Long-term histological response to intravenous Teflon and silicone in a rat model

Particle migration is one of the main concerns raised when implanted plastics are discussed, especially when used for the endoscopic treatment of vesicoureteric reflux in children. To study the histological response to migrated plastic material, we injected particulate plastics (Teflon and silicone) into the jugular vein of 21 Sprague-Dawley rats, 11 of which were killed at 12 months, 9 at 2 years, and 1 died at 18 months. The findings were similar for Teflon and silicone and unchanged after from 1 to 2 years. The plastic particles were seen outside pulmonary vessels, within aggregated multinucleate giant cells, surrounded by only small numbers of other types of inflammatory cells.     

Bjornstad syndrome

A 9-month-old boy presented with the complaints of loose motion, vomiting and difficulty in breathing. His scalp hairs were thin, brittle, and sparse and were of differing lengths with twisted appearance. Hair shaft microscopy revealed alternate light and dark segments and twisting of the hair shafts by 180 degrees along the axis. Serum copper levels were normal. The audiological testing revealed bilateral sensorineural hearing loss. Child was diagnosed as a case of Bjornstad Syndrome.     

Preparation of Large Porous Deslorelin-PLGA Microparticles with Reduced Residual Solvent and Cellular Uptake Using a Supercritical Carbon Dioxide Process

PURPOSE: The purpose of this study was to prepare large-porous peptide-encapsulating polymeric particles with low residual solvent that retain deslorelin integrity, sustain drug release, and exhibit reduced epithelial and macrophage uptake. We hypothesized that supercritical carbon dioxide (SC CO2) pressure-quench treatment of microparticles prepared using conventional approach expands these particles and extracts the residual organic solvent. METHODS: Initial studies with crystalline L-lactide (L-PLA) and amorphous copolymers of lactide-co-glycolide (PLGA) 50:50, 65:35, and 75:25 indicated that PLGA 50:50 was the most amenable to morphological changes upon SC CO2 treatment. Therefore, we prepared deslorelin-PLGA (50:50) microparticles using the conventional emulsion-solvent evaporation method, and in a second step equilibrated with SC CO2 at various temperatures (33-37 degrees C) and pressures (1200-2000 psi) for discrete intervals followed by rapid isothermal depressurization. The particles were then characterized for morphology, polymer thermal properties, particle size, porosity, bulk density, and residual solvent content. Also, deslorelin integrity, conformation, release, and cellular uptake before and after SC CO2 treatment was determined. RESULTS: Upon SC CO2 treatment (1200 psi, 33 degrees C for 30 min), the mean particle size of the deslorelin PLGA microparticles increased from 2.2 to 13.8 microm, the mean porosity increased from 39 to 92.38% the mean pore diameter increased from 90 to 190 nm, the mean bulk density reduced from 0.7 to 0.082 g/cc, mass spectrometry indicated structural integrity of released deslorelin, the circular dichroism spectrum indicated stabilization of beta-turn conformation, and the scanning electron microscopy confirmed increased particle size and pore formation. The deslorelin release was sustained during the 7-day study period. Also, the peak Tg of PLGA decreased from 51 to 45 degrees C, and the residual solvent content was reduced from 4500 ppm to below detection limit (< 25 ppm). The accumulation of drug from SC CO2 treated particles in cell layers of Calu-3, A549, and rat alveolar macrophages was reduced by 87, 91 and 50%, respectively, compared to untreated particles. CONCLUSION: An SCF-derived process could be successfully applied to prepare large porous deslorelin-PLGA particles with reduced residual solvent content, which retained deslorelin integrity, sustained deslorelin release, and reduced cellular uptake.     

Repeated episodes of endosulfan poisoning

INTRODUCTION: A number of families in a rural area of Jabalpur District (Madhya Pradesh), India, were affected by repeated episodes of convulsive illness over a period of three weeks. The aim of this investigation was to determine the cause of the illness. METHODS: The investigation included a house-to-house survey, interviews of affected families, discussions with treating physicians, and examination of hospital records. Endosulfan poisoning was suspected as many villagers were using empty pesticide containers for food storage. To confirm this, our team collected blood and food samples, which were transported to the laboratory and analyzed with GC-ECD. RESULTS: Thirty-six persons of all age groups had illness of varying severity over a period of three weeks. In the first week, due to superstitions and lack of treatment, three children died. In the second week, symptomatic treatment of affected persons in a district hospital led to recovery but recurrence of convulsive episodes occurred after the return home. In the third week, 10 people were again hospitalized in a teaching hospital. Investigations carried out in this hospital ruled out infective etiology but no facilities were available for chemical analysis. All persons responded to symptomatic treatment. The blood and food samples analyzed by our team showed presence of endosulfan, which was confirmed by GCMS. One of the food items (Laddu) prepared from wheat flour was found to contain 676 ppm of alpha-endosulfan. CONCLUSIONS: Contamination of wheat grains or flour with endosulfan and its consumption over a period of time was the most likely cause of repeated episodes of convulsions, but the exact reason for this contamination could not be determined. This report highlights the unsafe disposal of pesticide containers by illiterate farm workers, superstitions leading to delay in treatment, and susceptibility of children to endosulfan.     

