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Biomedical subjects

M Forbes

Publications and source records attributed to M Forbes.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1986

Complement and immunoglobulin levels in early childhood in homozygous sickle cell disease.

Complement levels, tests of complement function, and immunoglobulin levels were studied in 63 children with homozygous sickle cell (SS) disease and in 88 children with a normal haemoglobin (AA) genotype from birth to 2 yr of age. Levels of complement component C3 were consistently lower in SS children, the difference being highly significant (p less than 0.001) by the age of 2 yr and levels of C3d were significantly higher from the age of 6 months. These observations are compatible with increased turnover of C3 in SS disease from early in life. No consistent genotype differences were observed in the levels of C4, factor B, or functional assays. IgA levels in SS disease were significantly higher at age 2 yr but there were no consistent patterns with IgM or IgG. There was no difference in the prevalence of infections between groups with low C3 or low values of alternative pathway activity but the groups were small and only capable of detecting major differences. However, the findings cast some doubt on the role of individual complement deficiencies in the susceptibility to infection in SS children at this age.

Anemia, Sickle Cell↗
PubMed1985

Recurrent infections in sickle cell disease: haematological and immune studies.

Some haematological and immunological indices were compared in 19 children with sickle cell disease and a history of recurrent infections and in 16 children with sickle cell disease without any known infections. The recurrent infection group had significantly greater pitted red cell counts and greater absolute monocyte counts. No differences were apparent in routine haematological indices, foetal haemoglobin, immunoglobulin, or complement levels between the groups. The interpretation of these results is discussed.

Anemia, Sickle Cell↗
PubMed1985

A collaborative study of a preparation of normal human serum for use as a reference in the assay of beta 2 microglobulin.

A biological standard for beta 2 microglobulin (beta 2m) determination has been prepared from pooled human serum by sampling and freeze-drying. A preliminary study of parallelism between the dose-response curves of the preparation and pure beta 2m or biological fluids was made with four different methods of assay and gave satisfactory results. In a collaborative study in five laboratories in five countries using a common method of assay, evidence was obtained that the preparation coded 80-12-3200 was suitable to serve as a standard for the assay of beta 2 microglobulin. Criteria included the constancy of the amount of material per vial and the stability of the freeze-dried product. The technique used for beta 2m determination was a radioimmunoassay.

Drug Stability↗
PubMed1984

Congenital ectropion uveae with glaucoma.

Congenital ectropion uveae (CEU) is a rare, nonprogressive anomaly characterized by the presence of iris pigment epithelium on the anterior surface of the iris stroma, often associated with neurofibromatosis and occasionally with other ocular anomalies. We present eight patients with unilateral CEU. Seven patients had glaucoma in the involved eye, while the eighth was a 10-week-old infant. In the two patients with bilateral glaucoma, the second eye was similar to the first, but without CEU. Three patients had neurofibromatosis, two had facial hemihypertrophy, one had Rieger's anomaly, one had Prader-Willi syndrome, and one had no systemic anomalies. Two had initially been misdiagnosed as having a large pupil in the involved eye and one as having a Horner's syndrome in the uninvolved eye. The finding of CEU in an infant warrants continued observation for the development of glaucoma and disorders of neural crest origin.

Abnormalities, Multiple↗
PubMed1984

Pulpal response to a bis-acryl-plastic (Protemp) temporary crown and bridge material.

The pulpal response to Protemp (ESPE Gmbh) was compared to zinc oxide-eugenol, Super Syntrex (de Trey) and Protemp plus zinc oxide-eugenol liner in 144 vervet monkey (Cercopithecus pygerythus) incisor teeth, according to ADA Specification No. 41. Cellular displacement into dentinal tubules, superficial and deep inflammation were present only in the 3-day specimens in all materials. Mean scores for the test material were lower than both negative and positive controls. In the 30-day specimens the prevalence of reparative dentine under the test material was similar to the negative control, while at 90 days it was less than the negative control, although the severity in affected specimens was more than the positive control. Use of a zinc oxide-eugenol liner reduced the severity of reparative dentine formation.

Acrylates↗
PubMed1984

Non-gouty arthritis in sickle cell disease: report of 37 consecutive cases.

Arthritis in association with sickle cell disease was seen in 37 patients in a 21/2-year period. Cases of gout and of avascular necrosis of the femoral head were excluded. In 12 patients a non-inflammatory effusion occurred during the course of a painful crisis, in 12 patients an ankle effusion occurred in association with spontaneous development or deterioration of leg ulceration, and in 13 patients there was a group of miscellaneous arthritides. Ankle arthritis with leg ulceration has not been previously recognised, and its association with spontaneous ulceration, which is presumed to have a vaso-occlusive origin, is compatible with ischaemic synovial damage. The aetiology may therefore be similar to that believed to account for effusions in association with the painful crisis.

Adolescent↗
PubMed1982

Activity of a novel anthracenyl bishydrazone, 9,10-anthracenedicarboxyaldehyde Bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride, against experimental tumors in mice.

