Clinical observation of posterior decompression, fusion and fixation in the treatment of spinal gout: a case series.

OBJECTIVE: The aim of the present study was to assess the effect of posterior decompression, fusion and fixation in the treatment of spinal gout. Spinal gout is a disease of gouty arthritis involving the spine, which can affect all segments of the spine. At present, the etiology and pathogenesis of spinal gout are not clear, and there are no definite methods for the treatment of spinal gout. METHODS: This was a case series of seven patients (seven men) who underwent posterior decompression, fusion and fixation in the treatment of spinal gout between January 2016 and January 2020. Physical examination, radiography, CT, MRI, Japanese Orthopaedic Association (JOA) score and visual analog scale (VAS) score were used to evaluate the effect of this procedure. All patients were followed up every 3 months. The evaluation time point was 12 months after the operation. Comparisons of the functional indexes of the patients before and after the operation were performed using SPSS 22.0 (IBM, Armonk, NY, USA). RESULTS: The JOA score was 13.43 ± 6.55 and the VAS score was 7.43 ± 1.51 preoperatively. The JOA score was 24.43 ± 3.74 and the VAS score was 0.86 ± 0.90 postoperatively at 12 months after surgery. At 12 months after surgery, the JOA and VAS score showed significant improvements when compared with those before surgery (P = 0.004 and P = 0.002, respectively). None of the patients had re-surgery of the gout due to actively and reasonably controlling uric acid. No loosening or displacement of screws was reported. There was only one screw tail cap loosening. Radiographic examination revealed that there was no obvious accumulation of gout or surrounding bone destruction, and the segmental instability was significantly improved. There was no progressive aggravation of neurological symptoms of the seven patients. CONCLUSIONS: Posterior approach decompression, fusion and fixation can stabilize the vertebral body, remove gout and directly relieve local spinal cord compression. The method is a reliable surgical choice for the treatment of spinal gout.

LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p.

The article "LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p, by M.-M. Wu, W.-D. Shen, C.-W. Zou, H.-J. Chen, H.-M. Guo, published in Eur Rev Med Pharmacol Sci 2020; 24 (11): 6031-6038-DOI: 10.26355/eurrev_202006_21497-PMID: 32572917" has been withdrawn from the authors due to some technical issues in the data retrieval. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21497.

LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p.

OBJECTIVE: The aim of this study was to explore the functional changes of long non-coding ribonucleic acid (lncRNA)-HEIH on hepatocellular carcinoma (HCC) Huh7 and Hep3B cells. PATIENTS AND METHODS: The expression changes of HEIH in 18 pairs of HCC tissues and adjacent normal tissues were detected by quantitative real time-polymerase chain reaction (qRT-PCR). According to its expression changes in HCC cells silenced by short hairpin ribonucleic acid (shRNA) transfection in vitro, these cells were divided into sh-HEIH group and sh-NC group. The effects of lowly expressed HEIH on the proliferation, migration and apoptosis of HCC cells were examined through functional assays. Western blotting was adopted to determine the expression changes of epithelial-mesenchymal transition (EMT) proteins, vimentin, matrix metalloproteinase (MMP)-2 and MMP-3. In addition, the role of HEIH downstream effector micro RNA (miR)-199a-3p in HCC was explored. RESULTS: Compared with adjacent normal tissues, HEIH was highly expressed in HCC tissues (p<0.01). HEIH silencing significantly inhibited the proliferation and migration, but induced the apoptosis of Huh7 cells (p<0.05). The expressions of vimentin and MMP-2 in sh-HEIH group were remarkably lower than those in sh-NC group (p<0.05). Furthermore, miR-199a-3p was identified as the downstream effector of HEIH. The expression of miR-199a-3p increased markedly in Huh7 and Hep3B cells with silenced HEIH expression (p<0.01). Moreover, when miR-199a-3p expression was inhibited, the effects of HEIH on Huh7 and Hep3B cells were weakened, manifested as notably enhanced cell proliferation and migration capabilities (p<0.05). CONCLUSIONS: LncRNA-HEIH suppresses HCC cell growth and metastasis by up-regulating miR-199a-3p. Our findings suggest that HEIH may be a promising target for HCC treatment.

[Effect of endoscopic stent placement combined with neoadjuvant chemotherapy on short-term and long-term results in patients with acute left-sided malignant colorectal obstruction without distant metastases].

