Use Of H2 Antagonists Research Articles

Association of depression and suicidal ideation among adults with the use of H2 antagonists

H2 antagonists are a common class of medications used to treat gastroesophageal reflux disease. They can cross the blood-brain barrier and can affect the central nervous system. Studies have reported that the intake of H2 antagonists may lead to mental confusion, delirium, hallucinations, sleep disturbances, and depression. Using a national database, we examined the cross-sectional association between suicidal ideation and H2 antagonists. Data were obtained from the US National Health and Nutrition Examination Survey (NHANES) 2005-2018, in which Patient Health Questionnaire-9 (PHQ-9) scores were used to classify participants who had depression and suicidal ideation. The study population consisted of 13,533 adult Americans with PHQ-9 information, H2 antagonist use, and all other covariates. The results showed significant associations between the use of H2 antagonists and depression (P < 0.001) or suicidal ideation (P < 0.001). The covariates of education, race, marital status, poverty income rate, smoking, and a number of comorbidities were also statically significant with both depression and suicidal ideation. A multiple logistic regression model adjusted for these covariates showed that H2 antagonist users had a 2.94 (95% CI: 2.01–4.32) higher risk of suicidal ideation than non-users. This association was strongest among participants aged 50–59 years. This study shows that suicidal ideation and depression may be caused by several factors, and H2 antagonist use may be one of them. Further studies should be conducted to increase knowledge about the psychiatric effects of taking H2 antagonists, especially in long-term treatment.

A narrative review of gastroesophageal reflux in the pediatric patient.

Gastroesophageal reflux (GER) is the retrograde passage of gastric contents into the esophagus. It is a physiologic condition that is common in neonates, typically resolves spontaneously, and does not result in clinically significant complications. When pathologic, gastroesophageal reflux disease (GERD) can cause numerous complications including persistent emesis, failure to thrive, aspiration, and respiratory symptoms. While a diagnosis can often be made from a thorough history and physical, some patients may require further testing. In general, many clinicians will reserve extensive investigation such as multiple intraluminal impedance and pH monitoring for patients with a confounding clinical picture or relative contraindications to medical or surgical management. Whereas most pediatric GER resolves spontaneously, medical management including lifestyle changes, changes to feeds, and the use of H2-antagonists and/or proton pump inhibitors (PPIs) can be utilized to alleviate symptoms. Surgical treatment is reserved for patients who are refractory to medical management or have suffered significant complications as a consequence of GER. In this article we seek to provide a concise but detailed review of recent updates in the understanding, work up and management of GER in the pediatric patient. A summary of new technologies used in the diagnostic and therapeutic arms of this disease are included.

Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study.

The prevalence of vitamin B12 deficiency varies from 5.8% to 30% among patients undergoing long-term treatment with metformin. Because of the paucity of data on Brazilian patients, this study aimed to determine the frequency of B12 deficiency and related factors among Brazilian patients with type 2 diabetes mellitus (T2DM) using metformin. Cross-sectional study at a public university hospital. Patients with T2DM and a control group of non-diabetics were included. Serum B12 levels were measured and biochemical B12 deficiency was defined as serum levels < 180 pg/ml. Associations between B12 deficiency and age, duration of T2DM, duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) or histamine H2 antagonists were determined. 231 T2DM patients using metformin (T2DM-met) and 231 controls were included. No difference in the frequency of PPI or H2-antagonist use was seen between the groups. B12 deficiency was more frequent in the T2DM-met group (22.5% versus 7.4%) and this difference persisted after excluding PPI/H2-antagonist users (17.9% versus 5.6%). The factors that interfered with serum B12 levels were PPI/H2-antagonist use and duration of metformin use ≥ 10 years. Use of PPI/H2-antagonists was associated with B12 deficiency, with an odds ratio of 2.60 (95% confidence interval, 1.34-5.04). Among T2DM patients, treatment with metformin and concomitant use of PPI/H2-antagonists are associated with a higher chance of developing B12 deficiency than among non-diabetics.

Pharmacological treatment of children with gastro-oesophageal reflux.

Pharmacological treatment of children with gastro-oesophageal reflux.

