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Biomedical subjects

J C Barber

Publications and source records attributed to J C Barber.

At least 19 recordsLinked to original sources

Interstitial deletions without phenotypic effect: prenatal diagnosis of a new family and brief review.

A 39-year-old woman (G4P1SAB2) was referred for amniocentesis for advanced maternal age. An interstitial deletion of the G-dark band 11p12 was found in the fetus. Blood from the mother and her previous son was cultured and the same deletion was found in both. The absence of phenotypic effect in this family further confirms that G-dark euchromatic deletions are compatible with a normal phenotype, and underlines the importance of checking familial karyotypes even when apparently unbalanced structural rearrangements are found at prenatal diagnosis.

Adult

Fatal disseminated cryptococcosis following intraocular involvement.

A 33-year-old man was treated with systemic steroids for a retinal inflammatory lesion before the diagnosis of cryptococcal retinitis and meningitis was suspected. He died from central nervous system disease despite treatment with parenteral antifungals. Histopathological studies demonstrated ocular and disseminated systemic infection with Cryptococcus neoformans. Direct cryptococcal involvement of the eye is rare and is usually associated with disseminated disease. Systemic steroids must be used with caution, and patients who take these drugs require frequent monitoring.

Adult

The intraocular penetration of acyclovir after subconjunctival administration.

Five patients received a subconjunctival injection (25 mg) of acyclovir before undergoing scheduled enucleation. Seven hours after injection, the observed aqueous and vitreous levels of acyclovir were above the minimum inhibitory concentrations for many herpes simplex viruses types 1 and 2. Systemic absorption measured at two and seven hours after injection was negligible.

Acyclovir

A de novo X;13 translocation with abnormal phenotype.

We describe a female infant who presented with hypotonia and developmental delay. Her karyotype showed a de novo balanced translocation between the X chromosome and chromosome 13, with breakpoints at Xq13 and 13p11. The normal X was late replicating in all cells examined. The cause of this patient's abnormal phenotype is discussed.

Adult

Lead exposure in an "urban" peregrine falcon and its avian prey.

Necropsy of a 7-yr-resident peregrine falcon (Falco peregrinis) from Baltimore showed a Pseudomonas infection involving the pharynx as the immediate cause of death. Concentrations of lead in liver and kidney measured 0.74 and 1.40 ppm, respectively. A survey of lead exposure was performed on 40 urban rock doves (Columbia livia). Thirteen additional rock doves were collected from sites removed from lead contamination and served as controls. The mean concentration of lead in the blood of the urban rock doves was 0.96 ppm (range 0.29-17.0 ppm) compared to 0.05 ppm (0.01-0.07 ppm) for control birds. Ninety-eight percent (39/40) of the urban rock doves had elevated concentrations of lead in their blood, while 27% (11/40) had sublethal concentrations. None of the control birds had increased concentrations of lead in their blood. Concentrations of lead in liver and kidney of 13 urban rock doves were 3.48 ppm and 9.53 ppm, respectively, compared to concentrations of 0.43 ppm and 0.50 ppm for four control rock doves. From these data a mean total concentration of lead per rock dove was calculated at 4.60 ppm for urban birds and 0.33 ppm for control birds.

Animals

Conjunctivitis in rabbits caused by enterovirus type 70 (EV70).

