Biomedical subjects
J Davis
Publications and source records attributed to J Davis.
Organization of the proximal, orbital segment of the infraorbital nerve at multiple intervals after axotomy at birth: a quantitative electron microscopic study in rat.
Although much is known of the central consequences of infraorbital nerve (ION) transection at birth, little is known about the effects of this lesion on the organization of the ION itself. To advance our understanding of how deafferentation alters the developing trigeminal neuraxis, 19 newborn rats were subjected to left ION section and perfused 1, 2, 4, 7, 17, or 90 days later. Left IONs were removed in the orbit proximal to the nerve injury site, and axon numbers, types, and fasciculation patterns were assessed with light and electron microscopic methods. Complete axon counts demonstrated that the axotomized ION contained an average (+/- SD) of 13,945 +/- 10,335, 14,112 +/- 3,501, 16,531 +/- 1,904, 9,045 +/- 1,465, 7,018 +/- 4,212, and 8,672 +/- 1,030 axons at the above-listed ages, respectively. These values are well below the 33,059 axons in the normal adult ION (Jacquin et al. [1984] Brain Res. 290:131-135) and the 42,219 axons in the newborn ION (Renehan and Rhoades [1984] Brain Res. 322:369-373). The axotomized ION also contained lower than normal percentages of myelinated axons (26.7% +/- 6.3% on postnatal day 90 vs. 59.7% +/- 6.2% in normal adults). Unmyelinated fibers constituted the vast majority of the remaining fiber types; degenerating fibers never accounted for > 1.6% of all the axons. The number of fascicles making up the axotomized ION overlapped significantly with those found in the normal newborn and adult ION. We conclude that 1) extensive, though variable, axon elimination occurs proximally within one day of the lesion; 2) the 74% reduction in fiber number seen at 90 days is not reliably achieved until postnatal day 7; 3) the higher than normal proportion of unmyelinated axons in the injured ION may underly many of the known effects of neonatal ION injury on the developing whisker-barrel neuraxis; 4) gross changes in ION fasciculation patterns are not prerequisite to injury-induced pattern alterations in the developing trigeminal system.
Administration of human recombinant granulocyte colony-stimulating factor (filgrastim) accelerates granulocyte recovery following high-dose chemotherapy and autologous marrow transplantation with 4-hydroperoxycyclophosphamide-purged marrow in women with metastatic breast cancer.
Stem cell contamination by tumor is common in many diseases for which autologous bone marrow transplantation is used. In in vitro models chemotherapeutic purging reduces contamination and may have an impact on clinical outcome. Purging, however, delays engraftment. Little is known about the ability of granulocyte colony-stimulating factor (G-CSF) to accelerate myelopoiesis after purged autologous bone marrow transplantation. We treated 22 women with metastatic breast cancer with high-dose cyclophosphamide and thiotepa and, following the infusion of 4-hydroperoxycyclophosphamide-purged marrow, administered G-CSF, 16 micrograms/kg daily, from day 0 to engraftment. Results were compared with a control population of 24 women with breast cancer who received identical chemotherapy and purged marrow but not growth factor. Neutrophil recovery was accelerated in the G-CSF-treated population. An absolute neutrophil count of 500 was reached in 19 days compared with 29 for the historic controls. The median number of days febrile was reduced (8 versus 5.5) as were the number of days of hospitalization from marrow infusion (33 versus 25). There was no difference in the number of days on antibiotics or time to last platelet transfusion. G-CSF was administered without any notable toxicity. G-CSF accelerates myelopoiesis following the infusion of 4-hydroperoxycyclophosphamide-purged autologous marrow and shortens hospitalization.
An all age group study of the prevalence of asthma in Golden Bay.
AIMS: To determine the prevalence of asthma within the total population of a region defined by census and geographical boundaries. METHODS: Patients on the asthma register of the sole medical centre in the region of Golden Bay, during the period of six months before the March 1991 census, were compared by age and sex with the census figures for the whole population. The methods of verifying the numbers on the register are described. RESULTS: The total number of patients of all age groups under treatment for asthma was 260, giving a prevalence of asthma in the population of 4803 of 5.41% (males 5.67%, females 5.11%). In children between ages 1-14 years there were 9.21% with asthma. The prevalence, defined by percentage for each group, rises from infancy to peak in the mid teens at 10%, followed by a steady decline to the mid thirties to 3.4%, and thereafter a rather flat plateau between 3.5% and 4% into old age. CONCLUSIONS: Previous studies of the prevalence of asthma have been limited to schoolchildren. Whole population studies, within a defined region, are likely to offer more information for the planning of healthcare resources, and may give some clues to understanding the natural history of the disease.
