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Biomedical subjects

L E Davis

Publications and source records attributed to L E Davis.

At least 73 records · Page 4Linked to original sources
PubMed1993

Temporal bone histopathology 14 years after cytomegalic inclusion disease: a case study.

Temporal bones were examined from a 14-year-old male who died of sequelae of congenital cytomegalic inclusion disease (CID). Cytomegalovirus (CMV) was not isolated from inner ear fluid or multiple systemic tissues at the time of death. Examination of temporal bones revealed chronic pathology of both cochlear and vestibular sensory and nonsensory tissues. Endolymphatic hydrops was observed in the basal turn of the cochlear duct, while Reissner's membrane was collapsed in the more apical turns. Strial atrophy and a loss of cochlear hair cells were observed along the entire length of the basilar membrane. Vestibular neuroepithelial regions were degenerated and fibrosis was seen within the vestibular perilymphatic tissue spaces, suggesting prior labyrinthitis within the perilymph compartment in addition to the more typical pattern of endolabyrinthitis associated with human CMV infection. Distention of the saccular membrane was evident. In both cochlear and vestibular tissues, there were isolated regions of calcifications that appeared characteristic to that reported in other organ systems of individuals with CID. Collectively, these chronic, pathological findings in this case of CID demonstrate more extensive injury than has been identified in the previously reported acute temporal bone pathology of CID.

Cochlea↗
PubMed1993

Viruses and vestibular neuritis: review of human and animal studies.

There is increasing evidence in man and animals that several human viruses can damage the vestibular labyrinth. Clinical and serologic studies of patients with vestibular neuritis suggest that the viruses may play a role in the pathogenesis of this disease. Temporal bone studies of patients dying after vestibular neuritis have found maximal damage in the distal branches of the vestibular nerve. These changes are felt to be consistent with a viral etiology. No satisfactory animal viral model of vestibular neuritis currently exists. However, animal studies have demonstrated that several human viruses including rubeola, herpes simplex, reovirus, mouse and guinea pig cytomegalovirus, and neurotropic strains of influenza A and mumps virus, can infect the vestibular nerve and the vestibular membranous labyrinth.

Animals↗
PubMed1993

The influenza B virus mouse model of Reye's syndrome: pathogenesis of the hypoglycaemia.

Up to 40% of children with Reye's syndrome have hypoglycaemia that could contribute to the patient's encephalopathy. We developed a mouse model in which intravenous inoculation of influenza B/Lee virus produced a non-permissive infection of hepatocytes and cerebral endothelial cells and caused many clinical, biochemical and pathologic features of Reye's syndrome. We used this model to study the pathogenesis of the hypoglycaemia. Beginning 6 hours after virus inoculation and persisting to death 18-30 hours later, blood glucose levels fell by 40% and glycogen disappeared from the liver. Gluconeogenesis in liver slices from a pyruvate substrate was significantly impaired. Pyruvate carboxylase, normally present in hepatocyte mitochondria, was largely displaced into the cytosol, rendering that enzyme fraction relatively useless in the gluconeogenesis pathway. Brain glucose levels fell proportionately to the depressed blood glucose level to a mean of 44 mg/100 g compared to 108 mg/100 g in control brains. We conclude that hypoglycaemia in the mouse model developed largely as a result of a non-permissive influenza viral infection of hepatocytes which impaired the mitochondrial phase of gluconeogenesis. The hypoglycaemia may have contributed to, but did not solely account for, the encephalopathy. A similar non-permissive influenza B infection may cause hypoglycaemia in Reye's syndrome.

Animals↗
PubMed1993

Botulinum toxin. From poison to medicine.

Although thousands of people in the world each year continue to be poisoned with botulinum toxin-food-borne, infantile, or wound botulism-the neurotoxin is now sufficiently understood to allow it to be used as a medicinal agent to paralyze specific muscles, giving temporary symptomatic relief from a variety of dystonic neurologic disorders. I review some of the epidemiologic, clinical, and pathophysiologic aspects of botulinum toxin and how the neurotoxin may act as a poison or a medicine.

Botulinum Toxins↗
PubMed1992

Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease.

Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.

Aged↗
PubMed1992

Role of angiotensin II and alpha-adrenergic receptors during estrogen-induced vasodilation in ewes.

