Seasonal distribution and modeling of diesel particulate matter in the Southeast US.

The fine and ultra fine size of diesel particulate mater (DPM) are of great health concern and significantly contribute to the overall cancer risk. In addition, diesel particles may contribute a warming effect on the planet's climate. The composition of these particles is composed principally of elemental carbon (EC) with adsorbed organic compounds, sulfate, nitrate, ammonia, metals, and other trace elements. The purpose of this study was to depict the seasonality and modeling of particulate matter in the Southeastern US produced by the diesel fueled sources (DFSs). The modeling results came from four one-month cases including March, June, September, and December to represent different seasons in 2003 by linking Models-3/CMAQ and SMOKE. The 1999 National Emissions Inventory Version 3 (NEI99) was used in this analysis for point, area, and non-road sources, whereas the National Mobile Inventory Model (NMIM) was used to create the on-road emissions. Three urban areas, Atlanta, Birmingham, and Nashville were selected to analyze the DPM emissions and concentrations. Even though the model performance was not very strong, it could be considered satisfactory to conduct seasonal distribution analysis for DPM. Important hourly DPM seasonality was observed in each city, of which higher values occurred at the morning traffic rush hours. The EC contributions of primary DPM were similar for all three sites (approximately 74%). The results showed that there is no significant daily seasonality of DPM contribution to PM(2.5) for any of these three cities in 2003. The annual DPM contribution to total PM(2.5) for Atlanta, Nashville, and Birmingham were 3.7%, 2.5%, and 2.2%, respectively.

Tobacco abuse and its treatment. Turning old and new issues into opportunities for the occupational health nurse.

1. Tobacco use is linked to excessive rates of cardiovascular disease, lung disease, and many fatal neoplasms. In the United States it is the number one cause of illness and premature death. Cigarettes and other combusted forms of tobacco generate environmental tobacco smoke, a major contributor to asthma attacks, heart attacks, and lung cancer among nonsmokers. 2. Cigarettes are the most prevalent and abused form of tobacco, but other forms, such as cigars and smokeless tobacco, also contain nicotine and may cause dependency in high risk groups that consume these products. 3. The addictiveness of tobacco products, especially cigarettes, is particularly detrimental to vulnerable groups such as youth, women, blue collar workers, and other high risk and economically disadvantaged populations. 4. Effective treatment programs (e.g., individual and group counseling, close monitoring, drug treatment) are available to treat nicotine dependency, but many health care providers have been reluctant to educate their patients and clients about these programs. 5. Workplace tobacco use treatment programs, along with policies to restrict tobacco use, have special merit for employers concerned with worker health and safety, productivity, and profitability. Even the more successful tobacco treatment programs perform better when combined with additional efforts to reduce worker health risks and promote well being.

Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives.

Several methylated derivatives of a plant lignan, nordihydroguaiaretic acid (NDGA) were found to be potent anti-viral agents by suppressing Sp1 regulated transcription within the sexually transmitted viruses human immunodeficiency virus (HIV) and herpes simplex virus (HSV). A prominent Sp1 DNA binding site within many human papillomavirus (HPV) promoters has been noted to play an active role in HPV gene expression. In this report it is shown that the three NDGA derivatives, Mal.4, M(4)N, and tetra-acetyl NDGA can also inhibit gene expression from the early promoter P(97) of HPV16. The drug activity on gene expression was measured after DNA transfection of recombinant vector constructs linking the viral promoter and enhancer elements to the luciferase reporter gene. Using the specific luciferase activity as the indicator of gene expression, Mal.4 and M(4)N were found to be active in a dose dependent manner that is in the same range of concentrations reported for the promoters of HIV, HSV, and simian virus 40 (SV40) while tetra-acetyl NDGA was much more active in suppression of the HPV P(97) promoter activity than Mal.4 and M(4)N. The drugs showed limited to no effect on gene expression driven by the adenovirus major late promoter and the cytomegalovirus (CMV) promoter. Hence, such drug derivatives may be significant in the therapy of papillomavirus infections and their associated induced human cancers.

Resveratrol inhibition of herpes simplex virus replication.

Resveratrol, a phytoalexin, was found to inhibit herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) replication in a dose-dependent, reversible manner. The observed reduction in virus yield was not caused by the direct inactivation of HSV by resveratrol nor inhibition of virus attachment to the cell. The chemical did, however, target an early event in the virus replication cycle since it was most effective when added within 1 h of cell infection, less effective if addition was delayed until 6 h post-infection and not effective if added 9 h post-infection. Resveratrol was also found to delay the cell cycle at S-G2-M interphase, inhibit reactivation of virus from latently-infected neurons and reduce the amount of ICP-4, a major immediate early viral regulatory protein, that is produced when compared to controls. These results suggest that a critical early event in the viral replication cycle, that has a compensatory cellular counterpart, is being adversely affected.

