Severe Gastrointestinal Side Effects Research Articles

Challenges and new discoveries in the treatment of leishmaniasis

Leishmaniasis is a parasitic disease caused by a hemoflagellate, Leishmania spp. The parasite is transmitted by the bite of an infected female phlebotomine sandfly. The disease is prevalent throughout the world and in at least 88 countries. Human leishmanial infections may manifest in any of the four most common forms. Depending on the causative species, it can manifest as cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), diffused cutaneous leishmaniasis (DCL), or visceral leishmaniasis (VL). Although there are nearly 25 compounds having antileishmanial effects, only a few are used for humans and most of these are parenteral. The oldest was urea stibamine, developed in India in 1922. The original drug had severe toxic effects, and later on its pentavalent compounds were prepared, which remained the sole treatment modality for several decades and saved millions of lives. However, reports of unresponsiveness to pentavalent sodium antimony gluconate (SAG) started in the 1970s, and in some parts of India about a quarter of kala-azar cases are reported to have developed resistance even to its higher doses. This development led to successful clinical trials of pentamidine and amphotericine B. The latter, an antifungal compound, was also found to be highly nephrotoxic, and to minimize these side effects various colloidal and lipid formulations have been prepared. These preparations are comparatively safe but are exorbitantly costly. In the past two decades, more focus has been given to finding oral drugs to minimize injection-associated complications, including blood-borne infection. Various drugs were reported effective, including antifungal ketoconazole. However, the most promising drug found is an anticancer compound, miltefosine, that belongs to the alkylphosphocholine group. The drug has undergone experimental and clinical trials and found to be 94%-97% effective. However, the drug cannot be given during pregnancy and shows severe gastrointestinal side effects. Moreover, its cost will be another limiting factor. Other drugs such as paromomycin, allopurinol, and sitamaquine have been reported with variable cure rates. Because of these limitations, a combination therapy, preferably coupled with specific parasite enzyme inhibitors, is the only hope.

Farmacoeconomia dei COXIB nella patologia osteoarticolare: revisione della letteratura

A new class of anti-inflammatory agents, the selective inhibitors of cyclooxygenase-2 (COXIBs), has been recently introduced into the market for the treatment of osteoarthritis and reumatoid arthritis. Randomized and controlled clinical trials showed a similar efficacy and a better tolerability profile of COXIBs compared with conventional non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to perform a scientific literature review relating to the economic impact produced by COXIBs’ introduction. The research of references included the following databases: MEDLINE, EMBASE and the NHS (Economic Evaluation Database) of the York University. A total of 67 in extenso pubblications have been extracted. Of these 13 papers having the specific objective to evaluate the economic implications of COXIBs in comparison to conventional NSAIDs was analysed. In ten cases (77%), cost-effectiveness analyses were performed. The European context was considered in eight cases (62%), while that of North America and Asia were investigated in four and one case, respectively. The analysis of costs took always into account direct costs of the management of arthritis exclusively (drugs, and resources associated with the treatment of gastrointestinal side effects). Indirect and intangible costs were never considered. The results of this review highlight that the higher tollerability profile of COXIBs may generate a cost-saving. This cost-saving seems to be basically due to the reduced frequency of gastroprotective agents coprescription and also to a lesser appearance of severe gastrointestinal side effects compared with conventional NSAIDs. Besides the disease management improving, the cost-saving associated with COXIBs can completely or partially offset the net increase of expense induced by their higher price of purchase.

