Biomedical subjects
S Roy
Publications and source records attributed to S Roy.
Pediatric renal transplant experience in Memphis, Tennessee.
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The effects of spiramycin and/or scaling on advanced periodontitis in humans.
It has long been questioned whether antibiotics, used as a supplement to traditional therapy, provide any lasting benefit in the treatment of chronic periodontitis. This study was designed to evaluate Spiramycin as an adjunct to scaling and root planing in the treatment of advanced chronic periodontitis. In total, 193 patients with advanced periodontitis were recruited in seven centres using selection criteria previously described. After undergoing thorough scaling and root planing, all patients randomly received either Spiramycin, 1,500,000 international units, twice per day (IU, bid) for 14 days (96 patients), or a visually-identical placebo capsule (97 patients). The clinical parameters measured were plaque index, crevicular fluid level, probing depths, bleeding on probing and attachment level changes. Data was recorded at baseline, two-, eight-, 12- and 24-weeks visits. A total of 189 patients completed the study (96 placebo, 93 Spiramycin). Statistically significant differences in probing depth, favoring Spiramycin, were seen at two weeks (p < 0.0125), eight weeks (p < 0.0020), 12 weeks (p < 0.0032) and 24 weeks (p < 0.0075). Spiramycin also produced a significant improvement in attachment level at 12 weeks (p < 0.0146). All other clinical parameters showed no difference between drug and placebo. This study shows that Spiramycin, as an adjunct to thorough scaling and root planing, provides a statistically significant improvement in probing depths for up to 24 weeks when compared with scaling and root planing alone. Both longer studies and microbiologic evaluations are necessary to determine whether a more lasting benefit is possible.
Results of a double-blind, placebo-controlled clinical trial program of single-dose ceftizoxime versus multiple-dose cefoxitin as prophylaxis for patients undergoing vaginal and abdominal hysterectomy.
In a series of three double-blind, controlled, clinical studies, the efficacy and safety of a single 1 gram dose of ceftizoxime were compared with those of a standard regimen, three 2 gram doses of cefoxitin, for prophylaxis of perioperative infection in women undergoing abdominal or vaginal hysterectomy. Two hundred and twenty-seven patients received ceftizoxime prophylaxis and 234 patients received cefoxitin prophylaxis. Study 1 entered 110 patients in Dallas, Texas and Los Angeles, California. Study 2 entered 242 patients in Canada. Study 3 entered 109 patients in Denver, Colorado. Within studies, the distribution of surgical procedures was comparable between antibiotic groups. The groups were similar for demographic and medical factors at each center and overall. Analyses were performed within and across studies, applying consistent criteria to the selection of evaluable patients and to the definitions of prophylactic success and primary and secondary prophylactic failure. Three hundred and sixteen patients were evaluable, 160 who received ceftizoxime and 156 who received cefoxitin. Overall, complete prophylactic success occurred in 138 of 160 evaluable patients (86.3 percent) receiving ceftizoxime and 128 of 156 evaluable patients (82.1 percent) receiving cefoxitin. Prophylactic success rates differed by study as well as by type of hysterectomy. In studies 1 and 2, prophylactic success rates for ceftizoxime were 95.1 and 87.6 percent, respectively, versus 93.1 and 87.8 percent for cefoxitin. In study 3, success rates were lowest, 70.0 percent for ceftizoxime and 59.5 percent for cefoxitin. Among evaluable patients overall, prophylactic success rates after vaginal hysterectomy were 91.0 percent for those receiving ceftizoxime and 85.1 percent for those receiving cefoxitin. After abdominal hysterectomy, success rates were 78.3 percent for both groups. Febrile morbidity rates and duration of hospitalization were comparable for both groups across all studies and within individual studies. Ceftizoxime and cefoxitin were safe and well tolerated. The results of these controlled studies indicate that single-dose ceftizoxime is as effective and safe as multiple-dose cefoxitin when used as adjunctive chemoprophylaxis in patients at risk of postoperative infection after vaginal or abdominal hysterectomy.
A reanalysis of the Cu-7 intrauterine contraceptive device clinical trial and the incidence of pelvic inflammatory disease: a paradigm for assessing intrauterine contraceptive device safety.
