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Biomedical subjects

F Smith

Publications and source records attributed to F Smith.

At least 37 records · Page 2Linked to original sources

Enhancement of coxsackievirus B4 virulence by indomethacin.

The safety of nonsteroidal anti-inflammatory agents in viral infections was assessed in a mouse model of coxsackievirus B4 neonatal myocarditis. Two-day-old mice were infected intraperitoneally with 10(4) TCID50 coxsackievirus B4 and then randomized to receive indomethacin or saline for 7 days. A number of them were killed on designated days. Mortality, viral titers, antibody, and interferon levels plus histopathologic changes in the heart were compared. Among treated animals, mortality was greater (22/45 vs 7/27; p = 0.07) and viral titers were higher on days 4 and 7 (p = 0.038 and 0.028, respectively). Interferon levels were lower on days 4 and 7 (p = 0.028 and 0.008, respectively), and histopathologic changes were more extensive on days 7 and 21 (p = 0.008 and 0.028, respectively). These findings show that indomethacin decreased interferon production, increased coxsackievirus4 titers, and enhanced the virulence of coxsackievirus B4. These results raise significant concerns about the safety of indiscriminate use of nonsteroidal anti-inflammatory agents during severe viral infections.

Animals

Modification of exercise-aggravated coxsackievirus B3 murine myocarditis by T lymphocyte suppression in an inbred model.

The effects of T lymphocyte suppression on coxsackievirus B3 (CB3) myocarditis and its augmentation by exercise were determined in this study. Three-week-old male C3H/HeN mice were divided into four groups. Group 1 mice were infected intraperitoneally (IP) on day 0 with CB3 10(2.5) TCID50, were made to swim daily from days 1 to 9, and were immunosuppressed with daily doses of cyclosporine A (25 mg/kg IP) from days -2 to 8, plus 0.1 ml antithymocyte 1.2 IgG 2a monoclonal antibody IP on day 0. Mice in group 2 were infected and made to swim daily from days 1 to 9. Mice in group 3 were infected and immunosuppressed as outlined. Mice in group 4 were infected IP with CB3. Mortality rates during the acute phase of infection (days 1 to 9) were as follows: group 1, 4% (1/25); group 2, 52% (13/25); groups 3 and 4, 0. Overall mortality rates through day 21 were as follows: group 1, 67% (17/25); group 2, 72% (18/25); group 3, 40% (10/25); and group 4, 4% (1/25). Mean viral titers in serum were highest in the immunosuppressed groups throughout the study. Myocardial viral titers (mean log10 TCID50) were higher in group 2 mice than in group 1 on days 6 (10(6.9) vs 10(4.6)) and 9 (10(8.4) vs 10(7)); however, these titers peaked in group 1 mice on day 13 (10(9.7)). Myocardial inflammation, necrosis, and mean heart weight/body weight ratios were lower in group 1 compared with group 2 on days 6 and 9 but were maximal on day 13 in group 1. Neutralizing antibody titers were lower in immunosuppressed mice on days 6 and 9; however, a rebound increase occurred on day 13.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Intraoperative intra-arterial urokinase infusion as an adjunct to Fogarty catheter embolectomy in acute arterial occlusion.

Sixteen patients, seven men and nine women (mean age of 66 years), with acute arterial ischemia were treated with operative thromboembolectomy by Fogarty catheterization and urokinase. Seven patients were diabetic, ten were hypertensive and six had prior vascular surgical treatment. The operative arteriograms confirmed vascular occlusive phenomenon. The ankle to brachial ratio was a mean of 0.02. Perioperatively, patients had anticoagulation with heparin systemically. All patients underwent transfemoral embolectomy using a Fogarty catheter. An initial retrieval of clots was accomplished, with documentation by arteriography, instillation of urokinase (50,000 units) and clamping of vessel for 15 minutes. Subsequent passage of the Fogarty catheter and repeat urokinase infusion resulted in further retrieval of clots and improvement by repeat intraoperative arteriography. All interventions resulted in clinical restoration of perfusion to the affected limb. Six patients had amputations of the lower extremities (one transmetatarsal and one below the knee) during the 30 day postoperative period. Improvement in distal run-off was demonstrated by intraoperative arteriography and increases in the ankle to brachial ratio from 0.1 to 1.04, with a mean of 0.54, were noted. No complications from bleeding occurred. One patient died postoperatively because of myocardial infarction. Salvage of the limb may increase with combined embolectomy and thrombolytic therapy.

Acute Disease

Cerebral perfusion deficits in dysbaric illness.

