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Biomedical subjects

M Forbes

Publications and source records attributed to M Forbes.

At least 19 recordsLinked to original sources
PubMed1999

Long-term histologic changes in the dental pulp after posterior segmental osteotomies.

OBJECTIVE: The purpose of this study was to examine pulp tissue for 18 months after segmental osteotomy in nonhuman primates. STUDY DESIGN: In this long-term experimental study, subapical, posterior, maxillary, and mandibular osteotomies were done in 26 baboons (Papio ursinus). Baboons were killed humanely immediately after operation and at 3, 6, 12, and 18 months, when tissues were perfusion-fixed. Longitudinal step-serial sections of dental pulps were examined. RESULTS: There was a loss of the odontoblast layer as early as 3 months after surgery. Inflammatory cell infiltrate was most marked in the early postoperative stages, and the formation of osteodentin and secondary dentin was evident after 6 months. Foci of necrosis were present in the 3-month and 6-month groups but were replaced by pulp fibrosis in the 12-month and 18-month groups. All these changes were more frequent in experimental than control teeth. CONCLUSIONS: The histologic changes seen should not affect the prognosis of teeth in subapical osteotomy segments if clinicians are careful not to damage root apices and do regular, careful, clinical, and radiographic follow-up examinations. Because many pulps healed spontaneously in the study teeth, endodontic treatment should be delayed until it is clearly needed.

Animals↗
PubMed1998

Vascularity of the dental pulp after segmental osteotomy in the chacma baboon (Papio ursinus).

OBJECTIVE: To assess the vascularity of the dental pulp after segmental operations with and without interpositional autogenous bone grafting. DESIGN: Experimental study. SETTING: University Department, South Africa. ANIMALS: 26 chacma baboons. INTERVENTIONS: Maxillary and mandibular posterior segmental osteotomies were perfused with barium sulphate 3, 6, 12 and 18 months postoperatively. The animals were killed at 3, 6, 12 and 18 months after surgery and perfused with barium sulphate. Barium-filled vessels were counted in histological sections from 189 control and experimental teeth. MAIN OUTCOME MEASURE: Number of blood vessels. RESULTS: Blood vessel counts in mandibular teeth in osteotomy segments ranged from 0 to 1.15 compared with 2.27 to 4.58 in control teeth, while in maxillary teeth counts ranged from 0.54 to 2.22 for experimental teeth and 3.3 to 4.65 for controls. For both jaws, the numbers of vessels in experimental teeth gradually increased between 3 and 18 months but remained less than those in control teeth. Numbers of blood vessels were similar in graft and no-graft groups but both were less than half the counts in control teeth. CONCLUSION: Blood flow is present in the teeth at all times after posterior segmental osteotomy but there is a risk of ischaemia.

Animals↗
PubMed1996

Nerve degeneration within the dental pulp after segmental osteotomies in the baboon (Papio ursinus).

Following dentofacial surgical procedures, teeth in segments often do not sense thermal or electric stimuli. This study was undertaken to assess changes in the neural component of the dental pulp after posterior maxillary and mandibular segmental osteotomies, with or without interpositional autogenous bone grafting, in 26 Chacma baboons. Innervation was assessed histologically immediately after operation, and at 3, 6, 12 and 18 months. Statistically significant differences were present between the experimental and control groups. Even after 18 months no nerves were present in any of the mandibular teeth. In maxillary teeth, 50 per cent had demonstrable nerves in the graft group and 40 per cent in the no graft group. As nerve degeneration was present in the experimental teeth, patients should be warned of possible change in tooth sensibility, following these operations. Careful post-operative follow up for long periods in humans following dentofacial surgical procedures is thus essential.

Animals↗
PubMed1995

The Samaritans.

Explore the source record for details and available documents.

Confidentiality↗
PubMed1994

Sequential monotherapy of hypertension.

In most cases, the antihypertensive therapy for an individual patient is selected through a process of trial and error. This study determined if, by treating each hypertensive patient sequentially, with six antihypertensive drugs, one from each of the major classes, one could decide on the best possible drug for control of hypertension. In a randomized open-label crossover study, 19 patients (16 male and 3 female), 28-70 years of age with a sitting diastolic blood pressure of 95-110 mm Hg were given atenolol, captopril, clonidine, indapamide, prazosin, and verapamil in a sequential manner. Each drug was started at the minimum recommended or lower dose and titrated upwards every 2 weeks, if well tolerated, until blood pressure was controlled (diastolic BP < 90 mm Hg). If blood pressure was controlled, the drug was continued for another 2 weeks. A washout period of at least 2 weeks was allowed between drugs. Both systolic and diastolic blood pressures were reduced significantly with all of the six drugs. In 18 of the 19 patients, blood pressure was controlled with at least one of six drugs, frequently with the lowest dose. The authors conclude that if hypertension is not controlled with the lowest recommended dose of a drug, other antihypertensive drugs should be tried sequentially rather than increasing the dose or adding a second drug.

