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Biomedical subjects

R C Allen

Publications and source records attributed to R C Allen.

At least 109 records · Page 6Linked to original sources

Additive effect of betaxolol and epinephrine in primary open angle glaucoma.

Betaxolol hydrochloride is a topical beta 1-blocking agent that has been found to be safe and effective in lowering intraocular pressure (IOP) in patients with glaucoma. We administered open-label epinephrine for four weeks to 19 patients who were already being treated with masked 0.5% timolol maleate or 0.5% betaxolol. In patients receiving betaxolol, epinephrine produced a significant additional lowering of mean IOP from 24.5 +/- 0.7 to 19.4 +/- 0.6 mm Hg at one week (P less than .0001) and to 20.7 +/- 0.5 mm Hg at four weeks (P less than .0001). This was accompanied by a statistically significant increase in mean outflow facility from 0.12 +/- 0.1 to 0.17 +/- 0.03 microL/min/mm Hg at one week (P less than or equal to .05) and to 0.18 +/- 0.02 microliter/min/mm Hg at four weeks (P less than or equal to .004). Consistent with previous reports, patients receiving timolol exhibited no significant changes in IOP or outflow facility after the addition of epinephrine to their treatment regimen. These results suggest that epinephrine's agonist effect on the outflow channels is mediated through beta 2-adrenergic receptors and that combined therapy with betaxolol and epinephrine may be clinically useful.

Adrenergic beta-Antagonists↗

Renal papillary necrosis in children with chronic arthritis.

Five ambulatory children with various types of chronic arthritis developed renal papillary necrosis (RPN), as documented by intravenous pyelography. Each child was being treated with nonsteroidal anti-inflammatory drugs (NSAIDs) at the time of diagnosis of RPN and had had episodes of gross or microscopic hematuria for several months prior to diagnosis. In each child hematuria was associated with more than one NSAID, and three of the five children also had ingested acetaminophen intermittently. Glomerular function has remained normal and hypertension has not developed, but management of these children has necessitated reduction or elimination of NSAIDs. As evidenced by these five cases, microscopic or gross hematuria in a child with chronic arthritis treated with anti-inflammatory drugs should raise the possibility of RPN.

Acetaminophen↗

Intraarticular triamcinolone hexacetonide in the management of chronic arthritis in children.

The use of intraarticular triamcinolone hexacetonide in the management of persistent arthritis of the knee joint that is unresponsive to nonsteroidal anti-inflammatory drugs was prospectively evaluated in 40 children with chronic arthritis. Of 49 knees that were injected, 63.3% maintained complete resolution of effusion and other signs of inflammation at the 6-month followup. This favorable outcome correlated with a young age, a short disease duration, and a higher dose of triamcinolone hexacetonide. At the 12-month followup, 45% of the injected knees remained in remission.

Arthritis, Juvenile↗

Overlap connective tissue syndromes.

Twenty six children with overlapping features of more than one connective tissue disorder are reported. The median age of onset was 9.5 years and median duration of follow up 7.5 years. Common presenting symptoms included arthritis, tenosynovitis. Raynaud's phenomenon, myositis, and rashes. At follow up 14 patients had developed sclerodermatous skin changes, but significant systemic involvement was uncommon. Only 16 of the 26 cases had antibodies to nuclear ribonucleoprotein; therefore, 10 did not satisfy criteria for mixed connective tissue disease. It was not possible to differentiate clinical patterns by the presence or absence of any particular antibody profile.

Adolescent↗

Opsonic activity of antisera to ribosomal vaccine fractions with live and formalinized Pseudomonas aeruginosa.

The opsonic capacity of antisera to Pseudomonas aeruginosa ribosomal vaccine fractions was determined by a chemiluminescent technique. Antiserum to a vaccine fraction ("peak A") containing lipopolysaccharide (antiserum A), and antiserum to a vaccine fraction ("peak B"), which did not contain detectable amounts of lipopolysaccharide (antiserum B), were used to opsonify live or formalin-treated bacteria. Polymorphonuclear leukocytes were then stimulated by the opsonified bacteria in the presence of the chemiluminigenic probe, luminol, resulting in the observed chemiluminescence. The data obtained indicated that the antisera had comparable opsonic activity with live (untreated) bacteria. However, antiserum B had far less opsonic activity than did antiserum A when formalinized bacteria were used. Owing to the effects of formaldehyde on protein, these results were interpreted as evidence to suggest that the opsonic activities of the two antisera are dependent on different antigens on the bacterial cell surface. Antiserum A activity is probably dependent on lipopolysaccharide to a great extent, whereas antiserum B activity is most likely dependent primarily on a protein(s).

