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Biomedical subjects

D Armstrong

Publications and source records attributed to D Armstrong.

At least 163 records · Page 9Linked to original sources

Mycobacterium tuberculosis infection in a green-winged macaw (Ara chloroptera): report with public health implications.

Mycobacterium tuberculosis was isolated from the eyelid, skin, tongue, and lungs of a green-winged macaw (Ara chloroptera). Two persons living in the same household were culture positive for pulmonary tuberculosis 3 to 4 years before tuberculosis was diagnosed in the bird. Although humans have not been shown to acquire tuberculosis from birds, an infected bird may be a sentinel for human infection.

Animals↗

Determination of volumetric cerebrospinal fluid absorption into extracranial lymphatics in sheep.

We estimated the volumetric clearance of cerebrospinal fluid (CSF) through arachnoid villi and extracranial lymphatics in conscious sheep. Catheters were inserted into both lateral ventricles, the cisterna magna, multiple cervical lymphatics, thoracic duct, and jugular vein. Uncannulated cervical vessels were ligated. 125I-labeled human serum albumin (HSA) was administered into both lateral ventricles. 131I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, total volumetric absorption of CSF averaged 3.37 +/- 0.38 ml/h, with 2.03 +/- 0.29 ml/h (approximately 60%) removed by arachnoid villi and 1.35 +/- 0.46 ml/h (approximately 40%) cleared by lymphatics. With projected estimates for noncannulated ducts, total CSF absorption increased to 3.89 +/- 0.33 ml/h, with 1.86 +/- 0.49 ml/h (48%) absorbed by lymphatics. Additionally, we calculated total CSF drainage to be 3.48 +/- 0.52 ml/h, with 54 and 46% removed by arachnoid villi and lymphatics, respectively, using previously published mass transport data from our group. We employed estimates of CSF tracer concentrations that were extrapolated from relationships observed in the study reported here. We conclude that 40-48% of the total volume of CSF absorbed from the cranial compartment is removed by extracranial lymphatic vessels.

Animals↗

Raised intracranial pressure increases CSF drainage through arachnoid villi and extracranial lymphatics.

We demonstrated previously that about one-half of cerebrospinal fluid (CSF) removed from the cranial vault was cleared by extracranial lymphatic vessels. In this report we test the hypothesis that lymphatic drainage of CSF increases as intracranial pressure (ICP) is elevated in anesthetized sheep. Catheters were inserted into both lateral ventricles, cisterna magna, cervical lymphatics, and jugular vein. A ventriculocisternal perfusion system was employed to regulate CSF pressures and to deliver a protein tracer (125I-labeled human serum albumin) into the CSF compartment. 131I-labeled human serum albumin was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. ICP was controlled by adjusting the height of the inflow reservoir and the cisterna magna outflow catheter appropriately. The experimental design consisted of a 3-h period of lower pressure followed by a 3-h period of higher pressure in the same animal (10-20 or 20-30 cmH2O). We determined that incremental changes in ICP were associated with higher CSF transport through lymphatic and arachnoid villi routes in all eight animals tested (P = 0.004).

Animals↗

Omeprazole for refractory gastroesophageal reflux disease during pregnancy and lactation.

Symptomatic gastroesophageal reflux is a common complication of pregnancy and lactation. However, the safety of many effective medical therapies, including oral proton pump inhibitors, has not been well defined. The administration of oral omeprazole to a 41-year-old female during the third trimester of pregnancy, after ranitidine and cisapride failed to control her refractory gastroesophageal reflux, is reported. No adverse fetal effects were apparent, and the patient elected to continue omeprazole therapy (20 mg/day) while breastfeeding. Peak omeprazole concentrations in breast milk (58 nM, 3 h after ingestion) were less than 7% of the peak serum concentration (950 nM at 4 h), indicating minimal secretion. Although omeprazole is a potentially useful therapy for refractory gastroesophageal reflux during pregnancy and lactation, further data are needed to define better its safety and efficacy.

Adult↗

Detection of vascular endothelial growth factor and tumor necrosis factor alpha in epiretinal membranes of proliferative diabetic retinopathy, proliferative vitreoretinopathy and macular pucker.

PURPOSE: To evaluate epiretinal membranes in proliferative eye disease for the presence of vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-alpha). METHODS: Membranes were surgically removed from 66 patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular pucker (MP). Cytokine concentrations were determined by ELISA (VEGF) and bioassay (TNF-alpha). RESULTS: VEGF was detected in all 66 membranes investigated. The highest VEGF values were found in patients with type I diabetes (mean = 5,994 pg/mg protein). In patients with type II diabetes, the values were at a mean of 1,242 pg/mg protein. When coagulation therapy was performed for longer than 3 months prior to surgery, VEGF was significantly (p < 0.05) reduced. Intermediate levels of VEGF were found in PVR membranes (mean = 1,417 pg/mg protein). The lowest activity was found in MP (mean = 216 pg/mg protein). In contrast, TNF-alpha was present in 16 PDR membranes, 9 PVR membranes and 8 MP membranes. CONCLUSION: The presence of VEGF in all membranes investigated indicates that this cytokine plays an important role in angiogenesis in ischemic retinal disease and in membrane growth in proliferative disorders.

