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.     

Growth hormone resistance in uremia

Growth retardation is a major complication in children with uremia. Protein restriction, calorie deficit, metabolic acidosis, renal osteodystrophy, and endocrinologic disturbances contribute to the growth failure. The effect of these factors on growth retardation can be attenuated in part by therapy with vitamin D metabolites, adequate nutrition, alkalization, and dialysis. Linear growth in children with uremia is markedly retarded despite normal or increased levels of circulating serum growth hormone. An increased growth hormone level in children with uremia is due to normal growth hormone secretion from the pituitary gland and impaired growth hormone clearance in the kidney. However, the elevated growth hormone level does not lead to a commensurate rise in serum insulin-like growth factor I (IGF-I); the serum IGF-I level is decreased or normal in relation to the degree of renal failure. This discrepancy suggests growth hormone resistance in the liver in uremia. Recent molecular techniques open a new era in studying the gene expression for growth hormone or IGF-I. There is no doubt today that growth hormone treatment has the beneficial effect of growth promotion in children with uremia, which also suggests endogenous growth hormone resistance in target organs or target cells in uremia.     

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.     

Risk factors for placental abruption in a socio-economically disadvantaged region.

OBJECTIVE: This study was undertaken in order to determine the risk factors for pregnancies complicated by placental abruption in a socio-economically disadvantaged region in metropolitan Adelaide. METHODS: This was a retrospective case-control study including all singleton pregnancies resulting in placental abruption between 2001 and 2005. RESULTS: The overall incidence of placental abruption was 1.0%; the overall perinatal mortality among the births with abruption was 13%. Univariate analyses showed the following significant risk factors for placental abruption: preterm pre-labor rupture of the membranes (PRE-PROM; odds ratio (OR) 4.79, 95% confidence interval (CI) 1.52-15.08), non-compliance with antenatal care (OR 2.93, 95% CI 1.06-8.90), severe intrauterine growth restriction (IUGR), and elevated homocysteine levels (OR 45.55, 95% CI 7.05-458.93). Severe IUGR was significantly more common in the abruption group compared with the control group (p = 0.032). In the multivariate analysis, PRE-PROM remained a significant independent risk factor for placental abruption. Marijuana use, domestic violence, and mental health problems were more common (borderline significance) in the abruption group. Smoking and preeclampsia were not found to be associated with placental abruption in this study. CONCLUSIONS: In this high-risk population, PRE-PROM and elevated homocysteine levels appear to represent the major risk factors for placental abruption.     

Interactions between guanabenz and clonidine in their antinociceptive effects in the rat

Based on the hot-plate algesiometric assay in conscious Sprague-Dawley rats, we observed that both guanabenz and clonidine, at a subcutaneous dose of 5 and 1 mg/kg, respectively, exhibited significant antinociceptive potencies. Paradoxical actions on the hot-plate responses, however, were exerted by guanabenz at lower doses, varying from hyperalgesia (1 mg/kg) to no effect (2 mg/kg). A pretreatment of clonidine (1 mg/kg) substantially potentiated the antinociceptive efficacy of the two latter doses, but failed to further augment the pain-suppressive action of guanabenz at 5 mg/kg. These interactive effects of the two alpha-adrenoceptor agonists suggest that they may share a common mechanism(s) in their analgesic actions.     

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.