Clinical comparison of resorbable and non-resorbable barriers for guided periodontal tissue regeneration

The purpose of this study was to compare the clinical results of guided periodontal tissue regeneration (GPTR) using a resorbable barrier manufactured from a copolymer of polylactic and polyglycolic acids (Resolut Regenerative Material) with those of non-resorbable e-PTFE barrier (Gore-Tex Periodontal Material). 12 subjects participated, 6 with similarly paired class II furcations and 6 with 2 similar 2, 3-wall periodontal lesions. The resorbable and non-resorbable barriers were randomly assigned to 1 defect in each subject. Non-resorbable barriers were removed in six weeks. Plaque index (PlI), gingival index (GI), probing depth (PD), clinical attachment level (CAL) and gingival recession (R) were recorded at baseline, (i.e., immediately prior to surgery) and at 12 months postsurgically. The clinical healing was similar and uneventful in both groups. Intrabony pockets depicted significant changes from baseline (p < 0.05) for probing depth reduction and gain in clinical attachment levels. No differences were found between treatments. Class II furcations showed significant improvements from baseline (p < or = 0.05) for probing depth reduction and clinical attachment gain. No differences were detected between treatments. It is concluded that the resorbable barrier tested is as effective as the nonresorbable e-PTFE barrier for the treatment of class II furcations and intrabony defects.     

Understanding donors' motivations: a study of unrelated bone marrow donors

Medical advances in bone marrow transplantation techniques and immunosuppressive medications have dramatically increased the number of such transplants performed each year, and consequently, the demand for bone marrow from unrelated donors. Although physiological aspects of bone marrow donation have been thoroughly investigated, very few studies have examined psychosocial factors that may impact individuals' donation decisions and outcomes. To examine one particular set of donor psychosocial issues, this study investigated motives for bone marrow donation among 343 unrelated bone marrow donors who donated through the National Marrow Donor Program. Six distinct types of donor motives were identified from open-ended questionnaire responses. Donors most frequently reported motives reflecting some awareness of both the costs (to themselves) and potential benefits (to themselves and the recipient) of donation. A desire to act in accordance with social or religious precepts, expected positive feelings about donating, empathy for the recipient, and the simple desire to help another person were also commonly cited reasons for donating. Among a series of donor background characteristics, donors' gender was the variable most strongly associated with motive type; women were most likely to cite expected positive feelings, empathy, and the desire to help someone. Central study findings indicated that donor motives predicted donors reactions to donation even after the effects of donor background characteristics (including gender) were controlled. Donors who reported exchange motives (weighing costs and benefits) and donors who reported simple (or idealized) helping motives experienced the donation as less positive in terms of higher predonation ambivalence and negative postdonation psychological reactions than did remaining donors. Donors who reported positive feeling and empathy motives had the most positive donation reactions in terms of lower ambivalence, and feeling like better persons postdonation. These finding add substantially to the body of work concerning medical volunteerism generally, and also have important practical implications for the recruitment and education of potential bone marrow donors.     

Failure mechanisms of anterior cruciate ligament prostheses: in vitro wear study

Previous retrieval studies analyzing the cause of failure of anterior cruciate ligament (ACL) prostheses identified a wear mechanism. However, the relative importance of yarn on bone compared to yarn on yarn wear has not been clearly understood. Therefore, the objective of this study was to elucidate which type of wear is the dominant cause of clinical failure. A variety of ACL prosthetic structures were exposed to two in vitro tests: one for yarn on yarn and the other for a novel yarn on bone wear test system. The latter included the use of both smooth (uncut) and rough (cut) bone surfaces to simulate the conditions around the condyle and at the exit of the tibial tunnel, respectively. The damaged textile structures were viewed by SEM. The various fiber fracture morphologies were identified and classified for the two types of wear tests; for the smooth and rough bone surfaces; for the braided, knitted, woven, and twisted textile structures; and for the three types of fibers that were included: polyethylene terephthalate, polypropylene, and ultrahigh molecular weight polyethylene. The results confirmed that yarn on bone and yarn on yarn wear phenomena are associated with significantly different failure mechanisms. While the more aggressive rough (or cut) bone causes more rapid and intense fiber damage and faster ACL failure than the smooth (uncut) osseous surface, both abradants cause the same type of abrasive wear phenomenon. Differences in failure mechanisms were identified between the different textile structures and the different fiber types. By interpreting the damaged fiber images from clinically failed and retrieved ACL prostheses, we are now able to confirm that the predominant cause of synthetic ACL failure is yarn on bone abrasion. Improvements in future ACL prosthesis designs will only be possible by eliminating or minimizing the effect of this type of abrasive wear.     

