Down-regulation of dopamine D1 and D2 receptors in the basal ganglia of PTZ kindling model of epilepsy: effects of angiotensin IV

The present study examined the effect of pentylenetetrazol (PTZ) induced kindling as well as the action of the hexapeptide angiotensin IV (ANG IV) on the dopamine (DA) D1 and D2 receptor binding in the basal ganglia of the mouse brain. By using quantitative receptor autoradiography, it was found that PTZ kindling led to a decrease in DA D2 receptor density (about 20%) in all regions of the neostriatum (NS) as well as in the olfactory tubercle (OT), the nucleus accumbens (NA) and the globus pallidus, which persisted 24 h and 7 days after the kindling procedure. PTZ induced kindling also elicited a decrease in DA D1 receptor binding sites (about 10%), which however was, restricted to the rostral NS (rNA) and NA. ANG IV (0.2 mg/kg), injected prior to PTZ, not only prevented the development of the kindling process but it also reversed the kindling-induced down-regulation of both DA receptors to the control levels. Furthermore ANG IV induced an area-specific increase of DA D1 receptor density above control levels in the dorsal part of rNS. These findings suggest that DA D2 receptors could mainly contribute to epileptogenesis in the PTZ kindling model, whereas the role of DA D1 receptors is limited to particular regions in the basal ganglia. The anticonvulsant effect of ANG IV pretreatment might be influenced by a DA-related mechanism and particularly by preventing D2 receptor down-regulation as well as by an adaptive area-specific increase in DA D1 receptors.     

Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers

The common usage of extended spectrum beta-lactams co-administered with amikacin in everyday clinical practice for infections by multidrug-resistant isolates has created the need to search for pharmacokinetic interaction. Eighteen healthy volunteers were enrolled in the study; six were administered 1g of ceftazidime singly intravenously or combined with 0.5 g of amikacin; six received 0.5 g of imipenem singly or combined with 0.5 g of amikacin and six 1g of aztreonam singly or combined with 0.5 g of amikacin. Blood and urine samples were collected at regular time intervals and apparent serum levels were determined by a microbiological assay. Co-administration of ceftazidime and amikacin resulted in higher C(max) and AUC for amikacin than when administered alone. Co-administration of imipenem and amikacin resulted in higher C(max) for imipenem than when administered alone. The tested interactions did not affect plasma half-life (t(1/2)) and clearance rate of any antimicrobial compared with its single administration. All tested drugs were mainly eliminated by glomerular filtration. It is concluded that co-administration of ceftazidime, imipenem or aztreonam with amikacin in healthy volunteers might affect C(max) and AUC without influencing any other pharmacokinetic parameter. The probable clinical endpoint is that giving ceftazidime, imipenem or aztreonam with amikacin might result in a transient elevation of beta-lactam serum levels without further affecting the complete pharmacokinetic profile of each drug as obtained after administration of the drug alone.     

The influence of indomethacin co-administration on ofloxacin levels in plasma and cerebrospinal fluid in rats

The possible increase of ofloxacin levels in serum and cerebrospinal fluid (CSF) by concomitant indomethacin administration was investigated in 120 healthy adult rats. The animals were administered intramuscular doses of ofloxacin 30 mg/kg alone (Group A, n = 60) or with indomethacin 2 mg/kg (Group B, n = 60). Blood and CSF samples were obtained from both groups at 30, 45, 60 and 90 min post-administration. Concentrations of ofloxacin were estimated using a microbiological assay. Co-administration of indomethacin did not affect plasma levels of ofloxacin significantly; however, higher levels were found in all CSF samples after co-administration with indomethacin, particularly after 90 min with 0.59 microg/ml versus zero median values when only ofloxacin was administered (P = 0.05). No central nervous system adverse effects were observed clinically. No correlation between levels of ofloxacin in plasma and CSF could be established either in rats administered only ofloxacin or in rats administered both drugs. The presented pharmacokinetic findings revealed that co-administration of ofloxacin and indomethacin may result in protracted quinolone levels in the CSF. However, the absence of significant correlation between concentrations of ofloxacin in plasma and CSF upon co-administration of indomethacin, as well as of central nervous system adverse effects, make the probability of an epileptogenic interaction between them unlikely. These results merit further clinical evaluation.     

Autoimmune hemolytic anemia with myelodysplastic features followed by bilateral adrenal non-hodgkin lymphoma: a case report and review of the literature

Primary adrenal lymphoma is a rare entity characterized mainly by bilateral involvement, presenting predominantly diffuse large B-cell histology, adrenal insufficiency and poor prognosis. Approximately 85 cases have been described in the literature. We report here a case of a 77-year-old man who presented with autoimmune hemolytic anemia (AIHA), which preceded the diagnosis of lymphoma by more than 2 years. An ultrasound guided biopsy revealed diffuse, large B-cell, lymphoma; subsequent staging revealed no other disease site, and the patient was considered to have primary adrenal lymphoma. The patient had adrenal insufficiency at diagnosis. He received hormonal replacement and chemotherapy, but he succumbed to his disease because of sepsis and multi-organ failure a few days post diagnosis. To our knowledge, this is the first case in the literature in which AIHA preceded bilateral adrenal lymphoma. We also provide a summary of the current data for the clinical features, diagnosis and treatment of primary adrenal lymphoma.     