Estradiol-17 beta (E2 beta) produces uterine and systemic vasodilation in nonpregnant ewes without altering mean arterial pressure (MAP). Mechanisms responsible for maintaining MAP and thus uterine blood flow (UBF) may include activation of the renin-angiotensin and/or adrenergic systems. We therefore investigated the effects of systemic blockade of angiotensin II (ANG II) and/or alpha-adrenergic receptors in nonpregnant, castrated ewes, using saralasin (Sar) and/or phentolamine (Phen) in the presence or absence of intravenous E2 beta (1.0 microgram/kg). In nonestrogenized ewes neither antagonist alone had substantial cardiovascular effects; however, Sar + Phen decreased systemic vascular resistance (SVR) 20 +/- 7.4% (SE) and increased heart rate (HR) 50 +/- 19% (P < 0.01); MAP and UBF were unaffected. Following E2 beta treatment SVR fell 17 +/- 2.4% (P < 0.01), UBF increased more than fourfold, and MAP was unchanged. Compared with E2 beta alone, Phen + E2 beta decreased SVR 42 +/- 4.7%, and MAP fell 11 +/- 1.8% (P < 0.05) despite 40-50% increases in HR and cardiac output (P < 0.05). Responses to Sar + E2 beta were similar to E2 beta alone, except for a fall in MAP, whereas responses to Sar + Phen + E2 beta resembled those of Phen + E2 beta. E2 beta-induced uterine vasodilation was unaltered by Sar and/or Phen. During E2 beta-induced vasodilation, MAP is maintained by enhanced activation of the alpha-adrenergic and renin-angiotensin systems; however, uterine vascular responses to E2 beta are independent of both systems and perfusion pressure.

Angiotensin II↗
PubMed1992

Early viral brain invasion in iatrogenic human immunodeficiency virus infection.

We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood.

Aged↗
PubMed1992

No-scalpel vasectomy: a technique for family physicians.

Family physicians frequently perform outpatient vasectomies. A new approach to exposing the vas deferens, called the no-scalpel vasectomy, results in fewer complications and, the authors believe, improved patient acceptance. This technique, which calls for two specialized instruments, is described, along with patient selection and education issues, vasal occlusion techniques and post-vasectomy follow-up.

Counseling↗
PubMed1991

Displacement of hepatic ornithine carbamoyltransferase from mitochondria to cytosol in Reye's syndrome.

In two patients with fatal Reye's Syndrome, total ornithine carbamoyltransferase (OCTase) activity in the liver was 50 and 75% of that found in three control livers. The levels of enzymatic activity would not be expected to have resulted in the 7- and 17-fold elevations in plasma ammonia levels found in the patients. Levels of 47 and 60% of the OCTase activity, however, were found in the cytosolic fraction compared to an average of 7% for control livers. Thus, the amount of enzymatic activity in the mitochondrial fractions was only 20 and 30% of that found in control mitochondrial fractions. This study suggests that, if only mitochondrial OCTase is active in the urea cycle, the decreases in functional enzyme found in Reye's Syndrome may be considerably greater than that reflected in total enzyme assays.

Child↗
PubMed1991

Pharmacokinetics and elimination of salicylic acid in rabbits.

Sodium salicylate was administered to rabbits in order to compare its disposition with that in other major and minor agricultural species. A dose of 44 mg/kg was given orally (p.o.) or intravenously (i.v.), and plasma and urine samples were collected for 36 h and 96 h, respectively. The majority of the drug was excreted as salicylic acid (SA) within 12 h. The major metabolites following an oral dose were salicyluric acid (SUA) and the glucuronide conjugates of SA and SUA. Following i.v. dosing, sulfate conjugates of both SA and SUA were also evident. Both SA and SUA were detected in plasma. Following i.v. administration, SA was distributed with a Vss of 0.249 +/- 0.082 l/kg and cleared at a rate of 0.0432 +/- 0.006 l/h/kg. The biological half-life, calculated from the terminal disposition-rate constant, was 4.3 h (i.v.) or 9.7 h (p.o.). The urinary elimination pattern of SA and metabolites in the rabbit was similar to that previously reported by our laboratories for cattle and goats, although total recovery of the administered dose was not as high as for the latter two species. However, the volume of distribution was larger than for cattle and goats, and rabbits cleared the drug more slowly than those species. As a consequence, the biological half-life was eight to ten times longer than in the ruminants studied previously.

