PubMed Health⌕ Search

Biomedical subjects

D M Cummings

Publications and source records attributed to D M Cummings.

At least 19 recordsLinked to original sources
PubMed1998

Oral poisonings: guidelines for initial evaluation and treatment.

The initial evaluation and management of poisoned patients should be comprehensive and include an accurate history whenever possible, stabilization of the patient's condition, a physical assessment to evaluate the extent of poisoning and the presence of concurrent conditions, decontamination of the gastrointestinal tract using activated charcoal, gastric lavage, administration of ipecac or irrigation, poison-specific treatment with administration of antidotes when indicated and proper disposition. Consultation with a poison control center is often helpful in assessing and treating these patients.

Administration, Oral↗
PubMed1997

Olfactory bulb recovery after early sensory deprivation.

Olfactory bulbs retain the ability to acquire new neurons throughout life. Unilateral olfactory deprivation during the first postnatal month in rats results in a dramatic reduction in the size of the experimental olfactory bulb. Part of this reduction is attributable to the death of neurons and glia. To examine the regenerative capacity of the juvenile olfactory bulb, we developed a technique for reversible olfactory deprivation. Reversible blockade from postnatal day 1 (P1) to P20 or P30 results in reduced bulb volume and tyrosine hydroxylase immunostaining, and decreased depth in the olfactory mucosa. In another experiment, normal stimulation was restored for varying periods of time, and experimental and control bulb volumes were measured. Recovery of bulb size occurs after 40 d of normal stimulation. Rats injected with a thymidine analog to label dividing cells during the recovery period revealed that rescue results at least in part from the addition of new neurons and glia. Thus, cells born after the return of normal levels of environmental stimulation can replace some of the neurons and glia that are lost during olfactory deprivation. This system can be used to study mechanisms that underlie neuronal regeneration in the maturing mammalian brain.

Animals↗
PubMed1997

Effects of unilateral olfactory deprivation in the developing opossum, Monodelphis domestica.

Unilateral naris closure in young rodents leads to striking alterations in the development of the ipsilateral olfactory system. One of the most pronounced effects is a 25% reduction in the size of the experimental olfactory bulb, a change that stems in part from decreased cell survival. Since naris occlusion in rodents alters the system more during development than in adulthood, we investigated the consequences of olfactory deprivation in a species that is born in a very immature state, Monodelphis domestica. In this pouchless marsupial, offspring are born after a short 14-day gestation. In the present study, the thymidine analogue bromodeoxyuridine was used to examine early postnatal neurogenesis in the olfactory bulb. Unlike rats and mice, neurogenesis of the main output neurons (the mitral cells) continues into postnatal life. Unilateral naris closure was begun on postnatal day 4 (P4) or P5 in Monodelphis and continued for 30 or 60 days. Laminar volume measurements revealed a significant reduction in the size of the experimental bulb following 60, but not 30, days of early olfactory deprivation. Mitral cell number estimates indicated a significant reduction after both 30 and 60 days of naris closure. The immaturity of Monodelphis offspring may render the population of mitral cells susceptible to the effects of olfactory deprivation. These findings suggest that afferent activity plays a role in the survival of all bulb neurons, irrespective of cell class.

Animals↗
PubMed1997

The effects of variable periods of functional deprivation on olfactory bulb development in rats.