Adult↗
PubMed1992

Antibacterials. synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 4. Multiply-substituted aryl derivatives.

The synthesis and structure-activity relationship (SAR) studies of the effect of different polysubstitution patterns in the aromatic ring of 5-(acetamidomethyl)oxazolidinone antibacterials (I) on antibacterial activity are presented. Compounds I were prepared by the six-step synthesis described previously (Gregory, W. A.; et al. J. Med. Chem. [formula: see text] 1989, 32, 1673), electrophilic aromatic substitution reactions of 3-substituted compounds, and functional-group interchange reactions of 3,4-disubstituted compounds. Antibacterial evaluation of compounds I against Staphylococcus aureus and Enterococcus faecalis gave the following results. The 2,4- and 2,5-disubstituted derivatives have weak or no antibacterial activity. Antibacterial activities of 3,4-disubstituted compounds are comparable to those of the 4-monosubstituted analogues for small 3-substituents (smaller than Br), but decline rapidly for larger 3-substituents. 3,4-Annulated derivatives are comparable in activity to their open-chain analogues. 3,5-Disubstituted and 3,4,5- and 2,4,6-trisubstituted derivatives are devoid of antibacterial activity.

Anti-Bacterial Agents↗
PubMed1992

Regulation of cell proliferation: late down-regulation of c-myb preceding myelo-monocytic cell differentiation.

Expression of the c-myb nuclear oncogene during the cell proliferation and differentiation of HL-60 human promyelocytic leukemia cells was characterized and compared to the expression of c-fos, another nuclear oncogene with transcriptional regulatory activity. During progression through the cell cycle, the amount of c-myb protein increased. The increase was commensurate with total cell size, thus preserving the relative abundance of c-myb protein present at the onset of the cell cycle. In HL-60 cells, the induced metabolic cascade leading to terminal myeloid or monocytic differentiation segregates into two steps occurring over two division cycles. Expression of c-myb did not diverge from the control until late in this metabolic cascade when it declined prior to onset of terminal differentiation. This course of expression was similar for both the retinoic acid induced myeloid or the 1,25-dihydroxy vitamin D2 induced monocytic terminal differentiation of the cells. Bromodeoxyuridine, which induces proliferative arrest but not phenotypic differentiation of these cells, induced the same course of c-myb expression as the inducers of terminal differentiation. The same course of c-myb expression with growth arrest induced by these three different means is consistent with a potential proliferation regulatory role for c-myb in late but not early events leading to terminal differentiation. The dynamics of c-myb expression during this process were qualitatively, but not quantitatively, similar to the course of c-fos expression. Thus, taken with previous results, then amongst the nuclear oncogenes or tumor suppressor genes, c-myc, RB, c-fos, and c-myb, only c-myc and RB expression exhibit early regulation during induced HL-60 cell differentiation.

Bromodeoxyuridine↗
PubMed1992

Immunofluorescence on split skin for the detection and differentiation of basement membrane zone autoantibodies.

The autoimmune subepidermal bullous diseases are characterized by autoantibodies to the basement membrane zone of stratified squamous epithelium. Recent studies have shown that the antibodies have characteristic ultrastructural and antigenic binding properties and that differentiating between those properties can be useful in distinguishing one disease from another. Immunofluorescence microscopy is widely used to detect basement membrane zone autoantibodies. The test has traditionally used tissue substrates with an intact basement membrane zone. Those substrates are limited because autoantibody binding cannot always be detected and because autoantibodies with different ultrastructural and antigenic binding properties cannot be distinguished from each other. Normal human skin that has been separated through the basement membrane zone (i.e., split skin) has recently been used as a substrate for detecting and characterizing basement membrane zone autoantibodies by immunofluorescence. Studies indicate that split skin is a more sensitive substrate than intact skin for detecting the antibodies and that antibodies with different ultrastructural binding sites can often be differentiated from one another on split skin. Those studies suggest split skin is the substrate of choice for the routine immunofluorescence evaluation of autoimmune subepidermal bullous diseases.

