Cardiac sarcoidosis with complete metabolic response and resolution of left ventricular dysfunction complicated by subsequent VT storm.

Sarcoidosis is a multisystem granulomatous disease of unknown aetiology that involves primarily the lungs and lymph nodes. Cardiac involvement is less common but associated with a poorer prognosis. With contemporary diagnostic modalities such as cardiac magnetic resonance and fluorine-18-fluoro-deoxy-glucose positron emission tomography computed tomography, cardiac involvement in sarcoidosis is increasingly diagnosed with appropriate therapy improving outcomes. Although steroid therapy may be protective or therapeutic in preventing left ventricular scarring and preserving LV function, it may not be as effective in the late stages of disease. (Chiu et al in Am J Cardiol 95:143-146, 2005) We present a case of cardiac sarcoidosis with significantly impaired ejection fraction that was diagnosed late in the course of disease with complete metabolic response to therapy and an improvement of LV function, but with a subsequent complication of ventricular tachycardia storm.

Updating national standards for drinking-water: a Philippine experience.

The latest version of the Philippine National Standards for Drinking-Water (PNSDW) was issued in 2007 by the Department of Health (DOH). Due to several issues and concerns, the DOH decided to make an update which is relevant and necessary to meet the needs of the stakeholders. As an output, the water quality parameters are now categorized into mandatory, primary, and secondary. The ten mandatory parameters are core parameters which all water service providers nationwide are obligated to test. These include thermotolerant coliforms or Escherichia coli, arsenic, cadmium, lead, nitrate, color, turbidity, pH, total dissolved solids, and disinfectant residual. The 55 primary parameters are site-specific and can be adopted as enforceable parameters when developing new water sources or when the existing source is at high risk of contamination. The 11 secondary parameters include operational parameters and those that affect the esthetic quality of drinking-water. In addition, the updated PNSDW include new sections: (1) reporting and interpretation of results and corrective actions; (2) emergency drinking-water parameters; (3) proposed Sustainable Development Goal parameters; and (4) standards for other drinking-water sources. The lessons learned and insights gained from the updating of standards are likewise incorporated in this paper.

[Influences on Placental Growth Factor (PlGF) and Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Concentration Levels at the Time of First Trimester Screening]. / Einflussfaktoren auf die placental growth factor (PlGF) und soluble fms-like tyrosine kinase-1 (sFlt-1) Konzentration im Rahmen des Erst-Trimester-Screenings.

INTRODUCTION: The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are significantly altered in preeclampsia with elevated sFlt-1 levels and low PlGF in the continuation of pregnancies. Furthermore, patients with preeclampsia reveal significantly low PlGF levels in the first trimester. MATERIAL AND METHOD: We performed a retrospective study including 161 patients during the first trimester screening between 11+0 and 13+6 weeks of gestation. In addition, we analyzed sFlt-1 und PlGF in maternal serum with a Roche Elecsys(®) System. RESULTS: The mean values for sFlt-1 were 1 247,11±545,84 pg/ml and 47,00±22,62 pg/ml for PlGF. There is a positive correlation between sFlt-1 and PAPP-A MoM (rS=0,681, p<0,001), and PlGF and PAPP-A MoM (rS=0,465, p<0,001), respectively. There was a negative correlation between sFlt-1 and maternal body mass index (rS=-0,225, p=0,005). Overweight patients had significantly lower sFlt-1 values than patients with normal weight (p=0,003). PlGF and the crown-rump-length of the fetus showed a positive correlation (rS=0,27, p<0,001), whereas PlGF and the Pulsatility Index of the uterine arteries were negative correlated (rS=-0,235; p=0,012). Patients with a preexistent diabetes mellitus had significantly low sFlt-1 und PlGF (p<0,05) values. Smokers had significantly elevated PlGF-values (p<0,001). CONCLUSION: sFlt-1 and PlGF are influenced by various factors during the first trimester of pregnancy which can be relevant for correct interpretation. Further prospective studies may be necessary to validate our results. The aim should be to establish sFlt-1 and PlGF MoM values to allow for integration into a screening for preeclampsia in the first trimester.

Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) of actinic keratosis (AK) has shown preliminary efficacy and safety results comparable to conventional photodynamic therapy (c-PDT), using methyl aminolevulinate (MAL) cream. OBJECTIVES: To demonstrate the efficacy and safety of DL-PDT vs. c-PDT in treating mild facial/scalp AK. MATERIALS AND METHODS: This 24-week randomized, controlled, investigator-blinded, multicentre, intra-individual efficacy (non-inferiority) and safety (superiority regarding pain) study enrolled 100 subjects. AKs on the face/scalp were treated once, with DL-PDT on one side and c-PDT on the contralateral side. Primary end points for DL-PDT at week 12 were efficacy [non-inferiority regarding complete lesion response (mild AK)] and safety (superiority regarding subject's assessment of pain). Lesions with complete response 12 weeks after one treatment session were followed until week 24. The safety evaluation included incidence of adverse events. Subject satisfaction was classified using a questionnaire. RESULTS: At week 12, the complete lesion response rate with DL-PDT was non-inferior to c-PDT (89·2% vs. 92·8%, respectively; 95% confidence interval -6·8 to -0·3), confirmed by intention-to-treat analysis. Additionally, regardless of the treatment used, 96% of mild lesions were maintained in complete response 24 weeks after the PDT session. For DL-PDT, subject-reported pain was significantly lower (0·8 vs. 5·7, respectively; P < 0·001), with better tolerability and significantly higher subject satisfaction regarding convenience and outcome. CONCLUSIONS: Daylight-mediated PDT was not inferior in efficacy to Metvix c-PDT (mild AK response rate), better tolerated, nearly painless and more convenient for patients.

Autologous breast reconstruction in older women: A retrospective single-centre analysis of complications and uptake of secondary reconstructive procedures.

BACKGROUND: Women aged ≥65 years have the highest age-specific rates of breast cancer incidence in the UK. However, national audit results demonstrate that the rates of post-mastectomy breast reconstruction offered to and performed on this age group are considerably lower than in younger women (Jeevan, 2009). This discrepancy may arise from unsubstantiated concerns over greater medical and surgical risk in older patients (James, 2015). In the present study, the first of its kind in the UK, we sought to evaluate potential differences in postoperative complications following autologous breast reconstruction between young and older patient populations. METHODS: We conducted a retrospective review of 59 patients (31 'younger' <65 years; 28 'older' ≥65 years) who underwent autologous breast reconstruction at Oxford University Hospitals, between 2008 and 2017. Clinical, operative, and outcome variables were compared across the two age groups. To examine the complete multi-stage process of breast reconstruction as a whole, we also compared rates of uptake of multiple secondary reconstructive and revisional procedures across age groups. KEY RESULTS: Major surgical, minor surgical, and medical complication rates, as well as length of stay, did not differ significantly by age group. The scar revision rate (at the flap donor site) was higher in the <65 group (19.4% vs. 0.0%; p = 0.025). Otherwise, rates of secondary reconstructive and revisional procedures were comparable across both groups. CONCLUSION: Patients aged ≥65 years were not at a significantly greater risk of complications following autologous breast reconstruction compared to younger patients. Chronological age, in itself, should not influence treatment decisions surrounding breast reconstruction.

Patterns of middle-ear cholesteatoma and implications for surgical approach.

