The association between the socioeconomic status and anxiety-depression comorbidity in patients with psoriasis: a nationwide population-based study.

BACKGROUND: Numerous studies have indicated that comorbid anxiety and depression are associated with a more severe course of illness. Yet generally, the study of the effect of psoriasis on patients' mental health has considered anxiety and depression to be separate states. OBJECTIVE: To measure the association between psoriasis and anxiety, depression and anxiety-depression co-occurrence among patients according to their socioeconomic statuses (SES). METHODS: A nationwide population-based study of psoriasis patients and age and gender frequency-matched controls (n = 255 862) was designed. Diagnostic data were obtained from Clalit Health Services, the largest managed care organization in Israel. This database was established using continuous real-time input from healthcare providers, pharmacies, medical care facilities and administrative computerized operating systems. RESULTS: After controlling for demographic and clinical variables, psoriasis was associated with anxiety (OR 1.11, 95% CI 1.01-1.23, P < 0.05), depression (OR 1.17, 95% CI 1.08-1.26, P < 0.001), and anxiety and depression co-occurrence (OR 1.32, 95% CI 1.21-1.45, P < 0.001) among patients with low SES, yet was associated only with anxiety (OR 1.15 95% CI 1.04-1.27, P < 0.001) but not depression or comorbid anxiety-depression among patients with high SES. Survival analyses indicated that between the ages of 40 and 60, the cumulative probability of psoriasis patients with low SES to suffer from anxiety, depression and their co-occurrence inclined more sharply with age as compared to psoriasis patients with high SES. CONCLUSIONS: As psoriasis patients with low SES are prone to suffer from more severe courses of anxiety and depression, the choice of treatment of psoriasis should address the SES as well as the underlying psychiatric disease.

Minimally invasive colon resection for malignant colonic conditions is associated with a transient early increase in plasma sVEGFR1 and a decrease in sVEGFR2 levels after surgery.

INTRODUCTION: Plasma VEGF levels increase after minimally invasive colorectal resection (MICR) and remain elevated for 2-4 weeks. VEGF induces physiologic and pathologic angiogenesis by binding to endothelial cell (EC) bound VEGF-Receptor-1 (VEGFR1) and VEGFR2. Soluble forms of these receptors sequester plasma VEGF, decreasing the amount available to bind to EC-bound receptors. Ramifications of surgery-related plasma VEGF changes partially depend on plasma levels of sVEGFR1 and sVEGFR2. This study assessed perioperative sVEGFR1 and sVEGFR2 levels after MICR in patients with colorectal cancer. METHODS: Forty-five patients were studied; blood samples were taken from all patients preoperatively (preop) and on postoperative days (POD) 1 and 3; in most a fourth sample was drawn between POD 7-30. Late samples were bundled into two time points: POD 7-13 and POD 14-30. sVEGFR1 and sVEGFR2 levels were measured via ELISA. sVEGFR2 data are reported as mean +/- SD and were assessed with the paired samples t test. sVEGFR1 data were not normally distributed. They are reported as median and 95% confidence interval (CI) and were assessed with the Wilcoxon signed-Rank test (p < 0.05). RESULTS: Preoperatively, the mean plasma sVEGFR2 level (7583.9 pg/ml) was greater than the sVEGFR1 result (98.3 pg/ml). Compared with preop levels, sVEGFR2 levels were significantly lower on POD 1 (6068.2 pg/ml, +/-2034.5) and POD 3 (6227.6 pg/ml, +/-2007.0), whereas sVEGFR1 levels were significantly greater on POD 1 (237.5 pg/ml; 95% CI, 89.6-103.5), POD 3 (200.2 pg/ml; 95% CI, 159-253), and POD 7-13 (102.9 pg/ml; 95% CI, 189.7-253). No differences were found on POD 7-13 for sVEGFR2 or POD 14-30 for either protein. CONCLUSIONS: sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; sVEGFR2 changes dominate due to their much larger magnitude. The net result is less plasma VEGF bound by soluble receptors and more plasma VEGF available to bind to ECs early after surgery.

Colorectal resection, both open and laparoscopic-assisted, in patients with benign indications is associated with proangiogenic changes in plasma angiopoietin 1 and 2 levels.

