Indoor particles and symptoms among office workers: results from a double-blind cross-over study

BACKGROUND: We studied the effects of removing small airborne particles in an office building without unusual contaminant sources or occupant complaints. METHODS: We conducted a double-blind crossover study of enhanced particle filtration in an office building in the Midwest United States in 1993. We replaced standard particle filters, in separate ventilation systems on two floors, with highly efficient filters on alternate floors weekly over 4 weeks. Repeated-measures models were used to analyze data from weekly worker questionnaires and multiple environmental measurements. RESULTS: Bioaerosol concentrations were low. Enhanced filtration reduced concentrations of the smallest airborne particles by 94%. This reduction was not associated with reduced symptoms among the 396 respondents, but three performance-related mental states improved; for example, the confusion scale decreased (-3.7%; 95% confidence limits (CL) = -6.5, -0.9). Most environmental dissatisfaction variables also improved; eg, "stuffy" air, -5.3% (95% CL = -10.3, -0.4). Cooler temperatures within the recommended comfort range were associated with remarkably large improvement in most outcomes; for example, chest tightness decreased -23.4% (95% CL = -38.1, -8.7) for every 1 degrees C decrease. CONCLUSIONS: Benefits of enhanced filtration require assessment in buildings with higher particulate contaminant levels in studies controlling for temperature effects. Benefits from lower indoor temperatures need confirmation.     

Epirubicin glucuronidation and UGT2B7 developmental expression.

The usefulness of epirubicin in the treatment of adult and childhood malignant diseases is related in part to the potential reduction in cardiac toxicity compared with that of other anthracyclines given at equivalent doses. An important pathway for epirubicin detoxification is UGT2B7-dependent glucuronidation. This study was implemented to provide a preclinical evaluation of the metabolism of epirubicin with respect to age-related changes in epirubicin glucuronidation in pediatric liver microsomes. Rates of epirubicin glucuronidation and levels of UGT2B7 were determined for liver microsomes from four pediatric age categories (n = 32) and one adult age category (n = 8). Both sets of data showed an increase in UGT2B7 activity and content with increasing age. Epirubicin glucuronidation activity in the adult group was statistically higher compared with all pediatric age groups (p < or = 0.01). UGT2B7 expression also was statistically higher in adults compared with children below 11 years of age, with evidence of significant differences in protein levels among the pediatric age categories. A positive correlation (r = 0.68) between UGT2B7 levels and postnatal age was observed, suggesting a progressive increase in UGT2B7 protein expression with increasing age. However, allometric scaling using the (3/4) power rule suggested no difference in activity between any of the pediatric age categories and the adult, although only a single neonatal sample was included in the analysis. In summary, these in vitro data show differences in epirubicin glucuronidation and UGT2B7 content within pediatric age groups and support the use of epirubicin in pediatric patients at least 6 months of age.     

Management of carotid coils during routine carotid endarterectomy

BACKGROUND: A coil in the internal carotid artery (ICA), defined as a circular configuration or exaggerated S shape of the ICA, is occasionally encountered during endarterectomy for carotid bifurcation lesions. The significance of coils as an etiology for symptoms is difficult to determine. It is thought, however, that the failure to correct coils and kinks during routine carotid endarterectomy (CE) may lead to turbulence and failure of the CE. Various techniques have been discussed to repair coils. METHODS: Our technique consisted of complete dissection of the coil, routine use of a Javid shunt, standard endarterectomy, resection of the redundant ICA, re-approximation of the posterior wall of the ICA and patch angioplasty of the anterior wall. Three hundred and fifteen patients underwent CE between August, 1998 and February, 2000. Fifteen patients (4.7%) had a carotid coil that was repaired. There were ten men and five women. Mean age was 72.6+/-6.1 years. Ten patients had an asymptomatic stenosis. Four patients had lateralizing symptoms and one patient had dizziness. Fifteen patients underwent preoperative duplex scanning and 14 of these patients had MRA scans performed. All patients had a preoperative stenosis of 80-99% by duplex on the operated side. The right carotid artery was repaired in 12 patients. The left in three patients. The length of resected artery varied from 1.2-2.8 cm (1.93+/-0.49 cm). RESULTS: All patients survived surgery. One patient developed a cerebellar stroke on the third postoperative day. A postoperative carotid duplex scan demonstrated a widely patent repair. There were no cranial nerve injuries in this series. One patient died seven months after surgery from cardiac events with no follow-up duplex exam. There have been no long term strokes or anastomotic complications. Follow-up duplex scans demonstrated widely patent repairs (1-15% stenosis) in seven patients and low end 15-49% stenosis in five patients. CONCLUSIONS: Resection of redundant ICA with re-anastomosis of the posterior wall and patch reconstruction of the anterior wall gives acceptable perioperative and long term results.     

