A potential role for glucagon in the treatment of drug-induced symptomatic bradycardia

Nine cases of symptomatic bradycardia are presented in which treatment with intravenous glucagon was administered when atropine failed to improve the patient's condition significantly. Although the cause often was not obvious at presentation, all nine subjects took oral medications that could have contributed to the development of symptomatic bradycardia. Eight of nine patients demonstrated clinical improvement 5 to 10 min after glucagon administration, which was consistent with its peak clinical action. Beta-blockers, calcium channel blockers, and digoxin were ultimately thought to have contributed to the majority of these presentations. This report suggests that glucagon may have a role in the treatment of symptomatic bradycardia, particularly in the presence of beta-adrenergic blockade and perhaps calcium channel blockade. Furthermore, the results in these cases suggest that future clinical trials should not be limited to drug-induced symptomatic bradycardia.     

Theophylline for chronic symptomatic bradycardia in the elderly

The treatment of choice for chronic, symptomatic bradycardia is the placement of a cardiac pacemaker. Individuals who refuse or cannot tolerate pacemaker insertion usually require pharmacologic therapy. Hydralazine, prazosin, anticholinergics, and sympathomimetic agents have been administered for this indication, but adverse effects and limited data hinder routine, long-term use. Theophylline has emerged as a reasonable alternative strategy. For the medical management of bradycardia in the elderly, the literature supports theophylline dosages between 400 and 600 mg/d (approximately 8 mg/kg/d) administered in divided doses. This dosage range should result in a steady-state serum concentration between 5 and 15 mg/L. While some investigators recommend potentially higher initial doses (up to 12 mg/kg/d), lower dosages are more appropriate in the elderly due to decreased theophylline clearance. Initial dosage titration may be indicated and prolonged therapy is expected on the basis of the common etiologies of bradycardia in this patient group. Patient specifics such as altered theophylline metabolism (e.g., smoking), drug interactions (e.g., ciprofloxacin), and concomitant disease states (e.g., hepatic disease, heart failure) should always be considered in theophylline dosage recommendations. Clinicians should adjust the theophylline dose on the basis of patient response, including heart rate and clinical symptomatology, as well as measurement of occasional theophylline concentrations, if deemed appropriate. Theophylline should be avoided in the bradycardia-tachycardia manifestations of sick sinus syndrome or when ventricular ectopy is frequent. Additional investigation will further define the role of theophylline in elderly patients with chronic, symptomatic bradycardia.     

Extinction in fear conditioning: effects on startle modulation and evaluative self-reports

gamma-Hydroxybutyric acid (GHB) is unfamiliar to many physicians in the United States but enjoys clinical use elsewhere for applications in resuscitation, anesthesia, and addiction therapy. Use within the United States is restricted to Food and Drug Administration-approved clinical trials for treatment of narcolepsy. Recently illicit use of GHB has emerged within the United States where it is distributed for purported euphoric and "fat-burning" metabolic effects. Clinical effects can be severe, progressing rapidly to respiratory arrest and death. We provide an updated comprehensive review of the literature with particular emphasis on toxicology, including GHB pharmacodynamics, clinical effects, and suggestions for overdose management. Recommended management of acute GHB intoxication includes prevention of aspiration, use of atropine for persistent symptomatic bradycardia, consideration of neostigmine as a reversal agent, and treatment for coingested substances. Emergency physicians are urged to become familiar with GHB because of its potential for severe morbidity as well as its potential use as a future resuscitative agent.     

The Glasgow Coma Score: reliable evidence?

This study examined the selected hormonal responses to, and hormone-mediated glucose metabolism during minimally invasive surgery in, patients undergoing laparoscopic cholecystectomy for symptomatic gallstone disease. Thirty-two patients with symptomatic gallstone disease were included in this study and scheduled for open or laparoscopic procedure in a randomized trial. Results are expressed as mean and standard error of the mean. Statistical evaluations were performed with Mann-Whitney U and Wilcoxon signed-rank tests. Blood cortisol, glucagon, insulin, and glucose concentrations were measured immediately in the preoperative period and 6 h after surgery. Blood cortisol, glucagon, and glucose concentrations increased significantly after open and minimally invasive surgery, while insulin levels and the insulin:glucagon ratio remained unchanged. The rise of glucagon and cortisol values was found to be significantly higher in the postoperative period of the open procedure, than in the laparoscopic approach. However, in the patients who underwent open surgery, the increase in glucose concentrations was not significantly higher in the postoperative period. Surgery-induced hormonal effects on the islets increase glucagon and suppress insulin secretion. The glucagon-mediated increase in hepatic glucose production is excluded by the posttraumatic insulin levels from the insulin-sensitive tissues. A bihormonal setting favors a greater rate of hepatic glucose production in both open and laparoscopic surgery. Hormonal changes do reflect the degree of surgical stress, but their metabolic consequences are not parallel to the grade of surgical trauma in minimally invasive surgery.     