Time course of cytokine release and complement activation after implantation of the HeartMate left ventricular assist device.

Pro-inflammatory mediators, including interleukin-6 (IL-6), IL-8, and complement C3a, are released after cardiac surgery as part of the inflammatory response related to blood-biomaterial interaction in the cardiopulmonary bypass circuit. Post operative time course data for these mediators are not fully defined in patients receiving left ventricular assist device (LVAD) support. The authors performed enzyme linked immunosorbent assays for concentrations of IL-6, IL-8, and C3a in plasma in six HeartMate LVAD recipients at the following times: pre operatively; 4, 8, 16, 24, 36, and 48 hr post operatively; daily through the first week; and weekly thereafter for 6 weeks. All patients survived without major complications during the study. Pre operative concentrations of IL-6 and C3a in plasma were significantly increased compared with age matched controls. Post operatively, the concentrations of IL-6 and IL-8 in plasma took longer to return to baseline values after insertion of the LVAD than the trends reported in the literature after routine cardiopulmonary bypass alone. Concentrations of IL-6 and complement C3a continued to decrease to lower than baseline post operatively, reaching statistical significance after 6 weeks of LVAD support. The authors conclude that the presence of the HeartMate LVAD delays the return of pro-inflammatory mediator concentrations back to baseline values compared with routine cardiopulmonary bypass alone, but the device does not appear to be an ongoing source of cytokine release or complement activation.

Reversal of renal failure and paraplegia after thoracoabdominal aneurysm repair.

Repair of ruptured thoracoabdominal aortic aneurysms is complicated by high rates of perioperative paraplegia, renal insufficiency, and mortality. This report describes a patient with a ruptured thoracoabdominal aortic aneurysm in whom preoperative acute renal failure was reversed with hemodialysis, aortic replacement, and renal revascularization. Prompt cerebrospinal fluid drainage reversed delayed-onset postoperative paraplegia and led to immediate, complete neurologic recovery.

Uterine cervix adenocarcinoma with both human papillomavirus type 18 and tumor suppressor gene p53 mutation from a woman having an intact hymen.

Human papillomavirus (HPV) type 18 DNA was found in an aggressively invasive adenocarcinoma tumor from a woman who had an intact hymen and denied any prior sexual intercourse. The viral DNA was detected within the tumor tissue by polymerase chain reaction (PCR) using consensus primers for the L1 region of oncogenic high-risk genital HPVs. In order to determine mutations within the tumor suppressor gene p53, the gene exons were amplified by PCR followed by single-stranded conformation polymorphism (SSCP) analysis. The appearance of a mutation in exon 8 of the p53 gene suggested by SSCP was directly confirmed by DNA sequencing of the exon. The sequencing showed a single base deletion that may truncate the protein by introducing a early stop codon in the messenger RNA. This early truncation could be expected to affect the proper oligomerization of the p53 protein and hence its DNA-binding activity. The results show that genital oncogenic human papillomaviruses may be passed by nonsexual routes and suggest that the virus may work in concert with p53 mutations to help the infected tissue progress toward invasive cancer.

Tissue distribution, circulating half-life, and excretion of intravenously administered protamine sulfate.

Intravenous protamine reversal of heparin anticoagulation may cause adverse hemodynamic side effects, but little is known about protamine's tissue distribution, circulating half-life (t/2), and excretion. The latter were assessed by examining 125I Bolton-Hunter (125I BH) radiolabeled protamine kinetics in a rat model. Three groups were studied: Group I controls (n = 5) received intravenous 125I BH label alone; Group II (n = 10) received intravenous 125I BH radiolabeled protamine (0.15 mg/100 g); and Group III (n = 10) received intravenous heparin (15 IU/100 g) followed by intravenous 125I BH radiolabeled protamine (0.15 mg/100 g). Five animals in each group were killed at 3 min, and tissue radioactivity was quantitated. An additional five animals each in Groups II and III were followed up for 60 min to determine protamine's circulating t/2 and its renal excretion. The lungs, heart, and kidneys, compared with other organs, retained the most 125I BH radiolabeled protamine per gram tissue at 3 min. Retention of 125I BH radiolabeled protamine (Groups II & III) was greater (p < 0.05, Kruskal-Wallis) than control 125I BH label alone (Group I). Higher tissue 125I activity was observed in Group II than in Group III rats, suggesting that tissue retention of protamine was greater in the absence of prior heparin administration. Circulating t/2 was shorter (18 vs. 24 min) and urinary protamine 125I excretion was higher (34 vs. 24%) in Group III than in Group II, respectively, suggesting more rapid renal clearance of protamine in the presence of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and toxicity of differently charged polycationic protamine-like peptides for heparin anticoagulation reversal.