Small weight loss on long-term acarbose therapy with no change in dietary pattern or nutrient intake of individuals with non-insulin-dependent diabetes

OBJECTIVES: To see if the long-term treatment of non-insulin dependent diabetes (NIDDM) with the alpha-glucosidase inhibitor acarbose affects food intake and body weight. DESIGN: Randomized, double-blind, placebo-controlled, parallel design clinical trial of 12 months duration. SUBJECTS: Subjects with NIDDM in four treatment strata: 77 on diet alone, 83 also treated with metformin, 103 also treated with sulfonylurea and 91 also treated with insulin. MEASUREMENTS: Two 3 day diet records were obtained before randomization to acarbose or placebo therapy, and additional 3 day diet records were obtained at 3, 6, 9 and 12 months after randomization. Body weight was also measured at these times. RESULTS: Of the 354 subjects randomized, 279 (79%) completed at least 9 months of therapy and, of these, 263 (94%) provided at least one diet record during the baseline period and two diet records during the treatment period. After one year, subjects on acarbose had lost 0.46 +/- 0.28 kg, which differed significantly from the 0.33 +/- 0.25 kg weight gain on placebo (P = 0.027). The difference in weight change between acarbose and placebo did not differ significantly in the different treatment strata. Being in the study had significant effects on diet, including a reduction in energy intake from 1760-1700 Kcal/d (P < 0.05), a reduction in simple sugars intake from 18.5-17.4% of energy (P < 0.001), and reductions in the number of different foods consumed (33-30, P < 0.001) and the number of meals eaten per day (4.7-4.3, P < 0.001). However, compared to placebo treatment, acarbose had no effect on energy intake, nutrient intakes, or dietary patterns. CONCLUSIONS: In subjects with NIDDM on weight-maintaining diets, long-term acarbose therapy results in a small weight loss, but has no effect on energy or nutrient intakes. The weight loss induced by acarbose may be due partly to reduced doses of concomitant oral agents and insulin and partly to energy loss due to increased colonic fermentation.     

Intracranial pressure monitoring during intraarterial papaverine infusion for cerebral vasospasm

PURPOSE: Intraarterial papaverine infusions are performed to reverse cerebral arterial vasospasm resulting from subarachnoid hemorrhage, but such infusions may lead to increases in intracranial pressure (ICP). This study was undertaken to determine when ICP monitoring is indicated during papaverine treatment. METHODS: Seventy-eight vessels were treated in 51 sessions in 28 patients with symptomatic vasospasm. ICP, papaverine doses, and infusion rates were recorded during treatment sessions. The procedural data, Hunt and Hess scores, Fisher grades, Glasgow Coma Scale scores, and ages for all subjects were reviewed and analyzed retrospectively. RESULTS: Baseline ICP ranged from 0 to 34 mm Hg. With typical papaverine doses of 300 mg per territory and infusion times ranging from 5 to 60 minutes per vessel, ICP increases above baseline during papaverine infusion ranged from 0 to 60 mm Hg. Significant (> or = 20 mm Hg) ICP increases during therapy were observed even in patients with low baseline ICP and with papaverine infused at the slowest rate. Patients with a baseline ICP of more than 15 mm Hg were much more likely to have significant ICP increases than were patients with a baseline ICP of 0 to 15 mm Hg. Hunt and Hess scores, Fisher grades, age, and Glasgow Coma Scale scores on admission and immediately before treatment did not correlate with ICP increases during papaverine infusion. Patients with ICP increases of more than 10 mm Hg during therapy were more likely to experience adverse clinical events than were patients with ICP increases of < or = 10 mm Hg. Reduction in the rate of papaverine infusion, or termination of infusion, resulted in reversal of drug-induced ICP elevation. CONCLUSION: ICP monitoring during intraarterial papaverine infusions for cerebral vasospasm is recommended for all patients and is particularly important for patients with elevated baseline ICP. Continuous ICP monitoring facilitates safe and time-efficient drug delivery.     

Glutamine substitution at alanine1649 in the S4-S5 cytoplasmic loop of domain 4 removes the voltage sensitivity of fast inactivation in the human heart sodium channel