Autoantibodies↗
PubMed1991

Comparison of silver sulphadiazine 1 per cent, silver sulphadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent and mafenide acetate 8.5 per cent for topical antibacterial effect in infected full skin thickness rat burn wounds.

Silver sulphadiazine 1 per cent (SS), silver sulphadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent (SS + CD 0.2 per cent) and mafenide acetate 8.5 per cent (MA) were compared to assess the antibacterial effect of once daily application on experimental rat 20 per cent full skin thickness burn wounds seeded 24 h earlier with 10(8) microorganisms originally isolated from infected wounds of burned patients. Separate series evaluated Staph. aureus, Enterococcus faecalis, Enterobacter cloacae and Ps. aeruginosa. The mean concentration of all four organisms recovered after 1 week from full thickness biopsies of eschar and from separate biopsies of subjacent muscle was less in MA and SS + CD 0.2 per cent treated animals compared with those treated with SS alone. The mean concentration in muscle and eschar following treatment with MA was less for wounds seeded with Staph. aureus and Ps. aeruginosa than with SS + CD 0.2 per cent treatment, while the mean concentration in eschar application of SS + CD 0.2 per cent was less than with MA for E. faecalis seeded wounds.

Administration, Topical↗
PubMed1990

Structure-activity relationship of quinoline carboxylic acids. A new class of inhibitors of dihydroorotate dehydrogenase.

The novel anticancer drug candidate brequinar sodium [DuP 785, NSC 368390, 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinoline carboxylic acid sodium salt] inhibits dihydroorotate dehydrogenase, the fourth enzyme in the de novo pyrimidine biosynthetic pathway leading to the formation of UMP. Sixty-nine quinoline 4-carboxylic acid analogs were analyzed as inhibitors of L1210 dihydroorotate dehydrogenase. This structure-activity relationship study identified three critical regions of brequinar sodium and its analogs, where specific substitutions are required for the inhibition of the activity of dihydroorotate dehydrogenase. The three principal regions are: (i) the C(2) position where bulky hydrophobic substituents are necessary, (ii) the C(4) position which has a strict requirement for the carboxylic acid and its corresponding salts, and (iii) the benzo portion of the quinoline ring with appropriate substitutions. These results will be useful in the elucidation of the precise nature of the interaction between brequinar sodium and dihydroorotate dehydrogenase.

Animals↗
PubMed1989

Analysis of an anaesthetic gas scavenging system hazard.

The collapse of the reservoir bag in a circle circuit was observed during anaesthesia. This resulted from the incomplete closure of the pressure relief valve on the absorber whie it was connected to the scavenging system. Although the scavenging system was operating and installed according to the manufacturer's recommendations and to the CSA standard on Anaesthetic Gas Scavenging Systems (Z168.8), the patient was not protected from this hazard. Introducing an air break into the scavenging interface device will protect the patient. However, such a system would not meet the CSA standard and would make the relief valves on the scavenging interface device unnecessary.

Air Pollution↗
PubMed1989

Antibacterials. Synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 1. The "B" group.

The synthesis and structure/activity studies of the effect of varying the "B" group in a series of oxazolidinone antibacterials (I) are described. Two synthetic routes were used: (1) alkylation of aniline with glycidol followed by dialkyl carbonate heterocyclization to afford I (A = H, B = OH), whose arene ring was further elaborated by using electrophilic aromatic substitution methodology; (2) cycloaddition of substituted aryl isocyanates with epoxides to give A and B with a variety of values. I with B = OH or Br were converted to other "B" functionalities by using SN2 methodology. Antibacterial evaluation of compounds I with A = acetyl, isopropyl, methylthio, methylsulfinyl, methylsulfonyl, and sulfonamido and a variety of different "B" groups against Staphylococcus aureus and Enterococcus faecalis concluded that the compounds with B = aminoacyl, and particularly acetamido, were the most active of those examined in each A series, possessing MICs in the range of 0.5-4 micrograms/mL for the most active compounds described.

Anti-Bacterial Agents↗
PubMed1988

Distribution of the novel anticancer drug candidate Brequinar sodium (DuP 785, NSC 368390) into normal and tumor tissues of nude mice bearing human colon carcinoma xenografts.