OBJECTIVES: Understanding the pattern of middle-ear cholesteatoma becomes pertinent with the rise of endoscopic surgery as surgeons decide on the optimal approach to visualise and extirpate disease. With modifications to the Telmesani attic-tympanum-mastoid staging system, this study aimed to evaluate the commonest patterns of middle-ear cholesteatoma and their implications for surgical approach. METHODS: A retrospective study was conducted in a single tertiary institution in Singapore. All patients undergoing cholesteatoma surgery between January 2012 and June 2015 were included. Staging of cholesteatoma was based on clinical assessment corroborated by radiological findings. RESULTS: Out of the 55 ears included, 98.2 per cent had cholesteatoma involving the attic. The disease extended into the mastoid antrum and beyond in 43 cases (78.2 per cent). The facial recess and/or sinus tympanum was affected in 26 cases (47.3 per cent). CONCLUSION: The majority of cholesteatoma cases present with extensive attic disease and significant mastoid involvement. In these cases, endoscopes may be best suited to adjunctive rather than exclusive use in surgery.

Miss rate for colorectal neoplastic polyps: a prospective multicenter study of back-to-back video colonoscopies.

BACKGROUND AND STUDY AIM: Polyp miss rates during colonoscopy have been calculated in a few tandem or back-to-back colonoscopy studies. Our objective was to assess the adenoma miss rate while limiting technique or operator expertise biases, i. e. by performing a large multicenter study, with same-day back-to-back video colonoscopy, done by two different operators in randomized order and blinded to the other examination. PATIENTS AND METHODS: 294 patients at 11 centers were included. Among the 286 analyzable tandem colonoscopies, miss rates were calculated in both a lesion- and patient-based analysis. Each of these rates was determined for polyps overall, for adenomas, and then for lesions larger than 5 mm, and for advanced adenomas. Univariate and logistic regression analysis were performed to define independent variables associated with missed polyps or adenomas. RESULTS: The miss rates for polyps, adenomas, polyps > or = 5 mm, adenomas > or = 5 mm, and advanced adenomas were, respectively, 28 %, 20 %, 12 %, 9 % and 11 %. None of the masses with a carcinomatous (n = 3) or carcinoid component (n = 1) was missed. The specific lesion miss rates for patients with polyps and adenomas were respectively 36 % and 26 % but the corresponding rates were 23 % and 9.4 % when calculated for all 286 patients. The diameter (1-mm increments) and number of polyps (> or = 3) were independently associated with a lower polyp miss rate, whereas sessile or flat shape and left location were significantly associated with a higher miss rate. Adequacy of cleansing, presence of diverticula, and duration of withdrawal for the first procedure were not associated with adenoma miss rate. CONCLUSIONS: We confirm a significant miss rate for polyps or adenoma during colonoscopy. Detection of flat polyps is an issue that must be focused on to improve the quality of colonoscopy.

Secondary Analysis of Existing Datasets for Dementia and Palliative Care Research: High-Value Applications and Key Considerations.

OBJECTIVE: To provide a guide to researchers selecting a dataset pertinent to the study of palliative care for people with dementia and to aid readers who seek to critically evaluate a secondary analysis study in this domain. BACKGROUND: The impact of dementia at end-of-life is large and growing. Secondary dataset analysis can play a critical role in advancing research on palliative care for people with dementia. METHODS: We conducted a broad search of a variety of resources to: 1. identity datasets that include information germane to dementia and palliative care research; 2. review relevant applications of secondary dataset analysis in the published literature; and 3. explore potential validity and reliability concerns. RESULTS: We synthesize findings regarding: 1. Methodological approaches for determining the presence of dementia; 2. Inclusion and measurement of key palliative care items as they relate to people with dementia; and 3. Sampling and study design issues, including the role and implications of proxy-respondents. We describe and compare a selection of high-value existing datasets relevant to palliative care and dementia research. DISCUSSION: While secondary analysis of existing datasets requires consideration of key limitations, it can be a powerful tool for efficiently enhancing knowledge of palliative care needs among people with dementia.

Arteriovenous malformation and thyroid metastasis from underlying renal cell carcinoma, an unusual presentation of malignancy: A case report.