OBJECTIVE: We calculated and compared the incidence of pelvic inflammatory disease in a 10% random sample of the Cu-7 intrauterine contraceptive device (G.D. Searle & Co., Skokie, Ill.) clinical trial with the rates reported to the Food and Drug Administration and those in subsequent trials published in the world literature. STUDY DESIGN: A 10% random sample of the Cu-7 clinical trial was examined because calculations had demonstrated this random sample to be sufficient in size (n = 1614) to detect a difference in rates of pelvic inflammatory disease from those reported to the Food and Drug Administration. An audit of a subset of the patient files, compared with the original files in Skokie, Illinois, confirmed that the files available for analysis were complete. Standard definitions were used to identify cases of pelvic inflammatory disease and to calculate rates of pelvic inflammatory disease. The world literature on Cu-7 clinical trials was reviewed. RESULTS: The calculated crude and Pearl index rates of pelvic inflammatory disease were consistent with those rates previously reported to the Food and Drug Administration and published in the medical literature. Life-table pelvic inflammatory disease rates were not different between nulliparous and parous women and pelvic inflammatory disease did not differ from basal annual rates in fecund women. CONCLUSION: On the basis of the analysis of this 10% sample, the pelvic inflammatory disease patient rates reported to the Food and Drug Administration for the entire Cu-7 clinical trial are accurate and are similar to those published in the world literature.
Wartime colon injuries: primary repair or colostomy?
A retrospective non-randomized study, comparing primary repair with colostomy, was made on a series of 102 patients with penetrating intraperitoneal colon injuries, in a war surgery programme in Cambodia. The overall case fatality rate (CFR) was 25.5%, whereas in the primary repair group CFR was 20%, compared to 30.8% in the colostomy group. The difference was not statistically significant (P = 0.30). Adjustment for possible confounding factors in the two groups did not alter the results. Considering the numerous advantages to the patient of a primary closure in the precarious situations where war surgery is often performed, this technique merits consideration.
Piperacillin and tazobactam versus clindamycin and gentamicin in the treatment of hospitalized women with pelvic infection. The Piperacillin/tazobactam Study Group.
OBJECTIVE: To compare the efficacy and safety of a combination of piperacillin and tazobactam with that of clindamycin and gentamicin in the treatment of hospitalized women with infections of the upper genital tract. METHODS: This was a randomized open-label trial in hospitalized women with infections of the upper genital tract. Patients were recruited at 12 hospitals in the United States and two hospitals in Canada and were randomly assigned to one of two regimens in a 2:1 ratio. One group received piperacillin, 3 g every 6 hours, and tazobactam, 375 mg every 6 hours; the other group received clindamycin, 900 mg every 8 hours, and gentamicin, 2.5-5.0 mg/kg/day in three divided doses. Therapy with the assigned regimen was to be administered for a minimum of 3 days. Cultures for aerobic and anaerobic bacteria were obtained from the site of infection before initiation of therapy. Cultures for Chlamydia trachomatis were also obtained from patients with endometritis or pelvic inflammatory disease. Subjects were evaluated for clinical and bacteriologic response at 24-72 hours and 2-4 weeks after completing therapy. RESULTS: Two hundred ninety-nine patients were enrolled; 196 were in the piperacillin-tazobactam group and 103 were in the clindamycin-gentamicin group. The most common diagnoses were endometritis (146) and pelvic inflammatory disease (115). The most common microorganisms recovered included: Peptostreptococcus sp (99), Prevotella sp (87), black pigmented Bacteroides (29), B fragilis (11), enterococci (64), group B streptococcus (26), Escherichia coli (31), Neisseria gonorrhoeae (49), and C trachomatis (19). A favorable clinical response occurred in 84.7% (166 of 196) of piperacillin-tazobactam patients and 87.3% (90 of 103) of clindamycin-gentamicin patients. Among those evaluable for bacteriologic response, 78% (67 of 86) and 82% (23 of 28), respectively, had a favorable response. Diarrhea occurred significantly more frequently in the piperacillin-tazobactam group (9.7 versus 2.9%; P = .04), but the majority of episodes were mild to moderate. None of the adverse experiences in either treatment group were considered life-threatening and drug-related. CONCLUSION: The combination of piperacillin and tazobactam is an effective and well-tolerated antibiotic regimen for the treatment of infections of the upper genital tract in women.