The distribution of the novel anticancer drug candidate Brequinar Sodium (DuP 785, NSC 368390) was studied in control mice and mice implanted subcutaneously with human colon carcinoma xenografts. Mice were given radiolabeled 14C-Brequinar Sodium intravenously. Brequinar concentrations in blood and various tissues were determined at 1, 6, and 24 h after drug administration. Within 1 h Brequinar distributed to the tumor and all other tissues studied. The tumor-to-blood drug concentration ratios ranged from 0.19 to 0.41. Radioactivity in the liver and small intestine at 1 h accounted for 17% and 13%, respectively, of the dose given. Elimination rates of Brequinar from all tissues were approximately equal to that from blood. Comparison of blood concentrations determined by both radioactivity and HPLC methods suggests that the intact drug is probably the only form in the blood.

Adenocarcinoma↗
PubMed1987

Control of HL-60 cell differentiation lineage specificity, a late event occurring after precommitment.

Terminal cell differentiation of HL-60 promyelocytic leukemia cells results when they are continuously exposed to retinoic acid. This process involves an intermediate regulatory state, the precommitment memory state, which occurs before onset of differentiation or growth arrest in G0. The cellular processes occurring prior to onset of terminal differentiation can be resolved into early events anteceding development of the precommitment memory state and late events subsequent to it. While it has been suggested that retinoic acid induced early events regulate G1/0 specific growth arrest associated with terminal differentiation, the significance of induced late events is not known. Exploiting the capability of HL-60 cells to undergo either myeloid or monocytic differentiation in response to different inducers, the present studies examine the response of HL-60 cells to the sequential application of myeloid and monocytic inducers prior to onset of terminal differentiation. The results indicate that the precommitment state induced by retinoic acid is not differentiation lineage specific. Sequential application first of retinoic acid, a myeloid inducer, and then of 1,25-dihydroxyvitamin D3, a monocytic inducer, and vice versa, show that cellular choice of a specific differentiation lineage is regulated by late inducer driven events. The data support a two-step model for induction of terminal differentiation where early events anteceding precommitment regulate growth arrest and late events subsequent to precommitment regulate choice of a specific differentiation lineage. The results are of potential significance to the use of differentiation-inducing agents in chemotherapy. The potential toxicity of prolonged exposure to a single inducer might thus be mitigated by sequential brief exposures to different inducers.

Calcitriol↗
PubMed1987

Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721.

DuP 721 (p-acetylphenyloxooxazolidinylmethylacetamide) and DuP 105 (a methylsulfinyl derivative) are orally active representatives of the oxazolidinones, a new class of synthetic antibacterial agents. Their antibacterial spectrum includes staphylococci, streptococci, and Bacteroides fragilis strains. The compounds have equal activity against staphylococcal strains susceptible or resistant to beta-lactam antibiotics, including methicillin-resistant strains. The MICs for 90% of the strains (MIC90s) against staphylococcal isolates were 1 to 4 micrograms/ml for DuP 721 and 4 to 16 micrograms/ml for DuP 105, compared with 1 to 2 micrograms/ml for vancomycin, 0.5 microgram/ml for ciprofloxacin, and 2 to greater than 16 micrograms/ml for imipenem. The MIC90s against group D streptococci were 4 micrograms/ml for DuP 721, 16 micrograms/ml for DuP 105, and 2 micrograms/ml for vancomycin, ciprofloxacin, and imipenem. MIC90s against B. fragilis isolates were 4 micrograms/ml for DuP 721, 16 micrograms/ml for DuP 105, and 8 micrograms/ml for cefoxitin. DuP 721 and DuP 105 administered by either the oral or the parenteral route were protective against staphylococcal and streptococcal infections in mice. The 50% effective doses were 2 to 10 mg/kg for DuP 721, 9 to 23 mg/kg for DuP 105, and 2 to 12 mg/kg for vancomycin. These results indicate that further studies of compounds of the oxazolidinone series are warranted.

Animals↗
PubMed1986

Haemoglobin gene frequencies in the Jamaican population: a study in 100,000 newborns.

The gene frequencies of abnormal haemoglobins have been determined in a group of 100,000 Jamaican newborns screened over a period of 8 1/2 years. The population is predominantly of West African origin and the survey represents approximately one quarter of all island deliveries within the period of the study. The common beta globin chain abnormalities beta s and beta c occurred with gene frequencies of 0.055 and 0.019 respectively; beta thalassaemia was relatively rare. In contrast, alpha thalassaemia was quite common, occurring with a gene frequency of 0.183. In addition to these common abnormalities, the frequencies of 256 rare abnormal haemoglobins are described. This survey thus represents a complete and accurate documentation of the alpha and beta globin variants that occur in the Jamaican population.

Gene Frequency↗