One-Year Inhalation Toxicity Study of Chlorine in Rhesus Monkeys (Macaca mulatta)

Chlorine (Cl₂) gas is a potentially lung-damaging irritant whichis used in the chemical, plastics, and paper industries. Thereare no data published using experimental animals on the chronicinhalation toxicity of chlorine. The purpose of this study wasto investigate the chronic effects of Cl₂ inhalation in Rhesusmonkeys (Macaca mulatta). Rhesus monkeys were exposed to concentrationsof 0, 0.1, 0.5, or 2.3 ppm Cl₂ for 6 hr per day, 5 days perweek for 1 year. Pulmonary physiology (pulmonary diffusing capacityand distribution of ventilation), body weights, urinalysis,electrocardiographs, hematology, and clinical chemistry wereevaluated monthly during the study. Blood gas evaluations wereperformed at 3-month intervals during the study. Histopathologic,ophthalmologic, and neurologic parameters were evaluated afterthe 1-year exposure period. Monkeys exposed to 2.3 ppm Cl₂ exhibitedsigns of ocular irritation during the daily exposures and asuperficial conjunctival irritation was present in the 2.3 ppmgroup after the 1-year exposure regimen. Treatment-induced lesionsrevealed by histopathology were confined to the respiratorytract. Lesions associated with the nasal parasite Anatrichosomaspp. were present in the region of squamous epithelium of thenasal vestibule and did not interfere with interpretation ofCl₂ induced effects. Treatment-induced histopathologic changeswere found in the respiratory epithelium of the nasal passagesand trachea and were limited to focal, concentration-relatedepithe hal hyperplasia with loss of cilia and decreased numbersof goblet cells in affected areas. These changes in the noseand trachea were focal and mild in monkeys exposed to 2.3 ppmand were not found in all animals in these exposure groups.Tracheal lesions were confined to the 2.3 ppm group. The lesionsobserved at 2.3 ppm were not present in all animals. At thelower Cl₂ concentrations, similar though less prominent respiratoryepithelial lesions were observed. The latter changes were veryminimal and were confined to the nasal passages of some treatedmonkeys and one male control animal. The results of this studyindicate that 2.3 ppm chlorine acts as an upper respiratoryirritant in monkeys, while 0.5 and 0.1 ppm induce changes ofquestionableclinical significance. Furthermore, the monkey appears to beless sensitive than the rat to chlorine toxicity.     

Tricuspid Valve Perforation by a Permanent Pacing Lead in a Patient with Cardiac Amyloidosis: Case Report and Brief Literature Review

Tricuspid valve injury is a rare complication of transvenous pacemaker placement, We report such an injury in an elderly patient with cardiac amyloidosis. Because serious complications may result from such an injury, tricuspid valve perforation should be considered, along with the more common causes of new murmurs, in patients with pacemakers.     

Melanin Pigment Uptake Within Paget Cells

Cutaneous leiomyosarcoma typically presents as solitary, well‐circumscribed, firm plaques or nodules. We describe a case of cutaneous leiomyosarcoma clinically presenting as a skin tag on the thigh of a 50‐year‐old male. Histological examination of the lesion revealed a dome‐shaped tumor with interlacing fascicles of smooth muscle with pleomorphism, cellular atypia and multiple mitoses. Malignant tumors may rarely present as a skin tag, and these are most frequently basal cell carcinomas. We are unaware of previously reported leiomyosarcoma clinically presenting as a skin tag. This case suggests that solitary, wide‐based, papilloma‐like lesions or skin tags should be submitted for histologic examination to rule out malignancy.     

Risk Assessment in Immunotoxicology: I. Sensitivity and Predictability of Immune Tests

We have previously reported on the design and content of a screeningbattery involving a "tier" approach for detecting potentialimmunotoxic compounds in mice (Luster et al., 1988, Fundam.Appl. Toxicol. 10, 2–19). This battery has now been utilizedto examine a variety of compounds by the NIEHS ImmunotoxicologyLaboratory, the National Toxicology Programsponsored laboratories,and by the Cell Biology Department at the Chemical IndustryInstitute of Toxicology. The database generated from these studies,which consists of over 50 selected compounds, has been collectedand analyzed in an attempt to improve future testing strategiesand provide information to aid in quantitative risk assessmentfor immunotoxicity. Studies presented here have establishedthe ability of each of the tests or test combinations in thescreening battery to detect immunotoxic compounds. Efforts arecurrently underway using this database to determine the relationshipsbetween these immune tests and susceptibility to challenge withinfectious agents or transplantable tumor cells. The presentanalyses indicated that the performance of only two or threeimmune tests are sufficient to predict immunotoxic compoundsin rodents (>90% concordance). The tests that showed thehighest association with immunotoxicity were the splenic antibodyplaque forming cell response (78%) and cell surface marker analysis(83%). The relationship between immunotoxicity and carcinogenicity,as well as genotoxicity, was also determined. These analysessuggested that potential immunotoxic compounds are likely tobe rodent carcinogens (p = 0.019) although for compounds thatare not immunotoxic the carcinogenic status is unclear. Therewas no relationship observed between immunotoxicity and mutagenicityas determined using in vitro genotoxicity tests. The significanceof these observations is discussed in terms of the relationshipbetween immunotoxicity tests and biological/toxicological processesconcerned with human health (e.g., infectious disease).     

