Long-term cancer pain management in morphine pre-treated and opioid naive patients with transdermal fentanyl

There is emerging data supporting the use of TTS-F (transdermal therapeutic system-fentanyl) in opioid naive patients. Our study examines the safety and efficacy of TTS-F in the long-term control of cancer pain in opioid naive patients and those transferring from oral morphine. Pain was assessed in 589 patients (Group A: 268 opioid naive, Group B: 321 transferring from morphine) using a Visual Analogue Scale (VAS; 0-10), based on selected questions from the Greek Brief Pain Inventory (GBPI). Overall treatment satisfaction was assessed on a 4-point scale. Quality of Life (QOL) and ECOG (0-4) status were also recorded. These were assessed in relation to TTS-F dose, pain type (neuropathic, combined, nociceptive), concomitant use of anti-inflammatory drugs and other demographic data. Of 589 patients, 59 (10%) withdrew as a result of inadequate pain satisfaction or for other reasons. There were no discontinuations due to side effects; no Grade 3-4 events occurred. A total of 530 continued on-study, 211 patients died during study period and 295 departed; all (506; 89%) were satisfied with their pain relief. Analysis of patients at baseline, 28 days, 6 and 12 month time points (n = 153 Group A; n = 214 Group B) with respect to QOL and pain measures indicated a statistically significant (p < 0.001) improvement in all measures across time independent of pain type, or any other patient characteristic(s). In patients with intolerable pain, transfer to TTS-F offers an efficient and safe long-term analgesic option. TTS-F offers durable long-term maintenance of pain relief with acceptable side effects in opioid naive patients. In general, TTS-F as a first line analgesic approach for carefully selected and monitored patients experiencing moderate to severe cancer pain should be considered.     

Oxidative stress-mediated DHEA formation in Alzheimer's disease pathology

An alternative pathway for dehydroepiandrosterone (DHEA) synthesis has been suggested by treating rat and human brain cells with ferrous sulfate and beta-amyloid (Abeta). To determine if this pathway exists in human brain, levels of DHEA in hippocampus, hypothalamus and frontal cortex from Alzheimer's disease (AD) patients and age-matched controls were measured. DHEA is significantly higher in AD brain than control, and was highest in AD hippocampi. Cytochrome p450 17alpha-hydroxylase, responsible for peripheral DHEA synthesis, is not present in hippocampus. DHEA levels in AD cerebrospinal fluid (CSF) were significantly higher than age-matched controls. AD serum DHEA levels are lower than CSF, and not significantly different from controls. Treatment of control hippocampus, hypothalamus and serum with FeSO(4) increases DHEA, suggesting that levels of precursor are higher in control that in AD brain. This suggests that (i). an alternative precursor is present in control brain, (ii). AD brain DHEA is formed by oxidative stress metabolism of precursor, and (iii). CSF DHEA levels and serum DHEA formation in response to FeSO(4) may serve as an indicator of AD pathology.     

Adenomyoma of the small intestine in children: a rare cause of intussusception: a case report

Adenomyomas are hamartomas of the alimentary tract with exceptionally rare localization at the ileum. The case presented here concerns an infant aged 18 months suffering from adenomyoma of the ileum, which was responsible for the development of ileoileac intussusception. Our paper aims at underlining the particularities of this extremely rare entity, while adding the 13th case reported to the international bibliographic references.     

The effect of a modified Boston brace with anti-rotatory blades on the progression of curves in idiopathic scoliosis: aetiologic implications

The effect of a modified Boston brace with anti-rotatory blades on idiopathic scoliotic curves, mainly right thoracic with a compensatory left lumbar, was studied. METHOD AND MATERIAL: Twenty-eight scoliotic children divided into three sub-groups according to the curve type were included in the study. Cobb angle and rotation was measured on posteroanterior spinal radiographs taken during the first examination and also during the follow-up with the children in and out of the brace. RESULTS: Ten curves improved, 13 remained stable and 5 increased (Cobb angle change >5 degrees compared with the initial measurement). The brace treatment had more affect on the double curves, while single curves remained unaffected. Rotation remained unchanged in all curve types except in the lumbar component of double (right thoracic-left lumbar) curves. DISCUSSION: These findings indicate that in curves with a compensatory component (e.g. main thoracic with compensatory lumbar curve), a deforming rotatory force, which is blocked by the de-rotatory action of the blades of the above-modified Boston brace, is present and seems to be more active in the lumbar spine. It is hypothesized that this deforming rotatory force seems to be a major aetiological factor for double curves. In conclusion the conservative treatment using this brace is beneficially affecting the natural history of IS in children.     