Diabetic Retinopathy↗

Clinical Guidelines for Managing Topotecan-Related Hematologic Toxicity.

PURPOSE: Topotecan, a semisynthetic water-soluble camptothecin analog, was recently approved as a second-line treatment for women with ovarian cancer. In clinical trials, hematologic toxicity has been the predominant toxicity associated with its use. The purpose of this article is to provide guidelines on the clinical management of these toxicities. METHODS: The guidelines on the management of hematologic toxicities associated with topotecan therapy for advanced ovarian cancer patients were established through a review and analysis of phase I, II, and III clinical trials. RESULTS: In phase I studies, noncumulative neutropenia was the predominant toxicity associated with topotecan therapy. In subsequently conducted phase II trials, thrombocytopenia related to prior carboplatin and alkylating agent therapies has become a prominent toxicity, and neutropenia has been more severe than anticipated from phase I studies. The risk for both toxicities relates to the extent of prior myelosuppressive chemotherapy and to renal impairment. These toxicities can be managed through the identification of high-risk patients and implementation of appropriate prophylactic measures. Such measures include dose reductions or the use of hematopoietic growth factors. For patients with persistently low blood cell parameters, transfusion therapy remains a viable option. CONCLUSION: Hematologic toxicities associated with topotecan therapy are noncumulative. Consequently, once a dosing regimen is established, toxicity patterns are predictable. Pretreatment assessment of the nature and toxicities of prior therapy and renal function should assist the clinician in preventing complications caused by the myelosuppressive effects of topotecan therapy.

Journal Article↗

Oxidative stress and lung function.

It has been suggested that lung function can be altered by both free radical and oxidant exposure, while antioxidant vitamin intake is positively related to lung function. However, the information on the relation of blood levels of oxidants and antioxidants to lung function is sparse. The present cross-sectional study, conducted from September 1995 to May 1996, analyzes the association between lung function measured as forced expiratory volume in 1 second (FEV1) with 1) levels of thiobarbituric acid-reactive substances in plasma (p-TBARS) and in low and very low density lipoprotein cholesterol (LDL cholesterol/VLDL cholesterol-TBARS) as indicators of lipid peroxidation and 2) compounds with antioxidant activity, erythrocytic glutathione, plasma glutathione peroxidase, trolox equivalent antioxidant capacity, and serum bilirubin, which may protect against lipid peroxidation. The analysis was carried out in 132 nonsmoking subjects aged 37-73 years who were randomly selected from the residents of Erie and Niagara counties, New York. FEV1 in percent of the predicted value (FEV1%) was negatively and statistical significantly associated with p-TBARS (r = -0.19). A negative association with borderline statistical significance was observed between FEV1% with low density lipoprotein cholesterol/very low density lipoprotein cholesterol-TBARS (r = -0.16) and glutathione (r = -0.16), while FEV1% was positively related to serum bilirubin (r = 0.15). Participants in the lowest quartile of FEV1% showed significantly higher levels of p-TBARS (p = 0.02) and lower levels of bilirubin (p = 0.04) than did those in the highest quartile. Our results suggest that increased lipid peroxidation is associated with pulmonary airway narrowing in the general population.

Adult↗

Purification of a fatty acid-stimulated protein-serine/threonine phosphatase from bovine brain and its identification as a homolog of protein phosphatase 5.

An arachidonic acid-stimulated Ser/Thr phosphatase activity was detected in soluble extracts prepared from rat pituitary clonal GH4C1 cells, rat or bovine brain, and bovine heart. The enzyme activity was purified to homogeneity from bovine brain as a monomer with a Mr of 63,000 and a specific activity of 32 nmol of Pi released per min/mg of protein when assayed in the presence of 10 microM phosphocasein in the absence of lipid. Arachidonic acid stimulated activity 4-14-fold, with half-maximal stimulation at 50-100 microM, when assayed in the presence of a variety of phosphosubstrates including casein, reduced carboxamidomethylated and maleylated lysozyme, myelin basic protein, and histone. Oleic acid, linoleic acid, and palmitoleic acid also stimulated activity; however, saturated fatty acids and alcohol or methyl ester derivatives of fatty acids did not significantly affect activity. The lipid-stimulated phosphatase was identified as the bovine equivalent of protein phosphatase 5 or a closely related homolog by sequence analysis of proteolytic fragments generated from the purified enzyme. When recombinant rat protein phosphatase 5 was expressed as a cleavable glutathione S-transferase fusion protein, the affinity-purified thrombin-cleaved enzyme exhibited a specific activity and sensitivity to arachidonic acid similar to those of the purified bovine brain enzyme. These results suggest that protein phosphatase 5 may be regulated in vivo by a lipid second messenger or another endogenous activator.

Amino Acid Sequence↗

A national survey of immunization practices following allogeneic bone marrow transplantation.