Phase I–II Parallel Study of Docetaxel on a Bimonthly Schedule in Refractory Metastatic Breast Carcinoma

The 3-week schedule with docetaxel (DTC) 75-100 mg/2 is associated with severe neutropenia, gastro-intestinal side-effects and fluid retention in a significant proportion of patients, which may be of concern in more elderly or poor performance status patients. A phase I-II trial was carried out to test the feasibility and the activity of a new bimonthly schedule of DCT. The trial included a phase I study which aimed at the identification of dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of DCT on a bimonthly schedule. The first group of three patients received DCT 40 mg/m2, and in absence of DLT, DCT dosage was escalated by 10 mg/m2/cycle until DLT was reached. In the phase II study, patients were randomized to receive: (a) standard 3-weekly DCT at the dose of 75 mg/m2 (calibration arm); or (b) bimonthly schedule with DCT at the dose recommended in the phase I study. All patients were pretreated with chemotherapy, mostly anthracycline-based regimens, for advanced/metastatic disease. Analysis of response rates, toxicity, and dose-intensity were the main aims of the study. The DLT was represented by severe myelosuppression which was recorded in all patients treated at 70 mg/m2 dose level. Therefore, the MTD was 60 mg/m2 on a bimonthly schedule. However, the dose recommended for the phase II trial was 50 mg/m2, because no difference in delivered dose-intesity was seen between the 50 and 60 mg/m2 dose levels, and the latter dosage was still associated with grade 3 neutropenia in most patients. The parallel phase II study showed that the bimonthly schedule of DCT (50 mg/m2) allows to deliver the same dose-intensity of DCT 75 mg/m2 every 3 weeks. Grade 3-4 side-effects were rather infrequent in patients treated with the bimonthly schedule. Overall response rate (ORR) was 41 and 44% for the DCT 50 mg/m2 bimonthly and the DCT 75 mg/m2 every 3 weeks, respectively. Data achieved in the phase I part of the study showed that DCT 50 mg/m2 every 15 days is the recommended dose for phase II studies, while results achieved in the phase II trial suggest that DCT 50 mg/m2 in a bimonthly schedule is active as second-line chemotherapy for MBC being able to induce an ORR in the range reported for DCT 75-100 mg/m2 every 3 weeks. The bimonthly schedule is, however, associated with relatively low toxicity. This characteristic may render the bimonthly schedule particularly attractive for future phase II trials of DCT in combination with other antineoplastic agents.

Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria

Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.

Medical Management of Missed Abortion: A Randomized Clinical Trial

The use of ultrasound has facilitated early diagnosis of missed abortion in an increasing percentage of patients, but the optimal management of these women is not yet clear. This study investigated the efficacy of vaginally administered misoprostol in the treatment of women with an ultrasound diagnosis of nonviable pregnancy who were not experiencing any cramping or bleeding. Fifty women were randomly assigned to receive either misoprostol or placebo by vaginal insertion. Follow-up visits were at 24 hours, 48 hours, and 1 week after insertion of the medication. Treatment was repeated if there was no satisfactory response at 24 hours. If at 48 hours there was no response or if an incomplete abortion was suspected, patients were offered a dilation and curettage (D&C). β-Human chorionic gonadotropin (β-hCG) levels were measured at the time of initial treatment, again at the 48 hour visit, and 4 weeks after presumed successful conclusion of treatment. Hemoglobin was measured at the initial visit and again at 1 week. The patients in both groups were similar in clinical and demographic characteristics. Their median gestational age was 12 weeks. Cramping began within 24 hours for all of the women receiving misoprostol and for only five of those treated with placebo. After the first dose of misoprostol, 10 of the 25 women in this group appeared not to have a successful response to treatment. However, the results of the 48-hour follow-up visit indicated that 21 of 25 patients had aborted completely, 3 had evidence of an incomplete abortion, and I woman remained unchanged. Most patients reported heavy bleeding that waned after passage of a tissue mass from the vagina. Severe bleeding necessitated an emergency D&C in one patient whose hemoglobin dropped from a postoperative level of 141 g/liter to 129 g/liter on day 7. Two women with persistent bleeding underwent D&C, but no products of conception were found in the histologic specimen. One patients noticed the expulsion of necrotic tissue 2 weeks after treatment. At the 4-week visit, despite an apparent complete response, one patient continued to have a positive pregnancy test. When a D&C was performed, a small bit of trophoblastic tissue was found in the surgical specimen. Within 1 week of initial treatment, four women in the placebo group aborted completely, and two had incomplete abortions. No change was seen in the other 20 patients. Analysis of the laboratory data showed no significant differences between the two groups in hemoglobin changes or concentrations, mean serum β-hCG levels or changes, or gestational sac size. Among patients receiving misoprostol, one woman experienced severe gastrointestinal side effects, and two had severe pain that was not relieved with codeine. Nearly 80% of the patients who responded to a questionnaire indicated that they were very satisfied with the vaginal misoprostol approach and would undergo this method of treatment again should the need arise. A similar percentage would recommend this treatment to a friend.

