Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

Association Between Ocular Trauma and Activation of Ocular Toxoplasmosis.

PURPOSE: To evaluate the association between ocular trauma and activation of ocular toxoplasmosis. METHODS: Retrospective review of 686 patients with ocular toxoplasmosis and its association with trauma to the eye or the head within 1 week of activation. RESULTS: Ten patients with a history of trauma and activation of ocular toxoplasmosis were detected (10/686; 1.45%). Nine patients showed a primary focus of retinitis without a previous scar and one patient had a recurrent form of ocular toxoplasmosis. From these 10 patients, Toxoplasma IgG was positive in eight of them. The median age of the patients was 35.8 years-old (range 17 to 65). CONCLUSIONS: These cases suggest that trauma can be associated with activation of retinal bradyzoite cysts in ocular toxoplasmosis.

Surgery without papilla incision: tunneling flap procedures in plastic periodontal and implant surgery.

Diverse clinical advancements, together with some relevant technical innovations, have led to an increase in popularity of tunneling flap procedures in plastic periodontal and implant surgery in the recent past. This trend is further promoted by the fact that these techniques have lately been introduced to a considerably expanded range of indications. While originally described for the treatment of gingival recession-type defects, tunneling flap procedures may now be applied successfully in a variety of clinical situations in which augmentation of the soft tissues is indicated in the esthetic zone. Potential clinical scenarios include surgical thickening of thin buccal gingiva or peri-implant mucosa, alveolar ridge/socket preservation and implant second-stage surgery, as well as soft-tissue ridge augmentation or pontic site development. In this way, tunneling flap procedures developed from a technique, originally merely intended for surgical root coverage, into a capacious surgical conception in plastic periodontal and implant surgery. The purpose of this article is to provide a comprehensive overview on tunneling flap procedures, to introduce the successive development of the approach along with underlying ideas on surgical wound healing and to present contemporary clinical scenarios in step-by-step photograph-illustrated sequences, which aim to provide clinicians with guidance to help them integrate tunneling flap procedures into their daily clinical routine.

Development, psychometric evaluation and validation of a brief measure of emotional preoperative stress (B-MEPS) to predict moderate to intense postoperative acute pain.

BACKGROUND: Preoperative stress might influence postoperative pain, thereby, it is desirable to assess it more precisely. Thus, we developed and evaluated the psychometric properties of a brief measure of emotional preoperative stress (B-MEPS) index using Item Response Category Characteristic Curves. We validated and assessed whether the B-MEPS can predict moderate to intense acute postoperative pain (MIAPP). METHODS: We included 863 adult patients who underwent elective surgeries (ASA I-III physical status). The B-MEPS was constructed based on items selected from instruments to assess anxiety, depression, future self-perception and minor psychiatric disorders. We identified 24 items with greatest discriminant power to identify patients who should undergo surgery to treat cancer with MIAPP. The reliability was maximized using the Cronbach's alpha indices. Fifteen items remained, which were adjusted by the Generalized Partial Credit Model. The convergent validity was assessed correlating the B-MEPS index with the pain catastrophizing (n = 100). Finally, the B-MEPS was applied in a prospective cohort of patients who underwent an abdominal hysterectomy (n = 150). RESULTS: The Cronbach's alpha for selected items was 0.83. The correlation coefficient between B-MEPS index and catastrophizing was r = 0.37 (P < 0.01). A hierarchical regression model evidenced that the B-MEPS index was a factor independent to predict MIAPP after an abdominal hysterectomy [odds ratio (OR)=1.20, confidence interval (CI) 95% 1.05-1.43). CONCLUSIONS: The B-MEPS index presents satisfactory psychometric evaluations based on its internal consistency, convergent, and discriminant validity. The B-MEPS is a propensity index to MIAPP, which might help the clinician to decide on the best therapeutic approaches for acute postoperative pain.

Anaemia, Serum Iron Concentrations and δ-Aminolevulinate Dehydratase Activity in Laying Hens Infected Naturally by Salmonella Gallinarum.