Normal activation-inactivation coupling in sodium channels insures that inactivation is slow at small but rapid at large depolarizations. M1651Q/M1652Q substitutions in the cytoplasmic loop connecting the fourth and fifth transmembrane segments of Domain 4 (S4-S5/D4) of the human heart sodium channel subtype 1 (hH1) affect the kinetics and voltage dependence of inactivation (Tang, L., R.G. Kallen, and R. Horn. 1996. J. Gen. Physiol. 108:89-104.). We now show that glutamine substitutions NH2-terminal to the methionines (L1646, L1647, F1648, A1649, L1650) also influence the kinetics and voltage dependence of inactivation compared with the wild-type channel. In contrast, mutations at the COOH-terminal end of the S4-S5/D4 segment (L1654, P1655, A1656) are without significant effect. Strikingly, the A1649Q mutation renders the current decay time constants virtually voltage independent and decreases the voltage dependences of steady state inactivation and the time constants for the recovery from inactivation. Single-channel measurements show that at negative voltages latency times to first opening are shorter and less voltage dependent in A1649Q than in wild-type channels; peak open probabilities are significantly smaller and the mean open times are shorter. This indicates that the rate constants for inactivation and, probably, activation are increased at negative voltages by the A1649Q mutation reminiscent of Y1494Q/ Y1495Q mutations in the cytoplasmic loop between the third and fourth domains (O'Leary, M.E., L.Q. Chen, R.G. Kallen, and R. Horn. 1995. J. Gen. Physiol. 106:641-658.). Other substitutions, A1649S and A1649V, decrease but fail to eliminate the voltage dependence of time constants for inactivation, suggesting that the decreased hydrophobicity of glutamine at either residues A1649 or Y1494Y1495 may disrupt a linkage between S4-S5/D4 and the interdomain 3-4 loop interfering with normal activation-inactivation coupling.     

Path curvature in workspace and in joint space: evidence for coexisting coordinative rules in aiming

In this study we tried to establish whether point-to-point aiming movements are planned in workspace, joint space, or both. Eight right-handed subjects performed horizontal, vertical, and diagonal aiming movements on a transversal plane. Movements were performed at several speeds. Curvature variations of the hand and corresponding joint-space paths were investigated as a function of position, direction, and speed. Straightness of hand paths predominated for vertical movements but was systematically violated for horizontal and top-right to bottom-left movements. Furthermore, the hand-path curvature of the latter movements increased with speed. Joint-space paths showed more deviation from a straight line than hand paths except for top-left to bottom-right movements in which the paths were equally curved. A comparison of normalized path curvatures at the hand and joint level indicated that in aiming, the coordinative rule of straight-line production seems to apply to both workspace and joint-space planning. The present findings confirm Kawato's (1996) views that optimization processes operate concurrently at the two control levels of arm-trajectory formation under study.     

Identification of Db- and Kb-restricted subdominant cytotoxic T-cell responses in lymphocytic choriomeningitis virus-infected mice

Antiviral cytotoxic T-cells are critical for control of lymphocytic choriomeningitis virus (LCMV) infection in mice. In H-2b mice, the antiviral response is directed against three Db-restricted epitopes in the viral nucleoprotein (NP396-404) and glycoprotein (GP276-286 and GP33-41). Our present data revealed a clear hierarchy among these three epitopes, in which NP396-404 is immunodominant, followed by GP33-41 and GP276-286, respectively. In order to identify additional CTL epitopes in the LCMV nucleoprotein and glycoprotein, we used the motifs for Db2- and Kb-binding peptides, combined with MHC class I-binding assays. Out of 23 Db motif-fitting peptides, we identified 4 Db binders, one of which (GP92-101) turned out to be a new CTL epitope. Among 28 Kb motif-fitting peptides, 12 bound Kb, and one of these (NP205-212) was a CTL epitope. Both newly identified CTL peptides were recognized by LCMV-immune splenocytes after secondary in vitro stimulation. Both peptides bound their MHC class I molecules with intermediate affinity (470 and 170 nM for GP92-101 and NP205-212, respectively). Responses against these peptides were weaker than the responses against the three major epitopes. None of the high affinity binders were new epitopes, suggesting that high affinity binders are either immunodominant epitopes or no epitopes at all. Thus, analysis of 51 Kb and Db motif-fitting peptides yielded 2 new, subdominant epitopes. Immunization of C57BL/6 mice with these peptides, or vaccinia virus recombinants expressing these epitopes as minigenes, protected against chronic LCMV infection, demonstrating that immunization with subdominant epitopes can confer protection against chronic viral infection.     

Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer

BACKGROUND: The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. METHODS: Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with follow-up data received tamoxifen alone; 767 received methotrexate, fluorouracil, and tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and tamoxifen (CMFT). The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. RESULTS: Through 5 years of follow-up, chemotherapy plus tamoxifen resulted in significantly better disease-free survival than tamoxifen alone (90% for MFT versus 85% for tamoxifen [P = .01]; 89% for CMFT versus 85% for tamoxifen [P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for tamoxifen [P = .008]; 91% for CMFT versus 87% for tamoxifen [P = .006]) and survival (97% for MFT versus 94% for tamoxifen [P = .05]; 96% for CMFT versus 94% for tamoxifen [P = .03]). Compared with tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. CONCLUSIONS: Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy.