by 24-h oesophageal pH monitoring by varying degrees of H2-receptor blockade with famotidine. Subjects were 12 patients with complaints of daily heartburn who demonstrated at least 6% of acid mucosal contact time by 24-h ambulatory oesophageal pH monitoring. All subjects had a positive Bernstein test, and nine of the 12 subjects had erosive oesophagitis. The study was conducted as a double-blind crossover design utilizing 40 mg nocte, 20 mg b.d., and 40 mg b.d. and placebo treatments. Results indicated that all treatments significantly reduced the 24-h percentage acid contact time (P less than 0.05) compared to placebo. The two b.d. treatment regimens also significantly (P less than 0.05) reduced the number of episodes lasting longer than 5 min. Only the b.d. regimens successfully lowered the percentage of upright acid exposure. All treatments significantly (P less than 0.01) reduced the percentage of supine acid contact time, as well as the number of episodes lasting more than 5 min. It is concluded that gastro-oesophageal reflux disease may well require a b.d. dosing regimen with famotidine in order to achieve optimal mucosal healing and day time symptom control.

The timing of evening meal and ranitidine administration--effects on patterns of 24 hour intragastric acidity.

Intragastric pH-metry was utilized to assess the effect of the time of meal ingestion and ranitidine administration on 24-h intragastric acidity. Twelve volunteers with a documented history of duodenal ulcer were studied in a four-way crossover design. Subjects randomly received ranitidine at 18.00 and 22.00 hours, with and without food. Serial blood samples were collected and analysed for ranitidine by high pressure liquid chromatography. Over the interval of 18.00-0.700 hours, the mean hydrogen-ion activity was significantly lower with the 18.00 hour dose than with the 22.00 hour dose (P less than or equal to 0.05). There were no differences between the four treatments in median pH or mean hydrogen-ion activity over the 23-h study interval. There were no differences between treatments in peak ranitidine concentrations, time to peak concentration, area under the serum-concentration time curve or elimination half-life.

The effect of esophageal acid volume on arousals from sleep and acid clearance.

To assess the effect of different volumes of acid infused into the esophagus, seven normal volunteers were studied in the waking and sleep state. All subjects were studied for three nights in the sleep laboratory, which included complete polysomnographic monitoring and esophageal pH recording. Multiple infusions of either 5, 15, or 25 ml of 0.1 N HCL were administered each night. Similar infusions were also accomplished in the waking state. The results showed a significant (p less than 0.05) decrease in the arousal from sleep with 25-ml vs 5-ml infusions. During sleep, the latency to the first swallow was significantly (p less than .05) shorter with the 25-ml infusion when compared with that of the 5-ml infusion. While awake, the infusion volume did not affect the latency to the first swallow. The acid clearance times were not significantly altered by the different volumes infused. It is concluded that the larger volumes of acid in the esophagus create an afferent "warning" signal to the central nervous system to produce a rapid arousal from sleep along with a shortened interval to the first swallow. These responses rapidly empty the larger acid volumes from the esophagus.

Esophageal function and gastroesophageal reflux during sleep and waking in patients with chronic obstructive pulmonary disease.

This study was conducted to assess esophageal function and pulmonary resistance changes with esophageal acidification in patients with COPD. Twelve patients with COPD and a mean age of 55.6 years were studied. Each patient underwent standard esophageal manometry, 24-h ambulatory pH testing, esophageal acid clearance evaluation during sleep, and an assessment of pulmonary resistance with and without esophageal acid perfusion. Neither airway resistance nor conductance was altered by the esophageal acid infusion; LES pressures were normal and esophageal contractile pressures were mildly decreased. Acid exposure in the upright and supine positions was within normal limits. Acid clearance during sleep was similar to that in normal subjects; however, acid clearance during waking appeared to be somewhat prolonged in the COPD patients. We conclude that patients with COPD do not have a bronchoconstrictive reflex to distal esophageal acidification, and esophageal function in these patients appears to be relatively normal.

Double-blind, placebo-controlled study of ranitidine for gastroesophageal reflux symptoms during pregnancy.

