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Biomedical subjects

M Israel

Publications and source records attributed to M Israel.

At least 19 recordsLinked to original sources

[Epidemiology of attempted suicide using drugs. An inquiry from the Dresden University Clinic].

BACKGROUND AND OBJECTIVE: Little representative data of the epidemiology of attempted suicide exists in Germany. In this study the frequency of parasuicidal drug intoxication, the distribution of age and gender, as well as the kind and origin of used drugs were evaluated. Furthermore the knowledge about used drugs and possible adverse effects of a previously given medication were analysed. PATIENTS AND METHODS: Over a period of 2 years (January 1998-December 1999) 155 patients (41 males, 114 females, average age 40.5 years) with drug intoxication by attempted suicide were recruited at the University Hospital of Dresden, Germany, for further retrospective analysis. RESULTS: 74 % of these patients were women. Sedatives and hypnotics were most frequently used for parasuicide (44 %), followed by analgesics (18 %) and antidepressants (12 %). Benzodiazepines and benzodiazepine-agonists were the most commonly used drugs (32 %). Moreover, 80 % of all drugs used had been prescribed by physicians. Approximately half of the patients were well-informed about drugs taken. In 43 (47 %) of 92 patients with long-term medication an adverse effect was considered as a possible cause of the attempted suicide. CONCLUSION: Our data underline the importance of attempted suicide in view of the frequency of their use, the need of hospitalization, the required intensive care and possible relapses. Because the majority of drugs used were prescribed by physicians, before giving any medication to their possible suicidal use should be considered.

Adolescent↗

Bulimia nervosa with co-morbid avoidant personality disorder: behavioural characteristics and serotonergic function.

BACKGROUND: Separate lines of research link lowered serotonin tone to interpersonal submissiveness and bulimia nervosa (BN). We explored the impact of co-morbid avoidant personality disorder (APD), as a proxy for submissiveness, on behavioural inhibition and serotonin function in women with BN. METHOD: Participants included women with BN with co-morbid APD (BNA +, N = 13); women with BN but without APD (BNA-, N = 23), and control women with neither BN nor APD (N = 23). The women were assessed for psychopathological tendencies and eating disorder symptoms, and participated in a computerized laboratory task that measured behavioural inhibition and disinhibition. Participants also provided blood samples for measurement of serial prolactin responses following oral administration of the partial 5-HT agonist meta-chlorophenylpiperazine (m-CPP). RESULTS: The BNA+ group had higher scores than the other groups on self-report measures of submissiveness, social avoidance, restricted emotional expression, affective instability and self-harming behaviours. Compared with the other groups, the BNA+ group tended to be more inhibited under cues for punishment on the computerized task and to have blunted prolactin response following m-CPP. The bulimic groups did not differ from each other on current eating symptoms or on frequencies of other mental disorders. CONCLUSIONS: Findings indicate that women with BN and co-morbid APD may be characterized by interpersonal submissiveness and avoidance, affective instability, self-harm, behavioural inhibition in response to threat and lower sensitivity to serotonergic activation. These findings may indicate common, serotonergic factors, associated with social submissiveness, behavioural inhibition to threat and BN.

Adolescent↗

The effect of low level radiofrequency electromagnetic radiation on the excretion rates of stress hormones in operators during 24-hour shifts.

The aim of the study was to investigate the effect of long term exposure to low level radiofrequency (RF) electromagnetic (EM) radiation on the excretion rates of stress hormones in satellite station operators during 24-hour shifts. Twelve male operators at a satellite station for TV communications and space research were studied during 24-hour shifts. Dosimetric evaluation of the exposure was carried out and showed low level exposure with specific absorption of 0.1127 J.kg-1. A control group of 12 unexposed male operators with similar job task and the same shift system were studied, too. The 11-oxycorticosteroids (11-OCS), adrenaline and noradrenaline were followed by spectrofluorimetric methods on 3-hour intervals during the 24-hour shifts. The data were analyzed by tests for interindividual analysis, Cosinor analysis and analysis of variance (ANOVA). Significant increase in the 24-hour excretion of 11-OCS and disorders in its circadian rhythm, manifested by increase in the mesor, decrease in the amplitude and shift in the acrophase were found in the exposed operators. The changes in the excretion rates of the catecholamines were significant and showed greater variability of both variables. The long term effect of the exposure to low-level RF EM radiation evoked pronounced stress reaction with changes in the circadian rhythm of 11-OCS and increased variability of catecholamines secretion. The possible health hazards associated with observed alteration in the stress system need to be clarified by identification of their significance and prognostic relevance.