PURPOSE: The role of total cationic charge of synthetic protamine-like peptides in heparin anticoagulation reversal and accompanying adverse hemodynamic effects was studied. METHODS: Five protamine variants having specific total charges of [+8], [+16], [+18], [+20], and [+21] were synthesized by fluorenylmethoxycarbonyl procedures. Each of these lysine-containing peptides plus arginine-containing control salmine native protamine (n-protamine, [+21] charge) was studied in five dogs who received heparin 150 IU/kg intravenously followed by 1.5 mg/kg (intravenously during a 10-second period) of the synthesized peptide or control n-protamine. RESULTS: Anticoagulation reversal as assessed by a number of coagulation tests was more effective with peptides of greater cationic charge. In this regard, activated clotting time reversal 3 minutes after peptide administration was 7%, [+8]; 54%, [+16]; 81%, [+18]; 92%, [+20]; 81%, [+21]; and greater than 100% [n-protamine]. Reversal of heparin anticoagulation at 3 and 30 minutes, respectively, correlated significantly (*p < or = 0.05, p < or = 0.01 [see corresponding symbols within abstract]) with total cationic charge as assessed by activated clotting time (r = 0.97, 0.99 ), prothrombin time (r = 0.98, 0.87*), activated partial thromboplastin time (r = 0.99, 0.78), thrombin clotting time (r = 0.84,* 0.85*), heparin anti-Xa activity (r = 0.87,* 0.85*), and heparin anti-IIa activity (r = 0.79 at 3 minutes, p = 0.06). Maximum declines in systemic mean arterial pressure (MAP) were greater with more positively charged peptides: -1 mm Hg, [+8]; -3 mm Hg, [+16]; -31 mm Hg; [+18]; -31 mm Hg, [+20]; -35 mm Hg, [+21]; and -34 mm Hg [n-protamine]. Maximum decreases in MAP, cardiac output, and systemic oxygen consumption were highly correlated (p < or = 0.05) with total cationic charge: MAP, r = 0.87; cardiac output, r = 0.87; and systemic oxygen consumption, r = 0.86. A total toxicity score, reflecting adverse hemodynamic effects, was greater with increasing charge: -1.9 +/- 1.1, [+8]; -2.7 +/- 0.8, [+16]; -6.6 +/- 3.3, [+18]; -6.1 +/- 3.5, [+20]; -6.9 +/- 3.8, [+21]; and -7.0 +/- 5.2 [n-protamine]. The correlation of mean peptide total toxicity score to total cationic charge was significant (r = 0.89, p < 0.05). CONCLUSIONS: These data suggest for the first time that effective alternatives to salmine protamine for reversal of heparin anticoagulation can be synthesized. Furthermore, total cationic charge appears to be an important determinant for both anticoagulation reversal and toxicity of protamine-like peptides.

Inflammatory and procoagulant mediator interactions in an experimental baboon model of venous thrombosis.

Theoretic and in vitro evidence suggests that thrombosis and inflammation are interrelated. The purpose of the present study was to define the relationship between inflammation and deep venous thrombosis (DVT) in an in vivo model. Initiation of DVT was accomplished by administration of antibody to protein C (HPC4, 2 mg/kg) and tumor necrosis factor (TNF, 150 micrograms/kg); stasis; and subtle venous catheter injury. Thrombosis was assessed by thrombin-antithrombin assay (TAT), 125I-fibrinogen scanning (scan) over both the proximal and distal iliac veins, and ascending venography. Cytokines TNF, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8) were measured along with differential white blood cell counts, platelet counts, fibrinogen (FIB), and erythrocyte sedimentation rates (ESR). Baboon pairs were sacrificed on day 3 (T + 3d), T + 6d, and T + 9d and veins removed. All animals developed inferior vena cava and left iliofemoral DVT by venography; no right DVT was found. TAT was elevated by T + 1hr and peaked at T + 3hrs. Left iliofemoral DVT was found at T + 1hr by scan and reached a 20% uptake difference between the affected left and nonaffected right side at T + 3hrs. TNF peaked at T + 1hr; MCP-1 peaked at T + 6hrs; IL-8 and IL-6 peaked on T + 2d; all cytokines declined to baseline. TNF and TAT elevations were found to correlate with all cytokines; elevations in IL-8 were correlated with elevations in MCP-1 and IL-6 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Endovascular therapy of venous thromboembolic disease.

