PubMed Health⌕ Search

Biomedical subjects

B A Howard

Publications and source records attributed to B A Howard.

At least 19 recordsLinked to original sources
PubMed2000

Human breast development.

This review presents an atlas of the histology of the normal physiological states of the human breast including prenatal, prepubertal, and pubertal development, adult resting gland, pregnancy, lactation, and postinvolution. The aim is to produce a pictorial overview of the main stages in development and the common findings in the adult that are considered to be within the range of normality. Unlike inbred strains of animals, in humans it is clear that the chronology of ductal and lobular development is not predictable, either in the fetus, the infant, the peripubertal breast, or the adult. This is probably due to the individual variation in hormone levels both in utero and after birth. For many of the developmental time points there are very little data available. In this review we indicate the current state of knowledge of human breast development and some of the main similarities and differences with the rodent, the main animal model. The major phases of growth and development are described and accompanied by photographs that are representative of each stage. Stress is placed on terminology as there is confusion in the literature. This article is written as an accessory to the companion review on breast cancer.

Adolescent↗
PubMed1999

Lumbar spinal fusion using recombinant human bone morphogenetic protein in the canine. A comparison of three dosages and two carriers.

STUDY DESIGN: A randomized, prospective and controlled animal study. OBJECTIVE: To evaluate lumbar spinal fusion using recombinant human bone morphogenetic protein 2 in a canine model. SUMMARY OF BACKGROUND DATA: Spinal fusion using autogenous bone grafting is associated with donor site morbidity and a nonunion rate of 5% to 35%. The use of recombinant human bone morphogenetic protein 2 as a bone graft substitute would eliminate donor site morbidity and perhaps augment the rate of successful fusion. METHODS: Mature beagles underwent bilateral paraspinal exposure at L4-L5, followed by transverse process decortication and randomization into one of six groups using differing doses of recombinant human bone morphogenetic protein 2 implanted using either a Type I collagen carrier or a polylactic acid carrier. Two control groups were used: one group without recombinant human bone morphogenetic protein 2 and another group using autogenous rib graft alone. RESULTS: Groups treated with recombinant human bone morphogenetic protein 2 demonstrated complete fusion in all animals. Animals treated with collagen carrier alone (no recombinant human bone morphogenetic protein 2) demonstrated complete absence of fusion. Successful fusion occurred in one of three canines in the autogenous bone graft group. Fusion masses in the recombinant human bone morphogenetic protein 2 treatment groups were significantly larger in size at 3 months than in the autogenous bone graft group. The collagen carrier was more biocompatible and biodegradable because residual polylactic acid carrier was seen with adjacent multinucleated giant cells. There was no evidence of spinal canal or nerve root encroachment in the recombinant human bone morphogenetic protein 2 treatment groups. CONCLUSIONS: The use of recombinant human bone morphogenetic protein 2 implanted using a Type I collagen carrier resulted in 100% fusion without adverse effects.

Animals↗
PubMed1999

Safety of recombinant human bone morphogenetic protein-2 after spinal laminectomy in the dog.

STUDY DESIGN: This was a randomized, blinded trial of the safety of the application of recombinant human bone morphogenetic protein (rhBMP)-2 or autologous bone graft onto a laminectomy defect of the dog in the presence or absence of a dural membrane puncture. OBJECTIVE: To test the safety of rhBMP-2 in an application in which direct contact of the material with neural tissue occurs. SUMMARY OF BACKGROUND DATA: Application of rhBMP-2 in laboratory animals stimulates local bone formation to effect spinal fusion and healing of segmental bone defects. The use of rhBMP-2 as a bone graft substitute in spinal fusion would eliminate donor site morbidity and may augment the rate of successful fusion. Because rhBMP-2 may unintentionally come in contact with neural tissue, the consequences of such a safety issue must be addressed in an animal model before human trials. METHODS: Twenty skeletally mature beagles underwent spinal exposure followed by bilateral laminectomy at L5. In half of the dogs, a puncture wound was made to the dura with the expression of cerebrospinal fluid at the site of the puncture. In randomly selected animals, the exposed dural elements received either autologous bone graft with the bone removed from the laminectomy site or an implant of the rhBMP-2 device. The animals was observed for 12 weeks with periodic clinical examinations and monthly computed tomographic scans. RESULTS: There was no clinical, radiographic, or histologic evidence of neurologic abnormalities in these animals. The rhBMP-2 stimulated bone growth in the laminectomy defect and came into direct contact with the dural membrane. There was no evidence of abnormal mineralization within the thecal sac or in the spinal cord itself. CONCLUSIONS: The rhBMP-2 implant stimulated bone formation in the laminectomy site. Neither autologous bone, rhBMP-2, nor the dural puncture had deleterious consequences for the animals.