Antigens, Bacterial↗

Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses.

Integrated insulin secretion rates calculated from peripheral venous C-peptide measurements by two-compartment kinetic analysis were measured in six young normal subjects after increasing oral glucose loads of 25, 50, and 100 g and respective isoglycemic glucose infusions. The differences in B-cell secretory responses between oral and iv glucose challenges were attributed to factors other than glycemia itself (incretin effect). Both insulin and C-peptide concentrations as well as calculated integrated insulin secretion rates increased with increasing oral glucose loads. Due to the similarity in the glucose profiles after all oral loads, almost identical amounts of iv glucose (approximately 20 g) were infused in all "isoglycemic" infusion experiments, with resulting similar hormone profiles and insulin secretion rates. The percent contribution of incretin factors to total immunoreactive insulin responses after 25, 50, and 100 g glucose (85.6%, 74.9%, and 93.0%; response to oral load, 100%) was significantly higher than their contribution to integrated C-peptide responses (27.6-62.9%) or calculated integrated insulin secretion rates (19.2-61.0%). These findings indicate that the degree of incretin stimulation of insulin secretion depends on the amount of glucose ingested. A discrepancy between the estimates of the incretin effect derived from peripheral venous insulin responses, on the one hand, and C-peptide responses or calculated insulin secretion rates, on the other hand, exists. Inasmuch as peripheral insulin values reflect both insulin secretion and hepatic insulin removal, this discrepancy suggests that elimination kinetics of insulin differ between oral and iv glucose administration. This difference can be related to a significantly reduced fractional hepatic insulin extraction after oral (46.9-54.6%) compared to iv (63.4-76.5%) glucose administration when calculated by a three-compartment kinetic model. This reduction in fractional hepatic insulin extraction could be caused by gastrointestinal factors (hormones or nerves) stimulated in the course of glucose ingestion.

Administration, Oral↗

Topical acetazolamide and methazolamide delivered by contact lenses.

Topical acetazolamide has been previously found to be ineffective in lowering intraocular pressure (IOP). Using high-water-content soft contact lenses (Sauflon PW) soaked in acetazolamide, we observed a statistically significant ipsilateral decrease in IOP of 6.3 +/- 0.4 mm Hg in the treated eyes of albino rabbits. The duration of the effect was up to 7 1/2 hours. Methazolamide-soaked contact lenses produced a maximum unilateral reduction of similar magnitude but shorter duration. Both serum and aqueous humor analyses for pH, carbon dioxide pressure, bicarbonate, and base excess indicate that acetazolamide delivered by soft contact lenses is able to penetrate the cornea in sufficient concentration to lower IOP by a local mechanism in rabbits without significant systemic absorption.

Acetazolamide↗

Simmons' tamponade shell for leaking filtration blebs.

We used the Simmons' tamponade shell to successfully treat four of five patients who had leaking filtration blebs after glaucoma surgery. Bleb leaks in both the immediate postoperative period as well as many years following surgery were treated. In each case, previous pressure patching had been unsuccessful. Permanent closure of the leaks with the shell tamponade occurred within three days. Use of this technique is an effective alternative to surgical repair.

Adult↗

Technetium 99m-methylene diphosphonate bone scans in children with reflex neurovascular dystrophy.

Eleven children with reflex neurovascular dystrophy were investigated by technetium-labeled methylene diphosphonate bone scanning. Eight of 12 scans demonstrated abnormal findings, four showing diffusely decreased uptake and four diffusely increased uptake of the radionuclide in the affected site. Three scans showed normal findings initially, as did one previously abnormal scan when repeated in the asymptomatic patient 6 months later. Diffusely abnormal findings can be helpful in the diagnosis of childhood reflex neurovascular dystrophy, but a normal scan does not exclude the diagnosis.

Adolescent↗

Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles.

The synthesis of a series of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles is described. The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of [3H]spiroperidol binding. Structure-activity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents. Maximum neuroleptic activity was realized when there was a 6-fluoro substituent on the benzisoxazole ring. The 1-piperidinyl substituent appeared less significant, although in most cases, the (1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl group imparted maximum potency. The most potent compound in both assays was 6-fluoro-3-[1-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl) propyl]-4-piperidinyl]-1,2-benzisoxazole (11b).

Animals↗

The hypereosinophilic syndrome in acute lymphocytic leukemia.