Dramatic alterations occur in the developing olfactory bulb when air flow is reduced through one-half of the nasal cavity. Naris closure on the day after the day of birth (P1) in rats, for example, results in reduced cell survival in the ipsilateral bulb by P20 and a substantial (25%) decrease in bulb size by P30. Almost immediate changes in protein synthesis and cell metabolism are also observed, and one prevalent theory suggests that these changes may be important in specifying which cells are subsequently eliminated. In the present study we used a reversible technique for unilateral naris closure to examine the sensitive period for the effects of olfactory deprivation on bulb size and cell survival. This technique involves the insertion of removable plugs into a rat pup's external naris. We occluded the naris for increasing periods of time (P1-P10, P1-P15, or P1-P20), reared all animals to P30, and measured volumes of bulb laminae. In addition, we examined the duration of naris closure needed to affect cell survival by injecting animals with the thymidine analogue bromodeoxyuridine to label cells born soon after the onset of olfactory deprivation. Results indicate that relatively long periods of naris occlusion (P1-P15 or longer) are required to produce a substantial reduction in experimental bulb size. Cell survival was decreased following olfactory deprivation from P1 to P10, but not after deprivation from P1 to P3. These data support the hypothesis that changes that occur within 48 h of naris closure are not sufficient to affect cell survival.

Animals↗
PubMed1997

NSAIDs revisited: selection, monitoring, and safe use.

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesic and anti-inflammatory agents, they may have adverse effects on the gastrointestinal, hepatic, renal, pulmonary, and platelet aggregation systems in susceptible patients. Careful consideration of the risks and benefits, judicious dosing, and careful monitoring by the primary care physician are therefore essential. The authors of this article review both the therapeutic and adverse effects of NSAIDs and provide suggestions for safe clinical use.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Development of the anterior commissure in the opossum: midline extracellular space and glia coincide with early axon decussation.

While the anterior commissure has been shown to be an important route of information transfer in the forebrain, relatively little is known about its anatomical development. Glial substrates and extracellular spaces have been associated with the maturation of other large-fiber tracts, such as the corpus callosum and retinofugal pathway. The present study examined early stages in the maturation of the commissure in the gray short-tailed opossum, Monodelphis domestica. Monodelphis offspring are born after a short 14-day gestation, and, unlike in rats and mice, the anterior commissure develops entirely during the postnatal period. A number of techniques were employed: the carbocyanine dye Dil was used to label early axons in the region, semithin plastic sections were used to examine the extracellular environment of the developing commissure, and immunocytochemistry for glial fibrillary acidic protein (GFAP) was used to characterize glial components. Results suggest that the first commissural fibers that cross the midline pass through a region of large extracellular spaces and may use GFAP-immunoreactive cells and processes as guides during their midline decussation.

Animals↗
PubMed1995

Migrating luteinizing hormone-releasing hormone (LHRH) neurons and processes are associated with a substrate that expresses S100.

Luteinizing hormone-releasing hormone (LHRH) containing neurons arise in the region of the medial olfactory placode and migrate into the developing olfactory bulbs and basal forebrain along branches of the terminal and vomeronasal nerves. The neurons ultimately come to reside in olfactory and septo-preoptic areas and project extensively to several brain regions, including the preoptic area and median eminence. The present study examined the expression of a glial-associated guidance molecule, S100, as a possible substrate for this migration. Monodelphis domestica (the Brazilian grey, short-tailed opossum) was studied since this species gives birth to very immature, young, allowing access to early periods of mammalian forebrain development. Immunoreactivity for both S100 and LHRH-containing neurons and fibers were observed to be closely associated along the entire LHRH migratory route from the vomeronasal organ to the septo-preoptic areas as early as the day of birth (PO). By P10, S100-immunoreactivity was also seen in areas containing LHRH-immunoreactive fibers such as the preoptic area and median eminence. We suggest that S100, a protein with neurotrophic properties in vitro, acts as a guidance molecule for migrating LHRH-immunoreactive neurons and elongating processes.

Animals↗
PubMed1994

Effect of oral magnesium supplementation on selected cardiovascular risk factors in non-insulin-dependent diabetics.

