The importance of oral foci of infection in renal transplantation

During the treatment of patients with renal failure or renal transplants the most important consideration is to eliminate sources of infection before and after the treatment. Acute or chronic oral infections or bacteraemias resulting from dental procedures may cause serious complications in these patients who already have lowered host resistance caused by immunosuppressant therapy. In order to determine the latest concepts from some international transplantation centres relating to the importance of and the effect of infective sources in the oral cavity, a survey form was prepared which included several questions related to oral foci of infection and renal transplantations.
Results obtained from 22 centres from 12 countries indicated that the majority of the centres included a dental examination in their routine protocol and required completion of any necessary dental treatment before transplantation. However, full agreement among all these centres on the necessity for dental examination as part of the protocol has not yet been reached.     

Subacute sclerosing panencephalitis: brain stem involvement in a peculiar pattern

The most common pattern in subacute sclerosing panencephalitis, is in the cerebral hemisphere white matter on T2-weighted images with or without atrophy. Brain-stem lesions are rare. We report brain-stem involvement in two children with subacute sclerosing panencephalitis. A peculiar pattern, with involvement of the pons with extension to both middle cerebellar peduncles and substantia nigra but sparing the pontine tegmentum, is suggested. Received: 10 January 2000/Accepted: 18 April 2000     

Somatostatin infusion withdrawal in the diagnosis of childhood growth hormone deficiency

OBJECTIVE: An evaluation of growth hormone (GH) testing for GH deficiency (GHD) in childhood is confounded by the lack of a world-wide consensus on the definition of GHD. Although a single GH test remains the most powerful biochemical tool in the evaluation of a child with growth failure, the test remains far from ideal. Withdrawal of somatostatin (SS) infusion is followed by a rebound rise of GH thought to be mediated by endogenous GH-releasing hormone (GHRH) function. This study was designed to compare the GH response to 90 min SS infusion in children with normal GH secretion versus children with GH deficiency. METHODS: Ten children with GHD and 10 healthy controls (NC) have been evaluated for GH response to somatostatin infusion withdrawal (SSIW) and compared with response of two provocative tests, glucagon plus propranolol test and L-Dopa test. All children received constant infusion of somatostatin for 90 min (3 microg/kg per h, Stilamin, Serono, Aubonne, Switzerland). In order to determine GH, blood samples were obtained 90 min before the SS infusion and 0, 15, 30, 45, 60, 75, and 90 min after the cessation of infusion. RESULTS: Growth hormone peak levels with SSIW were significantly lower in GH deficient children than in healthy children (2.5 +/- 1.2 ng/dL, vs 21.9 +/- 5.3 ng/dL, respectively, P < 0.01). No adverse effects were observed during or after somatostatin infusion. CONCLUSION: In the present study, SSIW elicited a significant GH rise in healthy children but not in children with GH deficiency. Although further controlled studies using more data are necessary to expand these findings, the results suggested that children with GH deficiency can be reliably discriminated from healthy children by SSIW.     

Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats

To determine whether the possible oxidative effect of methotrexate (Mtx) on ovary and to evaluate the effectiveness of alpha lipoic acid (ALA), which may be useful in many oxidative stress models.

Thirty-two female Wistar-albino rats were randomly divided into four groups; control group, alpha lipoic acid group (ALA 100?mg/kg, 10?days), multiple dose Mtx group (Mtx 1?mg/kg 1, 3, 5, 7?days) and Mtx and ALA group (Mtx 1?mg/kg 1, 3, 5, 7?days and ALA 100?mg/kg, 10?days). Serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), tissue malondialdehyde (MDA) and activities of glutathione peroxidase (GSH-Px) and catalase (CAT) and anti-Mullerian hormone (AMH) and total ovarian follicle count were evaluated.

Mtx administration caused a significant decrease in TAS, a significant increase in TOS and OSI, a significant increase in MDA levels and a decrease in GSH-Px and CAT activity. Moreover the proinflammatory cytokine (TNF-α) was increased in the Mtx group. And AMH values and total follicle count were significantly decreased in Mtx group. However, ALA treatment reversed biochemical results and AMH levels and total follicle count.

Alpha lipoic acid ameliorates methotrexate induced oxidative damage of ovarian in rats.     

A phase I randomized,double‐blind,single subcutaneous dose escalation study to determine the safety,tolerability, and pharmacokinetics of rezafungin in healthy adult subjects

Rezafungin is a novel echinocandin being developed for the treatment and prevention of invasive fungal infections. The objectives of this randomized, double‐blind study in healthy adults were to determine the safety, tolerability, and pharmacokinetics of rezafungin after subcutaneous (s.c.) administration. The study design consisted of six sequential cohorts of eight subjects, except for the first cohort with four subjects. The subjects were randomized in a 3:1 ratio of rezafungin to placebo and were to receive a single dose of 1, 10, 30, 60, 100, or 200 mg. The most common adverse events (AEs) were increased alanine aminotransferase and sinus bradycardia (unsolicited) and erythema at the injection site (solicited). Unsolicited AEs were generally mild to moderate and not rezafungin‐related. Although the study was terminated after the 10 mg dose cohort due to concerns of potential increased severity of injection site reactions, no predetermined dose escalation halting criteria were met. Following the 10 mg single s.c. dose of rezafungin (n = 6), the geometric mean (GM) maximum concentration (C _max) was 105.0 ng/ml and the median time to C _max was 144 h. The GM area under the concentration‐time curve was 32,770 ng*h/ml. The median estimated terminal half‐life was 193 h. The GM apparent oral clearance was 0.255 L/h and the GM apparent volume of distribution was 68.5 L. This study demonstrates that a single s.c. dose of rezafungin in healthy adult subjects: (1) did not result in serious AEs, death, or withdrawal from the study due to an AE; and (2) produced a pharmacokinetic profile with long exposure period postadministration. In an effort to reduce the occurrence of injection site reactions, a re‐evaluation of the rezafungin s.c. formulation could be considered in the future.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Currently marketed antifungal agents of the echinocandin class are dosed by i.v. once daily and are therefore not practical for prolonged or outpatient prophylaxis. Rezafungin is an investigational echinocandin (currently in phase III trials studying once‐weekly i.v. administration) that has excellent activity against clinically relevant Candida and Aspergillus spp. and Pneumocystis jirovecii, a prolonged half‐life allowing for longer dosing intervals, and a stability/solubility profile that allows for the possibility of subcutaneous (s.c.) dosing.

• WHAT QUESTION DID THE STUDY ADDRESS?

The objectives of this randomized, double‐blind study in healthy adults were to determine the safety, tolerability, and pharmacokinetics (PKs) of rezafungin after s.c. administration.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study provided safety data regarding s.c. administration of rezafungin. Despite common solicited injection site reactions, s.c. administration of 10 mg of rezafungin did not result in serious adverse event (AEs), death, or withdrawals due to an AE in healthy adult subjects. The study also showed that rezafungin had a PK profile with a long exposure period.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

In an effort to reduce the occurrence of injection site reactions, these findings may lead to a future re‐evaluation of the s.c. formulation of rezafungin.     

Erratum to: Evaluation of cardiac functions in juvenile systemic lupus erythematosus with two-dimensional speckle tracking echocardiography

Clinical Rheumatology -