A report card for occupational injuries and illnesses

We present a case of cutaneous nerve hypertrophy possibly secondary to scratching or other trauma. The patient was symptomatic and sought surgical treatment, despite no clinical lesion being evident. This type of change has not been previously reported in this clinical setting. There was no clinical evidence of multiple endocrine neoplasia-type 2b (MEN-2b). Awareness of this entity may avoid unnecessary surgery.     

Brief twice-weekly episodes of hypoglycemia reduce detection of clinical hypoglycemia in type 1 diabetes mellitus

We tested the hypothesis that as few as two weekly brief episodes of superimposed hypoglycemia (i.e., doubling the average frequency of symptomatic hypoglycemia) would reduce physiological and behavioral defenses against developing hypoglycemia and reduce detection of clinical hypoglycemia in patients with type 1 diabetes mellitus (T1DM). Compared with nondiabetic controls, six patients with well-controlled T1DM (HbA1c, 7.5 +/- 0.7% [mean +/- SD]) exhibited absent glucagon responses and reduced epinephrine (P = 0.0027), norepinephrine (P = 0.0007), pancreatic polypeptide (P = 0.0030), and neurogenic symptom (P = 0.0451) responses to hypoglycemia as expected. In these patients, 2 h of induced hypoglycemia (50 mg/dl, 2.8 mmol/l) twice weekly for 1 month, compared in a random-sequence crossover design with an otherwise identical 2 h of induced hyperglycemia (150 mg/dl, 8.3 mmol/l) twice weekly for 1 month, further reduced the epinephrine (P = 0.0001) and pancreatic polypeptide (P = 0.0030) responses, tended to further reduce the norepinephrine and neurogenic symptom responses to hypoglycemia, and reduced cognitive dysfunction during hypoglycemia (P = 0.0271), all assessed in the investigational setting. In the clinical setting, induced hypoglycemia did not alter overall glycemic control, but did reduce the total number of symptomatic hypoglycemic episodes detected by the patients from 49 to 30 per month and lowered the mean +/- SE self-monitored blood glucose level during symptomatic hypoglycemia from 51 +/- 2 mg/dl (2.8 +/- 0.1 mmol/l) to 46 +/- 3 mg/dl (2.6 +/- 0.2 mmol/l) (P < 0.01). It also reduced the proportion of low regularly scheduled self-monitored values that were symptomatic by approximately 33%. Thus as little as doubling the frequency of symptomatic hypoglycemia further reduced both the key epinephrine response and clinical awareness of developing hypoglycemia, changes reasonably expected to increase the risk of severe iatrogenic hypoglycemia in T1DM.     

Zinc enrichment in prostasomes

A 54-yr-old woman with a pT2pN0 breast cancer developed a long-standing symptomatic breast edema after lumpectomy and radiation therapy. The breast edema did not respond to non-steroidal anti-inflammatory drugs (NSAIDs) and manual lymph drainage of her arm. Three years after completion of radiation therapy, hyperbaric oxygen (HBO2) treatment was initiated. Fifteen HBO2 sessions were performed at a pressure of 240 kPa over 90 min in a multiplace chamber. At the end of treatment, breast discomfort had subsided completely, and 5 mo. after completing HBO2 therapy the patient is still free of complaints. We conclude from this observation that the value of HBO2 in the management of symptomatic radiation-induced breast edema should be investigated in a clinical study, because other effective treatment options are not available for this condition.     

Fatal intoxication with amlodipine

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition of continuous calcium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of severe hypercalcemia and hyperglycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.     