Administration, Topical↗
PubMed1996

Effects of cold acclimation and central opioid processes on thermoregulation in rats.

Two experiments, using centrally administered [D-Ala2-MePhe4-Gly(ol)5]enkephalin (DAMGO), a selective mu-opioid agonist, assessed the thermoregulatory consequences of cold acclimation. Experiment 1 assessed whether cold acclimation influenced DAMGO hyperthermia at room temperature. Sialo-adenectomized rats were implanted with ICV cannulae and IP Mini-Mitters. After 3 weeks of exposure to 5 degrees C (cold acclimation) or 22 degrees C (non-cold acclimation) rats were pretreated with IP naltrexone HCl (2 mg/kg b.wt.) or vehicle (0.15 M saline) and later administered a 5-microliters ICV injection of 0.15 M saline, 0.1, or 1.0 microgram DAMGO. Cold acclimation exerted little effect on core temperature but potentiated DAMGO hyperthermia in a dose-dependent, naltrexone-reversible, activity-independent manner. Experiment 2 assessed the effect these same manipulations exerted on operant escape from a convective source of mild heat (37 degrees C). Duration of heat escape increased with cold acclimation in a naltrexone-resistant manner, yet was not influenced by DAMGO in either non-cold-acclimated or cold-acclimated rats. These findings suggest that two central adaptations occur with cold acclimation: A non-mu-opioid process that increases heat sensitivity and a mu-opioid process that potentiates hyperthermia but fails to alter heat escape due to mu-opioid-mediated analgesia.

Acclimatization↗
PubMed1996

Comparison of a DNA probe assay with the plaque reduction assay for measuring the sensitivity of herpes simplex virus and varicella-zoster virus to penciclovir and acyclovir.

A DNA probe assay was compared with the plaque reduction assay to determine the sensitivity of clinical isolates of herpes simplex virus (HSV) and varicella-zoster virus (VZV) to penciclovir and acyclovir in MRC-5 cells. In both assays, penciclovir and acyclovir shared comparable activity against cell-free virus (CFV) preparations of VZV and herpes simplex virus type 1 (HSV-1) isolates, whilst acyclovir was significantly more active than penciclovir against herpes simplex virus type 2 (HSV-2) isolates in both the DNA probe assay (P < or = 0.01) and the plaque reduction assay (P < or = 0.01). However, the 50% effective concentrations (EC50s) were generally lower in the DNA probe assay and the correlation between the plaque reduction and DNA probe assays was poor for either compound. Six acyclovir-resistant strains of HSV-1 derived in cell culture were also tested for susceptibility to penciclovir and acyclovir, in the DNA probe and plaque reduction assays. The relative susceptibilities of these strains were comparable, for example, one ACV-resistant strain was susceptible to penciclovir in both assays. Further comparisons of the assay methods were made using cell-associated VZV (CAV). As with CFV the EC50s were significantly lower in the DNA probe assay than the plaque reduction assay for penciclovir (P < or = 0.01) and acyclovir (P < or = 0.01). In the DNA probe assay there was no significant difference in the EC50s for either penciclovir or acyclovir when comparing CAV with CFV. However, in the plaque reduction assay the EC50s for CAV were significantly higher than those for CFV for both penciclovir (P < or = 0.01) and acyclovir (P < or = 0.01). Overall the DNA probe assay is objective, does not require prior titration of isolates and provides opportunities for automation. It is more suitable for sensitivity testing of large numbers of clinical isolates than the well-established plaque reduction assay.

Acyclovir↗
PubMed1996

Activity of penciclovir in antiviral assays against herpes simplex virus.