11-Hydroxycorticosteroids↗

Molecular models of N-benzyladriamycin-14-valerate (AD 198) in complex with the phorbol ester-binding C1b domain of protein kinase C-delta.

N-Benzyladriamycin-14-valerate (AD 198) is a semisynthetic anthracycline with experimental antitumor activity superior to that of doxorubicin (DOX). AD 198, unlike DOX, only weakly binds DNA, is a poor inhibitor of topoisomerase II, and circumvents anthracycline-resistance mechanisms, suggesting a unique mechanism of action for this novel analogue. The phorbol ester receptors, protein kinase C (PKC) and beta2-chimaerin, were recently identified as selective targets for AD 198 in vitro. In vitro, AD 198 competes with [3H]PDBu for binding to a peptide containing the isolated C1b domain of PKC-delta (deltaC1b domain). In the present study molecular modeling is used to investigate the interaction of AD 198 with the deltaC1b domain. Three models are identified wherein AD 198 binds into the groove formed between amino acid residues 6-13 and 21-27 of the deltaC1b domain in a manner similar to that reported for phorbol-13-acetate and other ligands of the C1 domain. Two of the identified models are consistent with previous experimental data demonstrating the importance of the 14-valerate side chain of AD 198 in binding to the C1 domain as well as current data demonstrating that translocation of PKC-alpha to the membrane requires the 14-valerate substituent. In this regard, the carbonyl of the 14-valerate participates in hydrogen bonding to the deltaC1b while the acyl chain is positioned for stabilization of the membrane-bound protein-ligand complex in a manner analogous to the acyl chains of the phorbol esters. These studies provide a structural basis for the interaction of AD 198 with the deltaC1b domain and a starting point for the rational design of potential new drugs targeting PKC and other proteins with C1 domains.

Antibiotics, Antineoplastic↗

Implications of impulsive and affective symptoms for serotonin function in bulimia nervosa.

BACKGROUND: Bulimic, impulsive and depressive syndromes have all been associated with abnormalities in brain serotonin (5-hydroxytryptamine; 5-HT) mechanisms. METHODS: We had 26 bulimic women and 22 normal-eater women report impulsive, affective, self-destructive and bulimic symptoms, and then provide serial blood samples for measurement of: [3H]-paroxetine binding in platelets; and, prolactin (PRL) responses following oral meta-chlorophenylpiperazine (m-CPP). RESULTS: Bulimic status was associated with markedly reduced density of paroxetine-binding sites, modest blunting of m-CPP stimulated PRL response, and greater nausea following m-CPP. Biological variables did not co-vary with most psychopathological or eating-symptom indices. However, there were inverse associations (in bulimic women only) between scores indicating impulsivity (largely 'unreflectiveness') and density of platelet 5-HT uptake sites. CONCLUSIONS: Our observations link bulimia nervosa to altered 5-HT functioning, and suggest that there may be a relatively symptom-specific association between impulsivity and reduced 5-HT reuptake.

Adult↗

Anthracycline drug targeting: cytoplasmic versus nuclear--a fork in the road.

The anthracycline antibiotics doxorubicin (Adriamycin; DOX) and daunorubicin (DNR) continue to be essential components of first-line chemotherapy in the treatment of a variety of solid and hematopoietic tumors. The overall efficacies of DOX and DNR are, however, impeded by serious dose-limiting toxicities, including cardiotoxicity, and the selection of multiple mechanisms of cellular drug resistance. These limitations have necessitated the development of newer anthracyclines whose structural and functional modifications circumvent these impediments. In this review, we will present recent strategies in anthracycline design and assess their potential therapeutic merits. Current anthracycline design has diverged to target either cytoplasmic or nuclear sites. Nuclear targets have been broadened to include not only topoisomerase II (topo II) inhibition through ternary complex stabilization and catalytic inhibition, but also topoisomerase I (topo I) inhibition and transcriptional inhibition. In contrast, cytoplasmic targeting focuses on anthracycline binding to protein kinase C (PKC) regulatory domain with consequent modulation of activity.

