Ointments and transdermal nitroglycerin patches for stable angina pectoris

Summary Nitroglycerin (NTG) ointment is used for the prophylaxis against angina pectoris, but there are no data to support its effectiveness during long-term therapy. Continuous, once-daily application of isosorbide dinitrate cream produces tolerance with complete loss of efficacy within 1 week. Nitroglycerin patches are very popular and continuous once-daily application is still claimed by some investigators to provide 24 hour antiischemic and antianginal efficacy. This claim is based on data from postmarketing studies in a very large number of patients and placebo-controlled studies in smaller groups of patients from Italy, Yugoslavia, Greece, and Germany. In contrast, studies from the United States, Canada, England, and some centers in Germany have failed to show superiority of patches over placebo during continuous therapy. This controversy was addressed by the NTG cooperative study group, in which a total of 562 patients who were responders to sublingual nitroglycerin were studied. Patients received either placebo or NTG patches delivering low (15–30 mg/24 hr), moderate (45–60 mg/ 24 hr), or large (75 and 105 mg/24 hr) amounts of NTG. Four hours after the initial application, NTG patches increased exercise duration compared to placebo, but this beneficial effect had disappeared by 24 hours. Furthermore, after 8 weeks of continuous therapy, none of the NTG patches were superior to placebo, whether patients were or were not taking concomitant beta-blockers. Therefore, current opinion is that continous therapy with NTG patches produces pharmacologic tolerance and is ineffective. Pharmacologic tolerance can be minimized when patches are applied every morning and removed after 10–12 hours at night. However, patches delivering >15 mg NTG/24 hr are required to maintain an increased exercise duration for up to hour 8 after the patch application. Intermittent therapy with patches, however, may lead to rebound nocturnal angina in some patients. Also, intermittent therapy with patches has been associated with worsening of exercise performance in the morning prior to the patch renewal, compared to therapy with placebo patches. This has been referred to as the zero-hour effect and probably represents a rebound phenomenon following nitrate withdrawal. Patients experiencing either nocturnal or early morning angina during intermittent therapy with patches should either be switched to oral long-acting nitrates or should in addition be treated with a beta-blocker, provided there are no contraindications to beta-blocker treatment.The opinions expressed here are those of the authors and should not be taken as those of FDA.     

Hypertrophic cardiomyopathy: Management issues in the new millennium

Hypertrophic cardiomyopathy is an inherited cardiac disorder. Sudden cardiac death frequently occurs in otherwise healthy individuals, and accounts for nearly 35% of all sudden deaths within this age group. Although symptoms occur commonly, they often go unreported. Despite this, a degree of functional limitation is often seen on objective assessment. Management of hypertrophic cardiomyopathy is aimed at relieving symptoms, identifying and treating those individuals at increased risk of sudden death, and screening family members.     

Response of porcine lower esophageal sphincter to increasing intraabdominal pressure

The response of lower esophageal sphincter pressure to increasing intraabdominal pressure was investigated in six anesthetized pigs while measuring the intraabdominal pressure directly with a perfused catheter and recording continuously from the lower esophageal sphincter using a manometric catheter incorporating a constantly perfused sleeve. Studies were conducted both before and after the administration of intravenous atropine. Resting lower esophageal sphincter pressure was 8 mm Hg (3-19 mm Hg). In response to inflation of the peritoneal cavity with carbon dioxide gas, lower esophageal sphincter pressure rose significantly more than intraabdominal pressure whether the stomach was empty or full. In three of the six pigs, phasic lower esophageal sphincter pressure variations occurred as intraabdominal pressure increased. These variations were unrelated to respiration. Resting lower esophageal sphincter pressure was little affected by 75 micrograms/kg intravenous atropine which also had no effect on the lower esophageal sphincter response to increasing intraabdominal pressure. We conclude that, in the pig, the lower esophageal sphincter pressure increases more than the intraabdominal pressure in response to challenge and that excitatory cholinergic fibers do not mediate this response.     

Urinary organ specific neoantigen

Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A₄₀₅:0.717±0.500) vs 27 controls [0.121 ±0.273 (P<0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N=13), adenomas (N=26), inflammatory bowel disease (N=8), or having a normal colonoscopic examination (N=24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P<0.05). The presence of the Mr 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC.The work reported in this paper was supported in part by a grant from the Israeli Cancer Association and Tel Aviv University, and in part by grants from the Israel Cancer Association and the Sackler School of Medicine, Tel Aviv, Israel.     

Does Bone Wax Induce a Chronic Inflammatory Articular Reaction?

Background  

Bone wax is used to control femoral neck bleeding during open femoroacetabular impingement (FAI) surgery. Despite its widespread use, only a few case reports and small case series describe side effects after extraarticular use. It is unclear whether intraarticular use of bone wax leads to such complications. However, during revision FAI surgery, we have observed various degrees of articular inflammatory reactions.