The effect of penciclovir and acyclovir on the replication of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) strains was determined in MRC-5 cells infected with 0.01 pfu/cell and exposed to the drugs for 72 h to allow multiple cycles of replication. Penciclovir was significantly more active than acyclovir against three strains of HSV-1 and three strains of HSV-2 at 1 mg/L (P = 0.009), 3 mg/L (P < 0.001) and 10 mg/L (P = 0.001). Further comparisons between the compounds were made in MRC-5 cells infected with HSV-1 strain SC16 using four different antiviral assays namely, the 24 h virus yield reduction assay, plaque reduction assay, viral antigen inhibition assay, and a viral DNA inhibition assay, to determine the relative merits of each. Penciclovir and acyclovir shared similar activities in the plaque reduction assay (with 50% effective concentrations, EC50, being 0.8 and 0.6 mg/L, respectively) and in the viral antigen inhibition assay (EC50s. 0.6 and 0.7 mg/L, respectively). The EC50 of penciclovir in the 24 h viral DNA inhibition assay was 0.01 mg/L compared with 0.06 mg/L of acyclovir. In the 24 h virus yield reduction assay in which MRC-5 cells were infected with 0.3 pfu/cell, penciclovir was more active than acyclovir with 99% effective concentrations of 0.6 mg/L and 1.1 mg/L, respectively. The activity of penciclovir in the 24 h virus yield reduction and antigen inhibition assays was inversely related to the multiplicity of infection, whereas this had considerably less effect on the inhibition of viral DNA synthesis. These results suggest that famciclovir, which is the oral form of penciclovir, will be at least as effective as acyclovir in treating infections caused by HSV-1 and HSV-2.

Acyclovir↗
PubMed1990

Detection of thoracolumbar vertebral body destruction with lateral spine radiography. Part I: Investigation in cadavers.

Despite few and inconclusive studies, radiography is generally believed to be insensitive for detection of osteolytic lesions of the spine. A more detailed investigation was undertaken to study the detectability of laboratory-produced osteolytic lesions in cadaveric thoracolumbar vertebral bodies using conventional lateral radiographs. The radiographs were presented to four radiologists in two sessions over a two month period. In the first session, the films were arranged in a composite of five vertebral bodies, T11 to L3 all from the same spine, in which one contained a lesion and the other four were normal. In the second session, each vertebral body film was presented individually. Area (Az) under the receiver-operating characteristic (ROC) curve was used to measure the performances of readers. Observer detection was similar in the two formats with Az ranging from 0.67 +/- 0.05 to 0.79 +/- 0.04 for the composite film arrangement and 0.57 +/- 0.08 to 0.85 +/- 0.10 for the films of individual vertebral bodies. Lesions were grouped into three relative size categories: 18% to 25%, 26% to 40%, and 41% to 60% of transverse vertebral body diameter. The mean increase in ROC area between the small and large lesions was 0.29 (P less than 0.04) for the composite films and 0.16 (P less than 0.05) for the individual films. In the composite study, all readers showed significant (P less than 0.05) increases in lesion detection in spines reflecting large increases (P less than 0.01) in bone mineral content.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadaver↗
PubMed1990

Detection of thoracolumbar vertebral body destruction with lateral spine radiography. Part II: Clinical investigation with computed tomography.

Conventional radiography in the lateral projection was used to evaluate 25 osteolytic lesions involving vertebral bodies of the thoracolumbar spine. Destruction was calculated as percentages of the maximum transverse diameter and volume of the vertebral body as measured by computed tomography (CT) and the effect of size of lesion on detection was evaluated. Areas (Az) under the receiver-operating characteristic (ROC) curves and the significance of differences were determined from the observations of four radiologists. The mean difference between areas under the ROC curve for lesions involving 32% to 60% of the transverse diameter and for larger lesions of 61% to 93% was 0.12 and significant (P less than 0.05). The effect of the presence of localized loss of vertebral body density, sclerotic bone tissue surrounding the lesion and cortical destruction was evaluated in a second session, in films with lesions the observers scored 4 (probably abnormal) or 5 (definitely abnormal). Cortical destruction was reported to be helpful for detection in 35% of lesions, sclerotic bone surrounding the lesions was helpful in 30%, and a qualitative local decrease in bone density was noted in all lesions. In comparison with the results obtained for the same four observers with experimentally produced lesions in our previous cadaveric study, the clinical lesions of comparable size were not as readily detected. The ROC area for the largest group of clinical lesions (61% to 93%, Az = 0.83 +/- 0.07) was not significantly different from that for a group of smaller cadaveric lesions (41% to 60%, Az = 0.83 +/- 0.05). The smaller clinical lesions (32% to 60%, Az = 0.71 +/- 0.08) were similar in detectability to the experimental lesions of relative diameter 26% to 40% (Az = 0.74 +/- 0.15). Caution should be exercised in the interpretation of conventional radiographs in the lateral projection if there is suspicion of vertebral body destruction.

Adult↗