Clonidine prolongs canine tetracaine spinal anaesthesia

Using a randomized blind cross-over design, the comparative efficacy of clonidine in prolonging tetracaine spinal anaesthesia was studied in six mongrel dogs. Lumbar subarachnoid injections (1 ml) of: tetracaine 4 mg with clonidine 150 micrograms, tetracaine 4 mg with epinephrine 200 micrograms, tetracaine 4 mg, clonidine 150 micrograms, epinephrine 200 micrograms, and five per cent dextrose in H2O (vehicle) were administered randomly to each animal at 5-7 day intervals. Subarachnoid tetracaine produced a motor blockade of 186 +/- 58 (mean +/- SEM) min. Both clonidine and epinephrine produced a similar prolongation of tetracaine motor blockade, 135 per cent (p less than 0.01) and 116 per cent (p less than 0.05) respectively, compared with tetracaine alone. No motor blockade was observed in dogs receiving clonidine, epinephrine or five per cent dextrose in H2O. The addition of clonidine to tetracaine spinal anaesthesia produced a significant increase in duration of sensory blockade, 56 per cent (p less than 0.01) and 107 per cent (p less than 0.01) respectively, when compared to tetracaine with and without epinephrine. Subarachnoid clonidine alone produced a sensory blockade of 76 +/- 17 minutes, while only one animal receiving subarachnoid epinephrine had a sensory blockade (40 minutes). No neurologic deficits were observed in any of the animals. The study concludes that during spinal anaesthesia with tetracaine in dogs, clonidine is as effective as epinephrine in prolonging motor blockade, but is more effective in prolonging sensory blockade.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.     

Is antibiotic prophylaxis necessary for routine urodynamic investigations? A controlled study in 100 patients

The value of a prophylactic antibiotic before a routine cystometrogram has been assessed in a controlled trial of 100 patients. The infection rate was low and not statistically different in both groups. Subsequent symptoms of dysuria and haematuria had a mechanical aetiology.     

Brain uptake of α-[14C]methyl-para-tyrosine in the rat

The blood-brain permeabilities of L-[³H]tyrosine and the tyrosine hydroxylase (TH) inhibitor β-[¹⁴C]methyl-para-tyrosine ([¹⁴C]AMPT) were determined in rat striatum, a brain region rich in TH activity, and in other brain regions containing relatively little TH activity. In striatum, the unidirectional clearance rate (K₁) for L-[³H]tyrosine (6.2 ml hg- ^?1 min^?1) was significantly greater than the rates for L-[¹⁴C]AMPT (2.8 ml hg^?1 min^?1) and D-[¹⁴C]AMPT (0.8 ml hg^?1 min^?1). The apparent volume of distribution (V_f) for L-[¹⁴C]AMPT in striatum (72.5 ± 4.0 ml hg-¹) did not differ from the V_f in other brain regions. The homogeneous distribution of L-[¹⁴C]AMPT in rat brain indicates that labeled AMPT is unsuitable for the study of TH in vivo by quantitative autoradiography. © 1994 Wiley-Liss, Inc.     

Crown of microfilaments in the extending cytoplasmic processes of medulloblastoma glial progenitors.

Microfilaments and microtubules play a part in the extension of neuronal processes but their roles in the formation of glial processes have not yet been determined. The objectives of this study were to determine the organization of microfilaments in differentiating glial progenitors (RB2 cells) and to study the effects of microfilament or microtubule disruption on process extension. Intense F-actin staining (crown of microfilaments) was observed at the leading edge of a small extending conical tip in differentiating RB2 cells, but was absent in process-bearing TE671 rhabdomyosarcoma cells. No significant difference was noted in the mean number of TE671 cells with processes treated with a microfilament disrupter from that of similarly treated controls. In contrast, a significant difference was noted in the mean number of RB2 cells with processes after microfilament disruption treatment from that of similarly treated controls. Microtubule disruption arrested extension and caused process retraction in both cell types. The results of this study demonstrate that microtubules play an equally important part in the extension and stabilization of the RB2 and TE671 processes. Moreover, the crown of microfilaments concentrated in the glial RB2 process (and not in the TE671 process) may be critical to its extension during differentiation.     

A multi-centre phase two study of intravesical epirubicin in the treatment of superficial bladder tumour

Epirubicin (4'-epi-adriamycin) was used in the treatment of widespread superficial carcinoma of the bladder. Thirty-seven patients received 50 mg in 50 ml of saline retained for 60 min. There was an overall response rate of 59% but this was of short duration. Thirty percent of patients progressed despite therapy. Therapy was associated with an incidence of side effects which necessitated therapy withdrawal in 12 (32.4%) patients. It is concluded that epirubicin, in the dose used in this study, cannot be recommended for routine intravesical chemotherapy and that further studies, at a reduced dosage, are necessary to evaluate this agent.     

Urinary kallikrein excretion in chronic renal failure: relationship to blood pressure and the acute effect of captopril

Previous studies of the renal kallikrein-kinin system in chronic renal failure (CRF) have given conflicting results. We have assessed activity of this vasoactive hormone system in CRF and investigated a possible relationship to hypertension in patients with CRF: 24-hour urinary kallikrein excretion (UKa) was measured in 22 patients with CRF (9 normotensive and 13 hypertensive) and 11 healthy controls. Age, sex, urine volume, and urinary sodium excretion were similar in each group. Compared with controls, UKa was reduced in both normotensive and hypertensive patients with CRF, with no difference between CRF groups. The reduction in UKa in CRF was less than the reduction in glomerular filtration rate (GFR), as assessed by endogenous creatinine clearance (CCr). When UKa was divided by CCr, UKa/mL CCr was therefore increased, to a similar extent, in both normotensive and hypertensive patients with CRF. This suggests that release of renal kallikrein from functioning nephrons is increased in CRF. The results do not support a role for deficient kallikrein release in the genesis of hypertension in CRF, as previously suggested; however, these abnormalities could be relevant to other aspects of renal function in CRF. The converting-enzyme inhibitor, captopril, was given to 5 patients with CRF, hypertension, and low UKa. Introduction of captopril was followed by a further reduction in UKa in all subjects. Captopril is known to inhibit kininase II, the principal enzyme involved in degradation of kinins; this potentiating effect may be counteracted by a reduction in renal kallikrein release and hence in kinin generation.