Gingival recession and exposure of barrier membrane: effect on guided tissue regeneration of Class II furcation defects

The purpose of the present study was to evaluate the effect of barrier membrane exposure on the success of guided tissue regeneration in Class II furcation defects. Twenty-six subjects with mandibular Class II furcation defects received initial periodontal therapy followed by guided tissue regeneration surgery. The membrane was placed and the flaps were repositioned so that the membrane was totally submerged. Membranes were removed 4 to 6 weeks later, at which time the extent of their exposure was recorded. An overall improvement in all clinical parameters was observed for all subjects 1 year after surgery. Half of the patients had experienced no membrane exposure, while the other 13 subjects had experienced mild to pronounced exposure; both groups showed similar improvement in all clinical and surgical parameters. In light of the comparable results obtained in exposed sites, and the anatomic difficulties sometimes encountered in covering a membrane completely, in some of these cases the membrane may be left only partially submerged. This approach will allow for tighter occlusal "seal" of the tooth-membrane interface and preservation of the keratinized gingiva.     

Effect of moditen-depot therapy on the duration and quality of remissions in schizophrenia patients

The authors studied the effectiveness of out-patient treatment by Moditen-Deppt of 128 schizophrenic patients. A comparison of the previous remissions appearing during usual pharmacotherapy and remissions seen during Moditen-Depot treatment depicted statistically significant differences, indicating a distinct prevention of exacerbations due to this preparation, an increase in the duration and improved quality of remissions. Such improved remissions were expressed in lesser severity, in a decrease of psychopathological disturbances, changes qualified as a "mollification of a defect" and an improvement of some socio-clinical indices.     

Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity

Endoplasmic reticulum-associated amyloid beta-peptide (Abeta)-binding protein (ERAB)/L-3-hydroxyacyl-CoA dehydrogenase type II (HADH II) is expressed at high levels in Alzheimer's disease (AD)-affected brain, binds Abeta, and contributes to Abeta-induced cytotoxicity. Purified recombinant ERAB/HADH II catalyzed the NADH-dependent reduction of S-acetoacetyl-CoA with a Km of approximately 68 microM and a Vmax of approximately 430 micromol/min/mg. The contribution of ERAB/HADH II enzymatic activity to Abeta-mediated cellular dysfunction was studied by site-directed mutagenesis in the catalytic domain (Y168G/K172G). Although COS cells cotransfected to overexpress wild-type ERAB/HADH II and variant beta-amyloid precursor protein (betaAPP(V717G)) showed DNA fragmentation, cotransfection with Y168G/K172G-altered ERAB and betaAPP(V717G) was without effect. We thus asked whether the enzyme might recognize alcohol substrates of which the aldehyde products could be cytotoxic; ERAB/HADH II catalyzed oxidation of a variety of simple alcohols (C2-C10) to their respective aldehydes in the presence of NAD+ and NAD-dependent oxidation of 17beta-estradiol. Addition of micromolar levels of synthetic Abeta(1-40) to purified ERAB/HADH II inhibited, in parallel, reduction of S-acetoacetyl-CoA (Ki approximately 1.6 microM), as well as oxidation of 17beta-estradiol (Ki approximately 3.2 microM) and (-)-2-octanol (Ki approximately 2.6 microM). Because micromolar levels of Abeta were required to inhibit ERAB/HADH II activity, whereas Abeta binding to ERAB/HADH II occurred at much lower concentrations (Km approximately 40-70 nM), the latter more closely simulating Abeta levels within cells, Abeta perturbation of ERAB/HADH II was likely to result from mechanisms other than the direct modulation of enzymatic activity. Cells cotransfected to overexpress ERAB/HADH II and betaAPP(V717G) generated malondialdehyde-protein and 4-hydroxynonenal-protein epitopes, which were detectable only at the lowest levels in cells overexpressing either ERAB/HADH II or betaAPP(V717G) alone. Generation of such toxic aldehydes was not observed in cells contransfected to overexpress Y168G/K172G-altered ERAB and betaAPP(V717G). We conclude that the generalized alcohol dehydrogenase activity of ERAB/HADH II is central to the cytotoxicity observed in an Abeta-rich environment.     

Hypocholesterolemic agents V: Inhibition of beta-hydroxy-beta-methylglutaryl coenzyme A reductase by substituted 4-biphenylylalkyl carboxylic acids and methyl esters

Eleven substituted 4-biphenylylalkyl carboxylic acids and three methyl esters were synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Five of the acids were analogs, resulting from various isosteric replacements of the carbonyl and ether oxygens of the previously described reversible inhibitor 1-(4-biphenylyl)pentyl hydrogen succinate. No significant change in activity was noted, except upon introduction of an amide linkage where a decrease in inhibition was found. Six carboxylic acids and three methyl esters, all containing the 4-biphenylyl radical but lacking the n-butyl side chain found in 1-(4-biphenylyl)pentyl hydrogen succinate, also were inhibitors of the reductase.     