Animals↗

Catalytic inhibition of DNA topoisomerase II by N-benzyladriamycin (AD 288).

N-Benzyladriamycin (AD 288) is a highly lipophilic, semi-synthetic congener of doxorubicin (DOX). Unlike DOX, which stimulates double-stranded DNA scission by stabilizing topoisomerase II/DNA cleavable complexes, AD 288 is a catalytic inhibitor of topoisomerase II, capable of preventing topoisomerase II activity on DNA. The concentration of AD 288 required to inhibit the topoisomerase II-catalyzed decatenation of linked networks of kinetoplast DNA was comparable to that for DOX. However, AD 288 did not stabilize cleavable complex formation or stimulate topoisomerase II-mediated DNA cleavage. In addition, AD 288 inhibited the formation of cleavable complexes by etoposide in a concentration-dependent manner. Human CCRF-CEM cells and murine J774. 2 cells exhibiting resistance against DOX, teniposide, or 3'-hydroxy-3'-deaminodoxorubicin through reduced topoisomerase II activity remained sensitive to AD 288. These studies suggest that AD 288 inhibits topoisomerase II activity by preventing the initial non-covalent binding of topoisomerase II to DNA. Since AD 288 is a potent DNA intercalator, catalytic inhibition is achieved by prohibiting access of the enzyme to DNA binding sites. These results also demonstrate that specific substitutions on the aminosugar of DOX can alter the mechanism of topoisomerase II inhibition.

Antineoplastic Agents, Phytogenic↗

Pilot study of the tolerability and toxicity of intravesical valrubicin immediately after transurethral resection of superficial bladder cancer.

OBJECTIVES: To assess in a pilot study the safety, tolerability, and technical feasibility of administering intravesical valrubicin immediately after transurethral resection of bladder tumors (TURBT) in patients with superficial bladder cancer and to evaluate the optimal dose of valrubicin and its systemic absorption. METHODS: Twenty-two patients with recurrent or newly diagnosed Stage Ta or T1 transitional cell tumors received a single dose of 400 mg, 600 mg, or 800 mg of intravesical valrubicin immediately after TURBT. Four patients thought to be at high risk of recurrence were followed up with five additional doses of 800 mg valrubicin, given weekly. RESULTS: The use of valrubicin after TURBT was generally well tolerated. Little evidence was found to suggest a direct relationship among the dose of valrubicin, the time between the end of TURBT and drug instillation, and the occurrence of most bladder symptoms. The most commonly reported adverse events included dysuria (77%), hematuria (59%), and urgency/frequency (23%). Pharmacokinetic analyses revealed that the mean systemic exposure to valrubicin and its metabolites depended on the extent of the TURBT and the damage to the bladder wall. CONCLUSIONS: The results of this study indicated that administration of valrubicin immediately after TURBT is feasible.

Administration, Intravesical↗

Rationale for intralesional valrubicin in chemoradiation of squamous cell carcinoma of the head and neck.

OBJECTIVES/HYPOTHESIS: With some advanced squamous cell carcinomas (SCCs) of the head and neck, chemoradiation therapy may obviate the need for surgical intervention. However, both modalities are known to produce organ toxicities, and tumor insensitivity remains problematic. Thus there is a clear need for the development of new treatment strategies. Accordingly, preclinical studies to evaluate the use of valrubicin, a contact-safe, mechanistically novel antitumor agent, combined with low-dose radiation for the therapy of SCC have been conducted. METHODS: The comparative in vitro antitumor activities of valrubicin with or without irradiation versus cisplatin were evaluated using human-derived sensitive and cisplatin-resistant SCC cell lines. A hamster cheek pouch model of SCC was used to assess the efficacy of weekly intratumoral valrubicin injections with and without concurrent low-dose irradiation. RESULTS: Valrubicin cytotoxicity was found to be comparable in both sensitive and platinum-resistant cell lines and superior to cisplatin. The addition of minimally cytotoxic cell irradiation (300-450 cGy) resulted in prolonged G2/M cell cycle arrest and a supraadditive increase in apoptotic cell death. In hamsters, once a week x 3 intratumoral drug injections (3, 6, or 9 mg) were growth inhibitory; however, when valrubicin (6 mg) was combined with minimally cytotoxic irradiation (150, 250, or 350 cGy) significant tumor shrinkage was observed. CONCLUSIONS: Valrubicin produces supra-additive effects against SCC when combined with low-dose irradiation. This effect appears to correlate with the ability of valrubicin, a cytoplasmic-localizing drug, to inhibit protein kinase C. Therapeutic use of valrubicin against SCC could provide for reduced radiation doses with consequent improved efficacy and reduction in host toxicity.