INTRODUCTION: Plasma vascular endothelial growth factor (VEGF) levels are increased after surgery and may stimulate tumor growth after cancer resection. Angiopoietin 1 (Ang 1) and Ang 2 are proteins that impact VEGF-related angiogenesis (VRA). Ang 1 stabilizes mature vessels and inhibits VRA, whereas Ang 2 destabilizes vessels and promotes VRA. The ratio of Ang 1 to Ang 2 reflects the net effect; a low ratio promotes VRA. This study's purpose was to determine the impact of open and minimally invasive (MIS) colorectal resection (CR) for benign indications on plasma Ang 1 and 2 levels. METHODS: A total of 30 patients operated by MIS and 26 operated by open procedure were studied. Plasma was obtained preoperatively (PO) and on postoperative days (POD) 1 and 3. Plasma Ang 1 and Ang 2 levels were assessed via enzyme-linked immunosorbent assay (ELISA) in duplicate. Data were compared using Wilcoxon's matched-pair test and the Mann-Whitney U-test (significance p < 0.05). RESULTS: Indications, types of resection, and morbidity for the groups were similar. The mean MIS incision length was 4.7 +/- 1.6 cm while it was 16.8 +/- 7.1 cm for the open group (p = 0.0001). For both groups Ang 2 levels were significantly higher and the Ang 1 to Ang 2 ratio was significantly lower on POD 1 and 3 compared with preoperative results. Ang 1 levels were significantly decreased on POD 1 and 3 in the MIS group but only on POD 1 in the open group. For unclear reasons, preoperative Ang 1 levels and Ang 1 to Ang 2 ratios were significantly different between the groups, which precludes comparison of the postoperative results between groups. CONCLUSION: CR for benign pathology results in higher Ang 2 levels, lower Ang 1 levels, and lower Ang 1 to Ang 2 ratios early after surgery. These alterations are proangiogenic. These results, plus the already noted VEGF increases, suggest that surgery results in proangiogenic plasma protein changes that may stimulate tumor growth early after surgery. The duration of the Ang 1 and 2 changes needs to be determined.

Minimally invasive colon resection is associated with a transient increase in plasma sVEGFR1 levels and a decrease in sVEGFR2 levels during the early postoperative period.

INTRODUCTION: Plasma vascular endothelial growth factor (VEGF) levels are elevated for 2-4 weeks after minimally invasive colorectal resection (MICR). VEGF induces wound and tumor angiogenesis by binding to endothelial cell (EC)-bound VEGF-receptor 1 (VEGFR1) and VEGFR2. Soluble receptors (sVEGFR1, sVEGFR2) sequester VEGF in the blood and decrease VEGF's proangiogenic effect. The importance of the MICR-related VEGF changes depends on the effect of surgical procedures on sVEGFR1 and sVEGFR2; this study assessed levels of these proteins after MICR for benign indications. METHODS: Blood samples were taken (n=39) preoperatively (preop) and on postoperative days (POD) 1 and 3; in most cases a fourth sample was drawn between POD 7 and 30. sVEGFR1 and sVEGFR2 levels were measured via enzyme-linked immunosorbent assay (ELISA), which detects free and VEGF bound soluble receptor. Late samples were bundled into POD 7-13 and POD 14-30 time points. Results are reported as mean and standard deviation. The data was assessed with paired-samples t-test. RESULTS: Preop, mean plasma sVEGFR2 level (9,203.7+/-1,934.3 pg/ml) was significantly higher than the sVEGFR1 value (132.5+/-126.2 pg/ml). sVEGFR2 levels were significantly lower on POD 1 (6,957.8+/-1,947.7 pg/ml,) and POD 3 (7,085.6+/-2,000.2 pg/ml), whereas sVEGFR1 levels were significantly higher on POD 1 (220.0+/-132.8 pg/ml) and POD 3 (182.7+/-102.1 pg/ml) versus preop results. No differences were found on POD 7-13 or 14-30. CONCLUSIONS: sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; due to its much higher baseline, the sVEGFR2 changes dominate. The net result is less VEGF bound to soluble receptor and more free plasma VEGF.

