Spontaneous miscarriages in patients with bladder pain syndrome/interstitial cystitis - effect of stress on inflammation?

Interstitial cystitis/painful bladder syndrome (IC/PBS) affects mostly women and is characterized by pelvic pain or pressure and frequency of voiding in the absence of urinary tract infection. Acute stress worsens IC/PBS symptoms and bladder inflammation associated with increased number of activated mast cells. We investigated retroactively the incidence of spontaneous miscarriages and any related stress in IC/PBS patients. A questionnaire was posted on an IC/PBS website and patients visiting the site were invited to complete and file it electronically. Limitations include the lack of defined diagnosis of those responding, and of a validated stress questionnaire. There were 193 respondents (mean age = 37.3 years) over two weeks. Of those responding, 87% (mean age = 33.2 years) had received a diagnosis of IC/PBS. Of those respondents with IC/PBS, 76% reported having had miscarriages: (a) 55% had one miscarriage, (b) 26% had two, and (c) 23% had three or more. These rates are much higher than those of in the general population: 10-20% with one and 1-2% with habitual spontaneous miscarriages. The majority of patients (78%) reported experiencing significant stress. IC/PBS patients appear to have a much high incidence of spontaneous miscarriages compared to the general population. Most patients reported experiencing stress that has been associated with miscarriages. This finding may be explained via stress stimulating bladder and uterine immune cells, especially mast cells, inhibition of which by the natural flavonoid luteolin may be beneficial.

Lipid peroxidation in Gram-negative bacteremia modulates the risk for septic shock and infections by resistant Klebsiella pneumoniae.

Controversies in outcomes with the parenteral administration of antioxidants as adjuvant therapies led to the measurement of malondialdehyde (MDA), a product of lipid peroxidation, in serum collected from 120 patients with primary Gram-negative bacteremia during the first 24 h from sepsis onset. MDA was measured by the thiobarbiturate assay, followed by high-performance liquid chromatography (HPLC) analysis. After receiver operator characteristic (ROC) curve analysis, patients were divided into those with high levels of MDA and low levels of MDA. The primary endpoint was the association of the level of MDA with septic shock. The level of MDA as an index of neutrophil function and associations with outcome and with infections by carbapenem-resistant Klebsiella pneumoniae were the secondary endpoints. In total, 63 patients had high and 57 had low MDA levels; 27% and 49.1%, respectively, had septic shock (p = 0.015). The rate of the concentration of MDA to the total neutrophil count was used as an expression of neutrophil function; this was lower among patients with septic shock. The odds ratio (OR) for death among patients without septic shock and low level of MDA was 4.00; this was 0.48 for patients with septic shock (p = 0.020 between the two ORs). The OR for resistance to carbapenems among patients with bacteremia by K. pneumoniae and low level of MDA was 7.50 (p = 0.011 compared to patients with bacteremia by other pathogens). Low level of circulating MDA is associated with susceptibility to septic shock and infections by carbapenem-resistant K. pneumoniae.

Vitamin D and bone disease.

Vitamin D is important for normal development and maintenance of the skeleton. Hypovitaminosis D adversely affects calcium metabolism, osteoblastic activity, matrix ossification, bone remodeling and bone density. It is well known that Vit. D deficiency in the developing skeleton is related to rickets, while in adults is related to osteomalacia. The causes of rickets include conditions that lead to hypocalcemia and/or hypophosphatemia, either isolated or secondary to vitamin D deficiency. In osteomalacia, Vit. D deficiency leads to impairment of the mineralisation phase of bone remodeling and thus an increasing amount of the skeleton being replaced by unmineralized osteoid. The relationship between Vit. D and bone mineral density and osteoporosis are still controversial while new evidence suggests that Vit. D may play a role in other bone conditions such as osteoarthritis and stress fractures. In order to maintain a "good bone health" guidelines concerning the recommended dietary intakes should be followed and screening for Vit. D deficiency in individuals at risk for deficiency is required, followed by the appropriate action.

Using scenarios to explain life expectancy in advanced cancer: attitudes of people with a cancer experience.