Animals↗

Laser de-epithelialization for enhanced guided tissue regeneration. A paradigm shift?

The rationale for laser de-epithelialization stems from the attempts to block the down-growth of epithelium into the healing periodontal wound after surgery and prevent formation of a long junctional epithelial attachment. This concept has seen numerous techniques for accomplishing the blockage of epithelium. The advent of GTR was an offshoot of this concept and led Gottlow et al [table: see text] to examine the effects of selectively blocking certain cell types from contacting the root surface during periodontal wound healing. The use of a CO2 laser to de-epithelialize the gingival flaps is an attempt to exclude this cell type from the healing wound and has been used with and without the benefit of GTR membranes. In a study on beagle dogs, the histologic results of using membranes and the laser procedure enhanced the wound healing and regeneration of new bone, cementum, and connective tissue attachment when compared with paired defects using the membranes alone. The results from the human studies and case reports combined with the animal studies indicate a positive benefit in wound healing because of the laser de-epithelialization technique. The use of an osseous graft in treatment of periodontal defects has been shown to stimulate new bone growth effectively and to regenerate new attachment. It has been speculated that the additional benefit of an osseous graft in GTR procedures is the organization of the blood clot at initial healing, which may tend to maintain the space needed for regeneration and to provide a matrix for the fibrin clot to retard epithelial down-growth. Studies comparing the results of osseous grafting with flap debridement always have shown that the amount of new bone formation and clinical new attachment favor the grafted sites versus paired nongrafted sites. The effects of removal of the pocket epithelium at the time of periodontal surgery have been studied by several authors, and these studies generally shown an incomplete removal of the sulcular epithelium by the inverse bevel incision. Epithelial excision was studied by Centty et al, who compared the removal of sulcular epithelium by the CO2 laser technique with conventional methods. Their results confirm that (1) a more complete removal of sulcular epithelium was obtained by laser than by knives, and (2) the technique effectively removes the oral and sulcular epithelium from a gingival flap without damaging the viability of the flap during wound healing. The technique as described in this article was used by Israel et al to verify further the ability to maintain a viable gingival flap during multiple laser deepithelialization procedures in humans during the first 30 days of healing. [table: see text] The concept of laser de-epithelialization as an adjunct to regenerative periodontal procedures currently is being studied in a multicenter university setting using a parallel study in controlled clinical trials. The first of these reports was mentioned previously (Araujo et al, unpublished data) and shows the enhanced wound healing of periodontal defects through use of the laser de-epithelialization technique. The authors believe that this technique has shown significantly better results than those obtained through conventional osseous grafting alone and appears to be comparable to the results reported for GTR procedures with barrier membranes. This concept provides a paradigm shift from the conventional use of GTR therapy by acknowledging the difficulty in controlling epithelium during the early wound healing. It also allows a more comprehensive therapy for treating periodontal disease that addresses the generalized nature of the disease, with multiple lesions being treated concurrently in an economical manner. The patient presenting with generalized advanced periodontal disease could have several defects definitively treated in one quadrant using the laser deepithelialization technique without the need for multiple membrane therapy. (ABSTRACT TRUNCATE

Alveolar Bone Loss↗

Naftazone reduces glutamate cerebro spinal fluid levels in rats and glutamate release from mouse cerebellum synaptosomes.

It is well known that an excessive release of glutamate in the mammalian brain plays a major role in several neurological diseases. Naftazone (Etioven) is a currently used vasoprotectant drug that is metabolized in humans by reduction and glucuronidation. In the present study naftazone was found to decrease glutamate levels in the cerebro spinal fluid (CSF) of rats treated for 15 days, as determined by a chemiluminescent glutamate assay reaction. Naftazone and its glucuronide derivative also reduced respectively spontaneous and high K+-evoked glutamate release from mouse cerebellum synaptosomes. It is likely that naftazone and its glucuronide metabolite contribute in vivo to decrease glutamate levels in the CSF through their inhibitory actions on glutamate release.

Animals↗

Pharmacology of N-benzyladriamycin-14-valerate in the rat.