Renal Clear Cell Carcinoma (RCC) comprises over 80% of renal malignancies in adults. Thyroid gland metastasis is rare in RCC. Few studies have described cases of RCC mistaken for benign arteriovenous malformation (AVM). To the best of our knowledge, an AVM arising from underlying RCC metastasis to the brain has not yet been reported. The current study presents a case of RCC metastasis to the thyroid gland, with an AVM identified to be a result of metastatic involvement in the brain. A 45-year-old African-American female presented with left-sided weakness, slurred speech, facial droop and seizure. The patient's medical history was notable for a diagnosis of RCC, 2010 American Joint Committee on Cancer Tumor-Node-Metastasis Stage 1B (T1B, N0, M0) grade III status post-right partial nephrectomy. Computed tomography (CT) imaging revealed a soft-tissue mass, suspected to be metastasis, in the left lobe of the thyroid, in addition to a 1.9 cm right intracranial mass in the parietal lobe. Positron emission tomography/computed tomography revealed a hypermetabolic area in the thyroid. Fine needle aspiration of the thyroid, and subsequent histopathological analysis, suggested a diagnosis of RCC metastasis. Subsequent immunohistochemical analysis of the thyroid tumor confirmed RCC metastasis. The patient also underwent a right partial craniotomy with resection of the intra-axial mass. Initial pathology was suggestive of an AVM. After several months, the patient was readmitted with headache, nausea and vomiting. Repeat imaging revealed recurrence of a 3.9 cm mass that was negative for AVM on biopsy; however, the immunostaining markers were positive for RCC. Recent literature suggests a link between AVMs and RCC as each exhibit highly vascular characteristics. RCC is a particularly vascular tumor that has been demonstrated to lead to the abnormal expression of various angiogenesis-promoting growth factors, including vascular endothelial growth factor. These angiogenic factors are vital to the pathophysiological pathway involved in the tumorigenesis and progression of RCC, and may explain the development of AVMs within these neoplasms, as demonstrated in the case presented in the current study.

Oesophageal-impacted denture requiring open surgery.

The successful removal of impacted denture in the oesophagus in a patient is reported, with a review of the literature. A 36-year-old Malay man complained of dysphagia after swallowing his denture. Following unsuccessful attempts at removal via a rigid oesophagoscope, open surgery was performed. Without further delay, the impacted denture was removed by cervical oesophagotomy, and the patient recovered uneventfully. Oesophageal foreign bodies are usually removed by endoscopy. However, in situations where this appears potentially hazardous, such as with impacted denture, open surgical extraction that is promptly performed is a safe option.

Translocation and binding of adenine nucleotides by rat liver mitochondria partially depleted of phospholipids.

1. Rat liver mitochondria were partially depleted of their phospholipids using phospholipase A prepared from porcine pancreas (substrate specificity, cardiolipin greater than phosphatidylethanolamine greater than phosphatidylcholine) or from Crotalus adamanteus venom (substrate specificity, phosphatidylethanolamine = phosphatidylcholine greater than cardiolipin). 2. Removal of only about 1% of the mitochondrial phospholipid with the pancreatic enzyme leads to 50% and 25% losses in ADP and ATP translocation, respectively. Concomitant with the loss in translocation is a decline in the ability of both carbonylcyanide m-chlorophenylhydrazone and Ca2+ to stimulate ATP translocation. 3. To achieve comparable losses in ADP and ATP translocation with the venom enzyme, it is necessary to remove about 8% of the total mitochondrial phospholipid. Following such treatment, carbonylcyanide m-chlorophenylhydrazone and Ca2+ are still capable of stimulating ATP translocation. 4. Control experiments involving treatment of the mitochondria with the products of phospholipase digestion indicate that the effects observed on the translocase reflect a loss of phospholipid from the membrane. 5. Binding studies indicate that the loss in adenine nucleotide translocation following phospholipase treatment cannot be accoundted for by an altered ability to bind adenine nucleotides to atractyloside-sensitive sites. 6. The data are interpreted in terms of a mechanism of adenine nucleotide translocation involving a lipoprotein carrier system, consisting of the translocator protein and phospholipids, possibly cardiolipin and phosphatidylethanolamine.