OBJECTIVES: To describe the frequency and patterns of use of routine childhood and hepatitis B, pneumococcal, influenza, and meningococcal vaccines following allogeneic bone marrow transplantation (BMT). DESIGN, SETTING, AND PARTICIPANTS: Survey of all US transplantation centers participating in the National Marrow Donor Program (NMDP) during 1994. MAIN OUTCOME MEASURES: Use, timing, and total doses of selected vaccines given to patients younger than 7 years and patients aged 7 years or older following allogeneic BMT. RESULTS: Of 66 centers associated with the NMDP, 45 (68%) responded. A total of 97% of centers performing transplants on patients younger than 7 years and 88% of centers performing transplants on patients aged 7 years or older gave either the diphtheria-tetanus vaccine or the diphtheria-tetanus-pertussis vaccine compared with 77% and 58% usage, respectively, of Haemophilus influenza type b conjugate vaccine (P=.03 and .003, respectively). Centers were more likely to administer inactivated poliovirus and measles-mumps-rubella vaccines to patients younger than 7 years than to the older age group (94% vs 73% for poliovirus, P=.02; and 94% vs 70% for measles-mumps-rubella, P=.01). About one half of centers routinely administer hepatitis B vaccine and approximately three quarters immunize with pneumococcal and influenza vaccines. Few programs, regardless of age of bone marrow recipient, use multiple vaccine (> or =2) doses. The number of schedules reported for specific vaccines varied widely (3-11 schedules per vaccine). CONCLUSIONS: Despite convincing evidence that patients lose protective antibodies to vaccine-preventable diseases following allogeneic BMT and accumulating data showing the safety and efficacy of many vaccines after BMT, vaccines are underutilized and schedules vary widely at US transplant centers. National guidelines for optimal doses and timing of vaccines after BMT are warranted.

Adolescent↗

99mTechnetium HMPAO imaging in children with the Sturge-Weber syndrome: a study of nine cases with CT and MRI correlation.

Demonstration of the full extent of abnormality in patients with the Struge-Weber syndrome (SWS) is important for prognosis and in planning surgery to remove the seizure focus. We compared single-photon emission computed tomography (SPECT), MRI and CT in nine children under the age of 4 years with seizures as part of SWS, in an attempt to determine the optimal method of imaging in different clinical settings. Seven unilateral and two bilateral cases were studied by interictal 99mtechnetium hexamethylpropyleneamineoxime (HMPAO) SPECT, and contrast-enhanced CT and MRI, giving information on 11 abnormal hemispheres. All imaging modalities showed abnormalities in every child. Perfusion imaging showed focal regions of decreased uptake in 9 of 11 (82%) abnormal hemispheres and demonstrated a widespread decrease but no focal defect in 2; it also revealed crossed cerebellar diaschisis in 2 cases. CT demonstrated typical gyriform calcification in 9 of 11 (82%) affected hemispheres. Contrast-enhanced MRI showed more extensive involvement than contrast-enhanced CT in 5 of 11 (45%) cases. The area of hypoperfusion shown by SPECT was smaller than the area of contrast enhancement on MRI in 6 of 11 cases (55%), comparable in 3 (27%) and larger in 2 cases (18%). CT is sufficient to confirm the clinical diagnosis of SWS, but MRI frequently shows more extensive abnormal areas. 99mTc HMPAO imaging is a useful addition when it is important to know the full extent of the disease, for example prior to surgery. It is likely to detect areas of hypoperfusion, representing ischaemic regions, which may act as an epileptogenic focus and may not be shown by CT or MRI.

Adolescent↗

Acute obstructive hydrocephalus and sudden death in children.

STUDY OBJECTIVE: Sudden death from obstructive hydrocephalus related to intracranial neoplasms has rarely been reported in the pediatric literature. We sought to review the presenting signs and symptoms of acute hydrocephalus resulting from intracranial mass lesions to guide clinicians in the early identification of these potentially reversible lesions. METHODS: All cases of sudden unexpected death attributable to obstructive hydrocephalus that occurred from 1990 through 1994 at the Hospital for Sick Children, Toronto, were retrospectively reviewed. RESULTS: During the study period, seven children, ages 10 months to 15 years, died unexpectedly with acute obstructive hydrocephalus. Six children were apparently normal, and none had any known neurologic disease. All patients had a previously undiagnosed intracranial tumor located at a critical site for CSF flow: colloid cyst(n = 2), astrocytoma (n = 2), ependymoma (n = 2), suspected lymphoma (n = 1). Presenting features included vomiting in all cases, vomiting for longer than 2 weeks in three, headache in four, and lethargy in three. Five patients were misdiagnosed with viral illnesses, including three with presumed gastroenteritis who received intravenous rehydration therapy Focal gastrointestinal signs were absent. CONCLUSION: This case series highlights a life-threatening but misleading presentation of intracranial tumors. The diagnosis of gastroenteritis should be made cautiously when headache and vomiting occur in the absence of focal intestinal complaints. A history of vomiting exceeding a few days' duration warrants further investigation. Persistent lethargy should be considered a neurologic rather than a nonspecific clinical sign. Heightened awareness of this neurosurgical emergency may lead to swift intervention and potential reversibility with diversion of CSF.

Brain Neoplasms↗