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Biomedical subjects

L Moore

Publications and source records attributed to L Moore.

At least 199 records · Page 11Linked to original sources

The immunology of tonsils in children: the effect of bacterial load on the presence of B- and T-cell subsets.

Tonsil core specimens of 54 children, (3 to 12 years) with clinical evidence of chronic tonsillitis and/or "idiopathic" tonsillar hypertrophy, were studied for the effect of the magnitude of aerobic bacterial load on tonsil size and the absolute numbers of B- and T-cell subsets. Tonsillar core specimens obtained from ten children with no history of ear, nose, or throat infections and normal appearing tonsils served as controls. The findings of this study indicate that tonsil size was directly proportional to the mean bacterial load in colony forming units/g tonsil (CFU/g) even in the absence of a clinical history of infection (p less than 0.01). A mean bacterial load of 2.4 +/- 2.1 X 10(5) CFU/g tonsil was seen in diseased tonsils as compared to 1.6 +/- 2.4 X 10(4) CFU/g tonsil in normal controls (p less than 0.01). Hemophilus influenzae (type B and non-B), Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes were the most common pathogens recovered in the largest numbers from diseased tonsils; control tonsils harbored few bacteria in their cores. The absolute number of immunocompetent cells/g tonsil including T-helper, T-suppressor and B-cells (S-Ig+), were significantly greater in diseased tonsils than in controls (p less than 0.001). Increasing microbial load (CFU/g tonsil) correlated with increased numbers of T-helper (p less than 0.01) and B-cells (p less than 0.01). These data strongly support a bacterial etiology for chronic tonsillitis as well as "idiopathic" tonsillar hypertrophy. Bacterial induced proliferation of immunocompetent cells may be one underlying mechanism for chronic tonsillar disease in children.

B-Lymphocytes↗

The role of Haemophilus influenzae in the pathogenesis of tonsillar hypertrophy in children.

The role of specific bacteria in the pathogenesis of tonsillar hypertrophy in children in unknown. To determine the effect of specific bacteria on the presence and nature of tonsillar hypertrophy (measured both clinically and by tonsil weight), quantitative aerobic bacteriology was performed on 54 tonsil-core specimens from 54 children undergoing tonsillectomy for chronic tonsillitis and/or tonsillar hypertrophy. Twelve tonsil-core biopsies from 12 children with no history of tonsil disease served as controls. Haemophilus influenzae (HI), Streptococcus pyogenes (SP), Streptococcus pneumoniae (SPn), and Staphylococcus aureus (SA) were the most common microorganisms cultured from diseased tonsils. Few bacteria were cultured from the cores of controls. HI was cultured as the dominant aerobic bacteria in 15 of 54 tonsils (27%). For HI alone, the number of bacteria/gram tonsil showed a significant positive correlation to tonsil weight (p less than 0.05). Fourteen of 15 (94%) tonsils with HI were found in patients with clinical tonsillar hypertrophy, while only 6 of 10 patients (60%) with SP and SPn had tonsillar hypertrophy. Of the 38 tonsils removed for obstructive symptoms (clinical hypertrophy), 14 of 38 (37%) cultured HI as the dominant microorganisms, whereas only 6 of 38 (16%) cultured SP. Neither the type of HI (b vs. non-b) nor the presence of beta-lactamase production had a significant correlation to tonsil weight, bacterial load or the number of B- or T-cell subsets. The number of T-helper (Th), T-suppressor (Ts) and B-cells (per gram/tonsil) was markedly greater in all diseased tonsils than in controls. For both HI and SP the total number of bacteria/gram tonsil correlated positively to the number of Ts cells (p less than 0.003 and p less than 0.007, respectively). In patients with HI type b (HI-b), the tonsil weight correlated to an increase in Ts and B-cells (p less than 0.004 and p less than 0.007, respectively). An increased presence of the Ts and B-cells in the HI-b tonsils (and not in tonsils with HI non-b) suggests a differential response by the tonsil to these distinct but related bacteria. The above data strongly support an etiological role for HI in the pathogenesis of tonsillar hypertrophy in children. Alterations in the relationship between Th and Ts cells may affect normal B-cell function and be implicated in this phenomenon. Clinical implications for pathogenesis, antimicrobial therapy, and future directions for research are discussed.