Left ventricular dyskinesia in infarction and angina.

In 29 patients, the site and extent of coronary artery obstruction were related to the position and area of abnormally contracting segments of the left ventricle, both in patients with a history of angina without myocardial infarction (group I) and in patients with prior documented myocardial infarction (group II). The degree of coronary artery obstructive disease was estimated in the standard manner and also by a coronary artery index which considered not only the degree of obstruction but also the total length of the obstructed segment. A kinetic or dyskinetic segments were present in 22 of the 29 patients. An abnormally contracting segment was present in 12 or 18 patients without prior myocardial infarction in comparison with 10 of the 11 patients with prior infarction. Complete obstruction of a coronary vessel and resultant dyskinesia were more frequent in the right coronary artery than in either the left anterior descending or the circumflex artery. There was a significant correlation between total per cent of vessel obstruction and degree of ventricular asynergy in both groups; consideration of length of obstructed segment did not improve this correlation.

Significance of reduced regional myocardial blood flow in asynergic areas evaluated with intervention ventriculography. Results of studies combining washout of xenon-133 and postextrasystolic potentiation.

Nineteen patients with coronary artery disease were studied to determine the significance of reduced regional myocardial blood flow (50 ml/min per 100 g or less) in areas of abnormal wall motion. Regional myocardial blood flow was measured in four regions of the left ventricle with an Anger camera after the injection xenon-133 into the left main coronary artery. Abnormal wall motion was evaluated with biplane left ventriculography at rest and during postextrasystolic potentiation, a potent inotropic stimulus. Abnormal wall motion was defined as hemiaxis shortening of less than 20 percent. Four hemiaxes were designated as corresponding to the four regions of myocardial blood flow. Of 76 hemiaxes evaluated in the 19 patients, 54 manifested normal wall motion and 22 abnormal wall motion; 8 of the 22 hemiaxes had reduced regional myocardial bood flow. In these 8, hemiaxis shortening increased 6 +/- 2 percent (mean +/- standard error of the mean) above values at rest during postextrasystolic potentiation (with normalization of hemiaxis shortening in only 1 of the 8), compared with an increase of 19 +/- 4 percent (P less than 0.001) in the 12 hemiaxes with borderline regional myocardial blood flow (with normalization of hemiaxis shortening in 9 of the 12, P less than 0.05). These results indicate that the presence of reduced regional myocardial blood flow in areas of abnormal wall motion usually predicts a poor response to post-extrasystolic potentiation, whereas abnormal wall motion without reduced regional myocardial blood flow usually predicts a good response. The combination of reduced regional myocardial blood flow and abnormal wall motion suggests scarred and nonviable myocardium.

Effect of Coronary Collateral Vessels on Regional Myocardial Blood Flow in Patients With Coronary Artery Disease.

The effect of radiographically graded coronary collateral vessels on regional myocardial blood flow was evaluated with intracoronary injection of xenon-1233 at rest and during contrast agent-induced coronary hyperemia in 24 patients with coronary artery disease. Eleven patients had no coronary collateral vessels demonstrated radiologically, whereas 13 had such vessels. In 7 of the 13 these were high grade and noncompromised, whereas in 6 they were of lesser grade. Regional myocardial blood flow at rest in patients with and without collateral channels was similar and increased during hyperemia. However, the increase in flow was significantly greater in the patients with high grade noncompromised collateral vessels than in those with lesser grade collateral vessels (80 +/- 16 versus 31 +/- 9 plercent, p < 0.05). To evaluate the functional significance of the high grade noncompromised collateral vessels against that of vessels of lesser grade, various indexes of global and regional ventricular function were compared in the 13 patients in the present study, as well as in 24 patients whose collateral vessels had been subjected to similar grading systems in previous studies of regional myocardial blood flow. There were no significant differences in degree of regional asynergy, ejection fraction or left ventricular end-diastolic pressure between the patients with high and lower grades of collateral vessels. Thus, high grade noncompromised collateral vessels do not appear to have a beneficial effect on resting left ventricular function despite their enhanced vasoldilatory reserve.