A rabbit enterovirus 70 (EV70) model infection that closely mimics human enteroviral conjunctivitis was developed. Conjunctivitis occurred 24 hr following topical application of EV70. The conjunctivitis was characterized by tearing, redness, swelling of the eye lids, follicles in the superior palpebral conjunctiva, and dilatation of subconjunctival blood vessels. Histologic examination of conjunctival and corneal tissue taken 1 and 2 days after infection revealed numerous punctate areas devoid of squamous epithelium on the upper palpebral conjunctiva. Also, follicles without germinal centers were observed microscopically in the palpebral and tarsal conjunctiva. Fibroblast infiltration characteristic of wound healing and a sparse mononuclear infiltration was noted by the second day. Peak levels of virus [10(3) to 10(6.2) plaque forming units (PFU)/ml] were detected 1 to 2 days after infection and declined to undetectable levels after 3 to 5 days. Interestingly, antiserum to parental EV70 was less effective (8-10-fold) in neutralizing EV70 adapted to animal and tissue culture systems. This finding suggests that an antigenic variant of EV70 arose during adaptation. Fibroblast interferon (IFN beta), which is indicative of viral infection, was detected in tears from 6 of 16 rabbits and declined to undetectable levels 3 days after infection. Serum antibody to EV70 was detectable 8 to 10 days after infection. However, the level of serum antibody was highly variable. The results indicate that the clinical disease, virologic and immunologic courses were similar to that of the human infection. Results suggest that this animal model provides a system for studying the natural antigenic variation of EV70, the natural host defenses of the eye, and antiviral treatments against enteroviral conjunctivitis.

Animal Diseases

Intraocular penetration of new antiviral agent, hydroxyacyclovir (BW-B759U).

9-[(2-hydroxyl-1-(hydroxymethyl)ethoxy]methyl)guanine (hydroxyacyclovir) is a nucleoside analogue with a high degree of efficacy against herpes simplex virus types 1 and 2 and cytomegalovirus (CMV). This antiviral agent demonstrates a low toxicity towards uninfected cells. Intraocular levels in rabbits were evaluated following subconjunctival, intravenous, intravitreal and topical administration. Retinal toxicity studies were performed. Hydroxyacyclovir may have applications in the treatment of deep herpetic infections, CMV retinitis, and acute retinal necrosis.

Acyclovir

Intraocular 9-([2-hydroxy-1-(hydroxymethyl) ethoxy] methyl) guanine levels after intravitreal and subconjunctival administration.

Clearance studies in rabbits following intravitreal injection of 400 micrograms of 9-([2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl) guanine demonstrated levels of the antiviral at 60 hours above the in vitro ID50 for several strains of human cytomegalovirus. Intravitreal administration of this new antiviral may have therapeutic application in the treatment of acute retinal necrosis and cytomegalovirus retinitis complicating acquired immune deficiency syndrome (AIDS).

Acyclovir

Virus-specific, early appearing neutralizing activity and interferon in tears of patients with acute hemorrhagic conjunctivitis.

Virus-specific, early appearing neutralizing activities (ENA) and interferon (IFN) were detected in tears collected from patients during epidemics of acute hemorrhagic conjunctivitis (AHC). In one study, ENA that neutralized enterovirus type 70 (EV70) was detected in tears collected from 114 of 130 AHC patients in Florida. In another study, ENA against coxsackievirus type A24 (CA24) was detected in tears collected from 39 of 57 patients in Singapore with AHC caused by CA24. No tear samples contained ENAs to both EV70 and CA24. Tear samples from uninfected eyes did not contain ENA to EV70 or CA24. ENA to EV70 was detected in 6 of 11 patients 1-6h before the onset of AHC. In addition, tears of 68% of patients seen on the day of onset produced tears that contained ENA to EV70. Thus, ENA to EV70 may be detected less than 24h after infection (based on 24h incubation period). IFN beta was detected in 30% of tear samples collected from patients on the day of onset of AHC caused by EV70. This finding suggested that ENA and IFN could act together to inhibit primary infections of AHC. It was found that the combination of ENA and IFN inhibited virus replication synergistically (greater than or equal to 300 fold reduction) in preinfected cells. Our findings suggest that ENA represents a previously unreported early defense mechanism of the eye, that endogenous ENA and endogenous IFN could inhibit viruses synergistically in vivo, and that ENA in tears could be useful in identifying the agent causing AHC.

Acute Disease

Familial Hirschsprung's disease and type D brachydactyly: a report of four affected males in two generations.

