PubMed HealthSearch

Biomedical subjects

M J Goldberg

Publications and source records attributed to M J Goldberg.

At least 19 recordsLinked to original sources

Sensitive method for the quantitation of nortriptyline and 10-hydroxynortriptyline in human plasma by capillary gas chromatography with electron-capture detection.

A method for the determination of nortriptyline and 10-hydroxynortriptyline concentrations in human plasma by capillary gas chromatography with electron-capture detection is described. The procedure requires 1.0 ml of plasma and uses maprotiline as an internal standard. The compounds are extracted from alkalinized plasma with hexane-2-butanol (98:2) and back-extracted into hydrochloric acid. The acid solution is then made basic and the compounds are re-extracted into n-butyl chloride. The extract is evaporated to dryness, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography on a fused-silica capillary column coated with phenylmethyl silicone. The calibration curves for nortriptyline and 10-hydroxynortriptyline are linear in the ranges 3-40 and 7-90 micrograms/l, respectively, with coefficients of variation for within-day and between-day precision of less than 12%. The quantitation limits for nortriptyline and 10-hydroxynortriptyline are 1 and 3 micrograms/l, respectively. This procedure was used to analyze more than 1400 samples following sub-therapeutic doses of nortriptyline in human subjects. The assay was sufficiently sensitive for use in pharmacokinetic analysis.

Chromatography, Gas

Intraosseous arteriovenous malformation in a pediatric patient.

An isolated tibial intraosseous arteriovenous malformation was diagnosed in a seven-year-old boy. This malformation was not associated with any major clinical symptomatology except pain. It had a paucity of physical findings and was not well visualized with conventional radiography. It was not associated with any soft-tissue or cutaneous manifestations and it was entirely intramedullary, with minimal cortical involvement. This case illustrates the value of magnetic resonance imaging in the localization of these lesions. The absence of radiation exposure, coupled with the noninvasive nature, makes magnetic resonance imaging important in evaluating an intramedullary process in a pediatric patient.

Arteriovenous Malformations

Aggressive fibromatosis.

Ten patients with aggressive fibromatosis of the extremities were prospectively followed for 2-6 years. Results of treatment methods were compared. Five patients underwent three-dimensional imaging with and without intravenous contrast, and the images were compared with the anatomic extent of the resected lesion. Pathologic specimens and control tissue were tested for the presence of estrogen and progesterone receptors and for expression of the c-sis oncogene and platelet-derived growth factor (PDGF), potent mitogens for fibrocytes. Wider surgical resection resulted in a lower recurrence rate, but current chemotherapeutic agents were not effective in eradicating the tumors. Intravenous contrast enhanced the lesions. Two thirds of the tumors tested had estrogen or progesterone receptors. All tumors tested had inappropriate expression of c-sis and PDGF. This inappropriate expression may be responsible for the underlying pathobiology and deregulation of control of growth in aggressive fibromatosis.

Adult

Unicameral bone cyst in the scapula of an adolescent.

Unicameral bone cysts of the scapula have been reported mainly in adult patients. The atypical location of the unicameral bone cyst in a 12-year-old girl presented a diagnostic dilemma. Curettage proved to be an effective method for both diagnosis and treatment of this benign lesion.

Bone Cysts

Intraaortic balloon pump insertion: a randomized study comparing percutaneous and surgical techniques.

To compare the percutaneous and surgical techniques of intraaortic balloon pump insertion, 101 patients referred for this procedure were randomly assigned to either percutaneous or surgical insertion. Insertion using the designated technique was successful in 45 (88%) of 51 patients with percutaneous insertion and 48 (96%) of 50 patients with surgical insertion (difference not statistically significant). The time from the beginning of the insertion procedure to the initiation of counterpulsation was 13 +/- 8 minutes for the percutaneous technique versus 31 +/- 16 minutes for the surgical technique (p less than 0.001). In the percutaneous group, 10 patients required Fogarty thrombectomy after balloon pump removal, and 1 patient developed severe leg ischemia requiring immediate termination of balloon pump support. In the surgical group, one patient developed leg ischemia requiring surgical intervention, three patients developed sepsis with bacteremia (including one patient who required vein patch repair of the femoral artery), one patient developed a wound infection requiring debridement and one patient had a cerebral embolus. Aortic dissection, aortoiliac perforation or amputation did not occur in either group. Major vascular complications occurred in 11 patients (22%) with percutaneous insertion versus 2 patients (4%) with surgical insertion (p less than 0.05). It is concluded that although the percutaneous technique for intraaortic balloon pump insertion is faster than the surgical technique and is technically easy, it is associated with a higher incidence of vascular complications.

Blood Pressure

The effect of sorbitol and activated charcoal on serum theophylline concentrations after slow-release theophylline.

