Quantitative assessment of ALZ-50 immunoreactivity in Alzheimer's disease.

A quantitative assay for ALZ-50 immunoreactivity was evaluated in samples of superior temporal gyrus taken at autopsy from 13 Alzheimer patients and 11 controls. The assayable immunoreactivity appears to be stable for at least 24 hours postmortem but was lost with formalin fixation. The mean value of the Alzheimer patients was tenfold higher than that of the controls (P less than .002). The values of four Alzheimer samples overlapped with the low levels seen in controls, but no controls had elevated levels. In this sample population, therefore, the assay had a sensitivity of 69% and specificity of 100%.     

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.     

Mobile intraventricular cyst of the third ventricle treated with stereotactic puncture. Report of a case

A case of a pedunculated arachnoid cyst within the third ventricle is presented. The cyst was small so as not to appear as a significant expanding lesion on CT. The clinical history, however, suggested intermittent increase of the intracranial pressure. On CT there was some widening of the lateral and third ventricles, while the fourth ventricle had normal width. This finding in combination with the clinical history prompted further neuroradiologic examinations, including pneumoencephalography and ventriculography. The presence of a pedunculated mobile cystic lesion within the third ventricle was shown and its nature further elucidated by stereotactic puncture combined with contrast injection into the cyst. After emptying of the cyst, the patient has been free of symptoms during an observation time of 2 years. The diagnostic and differential diagnostic aspects are discussed and the value of traditional neuroradiologic methods emphasized.     

Pharmacokinetics and pharmacodynamics of epidural and intrathecal morphine

Spinal opiate analgesia has opened an exciting new field of research and has also rapidly gained widespread clinical acceptance. This mode of administration has obvious and definite advantages over conventional pain therapy; however, the field is still at an early stage of development. More research is clearly needed to provide methods for coping with some of the drawbacks of this method of pain relief. Important areas for future research include (1) the CSF kinetics of opiates; (2) the physiological mechanisms underlying the rostral spread of drugs within the CSF compartment; (3) a search for safer and more selective drugs; and (4) an evaluation of the extent to which pain-modulating systems at different levels in the CNS can be regulated by opiates and drugs interfering with other neurotransmitters. In this context it is essential to emphasize the importance of simultaneous study of the pharmacokinetics and the pharmacodynamic/clinical effects in providing a rational basis for a better understanding of the mechanisms of actions underlying spinal opiate analgesia.     

Study on extensive lymph node dissection: metastatic lymph nodes in papillary carcinoma of the thyroid

Bilateral cervical lymph node dissection was performed in 71 cases of papillary thyroid carcinoma, considered to be relatively early cases because of mobility, irrespective of the size of tumor or presence of node enlargement. Of these, 33 cases received additional node dissection of the anterosuperior mediastinum through longitudinal sternotomy. The number of lymph nodes examined per subject averaged 89.9, the number of metastatic nodes was 13.8, and metastasis was noted in 88.7% of all cases. Lymph node metastasis tended to be more frequent on the affected side, but was simultaneously scattered over the whole cervical area. As to sites, metastasis of paratracheal nodes on the affected side occurred at a frequency of 66.2%, inferior and superior jugular nodes at 62.0% and 59.0% respectively, pretracheal nodes at 50.7%, and tracheoesophageal nodes at 47.9%. The high incidence of para- and pretracheal nodes suggests that the lymph flow in this direction is of great importance in metastasis. In fact, lymph nodes in the mediastinum, which were directly continuous with these nodes, showed as high as 39.4% metastasis in cases of anterosuperior mediastinal extirpation. This extensive node dissection is considered to be very preferable as at least the agony of survival with carcinoma can be lessened.     

Peripheral analgesic actions of opioid peptides and morphine analogues

Opiates and opioid peptides were administered in the order of 10(-9)-10(-6) mol peripherally, and their action on pain sensitivity was investigated by the modified formalin test which has two characteristic pain responses (the first and the second phase) in the mouse hindpaw. Opioid peptides (20-500 pmol) had dose-dependent analgesia against both first and second phases, and their action ranked dynorphin greater than [D-Ala2, Met5]-enkephalinamide greater than [Met5]-enkephalin. EKC and morphine (0.4-2.5 nmol) inhibited pain response of the first phase, but produced hyperalgesia in the second phase dose-dependently. Lidocaine hydrochloride had peripheral analgesic action, but was about 500-10000 times weaker than these substances. So, these peripheral analgesic actions have a different mechanism from that of local anesthetic action. N-methyl levallorphan which is thought to be a peripherally selective narcotic antagonist reversed these peripheral analgesic actions at the first and second phases and also prevented the hyperalgesic effects of EKC and morphine at the second phase. Naloxone reversed analgesia at only the first phase. These results suggest that an analgesic mechanism by opioids may exist at the peripheral site as well. Furthermore, it is estimated that a receptor exists which is antagonized by N-methyl levallorphan but not by naloxone and that there is a system of hyperalgesia by EKC and morphine in pain modulation.     

Colonoscopy and bacteraemia: an experience in 50 patients

There is little consensus concerning the incidence of bacteraemia during colonoscopy and the need for antibiotic prophylaxis in susceptible patients. Hepatic abscesses in one patient which may have been related to prior colonoscopic examinations led the authors to carry out a prospective study of 50 patients undergoing colonoscopy. Multiple blood cultures were carried out to maximise the positive yield of transient bacteraemia and to attempt to determine the time when bacteraemia is most likely to occur. Five patients had positive blood cultures. In two patients S epidermidis was isolated, but only from the precolonoscopic blood sample. In three subjects enteric organisms were cultured from blood samples obtained during the procedure. In one of these three the same organism was cultured from the preendoscopic blood sample so that in only two patients (4%) could the bacteraemia be attributed to the colonoscopy. These results would suggest that the risk of bacteraemia during colonoscopy is low.     

Different types of relationship between beta-adrenergic relaxation and activation of cyclic AMP-dependent protein kinase in canine saphenous and portal veins

We examined the relationships between the relaxation mediated by beta-adrenoceptor and either the associated cyclic AMP production or the activation of cyclic AMP-dependent protein kinase (A-PK) in canine saphenous and portal veins. In the saphenous vein constricted with methoxamine, isoproterenol caused concentration-dependent relaxation (maximum relaxation 92.7%), and concomitant increases in cyclic AMP and A-PK activity ratio (from 52.8 to 73.5%). The portal vein was only slightly relaxed by isoproterenol (14.7% in the longitudinal strips) after constriction with methoxamine, while cyclic AMP and A-PK activation increased significantly. Isoproterenol markedly activated A-PK of the portal vein after KCl constriction (from 52.6 to 74.6%) but the maximum relaxation was only slight (13.3%). The portal vein also showed a smaller relaxation response to either forskolin or dibutyryl cyclic AMP than the saphenous vein. These results indicated that the relationship between the relaxation response to isoproterenol and either cyclic AMP production or A-PK activation was different in the saphenous and portal veins.