The Changing Impact of Gastroesophageal Reflux Disease in Clinical Practice: An Updated Study

Objectives: (1) Understand evolving national trends in diagnosis and management of reflux disease. (2) Be able to analyze these by provider specialty. Methods: National Ambulatory Medical Care Survey (NAMCS) data for time periods 1998-2001, 2002-2005, and 2006-2009 were reviewed for number of visits, provider type, and prescriptions provided. Results: Addition of 2 more 4-year periods to previously reported data demonstrates increasing ambulatory visits for reflux across all races, sexes, and age groups. In 2006-2009, there were 15,750,000 visits for reflux, representing 6.9 visits per 100 people on a population basis. Overall visits increased across each sequential time period for internal medicine, family, and gastroenterology physicians. Among otolaryngologists, reflux visits increased from 1998-2001 to 2002-2005 but then decreased in 2006-2009; percentage of reflux visits to otolaryngologists fell from 4.4% in 2002-2005 to 2.9% in 2006-2009. Approximately two-thirds of reflux visits were among internal medicine and family practice providers. Among the 3 study periods, number of reflux prescriptions increased 233% with continuing trends toward increased proton pump inhibitor and reduced H2 antagonist use. Conclusions: Number of ambulatory visits for reflux continues to increase over time, across all demographic subgroups studied. Otolaryngologists are the only specialty who saw a decrease in overall reflux visits from 2002-2005 through 2006-2009; this may reflect real change in practice patterns, change in coding strategies or uncertainty in firmly establishing a reflux diagnosis. Understanding trends in this increasingly prevalent disease may focus attention on more precise diagnosis and improved treatment.

The use of H2 antagonists in treating and preventing NSAID-induced mucosal damage

Pain affects the quality of life for millions of individuals and is a major reason for healthcare utilization. As populations age, medical personnel will need to manage more and more patients suffering from pain associated with degenerative and inflammatory musculoskeletal disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective treatment for both acute and chronic musculoskeletal pain; however, their use is associated with potentially significant gastrointestinal (GI) toxicity. Guidelines suggest various strategies to prevent problems in those at risk for NSAID-associated GI complications. In this article, we review the data supporting one such strategy - the use of histamine type-2 receptor antagonists (H2RAs) - for the prevention of GI adverse events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone.

Use of Histamine2-Antagonists for the Treatment of Verruca Vulgaris

To review the evidence for histamine2 (H2)-antagonists in the treatment of common warts. Relevant publications were identified through a systematic search of PubMed English-language literature using the MeSH terms and key words cimetidine, ranitidine, famotidine, nizatidine, histamine H2-antagonists, and warts. Additional articles were identified using the same key words in the Cochrane Database and International Pharmaceutical Abstracts. Systematic searches were conducted through January 2007. In addition, pertinent references from identified articles were reviewed. The literature search retrieved 21 relevant citations, excluding review articles. Five open-label studies and 7 randomized controlled clinical trials were evaluated. Cimetidine was the focus of 11 studies, and ranitidine was evaluated in 1 study. No data regarding the other H2-antagonists were found. The other retrieved citations were not evaluated due to their design (case reports or case series) and/or focus on specific wart subtypes, not common warts. The use of H2-antagonists in the treatment of common warts is not associated with significant improvements in resolution rates. Open-label studies were promising with an estimated 48-81% response rate. However, randomized controlled trials have failed to show significant efficacy when cimetidine was compared with placebo or topical agents, and ranitidine has never been evaluated in a randomized controlled trial. Adverse effects, specifically gastrointestinal complaints, were documented. Efficacy may have been limited by inadequate dosing in some of the trials. The studies were limited by the small sample size and lack of power in a number of the trials, as well as the documented spontaneous resolution rate for warts. Several open-label trials evaluating the use of H2-antagonists for verruca vulgaris reported high response rates, but these results have not been corroborated by more rigorous clinical trials. Current data do not support the use of H2-antagonists for the treatment of common warts.