Effect of direct revascularization surgery on coronary collateral circulation in man.

In 63 consecutive patients with significant coronary artery disease (more than 75 percent stenosis), the effects of direct myocardial revascularization on coronary collateral channels were studied 6 to 29 days (mean 13.4 days) after operation. Collateral vessels were identified preoperatively and their angiographic regression or reappearance after operation was noted. In 15 patients (23 percent), there was no evidence of collateral flow before or after operation. The remaining 48 patients had 186 collateral channels preoperatively. Postoperatively, 84 (45 percent) of these collateral vessels were no longer apparent, 75 (40 percent) were unchanged and 27 (15 percent) were identical with the preoperative vessels but the pattern of blood flow was reversed. The findings suggest that in the presence of established collateral channels, direct revascularization acutely alters existing flow and pressure gradients in a complex manner. Collateral channels disappear or remain unchanged when a gradient is decreased or maintained; collateral flow is reversed when a gradient is increased. These data may permit (1) objective preoperative estimation of distal vessel runoff in vessels with collateral channels, and (2) evaluation of the completeness of revascularization in assessing long-term postoperative results.

Effect of sublingually administered nitroglycerin on regional myocardial blood flow in patients with coronary artery disease.

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drug's effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.

Regional myocardial blood flow during hyperemia induced by contrast agent in patients with coronary artery disease.

Regional myocardial specific blood flow (regional specific flow) was measured at rest and during contrast hyperemia after the intracoronary injection of xenon-133. The changes in regional specific flow were transient, resulting in some compromise in one of the underlying restraints of the inert gas washout method, namely, the presence of a steady state. Therefore, to determine the clinical utility of this technique, regional specific flow values obtained with this method were correlated with the presence and severity of coronary artery disease as assessed from the coronary arteriogram and left ventriculogram. Regional specific flow during contrast hyperemia was 186+/- 11 (mean +/- 1 standard error of the mean) ml/min per 100 g in control patients and 115+/-5 in patients with coronary artery disease. There was an inverse relation between regional specific flow during contrast hyperemia and the percent coronary stenosis when the stenosis was 40 percent or greater (r = 0.70, P less than 0.001). Regional specific flow was significantly less in patients with asynergy (77 +/- 10 ml/min per 100 g) than in patients with normal ventricular function (105 +/- 5) distal to coronary stenoses of greater than 75 percent. Thus regional specific flow measured during contrast hyperemia using the xenon washout technique and the Anger camera differentiated patients with normal coronary arteriograms from those with coronary artery disease. With this technique, good correlation was shown between regional specific flow and the percent coronary stenosis and presence of ventricular wall abnormalities. The information obtained with this method may provide prognostic information concerning suitability for surgical intervention.

Correlation of minimum coronary lumen diameter with left ventricular functional impairment induced by atrial pacing.

To understand whether quantitative measurement of minimal coronary luminal diameter is a better method than percent diameter narrowing for assessing the functional impairment of myocardial contractility produced by coronary artery stenoses, measurements were made from 37 stenotic segments in 27 patients with coronary artery disease and from corresponding segments in 10 subjects without coronary artery narrowing. An assessment of the reliability of the 2 types of measurements was made by correlating them with the physiologic parameters of both segmental wall motion and global ejection fraction response induced by atrial pacing. Digitally acquired coronary angiograms were used to facilitate quantitative analysis. Measurements by edge detection and videodensitometry correlated closely (r = 0.94). Percent diameter narrowing correlated moderately with the change in ejection fraction (r = -0.41) or with the change in segmental wall motion (r = -0.44). The measurement of minimal lumen diameter correlated with the change in global ejection fraction (r = 0.61) and did so even better with the change in segmental wall motion (r = 0.78, p less than 0.05). A minimal lumen diameter of less than or equal to 1.5 mm identified patients likely to have a functional impairment during atrial pacing as assessed by either global ejection fraction or segmental wall motion defects. We conclude that minimal coronary luminal diameter provides a better method than percent diameter narrowing calculations to measure the anatomic severity of coronary artery narrowing.