Objective: This study aimed to evaluate the outcomes of colorectal obstruction patients without distant metastases treated with different strategies. Methods: This retrospectively study included 82 patients who presented in Beijing Chaoyang Hospital from 2010 to 2015 with acute left-sided malignant colorectal obstruction. Patients with distant metastases were excluded. After informed consent, patients were divided into colonic stenting (SEMS group, n=28) , neoadjuvant chemotherapy(NCT group, n=15) or immediate emergency surgery(control group, n=39). Patients who had successful colonic stenting underwent elective surgery 1 to 2 weeks later or underwent neoadjuvant chemotherapy before elective surgery, while the other group had emergency surgery. Short-term data on postoperative mortality, morbidity, length of intensive care and hospital stay were compared. Overall survival and disease-free survival were also analyzed. Results: Patients in the three study arms had similar demographic profiles. The laparoscopic resection of the NCT and SEMS group was higher than that of the control group, the stoma rate was lower, and the differences were statistically significant[73.3% (11/15) , 42.9% (12/28) vs 25.6% (10/39) (P=0.006) and 13.3% (8/15) , 28.6% (8/28) vs 66.7% (26/39) (P<0.001) respectively].Compared with the SEMS and NCT group, the control group had a higher rate of postoperative complications, less of retrieved lymph nodes, longer of intensive care and lower total hospitalization expenses, and the difference was statistically significant[32.1% (9/28) , 13.3% (2/15) vs 59.0% (23/39) (P=0.004) , 21 (16,25) , 23 (19,34) vs 17 (13,25) (P=0.02) , 1.5 (0,3.0) , 1.0 (0,3.0) vs 3.0 (1.0, 4.0) (P=0.028) and 7.3 (2.8,14.1) , 11.1 (6.9,18.5) vs 7.1 (3.3,37.4) (P=0.004) respectively]. The overall and disease-free survival rate of the NCT group were higher than the SEMS group and control group, and the difference was statistically significant[93.3% (14/15) , 57.1% (16/28) vs 61.5% (24/39) (P=0.033) and 86.7% (13/15) , 53.6% (15/28) vs 51.3% (20/39) (P=0.047) respectively]. There was no significant difference among the NCT, SEMS and control group in the rate of systemic recurrence of the[6.7% (1/15) , 25.0% (7/28) vs 28.2% (11/39) (P=0.243) ]. Conclusions: For acute left-sided malignant colorectal obstruction without distant metastases, endoscopic stent placement combined with NCT not only is a bridge to elective operation, but also significantly improves the long-term results.

[The role of PACAP protein in chronic sinusitis with or without nasal polyps].

Objective:To investigate the expression of PACAP protein in chronic rhinosinusitis without/with nasal polyps and refractory chronic rhinosinusitis.Method: Fifty-three patients with nasal polyps,70 cases with chronic sinusitis, 28 patients with refractory chronic rhinosinusitis and 20 control cases were enrolled for this study. The expression of PACAP protein was detected by immunochemistry.Result: ①PACAP protein were expressed in nasal epithelium，glandular epithelium and goblet cells；②The positive intensity of PACAP was" +", " +++", "－-+",and " ++" in nasal polyps, chronic rhinosinusitis, refractory chronic rhinosinusitis, and control group, respectively.Conclusion:PACAP protein mainly locates in nasal epithelium，glandular epithelium and goblet cells. Reduced expression of PACAP may be related with onset of chronic rhiniosinusitis without/with nasal polyps.

Development of an antioxidant system after early weaning in piglets.

The objective of this experiment was to investigate oxidative injury and the development of an antioxidant system after early weaning in piglets. A total of 40 piglets (Landrace× Large White, weaned at 14 d after birth) were randomly slaughtered 0 (w0d), 1 (w1d), 3 (w3d), 5 (w5d), or 7 d (w7d; n = 8) after weaning. Concentrations of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and protein carbonyl and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase were measured in plasma. Gene expressions of antioxidant enzymes were determined by quantitative reverse transcription PCR analysis. The mediation of transcription factor 65 (p65) and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways by oxidative stress was determined by Western blot analysis. Results showed that the plasma MDA level was significantly higher at 3 d (P < 0.05) and that the protein carbonyl level increased at 1, 3, and 5 d (P < 0.05) compared with w0d. In addition, early weaning suppressed the plasma activity of SOD at 1 d (P < 0.05) and reduced the GSH-Px activity at 3 d (P < 0.05). The expression results in the jejunum indicate that the genes related to antioxidant enzymes were downregulated (P < 0.05) at 3 and 5 d after weaning. Uncoupling protein 2 (Ucp2), which is considered to be a feedback regulation on reactive oxygen species generation, tended to decrease in the ileum (P < 0.05) after weaning. Tumor protein 53 (p53), which regulates reactive oxygen species generation, was enhanced (P < 0.05) in the jejunum after weaning. Meanwhile, early weaning suppressed p65 (at 3, 5, and 7 d; P < 0.05) and Nrf2 (at 5 and 7 d; P < 0.05) signals in the jejunum, which might feedback-regulate antioxidant gene expression and promote the development of the antioxidant system. Therefore, we speculate that weaning disrupted oxidative balance and caused oxidative injury in piglets, and this imbalance can recover with the development of an antioxidant system via feedback regulation.

