Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy--a prospective, randomised, double-blind trial.

BACKGROUND: Peristomal infection can sometimes complicate percutaneous endoscopic gastrostomy (PEG) placement. Antibiotic prophylaxis has, in some studies, been shown to reduce the incidence. However, the use of prophylaxis varies widely, possibly because the design and findings of the studies have differed, making their relevance to clinical practice difficult to interpret. AIM: To determine the efficacy of antibiotics, either prophylaxis or concurrent antibiotics at the time of the procedure, in reducing peristomal infection after PEG insertion in the context of a study designed to reflect current practice. METHODS: One hundred and forty-one patients undergoing PEG placement were randomised to group one to receive either a single dose of 750 mg of intravenous cefuroxime (n=50) or placebo (n=51) 30 min before PEG insertion. Forty patients who, for various reasons, were already receiving antibiotics were allocated to group two. The peristomal site was evaluated on day 3, 5 and 7 following insertion. Erythema and exudate were scored on a scale from 0 to 4; induration was scored on a scale of 0-3. A maximum combined score of 8 or higher or the presence of pus was criteria for infection. The primary outcome measure was the occurrence of a peristomal wound infection at any time within one week of PEG insertion. RESULTS: Peristomal wound infection was significantly reduced in patients who received antibiotics either as a single dose of cefuroxime [one of 33 (3%)], or in those on antibiotics for prior indications [one of 36 (3%)], compared with placebo [six of 33 (18%)], P=0.04 and 0.03, respectively. CONCLUSION: Antibiotics, either prophylaxis or concurrent, reduce the incidence of peristomal wound infection after PEG placement.

Crohn's disease incidence in Cardiff from 1930: an update for 1991-1995.

OBJECTIVE: To report the incidence of Crohn's disease in the city of Cardiff between 1991 and 1995, in relation to the data of the preceding 65 years. METHODS: The incidence of Crohn's disease was studied by collecting information from clinical records, the department of pathology database and a questionnaire sent to local family practitioners. RESULTS: Eighty-four new patients with Crohn's disease, and resident in Cardiff, were diagnosed between 1991 and 1995. The mean incidence for this quinquennium was 56 cases per 10(6) population per year (95% confidence interval, 44-68). There was a female predominance, particularly in young adults, with an overall male to female ratio of 0.47. Colorectal disease was the most common site of disease at the time of diagnosis. CONCLUSIONS: In relation to the findings of our previous studies, the data suggest that the overall incidence of Crohn's disease is now stable, but that the proportion with colorectal disease continues to increase and there is a marked female preponderance in Crohn's disease presenting in young people.

A comparison of two rapid whole-blood tests and laboratory serology, in the diagnosis of Helicobacter pylori infection.

OBJECTIVE: To compare two rapid whole-blood serology tests for Helicobacter pylori and a laboratory serology assay against a gold standard. DESIGN: Prospective comparison of tests in 81 patients. SETTING: A hospital rapid access endoscopy clinic. PARTICIPANTS: Dyspeptic patients requiring assessment of H. pylori status. INTERVENTIONS: Measurement of H. pylori antibody status by Quickvue One-step, Helisal, and Premier H. pylori test; 13C urea breath test for H. pylori, and gastric biopsies for histology, culture and rapid urease test. MAIN OUTCOME MEASURE: Sensitivity and specificity of Quickvue One-step, Helisal and Premier tests, compared to a gold standard based on 13C urea breath test, biopsy culture, histology and urease test. RESULTS: The Quickvue assay has significantly greater sensitivity (81%) than Helisal (67%), but without appreciable loss of specificity (86% and 93%, respectively). The Premier laboratory assay is significantly more sensitive than both of the rapid blood tests (96%), with comparable specificity to the Quickvue assay. CONCLUSION: The rapid serology tests used in this study are quick and convenient to use, but do not approach the sensitivity of a laboratory assay in detecting H. pylori status in this group of dyspeptic patients attending an endoscopy clinic.

Chemotherapy rapidly alternating with accelerated radiotherapy for advanced carcinoma of the uterine cervix.

The objective of this study was to determine the feasibility of treating patients with advanced cervical carcinoma using a regimen combining chemotherapy with intermittent hyperfractionated teletherapy. Eight patients with advanced cervical carcinoma were treated with bleomycin, ifosfamide and cisplatin, followed by a 5-day course of hyperfractionated external radiation. Three such courses were given at 21-day intervals. Treatment was completed using standard brachytherapy. Seven of the eight patients were evaluable for response; all obtained a complete response. Two patients developed recurrence (one in the pelvis and one distant) and died of disease. One patient died of treatment complications. The remaining four remain alive and free of disease 9-42 months after treatment. The simultaneous use of chemotherapy and intermittent hyperfractionated teletherapy is a promising strategy for the treatment of cervical carcinoma, resulting in a high rate of complete response.

The etiology and management of diarrhea in the gynecologic oncology patient.