Decompression sickness (DCS) is usually categorised as type I (mild; peripheral pain, non-neurological) or type II (serious; neurological). Type II is regarded as predominantly a spinal cord disease with infrequent cerebral involvement. Cerebral perfusion was studied by injection of 99Tcm-hexamethylpropyleneamine oxime and single photon emission tomography in 28 divers with confirmed incidents of DCS and cerebral arterial gas embolism (CAGE). Cerebral perfusion deficits were present in all 23 cases of type II DCS and in all 4 cases of CAGE. No deficits were present in the single case of type I DCS. Type II DCS should be recognised as a diffuse, multifocal, central nervous system disease.

Adolescent

Hypoxic cardiomyopathy: acute myocardial dysfunction after severe hypoxia.

Five cases of acute transient myocardial dysfunction in previously well people after severe hypoxic episode are described. In all cases the hypoxic episode was associated with drug overdose and its complications. Pulmonary infiltrates on chest X-ray consistent with pulmonary edema developed in four cases and gated heart pool scanning confirmed severe cardiovascular dysfunction in all cases.

Adult

Arginine vasopressin and acute, intravascular volume expansion in the human fetus.

There is presently no information concerning the ontogeny and control of arginine vasopressin (AVP) in the human fetus. AVP was measured in 22 nonanemic control fetuses and 7 fetuses with hemolytic anemia undergoing 13 intravascular transfusions. Each transfused fetus received pancuronium (0.3 mg/kg) and furosemide (2 mg/kg). Compared to the control group of nonanemic fetuses with hemolytic disease, AVP was significantly lower in the anemic fetus prior to transfusion (2.6 +/- 0.4 microU/ml versus 10.4 +/- 4.1 microU/ml, p less than 0.05). This suggests that hemolytic anemia is associated with a relative increase in fetal intravascular volume. Intravascular transfusion was associated with a significant increase in AVP (p less than 0.05). These findings could not be explained by changes in either blood pressure, plasma osmolality, or fetal oxygenation.

Anemia, Hemolytic

[The Kleine-Levin syndrome].

Two boys, aged 12 and 13 years, showed relapsing periods of somnolence and excessive eating, starting after a viral illness. One of them also showed periodic disturbance of sexual impulse control. The symptomatic periods were followed by symptom-free intervals in a highly characteristic pattern. This gave the clue to the diagnosis Kleine-Levin syndrome. The cause of this syndrome is unknown, in some cases a relationship between infectious disease or traumatic brain damage has been postulated. A dysfunction of the hypothalamus and associated structures is suspected. The syndrome has a rather favourable prognosis. The symptoms can be relieved by amphetamines, methylphenidate and probably also by lithium carbonate.

Adolescent

Anatomy of femoral vessels in infants and guidelines for venous catheterization.

This study was performed to formulate femoral venous catheterization guidelines for infants from ultrasound observations. Femoral vessels were evaluated on both sides in 75 infants, 2 weeks to 24 months of age. The site of the greatest probability of successful venipuncture 1 cm below the skin crease at the groin is located 4 to 5 mm medial to the femoral artery pulse. If it is assumed that entry into the central half of the vein will result in successful catheterization, successive attempts 5 mm and 6 mm medial to the pulse would result in cumulative successful insertion in 53% and 61%, respectively, with no arterial punctures. A third attempt 4 mm medial to the pulse further increases cumulative success to 78%, but 3% arterial punctures would occur. These guidelines are intended to facilitate achievement of femoral venous catheterization, minimizing arterial punctures and number of needle passes required.

Bloodletting

Effect of indomethacin in the late phase of coxsackievirus myocarditis in a murine model.

Previous studies have shown that indomethacin administered during the early phase of experimental myocarditis may exacerbate the disease process. It is unknown whether late administration of this agent is safe. Therefore, the effect of indomethacin administration during the late phase of coxsackievirus B3 murine myocarditis was investigated. Forty 3-week-old CD1 mice each received a 3 x 10(4) median tissue culture-infective dose of coxsackievirus intraperitoneally. On day 10 of infection, mice were randomized to receive either indomethacin or normal saline solution for 10 days, and 10 mice from each group were killed on days 20 and 30 of infection. Heart weight and size and serum atrial natriuretic peptide were similar in both groups on days 20 and 30. On day 20, pathologic scores for the degree of inflammation and necrosis were 1.7 and 1.0 for the indomethacin group versus 1.4 and 1.7 for the saline solution group. On day 30, pathologic scores were 0.3 and 0.6 for the indomethacin group versus 0.5 and 0.6 for the saline solution group. In addition, mineralization was absent in indomethacin-treated animals on day 20 after infection, but it was present in half of the control animals at that time. The degree of mineralization did not differ on day 30 between the two groups. These findings suggest that indomethacin given in the late phase of coxsackievirus myocarditis has no deleterious effects at 30 days.