Direct target NOTES: prospective applications for next generation robotic platforms

Background

A new era in surgical robotics has centered on alternative access to anatomic targets and next generation designs include flexible, single-port systems which follow circuitous rather than straight pathways. Such systems maintain a small footprint and could be utilized for specialized operations based on direct organ target natural orifice transluminal endoscopic surgery (NOTES), of which transanal total mesorectal excision (taTME) is an important derivative.

Methods

During two sessions, four direct target NOTES operations were conducted on a cadaveric model using a flexible robotic system to demonstrate proof-of-concept of the application of a next generation robotic system to specific types of NOTES operations, all of which required removal of a direct target organ through natural orifice access. These four operations were (a) robotic taTME, (b) robotic transvaginal hysterectomy in conjunction with (c) robotic transvaginal salpingo-oophorectomy, and in an ex vivo model, (d) trans-cecal appendectomy.

Results

Feasibility was demonstrated in all cases using the Flex^® Robotic System with Colorectal Drive. During taTME, the platform excursion was 17 cm along a non-linear path; operative time was 57 min for the transanal portion of the dissection. Robotic transvaginal hysterectomy was successfully completed in 78 min with transvaginal extraction of the uterus, although laparoscopic assistance was required. Robotic transvaginal unilateral salpingo-oophorectomy with transvaginal extraction of the ovary and fallopian tube was performed without laparoscopic assistance in 13.5 min. In an ex vivo model, a robotic trans-cecal appendectomy was also successfully performed for the purpose of demonstrating proof-of-concept only; this was completed in 24 min.

Conclusions

A flexible robotic system has the potential to access anatomy along circuitous paths, making it a suitable platform for direct target NOTES. The conceptual operations posed could be considered suitable for next generation robotics once the technology is optimized, and after further preclinical validation.

     

Progress in individualizing autologous islet isolation techniques for pediatric islet autotransplantation after total pancreatectomy in children for chronic pancreatitis

Total pancreatectomy with islet autotransplantation is performed to treat chronic pancreatitis in children. Successful islet isolation must address the challenges of severe pancreatic fibrosis and young donor age. We have progressively introduced modifications to optimize enzymatic and mechanical dissociation of the pancreas during islet isolation. We evaluated 2 islet isolation metrics in 138 children—digest islet equivalents per gram pancreas tissue (IEQ/g) and digest IEQ per kilogram body weight (IEQ/kg), using multiple regression to adjust for key disease and patient features. Islet yield at digest had an average 4569 (standard deviation 2949) islet equivalent (IEQ)/g and 4946 (4009) IEQ/kg, with 59.1% embedded in exocrine tissue. Cases with very low yield (<2000 IEQ/g or IEQ/kg) have decreased substantially over time, 6.8% and 9.1%, respectively, in the most recent tertile of time compared to 19.2% and 23.4% in the middle and 34.1% and 36.4% in the oldest tertile. IEQ/g and IEQ/kg adjusted for patient and disease factors improved in consistency and yield in the modern era. Minimal mechanical disruption during digestion, warm enzymatic digestion using enzyme collagenase:NP activity ratio < 10:1, coupled with extended distension and trimming time during islet isolation of younger and fibrotic pediatric pancreases, gave increased islet yield with improved patient outcomes.     

Effect of intravenous lidocaine on ischemia-reperfusion injury in DIEP microsurgical breast reconstruction. A prospective double-blind randomized controlled clinical trial

BackgroundIschemia-reperfusion injury in free flaps is associated with tissue damage and is one of the main factors causing flap failure in reconstructive microsurgery. The aim of this study is to assess whether any ischemia-reperfusion injury takes place during a microsurgical flap reconstruction as seen through the levels of malondialdehyde (MDA) and superoxide dismutase, biomarkers of oxidative stress, and to analyze the effect of lidocaine in this process.MethodsTwenty-four patients operated for immediate breast reconstruction using the Deep Inferior Epigastric Perforator free flap technique were divided into two groups: one group was treated with a lidocaine intravenous perfusion and the other group with a saline perfusion. MDA and superoxide dismutase (SOD) levels were measured at several points before, during, and after surgery.ResultsThere was an increase in MDA levels in both groups, but the lidocaine group experienced a decrease during reperfusion. On the other hand, we observed a rise in SOD levels in both groups, but a decrease during reperfusion in the placebo group. However, these differences between groups were not statistically significant.ConclusionsThe decreased SOD activity and increased MDA content in our research prove a redox imbalance and high reactive oxygen species levels in flaps, indicating that tissues experience ischemia-reperfusion injury during microsurgical reconstruction. Lidocaine may have a protective effect in free flap surgery, but our results were not statistically significant, so further studies will be required.     

Streptococcus pneumoniae-induced haemolytic uraemic syndrome

Haemolytic uraemic syndrome secondary to infection with neuraminidase producing Streptococcus pneumoniae is well recognised, but was previously considered to be rare. This case report describes the course of a 9-month-old male with pneumococcal pneumonia, T activation and haemolytic uraemic syndrome. The clinical features of three other cases treated in Southeast Queensland in the past 2 years and 12 previously reported cases are summarised. The widespread availability of rapid diagnostic testing for this entity should allow for increased recognition, enabling appropriate use of low plasma volume blood products with improved patient outcome.