Association of blood arsenic levels with increased reactive oxidants and decreased antioxidant capacity in a human population of northeastern Taiwan.

Arsenic is a notorious environmental toxicant known as both a carcinogen and an atherogen in human beings, but the pathogenic mechanisms are not completely understood. In cell culture studies, trivalent arsenic enhanced oxidative stress in a variety of mammalian cells, and this association may be closely associated with the development of arsenic-related diseases. To investigate the effect of arsenic exposure on oxidative stress in humans, we conducted a population study to determine the relationships of blood arsenic to reactive oxidants and antioxidant capacity at the individual level. We recruited 64 study subjects ages 42-75 years from residents of the Lanyang Basin on the northeast coast of Taiwan, where arsenic content in well water varies from 0 to > or = 3,000 microg/L. We used a chemiluminescence method, with lucigenin as an amplifier for measuring superoxide, to measure the plasma level of reactive oxidants. We used the azino-diethyl-benzthiazoline sulphate method to determine the antioxidant capacity level in plasma of each study subject. We determined arsenic concentration in whole blood by hydride formation with an atomic absorption spectrophotometer. The average arsenic concentration in whole blood of study subjects was 9.60 +/- 9.96 microg/L (+/- SD) with a range from 0 to 46.50 microg/L. The level of arsenic concentration in whole blood of study subjects showed a positive association with the level of reactive oxidants in plasma (r = +0.41, p = 0.001) and an inverse relationship with the level of plasma antioxidant capacity (r = -0.30, p = 0.014). However, we found no significant association (p = 0.266) between levels of plasma reactive oxidants and antioxidant capacity. Our results also show that the lower the primary arsenic methylation capability, the lower the level of plasma antioxidant capacity (p = 0.029). These results suggest that ingestion of arsenic-contaminated well water may cause deleterious effects by increasing the level of reactive oxidants and decreasing the level of antioxidant capacity in plasma of individuals. Persistent oxidative stress in peripheral blood may be a mechanism underlying the carcinogenesis and atherosclerosis induced by long-term arsenic exposure.

Mechanisms of pH regulation in the regulated secretory pathway.

A precise pH gradient between organelles of the regulated secretory pathway is required for sorting and processing of prohormones. We studied pH regulation in live endocrine cells by targeting biotin-based pH indicators to cellular organelles expressing avidin-chimera proteins. In AtT-20 cells, we found that steady-state pH decreased from the endoplasmic reticulum (ER) (pH(ER) = 7.4 +/- 0.2, mean +/- S.D.) to Golgi (pH(G) = 6.2 +/- 0.4) to mature secretory granules (MSGs) (pH(MSG) = 5.5 +/- 0.4). Golgi and MSGs required active H(+) v-ATPases for acidification. ER, Golgi, and MSG steady-state pH values were also dependent upon the different H(+) leak rates across each membrane. However, neither steady-state pH(MSG) nor rates of passive H(+) leak were affected by Cl(-)-free solutions or valinomycin, indicating that MSG membrane potential was small and not a determinant of pH(MSG). Therefore, our data do not support earlier suggestions that organelle acidification is primarily regulated by Cl(-) conductances. Measurements of H(+) leak rates, buffer capacities, and estimates of surface areas and volumes of these organelles were applied to a mathematical model to determine the H(+) permeability (P(H+)) of each organelle membrane. We found that P(H+) decreased progressively from ER to Golgi to MSGs, and proper acidification of Golgi and MSGs required gradual decreases in P(H+) and successive increases in the active H(+) pump density.