CD4+ T cell clones obtained from Plasmodium falciparum sporozoite-immunized volunteers recognize polymorphic sequences of the circumsporozoite protein.
CD4+ T cell clones were derived from three volunteers who were protected against malaria after immunization with Plasmodium falciparum sporozoites. T cells specific for an epitope, Pf Th/Tc, contained in amino acids 326 to 345 of the circumsporozoite (CS) protein of P. falciparum (NF54) were derived from all three volunteers. DR1-, -4-, -7-, and -9-restricted T cell clones were found to recognize overlapping, but distinct, epitopes within a 20-mer peptide representing the amino acid 326 to 345 sequence. The Pf Th/Tc epitope contains part of the highly conserved region II as well as part of a polymorphic domain of the P. falciparum CS protein. All of the overlapping epitopes within peptide 326-345 contained at least three amino acids of the amino terminus of the conserved region II, in addition to a variable number of amino acids in the polymorphic region. The DR4-, -7-, and -9-restricted but not the DR1-restricted T cell clones recognized variant peptides representing this polymorphic region of the CS protein of P. falciparum isolates from Africa, Asia, and South America.
A masked, randomized, dose-response study between cyclosporine A and G in the treatment of sight-threatening uveitis of noninfectious origin.
Thirty-two patients with sight-threatening uveitis and a decrease in visual acuity requiring systemic therapy were randomly assigned to either cyclosporine A or G in a dose-escalation study. Groups received from 2.5 mg/kg of body weight/day to 10 mg/kg of body weight/day of either drug along with low-dose prednisone. More patients taking cyclosporine G had improved visual acuity and a decrease in macular edema, which occurred more rapidly than in the other group, even at the lower doses tested. No difference in renal function was noted between groups at any doses tested. Four patients receiving cyclosporine G had hepatic alterations, but only one required cessation of the drug. The study indicates the potential usefulness of cyclosporine G, particularly at lower doses (4 mg/kg of body weight/day), which could lower the potential for serious renal complications.
Vogt-Koyanagi-Harada syndrome in patients with Cherokee Indian ancestry.
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Deep venous thrombosis caused by femoral exostosis.
OBJECTIVE: To present the first case of deep venous thrombosis caused by femoral exostosis reported in Australia. CLINICAL FEATURES: An 11-year-old prepubertal Caucasian girl had a two-year history of a posterior femoral exostosis. She then presented with a deep venous thrombosis 24 hours after riding a horse for the first time. The deep venous thrombosis was diagnosed by Doppler ultrasound, which showed an intimate relationship between the femoral exostosis and the femoral vein. Coagulation abnormalities were excluded. INTERVENTION AND OUTCOME: The patient was given anticoagulation therapy with heparin intravenously and warfarin orally. The popliteal vein recanalised within two days. The exostosis was excised 10 weeks after initial presentation, with warfarin being continued for four weeks postoperatively. Two months after excision the patient was symptom free. CONCLUSIONS: It is possible for venous compression by an exostosis to result in thrombosis in a patient with no underlying coagulation abnormality. Palpation and plain radiography of the region will demonstrate the exostosis; ultrasound is the next investigation of choice.
X-linked lymphoproliferative disease.
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Interferon alfa-2a in the treatment of exudative age-related macular degeneration.
Nineteen patients (20 eyes) with the exudative form of macular degeneration were treated with parenteral interferon alfa-2a. Fifteen patients (16 eyes) had adequate follow-up for evaluation of outcome of the exudative macular lesion. The average follow-up was 8 months (range 5-11 months). Color photographs and fluorescein angiograms were evaluated independently by two masked readers for change in size, presence of fibrosis, and leakage of the neovascular lesion. During the follow-up, none of the exudative lesions resolved: one lesion became smaller, four remained the same, nine enlarged, and two could not be graded based on the photographs. Visual acuity remained 20/40 or better in four eyes. The proportion of eyes with visual acuity of 20/200 or worse increased from 35% at the initial visit to 59% at the final visit. Ten patients experienced significant but reversible side effects, including weight loss, depression, and/or hematopoietic suppression. The data from these cases do not support any significant treatment benefit from interferon alfa-2a at the doses used in exudative macular degeneration.
