Frontoethmoidal meningoencephaloceles: a review of 14 consecutive patients

Over a period of 4.5 years, 14 patients with frontoethmoidal meningoencephaloceles were treated. Most patients came from Northern Namibia. Precise delineation of all cranial abnormalities was obtained by modern imaging techniques, and specific patterns of cerebral abnormality were found. The malformation was corrected in a single stage, and significant modifications have been developed to render the procedure simpler and safer. Information from our series favors delayed neural tube closure as the primary pathogenesis of the defect and suggests a common teratogen as the most probable etiological agent. Our experience leads us to advocate early correction of even small defects.     

The secretory intestinal transport of some beta-lactam antibiotics and anionic compounds: a mechanism contributing to poor oral absorption

PURPOSE: To measure the effect of silicon diode detectors used for in vivo dosimetry on beam characteristics and determine whether this effect is clinically significant. METHODS AND MATERIALS: Commercially available photon and electron diodes were placed on the central axis of photon and electron beams. The beam characteristics were measured for 6- and 10-MV photon and 6-20-MeV electron energies from a Varian Clinac 1800 medical linear accelerator. Water was used for the medium, and measurements were made for various clinically common field sizes and depths. RESULTS: Beam attenuations along the central axis were 10 and 7.5% for 6- and 10-MV photons, respectively. Electron beam dose reductions were between 13 and 25% for 20-6-MeV electrons. Photon beam flatness varied up to 7% at different depths, but the symmetry was not affected much. Electron beam flatness and symmetry were significantly changed to as much as 18 and 6%, respectively. CONCLUSION: Use of diode detectors on central axis of photon and electron beams for in vivo dosimetry causes significant attenuation and alteration of the beam characteristics. The percentage of the volume affected is significant (e.g., 23% of the volume in a 4 x 4 field gets 10% less dose for a 6-MV photon beam), especially if these diodes are used for in vivo dosimetry on the central axis every day for every treatment, as is done in some clinics. Other beam parameters such as penumbra and skin dose are also affected. It is therefore recommended that the diodes be used only as needed.     

Long-term outcome of a prospective randomized trial of conversion from cyclosporine to azathioprine treatment one year after renal transplantation

BACKGROUND: Since the introduction of cyclosporine (CsA), 1-year renal allograft survival has improved, but concern persists about the long-term adverse effects of CsA, especially with respect to renal function and blood pressure. This randomized controlled trial was set up to establish whether withdrawal of CsA would alter long-term outcome. METHODS: Adult patients who, at 1 year after renal transplantation, had a stable serum creatinine of less than 300 micromol/L and who had not had acute rejection within the last 6 months were eligible for entry. Patients were randomized either to continue on CsA (n=114) or to stop CsA and start azathioprine (Aza, n=102). All patients remained on prednisolone. Median follow-up was 93 months after transplantation (range: 52-133 months). RESULTS: There was no significant difference in actuarial 10-year patient or graft survival (Kaplan-Meier), despite an increased incidence of acute rejection within the first few months after conversion. Median serum creatinine was lower in the Aza group (Aza: 119 micromol/L; CsA. 153 micromol/L at 5 years after randomization, P=0.0002). The requirement for antihypertensive treatment was also reduced after conversion to Aza; 75% of patients required antihypertensive treatment at the start of the study, decreasing to 55% from 1 year after randomization in the Aza group and increasing to >80% in the CsA group (55% (Aza) and 84% (CsA) at 5 years after randomization, P<0.005). CONCLUSIONS: Conversion from CsA to Aza at 1 year after renal transplantation results in improvement in both blood pressure control and renal allograft function, and is not associated with significant adverse effects on long-term patient or graft survival.     