PURPOSE: N-Benzyladriamycin-14-valerate (AD 198) is a semisynthetic anthracycline analogue superior to doxorubicin (DOX) both in vitro and in experimental rodent tumor models, and with differing mechanistic properties from those of the parental antibiotic agent. In the present study, we examined the metabolic fate and hematotoxicity of AD 198 in rats, with a view to determining whether some of the therapeutic properties observed for this drug might be due to a DOX prodrug effect. METHODS: Samples of plasma, bile and urine were obtained at various times following intravenous (i.v.) [14C]-AD 198 administration to rats and were analyzed by reversed-phase HPLC with flow-fluorescence detection and complementary liquid scintillography. In other animals, red blood cell and white blood cell (WBC) counts were determined for blood obtained by retrobulbar sampling on selected days from groups of animals receiving either AD 198 or DOX at several dose levels, as well as from vehicle controls. RESULTS: Following a single iv dose of [14C]-AD 198 (5 mg/kg; equivalent to the optimal murine antitumor dose) in anesthetized rats, a triphasic plasma decay pattern for parental drug was evident with extremely rapid alpha and beta phases followed by a very long terminal elimination phase. Principal plasma products included N-benzyladriamycin (AD 288) and N-benzyladriamycinol (AD 298) together with very low levels of DOX and doxorubicinol (DOXOL). Analysis of bile from anesthetized and conscious animals receiving AD 198 revealed DOX to be the principal biliary fluorescent species together with low levels of AD 288, AD 298 and DOXOL; no parental drug was seen. By contrast, AD 288 was the principal urinary product, together with low levels of AD 298 and DOX; again, no parental drug was evident. Dose recovery (8 h) in the respective bile and urine of anesthetized rats was 12.4% and 13.2% based upon total fluorescence versus 1% and 15.3% of the administered radiolabel. In conscious animals, 13.4% of drug fluorescence was recovered in the bile (48 h), while in urine 16.6% and 77.1% of drug fluorescence and radiolabel, respectively, were eliminated over 72 h. The discrepancy between recovery of drug fluorescence and 14C was due to the production of nonfluorescent hippuric acid (benzoylglycine) and N-benzyl daunosamine as a consequence of hepatic and renal drug metabolism. In the separate hematotoxicity studies, AD 198 (24.6 mg/ kg i.v.; equivalent to the murine LD50 dose), produced a 45% reduction (nadir day 3-5) in WBC count, with recovery by day 10. By contrast, DOX (10 mg/kg i.v.; equivalent to the mouse highest nonlethal dose) produced an 80% decline in WBC with only partial recovery by day 17. CONCLUSIONS: By virtue of the low systemic DOX levels and low hematotoxicity observed in rats receiving AD 198, the in vivo therapeutic superiority of AD 198 cannot be attributed to substantial intracellular DOX generation. The conclusion that the therapeutic superiority of AD 198 compared to DOX results from the mechanistic differences between these two drugs is further supported by recent observations on their biochemical differences with regard to protein kinase C and topoisomerase II inhibition.

Animals↗

Control of the calcium concentration involved in acetylcholine release and its facilitation: an additional role for synaptic vesicles?

2,5-Diterbutyl-1,4-benzohydroquinone, a specific blocker of Ca2+-ATPase pumps, increased acetylcholine release from an identified synapse of Aplysia, as well as from Torpedo and mouse caudate nucleus synaptosomes. Because 2,5-diterbutyl-1,4-benzohydroquinone does not change the presynaptic Ca2+ influx, the enhancement of acetylcholine release could be due to an accumulation of Ca2+ in the terminal. This possibility was further checked by studying the effects of 2,5-diterbutyl-1,4-benzohydroquinone on twin pulse facilitation, classically attributed to residual Ca2+. While preventing the fast sequestration of Ca2+ by presynaptic organelles, 2,5-diterbutyl-1,4-benzohydroquinone magnified both twin pulse facilitation observed under low extracellular Ca2+ concentration and twin pulse dysfacilitation observed under high extracellular Ca2+ concentration. Thus, it is concluded that 2,5-diterbutyl-1,4-benzohydroquinone, by preventing Ca2+ buffering near transmitter release sites, modulates acetylcholine release. As 2,5-diterbutyl-1,4-benzohydroquinone was also shown to decrease by 50% the uptake of 45Ca2+ by isolated synaptic vesicles, we propose that synaptic vesicles can control the presynaptic Ca2+ concentration triggering the release of neurotransmitter.

