Skin toxicokinetics of mustard gas in the guinea pig: effect of hypochlorite and safety aspects

Sulfur mustard (SM, mustard gas) is a chemical warfare vesicant that rapidly penetrates the skin due to its hydrophobicity. This study measured the rate of SM disappearance from the skin after topical application of the vesicant. In both fur-covered and hairless animals, the remaining toxicant levels measured 60 min after exposure to undiluted SM were 0.6% and 0.3%, respectively, of the initially applied SM amount. However, SM concentration reached 0.4% of the initial dose 3 h following exposure in female fur-covered guinea pigs. SM quantities extracted from skin of male fur-covered and hairless guinea pigs immediately after 16 min of exposure to SM vapor were 12.2 and 21.8 microg, respectively; levels declined to 1.6 and 1.7 microg at 30 and 15 min following termination of exposure of male fur-covered and hairless guinea pigs, respectively. Three swabbing treatments of undiluted SM-exposed skin with gauze pads soaked in 0.5% hypochlorite caused 68% reduction in skin SM content. Similar findings were obtained when hypochlorite was replaced by water (64% reduction). SM content in the gauze pads was 59, 38 and 25 microg, respectively, for the first, second and third decontamination processes with water. No SM was detected in the gauze pads soaked with hypochlorite. In vitro studies showed that incubation of SM with 0.5% hypochlorite at a ratio of 10:1 (v/v) did not cause SM inactivation, whereas 4% hypochlorite reduced SM levels by 17%. However, at a decontaminant:SM ratio of 1000:1, 0.5% and 4% hypochlorite reduced SM levels by 92% and 99%, respectively. These findings are important for health authorities and regulatory agencies in planning precautionary steps to be taken in case of emergency and in routine laboratory work.     

Venous air embolus during arthrography in a child: vital signs changes illustrated by the automated data recording system

We describe an 18-month-old boy who suffered venous air embolism during an arthrogram. Dangers associated with air injection are emphasized, illustrating the importance of careful monitoring to detect adverse events. We recommend caution when employing this method of hip joint evaluation.     

RNASEL mutation screening and association study in Ashkenazi and non-Ashkenazi prostate cancer patients.

Epidemiologic and genetic studies support the considerable effect of heritable factors on prostate tumorigenesis, although to date, no unequivocal susceptibility gene has been identified. The extensive study of RNASEL in prostate cancer patients worldwide has yielded conflicting results. We reevaluated the role of the RNASEL 471delAAAG Ashkenazi founder mutation in 1,642 Ashkenazi patients with prostate, bladder, breast/ovarian, and colon cancers; Ashkenazi controls; and in non-Ashkenazi prostate cancer patients and controls. The entire RNASEL coding sequence was also screened using denaturing high-performance liquid chromatography and multiplex ligation-dependent probe amplification for possible sequence variations or copy number changes in a population of prostate cancer patients. The 471delAAAG mutation was detected in 2.4% of the Ashkenazi prostate cancer patients; in 1.9% of patients with bladder, breast/ovarian, and colon cancers; and in 2.0% of the Ashkenazi controls. Seven additional variants were detected in RNASEL, including a novel potentially pathogenic splice site mutation, IVS5+1delG, although none were associated with increased prostate cancer risk. Multiplex ligation-dependent probe amplification analysis showed two RNASEL gene copies in all 300 prostate cancer patients tested. We estimated that the RNASEL 471delAAAG founder mutation, which was detected in 2% of the Ashkenazi Jews, originated between the 2nd and 5th centuries A.D., compared with the less frequent (1%) BRCA1 185delAG founder mutation, which originated hundreds of years earlier. Taken together, our analysis does not support a role for the RNASEL 471delAAAG Ashkenazi mutation nor for the other alterations detected in RNASEL in prostate cancer risk in Jewish men.     

Idiopathic hypercalciuria of childhood: 4- to 11-year outcome

Apart from a minority with urolithiasis, the majority of children diagnosed with idiopathic hypercalciuria present with macro- or microhematuria, abdominal or back pain, or voiding symptoms. With dietary and pharmacological interventions, most such children become asymptomatic and are lost to follow-up, hence their long-term outcome is unclear. In the present study, we evaluated the status of 14 males and 19 females aged 8-17 years (mean 11.9 years, median 11.2 years) 4-11 years (mean 6.9 years, median 6.5 years) after the initial diagnosis of idiopathic hypercalciuria not associated with urolithiasis. A questionnaire was answered and two random urine samples provided 3-4 weeks apart were analyzed for calcium (Ca), sodium (Na), potassium (K), and creatinine (Cr). Urine Ca/Cr ratio > or =20.21 (mg/mg) was defined as hypercalciuria. At the time of the study none were under follow-up, although 7 children were still exhibiting voiding symptoms. No child developed clinical urolithiasis. Based on the first urine specimen, 16 of the 33 (48.4%) were hypercalciuric. Their 2nd urinalysis showed persistent hypercalciuria in 8 and normocalciuria in 8. Urine Na/K ratio (mEq/mEq) decreased in the latter 8 from 5.08+/-2.67 to 3.03+/-2.23 (P<0.05). Of the 17 initially normocalciuric children, 5 did not submit a 2nd specimen, 11 remained normocalciuric, and 1 became hypercalciuric with an increase in urine Na/K ratio. Twenty-three children (all 8 persistently and 9 intermittently hypercalciuric plus 6 normocalciuric) were studied by ultrasonography. Only in 1 asymptomatic persistently hypercalciuric child was a single small renal calcification noted. Introduction of a low-Na/high-K diet in 7 persistently hypercalciuric children resulted in a decrease in UNa/K ratio from 7.34+/-2.15 to 4.14+/-3.09 (P<0.01) and UCa/Cr ratio from 0.25+/-0.04 to 0.13+/-0.03 (P<0.01). We conclude that even though over time most hypercalciuric children become asymptomatic, many remain hypercalciuric. Further follow-up is required to ascertain whether these children are at risk of developing kidney stones. If they are at risk then long-term compliance with a low-Na/high-K diet might be beneficial, as it can normalize calciuria in the majority of these children.     