Risk factors for Salmonella Enteritidis and Typhimurium (DT104 and non-DT104) infections in The Netherlands: predominant roles for raw eggs in Enteritidis and sandboxes in Typhimurium infections

Since 1996 Salmonella Typhimurium DT104 salmonellosis has increased in The Netherlands. This prompted a case-control study of risk factors for salmonellosis to inform transmission routes for this phage type. Cases were laboratory-confirmed patients with a Salmonella infection and controls were selected from population registries by frequency matching for age, sex, degree of urbanization and season. Cases and controls received a questionnaire on risk factors. Of the 1171 cases, 573 (49%) responded: 245 S. Enteritidis and 232 S. Typhimurium cases (both DT104 and non-DT104), of which 58 were DT104. Of the 10250 controls, 3409 (33%) responded. Use of H2 antagonists [odds ratio (OR) 4.4, 95% CI 1.6-12.2] and proton pump inhibitors (OR 4.2, 95% CI 2.2-7.9), consumption of raw eggs (OR 3.1, 95% CI 1.3-7.4) and products containing raw eggs (OR 1.8, 95% CI 1.1-3.0) were associated with endemic S. Enteritidis infection. Risk factors for endemic S. Typhimurium infection were use of proton pump inhibitors (OR 8.3, 95% CI 4.3-15.9), occupational exposure to raw meat (OR 3.0, 95% CI 1.1-7.9), playing in a sandbox (for children aged 4-12 years) (OR 2.4, 95% CI 1.6-3.7), consumption of undercooked meat (OR 2.2, 95% CI 1.1-4.1) and use of antibiotics (OR 1.9, 95% CI 1.0-3.4). Use of proton pump inhibitors (OR 11.2, 95% CI 3.9-31.9) and playing in a sandbox (OR 4.4, 95% CI 1.8-10.7) were the only risk factors for S. Typhimurium DT104 salmonellosis. This study confirms known risk factors for salmonellosis. However, playing in a sandbox was a predominant new risk factor for S. Typhimurium salmonellosis in children [population attributable risk (PAR) 14%], and especially for S. Typhimurium DT104 (PAR 32%).

Site specific therapy: An integrative approach to treating melanoma

There have been many proposed theories for effectively treating melanoma, especially through the regulation of histamine. Histamine has been proven to be a major regulator of the immune system's T-helper cell subset balance and major shifts in this balance towards TH2 cytokines have contributed to diseases such as asthma, lupus and cancer. Histamine also causes suppression of interferon-induced proteins needed for anti-tumor response and activates T-suppressor cell function in cancers such as squamous cell carcinoma and melanoma. Scientific evidence has suggested the possibility of an anthistamine approach as treatment to these diseases and for melanoma, there has been great promise. This is due to the fact that melanotic cells have been elucidated to express histamine receptors and as a result, regulation of histamine could occur specifically at the site of these epidermal growths. Another factor to consider is how effective an inflammatory response can be when combined with regulation of histamine. Inflammation is a very powerful tool against pathogenic environments by causing cytokine recruitment and migration of dendritic cells to infected sites. Adequate stimulation of an inflammatory response at the specific site of any cancerous region would greatly weaken its evasive mechanisms. However, there are no reports showing high efficacy utilizing the benefits of regulating inflammation and histamine that could cause TH1 subset levels to predominate, down-regulate T-suppressor cells, up-regulate interferon-induced proteins and properly sustain migration of dendritic cells concurrently. These benefits have been proven in separate instances for a range of diseases but have not been assessed as a combined modality for melanoma therapy. Therefore successful melanoma treatment should integrate these principles involving: the use of H2 antagonists for preventing the negative effects of histamine, monoclonal antibodies to ensure an effective dendritic cell response, and routine pro-inflammatory induction at the specific site of the melanotic tissue to ensure recognition of the cancer that has evaded immunity.

Causes of gynaecomastia in young adult males and factors associated with idiopathic gynaecomastia