Risk of internal cancers from arsenic in drinking water.

The U.S. Environmental Protection Agency is under a congressional mandate to revise its current standard for arsenic in drinking water. We present a risk assessment for cancers of the bladder, liver, and lung from exposure to arsenic in water, based on data from 42 villages in an arseniasis-endemic region of Taiwan. We calculate excess lifetime risk estimates for several variations of the generalized linear model and for the multistage-Weibull model. Risk estimates are sensitive to the model choice, to whether or not a comparison population is used to define the unexposed disease mortality rates, and to whether the comparison population is all of Taiwan or just the southwestern region. Some factors that may affect risk could not be evaluated quantitatively: the ecologic nature of the data, the nutritional status of the study population, and the dietary intake of arsenic. Despite all of these sources of uncertainty, however, our analysis suggests that the current standard of 50 microg/L is associated with a substantial increased risk of cancer and is not sufficiently protective of public health.

Anticalculus effect of two zinc citrate/essential oil-containing dentifrices.

PURPOSE: To assess the feasibility of incorporating zinc citrate, a known anticalculus ingredient, into a dentifrice formulation containing a fixed combination of essential oils, a known antiplaque/antigingivitis agent. MATERIALS AND METHODS: This randomized, parallel, double-blind study evaluated the potential of two essential oil dentifrice formulations containing different levels of zinc citrate (1.0% and 2.0% ZCT) to reduce supragingival calculus formation compared to a marketed control dentifrice, Crest Regular. Following a 3-month pre-test phase, subjects received a dental prophylaxis, were stratified into three balanced groups on the basis of Volpe-Manhold calculus scores and brushed twice daily with their assigned dentifrice for 3 months. RESULTS: One hundred ninety-six evaluable subjects completed all phases of the study. ANCOVA revealed that the 1.0% ZCT and 2.0% ZCT essential oil dentifrice formulations provided significant reductions in calculus formation of 26.4% and 29.0% (P< 0.001), respectively, compared to the control dentifrice, Crest Regular. The magnitude of calculus reductions is similar to those levels obtained by other zinc salt formulations.

DNA repair methyltransferase (Mgmt) knockout mice are sensitive to the lethal effects of chemotherapeutic alkylating agents.

We have generated mice deficient in O6-methylguanine DNA methyltransferase activity encoded by the murine Mgmt gene using homologous recombination to delete the region encoding the Mgmt active site cysteine. Tissues from Mgmt null mice displayed very low O6-methylguanine DNA methyltransferase activity, suggesting that Mgmt constitutes the major, if not the only, O6-methylguanine DNA methyltransferase. Primary mouse embryo fibroblasts and bone marrow cells from Mgmt -/- mice were significantly more sensitive to the toxic effects of the chemotherapeutic alkylating agents 1,3-bis(2-chloroethyl)-1-nitrosourea, streptozotocin and temozolomide than those from Mgmt wild-type mice. As expected, Mgmt-deficient fibroblasts and bone marrow cells were not sensitive to UV light or to the crosslinking agent mitomycin C. In addition, the 50% lethal doses for Mgmt -/- mice were 2- to 10-fold lower than those for Mgmt +/+ mice for 1,3-bis(2chloroethyl)-1-nitrosourea, N-methyl-N-nitrosourea and streptozotocin; similar 50% lethal doses were observed for mitomycin C. Necropsies of both wild-type and Mgmt -/mice following drug treatment revealed histological evidence of significant ablation of hematopoietic tissues, but such ablation occurred at much lower doses for the Mgmt -/- mice. These results demonstrate the critical importance of O6-methylguanine DNA methyltransferase in protecting cells and animals against the toxic effects of alkylating agents used for cancer chemotherapy.

A chemical and genetic approach together define the biological consequences of 3-methyladenine lesions in the mammalian genome.

DNA-damaging agents produce a plethora of cellular responses that include p53 induction, cell cycle arrest, and apoptosis. It is generally assumed that it is the DNA damage produced by these agents that triggers such responses, but there is limited direct evidence to support this assumption. Here, we used DNA alkylation repair proficient and deficient isogenic mouse cell lines to demonstrate that the signal to trigger p53 induction, cell cycle arrest, and apoptosis in response to alkylating agents does emanate from DNA damage. Moreover, we established that 3-methyladenine, a relatively minor DNA lesion produced by most methylating agents (which form mainly 7-methylguanine), can specifically induce sister chromatid exchange, chromatid and chromosome gaps and breaks, S phase arrest, the accumulation of p53, and apoptosis. This study was made possible by the generation of 3-methyladenine DNA glycosylase null mutant cells by targeted homologous recombination and by the chemical synthesis of a methylating agent that almost exclusively produces 3-methyladenine DNA lesions. The combined use of these two experimental tools has defined the biological consequences of 3-methyladenine, a DNA lesion produced by endogenous cellular metabolites, environmental carcinogens, and chemotherapeutic alkylating agents.