The aim of this study was to evaluate anaemia, serum iron concentrations and δ-aminolevulinate dehydratase (ALA-D) activity in laying hens infected naturally by Salmonella Gallinarum and having severe hepatic lesions. Liver and serum samples were collected from 27 laying hens (20 infected and seven uninfected). The δ-ALA-D activity, haematocrit and serum iron concentrations were evaluated. There were significant decreases in δ-ALA-D activity, haematocrit and serum iron concentrations (P <0.01) in birds infected by S. Gallinarum when compared with uninfected birds. There was a positive correlation (P <0.001) between serum iron concentration, haematocrit (r(2) = 0.82) and δ-ALA-D activity (r(2) = 0.75). A positive correlation was also observed between δ-ALA-D activity and haematocrit (r(2) = 0.78; P <0.01). Liver samples showed moderate focal coagulative necrosis associated with infiltration of lymphoplasmacytic cells, macrophages and heterophils. The anaemia in the infected hens may be related to reduction in δ-ALA-D activity and serum iron concentrations, since both are important for haemopoiesis.

A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study.

BACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT01303679.

A comparison between monitoring and dispersion modeling approaches to assess the impact of aviation on concentrations of black carbon and nitrogen oxides at Los Angeles International Airport.

Aircraft activity and airport operations can increase combustion-related air pollutant concentrations, but it is difficult to distinguish aviation emissions from traffic and other local sources. Emission inventories are uncertain and dispersion models may not capture aircraft plume complexity; ambient monitoring data require detailed statistical analyses to extract aviation signals. The goal of this study is to compare two modeling approaches including monitoring-based regression models and the EDMS/AERMOD dispersion model, informing improvements and allowing quantitation of aviation impacts on air quality through multi-pollutant sensitivity and multi-monitor fate/transport analyses. Aggregate concentration comparisons are similar, though diurnal patterns show potential weaknesses in near-field dispersion, treatment of overnight conditions, and emission inventory accuracy.

Predictive value of hemoperitoneum for outcome of methotrexate treatment in ectopic pregnancy: an observational comparative study.

OBJECTIVE: To assess the predictive value of hemoperitoneum for the outcome of methotrexate (MTX) treatment of ectopic pregnancy (EP). METHODS: This observational prospective single-center study included women presenting with EP treated with MTX from November 2007 to November 2009. The percentage of women with hemoperitoneum at the beginning of MTX treatment was compared between two groups: those whose treatment was successful and those whose treatment failed. The rate of hemoperitoneum in each group and its value in predicting the outcome of MTX treatment of EP were assessed. RESULTS: MTX treatment was successful in 69 of 93 (74%) cases. The percentage of women with hemoperitoneum at the beginning of treatment was significantly higher in women in whom MTX treatment failed as compared to those in whom it was successful (15/24 (62.5%) vs 17/69 (24.6%); P = 0.001). The likelihood of requiring surgery following treatment with MTX was higher in women with hemoperitoneum (odds ratio, 5.1; 95% CI, 1.74-15.14). Study of the diagnostic performance of hemoperitoneum in predicting the need for surgical treatment after MTX treatment revealed a sensitivity of 0.63, a specificity of 0.76, a positive predictive value of 0.47 and a negative predictive value of 0.85. CONCLUSIONS: The presence of hemoperitoneum appears to be a risk factor for MTX treatment failure. It is important to inform women as fully as possible about the risk of such failure. Nonetheless, the predictive value of this sign is insufficient for either routinely excluding women with hemoperitoneum from MTX treatment or omitting post-treatment monitoring.

The effect of palm oil addition to the diet of dairy sheep on the immune response.

