Dyspepsia in pregnancy.

Dyspepsia with or without nausea is common during pregnancy. Known ulcer disease, gastritis, and GERD may improve during pregnancy. Many women have a stoic and long-suffering posture during pregnancy owing to an unrealistic expectation concerning the teratogenicity of commonly used drugs. It is appropriate in medicine to alleviate pain and suffering when possible, and many drugs can be used safely and effectively to control upper gastrointestinal tract symptoms. When symptoms are persistent into the late second trimester, refractory to pharmacologic treatment, or severe, H. pylori infection, complications of ulcer disease, and underlying cancer should be suspected and sequentially ruled out. More timely treatment and work-up of nonobstetric disease during pregnancy is expected to lower perinatal complications.

Blood cocaine and metabolite concentrations, clinical findings, and outcome of patients presenting to an ED.

The purpose was to determine if blood cocaine or metabolite concentrations would accurately reflect the severity of clinical findings in patients presenting to the emergency department, identifying those requiring therapeutic intervention or those at risk for poor outcome. Blood for determination of cocaine and metabolite concentrations was drawn from patients and were determined by an extractive alkylation/mass spectrometry procedure. The mean blood concentrations (mg/L) in 111 patients were as follows: cocaine, 0.26 +/- 0.5; ecgonine 0.42 +/- 0.47; ecgonine methyl ester 0.21 +/- 0.37, norcocaine 0.03 +/- 0.17; benzoylecgonine 1.28 +/- 1.29, cocaethylene 0.02 +/- 0.06. Two patients died, 23 required hospital admission, and 88 were discharged from the ED. There was no statistical correlation between cocaine or any metabolite concentration and the severity of clinical symptoms, disposition, need for treatment or outcome. Blood cocaine and metabolite concentrations should be interpreted with caution because they vary widely and do not predict the severity of clinical findings, the incidence of adverse effects, outcome, or need for interventional therapy.

Cocaine metabolism in hyperthermic patients with excited delirium.

The half-life of cocaine in clinical experiments has been reported to range from 60 to 90 min. It has been previously suggested that elevated temperature may accelerate the metabolism of cocaine. However, there is no clinical data to indicate the presence of hyperthermia like that seen in excited delirium alters the half-life of cocaine. We report the results of half-life determinations from serial cocaine concentrations in two patients with excited delirium. Both patients presented to the emergency department with classic findings of excited delirium that included hyperthermia, agitation, and cardiovascular aberrations. One patient died despite aggressive therapeutic intervention. Cocaine and metabolite concentrations were determined by an extractive alkylation mass spectrometry procedure. Presenting cocaine concentrations in patient 1 and patient 2 were 0.387 and 0.266 mg/L respectively. Results from pharmacokinetic modeling of the serial concentrations show that the half-life of cocaine was not significantly accelerated, despite the presence of hyperthermia. Data from these two cases provide further evidence that catastrophic reactions to cocaine are independent of amount or route of administration, and that the metabolism of cocaine, at least in these patients, was not altered by hyperthermia.

Multiple cocaine-induced seizures and corresponding cocaine and metabolite concentrations.

The etiology of seizures associated with cocaine use is unclear. Because cocaine seizures are relatively uncommon, they should be diagnosed by exclusion and a neurological workup to rule out central nervous system (CNS) catastrophe should be made. This report describes the clinical findings, treatment, and blood cocaine and metabolite concentrations in a patient who, on two separate occasions, had seizures associated with crack cocaine ingestion. Approximately 1 hour after the ingestion incidents, the patient had multiple, generalized seizures that abated spontaneously. His workup for CNS bleeding, infection, and trauma was negative. Cocaine concentrations on the first incident peaked at 2.48 mg/L and on the second incident peaked at 3.9 mg/L. Other clinical findings included tachycardia, hypertension, diaphoresis, and disorientation. Blood cocaine and metabolite analysis revealed extremely high concentrations. Other than the incident of seizures and transient cardiovascular aberrations, these high concentrations were tolerated by the patient without further sequelae. A review of cocaine-induced seizures and treatment is included.

