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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

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

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

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

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

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

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

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

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

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

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

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

Argon laser photomydriasis.

Argon laser photomydriasis was used to enlarge 20 miotic pupils in 18 open-angle glaucoma patients, with beneficial visual results in patients properly selected before treatment. During eight months of observation, significant complications such as persistent iritis and lens changes did not occur. An increase in intraocular pressure occasionally occurred shortly after treatment, but chronic exacerbation of underlying glaucoma was not observed. Argon laser iris photocoagulation in rabbit eyes showed localized atrophy of the iris sphincter and stroma within the treatment zones. Discrete, anterior lens opacities occurred only at high-power levels, and these appeared to be nonprogressive during the eight-week observation period.

Animals

Haemoglobin F Victoria Jubilee (alpha 2 A gamma 2 80 Asp-Try).

A new A gamma chain haemoglobin variant, haemoglobin F Victoria Jubilee, with an electrophoretic mobility slightly anodal to haemoglobin F Port Royal, was found in a Jamaican infant. The amino acid residue substitution of 80 Aspartic Acid leads to Tyrosine was associated with alanine in position 136. Haemoglobin F Victoria Jubilee constituted about 7.0 percent of the total haemoglobin F.

Adult

Experimental horizontal transmission of Herpesvirus saimiri from squirrel monkeys to an owl monkey.

Herpesvirus saimiri was naturally transmitted from squirrel monkeys excreting the virus to one of two owl monkeys housed in the same cage. The owl monkey became infected approximately three months after contact was initiated. H. saimiri was consistently isolated from the peripheral lymphocytes until this animal died eight months later. During this period the owl monkey developed specific antibody to H. saimiri to a maximal neutralization index of 5.5 logs. The other monkey remained uninfected for an ovservation period of one year. The documentation of this horizontal transmission of H. saimiri infection from squirrel monkeys to an owl monkey suggests that owl monkeys developing spontaneous malignant lymphomas associated with H. saimiri infection may also have acquired the infection in this manner.

Animals

Efficacy of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide against influenza virus infections in mice.

1-beta-d-Ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) was effective against strains of influenza virus types A and F, whereas amantadine hydrochloride was effective only against strains of influenza virus type A. Dose-related protective effects against lethal influenza infections in mice were obtained with single oral doses of 25 to 400 mg of ribavirin per kg administered at the time of virus inoculation or up to 24 h thereafter. Therapeutic indexes (maximum tolerated dose/median effective dose) against various strains of influenza virus ranged from 5 to 35. With multiple-dose treatment initiated immediately after virus inoculation, oral doses as low as 12 to 25 mg/kg twice daily also afforded significant protection. Treatment with ribavirin inhibited the growth of influenza virus in the lungs of mice and delayed by about 24 h the attainment of maximal viral titers, which in nontreated mice were reached within 24 to 48 h. Inhibition of viral growth was correlated with a suppression of lung consolidation. Ribavirin appears to exert its protective effects against influenza infections by inhibiting virus growth, thereby preventing virus titers from reaching levels that result in massive lung tissue destruction and death of the mice.

Animals