Liver carcinogenesis by methyl carbamate in F344 rats and not in B6C3F1 mice.

Short-term and long-term carcinogenicity of methyl carbamate (MCB) was evaluated in F344 rats and B6C3F1 mice. In experiments lasting 6, 12, and 18 months, MCB was given in water by gavage to groups of 10 male and 10 female rats at 0 or 400 mg/kg body weight, 5 days per week, and to similar groups of mice at 0 or 1,000 mg/kg. At 6 months, MCB induced atypical mitoses, cytologic alterations, cytomegaly, pigmentation, necrosis, and neoplastic nodules of the liver in rats. At 12 and 18 months, carcinomas of the liver were induced by MCB in 80-90% of male rats and in 60-80% of female rats. None was observed in control rats or in mice. In the 2-year studies, MCB was given to groups of 50 male and 50 female rats at 0, 100, or 200 mg/kg and to similar groups of mice at 0, 500, or 1,000 mg/kg, 5 days/week. Chronic focal inflammation, cytologic alteration, hyperplasia, and neoplastic nodules and carcinomas (200 mg/kg groups only) of the liver were induced by MCB in rats. Liver tumor incidence data for combined experiments in rats were: males--5% in controls, 0% in 100 mg/kg group, 14% in 200 mg/kg group, and 77% in 400 mg/kg group; females--5% in controls, 0% in controls, 0% in 100 mg/kg group, 12% in 200 mg/kg group, and 63% in 400 mg/kg group. MCB was not shown to be carcinogenic in mice.     

An improved method of flexible endoscopic creation of tracheoesophageal fistula for voice restoration

We present improvements of a previously reported method of tracheoesophageal puncture for voice restoration in postlaryngectomy patients. Our method utilizes a flexible endoscope to enable the tracheoesophageal puncture to be made under direct visualization using only local anesthesia and intravenous sedation. After 3 days, the created tracheoesophageal fistula tract is mature enough to allow placement of a voice prosthesis in the office. This allows the entire procedure to be performed in an outpatient setting with minimal risk. Received: 24 October 1996/Accepted: 24 January 1997     

Involvement of Cerulospinal Glutamatergic Neurotransmission in Fentanyl-induced Muscular Rigidity in the Rat

Background: Investigators in the authors' laboratory previously established the critical participation of the cerulospinal noradrenergic pathway in muscular rigidity elicited by fentanyl. The identification of colocalization of glutamate with tyrosine hydroxylase in most locus ceruleus neurons suggests a role for cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity. This suggestion and the subtype(s) of glutamate receptors involved were investigated here.

Methods: Electromyographic signals activated by bilateral microinjection of 2.5 micro gram fentanyl into the locus ceruleus were recorded differentially from the left sacrococcygeus dorsi lateralis muscle of adult male Sprague-Dawley rats. The effect of intrathecal administration at the lower lumbar spinal cord of various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or agonists on this index of muscular rigidity was studied. Rats were under mechanical ventilation, and intravenous infusion of ketamine (30 mg [center dot] kg sup -1 [center dot] h sup -1) was maintained until 10 min before fentanyl was administered.

Results: Microinjection of fentanyl bilaterally into the locus ceruleus increased the root mean square and decreased the mean power frequency values of electromyographic signals. The efficacy of fentanyl to elicit muscular rigidity in this manner was significantly reduced by previous intrathecal administration of either 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), D-(-)-2-amino-5-phosphonovaleric acid (AP5), or (+/- (CPP). Intrathecal administration of kainic acid or NMDA also resulted in significant electromyographic activation.     

Statistical MUNE: A comparison of two methods of setting recording windows in healthy subjects and ALS patients

OBJECTIVE: To address the issue as to how best to perform statistical MUNE, we applied two different approaches and compared results in healthy subjects and ALS patients. METHODS: Twelve normal subjects (women 8, mean age 52years) and 11 ALS patients (women 4, mean age 54years) underwent two consecutive MUNE studies, which differed in terms of setting and modifying the recording window. These are referred to as the 'expansion' and 'narrowing' methods, respectively. Size-weighted average (Av) SMUP and MUNE values were obtained using the two methods, and compared in control and patient groups. RESULTS: Expansion method-derived Av SMUP sizes and MUNE values differed only slightly from those obtained using the narrowing method in healthy subjects, whereas the narrowing method resulted in significantly larger Av SMUP sizes and smaller MUNE values than the expansion method in ALS patients (Wilcoxon signed ranks test, p=0.003). The sizes of tested areas (mean+/-SD) were significantly larger for the narrowing method than the expansion method in both subject groups with much greater difference in ALS patients; 9.6+/-3.1% vs. 7.9+/-1.7% in healthy subjects and 16.1+/-5.1% vs. 11.2+/-3.0% in ALS patients (Student t-test, p<0.01). CONCLUSIONS: The present study shows, unlike that found in normal subjects, that the results of statistical MUNE in ALS patients are heavily dependent on the approach used to set and modify recording windows. SIGNIFICANCE: The expansion method using a 10%-sized window is likely to suffer from systemic errors due to the ceiling effect and the sampling of artifactually small motor units in ALS patients. The authors recommend that the narrowing method be considered as an alternative that avoids these problems.     