PURPOSE: We sought the attitudes of people with a cancer experience to using best case, worst case, and typical scenarios for survival to explain life expectancy. METHODS: Oncology clinic attendees and Breast Cancer Network Australia (BCNA) members completed a survey describing two formats for explaining life expectancy to a hypothetical patient with advanced cancer-providing either three scenarios for survival or just the median survival time. RESULTS: Characteristics of the 505 respondents from outpatient clinics (n = 251) and BCNA (n = 254) were median age of 58 years, female 74 %, and breast primary 64 %. More respondents agreed that explaining three scenarios (vs. median survival) would make sense (93 vs. 75 %), be helpful (93 vs. 69 %), convey hope (68 vs. 44 %), and reassure (60 vs. 40 %), while fewer respondents agreed that explaining three scenarios (vs. median survival) would upset people (24 vs. 36 %); all p values < 0.001. Most respondents agreed that each scenario should be presented: best case 89 %, worst case 82 %, and typical 92 %. For information about their own prognosis, 88 % preferred all three scenarios and 5 % a single estimate of the median. Respondents with higher education were more likely to agree that presenting three scenarios would be helpful (95 vs. 90 %, p = 0.05). Respondents with breast cancer were more likely to agree that explaining three scenarios would upset people (31 vs. 13 %, p < 0.001). CONCLUSIONS: Most respondents judged presentation of best case, worst case, and typical scenarios preferable and more helpful and reassuring than presentation of just the median survival time when explaining life expectancy to patients with advanced cancer.

GC-MS structural characterization of fatty acids from marine aerobic anoxygenic phototrophic bacteria.

The FA composition of 12 strains of marine aerobic anoxygenic phototrophic bacteria belonging to the genera Erythrobacter, Roseobacter, and Citromicrobium was investigated. GC-MS analyses of different types of derivatives were performed to determine the structures of the main FA present in these organisms. All the analyzed strains contained the relatively rare 11-methyloctadec-12-enoic acid, and three contained 12-methyl-octadec-11-enoic acid, which has apparently never been reported before. High amounts of the very unusual octadeca-5,11-dienoic acid were present in 9 of the 12 strains analyzed. A FA containing a furan ring was detected in three strains. Analytical data indicated that this FA was 10,13-epoxy-11-methyloctadeca-10,12-dienoic acid. A very interesting enzymatic peroxidation of the allylic carbon 10 of cis-vaccenic acid was observed in three strains. Deuterium labeling and GC-MS analyses enabled us to demonstrate that this enzymatic process involves the initial dioxygenase-mediated formation of 10-hydroperoxyoctadec-11(cis)-enoic acid, which is then isomerized to 10-hydroperoxyoctadec-11(trans)-enoic acid and converted to the corresponding hydroxyacids and oxoacids. Different biosynthetic pathways were proposed for these different compounds.

T lymphocyte subsets and immunoglobulins in intracranial tumor patients before and after treatment, and based on histological type of tumors.

It has been reported that nervous system and peripheral immune system communicate with each other and the peripheral immune status is depressed in some intracranial tumor (ICT) patients pre operatively. Little is known about the immune status of intracranial tumor patients during the post operative survival period. We thus investigated total T cells (CD 11+), helper/inducer (CD4+) T cells, suppressor/cytotoxic (CD8+) T cells, B cells (CD19+) and serum immunoglobulins in peripheral blood in certain ICT patients before and after treatment, and based on the histological type of the tumors. Post treatment analysis were conducted 30 days after surgical removal of tumor tissue in benign brain tumor patients and 30 days after chemo therapy (CT)/radiotherapy (RT) following surgical removal of tumor tissue in malignant brain tumor patients. Decreased CD11+, CD4+ and increased CD8+ T cell counts were observed in both benign and malignant tumor cases before treatment compared with control subjects. After treatment, CD4+ T cell count increased and CD8+ T cell count decreased than their pre treatment levels. Serum IgA and IgG levels were decreased in both benign and malignant brain tumor patients before treatment than in control subjects. Serum IgM level has been increased in both benign and malignant tumor patients before and after treatment than in control subjects. Anaplastic malignant astrocytoma, medulloblastoma and glioblastoma multiforme patients showed higher IgM level than astrocytoma, meningioma and ependymoma patients. In conclusions, the depressed host cellular immunity in benign and malignant tumor patients before treatment may be due to the changes in CD4+ and CD8+ counts in addition to tumour specific immunosuppressive factors. Treatment procedures such as surgery, CT and RT may play certain role in the post operative depressed immunosuppression in malignant tumor patients. Humoral immune mechanism (CD19+) in the ICT patients was less markedly affected.

IL-10 subfamily members: IL-19, IL-20, IL-22, IL-24 and IL-26.