This article discusses the background and status of inferior vena caval filtration and transvenous catheter techniques for pulmonary embolectomy in the management of venous thromboembolic disease.

Differences in the integration pattern and episomal forms of human papillomavirus type 16 DNA found within an invasive cervical neoplasm and its metastasis.

Human papillomavirus (HPV) type 16 DNA was found in three separate neoplastic lesions within a female patient. The physical state of the viral DNA in each lesion was determined by two-dimensional agarose gel electrophoresis. The primary cervical tumor contained large amounts of several distinct episomal forms as well as integrated HPV DNA. Metastatic tumor tissue found in the vagina had greatly reduced levels of episomal DNA and a viral DNA integration pattern that was different from that of the primary tumor. The vulvar carcinoma in situ had what appears to be free and integrated forms of viral DNA. The results show that although metastatic tissue retained HPV DNA, further rearrangements of the integrated viral DNA pattern found in the primary tumor may occur with a dramatic decrease of episomal forms during malignant progression.

Stress reduction at the worksite: an evaluation of two methods.

Abstract Stress is estimated to cost industry between 75 and 100 billion dollars annually as a result of absenteeism, medical claims and diminished productivity. Two types of stress management programs were studied to evaluate their effectiveness at the worksite. The Time-Life Stress Management Program and a Myers-Briggs Personality Type approach were used. The Time-Life program was given to 113 participants, and 35 participated in the Myers-Briggs program. Baseline stress (strain) scores were obtained using a standardized strain survey instrument. Follow-up strain scores were obtained six to eight months after baseline for 62 percent of the individuals. Both groups showed significant reductions in follow-up strain scores when compared to baseline. Reductions in strain were greater in the group with higher baseline strain scores (Time-Life). Worksite stress management programs have the potential to reduce strain among employees for at least six to eight months.

Prolonged, intravenous paraquat infusion in the rat. I. Failure of coinfused putrescine to attenuate pulmonary paraquat uptake, paraquat-induced biochemical changes, or lung injury.

Paraquat (PQ) was administered to rats for 7 days by iv infusion from osmotic minipump at dosage rates of 250 and 500 nmol PQ/hr. The efficacy of putrescine in attenuating pulmonary PQ accumulation in vivo and the resulting PQ-induced biochemical changes and lung injury were assessed in these animals by coinfusion of putrescine at rates of 2500 or 5000 nmol/hr. Dose-dependent, steady-state blood levels of both PQ and putrescine were achieved by 18 hr and maintained throughout the infusion period. Lung PQ content at 7 days was dose-dependent and up to 18-fold greater than corresponding blood levels. No evidence of toxicity was observed in low-dose PQ animals while weight loss and overt toxicity was observed in high-dose PQ rats between Days 4 and 5. Histopathological examination of high-dose PQ rat lungs revealed qualitative changes typical of PQ toxicity. Significant (p less than 0.05) increases in lung glutathione and activities of glucose-6-phosphate dehydrogenase and GSSG reductase resulted from both PQ doses, reflecting PQ-induced oxidant stress and increased demand on lung NADPH. A net decrease in lung NADPH (p less than 0.05) was directly measured in high-dose PQ rats and may have contributed to the PQ-induced lung injury. Although putrescine is an effective inhibitor of pulmonary PQ uptake in vitro, the blood putrescine levels achieved in this study did not appear to inhibit this process in vivo. This was evidenced by putrescine's failure to decrease 7-day lung PQ content, PQ-induced biochemical changes, or lung injury.

Prolonged, intravenous paraquat infusion in the rat. II. Paraquat-induced alterations in lung polyamine metabolism.

The effects of paraquat (PQ) on lung putrescine, spermidine, and spermine levels, and ornithine decarboxylase (ODC) activity were assessed in rats after 7 days of iv infusion of the herbicide via osmotic minipump. Paraquat administration at a rate of 250 nmol/hr [673 +/- 40 nmol/kg/hr (n = 15)] had no effect on these parameters. In contrast, significant (p less than 0.05) elevations in lung putrescine (407% of control), spermidine (202% of control), and ODC activity (174% of control were measured in lungs of rats given 500 nmol PQ/hr [1.31 +/- 0.53 mumol/kg/hr (n = 14)]. Since evidence of lung damage was, likewise, observed only in the high-dose PQ rats, these changes in polyamine metabolism could have been a nonspecific response to PQ-induced lung injury rather than a direct biochemical effect of PQ. The results suggest that stimulation of polyamine biosynthesis may play an important role in PQ-induced lung injury. This role may involve regulation of repair mechanisms or, conversely, the polyamines may actually mediate PQ-induced fibrotic changes in the lung.