Comparison of the expression and function of the transcription factor PU.1 (Spi-1 proto-oncogene) between murine macrophages and B lymphocytes.
The expression of mRNA encoding the DNA-binding protein PU.1 (Spi-1) is restricted to B lymphocytes and macrophages. The role of PU.1 in tissue-specific transcriptional regulation in the two cell types was examined by co-transfection of a PU.1 expression plasmid with vectors containing B cell (IgH enhancer) or macrophage-specific (c-fms) transcription control elements. Cotransfection of the PU.1 expression plasmid in MOPC31C B cells trans-repressed the IgH enhancer but trans-activated the c-fms promoter. The latter was insufficient to overcome a block to transcription elongation that determines macrophage-specific c-fms gene expression. In the macrophage line RAW264, PU.1 had no effect on the c-fms promoter, but trans-repressed the activity of a c-fms reporter plasmid containing the transcription attenuator. The effects of PU.1 in both cell types were distinct from those of c-ets-2, a related factor, which trans-activated the c-fms promoter in both B cells and macrophages but also repressed the IgH enhancer. PU.1 was shown to be one of several nuclear proteins that bound a critical cis-acting element of the IgH enhancer, microB, but analysis of nuclear extracts of a wide range of B cell and macrophage lines demonstrated a strong correlation between macrophage phenotype and nuclear PU.1 expression. The data suggest that differences in nuclear PU.1 expression and function between macrophages and B cells may play a role in lineage divergence.
Solitary intracranial plasmacytoma of the skull base.
Two cases of extradural solitary plasmacytoma (SIP) with infiltration of the dura, destruction of the skull base, multiple cranial nerve palsies and proptosis are presented. The cases were treated aggressively with surgery and radiotherapy and showed no signs of progressing to multiple myeloma after 15 months and four and a half years respectively.
Platelet parameters detected by cell counter in an unusual case of extreme thrombocytosis.
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Clinical trials and clinical practice.
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A study of colchicine tubulin complex by donor quenching of fluorescence energy transfer.
The utility of collisional quenching of energy donors in fluorescence energy transfer is described. In multi-donor single acceptor systems, which contain different classes of donors (as distinguished by their accessibility towards a collisional quencher), donor quenching may be used to assess the fraction of energy transfer from each class of donor. The tubulin-colchicine complex was used as a donor-acceptor system to show that two inaccessible tryptophans are at or near the colchicine binding site.
A fluorescence spectroscopic study of substrate-induced conformational changes in glutaminyl-tRNA synthetase.
Glutaminyl-tRNA synthetase from Escherichia coli is a member of a subgroup of aminoacyl-tRNA synthetases that do not catalyze ATP-PPi exchange in the absence of the cognate tRNA. Such behavior suggests conformational changes upon substrate binding. Two different fluorescent probes, pyrenylmaleimide and acrylodan, were used to specifically label a nonessential sulfhydryl group of GlnRS. Conformational changes induced by substrates were studied using glutaminyl-tRNA synthetase labeled with these two environment-sensitive probes. ATP was shown to cause a significant conformational change that alters the mode of binding to tRNA(Gln) to GlnRS. The alteration of the salt sensitivity pattern of tRNA(Gln) binding to GlnRS by ATP supports this. Binding of tRNA(Gln) causes a conformational change that may be different in nature for the ATP/GlnRS complex and free GlnRS. Hydrodynamic parameters deduced from fluorescence polarization studies and the use of a noncovalent probe indicate that the ATP-induced conformational change may not be global in character.
Solid-phase synthesis and conformational studies of glycosylated derivatives of helper-T-cell immunogenic peptides from hen-egg lysozyme.
3-Mercaptopropionic acid and N alpha-Fmoc serine, both with unprotected carboxyl groups, were stereospecifically glycosylated in 62-82% yields, using saccharide 1,2-trans peracetates and Lewis acid catalysis. The resulting glycosylated building blocks were used in the synthesis of derivatives of helper-T-cell stimulating peptides, with the carbohydrate moiety located at the amino terminus, or internally in the peptide chain. 1H NMR spectroscopy in Me2SO-d6 showed that the glycopeptides assumed random conformations, which were not influenced by the glycosylation or by single substitutions of amino acids in the peptide moiety.