High-Dose Indium 111In Pentetreotide Radiotherapy for Metastatic Atypical Carcinoid Tumor*

Indium In 111 pentetreotide imaging of neuroendocrine tumors that overexpress somatostatin receptors has become standard for localization of these tumors. This radioligand is internalized into the cell and can induce receptor-specific cytotoxicity by emission of Auger electrons. We hypothesized that high-dose 111In-pentetreotide could be therapeutic in patients with somatostatin receptor-expressing tumors. Our 35-year-old patient had atypical carcinoid tumor metastatic to cervical, supraclavicular, mediastinal, and mesenteric lymph nodes and to the liver and bone. Chemotherapy had stabilized the disease but with severe gastrointestinal side effects. After a diagnostic 111In-pentetreotide scan, the patient was given eight courses (180 mCi each) of 111In-pentetreotide therapy to selectively target somatostatin receptor-expressing tumor cells. The disease was stable for approximately 14 months. The patient had two additional courses of 111In-pentetreotide therapy (360 mCi each). She died of the disease approximately 18 months after initiation of 111In-pentetreotide therapy.

High-Dose Indium 111In Pentetreotide Radiotherapy for Metastatic Atypical Carcinoid Tumor*

Indium In 111 pentetreotide imaging of neuroendocrine tumors that overexpress somatostatin receptors has become standard for localization of these tumors. This radioligand is internalized into the cell and can induce receptor-specific cytotoxicity by emission of Auger electrons. We hypothesized that high-dose 111In-pentetreotide could be therapeutic in patients with somatostatin receptor-expressing tumors. Our 35-year-old patient had atypical carcinoid tumor metastatic to cervical, supraclavicular, mediastinal, and mesenteric lymph nodes and to the liver and bone. Chemotherapy had stabilized the disease but with severe gastrointestinal side effects. After a diagnostic 111In-pentetreotide scan, the patient was given eight courses (180 mCi each) of 111In-pentetreotide therapy to selectively target somatostatin receptor-expressing tumor cells. The disease was stable for approximately 14 months. The patient had two additional courses of 111In-pentetreotide therapy (360 mCi each). She died of the disease approximately 18 months after initiation of 111In-pentetreotide therapy.

Oral phentolamine (Vasomax).

Vasomax is an oral preparation of phentolamine mesilate (Zonagen Pharmaceuticals) currently undergoing worldwide regulatory approval for distribution. Phentolamine is primarily an alpha-adrenergic antagonist with mild sympatholytic action and a beta-adrenergic stimulating action. Over 30 years of clinical experience has shown it to be a strong direct vasodilator on muscular walled vessels, likely based on its inhibitory action on adenosine 5-triphosphate-sensitive potassium channels. This medication is not new, having been marketed in the United States in an oral formulation between 1952 and 1984. Phentolamine initially achieved FDA approval for preoperative use in patients with pheochromocytoma for control of blood pressure and paroxysmal hypertensive episodes. In the past it had been evaluated for hypertension, pulmonary disease, cardiac arrhythmias, angina pectoris and peripheral vascular disease. Unfortunately for most of these indications the clinical responses to oral phentolamine have been variable. The most clinically significant adverse events associated with oral phentolamine in the past were systemic hypotension and vasomotor collapse, severe gastrointestinal side effects especially diarrhea and some complaints of nasal congestion. In this review we will concentrate on phentolamine in a new preparation for on demand treatment of erectile dysfunction of mild to moderate degrees.

