Bromism caused by mix-formulated analgesic injectables.

Bromism, chronic bromide intoxication, can be caused by a variety of medicines, but bromism due to pain-relieving injectable medications has not been reported. In this study, the methods used were internet searching on bromide-containing injectables available in Taiwan and the first case report of bromism due to mixed-formulated injectable medication. Many analgesic/antipyretic and antihistamine injections containing bromides are still being used in Taiwan. They contain sodium bromide up to 1000 mg/ampoule or calcium bromide up to 800 mg/amp. A 25-year-old female suffered from forgetfulness and unstable gait after long-term frequent injections of a preparation to relieve head and neck pain. Blood tests showed hyperchloremia (171 mEq/L) and a negative anion gap (-48.7 mEq/L). Serum bromide measured 2150 mg/L. She recovered completely in 3 days with saline treatment. Many bromide-containing injections are still being used in Taiwan. Clinicians should keep alert on this issue to avoid iatrogenic bromism or making misdiagnoses.

A randomised clinical trial of oral steroids in the treatment of carpal tunnel syndrome: a long term follow up.

OBJECTIVES: To determine the efficacy of a two week and a four week course of oral steroids in the conservative treatment of carpal tunnel syndrome. METHODS: 109 patients with carpal tunnel syndrome were randomly divided into two treatment groups: (1) two weeks of prednisolone 20 mg daily followed by two weeks of prednisolone 10 mg daily (n = 53); (2) two weeks of prednisolone 20 mg daily and two weeks of placebo (n = 56). A symptom questionnaire was used to rate the five major symptoms of carpal tunnel syndrome (numbness, pain, weakness/clumsiness, tingling, and nocturnal awakening) on a scale of 0 (nil) to 10 (severe); the resulting global symptom score was used to evaluate the efficacy of treatment. Assessments were made at baseline and at one, three, six, nine, and 12 months. Electrodiagnosis was repeated at the end of the study to validate improvement. RESULTS: In an intention to treat analysis at the end of the study, improvement in the four week treatment group was achieved in 66.0% of the patients after one month and in 49.0% at the end of the study; in the two week treatment group, the respective values were 48.2% and 35.7%. In the four week treatment group, 51% were considered treatment failures (including those lost to follow up, receiving surgery, or with mild or no improvement), compared with 64.3% for the two week group. Though the percentage improvement was higher in the four week group, the difference did not reach a statistical significance. Persistence of improvement was 74.2% in the four week group v 74.1% in the two week group, suggesting no difference in the long term effect. Efficacy analysis showed no significant difference in global symptom score reduction between the two groups. Follow up electrodiagnosis showed significant improvement in all measured variables except for the amplitude of compound muscle action potentials. CONCLUSIONS: Short term low dose oral steroid are effective treatment for carpal tunnel syndrome. The dose of steroids and the duration treatment are not key determinants of efficacy.

Comparison of motor conduction techniques in the diagnosis of carpal tunnel syndrome.

OBJECTIVE: To compare the sensitivities of motor wrist-to-palm (W-P) conduction velocity and two median-ulnar motor latency differences with that of sensory W-P conduction velocity in the diagnosis of carpal tunnel syndrome (CTS). METHODS: This study included 116 consecutive patients with CTS (160 hands) referred for evaluation and 100 volunteers who served as controls. Median motor and sensory nerve responses with wrist and palm stimulation allowed for the determination of motor and sensory W-P CV (W-P MCV and SCV). Two motor distal latency (MDL) differences between the median-thenar and ulnar-hypothenar (M-U) muscles and between the median-second lumbrical and ulnar-interossei muscles (2L-INT) were measured and calculated. The mean values of controls plus or minus 2.5 SD served as the normal limits. RESULTS: Among the 160 hands with suspected CTS, 11 (6.88%) had normal electrodiagnostic studies and 149 (93.1%) had at least one abnormal electrodiagnostic study. Among the 149 hands with an abnormality, 139 (86.88%) had abnormal W-P MCV and 129 (80.63%) had abnormal W-P SCV. The sensitivity for 2L-INT was 77.5%, and it was 70% for M-U, 68.75% for median MDL, and 73.75% for sensory distal latency. Combining W-P MCV and W-P SCV allowed for the detection of abnormalities in 147 hands (91.88%) and yielded a markedly improved diagnostic rate compared with W-P SCV alone. CONCLUSION: Motor W-P conduction study is more valuable and no more difficult than sensory W-P conduction study for the diagnosis of CTS. In patients with suspected CTS in whom the results of conventional nerve conduction studies are normal, studying both motor and sensory W-P conduction increases the diagnostic yield.