Retropancreatic control of the suprarenal aorta.

An alternative approach to occluding the suprarenal abdominal aorta involves a Kocher maneuver and isolation of the retropancreatic aorta between the origins of the celiac axis and the superior mesenteric artery. The use of this approach is supported by operative dissections upon cadavers, as well as upon two patients in whom it was used without difficulty.

Compliance with mammography recommendations at the work site.

Mammography was recommended to 212 women, according to American Cancer Society guidelines, at the time of a work site-offered periodic health exam (PHE). Sixteen weeks later telephone follow-up determined compliance. A total of 56 (26%) had complied. A second phone contact to 82 noncompliers identified 18 additional women who complied after the first phone contact. Overall compliance (36%) was associated with the presence of physical findings upon breast examination (fibrocystic disease). Compliers did not differ from noncompliers with regard to age, time between PHE and follow-up, or insurance coverage. There was no association between compliance and age greater than or equal to 50 years or previous mammography.

Single-pump techniques for assisted circulation in cardiogenic shock: experimental evaluation and case report.

Acute cardiogenic shock or bridging to transplantation often involves the need for circulatory and cardiac support systems that are more effective than the intraaortic balloon pump. Biventricular failure, which is present in many cases, is generally treated with total cardiac replacement or with a complex of pumps and oxygenator that makes application difficult. With the goal of developing a universally applicable method of cardiac and circulatory support, we undertook a series of canine experiments designed to evaluate the effect of various treatment methods on survival, hemodynamics, and metabolic function. The series involved 123 dogs, in which cardiogenic shock was induced by means of multiple coronary artery ligations. The individual animals were then subjected to bypass, treated medically, or left untreated, depending on random selection. Each treatment lasted for 4 hours and was followed by a 2-hour period of observation. The following single-pump methods were tested: 1) left ventricular (LV) bypass, 2) left atrial (LA) bypass, 3) left ventricular and right atrial (LV + RA) bypass, 4) left atrial and right atrial (LA + RA) bypass, 5) LV + RA bypass, plus treatment with substrates (cysteine and ribose), and 6) LV + RA bypass, plus treatment with fluosol. Each bypass system incorporated a single reservoir and a centrifugal pump, and blood was returned to a femoral artery. Medical therapy consisted of either 1) treatment with sodium nitroprusside alone or 2) treatment with substrates alone. With respect to survival and hemodynamic effects (as reflected by oxygen consumption), LV + RA bypass and LA + RA bypass proved superior. During the posttreatment period, LV + RA bypass was associated with the highest survival rates and, therefore, with the most satisfactory recovery of myocardial or cardiac function. Despite the limited desaturation produced during venous shunting from the right atrium, perfusion of the entire body and consumption of oxygen were least in the LV + RA bypass group. The addition of substrates, or even of fluosol, caused a reduction in oxygen consumption. Our experience also includes one clinical case in which LA + RA bypass was used to support a 57-year-old man for 32 hours, after left atrial bypass alone proved inadequate. The dual-chamber technique brought about an improvement not only in hemodynamics but also in blood-gas values and pH. On the basis of this case and the canine experiments, we conclude that LV + RA and LA + RA bypass techniques offer safe, effective means of long-term temporary support for patients in severe cardiogenic shock.

The T-antigen-binding domain of the simian virus 40 core origin of replication.

The simian virus 40 origin of replication contains a 27-base-pair palindrome with the sequence 5'-CA-GAGGC-C-GAGGC-G-GCCTC-G-GCCTC-TG-3'. The four 5'-GAGGC-3'/5'-GCCTC-3' pentanucleotides are known contact sites for simian virus 40 T-antigen binding in vitro. We used oligonucleotide-directed cassette mutagenesis to identify features of this palindrome that are important for the initiation of DNA replication in vivo. Each base pair of a pentanucleotide is crucial for DNA replication. In contrast, sequences adjacent to pentanucleotides have little or no effect on replication. Thus, the pentanucleotide is the basic functional unit, not only for T-antigen binding but also for DNA replication. All four pentanucleotides are indispensable in the initiation process. The spacing of pentanucleotides is crucial because duplication of the single base pair between binding sites has a far greater effect on replication than does substitution of the same base pair. Inversion of any pentanucleotide blocks DNA synthesis. Thus, the pentanucleotide is not a functionally symmetrical unit. We propose that each pentanucleotide positions a monomer of T antigen at the proper distance, rotation, and orientation relative to other T-antigen monomers and to other origin domains and that such positioning leads to subsequent events in replication.