Retained common-duct stones after open cholecystectomy and duct exploration in children

A retrospective study was performed of 250 patients with cholelithiasis treated at the Royal Children's Hospital, (RCH) Melbourne, over 25 years by open operation; 32 (12.8%) had proven choledocholithiasis on either preoperative imaging, operative cholangiography (OpCG), or postoperative investigation. A further 3 had underlying congenital biliary abnormalities and were excluded from further study. Thirty-one of the 32 were explored at open operation, 27 after OpCG and 4 on clinical grounds. One retained common-bile-duct (CBD) stone was undetected until the postoperative period (1/250, 0.25%). Seven ducts were not cleared, giving a duct exploration failure rate of 22.6% (7/31). All 8 retained CBD stones were identified in the early postoperative period and managed with a variety of techniques, including endoscopic retrograde cholangio-pancreatography (ERCP). The incidence of retained stones after open CBD exploration was high (22.6%), and can be attributed to difficulties in operative technique dealing with the smaller paediatric CBD. In addition, haemolytic disease seems to induce a propensity for choledocholithiasis. Given the small numbers presenting with cholelithiasis to RCH (10 per year), it is suggested that a selective approach to CBD exploration is appropriate in children. With the increasing use of laparoscopic cholecystectomy in children and the inherent technical difficulties of laparoscopic operative cholangiography, ERCP may offer an alternative solution in dealing with CBD stones rather than open or laparoscopic CBD exploration.     

Effect of kappa opioid agonists on visceral nociception induced by uterine cervical distension in rats

Although uterine distension in rats results in an escape reflex, there exists no model of uterine cervical distension (UCD), the pain stimulus during the first stage of labor. The aims of this study were to develop such a model in virgin rats and to test whether peripherally restricted kappa opioid receptor (KOR) agonists (ADL 10-0101, ADL 10-0102, ADL 10-0116) inhibit responses to UCD. Under intravenous (i.v.) pentobarbital and alpha-chloralose anesthesia, fine metal rods were inserted in both uterine cervical osses through a small midline laparotomy. UCD was performed by manual separation of the rods (25-100 g). Single-unit afferent responses in hypogastric nerve or reflex rectus abdominis electromyographic (EMG) activity were determined before and after i.v. KOR agonists. UCD resulted in a stimulus-dependent increase in single-unit afferent activity. Units could be characterized as low threshold (mean threshold 6.6+/-2.7 g), or high threshold (mean threshold 55+/-8.8 g); all were C fibers, all responded to topical bradykinin. ADL 10-0116 (10 mg/kg) reduced the afferent response to UCD. Reflex EMG response occurred over a distension force range of 25-100 g, unaffected by i.v. saline. All three KOR agonists produced a dose-dependent, naloxone-reversible inhibition of the EMG response with a potency relationship of ADL 10-0102 (ED50 0.04 mg/kg)>ADL 10-0101 (ED50 0.65 mg/kg)=ADL 10-0116 (ED50 0.60 mg/kg). These data support the use of acute UCD as a noxious stimulus, inducing afferent and reflex activity. Like other visceral stimuli, UCD is sensitive to inhibition by KOR agonists.     

Revision anorectoplasty in the management of anorectal anomalies

Twelve patients who had a revision posterior sagittal anorectoplasty (PSARP) were evaluated by questionnaire. They were 11 months to 15 years old (median 5 years) at the time of revision surgery. All were born with an intermediate to high anorectal anomaly (ARM) and had ongoing problems of rectal prolapse (3), stenosis (1), faecal incontinence (9), or severe constipation (4). All but 1 had a huge megarectum with a poor anorectal angle and stool impaction, causing overflow incontinence. After revision surgery, marked improvement occurred in 7 and at least some improvement was achieved in the remaining 5. Previous severe constipation resolved in 2 and improved in another 2 children. The number of soiling episodes significantly decreased in 8 patients: while before surgery 8 had been wearing nappies all the time, only 2 use them postoperatively. The anorectal prolapse has resolved in 3 and sensation improved in 5, and as a group, there has been a reduced need for laxatives and rectal washouts. The favourable outcome of our patients confirms that PSARP is an excellent technique for revision surgery, and tapering of a secondary megarectum plus the formation of an anorectal angle can produce clinical improvement, even in more severe forms of ARM. Accepted: 7 February 2001     

Gabapentin's effect on agitation in severely and persistently mentally ill patients

OBJECTIVE: To study the effects of adjunctive gabapentin on agitation in severely and persistently mentally ill (SPMI) inpatients. METHOD: Eleven chronic SPMI inpatients on stable psychotropic medication regimens were evaluated before and after the initiation of adjunctive gabapentin for six months. The following psychometric tests were used: Brief Psychiatric Rating Scale (BPRS), Corrigan Agitated Behavior Scale (CABS), and Clinical Global Impression (CGI)-Severity. Data collection was accomplished via retrospective chart review. An internal reliability check indicated that a chart review BPRS is significantly predictive of one performed face-to-face. RESULTS: Statistically significant reductions were found at six months for each assessment instrument (p < 0.05, two-tailed). BPRS scores were reduced from 40.6 to 33.2, CABS from 34.4 to 25.0, and CGI-Severity from 5.9 to 5.3. The bulk of the BPRS reduction was accounted for by several subscores exclusive of those assessing affective/anxious symptomatology. Adverse effects were minimal. Two patients were discharged 12 and 17 months after implementation of gabapentin. CONCLUSIONS: Adjunctive gabapentin appears to be associated with a reduction in agitation in chronically hospitalized SPMI patients. Controlled, prospective trials are needed before any definitive conclusion can be drawn regarding the role of gabapentin in the treatment of this group of patients.