Foreign body ingestions in the Emergency Department: case reports and review of treatment.

We report a series of alleged ingestions of razor blades and other metal objects by prisoners presenting to an inner city Emergency Department. Fourteen claims of ingestions of razor blades or other metal objects involving eight prisoners occurred in a 5-week period. The motives behind the ingestions varied. Auditory hallucination was the most common reason given for the ingestions. Other motives included efforts to leave prison, depression, and accidental razor blade swallowing. Attempts were made in all patients to verify ingestions by radiograph. Some ingestions could not be confirmed by radiograph and were considered to be factitious. Only 1 of the 14 incidents resulted in hospital admission. All others were either treated in the Emergency Department or the patient was returned to jail with no treatment. No patient had a poor clinical outcome as a result of the ingestion, indicating that diagnostic radiographs and invasive procedures may not always be necessary. A review of treatment of foreign body ingestions is given as well as a summary of the treatment and outcome of these cases.

Clinical pharmacology of lysergic acid diethylamide: case reports and review of the treatment of intoxication.

Intoxication and overdose are common presenting complaints to the emergency department. Acute intoxication with lysergic acid diethylamide (LSD) has become a relatively rare event, especially when compared with the incidence of ethanol and cocaine intoxication. We recently had an outbreak of presumed LSD intoxications occurring over one weekend. All patients had attended a performance by the musical group The Grateful Dead. At present, LSD intoxication or overdose can only be suspected based on clinical findings because there are no readily available rapid laboratory tests for detecting either the parent compound or the metabolites of the drug. The clinical findings and outcomes of five patients with suspected LSD intoxication are presented. The pharmacological effects of LSD and treatment modalities of intoxication are reviewed. All patients were treated conservatively based on clinical signs and symptoms. Only one patient required hospital admission for combative behavior that was initially refractory to pharmacological restraint.

Pediatric growth and development.

Most children with congenital anomalies, teratogenesis, inborn errors of metabolism, and acquired toxicity or injury will have abnormal growth and development during the first few years of life. Many of the conditions are treatable, and early intervention is associated with improved prognosis. Developmental and growth assessment should be part of any routine visit to a primary care clinician. An overview of normal growth and development is outlined, and some common abnormalities are discussed.

Pharmacological considerations for the pediatric patient.

The use of pharmacological agents in children warrants special consideration because children have variable pharmacokinetic parameters. Not only are the pharmacokinetic properties of drugs different in children as compared with adults, but these properties can undergo rapid change as children grow and mature. Furthermore, many drugs that would be useful in the pediatric population lack the indication for use in children and, therefore, dosing guidelines are not available. This paper presents an overview of basic pharmacokinetics in children and pediatric dosing guidelines.

Determining the true cause of death in a dermatological disaster.

Adverse drug reactions that result in patient death warrant special consideration to determine if the outcome was preventable. We report the results of an investigation into the cause of death of a 63 year old male who was thought to have phenytoin-induced toxic epidermal necrolysis (TEN). Most dermatological reactions from drugs are minor and resolve without sequelae once the drug is discontinued. In some cases, reactions are severe and can be life threatening. The patient arrived at the emergency department with extensive exfolative dermatitis. The differential diagnosis included phenytoin-induced TEN, scalded skin syndrome, and phenytoin hypersensitivity. After he was admitted his clinical status deteriorated and he died 13 days after admission. Autopsy findings were significant for necrotizing dermatitis, necrotizing pneumonia, multiple herpetic ulcerations, multisystem organ failure and blood cultures grew Staphylococcus aureus (TSS toxin positive). Findings that indicate a cause of death other than a drug-induced dermatological reaction are presented as well as an overview of the patients' medical history. The differential diagnosis of drug induced skin lesions are also discussed.

Effect of short-term treatment with gastrin and related peptides on gastrointestinal histamine H2-receptors.