Paroxetine. A review of its pharmacology, therapeutic use in depression and therapeutic potential in diabetic neuropathy

Paroxetine is a selective serotonin reuptake inhibitor effective in a once-daily administration regimen in the treatment of depression. In elderly patients (aged > or = 60 years) with major depression, short term (6 weeks) treatment with paroxetine produces clinical improvements significantly superior to those seen with placebo and similar to those with tricyclic antidepressant agents, mianserin and fluoxetine. There is evidence that paroxetine has positive effects on co-existing anxiety and does not precipitate agitation. Paroxetine has also shown potential in the symptomatic treatment of diabetic neuropathy; however, further clinical experience is needed to confirm this preliminary result. Short term paroxetine therapy is associated with fewer anticholinergic and CNS adverse effects, but generally more gastrointestinal disturbances, than tricyclic antidepressants and mianserin. Unlike the tricyclic agents, paroxetine does not significantly affect cardiovascular function or impair psychomotor performance. This tolerability profile should be particularly beneficial in elderly patients, who are generally more susceptible than younger patients to the anticholinergic and CNS adverse events associated with tricyclic antidepressant drugs, and in whom there is a higher prevalence of pre-existing cardiovascular disease. It also suggests an important potential advantage over tricyclic antidepressants in the setting of overdosage. Thus, primarily because of its better tolerability profile and potentially lower toxicity in overdosage and in patients with cardiovascular disease, paroxetine appears to be a more attractive option than tricyclic antidepressants for the treatment of depression in late life. Future research should attempt to define more fully the efficacy of paroxetine as long term prophylactic therapy for recurrent depression and to assess how its overall therapeutic profile compares with other selective serotonin reuptake inhibitors in the elderly.     

Morbidity pattern, health care utilization and per capita health expenditure in a rural population of Tamil Nadu

This retrospective analysis intends to evaluate by histeroscopy the endometrial findings in a group of 63 patients in post-menopausal treated with tamoxifen for breast cancer. Our patients assumed tamoxifen for a different period between 6 and 120 months. Patients have been divided in two groups: I) patients undergoing hysteroscopy because of some clinical symptoms; II) patients who undergoing hysteroscopy as a routine examination. The most important observation of this work is the correlation between the presence of negative endometrium and low risk hyperplasia (LRH) associated to: symptomatology and duration of therapy. In the group of asymptomatic patients the LRH is found only after 3 years of treatment, while in the group of symptomatic patients, LRH is present within the first two years of treatment; beyond this period high risk hyperplasia (HRH) and endometrial carcinoma have been diagnosed. We also observed a higher incidence of endometrial polyps in this population than among the non treated group and among the symptomatic patients. From these data we conclude that hysteroscopy follow-up has to be performed in the group of patients treated with tamoxifen and that it would be necessary to have a hysteroscopy before the beginning of therapy and that this one has to be repeated once a year through the treatment. Obviously the symptomatic patients have to undergo hysteroscopy as soon as possible as a higher incidence of HRH and endometrial carcinoma has been detected in this group of patients.     

Diagnostic value of specific Giardia fecal antigen tests

Glucagonoma Syndrome is a rare syndrome comprising hyperglucagonemia, diabetes mellitus, necrolytic migratory erythema and hypoaminoacidemia in the setting of a glucagon producing, alpha cell tumour of the pancreas. We report a case of Glucagonoma Syndrome palliatively treated successfully with octreotide. In addition to classical clinical and biochemical findings, this patient also had a Glomus Jugulare tumour, and Empty Sella Syndrome and demonstrated an unusual pattern of plasma lactate dehydrogenase isoenzymes, features not previously reported in this syndrome.     

C-peptide levels in secondary sulfonylurea resistant diabetics

In the presence of clinical features of secondary drug failure--even after reeducation on diet and intensive control of patients--is difficult to make a decision to switch on insulin. Therefore the serum C-peptide concentrations were assessed in order to get supporting data. From 35 patients with suspected secondary drug failure the therapy of 11 patients was continued with insulin, 24 patients remained on glibenclamide therapy. The decision based on clinical criteria. All of the patients were studied in i.v. glucagon test and with a test meal to evaluate their basal and stimulated serum C-peptide concentrations. There were only three patients with subnormal basal C-peptide (< or = 0.30 nmol/l), on the other hand nine patients had lower post-glucagon serum C-peptide level than 0.60 nmol/l. The basal and stimulated C-peptide concentrations from i.v. glucagon test and test-meal indicated the need of insulin therapy with a sensitivity of 81.8 percent and with specificity of 70.8 percent. The further glibenclamide treatment on the basis of C-peptide concentrations in 89.5 percent of cases could be accurately established. The statistical analysis showed that the glucagon-stimulated C-peptide concentration was the most characteristic feature to discriminate the patients in order to make a decision on the further diabetes therapy.     