Multiple risk factors associated with arsenic-induced skin cancer: effects of chronic liver disease and malnutritional status.

In order to evaluate the prevalence and multiple risk factors of arsenic-induced skin cancer among residents in Taiwanese villages in which chronic arseniasis is hyperendemic, a total of 1571 subjects aged 30 or more years were recruited between September 1988 and March 1989. All of them were interviewed personally by a public health nurse using a structured questionnaire, and 1081 interviewed study subjects, including 468 men and 613 women, participated in physical examination, giving a participation rate of 68.8%. The overall prevalence of skin cancer was as high as 6.1%, showing an increase with age in both men and women. There was a significant dose-response relation between skin cancer prevalence and chronic arsenic exposure as indexed by duration of residence in the endemic area, duration of consumption of high-arsenic artesian well water, average arsenic exposure in parts per million (p.p.m.) and cumulative arsenic exposure in p.p.m.-years. Chronic carriers of hepatitis B surface antigen with liver dysfunction had an increased prevalence of skin cancer. Undernourishment, indexed by a high consumption of dried sweet potato as a staple food, was also significantly associated with an increased prevalence of arsenic-induced skin cancer. All these risk factors remained statistically significant in the multiple logistic regression analysis. Consistent with animal experiments, the findings imply that liver function and nutritional status may affect the metabolism of inorganic arsenic and the development of subsequent skin cancers.

Prevalence of human papillomaviruses 16 and 18 in transitional cell carcinoma of bladder.

It has been speculated that human papillomaviruses (HPV) might be a causative agent of transitional cell carcinoma of the bladder. With the polymerase chain reaction technic, fresh specimens of 53 transitional cell carcinomas of the bladder were examined, and bladder epithelium from 12 patients with hyperplasia of prostate and peripheral blood lymphocytes of 8 normal individuals served as controls. The primers set for HPV-16 and 18 were selected from E6/E7 regions of open reading frames. HPV-16 was positive in 52.8% of the specimens examined, whereas HPV-18 positive in only 3.7%. No controls showed either HPV-16 or 18. Reports on the role of HPVs in carcinogenesis of bladder are scanty and yet there exist conspicuous discrepancies among them. There is a diversity of opinions on the contamination and variation of technical procedures. More work should be done before the relationship between HPV-16 and development of bladder carcinoma can be clarified.

Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water.

In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.

Voltage dependence of current through the Na,K-exchange pump of Rana oocytes.

We have studied current (IStr) through the Na,K pump in amphibian oocytes under conditions designed to minimize parallel undesired currents. Specifically, IStr was measured as the strophanthidin-sensitive current in the presence of Ba2+, Cd2+ and gluconate (in place of external Cl-). In addition, IStr was studied only after the difference currents from successive applications and washouts of strophanthidin (Str) were reproducible. The dose-response relationship to Str in four oocytes displayed a mean K0.5 of 0.4 microM, with 2-5 microM producing 84-93% pump block. From baseline data with 12 Na(+)-preloaded oocytes, voltage clamped in the range [-170, +50 mV] with and without 2-5 microM Str, the average IStr depended directly on Vm up to a plateau at 0 mV with interpolated zero current at -165 mV. In three oocytes, lowering the external [Na+] markedly decreased the voltage sensitivity of Ip, while producing only a small change in the maximal outward IStr. In contrast, decreasing the external [K+] from 25 to 2.5 mM reduced IStr at 0 mV without substantially affecting its voltage dependence. At K+ concentrations of less than 1 mM, both the absolute value of IStr at 0 mV and the slope conductance were reduced. In eight oocytes, the activation of the averaged IStr by [K+]0 over the voltage interval [-30, +30 mV] was well fit by the Hill equation, with K' = 1.7 +/- 0.4 mM and nH (the minimum number of K+ binding sites) = 1.7 +/- 0.4. The results unequivocally establish that the cardiotonic-sensitive current of Rana oocytes displays only a positive slope conductance for [K+]0 greater than 1 mM. There is therefore no need to postulate more than one voltage-sensitive step in the cycling of the Na, K pump under physiologic conditions. The effects of varying external Na+ and K+ are consistent with results obtained in other tissues and may reflect an ion-well effect.