PURPOSE: We determined the etiology and evaluated the usefulness of diagnostic tests in 42 gynecologic oncology patients with diarrhea. METHODS: All inpatients who developed diarrhea during treatment for gynecologic cancer were prospectively evaluated during the 12-month study period ending June 1992. Diarrhea was defined as five or more loose stools per 24 hr lasting for 48 hr or more. Diagnostic tests were complete blood cell count; electrolytes; stool for occult blood, white blood cells, and Clostridia difficile toxin; and stool culture for Shigella, Salmonella, Yersinia, and Campylobacter. RESULTS: During the study period 351 women with gynecologic cancer received inpatient care. Forty-two (12%) patients developed diarrhea. One patient had three episodes and another had two episodes of diarrhea. There were 39 evaluable patients; 3 patients were excluded due to incomplete tests. The only cause of bacterial-associated diarrhea was C. difficile, which occurred in 4 of 39 (10.3%) patients. No patient had community-acquired diarrhea, and 1 patient had diarrhea due to Crohn's Disease. Surgery was performed on 265 patients; 29 of 265 (10.9%) developed postoperative diarrhea. Eighty-six patients had medical treatment and 13 (15.1%) developed diarrhea. The distribution by admission status of patients with diarrhea did not differ statistically from the patients without diarrhea. The four patients with C. difficile-associated diarrhea received appropriate therapy at the time of diagnosis. Nevertheless, the mean (SD) duration of C. difficile-associated diarrhea (342 (103) hr) was significantly longer than the mean (SD) duration of diarrhea not associated with this pathogen (79 (32) hr). The difference between the sample means is 263 hr with a 95% confidence interval for the difference between the means of 218 and 308 hr. Electrolyte abnormalities occurred in 20 patients (51%). Fecal leukocytes were present in 11 (28%) patients and occult blood in 5 (12.8%) of the 39 patients. Neither study was predictive for the presence of C. difficile. CONCLUSION: Hospital-acquired diarrhea in gynecologic oncology patients is common, although specific bacterial pathogens requiring antibiotic therapy account for only 10% of cases. Diagnostic tests for infectious causes besides C. difficile are infrequently useful and may be omitted unless the condition persists more than 72 hr.

Do we need second generation lithotripters in Hawaii?

The Kidney Stone Center of the Pacific (KSCoP) currently provides statewide services for kidney lithotripsy. The non-invasive technique uses shock waves to disintegrate kidney stones. Extracorporeal shock wave lithotripsy (ESWL) can be used successfully in 85% to 90% of kidney stone patients when surgery is indicated.

Incisional recurrence of squamous cell cervical carcinoma following operative staging.

A patient with FIGO Stage IIB cervical carcinoma underwent an extraperitoneal lymphadenectomy with exploratory laparotomy and washings for surgical staging. Intraperitoneal tumor was found. Seven months later, the tumor recurred as a subcutaneous nodule in the surgical incision. The implications of this recurrence are discussed.

Joint venture acquisition of expensive medical technology by Oahu hospitals. Planning, operations and impact of lithotripsy and magnetic resonance imaging.

Expensive diagnostic and treatment services and equipment are naturally suited to large, populous medical market areas, with sufficient forecasted service demand to justify the large investment in capital, construction and staffing. Only major tertiary or secondary medical centers with shared resources can justify the first-generation investment in the multimillion-dollar purchases of magnetic resonance imaging (MRI), megavoltage linear accelerators, or lithotripters. The regional referral system in most nations accommodates the outlying population in the less developed rural sectors.

A viable alternative to Medicare risk contracts and participation.

Throughout the 1980s, Medicare has 'turned against its service suppliers' and began to literally rewrite the rules of the health insurance game. This paper is set in that changing environment and describes one supplier's response.

Coronary artery-left ventricular communications: a report of two cases and review of the literature.

Two patients with chest pain had angiographically-demonstrated communications between the three coronary arteries and the left ventricular chamber. Communications between coronary arteries and the left ventricle are unusual and communications between all three coronary arteries and the left ventricle are rare. These anomalies are, however, commonly associated with symptoms of chest pain. The presence of left ventricular hypertrophy and a widened pulse pressure may suggest a greater hemodynamic effect of the shunt flow than often suspected angiographically.

Neuroleptic induced extrapyramidal symptoms.

All currently marketed neuroleptics induce extrapyramidal symptoms (EPS). These EPS are a function of biological sensitivity, neuroleptic molecular structure, dose, age, sex, and duration of neuroleptic treatment. Because of their association with EPS, at times irreversible, and their modest efficacy in the non-schizophrenic patients, neuroleptic administration should be limited predominantly to schizophrenic patients. Furthermore EPS should not be used as a guideline for the efficacy of neuroleptics as formerly assumed. For EPS may occur at subtherapeutic doses of neuroleptics and may be absent in patients experiencing clinical response. Neuroleptic dose should be the lowest efficacious dose required to provide symptom remission. In addition, antiparkinsonian (AP) agents should be administered predominently contraactively and not routinely in combination with neuroleptics. With the judicious administration of neuroleptic agents and AP medication, distressing EPS can be prevented or minimized, while providing control of schizophrenic symptoms.

Transient ST-segment elevation with postmyocardial infarction angina: prognostic significance.

Fifty-seven patients with acute myocardial infarction were observed for early postmyocardial infarction angina and associated transient ST-segment changes. Nine patients had postinfarction angina with transient ST-segment elevation (group 1), seventeen patients had postinfarction angina with ST-segment depression or no ST-segment changes (Group 2), and 31 patients had no postinfarction angina (Group 3). The patients in Group 1 had a statistically significant increased incidence of early reinfarction and death, when compared with the other two groups, singly or combined. There was no significant difference in the incidence of reinfarction and death when Group 2 is compared with Group 3. Patients with transient ST-segment elevation associated with early postmyocardial infarction angina may be an appropriate group in whom to consider newer, more aggressive modes of postinfarction management.