Adjuvant radiotherapy following radical hysterectomy for patients with early-stage cervical carcinoma (1984-1996)

Background and purpose: The aim of this study was to assess the results of treatment (surgery alone or surgery and postoperative radiotherapy) for early-stage cervical carcinoma and to determine the morbidity associated with adjuvant radiotherapy. A subset of these patients ( n=10) was irradiated postoperatively for tumor related negative prognostic factors only and this retrospective analysis was also performed to determine if this decision was right and if the selection for this treatment was based on the right criteria. Material and methods: From 1984 to 1996, 233 women underwent radical hysterectomy as primary treatment of stage I or IIA cervical carcinoma. One hundred and fifty-six patients were treated with surgery alone (67%) and 77 patients (33%) received adjuvant radiotherapy for a, tumor related negative prognostic factors: the combinaton CLS⊕, tumor size ≥40 mm and poor differentiation grade or the combination tumor size ≥40 mm and depth of invasion ≥15 mm ( n=10), or b, positive surgical margins ( n=17), and/or c. lymphnode metastases ( n=42) and/ or d. parametrial involvement ( n=6). Results: For the entire group the most important prognostic factor for survival and disease free survival was node positivity. Additional factors were depth of invasion and positive surgical margins. Thirty-five patients recurred of which 12 after surgery alone. In all these cases the relapse was in the pelvis (100%). Of the 23 recurrences after surgery and adjuvant radiotherapy 13 were seen in the pelvis (56%) ( P=0.003). All patients with negative prognostic factors and N 0, received adjuvant radiotherapy ( n=10) and none of these patients recurred. The incidence of severe gastrointestinal radiation related side effects was low (2%). The incidence of lymphedema of the leg was 11% which was similar in the surgery alone group. Conclusions: The relatively low percentage of radiation related side effects together with 0% recurrence in a subgroup of node negative patients with high risk of recurrence, and a relatively low percentage of recurrence in the surgery alone group lead us to the conclusion that postoperative radiotherapy in special subsets of node negative patients is justified.

SUCCESSFUL TRANSPLANTATION WITHOUT RECURRENCE IN HEMOLYTIC UREMIC SYNDROME OMITTING CALCINEURIN INHIBITORS FOR IMMUNOSUPPRESSION

359 Recurrence or de novo occurrence of Hemolytic-Uremic Syndrome (HUS) following renal transplantation has been associated with the use of calcineurin inhibitors (Cyclosprine, Tacrolimus) for maintenance immunosuppression. In order to evaluate the efficacy of a calcineurin inhibitor free immunosuppression patients transplanted for end stage renal disease due to HUS, or de novo onset of this disease in a renal allograft were prospectively assigned to a calcineurin inhibitor free immunosuppressive protocol. Since 5/96 six patients were included at two centers utilizing this protocol. Immunosuppression consisted of MMF 1.5 gm po bid given together with an induction therapy consisting of either daclizumab (n=1), OKT3 (n=1) or ATG (n=4). All patients received rapidly tapered steroids. Three patients had their first transplant, the other patients had their 3rd (n=2) and 4th (n=1) transplant. Those patients being retransplanted had lost their previous grafts due to HUS recurrence while receiving CyA. All patients received CRT, four patients were female and two male. The age ranged from 20 to 54 years. Follow-up is at 6 to 19 months. None of the patients have had an acute rejection episode. Five patients are still on MMF and steroids, while in one patient MMF was switched to AZA five months after transplantation due to severe gastrointestinal side effects. The actual serum creatinine ranges between 50 and 134 µmol/L. To date none of the patients developed recurrency of HUS or graft loss. These results demonstrate that patients who had native kidney HUS or developed de novo HUS in a previous allograft may be safely treated with a calcineurin free maintenance immunosuppression in combination with an antilymphocyte globulin induction therapy.

