In Vitro and in Vivo Evaluation of Whole and Half Tablets of Sustained-Release Adinazolam Mesylate

The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.     

Regional cerebral glucose transport in insulin-dependent diabetic patients studied using [11C]3-O-methyl-D-glucose and positron emission tomography

Regional cerebral [11C]3-O-methyl-D-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 mM), and four were studied at hyperglycaemic plasma glucose levels (mean 13 mM). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 mM had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and D-glucose for the passive facilitated transport carrier system for hexoses across the blood-brain barrier (BBB). It is concluded that the number and affinity of D-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of D-glucose across the BBB.     

Direct intracavernous obliteration of high-flow carotid-cavernous fistulas

Four cases of high-flow carotid-cavernous sinus fistula (CCF), three of them posttraumatic and one spontaneous, have been treated by a direct surgical approach to the cavernous sinus. The CCF's were obliterated by the introduction into the cavernous sinus of muscle fragments and/or fibrin sealant. In the three cases with a preoperatively patent internal carotid artery (ICA), the CCF was occluded and the ICA flow preserved. One of these also had a posttraumatic false aneurysm that enclosed the two avulsed ends of a transected intracavernous ICA. This was treated by cervical ICA ligation following resolution of the CCF. A fourth patient, who had previously undergone an unsuccessful ICA trapping procedure elsewhere, also obtained a good result. The case histories and the surgical technique are presented. Direct intracavernous obliteration with muscle fragments and fibrin sealant fulfills the criteria for treatment of high-flow CCF's: occlusion of the arteriovenous fistula and preservation of the ICA circulation. While this surgical technique is a therapeutic option in some cases, it appears to have precise indications in others.     

Localized osteolysis in stable, non-septic total hip replacement

We are reporting four cases of extensive, localized bone resorption adjacent to a rigidly anchored, cemented total hip replacement. None of these hips showed evidence of infection on clinical, bacteriological, or pathological evaluation. The tissue from the regions of osteolysis showed sheets of macrophages and foreign-body giant cells invading the femoral cortices. Abundant methylmethacrylate particulate debris was present in the tissues, but polyethylene wear debris was absent. The histological appearance of this tissue resembled that reported about loosened total hip implants with the exception of the synovial-like layer at the cement surface. The cases reported here show that aggressive bone lysis may occur around stable cemented total hip arthroplasties without the presence of sepsis or malignant disease.     

Spectral analysis of infant EEG and behavioral outcome at age five

Power spectral and discriminant analysis techniques were used to compare EEG records obtained at term and at 3 months past term from 5 groups of varying risk and developmental outcome. The groups were: healthy full-terms; healthy pre-terms with normal outcomes; sick pre-terms with normal outcomes; sick pre-terms with delayed development; sick pre-terms with later neurological problems. The EEG samples recorded at term were identified as belonging to the correct subject group at 52-70% accuracy, 20% being chance for 5 groups. The accuracy varied with the 4 classes of EEG patterns used. The individual subjects were also classified into their correct groups with few exceptions. Similar success was obtained with EEG samples selected from recording at 3 months past term. The predominant power spectral discriminating features were changes in intra- and inter-hemispheric coherence, and increased power, particularly in the middle and higher frequency range. Thus, computer analyses of EEG samples, using features not readily identified visually, differentiated risk from non-risk infants and also differentiated infants with substantial neonatal medical complications who have good or poor developmental outcomes.