Persistent elevation of plasma vascular endothelial growth factor levels during the first month after minimally invasive colorectal resection.

BACKGROUND: Elevations of plasma vascular endothelial growth factor (VEGF) have been noted early after colorectal resection. The duration of this increase is unknown. Because VEGF is a potent promoter of angiogenesis, which is critical to tumor growth, a sustained increase in blood VEGF levels after surgery may stimulate the growth of residual metastases early after surgery. This preliminary study aimed to determine VEGF levels during the first month after colorectal resection. METHODS: Patients from three prospective studies that had late postoperative blood samples available comprised the study population. Demographic, perioperative, pathologic, and complication data were collected. Plasma samples were obtained preoperatively for all patients: on postoperative day (POD) 1 for most patients and at varying time points thereafter during the first month after surgery and beyond. Levels of VEGF were determined via enzyme-linked immunoassay (ELISA) and compared using Wilcoxon's matched pairs test. Because the numbers of specimens beyond POD 5 were limited, samples from 7-day time blocks were bundled and averaged to permit statistical analysis. RESULTS: A total of 49 patients with cancer and 30 patients with benign indications, all of whom underwent minimally invasive colorectal resection, were assessed separately. With regard to the patients with cancer, the median preoperative plasma value was 150 pg/ml, and the peak postoperative median value for the POD 14 to 20 time block was 611.1 pg/ml. Furthermore, compared with the preoperative results, significant VEGF elevations were noted on POD 3 as well as during week 2 (POD 7-13), week 3 (POD 14-20), and week 4 (POD 21-27) (p < 0.05 for each). With regard to the benign patients, the median preoperative VEGF level was 112 pg/ml, and the peak postoperative value, 286 pg/ml, was noted during postoperative week 2. Significant elevations were noted on POD 3, and for weeks 2 and 3 as well as for POD 28 and later. Between 63% and 89% of the patients at each time point beyond POD 5 had elevated VEGF levels. CONCLUSION: This preliminary study demonstrates that after minimally invasive colorectal resection for cancer, median VEGF levels are significantly elevated on POD 3 and remain increased for as long as 4 weeks. Significant elevations in a similar pattern also were noted for the benign patients. However, the baseline and postoperative median values were lower. The clinical impact from increased blood levels of VEGF is uncertain. It is possible that the growth of residual tumor deposits may be stimulated early after surgery. These results warrant a larger study as well as endothelial cell in vitro assays to determine whether postoperative plasma stimulates proliferation and invasion.

Prevention of gram-negative bacillary pneumonia using aerosol polymyxin as prophylaxis. I. Effect on the colonization pattern of the upper respiratory tract of seriously ill patients.

A prospective study used polymyxin B by aerosol to reduce colonization of the upper respiratory tract with nosocomial gram-negative bacilli. 58 high-risk patients from the Respiratory-Surgical Intensive Care Unit entered the trial. 33 were randomly selected to receive 2.5 mg/kg/day of polymyxin B by hand atomizer into the pharynx, and tracheal tube if present. 17 of 25 control patients became colonized with gram-negative bacilli as compared with 7 of 33 polymyxin-treated patients (p < 0.01). Control patients became colonized with a total of 33 gram-negative bacilli: 3 were Pseudomonas aeruginosa, 21 were species of Enterobacteriaceae. The polymyxin-treated patients became colonized with a total of 11 gram-negative bacilli: no P. aeruginosa and only 3 species of Enterobacteriaceae were recovered. Colonization increased with duration in Respiratory-Surgical Intensive Care Unit and with time of required controlled ventilation. Polymyxin most effectively prevented the increase in colonization in treated patients who stayed in the Respiratory-Surgical Intensive Care Unit for longer than 1 wk and who required controlled ventilation for at least 72 h.

Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients.