Time course of c-FOS expression in status epilepticus induced by amygdaloid stimulation.

Decaying of c-FOS immunoreactivity (FIR) was studied in adult rats with 1 h self-sustaining limbic status epilepticus (SSLSE) induced by amygdaloid electrical stimulation. Rats that failed to enter SSLSE showed localized FIR in the ipsilateral limbic cortex, neocortex, and amygdala. FIR became bilaterally extensive, including the hippocampal formation 0.5 h after SSLSE. It decreased gradually between 2 and 6 h and returned to basal levels around 1 day. Neocortical FIR in clonic SSLSE persisted longer than in other types of SSLSE. We demonstrate for the first time that FIR in SSLSE lasts much longer than several hours, its decaying is related to the seizure behavior, and absent or weak FIR at the hippocampal formation is associated with failed SSLSE entry.

Neuropathology of limbic status epilepticus induced by electrical stimulation of naive rats.

Neuronal damage in relation to the duration of seizure was studied in limbic status epilepticus (SE) induced by electric stimulation of naive rats. Adult Sprague-Dawley rats were stimulated at the right amygdala to induce SE. To stop the seizures, diazepam was given to different groups of rats at 0.5 h (n = 4), 1 h (n = 6), 2 h (n = 6), and 3-4 h (n = 8) of SE. Eighteen hours after the end of SE, the rats were perfusion fixed. Naive (n = 6) and sham-operated (n = 4) rats served as controls. Horizontal paraffin sections were stained with acid fuchsin and cresyl violet. Neuronal damage was absent after 30 min of SE. Status epilepticus of 1 h or longer duration regularly caused neuronal damage to the cerebral cortex, thalamus, hippocampus, amygdala, and pars reticulata of the substantia nigra. Damage in the cerebral cortex predominated in the entorhinal, temporal, and pyriform regions. In the hippocampus, the dentate hilus was most severely affected, followed by CA3 and CA1. Damage to the dentate granule layer was mild. Further studies of the pathophysiology of excitotoxicity may help to protect patients from sequels of status epilepticus such as neuronal damage and epilepsy.

Molecular mechanisms of clarithromycin resistance in Helicobacter pylori.

Combination antibiotic therapy for Helicobacter pylori has now become the standard means of treating peptic ulcer diseases. Clarithromycin is a newly adopted antibiotic for H. pylori eradication. However, resistance to clarithromycin reduces the efficacy of clarithromycin-containing regimens. We explored mechanisms of clarithromycin resistance by evaluating H. pylori for macrolide resistance mechanisms reported in H. pylori and other bacteria. Degenerate polymerase chain reaction analysis of the H. pylori genome failed to yield products homologous to methylase, a drug inactivation enzyme, or efflux pumps. Clarithromycin selection in Escherichia coliNM522, transformed with an expression library that was constructed with genomic DNA from a clarithromycin-resistant strain of H. pylori, revealed six clones that conferred clarithromycin resistance consistently after retransformation. Southern hybridization and DNA sequencing revealed that four of the six clones contained the same locus. Comparison of DNA and amino acid sequences showed that the 1.3-kb DNA fragment had significant homology to the 3-oxoadipate CoA-transferase subunit A (yxjD) and subunit B (yxjE) of Bacillus subtilis. However, the clarithromycin inactivation assay and knockout mutation analysis showed that the gene increased clarithromycin resistance in E. coli, but not in H. pylori. In contrast, sequencing of the 23S rRNA gene in six clarithromycin-resistant H. pylori clinical isolates revealed an A to G transitional mutation at position 2515 of the 23S rRNA gene in all isolates. Natural transformation with the 23S rRNA gene from resistant strains conferred clarithromycin resistance in clarithromycin-sensitive strains. We conclude that the 23S rRNA mutation is sufficient to confer clarithromycin resistance and that it is the major mechanism of clarithromycin resistance in H. pylori.