Expression of the 32-Kd polypeptide of the Rh antigen.
To develop procedures for the expression of Rh antigen-containing proteins, we prepared a previously cloned Rh cDNA by isolation from a human bone marrow library using polymerase chain reaction (PCR). The cDNA that encodes either Rh(E) or (e) antigens was inserted into a vector (pGEM7ZRh) and transcription/translation performed in a reticulocyte lysate system. This produced a major (32 Kd) and minor (30 Kd) protein band in the region of sodium dodecyl sulfate (SDS) gels where Rh proteins are known to migrate. These same two proteins were immunoprecipitated by a rabbit anti-Rh antibody preparation that reacts with all Rh proteins, confirming that Rh protein was expressed in this cell-free system. Transient expression of Rh protein in COS-1 cells was also accomplished using a transfection vector (pBC12BIPLRh) containing inserted Rh cDNA. COS-1 cells transfected with this vector also produced a 32-Kd protein band that formed an immune complex with rabbit anti-Rh, while cells transfected with the same vector minus the Rh cDNA insert did not yield any detectable Rh immune-complexed protein. This system should prove useful for studying the transport of Rh proteins within the cell and the expression of Rh antigenicity at the cell surface.
N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)colcemid, a probe for different classes of colchicine-binding site on tubulin.
The nature of binding of 7-nitrobenz-2-oxa-1,3-diazol-4-yl-colcemid (NBD-colcemid), an environment-sensitive fluorescent analogue of colchicine, to tubulin was tested. This article reports the first fluorometric study where two types of binding site of a colchicine analogue on tubulin were detected. Binding of NBD-colcemid to one of these sites equilibrates slowly. NBD-colcemid competes with colchicine for this site. Binding of NBD-colcemid to this site also causes inhibition of tubulin self-assembly. In contrast, NBD-colcemid binding to the other site is characterised by rapid equilibration and lack of competition with colchicine. Nevertheless, binding to this site is highly specific for the colchicine nucleus, as alkyl-NBD analogues have no significant binding activity. Fast-reaction-kinetic studies gave 1.76 x 10(5) M-1 s-1 for the association and 0.79 s-1 for the dissociation rate constants for the binding of NBD-colcemid to the fast site of tubulin. The association rate constants for the two phases of the slow site are 444.4 M-1 s-1 and 11.67 M-1 s-1 [corrected], respectively. These two sites may be related to the two sites of colchicine reported earlier, with binding characteristics altered by the increased hydrophobic nature of NBD-colcemid.
A fluorescence anisotropy study of tetramer-dimer equilibrium of lambda repressor and its implication for function.
Tetramer-dimer equilibrium of lambda repressor has been studied by fluorescence anisotropy techniques. We have chosen 1-dimethylamino naphthalene-5-sulfonyl chloride (dansyl chloride)-labeled repressor to study the dissociation-association equilibrium, because of relatively long life-time of the probe (> 10 ns). Polarization of the dansyl-labeled repressor decreases with decreasing protein concentrations in the range of 20 to 0.2 microM. The decrease of anisotropy was shown to be due to reversible dissociation of the protein. Size exclusion high-performance liquid chromatography studies and polyacrylamide gel electrophoresis under native conditions (Ferguson plot) confirmed that at around 20 microM concentrations the repressor exists in predominantly tetrameric form, whereas in lower concentrations it exists in predominantly dimer form. A dissociation constant of 2.3 +/- 0.9 microM was estimated in 0.1 M potassium phosphate, pH 8.0, at 25 degrees C. A stoichiometric amount of isolated single operator shifted the tetramer-dimer equilibrium toward the dimer. Increased ionic strength had only a modest effect on the dissociation constant. The thermodynamic constants for the dissociation reaction calculated from the Van't Hoff plot was +26.6 kcal/mol for delta H and +64.7 e.u. for delta S. The rotational correlation times derived from isothermal Perrin plot indicated elongated dimers and tetramers.
Silver electrodeposits in ion-exchanged oxide glasses.
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