The hepatitis B immunization programme in Singapore

A voluntary immunization programme to prevent perinatal transmission of hepatitis B virus (HBV) infection in Singapore was implemented on 1 October 1985 as an integral component of the national childhood immunization programme. Up to April 1988, a total of 68,845 mothers who attended government maternal and child health clinics were screened for the disease. Of these, 2432 (3.5%) were positive for hepatitis B surface antigen (HBsAg) and 904 (1.3%) for hepatitis B e antigen (HBeAg). Virtually all the babies born to carrier mothers completed the full immunization schedule; and in addition, those of HBeAg-positive mothers were given a dose of hepatitis B immunoglobulin at birth. The hepatitis B immunization programme was extended on 1 September 1987 to cover all newborns. About 90% of the 15,943 babies delivered in government institutions from September 1987 to April 1988 were immunized at birth, with the subsequent doses being administered at maternal and child health clinics at 4-6 weeks and 5 months later. More than 85% of the children given the full course of plasma-derived and yeast-derived hepatitis B vaccine from birth continued to have protective antibody to HBV two years after immunization. The programme is being closely monitored to assess the duration of immunity and the need for booster doses, while seronegative adults are also being encouraged to be vaccinated.     

An algorithm for the treatment of pain in advanced cancer

An algorithm is presented that has been developed over the past three years to provide pain relief in advanced cancer. The hospital records of 92 patients were reviewed to evaluate the validity of the algorithm. The algorithm is as follows: the 24 hour oral consumption of opioids was converted to sustained release morphine. If ineffective usually over 360 mg daily the total 24 hour oral dose was divided by 6 to convert to I.V. If this was ineffective, usually over 10 mg/hr of morphine, the intravenous dose was divided by 10 and infused epidurally. Local anesthetic was added for plexus involvement. After four days, the patient was weaned from local anesthetic solution. If sharp pain or pain to movement persisted, 6% phenol in 1 to 2 ml aliquots was injected every 8-12 hours to a total of 5-8 ml. While the conversion from intravenous to epidural morphine was 10:1 that from epidural to intravenous was only 1:3. Intravenous dose converts directly to the subcutaneous. The conversion from intravenous to oral is 1:3. There view showed that the dosages at which the conversions were made varied considerably. The reasons for the wide variation are presented. In summary the algorithm is a good practical guide for treatment of cancer pain.     

Potential problem with fluorescence polarization immunoassay cross-reactivity to vancomycin degradation product CDP-1: its detection in sera of renally impaired patients

During the development of a homogeneous immunoassay for the antibiotic vancomycin, we observed in certain patient samples a quantitation difference between the enzyme multiplied immunoassay technique (EMIT) method and the comparison method, fluorescence polarization immunoassay (FPIA). This prompted us to evaluate the integrity of vancomycin in samples from renally impaired patients. Since it has been reported in the scientific literature that vancomycin degrades into an antibiotically inactive crystalline degradation product (CDP-1) in vitro, we developed high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) methods to determine whether CDP-1 is present in patient sera. HPLC and LC/MS analysis on samples from renally impaired patients positively identified CDP-1 in fresh samples. Next, we tested the cross-reactivity of three currently available vancomycin immunoassays, radioimmunoassay (RIA) FPIA, and EMIT, to CDP-1 prepared in our laboratory. Our data suggest that CDP-1 is recognized by FPIA and RIA, both polyclonal antibody-based methods, but not by EMIT, which uses a monoclonal antibody.     

Acute post-streptococcal glomerulonephritis followed shortly by acute rheumatic fever

A 16 year old girl with post-streptococcal glomerulonephritis developed acute rheumatic fever 19 days afterwards. Previous publications on concurrent post-streptococcal glomerulonephritis and acute rheumatic fever are reviewed.     

High-dose VP-16 with intermediate-dose cytosine arabinoside in the treatment of relapsed acute nonlymphocytic leukemia

Summary In a study of 11 adult patients with acute nonlymphocytic leukemia (ANLL), infusion therapy with high-dose VP-16 and intermediate-dose cytosine arabinoside was administered. Response was assessed with reference to bone marrow aspirations performed on days 1; 12, 13, or 14; and 21 of treatment. All 7 of the patients with ANLL in relapse achieved marrow hypoplasia, and 3 of them achieved complete response. LFTs were elevated in most patients but no evidence of hepatocellular necrosis was observed. It is concluded that the value of VP-16 in ANLL may have been underestimated in the past because of inadequate dosing.Abbreviations ANLL acute nonlymphocytic leukemia - CGL chronic granulocytic leukemia - DNR daunorubicin - VNC vincristine - ID Ara-C, intermediate-dose Ara-C (500 mg/m² for 12 doses) - HD Ara-C, high-dose Ara-C (3 g/m² for 12 doses) - SGGT serum glutamic transaminase - LDH lactic dehydrogenase - SGOT serum glutamic oxaloacetic transaminase     

Cerebral amyloid angiopathy and spontaneous intracerebral haemorrhage. Report of a sporadic case in a young Chinese.

A 49-year-old Chinese male with spontaneous intracerebral haemorrhage due to cerebral amyloid angiopathy is presented. This is the first case reported in the Chinese population, and the youngest patient described without a family history or associated mental disorder.