The effect of the addition of sorbitol to an oral regimen of multiple doses of activated charcoal on serum theophylline concentrations was studied after the ingestion of slow-release theophylline in nine healthy male volunteers. At 6, 7, 8, 10, and 12 hours after Theo-24 (1200 mg/70 kg) ingestion, each subject received, in a randomized crossover design, either 300 ml water, 20 gm activated charcoal in water, or 20 gm activated charcoal in water plus 75 ml 70% sorbitol at 6 and 8 hours only. The serum AUCs from 6 to 30 hours after Theo-24 ingestion during the water, charcoal, and charcoal plus sorbitol phases were 305 +/- 16, 113 +/- 6, and 85 +/- 10 mg-hr/L (mean +/- SE), respectively. We conclude that the addition of sorbitol to an oral regimen of multiple doses of activated charcoal decreased the serum theophylline concentrations after therapeutic doses of slow-release theophylline to a significantly greater extent than did the activated charcoal regimen alone.

Adult

Digoxin toxicity in patients with high serum digoxin concentrations.

A retrospective study of the clinical course and outcome of patients with serum digoxin concentrations (SDCs) greater than 3 ng/mL was conducted to determine the probability of a patient without initial signs or symptoms of digoxin toxicity subsequently developing signs or symptoms. Of 123 patients with SDCs greater than 3 ng/mL, 54 had no apparent signs or symptoms of toxicity at the time the index SDC was determined (group 1). Of these 54, two patients developed definite digoxin toxicity, although neither suffered significant morbidity. Digoxin administration was reduced or discontinued in all patients but one in group 1. There were no significant differences between the patients who had no signs or symptoms of digoxin toxicity (group 1) and those who did have signs or symptoms (group 2) in the mean SDC (3.9 +/- 0.1 vs 4.2 +/- 0.2 ng/mL, respectively), the serum creatinine (2.9 +/- 0.2 vs 3.4 +/- 0.4 mg/dL), or the incidence of atrial fibrillation (29/54 vs. 35/69) and coronary artery disease (21/54 vs. 18/69). The authors conclude that clinically stable patients receiving digoxin who have elevated SDCs but are without signs or symptoms of digoxin toxicity are at low risk of developing serious digoxin toxicity and do not generally require treatment beyond the discontinuation of digoxin therapy.

Aged

Transport of diphenhydramine in the central nervous system.

The transport and metabolism of diphenhydramine was studied in vitro in the isolated rabbit choroid plexus and in vivo in New Zealand white rabbits and Sprague-Dawley rats. In vitro, [14C] diphenhydramine was accumulated by a saturable, energy-requiring system in choroid plexus. In vivo, 20 min after intraventricular injection into rabbits, [14C]diphenhydramine was cleared from cerebrospinal fluid much more rapidly than [3H]sucrose, a molecule transported in the central nervous system by simple diffusion. In vivo, employing the in situ rat brain perfusion technique, [14C]diphenhydramine was cleared from the cerebral perfusion fluid as rapidly as [14C]diazepam. However, the clearance of [14C]diphenhydramine, but not [14C]diazepam, was inhibited by the addition of 10 mM unlabeled diphenhydramine to the perfusate. These in vivo and in vitro results show that diphenhydramine, unlike diazepam, is transported between blood, brain and cerebrospinal fluid, in part, by saturable, carrier-mediated transport processes at both the blood-brain and blood-cerebrospinal fluid barriers.

Animals

Treatment of theophylline intoxication.

The treatment of theophylline intoxication is reviewed. Efforts should be made to decrease the absorption of theophylline from the gastrointestinal tract by the oral administration of activated charcoal and sorbitol; stomach emptying procedures are recommended only in limited circumstances. Patients should receive intensive supportive care and appropriate treatment for complications of intoxication, including metabolic and cardiovascular abnormalities and seizures. Despite these treatments, morbidity (including residual neurological deficits) and mortality may occur. Therefore, efforts to actively remove theophylline from the body before complications occur should be considered in an attempt to reduce morbidity and mortality. The oral administration of multiple doses of activated charcoal (which increases theophylline clearance) is recommended for nearly all patients with theophylline intoxication. Although controversial, hemoperfusion--an efficient but invasive active removal procedure--is recommended in severely intoxicated patients who satisfy specific indications; the prophylactic administration of phenobarbital to prevent seizures should also be considered in these patients. Although these recommendations are rationally based on the extant evidence, controlled clinical trials in patients with theophylline intoxication are needed to prove their utility.

Antidotes

QT prolongation after ampicillin anaphylaxis.

Tall T waves and pronounced prolongation of the QT interval developed 24 hours after an apparently complete recovery from an acute anaphylactic reaction to oral ampicillin in a previously healthy woman of 29. These electrocardiographic abnormalities gradually subsided over five days. The prolongation of the QT interval has not previously been reported after anaphylaxis.

Adult

Phenobarbital improves survival in theophylline-intoxicated rabbits.