Administration, Oral↗
PubMed1991

Hemodynamics and organ blood flow in fetal sheep subjected to chronic anemia.

To investigate cardiovascular adaptation to chronic anemia we studied eight ovine fetuses made anemic by serial isovolemic hemorrhage and seven nonanemic controls. After 1 wk carotid arterial oxygen content was reduced to 1.6 +/- 0.2 ml/dl and hematocrit to 13.3 +/- 1.6% in anemic fetuses compared with 6.9 +/- 1.2 ml/dl and 32.4 +/- 3.9% in controls. Cardiac output was higher in the anemic group (753 +/- 102 vs. 490 +/- 66 ml.min-1.kg fetus-1) as stroke volume and heart rate both increased. Blood flow to the carcass, skin, kidneys, intestines, brain, and heart was increased. Vascular resistance fell in all tissues except the placenta. Central venous pressure, arterial pH, plasma total protein, and blood volume were not different although extravascular fluid accumulated in six of the anemic fetuses. The estimated capillary hydrostatic pressure was greater in anemic (7.6 +/- 1.8 mmHg) than control fetuses (5.0 +/- 1.5 mmHg) and the ratio of precapillary to postcapillary resistance was less. We conclude that reduction in the ratio of precapillary to postcapillary resistance in chronic fetal anemia increases blood flow, oxygen delivery, and capillary hydrostatic pressure.

Anemia↗
PubMed1991

Neurocysticercosis: neurologic, pathogenic, diagnostic and therapeutic aspects.

Worldwide neurocysticercosis is the most common parasitic infection of the human brain and meninges. Clinical features of the illness vary with the stage of ova infection, but most problems arise when the mature cyst degenerates. Seizures, increased intracranial pressure, and focal neurologic signs then often develop. Computed tomography and magnetic resonance usually demonstrate Cysticercus cellulosae cysts in the brain. A new immunoblot test for antibodies to the cysticercus seems both sensitive and specific. Treatment with praziquantel or albendazole has hastened the disappearance of the cysts on computed tomography and improved clinical symptoms.

Albendazole↗
PubMed1991

Neuropathologic findings in Reye syndrome.

Brain tissue from three patients with a clinical diagnosis of Reye syndrome was compared with tissue from three control patients. All Reye syndrome patients demonstrated cytotoxic cerebral edema, with swelling of astrocyte foot processes, which was not seen in controls. Myelin sheath splitting was seen both in controls and patients, but myelin blebs were uncommon in both. Mitochondrial changes also were not seen. Although cerebral edema is a nonspecific finding, it appears to be characteristic of Reye syndrome.

Adolescent↗
PubMed1991

Aiding the Alzheimer's dementia patient to live in safety and security.

Alzheimer's is truly a "family" disease, affecting not only the patient but the entire family. The patient's emotional/psychological safety and security are as important as his or her physical condition, and therefore must be addressed. Families should be encouraged to use every resource that is available. The nurse/caregiver is in an excellent position to offer support and suggest resources. The key is understanding the course of the disease and measures that can be employed to maintain the patient in optimal safety and security.

Activities of Daily Living↗
PubMed1991

Influenza A virus in the mouse: hepatic and cerebral lesions in a Reye's syndrome-like illness.

To develop an animal model of Reye's syndrome using a virus associated with the human disease, mice were intravenously inoculated with influenza A/PR8 virus (LD50 4000 haemagglutinin units). One to 3 days later the mice developed lethargy, seizures, coma and death. The cerebrospinal fluid cell count was normal. Serum aspartate aminotransferase levels increased 24-fold. Diffuse microvesicular fatty metamorphosis along with multiple small foci of necrosis developed in the liver. Influenza virus-like particles were seen by electron microscopy in the liver, primarily in areas of liver necrosis, but were not seen in the brain. Cerebral oedema without inflammation developed in the brain. Limited viral replication occurred within the liver. Influenza viral antigens were seen in 5-20% of hepatocytes from both necrotic and non-necrotic areas as well as in brain endothelial cells. Many of the clinical, biochemical and pathologic features of the mouse illness resemble those seen in Reye's syndrome. However, this model differs from the human disease in that focal areas of liver necrosis occurred along with limited complete viral replication in liver.

Animals↗