Skeletal resistance to the calcemic action of parathyroid hormone in uremia: role of 1,25 (OH)2 D3

Studies were carried out to investigate the role of 1,25(OH)2D3 in the skeletal resistance to the calcemic action of parathyroid hormone. The change in serum calcium after the intravenous infusion of 2 U of parathyroid extract (PTE)/kg body wt/hr for eight hours was evaluated in thyroparathyroidectomized (T-PTX) dogs before, and one, two and three days after, induction of uremia by bilateral ureteral ligation (11 dogs) or by bilateral nephrectomy (8 dogs). In another six nephrectomized and T-PTX dogs, 0.68 ug of 1, 25 (OH)2D3/day was given on the day of nephrectomy and for two days thereafter. Serum creatinine in each day of the study was not different among the three groups. The study also included the evaluation of the effect of sham operation (five dogs) and the administration of 1,25 (OH)2D3 to dogs with normal renal function (four dogs) on the calcemic response to PTE, as well as the reproducibility of such a response in the same animal. The results showed that 1) the calcemic response to PTE was markedly impaired after one day of bilateral ureteral ligation or nephrectomy, but the impairment was more severe after nephrectomy; 2) the calcemic response to PTE after two or three days of bilateral ureteral ligation was similar to that seen at one day after nephrectomy; 3) 1, 25 (OH)2D3 partially restored the calcemic response to PTE in the nephrectomized animals to levels similar to those seen after one day of bilateral ureteral ligation; 4) sham operation did not affect the response to PTE, and repeated infusion of PTE produced similar changes in the concentrations of serum calcium. The data indicate that (a) a deficiency of 1,25 (OH)2D3 is at least partly responsible for the skeletal resistance to the calcemic action of PTH in uremia; (b) uremia, per se, may also contribute to this phenomenon; and (c) the kidney after one day of complete bilateral ureteral ligation may still produce 1,25 (OH)2D3, but this ability is compromised after two days of ureteral obstruction.     

Bilateral projection of the canine tooth pulp to bulbar trigeminal neurons

Unit activity was recorded extracellulary from neurons of the cat medulla following electrical stimulation of the ipsilateral and/or contralateral cannine tooth pulps. The majority of the cells (67%) were only responsive to ipsilateral stimulation. However, many (28%) responded to stimulation of either canine pulp and a few (5%) responsed to contralateral stimulation alone. The neurons were localized histologically in the necleus proprius of the rostral trigeminal nucleus caudalis (NVCaud) and in dorsal portions of the ventromedially contiguous lateral reticular formation (LRF). Cells exclusively responsive to ipsilateral stimuli had a relatively wide dorsoventral distribution. In contrast, 'bilateral' and 'contralateral' cells were situated only in the deep NVCaud-LRF border zone or in immediately adjacent portions of the LRF. Generally, ipsilateral stimuli evoked response bursts with shorter latencies, more spike potentials and briefer interspike intervals than equivalent contralateral stimuli. In experiments designed to study afferent interactions, a conditioning stimulus, applied to either the ipsilateral or the contralateral canine, preceded a test stimulus applied to the other canine at predetermined interstimulus intervals. Responses to the test stimulus were either totally or partially suppressed when intervals of moderate duration (90-500 msec) were used. However, responses to the test stimulus frequently were enhanced when the intervals were breif (less than or equal to 60 msec) or when the teeth were stimulated simultaneously. The results reveal that bilateral afferents from the pulps of the canine teeth converge upon neurons of bulbar trigeminal structures, that the neurons are differentially responsive to the activation of ipsilateral and contralateral pulpal receptors and that bilateral afferent barrages originating in the canine pulps interact to modulate the firing patterns of the neurons.     

Exercise tests before and after heart valve replacement

A simple progressive exercise test was performed before and after operation on five subjects undergoing mitral valve replacement and on five subjects undergoing aortic valve replacement. The responses of heart rate and ventilation were related to work rate )kilopond metres/min). The patients were also assessed clinically by the New York Heart Association grading and radiologically before each exercise test. The clinical grading was shown to be a poor guide to observed exercise tolerance, as the improvement noted in symptoms was not matched by the objective measurement of working capacity. Only two patients had normal exercise tolerance after surgery, although six of the ten patients claimed that they had no exertional dyspnoea after operation. The changes in simple ventilatory function tests before and after operation were generally small. We suggest that measurements of exercise tolerance before and after operation should be an essential part of heart valve replacement surgery.     

Enhanced toxicity for mice of combinations of bacterial lipopolysaccharide and vincristine

Sublethal doses of vincristine (VNC) and bacterial lipopolysaccharide (LPS) administered simultaneously to adult male mice resulted in markedly enhanced mortality. All of 10 strains of Pseudomonas aeruginosa tested, 4 of 7 strains of Bacteroides, and 6 of 10 strains of Listeria monocytogenes were able to substitute for purified LPS in enhancing mortality in VNC-treated mice. Inoculation of mice with each of 10 strains of Pseudomonas, each of 7 strains of Bacteroides, and about half of the 10 strains of Listeria tested elicited increased resistance to the lethal action of purified LPS. The patterns of responses of mice receiving a lethal combination of 2 mg of LPS/kg and 1 mg of VNC/kg resembled those of mice receiving a lethal dose of 10 mg of VNC/kg alone or 15 mg of LPS/kg alone with respect to (i) serum glutamic pyruvate transaminase activity, (ii) hematocrit values, and (iii) thrombocytopenia. The patterns of responses of mice receiving a lethal combination of LPS and VNC resembled those of mice receiving a lethal dose of LPS alone with respect to (i) hypothermia, (ii) retention of sulfobromophthalein, (iii) fibrinogen level, (iv) prothrombin activity, (v) blood urea nitrogen levels, and (vi) time of death. These data are consistent with the proposition that the combination of VNC and LPS produces a fatal renal failure. Histological studies confirmed that there was extensive renal damage in mice treated with lethal doses of LPS alone or a lethal combination of LPS and VNC.     

Present morality in parkinson's disease: the ratio of observed to expected deaths with a method to calculate expected deaths

Excess mortality, i.e. more deaths than expected in a similar normal population, has been reduced in Parkinson's disease by levodopa. A California series and a large collaborative study throughout the United States show the ratio of observed to expected deaths to be normal. In contrast, a New York study was similar patients and a Montreal group of much more severely disabled patients showed greater mortality. The reasons for these differences are unclear, but some variations in results may be attributed to different methods of calculating expected deaths to derive the ratio of observed to expected deaths.