It has been reported that the CD4+ T cell is a very important source of interleukin 10 (IL-10), while CD8+ cells produce low amounts. IL-10 exerts several immune stimulating, as well as inhibitory effects. There are at least five novel human IL-10 family-related molecules: IL-19, IL-20, IL-22, IL-24, and IL-26. Activated T cells produce IL-19, IL-22 and IL-26, while IL-24 is produced by activated monocytes and T-cells. IL-20 induces cheratin proliferation and Stat-3 signal transduction pathway, while IL-22 induces acute-phase production by hepatocytes and neonatal lethality with skin abnormalities reminiscent of psoriasic lesions in humans. In addition, IL-22 mediates inflammation and binds class II cytokine receptor heterodimers IL-22 RA1/CRF2-4. This cytokine is also involved in immuno-regulatory responses. IL-26 (AK155) is a novel cytokine generated by memory cells and is involved in the transformed phenotype of human T cells after infection by herpes virus. All these new IL-10 subfamily member cytokines are strongly involved in immune regulation and inflammatory responses.

Nucleotide sequence of a Drosophila melanogaster cDNA encoding a calnexin homologue.

A cDNA which encodes a calnexin (Cnx)-like protein from Drosophila melanogaster has been characterized. The deduced amino acid sequence shares several regions of homology with Cnx from other sources with two conserved motifs each repeated four times. The gene was found to be transcribed in various tissues and at all developmental stages. We have mapped the gene at chromosomal position 99A and we have also mapped the related gene coding for Drosophila calreticulin at 85E.

Audit and its impact in the management of advanced prostatic cancer.

From a prospective database of 614 consecutive men with newly diagnosed prostatic cancer an audit of outcome was studied in 169 men who presented with bone metastases and subsequently received hormonal manipulation in the form of monotherapy. The cohort was divided into 2 groups according to serum alkaline and acid phosphatase enzyme levels. Men with normal alkaline phosphatase levels (41.5%) had a better prognosis (median survival 38 months) than those with elevated levels at presentation (58.5%) (median survival 19 months). This difference was highly significant. A similar stratification on prostatic acid phosphatase levels did not yield any prognostic significance. With regard to cause-specific survival, serum alkaline phosphatase was an even more powerful prognosticator, with a median survival of 45 and 21 months for patients with normal and elevated levels respectively. Thus monotherapy is recommended for metastatic prostate cancer patients with normal serum alkaline phosphatase, but for those with elevated alkaline phosphatase the alternative avenues of treatment must be explored.

Audit and its impact in the management of early prostatic cancer.

An analysis was made of a prospective database of 614 men with newly diagnosed carcinoma of the prostate who presented between January 1978 and December 1990; 3-monthly updates were available on their clinical, haematological and biochemical parameters and 6-monthly updates on chest X-rays, bone scans and skeletal X-rays. It was found that 107 men (mean age 73.5 years) had early disease at presentation. Their management was based on regular surveillance and the treatment deferred until disease progression or development of symptoms. The audit of outcome measured various clinical events. Four patients (3.7%) developed local failure, 11 (10.3%) developed bone metastases, 3 (2.8%) died of cancer with a median survival of 6.3 years, and 34 (31.8%) died of intercurrent disease with a median survival of 2.6 years. The observed survival for 12 years of the whole group was similar to the expected survival for an age-matched population in Scotland. The standardised mortality ratio was 81 (95% confidence limits 57-112).

Effect of nifedipine in the protection of renal function during in situ preservation.

In an experimental study on six healthy dogs both kidneys were exposed and subjected to 1 h of ischaemia by clamping both renal vessels. To the left renal artery, 300 ml of cold (4 degrees C) Euro-Collins solution in which nifedipine (Bay a 1040--20 micrograms/kg per min) was diluted, was infused for 15 min. Simultaneously 300 ml of cold Euro-Collins solution plus 20 micrograms/kg per min of placebo (Bay a 1040--placebo) was infused in the right renal artery. The 1 h of ischaemia was divided in a 15-min period of cold ischaemia and 45 min of warm ischaemia, at the end of which both clamps were removed. During the 2 h (4 X 30 min) following the removal of the clamps, urine volume, urea and creatinine clearances, urine sodium concentration, sodium fractional excretion (%) and urine/plasma osmolality ratio measurements were made and results compared to the pre-ischaemia values. Both kidneys were then removed for histological study. The nifedipine group restored diuresis of 0.43 +/- 0.23 ml/min within 30 min, while this degree of diuresis (0.64 +/- 0.16 ml/min) was achieved by the placebo group at 120 min. Urine volume as well as creatinine and urea clearances of the nifedipine group were significantly higher in all studied periods compared to the placebo group (P less than 0.01 or P less than 0.025). Urine sodium and FENa (%) were not different between the two groups, and urine/plasma osmolality ratio was above 1.1 in all studied periods for both groups. The microscopic study did not show any significant differences between the two groups. We conclude that nifedipine is effective in the protection of renal function when it is administered during experimental in situ preservation.