Hirschsprung's disease usually occurs as an isolated malformation as a result of multifactorial causation. A family in which four males (two brothers and two maternal uncles) had Hirschsprung's disease and absence or hypoplasia of the nails and distal phalanges of the great toe and thumb (type D brachydactyly) is described. Hand abnormalities were not present in any other family members, and the obligate heterozygous females were without gastrointestinal problems. The pattern of inheritance was consistent with X-linked recessive inheritance; however, autosomal dominant inheritance with incomplete penetrance in females or multifactorial causation could not be completely excluded.

Adolescent

Trabeculectomy in black patients.

A series of 122 trabeculectomies in black patients is presented, with a minimum postoperative follow-up of 12 months. Glaucoma was controlled in 57% of the cases (39% without medication and 18% with medication) and 43% were uncontrolled at 12 months. Several characteristics were observed in these patients that seem to influence success. A high correlation was found between the presence of a bleb and successful control of pressure without medication. The rate of success was found to decrease little after 12 months postoperative follow-up.

Adolescent

Human fibroblast interferon in tears of patients with picornavirus epidemic conjunctivitis.

We report the levels of coxsackievirus type A24 (CA24) and the levels and type of interferon produced early during naturally acquired picornavirus epidemic conjunctivitis. Virus levels ranging from 10(1.8) to 10(5.8) 50% tissue culture infective doses per ml were detected in 29 of 37 acute (collected 1 to 4 days after onset of conjunctivitis) tear samples. Interferon (10(1.5) to 10(3.3) U/ml) was detected in 12 of 29 tear samples collected on day 1, in 2 of 6 tear samples collected on day 2, and in 1 tear sample collected on day 3 after onset of conjunctivitis. The interferon activity in pooled tear samples was completely neutralized by antiserum against human fibroblast interferon, stable at pH 2.0, and active against different viruses. In addition, the interferon activity in tears, like human fibroblast and leukocyte interferons produced in vitro, protected human and rabbit, but not mouse, cells. This is the first report of production and identification of the antigenic type of interferon induced by an enterovirus during natural infection. The early appearance of fibroblast interferon suggests that it may be an important host defense at the local site of implantation against this and possibly other enterovirus infections.

Animals

The acceptance of a vitreous carbon alloplastic material, Proplast, in the rabbit eye.

Proplast, a vitreous, carbon-Teflon, fluorocarbon polymer, was tested in rabbits for corneal tolerance and acceptance. Toxicity, vascularization, epithelialization, infection, and extrusion were studied clinically and histologically. Four techniques were used: implantation of irregular-shaped pieces of material in an interlamellar corneal pocket, lamellar graft implantation with one exposed surface, full-thickness corneal implants in a manner similar to penetrating keratoplasty, and full-thickness implants covered by a conjunctival flap. Results showed that Proplast allows fibrovascular ingrowth and stabilization without a significant foreign body response or encapsulation for a period of observation from 6 weeks to 4 months. Evidence of epithelial coverage and epithelial ingrowth was also found. Coverage of the Proplast with conjunctiva or corneal tissue was essential to prevent extrusion and infection.

Animals

Early-appearing antiviral activity in human tears during a case of picornavirus epidemic conjunctivitis.

The clinical, virological, and immunological courses of a laboratory-acquired hemorrhagic conjunctivitis were followed. Coxsackievirus type A24 (CA24) was isolated from tears for only two days but from sputum and fecal samples for 20 days. Maximal levels of virus were detected in the right eye (10(5.1) 50% tissue culture infective doses/ml) 5-7 hr before conjunctivitis in the right eye, and in feces (10(2.8) 50% tissue culture infective doses/g) and sputum (10(2.5) 50% tissue culture infective doses/ml) five and eight days after onset of conjunctivitis, respectively. Specific neutralizing activity against CA24 was detected in tear samples 48-56 hr after exposure, and elimination of virus was associated with the rise in the neutralizing activity in tears. This activity was detected earlier than previously reported antibody responses of the eye. The absence of interferon and the association of this early neutralizing activity in tears with early elimination of virus from the eye suggest that neutralizing activity may play a major role in the clinical and pathological manifestations of this infection.

Antibodies, Viral