All 744 patients admitted to a Respiratory-Surgical Intensive Care Unit (RSICU) were included in a prospective study of the effects of a polymyxin (2.5 mg/kg body wt/day in six divided doses) or a placebo aerosol sprayed into the posterior pharynx and tracheal tube (if present), during 11 alternating 2-mo treatment cycles. The incidence of upper airway colonization in the RSICU with Pseudomonas aeruginosa was 1.6% during the polymyxin treatment cycles (total 374 patients) and 9.7% during the placebo cycles (370 patients) (X2 equals 23.2, P less than 0.01). 3 patients in the RSICU acquired Pseudomonas pneumonia, as defined by independent "blinded" assessors, during the polymyxin cycles while 17 acquired a Pseudomonas pneumonia during the placebo cycles (X2 equals 10.2, P less than 0.01). The overall mortality was similar in both placebo and polymyxin-treated groups (12.2 vs. 12.0%). Systemic antibiotic usage was similar in the different cycles; 49% of patients in the placebo and 53% in the polymyxin-treated groups received systemic antibiotics while in the RSICU.

L-Rhamnose dehydrogenase of pullularia pullulans.

Growth of Pullularia pullulans on L-rhamnose induces formation of L-rhamnofuranose dehydrogenase, whichreversibly converts L-rhamnofuranose to L-rhamnono-gamma-lactone with the concomitant reduction of NAD, but not of NADP. The dehydrogenase was purified 100-fold by MnCl(2) treatment...

UDP-glucose dehydrogenase from Escherichia coli. Purification and subunit structure.

UDPglucose dehydrogenase from Escherichia coli has been purified 330-fold with an overall yield of 27%. A single homogeneous subunit was demonstrated by ultracentrifugation in 6 M guanidium chloride and by dodecyl sulfate-polyacrylamide gel electrophoresis. Since the molecular weight of the intact dehydrogenase is in the order of 86 000 and the subunit weight determined by the dodecyl sulfate-polyacrylamide gel electrophoresis is 47 000, the enzyme consists of two polypeptide chains. The sole amino terminal acid shown by the dansylation technique was arginine. Forty-four tryptic peptides were obtained by peptide mapping, in agreement with the number of arginine and lysine residues/mole protein [43] determined by amino acid analysis. The data are consistent with the presence of two identical or very similar polypeptide chains in E. coli UDPglucose dehydrogenase.

Special effects of UDP-sugar binding to bovine liver uridine diphosphoglucose dehydrogenase.

The binding of NADH to uridine diphosphate glucose dehydrogenase has been examined by equilibrium dialysis. There is an absolute requirement for the presence of UDP-glucose for the binding of NADH. Other analogs such as UDPxylose, UDPgalactose and UDPglucuronic acid cannot replace UDPglucose as an effector of NADH binding. UDPxylose competes with UDPglucose for the UDP-sugar-binding site, and in so doing releases the bound NADH. The binding of NADH to UDPglucose dehydrogenase in the presence of UDPglucose reaches a saturation limit of 3 mol NADH bound per enzyme hexamer, and displays positive cooperativity, Hill number = 1.34. The effects of UDP-sugars on the fluorescence of UDPglucose dehydrogenase derivatized at the catalytic sites with a fluorophore have also been studied. Two classes of UDPxylose-binding site have been detected. One class has high affinity (Kdiss = 3 microM, determined by equilibrium dialysis) but does not affect fluorophore fluorescence, and the other has lower affinity (Kdiss = 120 microM) and leads to red-shifted fluorescence quenching, presumably by effecting exposure of the fluorophore to solvent. The high-affinity sites are identified as the UDP-sugar subsites of the underivatized catalytic sites, and the low-affinity sites as UDP-sugar subsites of the fluorophore-labeled catalytic sites.

Induced versus pre-existing asymmetry models for the half-of-the-sites reactivity effect in bovine liver uridine diphosphoglucose dehydrogenase.