As in humans, theophylline intoxication in rabbits causes seizures and death. We studied whether the administration of phenobarbital or phenytoin following a toxic dose of theophylline would improve survival in rabbits. New Zealand white rabbits were infused intravenously with theophylline, 115 mg/kg over 50 minutes. Upon completion of the infusion, rabbits were randomized to receive either saline (control) (N = 60) or saline containing phenobarbital 20 mg/kg (N = 60), or phenytoin 12 mg/kg (N = 30), infused over 30 minutes. The number (and percentage) of rabbits surviving 24 hours in each group was: control 12 (20%), phenobarbital 30 (50%), and phenytoin 7 (23%) [X2; p less than 0.005; two-tailed]. In all fatal cases, death was preceded by a seizure; rabbits that survived did not seize. These results show that phenobarbital administered intravenously to theophylline-intoxicated rabbits prevented seizures and improved survival whereas phenytoin administration had no significant effect.

Animals

Expanded role of charcoal therapy in the poisoned and overdosed patient.

Activated charcoal is widely used as an adsorbent for the management of patients with drug overdoses and poisonings. Activated charcoal can be used orally to prevent drug and poison absorption in cases of overdose and poisoning. Multiple oral doses of charcoal increase the elimination of several, but not all, drugs and poisons. The effectiveness of multiple oral doses of charcoal in accelerating drug clearance is dependent primarily on the endogenous clearance of the drug or poison and its volume of distribution. Multiple doses of charcoal are used to shorten the period of supportive care in certain patients or to more rapidly remove drugs or poisons that may cause tissue damage, eg, theophylline. Charcoal is a safe, effective, and inexpensive alternative to more invasive treatments for some cases of drug overdose and poisoning.

Administration, Oral

An approach to the management of the poisoned patient.

Our systematic approach to the evaluation and treatment of the acutely poisoned patient involves establishing an accurate diagnosis and prognosis that often may be based on quantitation of the blood concentration of the toxic substance. The major feature of this approach is the proper selection of treatment(s) for the poisoned patient, ie, decontamination and supportive care and, in some cases, antidotal therapy and/or active removal of the toxic substance. Invasive, expensive methods of active removal (eg, hemodialysis or hemoperfusion) are generally recommended only if specific criteria are satisfied. Noninvasive, inexpensive methods of active removal (eg, manipulation of urinary pH or the oral administration of multiple doses of activated charcoal) may have significant utility in the treatment of poisoned patients not requiring invasive methods. This systematic approach to the poisoned patient should lead to an effective use of treatment modalities with minimal risks and optimal clinical results.

Acute Disease

Lack of effect of oral activated charcoal on imipramine clearance.

The effect of oral activated charcoal on the pharmacokinetics of intravenous imipramine was studied in a randomized, crossover trial. Four normal men received intravenous imipramine (12.5 mg/70 kg) on two separate occasions, followed by either water or water plus high-surface-area activated charcoal (180 gm) in divided doses over 24 hours. Serum imipramine concentrations were measured from 0 to 24 hours after the imipramine infusion. There was no difference in the mean (+/- SE) t1/2 (9.0 +/- 0.8 vs. 10.9 +/- 1.6 hours), apparent volume of distribution (11.2 +/- 2.1 vs. 12.4 +/- 2.1 L/kg), or systemic clearance (992.2 +/- 138.3 vs. 930.3 +/- 101.9 ml/min/70 kg) of imipramine after dosing without and with oral activated charcoal, respectively (P greater than 0.05; paired t test). These results suggest that multiple oral doses of activated charcoal do not increase the clearance of imipramine in man.

Absorption

The effects of activated charcoal on digoxin and digitoxin clearance.

The effect of multiple oral doses of activated charcoal on digitalis glycoside kinetics was studied to determine whether an activated charcoal regimen might have utility in treating patients with digitalis toxicity. Normal subjects were given intravenous infusions of digoxin 0.75 mg/70 kg or digitoxin 1 mg/70 kg iv followed by either water alone or water with activated charcoal in divided doses in a randomized crossover design. A subject with chronic renal failure was also given digoxin 0.5 mg/70 kg iv followed by water alone or water with activated charcoal. In six normal subjects, treatment with activated charcoal did not increase digoxin clearance (Cl) significantly (16.79 +/- 1.70 vs. 22.68 +/- 3.51 L/h). However, digitoxin Cl did increase significantly, from 0.24 +/- 0.01 to 0.47 +/- 0.04 L/h. In the renal failure subject, digoxin Cl increased from 3.6 L/h to 10.1 L/h. We conclude that the activated charcoal regimen is probably useful in patients with digitoxin toxicity. Although similar benefit is limited in patients with normal renal function who develop digoxin toxicity, it is possible that activated charcoal will be useful in patients with prolonged digoxin elimination due to renal dysfunction.

Adult