Acetylcholine↗

Increase in syntaxin 1B and glutamate release in mossy fibre terminals following induction of LTP in the dentate gyrus: a candidate molecular mechanism underlying transsynaptic plasticity.

A growing body of evidence suggests that modulation of certain proteins of the exocytotic machinery is, in part, involved in the biochemical changes that underlie long-term synaptic plasticity. We have previously shown that the induction of long-term potentiation (LTP) at perforant path to dentate granule cell synapses in the rat hippocampus induces changes in the mRNA levels of syntaxin 1B and synapsin I, known to be involved in neurotransmitter release. Immunohistochemical staining suggested that concomitant changes in these proteins occurred at mossy fibre synapses, downstream of those synapses at which LTP was induced, leading us to postulate that such a mechanism might underlie a form of transsynaptic plasticity. Here we have used a specific mossy-fibre synaptosome preparation to quantify levels of proteins and measure, using a chemiluminescent glutamate assay, depolarization-induced glutamate release from these synaptosomes after induction of LTP in the dentate gyrus in vivo. We show that 5 h after the induction of LTP, there is an increase in the protein levels of syntaxin 1B and, although to a lesser extent, the synapsins I and II, associated with an increase in depolarization-induced release of glutamate within these terminals. Increases in both the protein levels and glutamate release were not observed when dentate gyrus LTP was blocked by an NMDA receptor antagonist. From these results we propose a molecular mechanism for the propagation of synaptic plasticity through hippocampal circuits.

Animals↗

Cytotoxicity and intracellular biotransformation of N-benzyladriamycin-14-valerate (AD 198) are modulated by changes in 14-O-acyl chain length.

N-benzyladriamycin-14-valerate (AD 198) is pharmacologically superior to Adriamycin (ADR) based upon comparable cytotoxicity, decreased cardiotoxicity and the ability of AD 198 to circumvent multidrug resistance conferred by either P-glycoprotein overexpression or reduced topoisomerase II activity. AD 198, however, suffers from systemic lability of the 14-O-valerate moiety to enzymatic and non-enzymatic cleavage to yield N-benzyladriamycin (AD 288), which is more similar to ADR in activity. The purpose of this study was to determine whether stability of the ester linkage could be achieved while preserving the favorable characteristics of AD 198 by using a series of N-benzylated ADR congeners containing 14-O-acyl substitutions of incrementally shorter carbon chain lengths. Results from this study indicate that the linear five-carbon valerate substitution is the minimum length necessary to circumvent P-glycoprotein and prevent inhibition of topoisomerase II activity. In addition, although AD 198 is not a pro-drug of AD 288, intracellular 14-O-acyl cleavage appears to contribute to the cytotoxicity of AD 198.

Animals↗

Differences in whole blood serotonin levels based on a typology of parasuicide.

Suicidal behavior has to be considered as a multifactorial phenomenon, which can be analyzed in a classifying-phenomenological manner. We have examined the relation of parasuicide typology to whole blood concentrations of serotonin, HVA, and tryptophan in 58 patients classified into 4 groups of parasuicide typology compared to 22 nonsuicidal depressed patients and 20 healthy subjects. Suicidal patients classified as impetuous, desperate and ambivalent types had significantly reduced whole blood 5-HT levels in comparison with the appealing type as well as nonsuicidal subjects. No differences were detected in the HVA content, but whole blood tryptophan concentrations were significantly reduced in impetuous suicidal patients and depressed patients compared to healthy subjects. This study provides evidence for reduced whole blood serotonin content based on different types of parasuicide.

Adult↗

An epithelial exclusion technique using the CO2 laser for the treatment of periodontal defects.

When treating osseous defects associated with periodontitis, the healed result is a compromised regeneration of the attachment apparatus from epithelial downgrowth. This article demonstrates a laser ablation technique for excluding the epithelium from contacting the root surface of the periodontal wound. In accordance with the principles of guided tissue regeneration, the epithelium should be excluded for at least 30 days after surgical therapy. A series of case reports demonstrate the technique and the 6-month results that can be obtained using this approach. The regenerated tissue is confirmed through reentry procedures and radiographs.

Alveolar Bone Loss↗