Half-of-the-sites reactivity of the catalytic site thiol groups of UDPglucose dehydrogenase (UDPglucose:NAD+ 6-oxidoreductase, EC 1.1.1.22) can be ascribed either to the induction of conformational asymmetry following derivatization of one half of the subunits or to intrinsic conformational differences in the subunits of the native enzyme. If the half-sites reactivity behavior is due to induction effects, the magnitude of the induction could be expected to depend on the nature of the covalent modification. On the other hand, if the half-sites reactivity behavior is due to pre-existing asymmetry and there is no communication between catalytic centers, the properties of unmodified sub-units should be independent of the nature of the covalent derivative introduced on the modified subunits. According to the induced asymmetry hypothesis, the catalytic activity of half-sites modified enzyme might be different for different covalent modifications, whereas for the rigid pre-existing asymmetry hypothesis the catalytic activity of half-sites modified enzyme should be the same regardless of the modifying group. During the course of catalytic site thiol group modification by a number of thiol specific reagents, the loss of enzyme activity was equivalent to the degree of modification for most of the reagents employed. However, with iodoacetate and 5-(iodoacetamidoethyl)aminonaphthalene-1-sulfonic acid, half-sites modification of UDPglucose dehydrogenase reduced catalytic activity by 58 and 78%, respectively, of the initial activity. These observations are consistent with a model in which there is communication between catalytic sites. Electron microscopy shows that the six subunits of UDPglucose dehydrogenase are arranged as a hexagonal planar ensemble.

UDP-glucose dehydrogenase from bovine liver: primary structure and relationship to other dehydrogenases.

The primary structure of bovine liver UDP-glucose dehydrogenase (UDPGDH), a hexameric, NAD(+)-linked enzyme, has been determined at the protein level. The 52-kDa subunits are composed of 468 amino acid residues, with a free N-terminus and a Ser/Asn microhetergeneity at one position. The sequence shares 29.6% positional identity with GDP-mannose dehydrogenase from Pseudomonas, confirming a similarity earlier noted between active site peptides. This degree of similarity is comparable to the 31.1% identity vs. the UDPGDH from type A Streptococcus. Database searching also revealed similarities to a hypothetical sequence from Salmonella typhimurium and to "UDP-N-acetyl-mannosaminuronic acid dehydrogenase" from Escherichia coli. Pairwise identities between bovine UDPGDH and each of these sequences were all in the range of approximately 26-34%. Multiple alignment of all 5 sequences indicates common ancestry for these 4-electron-transferring enzymes. There are 27 strictly conserved residues, including a cysteine residue at position 275, earlier identified by chemical modification as the expected catalytic residue of the second half-reaction (conversion of UDP-aldehydoglucose to UDP-glucuronic acid), and 2 lysine residues, at positions 219 and 338, one of which may be the expected catalytic residue for the first half-reaction (conversion of UDP-glucose to UDP-aldehydoglucose). A GXGXXG pattern characteristic of the coenzyme-binding fold is found at positions 11-16, close to the N-terminus as with "short-chain" alcohol dehydrogenases.(ABSTRACT TRUNCATED AT 250 WORDS)

Augmentation of natural killer cell activity in mice by Bru-Pel.

The immunomodulatory and anti-tumor activity of Bru-Pel, an aqueous-ether extracted residue of Brucella abortus (strain 456), was investigated. Bru-Pel was administered to C57BL/6 mice intraperitoneally (i.p.) and tested for its effect on natural killer (NK) cell activity in spleen cells, liver, and peritoneal cavity. Three days after injecting 100 micrograms of Bru-Pel i.p., the cytotoxicity of spleen cells against YAC-1 target cells, assessed by LU20 increased by approximately two-fold and nonparenchymal cells of liver by greater than six-fold. The highest stimulatory effect of Bru-Pel was seen with peritoneal exudate cells, and 47-fold augmentation of NK cell activity was observed. Bru-Pel treatment made spleen, liver, and peritoneal exudate cells capable of lysing P815 mastocytoma cells, a tumor cell line highly resistant to lysis by unstimulated NK cells. In vivo, Bru-Pel inhibited the formation of experimental BL6 melanoma metastases; however, there was no significant effect on the eradication of established pulmonary metastatic lesions. These results demonstrate that in addition to its previously described macrophage-activating ability, Bru-Pel is highly efficient in stimulation of NK cell-mediated cytotoxicity in mice.

Detection of 3-hydroxy fatty acids at picogram levels in biologic specimens. A chemical method for the detection of Neisseria gonorrhoeae?