Demethylation pathways in caffeine metabolism as indicators of variability in 1,1,1-trichloroethane oxidation in man.

Twenty volunteers were exposed to 191 +/- 7 p.p.m. 1,1,1-trichloroethane or 50 +/- 2 p.p.m. perchloroethylene vapour for 6 hr. They were then evaluated for their rate of caffeine metabolism, mephenytoin hydroxylation and debrisoquine hydroxylation. Seven subjects were identified as 'fast acetylators' of caffeine and one person as a slow metabolizer of debrisoquine. The "slow acetylators" exposed to perchloroethylene excreted an average of 3.83 +/- 0.35 mg trichloroacetic acid within 24 hr (N = 13, +/- S.E.) and the 'fast acetylators' 3.58 +/- 0.48 mg (N = 7, +/- S.E.). The excretion of trichloroethanol by the same persons after 1,1,1-trichloroethane exposure was 14.1 +/- 1.12 mg and 16.7 +/- 1.48 mg, respectively. The excretion of trichloroacetic acid in the latter exposure varied significantly between the seven 'fast' and 13 'slow acetylators' (0.43 +/- 0.08 mg versus 1.03 +/- 0.19 mg; +/- S.E.; P = 0.037). A multiple linear regression analysis confirmed this association when other factors, such as body weight, creatinine clearance, smoking habit and alcohol consumption, were taken into account. One volunteer proved to be a poor hydroxylator of debrisoquine and excreted half the amount of trichloroacetic acid in the perchloroethylene exposure and half the amount of trichloroethanol in the 1,1,1-trichloroethane exposure compared to the others. A reduction in the solvent metabolism could thus be predicted by the debrisoquine test. On the other hand, the caffeine test predicted faster oxidation of trichloroethanol which could be of toxicological and pharmacological importance e.g. in the clinical use of chloral.

Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group.

Serum concentrations of immunoreactive tumor necrosis factor/cachectin (TNF), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), and interferon-alpha (IFN alpha) were prospectively measured in 70 patients with septic shock to determine their evolution and prognostic values. In a univariate analysis, levels of TNF (P = .002) and IL-1 beta (P = .05) were associated with the patient's outcome, but not IFN alpha (P = .15) and IFN gamma (P = .26). In contrast, in a stepwise logistic regression analysis, the severity of the underlying disease (P = .01), the age of the patient (P = .02), the documentation of infection (nonbacteremic infections vs. bacteremias, P = .03), the urine output (P = .04), and the arterial pH (P = .05) contributed more significantly to prediction of patient outcome than the serum levels of TNF (P = .07). After 10 days, the median concentration of TNF was undetectable (less than 100 pg/ml) in the survivors, whereas it remained elevated (305 pg/ml, P = .002) in the nonsurvivors. Thus, in patients with septic shock due to various gram-negative bacteria, other parameters than the absolute serum concentration of immunoreactive TNF contributed significantly to the prediction of outcome.

Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases.

Age-adjusted mortality rates were analyzed to examine the dose-response relation between ingested arsenic levels and risk of cancers and vascular diseases among residents in the endemic area of blackfoot disease, a unique peripheral vascular disease associated with long-term exposure to high-arsenic artesian well water and confined to the southwestern coast of Taiwan. The arsenic levels in well water determined in 1964-1966 were available in 42 villages of the study area, while mortality and population data during 1973-1986 were obtained from the local household registration offices and Taiwan Provincial Department of Health. Age-adjusted mortality rates from various cancers and vascular diseases by sex were calculated using the 1976 world population as the standard population. A significant dose-response relation was observed between arsenic levels in well water and cancers of the bladder, kidney, skin, and lung in both males and females, and cancers of the prostate and liver in males. However, there was no association for cancers of the nasopharynx, esophagus, stomach, colon, and uterine cervix, and for leukemia. Arsenic levels in well water were also associated with peripheral vascular diseases and cardiovascular diseases in a dose-response pattern, but not with cerebrovascular accidents. The dual effect of arsenic on carcinogenesis and arteriosclerosis and the interrelation between these two pathogenic mechanisms deserve more intensive study.