The aim of this study was to evaluate whether a diet based on palm oil has any influence on the immune response and on the number of eggs per gram of faeces (EPG) of gastrointestinal nematodes (GIN) in dairy sheep. To address this issue, 30 ewes in early lactation were confined and divided into three groups (n = 10) receiving a daily isoproteic and isoenergetic diet. Palm oil was added to the feed at different concentrations: 0% (control; group A), 4% (group B) and 6% (group C). The animals were treated with levamisole 10 days before the beginning of the experiment. Faecal samples were collected and analysed for EPG on day zero of the experiment. On days 60 and 120, individual faecal and blood samples were collected, and the FAMACHA(©) score for assessing clinical anaemia was carried out. The groups receiving palm oil showed a significant reduction in EPG in relation to the control group (A) on day 120. Serum immunoglobulin levels (IgG, IgM and IgE) and proinflammatory cytokine levels (TNF-α, IL-1 and IL-6) were significantly increased on days 60 and 120 (p < 0.05) in groups B and C. Therefore, these results suggest that palm oil stimulates the immune response in sheep, thus reducing EPG of GIN. The hypothesis that palm oil has direct anthelmintic activity should be tested in future studies.

Development of a geriatric vulnerability score in elderly patients with advanced ovarian cancer treated with first-line carboplatin: a GINECO prospective trial.

BACKGROUND: Two previous GINECO elderly specific studies in advanced ovarian cancer (AOC) patients highlighted the prognostic value of geriatric covariates for overall survival (OS). PATIENTS AND METHODS: This open-label prospective trial was designed to identify the impact of geriatric covariates on OS in AOC patients ≥70 years treated with first-line carboplatin. RESULTS: Geriatric covariates of the 111 patients included median age 79 years (≥80 years: 41%); performance status (PS) ≥2: 47%; ≥3 major comorbidities: 24%; ≥4 comedications: 68%; activities of daily living (ADL) score <6: 55%; instrumental activities of daily living (IADL) score <25: 69%; Hospital Anxiety and Depression Scale (HADS) >14: 37%. The median OS was 17.4 months. Overall, 74% of patients completed the six planned chemotherapy cycles. Grade 3-4 haematological toxic effects were frequent (50%) but manageable. Grade 3-4 non-haematological toxicities included fatigue (15%), anorexia (12%), infections (9%) and thrombosis (2%). A survival score = exp(0.327*GVS) was developed, where the geriatric vulnerability score (GVS) is the sum of the following (each assigned a value of one): albuminaemia <35 g/l; ADL score <6; IADL score <25; lymphopaenia <1 G/l; and HADS >14. With a cut-off ≥3, GVS discriminated two groups with significantly different OS, treatment completion, severe adverse events and unplanned hospital admissions rates. CONCLUSIONS: The GVS is a valuable tool for identifying vulnerable patients when treating an elderly AOC population.

First human treatment of resistant neoplastic meningitis by intrathecal administration of MTX plus (125)IUdR.

PURPOSE: Neoplastic meningitis is often the final outcome of disseminated cancer and is rapidly lethal. Its limited treatment relies on systemic or intrathecal chemotherapy with methotrexate (MTX) or thiotepa. When 5-iodo-2'-deoxyuridine labeled with (125)I ((125)IUdR) is incorporated into the DNA of mitotic tumor cells, the Auger electrons emitted during iodine decay are highly cytotoxic. The radiotherapeutic efficacy of (125)IUdR administered intrathecally has also been established in animals bearing spinal cord tumors, and MTX is known to potentiate the response. This approach has not been tested in the clinic. METHODS: A 44-year-old woman, with locally advanced pancreatic cancer, was treated for three years with complete systemic remission, but then relapsed with cytologically proven neoplastic meningitis. The patient was given four successive intrathecal injections of MTX (10 mg) every 12 h and, with the fourth dose, 1850 MBq (125)IUdR, followed by four additional MTX doses. The response was monitored by cytology and CA19.9 (carbohydrate antigen 19.9) levels in the cerebrospinal fluid (CSF) as well as by clinical status of the patient. RESULTS: The follow-up of cytology and CA19.9 levels in the CSF showed dramatic improvement within 26 days followed by a biological relapse on Day +36. There was no evidence of local central nervous system toxicity. Three months later, neoplastic meningitis recurred and meningeal tumor infiltration was observed on magnetic resonance imaging. Six months after MTX-(125)IUdR treatment, the patient died. CONCLUSION: (125)IUdR treatment proved to be feasible without acute neurological toxicity and seemed to have produced a biological response. This attempt provides the basis for designing prospective clinical trials.