A method for the detection of 3-hydroxy dodecanoic acid at low picogram levels is described. The procedure involves preparation of a heptafluorobutryl derivative of the butyl ester of the fatty acid and its detection by gas-liquid chromatography using an electron capture detector. The method was adapted for use with biological specimens. Potential of the method for screening for gonococcal infection is discussed. Limitations of the method are that about 105 Neisseria gonorrhoeae cells are required for detection and that interfering substances are a major problem working at maximum sensitivity of the electron capture detector necessitating complex purification procedures. The method eliminates the need to maintain the viability of cells in specimens, thus facilitating collection and transport of specimens.

Mechanisms of action of the antimycotic imidazoles.

The mechanism of the antifungal action of the imidazole antimycotics, miconazole ano clotrimazole, on Saccharomyces cerevisiae was explored. When grown aerobically both drugs were fungistatic at low concentrations and fungicidal at high concentrations. When grown anaerobically the fungistatic effect was not seen, but killing still occurred at high concentrations. The fungistatic effect correlated with inhibition of ergosterol synthesis and elevated lanosterol/ergosterol ratios in the organisms. The fungicidal effect involved rapid membrane damage and was unrelated to the imidazole-induced block in ergosterol synthesis. These agents each have 2 distinct antifungal actions.

Frequency and some properties of clinical isolates of methicillin-resistant Staphylococcus aureus.

Of 420 Staphylococcus aureus isolates, 3.1% were methicillin resistant. Most of the 13 isolates were from the flora of hospitalized patients. The organisms were also resistant to nafcillin and cephalothin. They shared many of the properties with methicillin-resistant staphylococci accumulated from other sources except for the lack of lysozyme-like activity.

Ultrasound and sestamibi scan as the only preoperative imaging tests in reoperation for parathyroid adenomas.

BACKGROUND: In an effort to determine an efficient algorithm for the evaluation of patients with parathyroid adenomas in the reoperative setting, we explored the combination of using ultrasound scans (US) and sestamibi scintigraphy as the only preoperative imaging tests. METHODS: We analyzed the outcomes of 62 consecutive patients who were treated between January 1995 and May 1999 and who were referred for persistent primary hyperparathyroidism after initial surgical exploration, at which time no abnormal parathyroid glands had been found. Although all patients underwent US, computed tomography scan, magnetic resonance imaging, and sestamibi scan, we analyzed the success of localization and reoperation using only the results of US and sestamibi scan. RESULTS: Sixty-one patients (98%) underwent curative reoperations. The sensitivity, positive predictive value, and accuracy for US were 90%, 86%, and 84%, respectively; the corresponding values for sestamibi imaging were 78%, 94%, and 74%, respectively. In 58 of 62 cases (94%) preoperative US and/or sestamibi scan accurately identified the adenoma. In 3 patients for whom combined US and sestamibi scan were inaccurate, 1 adenoma was found by intraoperative US in the strap muscle; 1 adenoma was found by blind cervical thymectomy, and 1 adenoma was found by planned sternotomy that was based on computed tomography findings. CONCLUSIONS: This study supports an algorithm of obtaining US and sestamibi scan as the initial and perhaps only preoperative localization tests for patients with primary hyperparathyroidism after failed operation, at which time no abnormal glands had been found.

Adverse drug interactions clinically important for the dermatologist.

BACKGROUND: All physicians, including dermatologists, are at risk for prescribing drugs that interact in a harmful way. Although prescribing a harmful drug combination may have serious consequences, no review has examined the drug-drug combinations that are of greatest concern for dermatologists. Our goal is to review the pharmacologic mechanisms of adverse drug interactions, the risky drugs, and the patients who are most vulnerable. In so doing, we hope to provide guidance through a potential minefield of adverse interactions. OBSERVATIONS: Although there are only sparse epidemiologic data regarding the prevalence or cost of adverse drug interactions in dermatology, the consequences may range from a minor loss of therapeutic effect of an administered agent to a life-threatening toxic reaction. We will review methotrexate, cyclosporin A, antifungal agents, antibiotics, retinoids, and antihistamine interactions with each other and with other systemic medications. CONCLUSIONS: An organized reporting system needs to be developed so that statistically meaningful epidemiologic data can be obtained for adverse drug interactions, such as the Medwatch program recently proposed by the Food and Drug Administration. Such a system will provide valuable data regarding drug combinations that may be dangerous and determine the scope of the problem as a public health issue.