Child↗

Transdermal drug delivery: a review of pharmaceutics, pharmacokinetics, and pharmacodynamics.

This article provides a critical literature review on the recent advances in the research and development of rate-controlled transdermal therapeutical systems for systemic medication. The article focuses its discussion on the recent development in the fundamentals, developmental concepts, and biomedical assessment of the transdermal controlled drug administration. The scope of the review consists of the following areas: mechanism of percutaneous absorption; enhancement of skin permeability; in vitro and in vivo evaluations of transdermal permeation kinetics and assessment of in vitro-in vivo relationship; pharmacokinetics and pharmacodynamics of transdermal controlled drug administration and establishment of pharmacokinetic/pharmacodynamic relationship; clinical performance of rate-controlled transdermal therapeutic systems; and potential development in rate-controlled transdermal drug delivery.

Administration, Cutaneous↗

Cytosolic calcium after carbon tetrachloride, 1,1-dichloroethylene, and phenylephrine exposure. Studies in rat hepatocytes with phosphorylase a and quin2.

Carbon tetrachloride (CCl4) and 1,1-dichloroethylene (DCE), both hepatotoxins, inhibit sequestration of Ca2+ by rat liver endoplasmic reticulum (ER) both in vivo and in vitro. It is possible that, as a result, cytosolic Ca2+ concentrations rise in liver cells. In experiments presented here, isolated hepatocytes were exposed to CCl4, DCE, and phenylephrine (PE), a non-hepatotoxic alpha 1-adrenergic agent that mobilizes Ca2+. Cytoplasmic Ca2+ concentrations were evaluated by two methods: indirectly by assaying the activity of glycogen phosphorylase a, and directly by monitoring the fluorescence of quin2. In primary hepatocyte cultures, CCl4, DCE, and PE exposure increased the activity of phosphorylase a at 5 min from 39 +/- 2 to 130 +/- 12, 80 +/- 13, and 97 +/- 10 nmoles PO4(3-)/mg protein/min respectively. In rat hepatocyte suspensions loaded with quin2 and exposed to CCl4, DCE, or PE, cytosolic Ca2+ concentrations were elevated within 20 sec to 0.83 +/- 0.13, 0.59 +/- 0.06 and 0.99 +/- 0.14 microM Ca2+ respectively. Basal Ca2+ levels in these cells averaged 0.25 +/- 0.03 microM. Thus, CCl4 and PE apparently increased cytosolic Ca2+ levels to approximately the same extent, whereas DCE was somewhat less effective. The durations of the effects of CCl4 and PE were examined further by determining their time courses of elevated phosphorylase a activity. In hepatocyte cultures, increased phosphorylase a activity persisted through at least 60 min following CCl4 exposure. In contrast, phosphorylase a activity returned to basal levels by 20 min after PE. Increases in cytoplasmic Ca2+ levels that are sustained rather than transient may distinguish these hepatotoxic chlorinated aliphatic hydrocarbons from non-toxic hormonal agents.

Aminoquinolines↗

The polymorphic metabolism of dextromethorphan.

The ability of healthy male volunteers to metabolize a 30-mg oral dose of dextromethorphan (DM) was studied in 252 Americans. Two blood samples were collected at four and 24 hours after administration of the dose. The resulting plasma was analyzed for unchanged DM. The volunteers were classified as slow, intermediate, or fast metabolizers on the basis of plasma concentrations of DM. Further differentiation of slow and intermediate metabolizers was achieved by comparing the two-point estimates of elimination-rate constants. In the population studied, 84.3% were fast DM metabolizers, 6.8% were intermediate metabolizers, and 8.8% were slow metabolizers. Previous reports have related the slow DM metabolizers to slow debrisoquin metabolizers, but no such correlations have been achieved with intermediate DM metabolizers. These intermediate DM metabolizers may suggest a new polymorphism not related to debrisoquin or may suggest that "debrisoquin gene" regulation is more complex than originally suggested.

Adolescent↗

A comparison of tonsillar size and oropharyngeal dimensions in children with obstructive adenotonsillar hypertrophy.