OBJECTIVE: To determine whether ranitidine (Zantac) taken once or twice daily is effective for relieving symptoms of gastroesophageal reflux among pregnant women who had failed conservative measures. METHODS: Volunteers with heartburn despite antacids were sought among our obstetrics clinic population for this double-blind, placebo-controlled, triple crossover trial. After a baseline week, 20 patients were randomized to receive the three following weekly regimens: ranitidine 150 mg twice daily, placebo in the morning and ranitidine 150 mg in the evening, or placebo twice daily. Daily scores on symptom diaries, global assessments, and number of antacids taken were compared among the 18 patients completing the study. RESULTS: The twice-daily dosage of ranitidine was the only regimen found to reduce heartburn symptoms when compared with the baseline (P < .001) or a placebo (P < .01). Compared with ranitidine taken once daily, the twice-daily dosing prompted less need for antacid tablets compared with the placebo (P < .05 versus P > .05) and to the baseline (P < .001 versus P < .05). The average reduction of heartburn severity using twice-daily ranitidine was 55.6% when compared with baseline (95% confidence interval [CI] 34.8%, 76.5%) was 44.2% when compared with placebo (95% CI 15.4%, 72.9%). CONCLUSION: This study indicates the efficacy of ranitidine 150 mg taken twice daily, rather than once daily, for relief of gastroesophageal reflux symptoms during pregnancy.

Unilateral retinoblastoma with acquired monosomy 7 and secondary acute myelomonocytic leukemia.

Patients with a nongenetic form of retinoblastoma are not particularly at high risk of developing second malignant neoplasms. We report here a case of treatment-related leukemia (secondary leukemia) with acquired monosomy 7, in a child with unilateral retinoblastoma.

Monozygotic twins with congenital acute lymphoblastic leukemia (ALL) and t(4;11)(q21;q23).

Congenital acute lymphoblastic leukemia (CALL) is a rare disorder and is frequently associated with t(4;11)(q21;q23). To our knowledge this is the first case report of monozygous twins with CALL and t(4;11)(q21;q23).

Patients with symptomatic ischemia have larger thallium perfusion abnormalities and more adverse prognosis than patients with silent ischemia.

OBJECTIVE: To evaluate the mechanism for silent ischemia and the effect on prognosis. DESIGN: To test the hypothesis that patients with silent (compared with symptomatic) ischemia have less severe ischemia and a more favorable prognosis, the authors prospectively evaluated 152 consecutive patients with a positive exercise electrocardiogram with exercise thallium scintigraphy and followed them for two years. SETTING: Tertiary care university-based hospital. RESULTS: Asymptomatic patients during the exercise test had a greater exercise duration (9.4 +/- 3.1 versus 6.3 +/- 2.5 mins, P < 0.01), maximal heart rate (155 +/- 20 versus 136 +/- 20 beats/min, P < 0.01), systolic blood pressure (184 +/- 21 versus 176 +/- 23 mmHg, P < 0.05) and double product than patients who were symptomatic with chest pain. Although there was no difference in the magnitude of ST depression, time to ST depression was greater in the asymptomatic (5.6 +/- 2.7 mins), compared with symptomatic (4.6 +/- 2.6 mins), group (P < 0.01). Thallium ischemic score was smaller during asymptomatic ischemia (2.1 +/- 2.7) compared with symptomatic ischemia (3.9 +/- 3.1, P < 0.01). These findings were also demonstrated in a subgroup of 107 patients with both a positive exercise electrocardiogram and positive thallium scan. The patients with asymptomatic ischemia had a two-year cardiac event rate of 5.1% compared with 13.8% in the symptomatic patients (P = 0.065). CONCLUSIONS: Patients with asymptomatic ischemia have less severe myocardial ischemia and a better prognosis than patients with symptomatic myocardial ischemia during exercise testing.

Intractable diarrhea in children with VIP-secreting ganglioneuroblastomas.

