Inhibitory effects of okadaic acid on rat uterine contractile responses to different spasmogens

Summary— In the present study, we examined the effects of okadaic acid, a selective inhibitor of type 1 and 2A protein phosphatases, on the mechanical responses evoked by oxytocin, K⁺- and Na+-modified solutions and ouabain in estrogen-primed rat myometrium. Oxytocin elicited a rapid, phasic contraction followed by rhythmic oscillations. The phasic response was partially resistant to the absence of external Ca²⁺. Okadaic acid (1 μM) and the L-type calcium channel blocker nifedipine (1 μM) abolished the oscillatory component and reduced the initial, phasic response to about 80% of the control response. High K⁺ (60 mM) solution, ouabain (1 mM), K⁺-free medium and low Na⁺ (25 mM) solution induced extracellular Ca²⁺-dependent biphasic responses composed by an early rapid (KCl, ouabain and K⁺-free solution) or slower developed (25 mM Na⁺ solution) phasic contraction followed by a sustained increase in tension. Okadaic acid and nifedipine, alone or in combination, abolished or decreased similarly the contractile response evoked by these stimulants. The okadaic acid- and nifedipine-insensitive responses to ouabain, K⁺-free and low Na⁺ solution were enhanced by increasing the extracellular concentration of Ca²⁺ in the medium and were inhibited in a dose-dependent manner by amiloride (0.05–0.5 mM). These data suggest that, in estrogen-primed rat uterus, dephosphorylating mechanisms by OA-sensitive protein phosphatases play an important role in regulating myometrial contractions elicited by Ca²⁺ entry through voltage-sensitive Ca²⁺ channels.     

Thoracic spine: percutaneous trephine biopsy

Forty-one percutaneous trephine biopsies of thoracic vertebral bodies or disks from T-3 to T-12 were performed under fluoroscopic guidance without complications. Biopsy technique was improved by a new set of trephine needles using a procedure similar to vascular catheterization and specific prone-oblique positioning of the patient. On a 35 degrees prone-oblique view, the heads (dorsal extremities) of the ribs determine the direction of puncture. Both pleura and spinal canal are easily recognized and avoided. Of 40 cases, there were 31 true-positive results, six contributory results, and three false-negative results. Percutaneous biopsy of the thoracic spine with this technique is a safe, rapid, and reliable procedure.     

Gianturco expandable metallic biliary stents: results of a European clinical trial

Eleven patients with benign strictures (after choledochojejunostomy, n = 10; chronic pancreatitis, n = 1) and 16 with malignant biliary strictures (cancer of the pancreas, n = 7; cholangiocarcinoma, n = 5) were treated with a self-expanding metallic biliary stent. The patients with benign disease had failed treatment with surgical reconstruction and transhepatic balloon dilation. All patients had immediate relief of jaundice and cholangitis. In a follow-up period of 6-21 months, nine of the 11 patients with benign disease had no difficulties with infection, pruritus, or recurrent jaundice. In patients with malignant strictures, the stent produced relief of biliary obstruction unless recurrent tumor invaded the bile ducts. With careful patient selection, this stent appears to be useful in the management of biliary obstruction, particularly in benign disease.     

Acute epiphyseal osteomyelitis in children

Nine children over 20 months of age had acute osteomyelitis of the epiphysis of a long bone. The clinical features varied, but all of the patients had pain at the infected site and an elevated erythrocyte sedimentation rate. The distal femur was involved in seven cases, the proximal tibia in two, and the proximal humerus in one. In two patients there was a contiguous metaphyseal lesion, while the other seven patients (eight sites) had lesions limited to the epiphysis. Bone scintigraphy clearly identified the infected sites in all seven patients in whom it was performed, and allowed an early diagnosis in four cases. Radiographs showed a lytic lesion of the epiphysis that corresponded to the scintigraphic findings in all cases. The vascular supply to the epiphysis and the microscopic structure of the epiphyseal venous sinusoids provide locations that favor lodgement of blood-borne organisms. The epiphysis of the child should be recognized as another site of hematogenous osteomyelitis.     

Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination

Background

In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use.

Methods

We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage.

Results

With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin.

Conclusions

Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts.     

Bedwetting and behavioural and/or emotional problems

Objective: To assess the link between enuresis nocturna and the severity of behavioural and/or emotional problems in Dutch children and the course of these problems. Setting: West-Mine Region in the Netherlands. Subjects and methods: Prospective cohort study involving 66 of the 80 bedwetting children from all 1652 children born in 1983 in this region. After 1 y, contact was still possible with 64 of the enuretics. We used the Dutch version of the Child Behaviour Checklist (CBCL) and a questionnaire about bedwetting. Results: The mean T-score for Total Problems (CBCL score) in 1992 (M1; mean age 8. 6) was 52. 1, and 1 y later was 49. 2 (M2). There was no significant difference in the CBCL scores for Ml, M2 and a matching group from the Dutch CBCL norm population, either in the group who remained wet or in the group who became dry. There were no differences between the sexes. There was no link between the severity of behavioural and emotional problems and the frequency of bedwetting. However, more children with bedwetting than expected were in the clinical range. Conclusion: There was no difference in behavioural and/or emotional problems between the first and the second measurement and the matching group from the CBCL norm group. There were no differences in behavioural and/or emotional problems between primary and secondary bedwetters, nor were there any consequences related to the frequency of bedwetting.