Gynaecomastia is a common clinical condition. Persistent pubertal or late onset idiopathic gynaecomastia is the leading cause of gynaecomastia in different series. The aim of this study was the assessment of the prevalence and characteristics of different causes of gynaecomastia in young adult males, and evaluation of the factors associated with idiopathic gynaecomastia. Fifty-three male patients (mean age 22.04 +/- 2.22, range 19-29), who had been admitted to our outpatient clinics with gynaecomastia as the main presenting symptom were enrolled in the study. Patients were evaluated with breast palpation, breast ultrasonography, anthropometric measurements and sex steroid levels. Secondary causes of gynaecomastia were ruled out. Thirty age-matched healthy individuals were also studied as healthy control group. Idiopathic gynaecomastia was diagnosed in 31 of 53 patients (58%), with 17 (32%) persistent pubertal and 14 (24%) late onset course. Other causes of gynaecomastia were hypogonadism in 13 cases (25%), hyperprolactinaemia in five (9%), chronic liver disease in two (4%), and drug induced (prolonged use of H2 antagonists) in two (4%). Patients with idiopathic gynaecomastia, either pubertal or late onset, were compared with the healthy control group in order to find out associated factors. Anthropometric measurements revealed a significant increase in body weight and body mass index (BMI) in the patient group compared with healthy controls (72.4 +/- 13.3 vs. 63.6 +/- 7.9 kg, p = 0.0086 and 25.2 +/- 4.0 vs. 21.5 +/- 2.7 kg/m2, p = 0.0001). Total skin fold thickness (SFT) of four different regions were also higher in the patient group (50.9 +/- 22.1 vs. 32.6 +/- 10.2 mm, p = 0.0006) indicating a higher body fat percentage. Total serum testosterone (4.76 +/- 1.31 vs. 5.70 +/- 1.06 microg/mL, p = 0.0038) and luteinizing hormone (LH) (4.80 +/- 1.92 vs. 7.32 +/- 1.90 mIU/mL, p < 0.0001) levels were significantly lower in the patient group while oestradiol levels were similar. There was a significant correlation between total testosterone and LH levels (r = 0.27, p = 0.0445). Total testosterone and LH levels were negatively correlated with BMI and total SFT. As a result most common form of gynaecomastia is idiopathic gynaecomastia either as persistent pubertal or late onset forms in young adult males. Idiopathic gynaecomastia is closely correlated with generalized obesity, reduced LH and testosterone levels which may be the result of increased conversion of testosterone to oestradiol in increased adipose tissue mass.

Evolution of the need for operation for peptic pyloric stenosis over a period of 24 years (1976-1999).

To analyse the need for operation for pyloric stenosis caused by duodenal ulcer over a period of 24 years (1976-1999). Retrospective study. University hospital, Spain. 156 patients operated on for peptic pyloric stenosis. The number of patients operated on yearly were grouped into 4-year periods for statistical comparison. The number of cases operated on each year steadily decreased between 1976 and 1999. In the 1988-1991 period there was a significant reduction (p <0.05), which continued over the next two 4-year periods, particularly the last (p <0.01). Although we cannot use this study to establish a direct relation between the decrease in the indication for operations for peptic pyloric stenosis and the use of H2 antagonists, proton pump inhibitors, or treatment to eradicate Helicobacter pylori, we did find a significance difference between the years before and after the introduction of these drugs.

Histamine receptor antagonists, proton pump inhibitors and their combination in the treatment of gastro-oesophageal reflux disease

The medical treatment of gastro-oesophageal reflux disease is accomplished with the appropriate use of anti-secretory therapy, principally H2-receptor antagonists and proton pump inhibitors. In fact, there is a direct correlation between the length of time, in terms of the number of hours per day that the intragastric pH is above 4, and the healing of the oesophagitis. Nowadays, H2-receptor antagonists are of limited use as primary treatment, being inferior to proton pump inhibitors in both healing and symptom relief. Although the majority of patients can be effectively managed with carefully titrated doses of proton pump inhibitors, a small number will continue to show difficulty in the management of their disease, principally because of inadequate nocturnal acid control. These patients may benefit from a combination of proton pump inhibitors twice daily with an H2-receptor antagonist at bedtime. This article reviews the use of H2-antagonists, proton pump inhibitors and their combination in the management of the patient with gastro-oesophageal reflux disease.