Topical gentamicin and ethacrynic acid: effects on cochlear function

OBJECTIVE: To determine whether concurrent intravenous administration of the loop diuretic ethacrynic acid potentiates the toxicity of the aminoglycoside antibiotic gentamicin applied topically on the round window. STUDY DESIGN: The authors studied the effects on cochlear sensitivity of co-administered intracardiac ethacrynic acid (40 mg/kg) and high-dose topical gentamicin solution (100%) applied to the round window. Comparisons were made with animals receiving ethacrynic acid plus systemic gentamicin (100 mg/kg); topical gentamicin alone; systemic gentamicin alone; and intravenous ethacrynic acid alone. METHODS: Experiments were carried out on pigmented guinea pigs weighing 400 to 500 g. Changes in cochlear function were characterized by monitoring shifts in compound action potential (CAP) thresholds by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. RESULTS: After 20 days animals receiving ethacrynic acid in combination with topical gentamicin to the round window failed to demonstrate a significant deterioration in cochlear sensitivity, whereas all animals receiving systemic gentamicin plus ethacrynic acid experienced profound increases in CAP thresholds. CONCLUSIONS: This study supports the contention that ethacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph. In addition, this study answers important clinical concerns regarding the safety of the use of topical aminoglycoside agents in combination with loop diuretics.     

Antisense inhibition of striatal GABAA receptor proteins decreases GABA-stimulated chloride uptake and increases cocaine sensitivity in rats

The functional status of striatal GABAA receptors appears to be inversely related to the magnitude of cocaine-induced behaviors. Exposure of striatum to antisense oligodeoxynucleotides (ASODNs) targeted to the mRNAs for the alpha 2 and the beta 3 subunits of the GABAA receptor should decrease expression of receptor proteins and therefore might be expected to increase cocaine sensitivity. ASODNs, scrambled ODNs or saline were injected into right lateral ventricle of rats and behavioral responses to cocaine were tested 18-20 h after treatment. Animals injected separately with alpha 2 or beta 3 ASODNs exhibited increased behavioral sensitivity to cocaine compared to rats injected with saline or scrambled ODNs including performing more 360 degrees turns to the left than to the right. There was significantly less GABA-stimulated Cl uptake in right striatum compared to left striatum of ASODN-treated rats with no significant difference between sides in control animals. Specific binding to benzodiazepine and convulsant sites on the GABAA receptor was not selectively altered by ASODN treatment. Combined alpha 2 beta 3 ASODN treatment did not affect either cocaine sensitivity or GABAA receptor function. There was no difference between the density of Nissl stained cells in the left and right edges of striatum in control or ASODN-treated rats indicating the absence of significant neurotoxic effects of the ASODN treatment. Injection of fluorescein-conjugated ASODNs indicated that ASODN is present in striatum at times during which behavioral and neurochemical indices of GABA receptor function are decreased. Thus, the functional status of GABAA receptors in striatum may be involved in determining cocaine sensitivity.     

The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study

1. We have studied the effects of muscarinic cholinoceptor agonists and subtype-preferring antagonists on the isometric contraction of smooth muscle strips from dog prostate. 2. Acetylcholine and carbachol induced contraction of prostate strips from the peripheral zone, ('the capsule'). Bethanechol contracted the tissue but not at lower doses. McN-A-343 and oxotremorine-M showed the same effects. 3. Blocking alpha- and beta-adrenoceptors with phentolamine and propranolol, respectively, did not modify carbachol-induced contractions. 4. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M) did not affect the contractile response evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic receptor antagonist, atropine (10(-11)-10(-9) M), inhibited it in a competitive manner. 5. The muscarinic M1 (pirenzepine), M2 [AF-DX 116, himbacine (M2/M4) and methoctramine], M3 (HHSID and f-F-HHSID), and putative M4 (tropicamide) antagonists reduced significantly the carbachol-induced contractions. The pIC50 values were: atropine (10.01) > himbacine (8.3) > methoctramine (7.85) > AF-DX 116 (7.60) > HHSID (7.21) > p-F-HHSID (7.10) > pirenzepine (7.30) > tropicamide (7.00). 6. The antagonist profile indicates that an predominant M2 receptor subtype could mediate the muscarinic contraction in the canine prostate.