The effects of short-term, 7-day, treatment with synthetic 15-leucine human gastrin I, pentagastrin or sulfated cholecystokinin-8 on the activity of histamine (HA)-stimulated adenylate cyclase in membranes isolated from guinea pig gastric mucosa and H2-receptor-mediated contractions of isolated ilea were evaluated. Treatment with each of the peptides produced a decrease in the maximal rate of HA-stimulated adenylate cyclase. The decreases in the maximal rate occurred without any effect on the potency of HA or any effect on basal rates of activity. In animals treated with pentagastrin, but not with cholecystokinin octapeptide sulfate, the contractile activity of dimaprit, a selective H2-agonist, was decreased. In animals treated with pentagastrin, the contractile actions of pentagastrin on isolated ileal preparations were increased. A 7-day treatment with the H2-antagonist, tiotidine, did not alter the potency of or the maximal response for HA-stimulated adenylate cyclase activity. Co-treatment with tiotidine prevented the effects of pentagastrin on gastric mucosal HA-stimulated adenylate cyclase. Treatment with pentagastrin did not alter the sensitivity of the gastric mucosal H2-receptor to inhibition by tiotidine. The effects of treatment with gastrin on NaF-stimulated adenylate cyclase activity also were determined. Treatment with gastrin did not alter the actions of NaF, suggesting that the coupling between the Gs subunit and the catalytic subunit of adenylate cyclase was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Lowering extracellular calcium decreases the length of isolated outer hair cells.

Transduction by the inner hair cells is hypothesized to be modulated through a change in the length of the outer hair cells (OHC). It has been suggested that the slow change occurring in OHC length is mediated by an actin-myosin system requiring Ca2+ and ATP. This study was designed to systematically examine the effects of lowering extracellular Ca2+ on OHC length. OHCs were isolated from guinea pig cochleae, mechanically dissociated and dispersed, and placed in a Hank's balanced salt solution (HBS). Exposing the cells to a Ca(2+)-free HBS supplemented with 200 microns EDTA produced a shortening in OHC length with a concomitant increase in cell width. The shortening was reversed successfully by bathing the cells in 8 mM Ca2+. We speculate that the decrease in length due to lowering extracellular Ca2+ may be caused by a relaxation of a circumferential contractile mechanism which is thought to cause elongation of intact OHCs (Slepecky, 1989; Dulon et al., 1990).

Supersensitivity and changes in the active population of beta adrenoceptors in rat right atria in early sepsis.

We have investigated the effect of sepsis induced by cecal ligation and puncture on the chronotropic actions of beta adrenoceptor agonists on isolated right atria. The present findings show that right atria obtained from rats in an early stage of sepsis were supersensitive to the chronotropic actions of the beta-agonists, isoproterenol (ISO), fenoterol (FEN) and prenalterol (PREN). The supersensitivity to the chronotropic actions of ISO and FEN was much greater than that which developed to PREN. The positive chronotropic actions of isobutylmethylxanthine and forskolin were not affected by sepsis. The receptor subtypes mediating the responses to ISO, FEN and PREN by control and septic right atria were characterized by functional assays using selective beta-1 and beta-2 antagonists. The results showed that the chronotropic response produced by all three agonists on right atria obtained from control rats were mediated by beta-1 receptors. In contrast, the chronotropic actions of ISO and FEN on atria from septic rats were mediated by what appears to be beta-2 receptors and those of PREN by beta-1 receptors.

Cardiac function and chronotropic sensitivity to beta-adrenergic stimulation in sepsis.

An organism's cardiovascular response to sepsis is at least partly dependent on hormonal and neural modulation of myocardial function. We have investigated both intrinsic myocardial performance and one aspect of myocardial sensitivity to beta-adrenergic stimulation in a model of sepsis in which animals, at the time studied, exhibited bacteremia, normal arterial blood pressure and cardiac output, elevated heart rate, and elevated plasma catecholamines. Intrinsic myocardial contractile function, studied with the isolated, perfused working heart preparation, was depressed over a range of preloads in septic animals, whereas heart rate was elevated. To determine whether hearts from septic animals could respond normally to beta-adrenergic stimulation, we studied chronotropic responses to isoproterenol in both Langendorff perfused hearts and in isolated right atria. In langendorff perfused hearts from septic animals, basal rates were significantly increased and lower concentrations of isoproterenol elicited greater increases in heart rate. In isolated right atria from septic animals, basal rates were also elevated and the EC50 for the chronotropic response to isoproterenol was significantly less than in atria from control animals. The maximal heart rate response to isoproterenol was not significantly different from control. These results indicate that in sepsis, despite apparently adequate in vivo cardiac performance, intrinsic myocardial function is depressed, but chronotropic sensitivity to beta-adrenergic stimulation is increased.