Anti-GT1b and anti-GM1 antibodies can increase after stroke but neither is associated with late post-apoplectic epilepsy.

The role of antiganglioside antibodies (AGAs) in late post-apoplectic epilepsy (LPAE) was studied. Serum AGAs from 8 patients with large lobar infarctions were serially checked for 2.5 months. Sera from another 30 patients with fronto-temporoparietal (FTP) or frontal (F) infarction were obtained 3 months to 3 years after a stroke for AGA analysis. These 30 patients were followed up for 3 years following their strokes to determine if LPAE developed. Results showed that 7/8 patients with large lobar infarction showed increase in either anti-GT1b or anti-GM1 (IgM or IgG) within a few weeks, but levels returned to the baseline 2-3 months after stroke. LPAE occurred in 9/21 patients with FTP infarction and 5/9 with F infarction. There was no difference in AGAs among patients with FTP and F infarctions. Pooled data from these 2 groups showed no correlation between AGAs and LPAE. These data document for the first time that anti-GT1b and anti-GM1 antibodies can transiently increase after stroke, but their late titers are not associated with LPAE.

Dentate hilar cell damage in electric stimulation-induced limbic status epilepticus.

The study explored for the first time the quantitative dentate hilar cell damage in relation to the duration of limbic status epilepticus (SE) induced with electric stimulation on naive rats. SE was induced in adult S-D rats with electric stimulation delivered through a stimulating/recording electrode targeted at the right amygdala. Once SE was established, no further stimulation was given. The rats were treated with diazepam at various times to stop SE, and perfused 18 hours later. Naive and sham operated rats served as controls. Horizontal paraffin sections at the level of the ventral hippocampus were stained with acid fuchsin/cresyl violet. Irreversibly damaged neurons in the right dentate hilus were counted. Neuronal damage was absent with sham operation (n = 4, p > 0.05) and 30-min SE (n = 4, p > 0.05), but it became significant with 1 hour (n = 6, p < 0.05) and longer durations (n = 14, p < 0.05) of SE, compared with the naive controls (n = 10). The severity of SE-induced neuronal damage was not related to the current intensity, induction time, stimulation intensity, or number of class 3-5 seizures. We demonstrate for the first time the relation between seizure duration and the severity of dentate hilar cell damage in limbic SE induced by electric stimulation of naive rats. Further study of this model may elucidate the pathophysiology of SE and improve patient care.

Leptomeningeal malignant melanoma arising in neurocutaneous melanocytosis: a case report.

A rare case of histology-proved giant congenital melanocytic nevus (GCMN) with symptomatic leptomeningeal melanocytosis is reported. A 26-year-old man had had a large patch of pigmented nevus over his back and left arm since birth. He had begun to have seizures as well as symptoms and signs of increased intracranial pressure about six months before admission. Serial computed tomography of brain showed hydrocephalus, diffuse leptomeningeal enhancement and multiple well-enhanced, rapid-growing nodules on the surface of the cerebellum and left parietal lobe. Magnetic resonance imaging (MRI) revealed T1 shortening of leptomeninges on precontrast T1 weighted imaging. Skin biopsy was done twice and showed intradermal nevus. Biopsy on one of the intracranial nodules revealed malignant melanoma arising in the melanocytosis. He died one year after the onset of neurologic symptoms. For early diagnosis of neurocutaneous melanocytosis, we suggest 1) MRI, and 2) leptomeningeal biopsy in patients with suspected leptomeningeal malignant melanoma.

Tourette syndrome and complex partial epilepsy--a case report.