Negative effect of ranitidine on the results of urea breath test for the diagnosis of Helicobacter pylori

OBJECTIVES: In analogy with proton pump inhibitors, H2- antagonists may also be responsible for false-negative results on urea breath test for the detection of Helicobacter pylori. In this study we assessed the frequency and duration of false-negative urea breath tests in patients given different doses of ranitidine. METHODS: A total of 120 consecutive dyspeptic patients infected with H. pylori on the basis of concomitant positive results of CLO-test, histology and urea breath test were recruited for this prospective, open, parallel-group study performed in an urban university gastroenterological clinic. They were randomized to receive an acute treatment with either ranitidine 300 mg once a day in the evening, ranitidine 300 mg once a day in the morning, ranitidine 150 mg b.i.d., or ranitidine 300 mg b.i.d. for 14 days. The urea breath test was performed on day 14 while patients were still taking ranitidine, and on day 21, 1 wk after completion of therapy. The test was repeated on day 28 in those patients who were still negative on day 21. Duplicate breath samples were collected after ingestion of 75 mg 13C-urea plus citric acid. A δ value >5‰ was considered positive. RESULTS: Of 118 patients infected with H. pylori, 15 (13%) had a negative urea breath test on day 14. The false-negative results were equally distributed among the four groups of ranitidine dosage. Nine of these patients reverted to positive at 7 days and the remaining six at 14 days after completion of therapy. CONCLUSIONS: Our study shows that ranitidine negatively affects the results of urea breath testing, independent of the given dosage. Patients undergoing this examination for H. pylori diagnosis should discontinue use of H2-antagonists 2 wk before testing.

Clinical pharmacokinetics of slow release mesalazine.

Slow release oral mesalazine (Pentasa) contains microgranules covered by a semipermeable ethylcellulose membrane. The microgranules continuously release their content from duodenum to ileum in a pH- and time-dependent way. About 75% of the microgranules pass into the colon, where further release is slower. This release pattern does not appear to be affected by food, diarrhoea or the simultaneous use of H2 antagonists. Rectal forms of mesalazine deliver active drug directly to the rectum and left colon. Plasma concentrations of mesalazine and its metabolite acetyl-5-aminosalicylic acid after oral or local administration are the result of systemic absorption and hepatic metabolism by N-acetyltransferase. Most studies report maximal plasma concentrations of less than 1 mg/L after oral administration of slow release mesalazine, much lower than those observed after uncoated mesalazine but generally higher than after azo-bound drugs such as sulfasalazine. Urinary recovery is an indicator of absorption and metabolism, and is lower after rectal administration (10 to 30%) than after oral administration (30 to 40%). Faecal recovery after oral administration of slow or delayed release mesalazine is lower than with azo-bound drugs. Mesalazine acts locally after absorption by colonic and ileal mucosa. Mean steady-state concentrations of 25.7+/-2.2 microg/kg wet weight are found in ileocolonic biopsy specimens from patients with irritable bowel syndrome treated for 1 week with slow release mesalazine 1.5 g/day. Intramucosal concentrations after slow release mesalazine differ little between healthy individuals and patients with inflammatory bowel disease. Although significant differences are found between the various aminosalicylates in release patterns and the resulting pharmacokinetic parameters, no differences in therapeutic effects have been found in comparative studies. High doses of oral mesalazine (2 to 4 g/day) are more effective than lower doses in the treatment of patients with mild to moderate active ulcerative colitis. High doses (4 g/day) are also effective in the treatment of Crohn's disease, predominantly in patients with ileitis. In contrast, no dose ranging effects were demonstrated with local treatment forms: mesalazine 1g enema seems sufficient for patients with distal colitis. Higher serum concentrations and urinary recoveries after the administration of slow or delayed release mesalazine compared with azo-bound drugs suggest a higher risk for renal adverse effects, although the reported occurrence is extremely low. Although preliminary data support an association between mucosal concentrations of mesalazine and its clinical activity, further studies are needed to correlate the effects of this drug with its pharmacokinetic parameters.

Helicobacter pylori eradication in clinical practice: one-week low-dose triple therapy is preferable to classical bismuth based triple therapy.