This paper describes two children with diarrhea, hypokalemia, and VIP-secreting ganglioneuroblastomas, and includes further evidence that VIP is the cause of the loose stools among patients with such tumors. It suggests that the level of this peptide should be measured in pediatric patients with intractable diarrhea of unknown etiology. Clinicians have long recognized intractable diarrhea as an occasional feature of neuroblastoma, ganglioneuroblastoma or ganglioneuroma. Until recently catecholamine was thought to cause the frequent stools in some patients with these tumors. New radioimmunoassay methods, the identification of new hormones and hormone-like substances, and the discovery that some of the tumors which cause diarrhea secrete Vasoactive Intestinal Peptide (VIP), make it probable that this substance is responsible for the diarrhea in such patients.

Gastroesophageal reflux: clinical diagnosis, current therapy, future trends.

In the usual clinical setting, symptomatic gastroesophageal reflux can be equated with heartburn; however, the diagnosis of gastroesophageal reflux disease (GERD) can be obscure. Recent improvements in the quality of fiberoptic endoscopy along with other imaging and diagnostic techniques have permitted a more complete understanding of the pathophysiology of gastroesophageal reflux. The continued development of antisecretory, prokinetic, and mucosal protective agents allows the gastroenterologist a choice of effective therapeutic approaches to deal with contributing factors such as gastric acid secretion, lower esophageal sphincter pressure, or gastric motility. Although standard doses of potent H2-receptor antagonists are the focus of current reflux disease therapy, increasingly aggressive regimens will probably become available for refractory patients.

Chronic subclinical ovine fascioliasis: plasma glutamate dehydrogenase, gamma-glutamyl transpeptidase and aspartate aminotransferase activities and their significance as diagnostic aids.

The effect of low grade chronic Fasciola hepatica infection on the concentration of plasma glutamate dehydrogenase (GD), gamma-glutamyl transpeptidase (gamma-GT) and aspartate aminotransferase (AST) was investigated in sheep dosed daily with three (AL3), eight (AL8) or 14 (AL14) metacercariae over 22 weeks or given a single dose of 200 metacercariae. Significant increases in plasma GD activity first occurred after nine, 12 and 23 weeks and in gamma-GT activity after 12, 24 and 32 weeks for groups AL14, AL8 and AL3 respectively. Changes in AST activity were not as clearly related to dose level. In sheep with single infection, both GD and gamma-GT were capable of detecting liver damage resulting from the migration of 10 or more flukes. Plasma GD and gamma-GT activities are more sensitive indicators of liver cell damage in chronic subclinical fascioliasis than AST activity and gamma-GT may be more suitable as a diagnostic aid on account of its greater stability.

Choroid plexus carcinoma. Report of a case with cytopathologic differential diagnosis.

The cytopathologic features of choroid plexus carcinoma in the cerebrospinal fluid of a 13-month-old male infant were reviewed and compared with those of other small-cell malignant neoplasms of childhood and young adulthood involving the central nervous system. The cytologic features of the choroid plexus carcinoma (tight spatial clusters and isolated anaplastic cells with striking nuclear lobulation) were distinct from those of lymphoma, leukemia, neuroblastoma, ependymoma and pineal germinoma. However, the cells had a striking resemblance to those of anaplastic ependymoma and metastatic adenocarcinoma.

The effect of chronic fluoride administration on rat condylar cartilage.

Morphometrical and histochemical techniques were used to demonstrate changes to the cartilage layer of the rat temporomandibular joint condyle following chronic exposure to fluoride. An increase in thickness of the cartilage layer was noted in rats given 100 parts per million sodium fluoride in drinking water. No significant changes were observed with either control or low dose (10 parts per million) groups. The observed thickening was attributable to an increase in number and size of cells of the lower hypertrophic zone. Accumulations of glycogen were observed in these cells, which reflects the inhibitory effect of fluoride on glycolysis. Stimulation of chondrocytes by fluoride may have delayed the normal processes of capillary invasion, resulting in thickening of the cartilage layer. No changes to staining patterns of immature or mature types of collagen were observed, nor did the staining pattern of detectable glycosaminoglycans change due to fluoride.