Porcelain gallbladder is not associated with gallbladder carcinoma

The surgical management of porcelain gallbladder is based on studies performed in 1931 and 1962, which indicated a correlation between porcelain gallbladder and carcinoma. We sought to evaluate the characteristics of patients with porcelain gallbladder and the risk for gallbladder carcinoma. The medical records of 10,741 cholecystectomies performed between 1955 and 1998 were reviewed and recorded. The pathology slides were evaluated for evidence of calcification and gallbladder carcinoma. Fifteen (0.14%) of 10,741 specimens were porcelain gallbladders. Ten patients (67%) had symptoms suggestive of biliary colic or cholecystitis. Five (33%) were asymptomatic and diagnosed incidentally. All specimens demonstrated chronic cholecystitis and partial calcification of the gallbladder wall. Nine (60%) had cholelithiasis. None had gallbladder carcinoma by recent review of pathologic material. During this same period 88 (0.82%) patients had gallbladder carcinoma, none of which showed calcification of the wall. This report represents the largest modern review of porcelain gallbladders. No carcinoma was identified among patients with porcelain gallbladder. In addition no patient with gallbladder carcinoma had calcified gallbladder. With a better understanding of the natural history of the porcelain gallbladder the current management of these patients may change.     

Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia

Two children with acute lymphoblastic leukaemia (ALL) taking daily 6-mercaptopurine as part of a national UK therapeutic trial repeatedly developed profound myelosuppression on 25% of the standard protocol dose. Both were found to have undetectable intracellular activity of thiopurine methyltransferase (TPMT), an enzyme controlling one of the major alternative catabolic pathways of 6-mercaptopurine, and both produced higher concentrations of cytotoxic drug metabolites at 10-25% of the protocol dose than other patients taking 100%. It is supposed that these patients represent the 0.33% of the normal population constitutionally lacking TPMT. It is important to recognise such individuals both to avoid fatal bone marrow failure through inadvertent overdosage, and to be reassured that an adequate drug effect can be achieved at around 10% of the standard dose.     

Intravenous nitrogen mustard given immediately after mastectomy: possible effect on local recurrence.

A small group of patients with Stage I and II ductal breast carcinomas were treated with intravenous nitrogen mustard the day of mastectomy and the first two postoperative days. Long term follow-up revealed that only one patient developed isolated local recurrence, a rate much lower than usually reported. It is possible that early use of chemotherapy could reduce local recurrences in the recently traumatized tissue.     

Photochemical inactivation of duck hepatitis B virus in human platelet concentrates: a model of surrogate human hepatitis B virus infectivity

BACKGROUND: Photochemical decontamination of platelet concentrates (PCs) has been demonstrated by the use of 8-methoxypsoralen and ultraviolet A light. Systems for studying the inactivation of blood- borne viruses facilitate the evaluation of photochemical decontamination protocols. STUDY DESIGN AND METHODS: Duck hepatitis B virus (HBV), a model for human HBV, was adapted for the study of hepadnavirus inactivation. A highly specific in vitro infectivity assay used primary duck hepatocyte cultures and was followed by the detection of replicated duck HBV sequences. RESULTS: Duck HBV-infected primary duck hepatocyte cultures produced authentic infectious virus. High- titer (> 10(9) virus genome equivalents/mL) duck HBV-infected sera were completely inactivated in serum or PCs by the use of 100 micrograms per mL of 8-methoxypsoralen and 70 J per cm2 of ultraviolet A light. Intracellular duck HBV (> 4.2 log10) in PCs was also inactivated. Culture results were confirmed by a sensitive duckling infectivity assay that indicated that 6.3 log10 of infectious duck HBV had been inactivated by photochemical decontamination. CONCLUSION: The sensitivity of the culture assay was comparable to that of the duckling assay using polymerase chain reaction gene amplification to detect duck HBV. Duck HBV inactivation in PCs was dependent on the dose of ultraviolet A light and independent of 8-methoxypsoralen concentrations of 100 to 300 micrograms per mL: 100 micrograms per mL 8- methoxypsoralen inactivated 4 to 5 log10 of virus in conjunction with 20 to 40 J per cm2 of ultraviolet A light. The polymerase chain reaction-enhanced duck HBV culture system has utility in optimizing photochemical decontamination protocols.