Subchronic Inhalation Study with Vinyl Fluoride: Effects on Hepatic Cell Proliferation and Urinary Fluoride Excretion

Subchronic Inhalation Study with Vinyl Fluoride: Effects onHepatic Cell Proliferation and Urinary Fluoride Excretion. BOGDANFFY,M. S., KEE, C. R., KELLY, D. P., CARAKOSTAS, M. C, AND SYKES,G. P. (1990). Fundam Appl Toxicol. 15, 394/406. Vinyl fluorideis used widely in the manufacture of fluoropolymers. Based inpart on the structural similarity of vinyl fluoride to the hepatocarcinogensvinyl chloride and vinyl bromide, a TSCA Section 4 test rulemandated the testing of vinyl fluoride for oncogenicity. Thisreport presents the results of a 90-day inhalation study inrats and mice with vinyl fluoride designed to set test concentrationsfor a subsequent oncogenicity study. Groups of 15 male and femalerats and mice were exposed 6 hr per day, 5 days per week forapproximately 90 days to target concentrations of 0, 200, 2000,or 20,000 ppm vinyl fluoride. Clinical chemical, hematological,and urine analyses were performed on rats after 45 and 90 daysof exposure. A hematological evaluation was performed on micefollowing 45 and 90 days of exposure. A complete gross and microscopicevaluation was conducted at the end of the study. After 93 dayson test, groups of five rats and five mice per sex were implantedwith osmotic minipumps containing [3H]thymidine and were exposedfor an additional 5 days to measure cell proliferation in liver,kidney, lung, and nasal cavity tissues. Results of the histopathological,clinical chemical, and hematological evaluations showed no significanteffects of vinyl fluoride exposure at any concentration followingeither 45 or 90 days of exposure. A concentration-related increasein fluoride ion in urine was observed in rats at 45 and 90 daysof exposure. A plateau in urinary fluoride excretion was observedat approximately 2000 ppm, suggesting saturation of vinyl fluoridemetabolism. Vinyl fluoride-related cell proliferation effectswere largely restricted to liver. Hepatic cell proliferationin male and female rats and mice was elevated at all concentrations.The response was similar at concentrations of either 2000 or20,000 ppm and was consistent with concentration-response relationshipsfor other haloethylenes. Taken together, the urinary fluorideexcretion and hepatic cell proliferation data suggest a mechanisticlink between the two effects. On the basis of these findingsand experience with other haloethylenes, concentrations of vinylfluoride to be tested for oncogenicity should be chosen suchthat the full linear range of the concentration-response curveis evaluated. The present study demonstrates through examplethe value of incorporating cell proliferation studies in standardtesting protocols     

Review article: Luminex technology for HLA antibody detection in organ transplantation

Since its inception in the early 1960s, the serologically based complement-dependent cytotoxicity (CDC) assay has been the cornerstone technique for the detection of human leucocyte antigen (HLA) antibodies, not only in pre-transplant renal patients, but also in other forms of organ transplantation. Recently, solid phase assays have been developed and introduced for this purpose, and in particular the Flow-based bead assays such as the Luminex system. This latter assay has proved to be far more sensitive than the CDC assay and has revealed pre-sensitization in potential transplant recipients not detected by other methods of HLA antibody detection. However, the clinical implications of this increased sensitivity have not been convincingly demonstrated until recently. This technology for HLA antibody detection permits the evaluation of the clinical importance of antibodies directed at, for example, HLA-DPB1 and HLA-DQA1, which has not been possible to date. There are Luminex issues, however, requiring resolution such as the ability to distinguish between complement fixing and non-complement fixing antibodies and determination of their relative clinical significance. Luminex technology will permit a re-evaluation of the role of HLA antibodies in both early and late antibody-mediated rejection.     

Primary hepatic lymphoma in a patient with chronic hepatitis C

The case is presented of a woman with chronic active hepatitis C who developed primary hepatic lymphoma. The possible roles of viral hepatitis and therapeutic interferon in the pathogenesis and progression of this unusual maligancy are discussed. In addition, the importance of accurate tissue diagnosis to identify potentially treatable hepatic tumours is emphasized.     