Animals

Campylobacter pylori and gastroduodenal disease: a prospective endoscopic study and comparison of diagnostic tests.

A series of 72 adult patients undergoing 76 upper gastrointestinal (GI) endoscopies because of GI signs or symptoms were studied for the presence of Campylobacter pylori by culture, histology, and rapid urease determination of gastric antral biopsy specimens. C. pylori was found by culture or histology in all 10 cases of gastric and duodenal ulcer, and in 77% of endoscopies with histologically proven active gastritis. Positive culture for C. pylori was highly correlated pathologically with active gastritis, but not endoscopically, and was rarely seen in the absence of acute inflammation on biopsy. There was no correlation between C. pylori and alcohol ingestion, smoking, age, sex, antibiotics, or nonsteroidal anti-inflammatory drug use. The rapid urease test was positive in 70% of cases with positive cultures and 89% with positive cultures or acridine orange stains. Acridine orange-stained histological samples were positive in 97% of cases with positive cultures. In addition, 31% of endoscopies with negative cultures were also positive by acridine orange stain. Acridine orange stain, culture, and urease reaction of antral mucosal biopsies all are effective methods for demonstration of mucosal C. pylori-like organisms. However, of the three methods used, acridine orange staining is positive in the largest group of patients and is the most sensitive method for detecting colonization of gastric antral mucosa. In general, positive urease and culture identify those patients with larger numbers of organisms on the mucosa. Differences in urease and culture positivity from case to case suggest that factors other than numbers of organisms, such as viability and urease levels, affect the results. All these results support a role for C. pylori as an aggressive factor in peptic ulcer disease and gastritis.

Acridine Orange

Dietary molybdenum as a putative copper antagonist in the horse.

Four horses were stabled and fed a diet of hay ad libitum, and 2 kg oats per animal per day, for a month. The basic diet was then supplemented with molybdenum, at a rate of 20 mg/kg dry matter for 4.5 months. For one month of this period the diet was supplemented also with sulphur at a rate of 1.2 g/kg dry matter. Analyses of jugular blood samples, obtained at intervals varying between two and 20 days, showed no evidence of a decline in total plasma copper or of an increased proportion of trichloroacetic acid (TCA) insoluble copper in plasma over this period. In separate studies, two other horses were given 99molybdenum (molybdate, 20 to 28 mg Mo, 4 mCi per animal) per os, initially while being fed the basic diet and later while maintained on the molybdenum supplemented diet. 99Molybdenum appeared rapidly in plasma, but the radioactivity was then quickly cleared (half-life 7 to 10 h). The 99molybdenum present was identified as (99Mo)-molybdate. There was no evidence of the persistent, protein-bound (99Mo)thiomolybdates which appear in ruminants. These studies indicate that increased dietary molybdenum is unlikely to interfere with copper metabolism in horses.

Administration, Oral

Coxsackievirus-positive cervices in women with febrile illnesses during the third trimester in pregnancy.

Coxsackievirus B5 infection was demonstrated in five of seven third-trimester pregnant women with undifferentiated febrile illnesses or aseptic meningitis. Coxsackievirus B5 was recovered from the cervix and throat in four women and from the rectum in three. No obvious illnesses were evident in the babies. These findings suggest that previously unrecognized cervical enterovirus carriage or infection is common in infected pregnant women in the last trimester and that subsequent neonatal infection at delivery may result.

Antibodies, Viral

What causes allergy?

Allergy is a generalised phenomenon which must have a basic general cause. Many causative factors and different kinds of reaction may be involved in this condition; but any theory as to its underlying causation must be capable of applying to every form of allergy. Only deficient immune system function satisfies this requirement. Immunologists' definition of allergy is distorted, and their classification of immunological reactions is unduly restrictive and in one of its types not soundly based.

B-Lymphocytes

Application of iodine-123-labeled isopropylamphetamine imaging to the study of dementia.

Forty-seven patients diagnosed as clinically demented were imaged with 123I isopropylamphetamine (IMP). All of these patients also had a nuclear magnetic resonance (NMR) study. In those patients diagnosed as having senile dementia of the Alzheimer type a bilateral reduction in IMP uptake in the temporo-parieto-occipital region was always seen. The NMR appearances were normal in 64% of these sites. The IMP images of patients with multi-infarct dementia varied from normal to marked focal deficits. There was, however, a much closer agreement between the abnormalities seen on the IMP and NMR images. In alcoholic dementia no focal areas of reduced IMP uptake were seen, although the uptake was generally irregular. In both Korsakoff's psychosis and Huntington's chorea the IMP uptake pattern and the NMR study were normal.

Aged