A Phase II Trial of Edatrexate in Patients with Advanced Renal Cell Carcinoma

We performed a Phase II trial of edatrexate in 44 chemotherapy-naive patients with advanced renal cell carcinoma. Prior therapy with one biological-response modifier was permitted. Most patients had multiple sites of metastatic disease and were considered to have a poor prognosis using Eastern Cooperative Oncology Group criteria. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly with 5 weeks of therapy considered one cycle. Oral cryotherapy using ice chips was administered before each edatrexate dose. Thirty-seven patients were eligible and evaluable for toxicity and response. Two patients obtained a partial response, for an overall response rate of 5.4% (95% confidence interval of 0.6%, 18.2%); one patient remained in remission at 26+ months. Three treatment-related deaths occurred. Toxicity was severe, with stomatitis, myelosuppression, and other gastrointestinal side effects most prominent. Edatrexate in this dose and schedule has minimal activity in advanced renal cell carcinoma and is toxic.

Severe gastrointestinal side effects have been reported by Merck & Co in association with the use ofthe drug Fosamax

Severe gastrointestinal side effects have been reported by Merck & Co in association with the use ofthe drug Fosamax

Efficacy of dietary fiber in lowering serum cholesterol

I n the last few years, increasing attention has been given to lowering serum cholesterol levels to reduce high rates of coronary artery disease in the U.S. population.Q Using the new classification, it is estimated that approximately 32% of adult men and 27% of adult women in the United States require intervention for either borderline-high or high serum cholesterol levels.3 Considering the magnitude of the problem, in order to minimize health care costs, more emphasis is being given to dietary therapy and physical activity.2 Although the benefits of reducing consumption of cholesterol-raising saturated fats and cholesterol are well recognized and form the basis of Step-One and Step-Two Diets,1)2 an increase in dietary fiber has not been included as an essential component of dietary therapy. In this issue of the Journal, Hunninghake et al4 report the results of a nearly year-long multicenter trial of the efficacy of dietary fiber in the treatment of hypercholesterolemia. Using 20 g per day of a mixed dietary fiber supplement consisting mainly of watersoluble fibers (guar gum and pectin), and some water-insoluble fibers (pea, soy, and corn bran), the investigators observed, on average, a 5% lowering of total cholesterol and 9% lowering of low-density lipoprotein (LDL) cholesterol levels in 59 of the 93 hypercholesterolemic patients who complied with the therapy and Step-One Diet. Although the reductions in serum cholesterol values ranged from 1.6% to 6.6%, and in LDL cholesterol levels from 4.3% to 10.9%, the persistence of the hypocholesterolemic effect of dietary fiber over the long term was noteworthy. The study, however, has some limitations, which include exclusion of 34 subjects due to various reasons and lack of an intent-to-treat analysis. In addition, information on the nature and severity of gastrointestinal side effects that led 7 patients to withdraw from the study was not provided. The study, nevertheless, contributes importantly to our knowledge of long-term persistence of lipid-lowering action of dietary fiber over and above that of a Step-One Diet. Still, some questions remain unanswered. Is there a place for dietary fiber or its supplements in the management of hypereholesterolemia?

Randomised comparison of amoxycillin and erythromycin in treatment of genital chlamydial infection in pregnancy