9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride (CL 216942; bisantrene hydrochloride; NSC 337766), a member of a new chemical class of compounds with antineoplastic properties, has been evaluated for antitumor activity in experimental murine tumor systems. The compound produced significant increases in life span (LS) and long-term survivors among mice bearing transplantable leukemias and solid tumors. Optimal treatment regimens resulted in an ILS of greater than 173 and 151% in mice with P388 and L1210 leukemia, respectively, an ILS of greater than 85% in mice with Lieberman plasma cell tumor, and an ILS of greater than 200, 150, and 63%, respectively, in mice with B16 melanoma, colon tumor 26, and Ridgway osteogenic sarcoma. An adriamycin-resistant subline of P388 leukemia showed complete cross-resistance to CL of 216942. The compound was active when administered by the i.p., i.v., and s.c. routes, but p.o. activity was not observed. Significant schedule dependency was not observed when the drug was administered once daily for 9 days, once every 4 days, or as a single dose, but single doses typically produced the best effects. CL 216942 was a potent inhibitor of DNA and RNA synthesis in L5178Y lymphoma cells cultured in vitro, and preliminary studies indicated the drug was a DNA-intercalating agent. The drug was cytotoxic for rapidly proliferating and nonproliferating (G0) human colon carcinoma WiDR cells in vitro.U

Animals↗
PubMed1981

In vitro and in vivo antibacterial effects of combinations of beta-lactam antibiotics.

The effects of combining the new broad-spectrum penicillins piperacillin and mezlocillin with cefoxitin, cefamandole, or cephalothin on the antibacterial activities of these antibodies were determined in vitro against 50 to 109 bacterial strains and in six experimental infections in mice. Against strains of Escherichia coli, Klebsiella, Proteus mirabilis, Salmonella, Acinetobacter, Enterococcus, and Staphylococcus, the combinations exhibited synergistic, indifferent, or additive effects, but no antagonism. Against strains of four groups of organisms (Pseudomonas, Serratia, Enterobacter, and indole-positive Proteus), a high incidence of antagonism was observed, particularly with combinations containing cefoxitin (60 to 100%). The penicillins were antagonized by the cephalosporin antibiotics. In vitro effects were reflected in vivo. Mice infected with cultures associated with synergistic or additive in vitro effects were protected with lower doses of piperacillin when this antibiotic was administered with ineffective doses of cefoxitin than when piperacillin was used alone. Infections with cultures associated with in vitro antagonism required two- to eightfold higher doses of piperacillin and mezlocillin when these antibiotics were used in combination with the cephalosporins. The clinical implications of these effects should be considered.

Animals↗
PubMed1981

Argon laser goniophotocoagulation of the trabecular meshwork in open-angle glaucoma.

Argon laser goniophotocoagulation of the trabecular meshwork (ALGTM) after the method of Wise and Witter (1979) was performed on 66 eyes of 57 patients with phakic open-angle glaucoma. The duration of follow-up ranged from six to 21 months. The intraocular pressure decreased from a pre-treatment mean of 26.9 mm Hg to a post-treatment mean of 18.9 mm Hg and the mean number of medications used per eye decreased from 3.0 to 2.1 Of the 6 eyes, 54 (82%) were successfully controlled. The pressure-lowering effect was sustained rather than transient. The laser procedure was performed on an out-patient basis using only topical anesthesia. Complications were minimal in most cases. An early post-treatment rise in pressure greater than 6 mm Hg (range 7 mm Hg to 27 mm Hg) occurred in 14 eyes but two-thirds of this group were, nevertheless, successfully controlled. Failure did not adversely influence the outcome of subsequent glaucoma surgery.

Adolescent↗
PubMed1978

Retinal detachment and miotic therapy.

We studied a series of 34 eyes in 31 patients in whom retinal detachment occurred during miotic therapy. In 14 eyes, the duration of miotic use before the development of detachment was two months or less. Most detachments occurred in detachment-prone eyes either by virtue of myopia (62%), aphakia (24%), ipsilateral lattice degeneration (38%) or retinal pathology, in the fellow eye (50%). Virtually all detachments were rhegmatogenous. Distributions of retinal breaks are similar to the corresponding profiles in detached eyes not receiving miotics. The observed phenomena may be accounted for mechanistically, either with or without the role of miotics, so a specific causal role cannot be assigned to any given miotic in any given case. However, our data suggest that detachment-prone eyes may be at increased risk with miotic use, and thus demand careful retinal evaluation and prophylaxis when ominous peripheral symptoms are present.

Adult↗
PubMed1978

Suspension of the globe during intraocular surgery.

The unopened eye maintains a relatively stable spherical contour due to the expansile influence of the intraocular pressure. When the eye is opened this expansile pressure is lost and some degree of collapse of the scleral shell ensues. In eyes with a relatively flaccid sclera an anterior segment incision may induce significant reduction in the volume of the posterior segment of the globe. During intracapsular cataract extraction on such eyes, scleral collapse can cause anterior displacement of the lens and iris when the eye is opened and vitreous loss as soon as the lens is extracted. Scleral collapse tends to occur during intraocular surgery on previously aphakic eyes. In this situation it may become difficult to achieve a vitreous-free anterior sement by open sky vitrectomy. Metallic scleral supporters prevent inward collapse of that portion of the sclera to which they are attached. They do not prevent downward collapse of the posterior sclera shell. Upward traction is required to prevent the downward component of scleral collapse. A system for controlled suspension of the globe during intraocular surgery has been devised and used in a variety of surgical procedures. The apparatus is simple and it does help to minimize downward scleral collapse. It does not prevent scleral identation or distortion by external forces and cannot substitute for inadequate anesthesia and akinesia or faulty surgical technique.

Aphakia↗