Antinociceptive effects of intracerebroventricular administration of guanine-based purines in mice: evidences for the mechanism of action.

It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines (GBPs) on pain transmission. The aim of this study was to investigate the effects of intracerebroventricular (i.c.v.) guanosine and GMP on mice pain models. Mice received an i.c.v. injection of vehicle (saline or 10 muM NaOH), guanosine (5 to 400 nmol), or GMP (240 to 960 nmol). Additional groups were also pre-treated with i.c.v. injection of the A(1)/A(2A) antagonist caffeine (15 nmol), the non-selective opioid antagonist naloxone (12.5 nmol), or the 5'-nucleotidase inhibitor AOPCP (1 nmol). Measurements of CSF purine levels and cortical glutamate uptake were performed after treatments. Guanosine and GMP produced dose-dependent antinociceptive effects. Neither caffeine nor naloxone affected guanosine antinociception. Pre-treatment with AOPCP completely prevented GMP antinociception, indicating that conversion of GMP to guanosine is required for its antinociceptive effects. Intracerebroventricular administration of guanosine and GMP induced, respectively, a 180- and 1800-fold increase on CSF guanosine levels. Guanosine was able to prevent the decrease on cortical glutamate uptake induced by intraplantar capsaicin. This study provides new evidence on the mechanism of action of GBPs, with guanosine and GMP presenting antinociceptive effects in mice. This effect seems to be independent of adenosine and opioid receptors; it is, however, at least partially associated with modulation of the glutamatergic system by guanosine.

Carboplatin/cyclophosphamide or carboplatin/paclitaxel in elderly patients with advanced ovarian cancer? Analysis of two consecutive trials from the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens.

BACKGROUND: To determine the feasibility of two chemotherapy regimens in elderly patients with advanced ovarian carcinoma (AOC). PATIENTS AND METHODS: Eighty-three patients >or=70 years were previously enrolled in a trial evaluating carboplatin and cyclophosphamide (CC). On the basis of identical eligibility criteria, 75 further patients were enrolled in a trial evaluating carboplatin and paclitaxel (Taxol) (CP). The primary end point of these studies was the feasibility of six courses of chemotherapy. Comprehensive geriatric assessment (CGA) parameters were assessed in terms of prognostic factors. RESULTS: More patients in the CC group presented with performance status of two or more, depression symptoms, use of co-medications, hypoalbuminemia, abnormal Mini-Mental Status score, or sub-optimal surgery. Both regimens appeared feasible: 75.6% in the CC group and 68.1% in the CP group completed six courses. CC and CP groups had similar overall survival (OS). Independent prognostic factors of poorer OS were the following: increasing age (P = 0.013), depression symptoms at baseline (P < 0.001), International Federation of Gynecology and Obstetrics stage IV (P = 0.001), and use of paclitaxel (P = 0.025). CONCLUSION: As this is a non-randomised retrospective review of two consecutive studies, no firm conclusion can be drawn. It seems, however, that in elderly patients with AOC the use of paclitaxel results in more toxicity. CGA parameters and particularly emotional disorders might help to determine a priori the risk/benefit ratio of chemotherapy in this patient population.

[Treatment of malignant intestinal obstruction. A prospective study over 80 cases]. / Traitement de l'occlusion intestinale sur carcinose péritonéale. Etude prospective à propos de 80 cas.