Delivery outcomes following loop electrosurgical excision procedure for microinvasive (FIGO stage IA1) cervical cancer

OBJECTIVE: The goal of this study was to report the delivery outcomes in women who had loop electrosurgical excision procedure (LEEP) for microinvasive cervical cancer (stage IA1 without lymphovascular invasion) and became pregnant and progressed beyond 24 weeks. METHODS: A case-control study was performed. Twenty-eight women who were managed exclusively with LEEP for microinvasive cervical carcinoma had at least one pregnancy beyond 24 weeks and were the cases. Each case was matched with one woman who delivered at the same department without prior treatment of her cervix (controls) and their delivery outcomes were compared with those of the cases. Known risk factors for preterm delivery were used as matching factors. RESULTS: There was no statistically significant difference (P > 0.05) between cases and controls in the duration of pregnancy (37.6-38.4 weeks respectively), birth weight (3212-3315 g), cesarean section rate (17.8-32.1%), neonatal unit admission rate (21.4-10.7%), and precipitate labor rate (13-10.5%). The duration of labor was significantly shorter in cases (5.5-7.1 h, P = 0.032). After LEEP the relative risk for preterm delivery is 3.67 (95% confidence interval, 0.97-20.27), for low birth weight infant 0.67 (0.06-5.8), for precipitate labor 1 (0.05-3.88), and for delivery by cesarean section 0.5 (0.17-4.46). CONCLUSIONS: Women treated for microinvasive cancer with LEEP did not have significantly more delivery complications compared with controls apart from shorter duration of labor. There was a possible non-statistically significant trend toward shorter duration of pregnancy in cases. While caution should be advised when selecting and treating women with microinvasive carcinoma by LEEP, the apparent safety of the management and the satisfactory delivery outcome seem to justify this approach in many cases.     

Ex vivo synergy of arachidonate-enriched serum with ceftazidime and amikacin on multidrug-resistant Pseudomonas aeruginosa

Three multidrug-resistant strains of Pseudomonas aeruginosa were incubated ex vivo with sera sampled after a 10 min intravenous infusion of 25 mg/kg of arachidonic acid (AA) in 10 rabbits in the presence of ceftazidime and amikacin. Lipid peroxidation was assessed during bacterial growth. A statistically significant decrease in bacterial cells was found by the interaction of antimicrobials and serum sampled in the middle of infusion and 15 and 30 min after infusion of AA and was accompanied by elevated levels of malonodialdehyde. This effect of AA is probably attributed to lipid peroxidation and raises the possibility of its application in experimental infections.     

Low dose melphalan is a treatment option in elderly patients with high risk myelodysplastic syndrome or secondary acute myeloblastic leukaemia

We present the case of a 71 year-old man with secondary acute myeloblastic leukemia, who was successfully treated with low dose melphalan plus Epo plus G-CSF. We treated the patient with 2 mg of melphalan once a day orally, G-CSF 5 mg/kg 3 times a week and Epo 10.000 ui subcutaneously 3 times a week until the maximum response was obtained. Complete remission was achieved after 16 weeks of continuous treatment. Treatment-related toxicity was not significant. We recommend the use of low dose melphalan in elderly patients with high risk MDS as a treatment option.     

Multiple failed urethroplasties: definitive repair with the Duckett island-flap technique

Background/Purpose:

The correction of postoperative complications after hypospadias repair presents frequently serious problems, and the results are not always satisfactory. The aim of this study is to present our experience with the tubularized island flap technique (Duckett procedure) in patients who had been submitted to repeated unsuccessful attempts for the repair of hypospadias and its complications.

Methods:

During an 8-year period (1994 through 2001), 21 patients, aged 4 to 18 years, presented with severe recurrent hypospadias (3 to 13 times). In all patients, the urethral orifice was quite proximal because of disruption of the neourethra and was associated with severe penile ventriflexion. In addition, there were diverticula with hair ingrowth in 5 boys and lack of the prepuce in 4. All patients underwent the Duckett island-flap technique. The inner layer of the prepuce was used in 17. The dorsal penile skin was used for the island flap formation in the remaining 4 patients in whom the prepuce had been resected during the previous operations.

Results:

After repair, the meatus was located at the top of the glans in all patients. There were 5 complications (24%): distal fistula near the glans (n = 1), meatal stenosis (n = 1), diverticula at the proximal anastomosis (n = 2), and anastomotic stenosis (n = 1). All of them were treated successfully by meatotomy, fistula closure, diverticula tapering, and dilatations, respectively.

Conclusions:

The island-flap technique gives satisfactory results in patients with multiple failed urethroplasties; it is applicable even in boys with resected prepuce and has an acceptable complication rate.