OBJECTIVE: To evaluate the impact of oral magnesium supplementation on risk factors for end-organ disease in patients with non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: A 16-week randomized, double-blind, placebo-controlled crossover trial. SETTING: Outpatient center of an academic family medicine residency program. PATIENTS: Twenty-eight patients (age range, 28 to 84 years; 57.1% black; 85.7% women) with NIDDM controlled by diet and/or an oral hypoglycemic, with a serum cholesterol levels over 5.20 mmol/L (200 mg/dL). INTERVENTION: Following a 2-week placebo run-in period, each patient was randomized to receive either sustained-release magnesium chloride (Slo-Mag), 384 mg/d, or an identical-appearing placebo for 6 weeks. After a 2-week interim washout period, each patient was then treated with the alternative regimen for an additional 6-week period. MAIN OUTCOME MEASURES: The systolic and diastolic blood pressure and levels of serum glucose, low-density and high-density lipoprotein and total cholesterol, triglycerides, and serum and total erythrocyte magnesium were measured at the beginning, midpoint, and end of each 6-week treatment phase. RESULTS: Systolic blood pressure fell an average of 7.4 mm Hg (P < .05) with treatment. There was no significant change in diastolic blood pressure or levels of serum glucose, low-density and high-density lipoprotein and total cholesterol, triglycerides, or serum and erythrocyte magnesium. CONCLUSIONS: Oral magnesium supplementation in the doses and duration studied is modestly effective in reducing systolic blood pressure in patients with NIDDM but has little impact on other important biochemical parameters related to diabetes-associated end-organ disease.

Administration, Oral↗
PubMed1994

Changes in cell proliferation in the developing olfactory epithelium following neonatal unilateral naris occlusion.

Surgical closure of an external naris reduces airflow through one side of the nasal cavity. Previous studies using [3H]thymidine autoradiography have demonstrated that rats subjected to the procedure on Postnatal Day 1 (P1) exhibit reduced cellular proliferation in the olfactory mucosa by P30. We investigated cell production at earlier ages to determine (a) when the effect first emerges, and (b) whether septal, dorsal, and lateral regions of the nasal cavity responded similarly. Both short (2-h) and long (30-day) survival groups were tested. Results from the first group indicate that changes in proliferation emerge between P10 and P20, and that the septum is more affected than other regions of the nasal cavity. No differences were observed in the long survival groups, perhaps due to changes in patterns of cell production or death.

Airway Obstruction↗
PubMed1994

A review of selected newer nonsteroidal anti-inflammatory drugs.

Development of nonsteroidal anti-inflammatory drugs (NSAIDs) with a goal of improved efficacy and lower toxicity has continued, resulting in the introduction of etodolac, ketorolac, nabumetone and oxaprozin on the market. Each of these agents appears to be as effective as other commonly used NSAIDs in the treatment of rheumatoid arthritis or osteoarthritis. Studies of nabumetone and etodolac show a lower incidence of serious gastrointestinal toxicity with both drugs, but additional large clinical trials are necessary to confirm these findings. Although ketorolac, which is now available in oral form, is an effective analgesic, its long-term use is limited by a high incidence of gastrointestinal toxicity. Oxaprozin is an effective, long-acting anti-inflammatory analgesic, but its comparative advantages remain undefined.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Influence of digoxin immune Fab therapy and renal dysfunction on the disposition of total and free digoxin.