SummaryErythromycin, the standard treatment for chlamydial infection in pregnant women, commonly causes side-effects, which limits its efficacy. In a randomised, double-blind study, we compared amoxycillin with erythromycin in this setting. 210 pregnant women with Chlamydia trachomatis infection were randomly assigned 7 days' treatment with amoxycillin (500 mg three times daily) or erythromycin (500 mg four times daily). Control cultures were obtained 21 days after treatment, during late pregnancy, and from the infant within a week of birth. Treatment was judged a failure if any post-treatment culture was positive or if the patient had to stop therapy because of severe side-effects.11 women (5·2%) were lost to follow-up. 1 (of 100) amoxycillin-treated women had to stop treatment because of severe side-effects compared with 12 (of 99) erythromycin-treated women (p=0·002). 1 woman in the amoxycillin group had a positive culture at the third-trimester examination. No positive post-treatment culture was found in the erythromycin group. Severe gastrointestinal side-effects were more common in women who received erythromycin (31 vs 6%, p<0·001). The overall failure rate was therefore 2% in the amoxycillin group and 12% in the erythromycin group (p=0·005). These results suggest that amoxycillin is an acceptable alternative to erythromycin for C trachomatis infection in pregnant women.

TOXICITY IN LONG-TERM SURVIVORS AFTER ADRIAMYCIN CONTAINING CHEMOTHERAPY OF MALIGNANT GERM-CELL TUMORS

In order to assess overall treatment-induced long-term morbidity after high-dose adriamycin-based chemotherapy +/- radiotherapy, clinically significant toxicity was studied in survivors after treatment of advanced germ-cell cancer who had received adriamycin-containing chemotherapy before cisplatin became available in Norway. Most of the patients were also irradiated. The study comprises 47 patients with advanced germ-cell cancer who survived for at least 5 years after chemotherapy containing adriamycin (VACAM: vincristine, adriamycin, cyclophosphamide, actinomycin-D and medroxyprogesterone acetate) as part of their primary systemic treatment (before 1978) or as maintenance chemotherapy after initial cisplatin-based cytotoxic treatment (after 1978). Thirty-two patients also had radiotherapy. The median follow-up was 12.3 years. Forty-one events of late toxicities were recorded in 25 patients, 37 of these were observed after combined radiotherapy and chemotherapy. The most frequent late side effects were cardiotoxicity, gastrointestinal toxicity and neurological disorders observed in 7, 12 and 8 patients, respectively. Three patients who were irradiated to the cardiac region, died of heart failure. Secondary solid cancer developed in 7 patients after a median follow-up of 10.5 years (relative risk 4.8, 95% confidence interval 1.9 to 9.9). In a historical perspective high-dose adriamycin-containing combination chemotherapy if applied with cyclophosphamide and/or radiotherapy, may occasionally be curative in selected patients with advanced germ cell tumours, but leads to an unacceptable high incidence of severe cardiac, gastrointestinal and neurological late side effects. The present follow-up study highlights that such treatment should be avoided in the curatively intended treatment of cancer patients and emphasizes the need of long-term follow-up studies in surviving cancer patients.

Effects of α‐Glucosidase Inhibition and Viscous Fibre on Diabetic Control and Postprandial Gut Hormone Responses

Twelve sulphonylurea-treated Type 2 diabetic patients underwent treatment for 2-week periods with the absorbable alpha-glucosidase inhibitor BAY m1099 (50 mg thrice daily) and with guar granules (5 g thrice daily) separately and together in a sequence-randomized double-blind placebo-controlled study. BAY m1099 and guar reduced the mean fasting plasma glucose from 10.0 +/- 0.7 mmol l-1 to 8.7 +/- 0.5 (p less than 0.05) and 8.3 +/- 0.7 mmol l-1 (p less than 0.01), respectively. Both agents also lowered home-monitored postprandial blood glucose, with BAY m1099 exerting the greater effect. Guar, but not BAY m1099, lowered serum cholesterol from 5.43 +/- 0.52 to 5.29 +/- 0.31 mmol l-1 (p less than 0.05). BAY m1099 reduced the test breakfast plasma responses of glucose (p less than 0.001) and gastric inhibitory polypeptide (GIP, p less than 0.01) and increased those of peptide tyrosine-tyrosine (p less than 0.05) and motilin (p less than 0.01). Guar also reduced plasma glucose concentrations after a test breakfast (p less than 0.05) and increased the response of neurotensin (p less than 0.05). Combining treatments gave no further reduction of postprandial blood glucose concentration and was associated with an increased incidence and severity of gastrointestinal side-effects.