Noise detection during bradycardia pacing with a hybrid nonthoracotomy implantable cardioverter defibrillator system: incidence and clinical significance

The purpose of this study was to prospectively evaluate the incidence of noise detection during bradycardia pacing by an FDA approved hybrid nonthoracotomy ICD system. An illustrative case report which prompted this investigation is provided. Backup bradycardia pacing by tiered therapy cardioverter defibrillators has been useful in preventing postshock bradycardia and occasionally for chronic rate support in bradycardic patients. Unexplained "noise" detected by real-time telemetry has been previously described during bradycardia pacing by a device utilizing automatic gain control for sensing. Eighteen patients were prospectively evaluated for noise detection during ventricular pacing by the ICD. Real-time telemetry was analyzed with each patient: (1) supine, (2) supine with deep inspiration/expiration, (3) supine during Valsalva, and (4) during a change in position from supine to sitting. Analysis of pacing threshold and lead impedance was made in each patient. Eleven of 18 patients had noise detected on real-time telemetry during bradycardia pacing. In 10 patients this was noted during deep inspiration/expiration, in 2 during Valsalva maneuver, and in 5 with position change. There was no evidence in any patient of lead malfunction nor any difference in pacing threshold or lead impedance between patients with noise detected versus those without it. Noise detection by an approved hybrid ICD system is common and may be due to the automatic gain control which maximizes sensitivity during bradycardia pacing. This may lead to clinically significant events, with both suppression of bradycardia pacing and triggering of tachycardia therapy in the absence of ventricular tachyarrhythmias in pacemaker-dependent patients.     

Clofibrate-induced changes in glucagon and insulin secretion in patients with angiographically documented coronary artery disease

This study examines insulin and glucagon secretion in the basal state and in response to clofibrate therapy in patients with angiographically proven coronary artery disease. When compared with weight matched subjects without coronary artery disease, neither insulin nor glucagon secretion were abnormal in response to L-arginine stimulation. However, in response to clofibrate, a marked reduction in insulin secretion and simultaneous elevation in glucagon secretion characterized all patients. Our data suggest the hypothesis that altered insulin and glucagon secretion in response to clofibrate therapy may participate in the reduction of new coronary events reported to occur during therapy with this drug.     

A method of assessing retraction of a blood clot and spontaneous fibrinolysis and use of this method in evaluating the effects on infusion media on hemostasis

The results of a clinical observation of 30 patients with oral mucosa disease are presented in the article. All patients got "Tantum Verde" as a local treatment in the dose of 15.0 ml 4 times a day for 6 days. The efficiency of the medicine as a mean of symptomatic therapy of acute and chronic oral mucosa diseases is proved as well as prospects for its use both separately and for complex therapy of these diseases.     

Prenatal diagnosis by FISH of a 22q11 deletion in two families

OBJECTIVE: To investigate the predictive value of an intravenous fluid bolus during tilt table testing on clinical outcome and to evaluate of oral therapy is an effective treatment for patients with vasodepressor syncope. DESIGN: Retrospective cohort. SETTING: Regional pediatric cardiology outpatient clinic. PATIENTS: Patients (N = 58) with a positive baseline tilt table testing result who were treated with oral fluid therapy between February 1991 and March 1996. INTERVENTIONS AND MAIN OUTCOME MEASURES: Patients with a positive tilt table test result were given an intravenous bolus of isotonic saline solution. Responders were identified as having a negative tilt table test result after the bolus. Patients were prescribed a protocol of oral fluid therapy. Data were obtained from the medical record and a mailed survey. RESULTS: Of the 58 subjects, 90% had no recurrent syncope while receiving oral fluid therapy. During tilt table testing, the mean decrease in mean arterial pressure seen with symptomatic events was lower after the intravenous fluid. The heart rate, which dropped during the initial test, increased during the rests after the intravenous bolus. In the nonresponders, symptomatic episodes occurred significantly later in the tilt table test when given fluids. The response to intravenous fluid bolus had positive predictive value of 92% and negative predictive value of 11% of clinical outcome. CONCLUSIONS: Our data suggest that oral fluid therapy is an effective treatment for vasodepressor syncope in our population. Fluid bolus response during tilt table testing has a high positive but a low negative predictive value of response to oral fluid therapy. We now recommend oral fluid therapy as a primary intervention and reserve tilt table testing for oral fluid therapy failures.     