A 21-year-old white man presented with marked peripheral blood eosinophilia that later evolved into acute lymphocytic leukemia (FAB2 ALL). He died precipitously from refractory congestive heart failure immediately after antileukemic therapy was started. Autopsy revealed multiorgan infiltration with eosinophils and the typical cardiac findings of Löfflers endocarditis. Clinical and pathologic features of this and the 14 other cases of ALL and the hypereosinophilic syndrome (HES) reported in the English-language literature are described. The eosinophilia in these cases is reactive and resolves with successful leukemia remission induction. Hydroxyurea is effective in rapidly lowering eosinophil counts. Early use of hydroxyurea in this disease may improve patient survival and decrease the risk of sudden cardiac death.

Adult↗

A one-year multicenter clinical trial of pilocarpine gel.

In a one-year clinical trial of pilocarpine gel, a form designed for once-a-day administration, in 83 patients with glaucoma, average intraocular pressures during gel therapy were equal to or slightly lower than previous values during pilocarpine eyedrop therapy (morning values, 18.7 mm Hg vs 19.7 mm Hg; afternoon values, 20.9 mm Hg vs 20.2 mm Hg). Monitoring of diurnal intraocular pressure showed that 33 of 77 patients (43%) using the gel and 25 of 77 (33%) using eyedrops had afternoon values more than 2 mm Hg higher than their morning values. This difference was not statistically significant. Fifteen of 76 patients (20%) who used the gel for more than eight weeks developed a diffuse superficial corneal haze with gel treatment. The haze persisted 12 months after the gel was discontinued. Although the haze produced no symptoms, its long-term consequences are unknown.

Adult↗

Molecular analysis of the lymphocyte membrane.

Methods for the molecular analysis of lymphocyte membranes are reviewed briefly, and wherever possible presented in a manner relevant to comparative studies. The specific areas reviewed include the bulk isolation of lymphocyte membranes, the use of radioisotopes to covalently label lymphocyte membrane molecules, the use of lectins to characterize membrane glycoconjugates, and our current understanding of lymphocyte membrane immunoglobulins.

Animals↗

Novel tetracyclic spiropiperidines. 4. Synthesis and pharmacological evaluation of spiro- and 6,7-dihydrospiro[benzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-2 (1H),4'-piperidine]s.

A previously described series of 1-arylspiro[indoline-3,4'-piperidine]s was reported by us to possess significant antidepressant properties. This biological activity was found to be at a maximum among those compounds bearing an ortho substituent (e.g., NH2 as in 1) in the pendant aryl ring. In order to explore further this "ortho effect", we synthesized cyclic analogues of type 3 and 4 in which the position of the o-NH2-substituted aryl group is conformationally restricted and defined. When tested for antidepressant activity by tetrabenazine ptosis prevention in mice, it was found that restriction of rotation of the pendant o-aminophenyl group in these rigid analogues resulted in a loss of antidepressant properties. However, analgesic activity was retained and even improved by this molecular constraint.

Animals↗

Kinetic analysis of microbe opsonification based on stimulated polymorphonuclear leukocyte oxygenation activity.

With Pseudomonas aeruginosa as the target microbes and polymorphonuclear leukocytes (PMNL) as effector phagocytes, the microbe-specific, immunoglobulin G (IgG)-dependent opsonic capacities of preimmune and immune sera were measured as the rate of stimulated PMNL dioxygenation of luminol yielding chemiluminescence (CL). When the reactants other than opsonin are present in concentrations that are not rate limiting, the information-effector relationship linking specific opsonin concentration to effector PMNL stimulation is described by the rate equation: L' = k'[IgG]i, where L' is the peak CL velocity (photons per minute), k' is the proportionality constant, [IgG] is the concentration of specific opsonin, and the exponent i is the order of the reaction with respect to opsonin. Since the specific opsonins were polyclonal IgG of unknown absolute serum concentration, the reciprocal rate expression, L' = k'D-i, was employed for data presentation; D is the serum dilution (final volume/initial serum volume), and the sign of i is changed to negative. The relationships of integral, first-derivative, and second-derivative expressions of the CL response to opsonin concentration are illustrated with experimentally obtained data. Based on peak CL velocity or peak CL acceleration measurements taken over different time intervals of testing, the estimated order with respect to opsonin is highest, and probably most accurate, using the shortest test interval allowing reasonably good precision of measurement. As an alternative temporal approach, microbe opsonification kinetics are analyzed based on nodal time (Tn) measurements. The Tn is the time point separating the acceleration and deceleration phases of the PMNL oxygenation response to stimulation and as such satisfies the criterion of a selected condition of PMNL activation.

Kinetics↗