Hypertrophy of the tonsils and adenoids is the most common cause of obstructive sleep apnea in children. There is relatively little known about the occurrence of subclinical variations in the dimensions of the oropharynx which may predispose to the development of obstructive sleep apnea in children without obvious craniofacial abnormalities. Fifty-one children (3-10 years) were divided into two groups: the first group consisted of 18 patients with small tonsils and no history of snoring who underwent tonsillectomy for chronic tonsillitis. They were compared to a second group of 33 patients with large tonsils who underwent tonsillectomy and adenoidectomy for symptoms of obstructive sleep apnea. Age, height, weight, body surface area and tonsil weight were correlated to the dimensions of the oropharynx obtained by direct measurement intraoperatively including the length of the soft palate, anterior-posterior depth of the nasopharynx and the distances between the medial tonsillar surfaces, anterior tonsillar pillars and lateral pharyngeal walls at mid-tonsil level. Increased patient height, weight and surface area correlated positively to increased distance between the lateral pharyngeal walls and to the length of the soft palate in the patients with small tonsils. No such correlation existed in the patients with obstructive adenotonsillar hypertrophy. In addition, the distance between the lateral pharyngeal walls was significantly decreased in the group with large, obstructing tonsils as compared to those with small tonsils and no history of obstruction (P less than 0.01). However, the patients with small tonsils and no obstruction had significantly longer soft plates (P less than 0.01) and less depth tot eh nasopharynx (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoidectomy↗

Percutaneous ureteral fulguration: a nonsurgical technique for ureteral occlusion.

Three patients with lower urinary tract fistulas after multiple operations and radiation therapy for pelvic cancer were treated with percutaneous ureteral fulguration and nephrostomy tube drainage. This technique occluded the ureter and allowed for maintenance of a dry fistula site in all 3 patients. There were no complications. The longest followup in these patients was 21 months. The procedure is simple technically and it can be performed with the patient under local anesthesia. The technique of percutaneous ureteral fulguration is described and other techniques for nonoperative occlusion of the ureter are discussed.

Electrosurgery↗

Inhibition of liver endoplasmic reticulum calcium pump by CCl4 and release of a sequestered calcium pool.

One of the earliest effects observed in rat liver after CCl4 administration is inhibition of an ATP-dependent calcium pump found at the endoplasmic reticulum. This report confirms that the amount of calcium associated with the microsomal fraction is reduced after CCl4 administration and, for the first time, demonstrates time-, dose-, and metabolism-dependent relationships between inhibition of the liver microsomal calcium pump and the amount of calcium found in the microsomal fraction. Furthermore, release of calcium from the endoplasmic reticulum is shown to cause activation of a cytoplasmic enzyme that responds to increases of ionized calcium, glycogen phosphorylase. This suggests that the endoplasmic reticulum calcium pump sequesters an intracellular pool of calcium within the endoplasmic reticulum. This pool of calcium may be released into the cytoplasm as a consequence of inhibition of the calcium pump by CCl4.

Animals↗

Liver plasma membrane calcium transport. Evidence for a Na+-dependent Ca2+ flux.

Plasma membrane vesicles isolated from rat liver exhibited an azide-insensitive Mg2+-ATP-dependent Ca2+ pump which accumulated Ca2+ at a rate of 5.1 +/- 0.5 nmol of calcium/mg of protein/min and reached a total accumulation of 33.2 +/- 2.6 nmol of calcium/mg of protein in 20 microM Ca2+ at 37 degrees C. Equiosmotic addition of 50 mM Na+ resulted in a loss of accumulated calcium. Measurement of Mg2+-ATP-dependent Ca2+ uptake in the presence of 50 mM Na+ revealed no effect of Na+ on the initial rate of Ca2+ uptake, but a decrease in the total accumulation. The half-maximal effect of Na+ on Ca2+ accumulation was achieved at 14 mM. The Ca2+ efflux rate constant in the absence of Na+ was 0.16 +/- 0.01 min-1, whereas the efflux rate constant in the presence of 50 mM Na+ was 0.25 +/- 0.02 min-1. Liver homogenate sedimentation fractions from 1,500 to 105,000 X g were assayed for azide-insensitive Mg2+-ATP-dependent Ca2+ accumulation. Na+-sensitive Ca2+ uptake activity was found to specifically co-sediment with the plasma membrane-associated enzymes, 5'-nucleotidase and Na+/K+-ATPase, whereas Na+-insensitive Ca2+ uptake was found to co-sediment with the endoplasmic reticulum-associated enzyme, glucose-6-phosphatase. The plasma membrane Ca2+ pump was also distinguished from the endoplasmic reticulum Ca2+ pump by its sensitivity to inhibition by vanadate. Half-maximal inhibition of plasma membrane Ca2+ uptake occurred at 0.8 microM VO4(3-), whereas half-maximal inhibition of microsomal Ca2+ uptake occurred at 40 microM.