AIM: Of the work: evaluation of a multidisciplinary strategy and a prospective medicosurgical protocol for the treatment of occlusion due to unresectable peritoneal carcinomatosis. PATIENTS AND METHODS: All the included patients had occlusion and intraabdominal carcinomatosis. None could benefit a curative treatment. 75 patients were included for 80 episodes of intestinal obstruction. The protocol involved three successive therapeutic phases. (i) Treatment during five days by corticosteroids associated to antiemetic agents, anticholinergic antisecretory agents, and analgesics as needed (Phase I); (ii) In the event of refractory occlusive symptoms treatment by somatostatin analog during 3 days (phase II); (iii) If this treatment was ineffective a gastrostomy was performed (phase III). RESULTS: Median survival was 31 days. Outcome showed that for the 80 episodes of obstruction, phase I medical treatment enabled relief in 50 cases (63%) and phase II medical treatment (somatostatin) enabled relief in 11 cases (14%). 10 more patients (13%) were relieved by the gastrostomie and one by a duodenal endoprothesis. Symptom control without a long-term nasogastric tube was achieved for 72 of the 80 episodes (90%). Fifty-eight episodes (72% of overall total) were controlled for 10 days or less. Median time to gastrostomy was 17 days. Eight patients experienced persistent vomiting and required a nasogastric aspiration until death. CONCLUSION: This multidisciplinary approach between Palliative Care and Specialized Medical and Surgical teams enabled relief of the occlusive symptoms for 90% of the patients of the study. The protocol was useful for the caregivers for the management of terminally ill patients. To enhance these results, it would be necessary to shorten the delay of relief, which has been longer than ten days for one third of the patients. The simplification of the protocol including two steps instead of three is on study.

Estradiol induces hypothalamic progesterone receptors but does not activate mating behavior in male hamsters (Mesocricetus auratus) before puberty.

This study investigated pubertal changes in neural and behavioral responses to estradiol. Gonadectomized pre- and postpubertal male hamsters (Mesocricetus auratus) were treated with 0.00, 0.05, 0.10, or 0.25 mg estradiol and tested 1 week later for sexual behavior with a receptive female. Estradiol activated behavior in postpubertal, but not prepubertal, males. In contrast, estrogen receptor alpha (ERalpha) and progesterone receptor (PR) immunoreactivity in forebrain nuclei that mediate mating behavior was similar in pre- and postpubertal males. Thus, absence of a behavioral response before puberty is not associated with reduced levels of steroid receptors. Because estradiol induced PR in prepubertal males, these data also suggest that ERa is functional before puberty. Therefore, gonadal steroids facilitate male reproductive behavior only after as-yet-unidentified developmental processes occur during puberty.

C-type natriuretic peptide does not affect plasma and urinary adrenomedullin in man.

To investigate whether C-type natriuretic peptide (CNP) at pathophysiological plasma levels stimulates the release of adrenomedullin (ADM) in man, six healthy subjects (three men and three women, mean age 35 +/- 3 years, range 33-40 years) received an intravenous infusion of synthetic human CNP-22 (2 pmol kg-1 min for 2 h), in a single-blind, placebo-controlled, random order, cross-over study, with measurements of the plasma levels of cyclic guanosine monophosphate (cGMP), ADM, renin and atrial natriuretic peptide (ANP), arterial pressure, heart rate, renal blood flow (para-aminohippurate clearance), glomerular filtration rate (creatinine clearance), and the urinary excretion rates of cGMP, ADM and sodium. Infusion of CNP induced increases in its own levels (from 1.17 +/- 0.11 up to 21.13 +/- 1.41 pmol l-1) without modifying the plasma levels of cGMP, ADM, renin and ANP, the urinary excretion rate of ADM and cGMP, renal haemodynamics and sodium excretion. These data indicate that circulating CNP is not involved in the regulation of ADM release, renal haemodynamics and sodium excretion in man.

Apraclonidine protection of the blood-aqueous barrier from traumatic break-down.