Sieving coefficient inaccuracies during hemodiafiltration in patients with hyperbilirubinemia

Hemodiafiltration has assumed an important role in the supportive therapy of critically ill patients. The viability of the filter used for hemodiafiltration can be monitored by estimating the sieving coefficient of small molecules such as creatinine and/or urea. We report on three patients with severe hyperbilirubinemia whose creatinine sieving coefficient was spuriously elevated as a result of discordance in the accuracy of creatinine measurement in plasma and ultrafiltrate respectively. This discordance was a consequence of lack of bilirubin clearance during hemodiafiltration. As a result, while the plasma creatinine determination by the kinetic Jaffe method was negatively influenced by the hyperbilirubinemia, the ultrafiltrate creatinine was not. This report is the first to document the lack of bilirubin clearance during hemodiafiltration and its impact on the calculation of sieving coefficient based on creatinine. The use of urea as the solute for determining the sieving coefficient allows for an accurate estimate and provides a valid means of monitoring this parameter in the setting of hyperbilirubinemia. Received: 18 April 2000 / Revised: 16 June 2000 / Accepted: 20 June 2000     

Cystic fibrosis and neonatal calcified scrotal masses

We report a case of an infant who presented with failure to thrive and in whom the identification of calcified scrotal masses led us to the diagnosis of cystic fibrosis.     

Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction

BACKGROUND: Carboplatin-based regimens have demonstrated activity in unresectable low-grade glioma (LGG) in children. Despite an interesting toxicity profile, the use of these regimens has been limited by the development of carboplatin hypersensitivity reaction (HSR) in up to 30% of patients. Desensitization has been the recommended approach for HSR. However, no guidelines have existed to aid physicians when carboplatin desensitization techniques fail. METHODS: A pilot study of monotherapy with weekly vinblastine for LGG in 9 children who developed carboplatin HSR on a carboplatin and vincristine regimen was performed. RESULTS: Vinblastine toxicity was moderate and readily manageable. None of the 9 patients had disease progression on therapy. Magnetic resonance imaging evaluation of tumor size from diagnosis to the end of vinblastine treatment showed 1 complete response (CR), 1 partial response (PR), 5 objective effects (OE), and 2 stable diseases (SD). CONCLUSIONS: This experience suggested that weekly vinblastine has a good efficacy to toxicity ratio in the treatment of LGG and can be a valuable option for children who develop severe HSR.     

Resolution of medullary nephrocalcinosis in children with metabolic bone disorders

Ultrasonographic resolution of nephrocalcinosis (NC) has been reported in children with furosemide-induced NC, but not in other entities. We report the cases of four children with metabolic bone disease, two with hypophosphatasia and two with X-linked hypophosphatemic rickets, in whom we observed resolution of renal calcifications. At the time of ultrasonographic resolution of NC, 3 of the patients were on anticalciuric diuretics, and all 4 had normal urinalysis, serum creatinine and electrolyte profiles, as well as estimated creatinine clearance. In 3 of the children, evidence of mild tubular dysfunction was found. It thus seems that in some children with bone and mineral disorders who develop NC, ultrasonographic resolution of the renal calcifications can be seen; however, mild tubular dysfunction may remain and require follow-up. Further studies are suggested to explore the possible role of anticalciuric diuretics in promoting the resolution of NC.     

Orbital hydatid cyst manifested as expanding exophthalmos following blunt orbital trauma

A 14-year-old boy suffered right blunt orbital trauma. X-ray revealed a compressed fracture of the right ethmoidal sinuses. Three months after the trauma, progressive, painless right proptosis developed. Ocular examination revealed a severe proptosis and pronounced down displacement of the right globe without signs of orbital inflammation. A well-demarcated, extraconal right orbital cystic mass was seen on computerized tomography scan. The cyst contents were aspirated and found to contain echinococcal scolices and "hydatid sand." Hypertonic saline was injected and the cyst was excised. Progressive proptosis after blunt orbital trauma in patients from endemic areas should be suspected of being an orbital hydatid cyst.