Symptomatic improvement following emergency department management of asthma: a pilot study of intramuscular dexamethasone versus oral prednisone

Systemic corticosteroid therapy is an established adjunct to beta-adrenergic medications in acute exacerbations of asthma. To date, no study has defined the role of long-acting intramuscular preparations of corticosteroids in pediatric patients with asthma. A pilot study was conducted to prospectively compare symptomatic improvement following a single injection of intramuscular dexamethasone (IMD) to a 3-day regimen of oral prednisone (OP) for children with mild to moderate wheezing episodes that are responsive to nebulized medications in the Pediatric Emergency Department (PED). The following children presenting with acute exacerbations of asthma to the PED were eligible for enrollment: age 3-16 years; more than two prior wheezing episodes; mild to moderate wheezing; and oxygen saturation 95% or more in room air. The study patients were randomly assigned to receive either IMD (n = 21) or OP (n = 21) in addition to a standardized treatment regimen of nebulized albuterol. All of the children were clinically rated for wheezing severity by the Pulmonary Index (PI) score at regular intervals during the study. Discharge home was based on clinical improvement during treatment in the PED; patients who were admitted to the hospital were removed from the study. Follow-up was conducted the fifth day after discharge from the ED either by clinic visit or by telephone. Patients were assessed for symptomatic improvement and relapse or clinical deterioration during the study period by a clinician blinded to group assignment. Forty-two children participated in this pilot study. There were no significant differences between the IMD and OP groups for gender or age. Mean ages were: 82 months (SD 46 months), IMD group; 63 months (SD 36 months), OP group. Clinical progress (based on PI) with treatment in the PED was the same in both groups: pretreatment median, PI = 6; PED discharge median, PI = 2. None of the study patients were hospitalized during the follow-up period, and all reported symptomatic improvement since initial treatment. The data of this pilot study suggest that IMD may be a feasible alternative to OP for treatment of acute wheezing episodes in children with asthma. IMD provides sufficient treatment to prevent clinical deterioration within 5 days after initial therapy for mild to moderate pediatric exacerbations of asthma that are responsive to nebulized medications.     

Failure of platelet angiotensin II binding to predict pregnancy-induced hypertension

OBJECT: Nimodipine therapy has become a standard component of the treatment regimen used in patients with aneurysmal subarachnoid hemorrhage (SAH). Its prescribed use at 60 mg every 4 hours for 21 days is based on reputable, randomized prospective studies. However, because only 20 to 30% of patients with SAH suffer clinical cerebral vasospasm, it is clear that most patients do not actually need the drug. Of course, this fact is not evident until several treatment days have passed. It is common practice, without well-documented consequences, to terminate nimodipine therapy before 21 days in certain clinical circumstances. The aim of this study was to evaluate the effectiveness of abbreviating the duration of nimodipine treatment in the setting of a good-grade aneurysmal SAH. METHODS: A retrospective clinical review was made of 90 consecutive patients who experienced a Hunt and Hess Grade I through III aneurysmal SAH and were treated with nimodipine for 15 days or less. CONCLUSIONS: None of the patients studied suffered a delayed neurological deficit as a result of the abbreviated course of nimodipine.     

Effect of sijunzi decoction on motilin and pharmacokinetic characteristics of tetramethylpyrazine in rat model of spleen deficiency syndrome]

Glucagon does not supplant epinephrine or other standard therapies for the initial treatment of severe allergic reactions and anaphylaxis. However, in selected cases, glucagon appears to play a potentially lifesaving role as a supplemental therapy.