The capacity of a combined liposomal hepatitis B and C vaccine to stimulate humoral and cellular responses in mice.

Combined hepatitis B surface antigen and hepatitis C antigen were encapsulated into 1, 2, and 5 microm discrete liposomes and then lyophilized. Groups of adolescent CD-1 mice were given a single 0.3 mL oral dose of these liposomes containing 50 microg/mL hepatitis B surface antigen and hepatitis C antigen, 50 microg/mL of the same antigens or liposomes alone. Animals in each group were sacrificed every 2 weeks for 10 weeks and the humoral response investigated by enzyme-linked immunosorbent assay (ELISA) and the cellular response by splenic lymphocyte proliferation to 10 microg of either antigen. Seroconversion to both antigens in the mice receiving liposomal antigens occurred in 87.5% of animals sacrificed at 4 weeks and later. One animal (12.5%) receiving antigen alone seroconverted to hepatitis B virus at 6 weeks, but all animals receiving liposomes alone remained negative. Proliferation indexes (PI) greater than 3 were observed in all animals receiving liposomal antigens, with the greatest response seen at 10 weeks. PI was less than 2 for all animals in the other two groups. Thus, a single oral dose of liposomes of three sizes containing both hepatitis B and C antigens given to mice resulted in rapid seroconversion and a progressive robust cellular immune response, whereas the antigens alone or liposomes without antigen did not.

A randomized double-masked crossover study comparing latanoprost 0.005% with unoprostone 0.12% in patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE: To compare the intraocular pressure)-lowering effect and side effects of latanoprost 0.005% once daily with unoprostone 0.12% twice daily. METHODS: Sixty patients with primary open-angle glaucoma or ocular hypertension were randomized to receive either latanoprost once daily in the evening and placebo once daily in the morning, or unoprostone twice daily in the morning and evening. The study was double masked and followed a crossover design with two treatment periods of 1 month separated by a 3-week washout period. The intraocular pressure was measured at 9 AM and 5 PM on the baseline and day 28 visits, and at 9 AM on day 2 and day 14 visits of each treatment period. The 9 AM measurement was taken 2 hours and 13 hours after the last drop of unoprostone and latanoprost, and the 5 PM measurement was at 10 and 21 hours, respectively. The mean of the measurements was calculated. Safety parameters were also recorded. RESULTS: Fifty-six patients completed both treatment periods and had intraocular pressure data available for evaluation. After 1 month of treatment, latanoprost significantly reduced intraocular pressure (mean +/- SEM) by 6.1 +/- 0.5 mm Hg (P <.001) and unoprostone by 4.2 +/- 0.4 mm Hg (P <.001) adjusted from an overall baseline of 22.3 +/- 0.5 mm Hg and 23.2 +/- 0.4 mm Hg, respectively. The difference of 1.9 mm Hg between treatments was statistically significant in favor of latanoprost [P =.003, analysis of covariance (ANCOVA)]. Unadjusted analysis of responders using the percentage decrease in intraocular pressure showed that the proportion of responders in the latanoprost-treated group was greater than in the unoprostone-treated group. Adverse ocular symptoms and findings were mild in both treatment groups. Eye redness and ocular irritation were the most frequently reported events. CONCLUSIONS: Latanoprost once daily was significantly more effective in reducing intraocular pressure compared with unoprostone twice daily after 1 month of treatment in patients with primary open-angle glaucoma and ocular hypertension. Both drugs were well tolerated with few ocular adverse events.