Both classical 2-week bismuth based triple therapy and the newer 1-week low-dose omeprazole based triple therapies achieve high Helicobacter pylori eradication rates in controlled clinical trials and are in widespread use in routine clinical practice. However, their efficacy and acceptability in this setting is unproved. Over a 1-year period, the notes for patients attending a dedicated H. pylori treatment clinic were audited. Assessments were made of patient demographics, diagnosis, smoking habits, use of H2-antagonists, regimen used, efficacy of treatment, compliance and side-effects experienced. 223 sets of notes were audited. 89 patients received bismuth, tetracycline and metronidazole for two weeks and 111 patients received omeprazole, clarithromycin and either metronidazole (63 patients) or tinidazole (48 patients) for 1 week. Successful eradication was achieved in 75/89 (84.3%), 56/63 (89%) and 42/48 (88%), respectively, (P = N.S.). Severe side-effects occurred in 11 (12%) of patients receiving bismuth based treatment compared to 1 (0.9%) patient receiving omeprazole based regimens (P < 0.02). Treatment failure in patients receiving omeprazole based treatment was associated with smoking (P < 0.05). Outside the context of clinical trials, both regimens achieved acceptable eradication rates. However, 1-week low-dose therapy is preferable due to the lower incidence of severe side-effects.

Cost effectiveness of screening for and eradication of Helicobacter pylori in management of dyspeptic patients under 45 years of age.

To assess the cost effectiveness of screening for and eradicating Helicobacter pylori in patients under 45 years of age presenting with dyspepsia. A decision analytic model composed of a decision tree to represent the epidemiology of dyspepsia and a Markov process to model the outcomes of treatment. Patients under the age of 45 years presenting to their general practitioner with (peptic type) dyspepsia. Conventional empirical treatment with healing and maintenance doses of cimetidine v eradication treatment solely in patients with confirmed peptic ulcer; and conventional empirical treatment for all dyspeptic patients compared with the use of a serology test to identify patients with H pylori, who then receive endoscopy to investigate the presence of peptic ulcer disease and, when disease is found, are given eradication treatment with a breath test to confirm successful eradication. Expected cumulative costs over a period of 10 years. The proportion of time patients spend without a recurrent ulcer. After receiving eradication treatment, patients with confirmed ulcer spend an average of 99% of their time free from recurrent ulcer disease compared with 95% after treatment with cimetidine. Eradication treatment costs less than that with cimetidine. When the initial cost of identifying appropriate patients to receive eradication treatment is added to the analysis, however, these cost savings take almost eight years to accrue. Enthusiasm for introducing testing for and eradication of H pylori for dyspeptic patients in general practice should be tempered by an awareness that cost savings may take many years to realise.

Characterization and Function of Histamine Receptors in Corpus Cavernosum

Widespread clinical use of H2 antagonists for peptic ulcer disease has been associated with reports of impotence. Histamine is a vasoactive amine which is endogenously produced in many organs including the penis. To date, 3 histamine receptor subtypes (H1, H2 and H3) have been identified. However, the role and function of histamine in the corpus cavernosal physiology are poorly understood. This study evaluates the in vitro functional characteristics of the 3 histamine receptor subtypes in the isolated corpus cavernosal strips from New Zealand White rabbits. The isometric responses to histamine and specific histamine receptor subtype agonists were assessed, following cyclooxygenase (indomethacin, 10(-5) M.), adrenergic (guanethidine, 5 x 10(-6) M.) and cholinergic (atropine, 5 x 10(-6) M.) blockade, at resting tension and after submaximal precontraction with norepinephrine (NE, 2 x 10(-5) M.). Histamine (10(-8) M. to 10(-3) M.) produced concentration-dependent contraction from basal and precontracted states and did not relax precontracted tissue. The H1 agonist, 2-(2-thiazolyl)ethylamine (10(-8) M. to 10(-3) M.), produced a contractile response from both basal and precontracted states, while the corporal tissue did not respond to either dimaprit, an H2 agonist (10(-8) M. to 10(-5) M.) or R(-)-alpha-methyl-histamine, an H3 agonist (10(-8) M. to 10(-5) M.). The response to histamine was progressively attenuated by an H1 antagonist (mepyramine; 10(-8) M. to 10(-5) M.), while neither an H2 antagonist (cimetidine; 10(-4)M.) nor an H3 antagonist (thioperamide; 10(-4)M.) had any inhibitory effects. H1 antagonism enhanced relaxation induced by electrical field stimulation (neurally mediated). Such relaxation increased after preincubation with 10(-6) M. or greater of mepyramine (p < 0.05). This study suggests that the principal histamine receptor subtype that mediates smooth muscle cell contraction in the corpus cavernosum is the H1 subtype. Since histamine H1 receptor antagonism increased NANC neurally mediated corporal relaxation, it possesses potential as an intracavernosal pharmacotherapeutic agent for the treatment of erectile dysfunction. This study, therefore, strongly indicates that H2 receptor antagonists are unlikely to have direct effects on penile erection.