Changes in the level of perforin and its transcript during effector and target cell interactions.
Perforin is a cytoplasmic granule protein expressed in cytotoxic lymphocytes, and is capable of lysing target cells. This protein is induced as cytotoxic T cells are activated, and the mRNA expression is modulated by various stimulators. These observations suggest possible changes in the level of perforin transcripts and protein when killer lymphocytes meet specific target cells leading to target cell death. To address this question, we examined three murine T-cell clones and primary human NK cells in perforin expression. When the cytotoxic lymphocytes were exposed to sensitive targets, perforin mRNA disappeared within 5 to 30 min and appeared within an hour thereafter. Among the murine T cell clones, L3 and OE4 showed two phases of mRNA decrease while human NK cells and the third murine T cell clone, AB.1, showed only one phase of mRNA loss during a 240 min period. The data indicate that when cytotoxic lymphocytes receive signals from a sensitive target, the cells rapidly degrade previously accumulated perforin mRNA and synthesize new transcripts. Interestingly, heat shock protein 70 mRNA was induced as the perforin mRNA levels recovered, while P55 Il-2 receptor mRNA was downregulated within 5 min after exposure to targets. The perforin protein level also rapidly decreased immediately after the interaction with the target, followed by a recovery, and then another decrease as seen in primary human NK cells, OE4 and L3 cells. However, in the AB.1 clone, no change in perforin content was detectable, despite the loss of perforin mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Sézary syndrome in an 11-year-old girl.
All forms of cutaneous T-cell lymphoma are rare in children. We describe an 11-year-old girl who had generalized exfoliative erythroderma, intense pruritus, peripheral lymphadenopathy, mycosis cells in the skin and lymph nodes, and Sézary cells in the peripheral blood. Results of a biopsy specimen of involved skin showed changes consistent with mycosis fungoides. A classic case of Sézary syndrome has not previously been reported in childhood or preadolescence.
Wrist anatomy: incidence, distribution, and correlation of anatomic variations, tears, and arthrosis.
We dissected 393 wrists to evaluate the incidence and distribution of anatomic features, arthrosis, chondromalacia, and soft tissue lesions. The data were then analyzed for any statistically significant associations among the different variables. The most common (73%) lunate morphology had a separate medial facet on its distal surface for the hamate. The capitate had a separate facet for the fourth metacarpal in 86% of the wrists. Fourth metacarpals with a dorsal radial facet, either separate from or connected to the rest of the fourth metacarpal base, were the most common types of fourth metacarpal. Cartilage erosion with exposed subchondral bone was identified in 58% of the wrists. It was most commonly at the proximal pole of the hamate (28%). Tears of the ligaments and/or the triangular fibrocartilage complex were identified in 56% of the wrists. The triangular fibrocartilage complex was found torn in 36% of the wrists. The lunotriquetral interosseous ligament was torn in 36% of the wrists, and the scapholunate interosseous ligament was torn in 28% of the wrists. There was a communication between the proximal wrist joint and the pisotriquetral joint in 88% of the 76 wrists, which were further dissected to assess this issue. Statistical analysis of the data found a significant correlation between the presence of cartilage erosion at the proximal pole of the hamate and the presence of a lunate facet. There was also a significant correlation between the presence of a tear in the scapholunate interosseous ligament and the presence of cartilage erosion in the scaphoid-trapezium-trapezoid joint. Analysis of the paired wrists from 169 cadavers revealed that the same soft tissue tear or combination of tears was present bilaterally in 39% of the pairs. Cartilage erosion was present bilaterally in the same location or locations in 27% of the pairs.
Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy.