Metronidazole and 5-aminosalicylic acid enhance the contractile activity of histaminergic agonists on the guinea-pig isolated ileum.

The effects of metronidazole and 5-aminosalicylic acid (5-ASA) on histamine receptor-effector systems in the small intestine and right atrium of the guinea pig were studied. In an apparently all-or-none manner, both caused a sinistral shift in dose-response curves for the phasic component of the contractile response to histamine at H1 receptors on the ileum. In the presence of either, the EC50 value for histamine was reduced from 0.07 to about 0.03 microM. Similarly, in an apparently all-or-none fashion, both produced an elevation in the dose-response curve for the actions of dimaprit at H2-receptors in the ileum; the response to all doses was increased about 30% with no significant change in the EC50 value. Metronidazole and 5-ASA did not alter dose-response curves for the tonic contractile response to histamine or curves generated by the cumulative addition of histamine. Also, neither altered the positive chronotropic response on isolated right atria or the phasic contractile response on isolated segments of jejunum and duodenum to histamine or dimaprit. Likewise, neither altered dose-response curves for the direct action of carbamylcholine at muscarinic receptors or for the indirect actions of dimethylphenylpiperazinium on the ileum. The effects of 5-ASA or metronidazole on the response to histamine could be prevented as well as reversed by scopolamine or tetrodotoxin. The results suggest that metronidazole and 5-ASA enhance the actions of histamine and dimaprit on the ileum by an action on myenteric plexus neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative actions of quisqualate and N-methyl-D-aspartate, excitatory amino acid agonists, on guinea-pig cochlear potentials.

We examined dose-dependent changes in the amplitude of guinea-pig cochlear microphonic potentials (CM), summating potentials (SP) and compound auditory nerve action potentials (CAP) produced after perfusing perilymphatic scalae with artificial perilymph containing either the transmitter candidate, L-glutamate; one of the excitatory amino acid agonists, quisqualate, kainate, N-methyl-D-aspartate (NMDA) or D-glutamate; or the control, alpha-ketoglutarate. None of these compounds significantly altered CM or SP. Kainate abolished CAP, but only partial suppression occurred using maximal effective doses of quisqualate (67%) or L-glutamate (82%). The remaining compounds had only marginal effects on CAP. The potency of quisqualate (EC50 = 14.8 microM) exceeded that of both kainate (EC50 = 66.9 microM) and L-glutamate (EC50 = 1.41 mM). These data suggest the presence of neuronal, possibly postsynaptic, excitatory amino acid receptor subpopulations which are preferentially sensitive to quisqualate and to kainate, but not to NMDA. These findings are discussed in the framework of our hypothesis that the proposed quisqualate and kainate receptors are normally activated by an endogenous excitatory amino acid such as L-glutamate which the hair cells release as a neurotransmitter.

Comparative actions of GABA and acetylcholine on the Xenopus laevis lateral line.

The effects of GABA, acetylcholine and carbachol on the spontaneous activity of afferent nerve fibers in the lateral line of Xenopus laevis are characterized. Atropine and bicuculline were also tested on drug- and water motion-evoked activity. GABA (0.019-1.25 mM) suppressed and both acetylcholine (1.25-80 microM) and carbachol (1.25-40 microM) increased spontaneous activity. These actions were blocked by bicuculline (100 microM) and atropine (4 microM) respectively. Atropine (20 microM) and bicuculline (100 microM) had no effect on water motion-evoked activity. The results characterize actions of GABA and acetylcholine not previously described and provide evidence that does not support the hypothesis that GABA or acetylcholine are the afferent transmitter.