Controversy exists over the pathophysiology of Tourette syndrome (TS). The case reported is a 37-year-old unmarried man suffering from both TS and complex partial epilepsy (CPE). He began to have seizures at 2-3 months of age. The CPE featured dark vision, dizziness, followed by unresponsiveness, a blank stare, occasional loss of posture control, and occasional automatism consisting of going to the toilet to urinate. TS gradually began to develop when he was 3-4 years of age. The tics were characterized by stereotypic stuttering, vocalization, hiccups, grimacing, snorting, and jerky supination of both forearms. EEG sharp waves with phase reversal at the left frontotemporal region were present but they were not related to the tics. Magnetic resonance imaging revealed atrophy of the left temporal and frontal lobes, as well as absence of normal asymmetry of basal ganglia. This case supports the theory that TS is related to the left frontal lobe, limbic system, and basal ganglia, but contradicts the hypothesis that the tics are ictal events.

Sclerotherapy on liver cirrhosis with esophageal variceal bleeding: eight years of experience.

BACKGROUND: Patients with liver cirrhosis usually die of hepatic failure and variceal bleeding. Successful treatment of the latter can reduce mortality. Sclerotherapy is one method often used. This study compared (a) the successful rate of acute bleeding control; (b) short- and long-term survival rate between those with and without treatment with sclerotherapy to evaluate the clinical benefit of sclerotherapy for liver cirrhosis patients with esophageal variceal bleeding. METHODS: Between August 1983 and December 1991, 183 cirrhotic patients with esophageal variceal bleeding receiving endoscopic injection sclerotherapy (EIS) was compared with 123 patients without sclerotherapy treatment retrospectively. The severity of underlying liver disease was classified using a modified Child's classification. Sclerotherapy was done within 48 hours after active bleeding in the sclerotherapy-treated group, while the medical treatment group received Sengstaken-Blakemore (SB) tube or pitressin infusion only. RESULTS: Successful rate of acute bleeding control was 81.63% (120/147) in the EIS group and 59.35% (73/123) in the medical treatment group. The worse the hepatic function of the patients, the lower the success of acute bleeding control in both groups. Fifty subjects (74.63%) had varices eradicated in 67 sclerotherapy treatment patients with regular follow-up. Patients receiving EIS had a better long-term survival than those without treatment. Benefit of EIS on long-term survival was more significant in Child B patients and less in Child C and Child A patients. Death from variceal bleeding was lower in the EIS group than in the medical treatment group (32% vs 62.6%). Complications of EIS were rare. Eight patients died of aspiration pneumonia, spontaneous bacterial peritonitis or acute renal failure after sclerotherapy, and most were Child B and C patients. Sixteen patients had esophageal stricture. Four needed dilatation treatment. CONCLUSIONS: The sclerotherapy-treated group had a higher control rate of acute bleeding and lower mortality rate from esophageal variceal bleeding compared with the medical-treated group. The procedure prolonged long-term survival in Child B patients but did so less frequently in Child A and Child C patients. The incidence of complications was low. As a whole, EIS is a safe and efficient method for control of esophageal variceal bleeding.

Sclerotherapy for esophageal variceal bleeding in advanced hepatocellular carcinoma: an 8-year experience in Taiwan.

Between August 1983 and December 1991 at the Taichung Veterans General Hospital, Taiwan, 65 advanced hepatocellular carcinoma (HCC) patients with esophageal variceal bleeding received endoscopic injection sclerotherapy (EIS) and 60 such patients received conservative medical treatment without EIS. The rate of successful control of acute bleeding was 72.5% (27/40 patients) in the EIS group and 56.7% (34/60 patients) in the non-EIS group. The rebleeding rate was lower in the EIS group than in the non-EIS group (26.9% vs 73.5%). Thirty-one of the EIS and 44 of the non-EIS treatment patients, mainly Child's B and C patients, died within 2 months after the first bleeding. In the short term, EIS decreased the mortality due to esophageal variceal bleeding, but the survivors still had to face hepatic failure and tumor growth. Thus, benefits of EIS were noted on short- but not on long-term survival. The mean survival times were 2.38 months for the EIS group and 1.79 months for the non-EIS group. Since EIS had no beneficial effects on long-term survival it is doubtful whether sclerotherapy applied to esophageal variceal bleeding in patients with advanced HCC would be worthwhile, as the endoscopic procedure would only add to their suffering.