Efficacy and Safety of Nabumetone in 4541 Elderly Patients From a Drug Monitoring Study

Nabumetone, a new nonsteroidal anti-inflammatory drug (NSAID) has been investigated in several clinical trials and over 18 000 patients in a drug monitoring study (Lemmel & Stroehmann 1988). An elimination half-life of 22 hours permits oncedaily dosing. The standard recommended dose is 1000mg for patients under 65 years and 500mg for patients over 65. Elderly patients, especially females, represent a subgroup with an increased risk for NSAID therapy because of frequent co-medication, decreased gastrQintestinal tolerance and potential impaired renal and hepatic function. Furthermore, elderly patients with chronic rheumatic disease often present with a higher incidence of severe gastrointestinal side effects due to previous NSAID treatment, and an eventual history of gastroduodenal ulcers or gastropathy. The objectives of the present study were:

Current status of proximal gastric vagotomy.

Proximal gastric vagotomy is nearing its twentieth year in clinical use as an operation for peptic ulcer disease. No other acid-reducing operation has undergone as much scrutiny or study. At this time, the evidence of such studies and long-term follow-up strongly supports the use of proximal gastric vagotomy as the treatment of choice for chronic duodenal ulcer in patients who have failed medical therapy. Its application in treating the complications of peptic ulcer disease, which recently have come to represent an increasingly greater percentage of all operations done for peptic ulcer disease, is well-tested. However, initial series suggest that it should probably occupy a prominent role in treating some of these complications, particularly in selected patients, in the future. The operation has the well-documented ability to reduce gastric acid production, not inhibit gastric bicarbonate production, and also minimally inhibit gastric motility. The combination of these physiologic results after proximal gastric vagotomy, along with preservation of the normal antropyloroduodenal mechanism of gastrointestinal control, serve to allow patients with proximal gastric vagotomy the improved benefits of significantly fewer severe gastrointestinal side effects than are seen after other operations for peptic ulcer disease.

Dihydroergotoxine Mesylate in the Treatment of Functioning Pituitary Adenoma

Although it is well known that bromocriptine (BC) is effective in the treatment of functioning pituitary adenoma, this agent sometimes causes severe gastrointestinal side effects. In this study, dihydroergotoxine mesylate (EX), which is composed of ergot alkaloids and is similar to BC, was administered to 11 patients with functioning pituitary adenomas who could not tolerate the adverse effects of BC. Three patients (27%) showed clinical improvement with EX treatment alone (1 to 6 mg/day). In another patient, computed tomography demonstrated tumor shrinkage. The remaining seven patients experienced adverse effects while taking EX. These results indicate that EX is a useful alternative to BC in the treatment of functioning pituitary adenoma, particularly in patients who cannot tolerate the side effects of BC. Moreover, pretreatment with EX appears to reduce the incidence of side effects of BC.

Prevalence, predictors, and course of anticipatory nausea in women receiving adjuvant chemotherapy for breast cancer.

Factors related to the prevalence, prediction, and course of anticipatory nausea (AN) in women (n = 77) receiving adjuvant chemotherapy for breast cancer were examined. Using a prospective longitudinal research design, patients were interviewed both before and after each chemotherapy infusion. Fifty-seven percent of the patients developed AN. These patients were characterized by more severe gastrointestinal side effects following the initial infusion and greater expectations for experiencing chemotherapy-related nausea. A more rapid development of AN was related to a history of experiencing nausea across a greater variety of situations, higher IV drug doses, and less infusion-related anxiety at the initial infusion. Although AN occurred intermittently across treatment sessions, severity was constant. Results provided strong support for the hypothesis that classical conditioning processes are instrumental in AN acquisition. The role of anxiety in the development of AN is considered as are clinical implications for the prevention of AN and recommendations for future research.