Preparation of bupivacaine-loaded poly(epsilon-caprolactone) microspheres by spray drying: drug release studies and biocompatibility.

Poly(epsilon-caprolactone) microspheres containing bupivacaine were prepared by the spray-drying process. The average size of drug loaded microspheres was less than 3 microm in diameter, and the percentage of entrapment efficiency was 91 +/- 3%. In vitro drug release kinetic in phosphate buffer at 37 degrees C showed a hyperbolic profile, with a burst-effect during the first hour. Subcutaneous injection of bupivacaine-loaded microspheres in the back of rats caused an increase in drug concentration in plasma. Maximum bupivacaine concentration in plasma was 237 +/- 58 ng/ml at 105 h, and drug was detected in plasma for 16 days. The half-life time of the drug was increased by more than 125 times with regard to that of the drug administered in a solution by intraperitoneal injection. After 30 days of injection, a mass formed by microspheres surrounded by a thin fibrous capsule was observed. Small blood vessels and multinucleate foreign body giant cells with macrophagic function around microspheres were detected. After 60 days of injection a subcutaneous mass was also observed, which was formed of more degraded dispersed microspheres in conjunctive tissue, which had a normal structure. Thus, bupivacaine-loaded poly(epsilon-caprolactone) microspheres could be considered as a device to be used in the treatment of severe pain that is not responsive to opioids for example in cancer-related syndromes or in intractable herpetic neuralgia.     

Antibody Responses to Asian and American Genotypes of Dengue 2 Virus in Immunized Mice

The possibility of a correlation between dengue virus genotype groups and disease severity is currently under discussion. The objective of this investigation was to identify any immunogenic difference between the American and Asian dengue 2 virus genotypes through the study of antibody development (virus-binding immunoglobulin G and neutralizing antibodies) in mice. Differences in the neutralization pattern between the strains studied were observed, suggesting the presence of slight antigenic variations among them. The lack of recognition of one of the Asian genotype strains was remarkable.     

Urofacial (Ochoa) syndrome

Between 1965 and 1986 we saw 36 children with enuresis and urinary tract infection in association with “inversion” of facial expression when laughing. Urologic work-up of these patients disclosed characteristic findings of mild neuropathic bladder in all cases, with severe urinary tract damage in most of them. The clear association of distortion in facial expression and neuropathic bladder with resultant damage to the genitourinary tract should prompt urological evaluation of individuals with “inversion” of facial expression. About two thirds of the patients also had moderate to severe constipation. We suggest the term urofacial syndrome for this disorder. The occurrence of the disorder in multiple sibs, normal parents, increased parental consanguinity, and equal sex ratio indicate autosomal recessive inheritance.     

CORRELATION OF SKIN POTENTIAL AND SKIN RESISTANCE MEASURES

Simultaneous measurements of skin potential (SP) and skin resistance (SR) obtained from 20 male and 20 female adult subjects during 2 sessions held 2 to 9 days apart were used in studying (1) the correlation of change measurements and prestimulus level in the two measures, and (2) the amount of correlation between SP and SR using both simple difference and residual change scores in which the regression of poststimulus values on initial level (prestimulus) has been controlled. Correlations within Ss and correlations among Ss showed large individual variability, correlation differences between males and females, and high correlation between SP and SR change scores. Although the law of initial value (LIV) seemed to have little applicability to the measurement of electrodermal responses, the results underscored the need to control for contamination of change measures by initial level regardless of direction.     

Recovery of response to adriamycin and cyclophosphamide by lonidamine in previously treated metastatic breast-cancer patients

Thirty-one patients with metastatic breast cancer not responding or progressing after initial response to adriamycin + cyclophosphamide (AC) treatment entered a phase 11 study with oral lonidamine in association to AC. Objective clinical responses were observed in 10 patients (32%) and consisted of 1 complete + 9 partial remissions. Disease stability and progression were observed in 8 and 13 cases, respectively. These results were obtained with a marginal toxicity in addition to that already reported for AC therapy, the main additional side effect being myalgia, which was easily manageable in most cases.     

Fentanyl-induced electrocorticographic seizures in patients with complex partial epilepsy.

Although electrical seizure activity in response to opioids such as fentanyl has been well described in animals, scalp electroencephalographic (EEG) recordings have failed to demonstrate epileptiform activity following narcotic administration in humans. The purpose of this study was to determine whether fentanyl is capable of evoking electrical seizure activity in patients with complex partial (temporal lobe) seizures. Nine patients were studied in whom recording electrode arrays had been placed in the bitemporal epidural space several days earlier to determine which temporal lobe gave rise to their seizures. The symptomatic temporal lobe was localized by correlating clinical and electrical seizure activity obtained during continuous simultaneous videotape and epidural EEG monitoring. In each patient, clinical seizures and electrical seizure activity were consistently demonstrated to arise unilaterally from one temporal lobe (four on the right, five on the left). During fentanyl induction of anesthesia in preparation for secondary craniotomy for anterior temporal lobectomy, eight of the nine patients exhibited electrical seizure activity at fentanyl doses ranging from 17.7 to 35.71 micrograms.kg-1 (mean 25.75 micrograms.kg-1). More importantly, four of these eight seizures occurred initially in the "healthy" temporal lobe contralateral to the surgically resected lobe from which the clinical seizures had been shown to arise. These findings indicate that, in patients with complex partial seizures, moderate doses of fentanyl can evoke electrical seizure activity. The results of this study could have important implications for neurosurgical centers where electrocorticography is used during surgery for the purpose of determining the extent of the resection.     

Chemolysis of urinary calculi

Irrigant chemolysis was developed to collaborate with open surgery, removing the residual fragments. With the worldwide diffusion of the procedures performed by the endourologist in the early 1980s and the present availability of ESWL, however, direct irrigation of stones has a reduced field of influence even as an adjunctive measure. Urologists have applied economic analysis to their clinical practices, and the findings related to irrigant chemolysis made this technique an unusual procedure. The cost to the providers of medical care, the burden on the patient in terms of suffering and loss of productivity, and the amount of time required to liberate the patient even partially from the stones make irrigant chemolysis an inauspicious scenario. In this era of cost containment and decreasing length of stay, it is increasingly difficult to justify hospital admissions for this form of therapy. Being simultaneously more expensive and less effective than the existing alternatives, local chemolysis should be discarded, except for special situations, such as patients at high risk for any surgical procedure. Oral chemolysis preserves reduced indications, for example as an adjuvant to an endourologic operation or ESWL in special situations. As long as urinary stones continue to afflict humans, chemolysis is likely to retain a limited but important role in their management.