Adenosine Triphosphate↗

Computed tomography of acute radiation nephritis.

A patient with Hodgkin's disease received a fractionated 3,740 rad dosage over 4 weeks to a portal that included both kidneys. Three months later a computed tomographic scan obtained 2 hours after intravenous contrast injection demonstrated sharply demarcated, dense, persistent nephrograms corresponding to the irradiated areas. These changes are ascribed to acute radiation nephritis, reflecting tubular stasis and ischemia.

Child↗

Carbon tetrachloride-induced release of calcium from isolated hepatocytes.

Studies have shown that CCl4 administration to rats inhibits endoplasmic reticulum calcium pump activity and reduces the amount of calcium associated with subsequently isolated microsomal subcellular fractions. This report confirms that exposure of isolated hepatocytes to CCl4 rapidly produces these effects in isolated parenchymal cells and demonstrates that when isolated hepatocytes are exposed to CCl4, calcium is rapidly released from cells. This release can be detected with a calcium ion-selective electrode when cells are incubated in a medium with low extracellular calcium. Calcium released from an intracellular pool(s) may initiate hepatotoxic changes in liver.

Animals↗

Elevated cytosolic calcium in rat hepatocytes exposed to carbon tetrachloride.

CCl4 rapidly and severely inhibits hepatic endoplasmic reticulum calcium (Ca++) sequestration in rats exposed to this hepatotoxin in vivo. As a consequence, it is possible that cytosolic Ca++ concentrations become elevated in liver cells. In this study, the authors examined intracellular Ca++ concentrations in cultured rat hepatocytes exposed to CCl4 by monitoring the activity of phosphorylase a. Glycogen phosphorylase is converted to its a form in response to increases in cytoplasmic Ca++. Elevated phosphorylase a activity was observed within 2.5 min and was maintained for at least 30 min after exposure of hepatocytes to CCl4. Endoplasmic reticulum Ca++ pump activity decreased in a parallel manner. Phosphorylase activation was cyclic AMP independent and did not require extracellular Ca++. Cytoplasmic enzyme was released from hepatocytes within 30 min after CCl4 addition. Thus it was confirmed that exposure of hepatocytes to CCl4 causes release of Ca++ from an intracellular store (likely endoplasmic reticulum) and resultant activation of a Ca++-responsive cytosolic enzyme. From a calibration curve, it was estimated that cytosolic Ca++ is elevated up to 100-fold in rat hepatocytes exposed to the model hepatotoxin CCl4. It is postulated that prolonged elevation of intracellular Ca++ concentrations may trigger excessive stimulation of Ca++-sensitive enzymes capable of initiating irreversible liver cell injury.

Alanine Transaminase↗

Effect of oral nalmefene, an opiate-receptor antagonist, on meal-stimulated gastric acid secretion and serum gastrin concentration in man.

We evaluated whether nalmefene, an orally administered opiate-receptor antagonist, would inhibit gastric acid secretion in response to a meal in healthy humans. On separate days either 50 mg nalmefene or a placebo tablet was administered by mouth 90 min before a blenderized steak meal was infused into the stomach through a nasogastric tube. Compared to placebo, nalmefene inhibited meal-stimulated acid secretion in each of 6 subjects studied (P less than 0.05). During the second and third hours after the meal, nalmefene inhibited mean acid secretion by 16%. Nalmefene also resulted in significantly higher meal-stimulated serum gastrin concentrations than placebo (P less than 0.05) even though intragastric pH was kept constant at 5.0 in both experiments. These studies indicate that an orally administered opiate-receptor antagonist can inhibit gastric acid secretion in response to a meal in humans, yet increase meal-stimulated serum gastrin concentrations.

Adult↗

Expansile radiolucent mass in the maxilla.

The adenomatoid odontogenic tumor is an uncommon, extremely benign odontogenic lesion that should be differentiated from the other osseous lesions. The surgical management should be conservative without expectation of recurrence.

Adolescent↗