This study investigated the effects of apraclonidine hydrochloride 1% eye drops on blood-aqueous barrier in 108 pigmented rabbits. The effects of pretreatment with dapiprazole and yohimbine, and a comparison with clonidine 0.125% eye drops are also reported. The disruption of blood-aqueous barrier was obtained by argon laser burning of the iris. The degree of permeability of the barrier was deduced by the amount of proteins in aqueous humor 60 min after laser application. Intraocular pressure and pupil diameter were also studied. Protein content in aqueous humor was 0.72 +/- 0.26 g/l in control rabbits that did not receive any treatment; 5.98 +/- 4.23 g/l in rabbits instilled with placebo eye drops and treated by laser burning of iris; 0.43 +/- 0.25 g/l in rabbits that received apraclonidine eye drops prior to laser burning; 2.19 +/- 1.3 g/l in rabbits that received apraclonidine eye drops immediately after laser application; 0.35 +/- 0.08 g/l in rabbits that received apraclonidine 1% eye drops both before and after laser application. Rabbits treated with clonidine 0.125% had a protein content in aqueous humor of 5.45 +/- 2.08 g/l after laser application. Dapiprazole 0.5% eye drops prior to apraclonidine led to a protein content in aqueous humor of 1.93 +/- 2.13 g/l; yohimbine 0.3% eye drops prior to apraclonidine led to a protein content of 0.70 +/- 0.40 g/l. Protein content in aqueous humor was 0.93 +/- 0.36 g/l, 0.82 +/- 0.899 g/l and 1.68 +/- 1.39 g/l in rabbits treated with yohimbine 0.3, 0.6 and 1.2 mg/kg i.v. and then with apraclonidine 1% eye drops. In one group of rabbits, the penetration into the aqueous humor of Evans blue injected intravenously was also studied. Evans blue content in aqueous humor was 0.03 +/- 0.08 mg/100 ml in control rabbits; 0.92 +/- 0.53 mg/100 ml in placebo rabbits treated by laser; and 0.28 +/- 0.19 mg/100 ml in apraclonidine rabbits treated by laser. Apraclonidine eye drops led to a decrease in IOP and prevented IOP rise following argon laser application. Placebo treated rabbits had a 20% increase in IOP following laser application. Apraclonidine-treated eyes showed mydriasis and blanching of the conjunctiva. These effects were not affected by pretreatment with dapiprazole or yohimbine. In these experiments, the treatment with apraclonidine 1% eye drops completely protected the blood aqueous barrier from the disruption caused by laser burning of the iris. The protection was less effective when apraclonidine was applied after laser burnings.

Effect of bisphosphonate therapy and parathyroidectomy on the urinary excretion of galactosylhydroxylysine in primary hyperparathyroidism.

BACKGROUND: In patients with mild or asymptomatic primary hyperparathyroidism a reliable index of bone resorption might be useful for appropriate management. Hydroxyproline is the most commonly used marker of bone resorption but its low specificity and sensitivity are known. Galactosylhydroxylysine, an amino acid mainly represented in bone collagen, has been proposed as a more suitable index of bone resorption. In this study we evaluated the sensitivity of galactosylhydroxylysine and hydroxyproline assays in following the changes of their urinary levels in 12 patients with mild primary hyperparathyroidism before and after treatment with bisphosphonate and surgery. METHODS: Serum and fasting urine specimens were obtained from 12 women with mild primary hyperparathyroidism before and after bisphosphonate treatment (2.5 mg daily for 5 days, intravenously) and after a further 25 days; in 7 patients biochemical tests were also performed 1 and 6 days after parathyroidectomy. Galactosylhydroxylysine was assayed by an HPLC method and hydroxyproline by a RIA commercial kit. RESULTS: Baseline galactosylhydroxylysine urinary levels were far above the normal range in all the patients whilst in 8 of them baseline hydroxyproline levels were normal. Bisphosphonate treatment significantly decreased bone turnover as shown by a significant fall in serum calcium (from 2.9 to 2.6 mmol/l; P < 0.001) and in galactosylhydroxylysine and hydroxyproline (-55 and -31% respectively). Twenty-five days after the end of treatment, resorption increased again and serum calcium and galactosylhydroxylysine, but not hydroxyproline, rose significantly towards basal levels. One day after parathyroidectomy serum calcium, galactosylhydroxylysine and PTH showed reduction below normal ranges. PTH and galactosylhydroxylysine returned to normal values at day 6 after parathyroidectomy. No changes in hydroxyproline levels were seen. Galactosylhydroxylysine, but not hydroxyproline, correlated significantly with serum calcium and PTH. CONCLUSION: Galactosylhydroxylysine appears to be a sensitive index of bone resorption, useful in the clinical assessment of bone involvement and in the management of patients with mild primary hyperparathyroidism.