OBJECTIVE: To characterize the disposition of total and free serum digoxin following the administration of digoxin Fab antibody in patients with varying degrees of renal function. DESIGN: Observational study of pharmacokinetics and pharmacodynamics. SETTING: Critical care and telemetry units of two university-affiliated teaching institutions, Hartford Hospital and Henry Ford Hospital. PATIENTS: Fourteen digoxin-intoxicated patients (baseline total digoxin > 3.2 nmol/mL) with mean (+/- SD) serum creatinine of 380.1 +/- 212.2 mumol/L who received digoxin Fab antibody therapy. MEASUREMENTS: Serum was drawn every 12 to 24 hours for 80 to 327 hours after Fab administration. Total and free digoxin were assayed in serum by fluorescence polarization immunoassay or modified immunofluorometric assay. RESULTS: Before Fab was administered, total digoxin ranged from 3.5 to 10.5 nmol/mL. After treatment with Fab, total digoxin increased rapidly to a mean (+/- SD) maximum of 51.8 +/- 22.7 nmol/mL and decreased to 7.2 +/- 4.7 nmol/mL at the last measurement. Total digoxin was eliminated in a two-phase fashion. The half-life of the initial phase of total digoxin decline was 11.6 +/- 4.1 hours, and the half-life of the second or terminal elimination phase was 118 +/- 57 hours. Free digoxin levels decreased rapidly following Fab therapy, to a mean nadir of 0.6 +/- 1.1 nmol/mL, but rebounded to a mean maximum free digoxin concentration of 1.7 +/- 1.3 nmol/mL in 77 +/- 46 hours. The time to maximum free digoxin rebound occurred later in patients with end-stage renal disease (n = 4) compared with other patients (127 +/- 40 hours compared with 55 +/- 28 hours). CONCLUSION: Elimination of digoxin following Fab therapy is prolonged in digoxin-toxic patients with renal dysfunction. In addition, rebound of free digoxin is delayed in anephric patients. Monitoring free digoxin following the administration of Fab may be of value in selected patients to guide additional Fab dosing, confirm possible rebound toxicity, or guide the reinitiation of digoxin therapy.

Adult↗
PubMed1993

Disposition of digoxin immune Fab in patients with kidney failure.

Digoxin and digoxin immune Fab, its antidote, are eliminated renally. However, the disposition of Fab in severe kidney disease is poorly described. Therefore, the disposition of Fab and its relationship to total and free digoxin were studied in five digoxin-toxic patients with end-stage renal disease (n = 4) or severe renal dysfunction (n = 1) with a mean (+/- SD) serum creatinine of 5.9 +/- 1.2 mg/dl (four patients were receiving long-term hemodialysis). Serum was drawn after a clinically neutralizing Fab dose (80 to 160 mg) every 12 to 24 hours for 204 to 327 hours. Fab concentrations were assessed by radioimmunoassay, whereas total digoxin concentrations were assessed with a modified radioimmunoassay or fluorescence polarization immunoassay. The concentration-time profile of Fab appeared to be similar to the concentration-time profile of total digoxin. The mean (+/- SD) half-lives of the alpha and beta disposition phases of Fab were 13 +/- 5 hours and 96 +/- 31 hours, respectively, which were similar to the alpha and beta parameter estimates of total digoxin (14 +/- 4 and 123 +/- 16 hours, respectively). Steady-state volume of distribution and systemic clearance of Fab were 0.29 +/- 0.11 L/kg and 0.057 +/- 0.022 ml/min/kg, respectively. Thus, in comparison to values reported in patients with normal renal function, the elimination of Fab and total digoxin are markedly delayed in patients with end-stage renal disease, which may necessitate prolonged clinical monitoring.

Aged↗
PubMed1993

Nonsteroidal anti-inflammatory drugs. Tailoring therapy to achieve results and avoid toxicity.

When used appropriately, non-steroidal anti-inflammatory drugs (NSAIDs) are safe and effective for treating pain and inflammation. NSAIDs that block both the lipoxygenase and cyclooxygenase pathways may be advantageous in some patients. New classes of NSAIDs that may have a more favorable safety profile than older agents may improve patient outcome. However, all patients receiving NSAIDs, especially the elderly, should be carefully monitored for possible drug-related complications.

Absorption↗
PubMed1992

Lack of effect of pentoxifylline on red blood cell deformability.

The proposed mechanism of action for pentoxifylline's beneficial effect in peripheral vascular disease is an improvement in red blood cell deformability. Likewise, single doses of pentoxifylline in healthy volunteers have been shown to improve whole blood filterability, which was suggested to occur as a result of augmented red blood cell deformability. To further assess this, the authors studied the effects of short-term pentoxifylline administration (400 mg three times daily for 7 days) on red blood cell deformability in ten healthy, methylxanthine-free, nonsmoking volunteers. Blood samples were obtained at baseline and after 1 week of therapy (steady-state). Samples were analyzed for red blood cell deformability by ektacytometry, which showed no significant change in deformability in any subject. Despite the improvement in whole blood filterability associated with both single-dose and short-term administration of pentoxifylline, the current study demonstrates no effect on red blood cell deformability after short-term administration in healthy volunteers.