Ocular Availability of Gentamicin in Small Animals After Topical Administration of a Conventional Eye Drop Solution and a Novel Long Acting Bioadhesive Ophthalmic Drug Insert

Purpose. Gentamicin eye drop solutions have a short precorneal residence time. The present study investigates the effect of gentamicin using a new long acting delivery Bioadhesive Ophthalmic Insert (BODI) in healthy dogs and rabbits and compares the results with a conventional regimen using an eye drop solution. Methods. In vivo assays were performed on animals after deposition of one BODI and instillations of an eye drop solution. Tear samples were collected over 72 hours and 60 minutes, in the case of inserts and eye drop solution respectively. The gentamicin concentration profiles in tear fluid (determined by a fluorescent polarization immunoassay technique) was individually analyzed, in each animal, in relation with the minimum inhibitory concentration observed in vitro against some bacteria. A non classical pharmacokinetic approach was used for the analysis of the topically applied drug substance, involving two parameters: the efficacy area under the curve (AUC_eff) and the efficacy time (t_eff). Results. In the case of the eye drop solution, the AUC_eff were higher in dogs (2.80 10³ – 3.64 10³ [µg ml^–1 h]) than in rabbits (0.64 · 10³ – 0.95 · 10³ [µg ml^–1h]); the t_eff had a similar behavior: 6-15 [h] in dogs and 2-6 [h] in rabbits. In the case of BODIs, the AUC_eff and the t_eff were quite similar between dogs and rabbits: 190 10³ – 205 10³ [µg ml^–1 h] and 70-76 [h], respectively. The AUC_eff and the t_effwere always much higher in the case of BODIs than for the eye drop solution both in dogs and rabbits. Conclusions. This study shows that topical administration of gentamicin using BODIs can improve treatment due to the decreasing number of applications while ensuring an effective level of antibiotic in tears controlled by the device.     

The microcirculation of cerebral arteries: A morphologic and morphometric examination of the major canine cerebral arteries

A morphologic and morphometric examination of the major cerebral blood vessels in the dog was carried out to determine whether there were vasa vasorum in these arteries and what features might be associated with them. True vasa vasorum confined to the media were not seen in any of the vessels examined. Microvessels confined to the adventitia, however, were found in the internal carotid and vertebral arteries but not in the basilar, middle cerebral, or anterior spinal arteries. Animal size, vessel size as determined by adventitial and medial area, and the number of smooth muscle cell lamellae were not associated with the presence of these adventitial vessels; they occurred only in arteries with both an intra- and extradural portion. It therefore appears that most canine cerebral arteries do not have vasa vasorum.     

Central corneal mechanical sensitivity in pseudoexfoliation syndrome

PURPOSE: Corneal involvement and disturbances of the tear film have been reported in pseudoexfoliation syndrome (PEX). Tear film deficiencies are correlated with changes in corneal sensitivity. The present study aims at evaluating central corneal mechanical sensitivity (CCMS) in PEX. METHODS: Patients with unilateral or bilateral PEX findings constituted the study group (SG). Age- and gender-matched patients without PEX in either eye constituted the control group (CG). Patients with conditions affecting corneal sensitivity were excluded. CCMS and central corneal thickness (CCT) were measured (using a Cochet-Bonnet esthesiometer and an ultrasonic pachymeter, respectively). Schirmer (ST) and break-up time (BUT) tests were also performed. RESULTS: The SG included 40 patients (24 male, 60%). The CG included 38 patients (25 male, 65.78%). ST scores were significantly lower in the SG compared with the CG (11.45 +/- 2.52 mm and 14.27 +/- 1.18 mm, respectively, P = 0.04). BUT scores were also significantly lower in the SG compared with the CG (7.64 +/- 2.37 mm and 12.43 +/- 3.14 mm, respectively, P = 0.03). CCMS was significantly (P = 0.02) reduced in the SG compared with CG (4.54 +/- 0.23 cm and 5.73 +/- 0.44 cm, respectively). Differences in CCT between the SG and the CG were not statistically significant. CONCLUSIONS: The decrease in CCMS in PEX eyes may be related to decreased BUT and ST scores in PEX, as previously described. However, a direct involvement of sensory nerves may also participate. The reduction in CCMS may have implications for the clinical management of PEX patients.     

Literature review regarding the methodology of assessing third nerve paresis associated with non-ruptured posterior communicating artery aneurysms

The association of third cranial nerve palsy subsequent to an enlarging posterior communicating artery (P-Com A) aneurysm has been well described. In our current communication, we review the relevant literature and propose a classification system for the severity of the third cranial nerve palsy, correlating it to the postoperative recovery. Our four grade scale (I–IV) included the degree of the levator palpebrae muscle paresis, the presence of pupillary reaction and the impairment of the third nerve mediated extraocular muscle movement. We evaluated five patients with third nerve palsy secondary to non-ruptured, P-Com A aneurysm. Patients were re-evaluated at 2, 4, 8, 24 weeks postoperatively. Four of the five patients had complete recovery within 4–8 weeks after surgery. One patient had grade II third nerve paresis and complete resolution of the third nerve symptoms within 4 weeks, whereas three patients with grade III and IV had complete resolution 4–8 weeks after surgery. The fifth patient, with grade IV paresis, had minimal (grade III) improvement 6 weeks after surgery, and incomplete recovery (grade I) 6 months postoperatively. Our simple grading system of third nerve palsy associated with P-Com A aneurysms, can be a helpful tool for the initial evaluation and for the monitoring of recovery in these patients.