OBJECTIVES: This study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy. BACKGROUND: Several beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement. METHODS: Twenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were entered into a double-blind randomized trial of nebivolol, a new, potent, selective beta 1-antagonist. Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13). RESULTS: Heart rate decreased (group mean 85 to 71 beats/min vs. 87 to 87 beats/min with placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs. 42 to 43 ml) with nebivolol; decreases in systemic resistance, systemic arterial pressure, wedge pressure and pulmonary artery pressure were not significantly different from those with placebo. Similar hemodynamic results were obtained in the catheterization laboratory. Analysis of high fidelity measurements of left ventricular pressure showed a decrease in left ventricular end-diastolic pressure in the nebivolol group (group mean 21 to 15 vs. 24 to 20 mm Hg with placebo) but no change in the maximal rate of pressure development or in two variables of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dtmax] and the time constant tau). Left ventricular mass decreased (p = 0.04). Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS). End-systolic volume tended to decrease (p = 0.07) despite no reduction in end-systolic stress. The net result was a significant increase in ejection fraction (group mean 0.23 to 0.33 vs. 0.21 to 0.23 with placebo), presumably as a result of an increase in contractile performance. This effect was corroborated by an increase in a relatively load-independent variable of myocardial performance. CONCLUSIONS: Nebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance.
Acidic fibroblast growth factor infusion reduces ischemic CA1 hippocampal damage in the gerbil.
Occlusion of the carotid arteries for 5 minutes in the Mongolian gerbil results in selective necrosis of CA1 pyramidal neurons. In the present experiments we studied whether intraventricular infusion of acidic fibroblast growth factor (aFGF) could attenuate this damage. Intraventricular infusions of bovine serum albumin (BSA-10 ng/h) or aFGF (1, 10 or 100 ng/h) were started 2 days prior to 5 minutes of bilateral carotid occlusion and continued for 5 days post-ischemia. The brains were perfused and fixed at 5 days post-ischemia and histological assessment of CA1 damage was made. Animals receiving intraventricular infusions of 10 or 100 ng/h aFGF showed a significant reduction of CA1 neuronal damage in comparison to no treatment ischemic controls (no treatment-8 +/- 1; aFGF 10 ng/h-147 +/- 28; aFGF 100 ng/h-168 +/- 35 cells/mm CA1; P < 0.05 for both aFGF groups). The results indicate that aFGF infusion can attenuate the severity of ischemic neuronal necrosis in the gerbil hippocampus.
Failure of iron chelators to protect against cerebral infarction in hypoxia-ischemia.
In this study the ability of iron chelators to attenuate hypoxic-ischemic brain damage was assessed in hyperglycemic rats that were exposed to 1% carbon monoxide and right carotid occlusion. The animals received deferoxamine (50 mg/kg), manganese-deferoxamine (50 mg/kg) or vehicle i.p. 0.5 h prior to hypoxemic-ischemic exposure and at 0.5, 3 and 24 h post-exposure; with subsequent histological examination of the brain at 7 days recovery. The area of cerebral infarction was measured at three levels using video imaging methods. The mean percentage of total hemisphere that was infarcted in the three groups was: vehicle--28.5 +/- 5.0; deferoxamine--31.7 +/- 12.1; and manganese deferoxamine--30.6 +/- 6.8 (p-n.s.). The results as obtained in this preliminary study indicate that aggressive pre- and post-treatment with iron chelators has no ability to attenuate cerebral infarction in this model.
Amyloid plaque of the lower eyelid: a patient report and review of the literature.
Localized conjunctival amyloid plaque is a rare disorder. It usually remains localized and is only rarely associated with systemic disease, unlike cutaneous amyloid deposits of the eyelid. The pathogenesis is unknown, but appears to be related to long-standing chronic inflammation. There may be a localized immunological disorder or an underlying systemic disease in rare instances. Because of this possible association, all patients should undergo through physical examination with close follow-up to rule out systemic disease. Plastic surgeons need to be aware of this lesion because the diagnosis is easily missed, clinically. The primary clinical working diagnosis before biopsy is a neoplasm, and recognition of this entity can prevent unnecessarily radical surgery.
Primary lymphoma of the gallbladder.
A case of primary lymphoma of the gallbladder is described which is rare in the medical literature. A 76 year old man presented with acute cholecystitis and septicaemia. Investigation showed a lung abscess and a gallbladder mass. The mass was thought to be an empyema and cholecystostomy was performed. Biopsy of the gallbladder wall showed high-grade B cell lymphoma. The patient unfortunately succumbed to overwhelming septicaemia in the postoperative period. Postmortem examination confirmed primary lymphoma of the gallbladder without dissemination.