Adult↗
PubMed1992

Determination of free serum digoxin concentrations in digoxin toxic patients after administration of digoxin fab antibodies.

Digoxin fab antibody therapy is known to interfere with digoxin immunoassays causing spurious serum digoxin concentrations. The reliability and precision of three digoxin immunoassays--Baxter Dade Stratus (BDS), Syva affinity column enzyme-mediated immunoassay (EMIT), and the reference assay Abbott TDx fluorescence polarization immunoassay following ultrafiltration (FPIA-UF)--were compared in eight digoxin toxic patients treated with digoxin fab antibodies. Five to eight blood samples were drawn serially up to 204 h post digoxin fab therapy. The serum digoxin concentration in each sample was determined by each of the three assays. The mean (+/- SD) area under the serum digoxin concentration-time curve was significantly lower for FPIA-UF than for BDS or EMIT (86.1 +/- 58.2 vs 158.1 +/- 88.6 and 176.3 +/- 115.3 h.ng/ml p less than 0.01, respectively). BDS correlated better with FPIA-UF (r2 = 0.71) than did EMIT (r2 = 0.45). Predictive performance of the BDS and EMIT assays demonstrated that the mean prediction error (bias) (0.62 vs 0.78 ng/ml) and the mean squared prediction error (precision) (0.48 vs 0.76) differed significantly from zero (p less than 0.05). However, BDS had significantly less bias and greater precision than did EMIT (p less than 0.05). In the presence of digoxin fab antibodies, BDS is a better predictor of free serum digoxin concentration than is EMIT, but both have considerable bias. Based on these results, FPIA-UF should be the assay of choice for determining free serum digoxin concentrations during fab therapy.

Adult↗
PubMed1991

Monitoring serum digoxin concentrations during digoxin immune Fab therapy.

Measurement of serum digoxin concentrations (SDCs) is used routinely in the diagnosis of digoxin toxicity. Following administration of the antidote, digoxin immune antigen binding fragments (Fab), SDC monitoring is hampered by assay-related problems because of the presence of Fab in the serum. Recent evidence has suggested several available methods to monitor free SDC during Fab therapy. This report describes the utility of monitoring free SDC following Fab administration. Free SDCs were obtained using an ultrafiltration and fluorescence polarization immunoassay system in three patients over periods of up to 204 hours after Fab administration. In each case, the decline in free SDC was temporally related to the resolution of digoxin toxicity; in one case, digoxin intoxication recurred and was associated with a rebound increase in free SDC. In addition to the therapeutic benefits, prospective monitoring of free SDC in two of the patients also may have resulted in cost savings secondary to reduced hospital stay or less use of Fab.

Adult↗
PubMed1991

The role of calcium channel blockers in the treatment of essential hypertension.

Calcium channel blockers, originally developed for the treatment of angina and supraventricular arrhythmias, have been shown to lower elevated blood pressure effectively in hypertensive patients. Verapamil, nifedipine, and diltiazem represent prototype compounds for unique chemical classes with differing pharmacologic properties. These drugs lower elevated blood pressure with efficacy comparable with other commonly used antihypertensives. Combination therapy with other agents usually results in an additive response. Side effects are usually mild and reversible and usually are an extension of the drug's pharmacologic effects. Moreover, adverse metabolic effects on lipid, glucose, or potassium levels are not common. Because of the excellent antihypertensive effects of calcium channel blockers and their potential importance in a variety of other disease states, these agents should be routinely considered for use as a first-line antihypertensive agent in appropriately selected patients with hypertension of any severity as part of a comprehensive plan to minimize cardiovascular risk.

Animals↗