Adjusting Heart Rate During Sleep Using Activity Variance

In order to mimic the natural decrease in heart rate that occurs during sleep, an algorithm was devised to decrease the base rate to a programmable sleep rate. The algorithm was developed using activity and sinus rate data obtained from 18 normal subjects ranging in age from 22–80 years. The data were recorded in the event record of a "taped-on" pacemaker. The surface ECG signal was used to inhibit a pacer programmed to VVI at 45 ppm. The ECG documented the sinus rate while the accelerometer-based activity signals were recorded in an event record. An algorithm was used to estimate the smoothed acceleration variance every 26 seconds. The activity variance was stored in a histogram. Results : The lower 7/24ths of the histogram entries were primarily attributable to sleep. If the activity variance was entered into the lower 7/24ths of the histogram and the accelerometer reading was below rate responsive threshold, the base rate was switched to sleep rate. Using least mean squares to estimate optimal slope, base rate, and sleep rate, the root mean square error between activity derived heart rate and sinus rate was 12 beats/min. Conclusion : This study supports using an estimate of activity variance to automatically decrease pacing rate below programmed base rate. This decrease may be actuated during an afternoon nap or nighttime sleep.     

A Comprehensive Approach to the Recognition, Diagnosis, and Severity-Based Treatment of Focal Hyperhidrosis: Recommendations of the Canadian Hyperhidrosis Advisory Committee

BACKGROUND: Hyperhidrosis can have profound effects on a patient's quality of life. Current treatment guidelines ignore disease severity. OBJECTIVE: The objective was to establish clinical guidelines for the recognition, diagnosis, and treatment of primary focal hyperhidrosis. METHODS AND MATERIALS: A working group of eight nationally recognized experts was convened to develop the consensus statement using an evidence-based approach. RECOMMENDATIONS: An algorithm was designed to consider both disease severity and location. The Hyperhidrosis Disease Severity Scale (HDSS) provides a qualitative measure that allows tailoring of treatment. Mild axillary, palmar, and plantar hyperhidrosis (HDSS score of 2) should initially be treated with topical aluminum chloride (AC). If the patient fails to respond to AC therapy, botulinum toxin A (BTX-A; axillae, palms, soles) and iontophoresis (palms, soles) should be the second-line therapy. In severe cases of axillary, palmar, and plantar hyperhidrosis (HDSS score of 3 or 4), both BTX-A and topical AC are first-line therapy. Iontophoresis is also first-line therapy for palmar and plantar hyperhidrosis. Craniofacial hyperhidrosis should be treated with oral medications, BTX-A, or topical AC as first-line therapy. Local surgery (axillary) and endoscopic thoracic sympathectomy (palms and soles) should only be considered after failure of all other treatment options. CONCLUSIONS: These guidelines offer a rapid method to assess disease severity and to treat primary focal hyperhidrosis according to severity.     

5% 5-Fluorouracil Cream for the Treatment of Small Superficial Basal Cell Carcinoma: Efficacy, Tolerability, Cosmetic Outcome, and Patient Satisfaction

BACKGROUND: Five percent 5-fluorouracil (5-FU) cream is approved by the FDA for the treatment of superficial basal cell carcinomas but has been underutilized. OBJECTIVE: The objective was to evaluate the efficacy, tolerability, cosmetic outcome, and patient satisfaction of 5% 5-FU in the treatment of superficial basal cell carcinomas. MATERIALS AND METHODS: A total of 29 patients with 31 biopsy-proven superficial basal cell carcinoma lesions on the trunk or limbs were treated with 5% 5-FU cream twice daily for up to 12 weeks. Treatment could be stopped sooner if the lesion was clinically resolved. The lesional site was surgically excised 3 weeks after the end of treatment for histologic evaluation of cure. RESULTS The histologic cure rate was 90% (28/31 lesions cured) and the mean time to clinical cure was 10.5 weeks. 5-FU was generally well tolerated with a good cosmetic outcome-the majority of patients had no pain or scarring and only mild erythema. Patients were generally very satisfied with their treatment. CONCLUSION: Five percent 5-FU is a highly effective and well-tolerated treatment option for superficial basal cell carcinomas offering a generally good cosmetic outcome and high levels of patient satisfaction.