Medical Therapy Versus Laparoscopic Surgical Treatment for Ulcer Disease.

The development of low morbidity vagotomy and H2 antagonists in the early 1970s began the debate as to which was the most appropriate treatment for uncomplicated duodenal ulcer. A review of Australian Medicare and Pharmaceutical Benefits Scheme data shows that medical treatment in this country was the preferred option. In the past 12 years, vagotomies have decreased 15-fold while, in the same period, H2 antagonist prescriptions have increased from 0 to 2.5 million per year, doubling in the past 3 years, and currently costs $96 million per year or 6.7% of the country's entire pharmaceutical budget. Similarly, upper gastrointestinal tract endoscopies have increased, costing $15 million per year, doubling in the past 6 years and representing a cost almost equivalent to all other upper gastrointestinal procedures combined. Despite known efficacy and recommendations for use, triple therapy for Heliobacter species is not being used with prescriptions for surface agents actually decreasing to 40,000 per year. A review of the outcome of medical and surgical therapy shows that this expense is not justified; surgery would be more costeffective than medicine at 2 years and safer than medicine after 4 years as a result of complications from failed medical treatment. This margin of benefit is predicted to be greater with laparoscopic vagotomy. Failed medical treatment needs to be redefined by limiting H2 antagonists to a 6-week course. Recurrences or failures are than evaluated endoscopically and those diagnosed with having chronic duoderal ulcers have biopsies taken. Heliobacter pylori positive patients are treated with triple therapy. Failures, recurrences, and originally H pylori negative patients have laparoscopic vagotomy. For such a trial protocol to be evaluated, it requires the long-term use of H2 antagonists to be restricted and laparoscopic vagotomists to document the efficacy of their surgery, including gastric secretion tests.

Recent treatment with H2 antagonists and antibiotics and gastric surgery as risk factors for Salmonella infection.

Experimental evidence shows that gastric acid protects against enteric infections,1,2 and patients who have had gastric surgery seem to be more susceptible to salmonella infection.3,4 Whether H2 antagonists are also associated with salmonella infection is not known, although diarrhoea is a recognised side effect. Statutory notifications of salmonella infection have increased in recent years and the use of H2 antagonists has become widespread, suggesting that suppression of acid by these drugs may have been contributory. We conducted a case-control study to assess whether H2 antagonists are associated with salmonella infection. From March 1990 to September 1992, 218 notified cases of salmonella infection, confirmed by faecal culture, occurred in people aged >=45 in the Nottingham area. Thirty cases were excluded because the …

Cephalosporin-Associated Hypoprothrombinemia: Case and Review of the Literature

Objective: To present a case of cefotetan-associated hypoprothrombinemia and to review the literature concerning cephalosporin-associated hypoprothrombinemia. Data Sources: Information was collected by conducting a MEDLINE search for cases, clinical trials, reviews, and other articles pertaining to cephalosporin use and the development of hypoprothrombinemia. Study Selection: Studies, cases, and letters were selected if they addressed the development of hypoprothrombinemia in cephalosporin-treated patients. Data Synthesis: A case of hypoprothrombinemia is described in an 82-year-old woman who received cefotetan for the treatment of a urinary tract infection. A review of the literature revealed more than 50 reported cases and multiple clinical studies evaluating this adverse effect. The postulated mechanism behind this occurrence is the inhibition of the synthesis of vitamin K-dependent clotting factors by the N-methyl-thiotetrazole (NMTT) moiety found in certain cephalosporin side chains. Risk factors associated with the development of this adverse effect include advanced age, renal and hepatic impairment, recent surgical procedures, malnutrition, and the use of H2-antagonists. Conclusions: Cephalosporins containing the NMTT side chain are associated with the development of hypoprothrombinemia and possibly bleeding, especially in high-risk patients.