Tumor cell-induced deactivation of human monocytes

Although blood monocytes exhibit significant cytotoxic activity against tumor cells, the function of tumor infiltrating macrophages (TIM) is depressed in cancer patients. This study addresses the question of how the antitumor response of human monocytes, assessed by production of cytokines (tumor necrosis factor alpha, TNF; IL-10; IL-12p40) and cytotoxicity, is altered by exposure to cancer cells. Tumor cell--pre-exposed monocytes restimulated with tumor cells showed significantly decreased production of TNF, IL-12, increased IL-10 (mRNA and release) and inhibition of IL-1 receptor-associated kinase-1 (IRAK-1) expression. This down-regulation of cytokine production was selective, as the response of pre-exposed monocytes to lipopolysaccharide (LPS) was unaffected. Treatment of tumor cell--pre-exposed monocytes with hyaluronidase (HAase) improved their depressed production of TNF, while HAase-treated cancer cells did not cause monocyte dysfunction. The response of hyaluronan (HA)--pre-exposed monocytes to stimulation with tumor cells was also inhibited. Cytotoxic activity of monocytes pretreated with cancer cells was also decreased. This study shows that tumor cells selectively deactivate monocytes and suggests that tumor cell-derived HA by blocking CD44 on monocytes inhibits their antitumor response. These observations may provide some explanation for the depressed function of TIM in human malignancy.     

Hyperthyroxinemia at birth: a cause of idiopathic neonatal hyperbilirubinemia?

Background

Some neonates develop idiopathic hyperbilirubinemia (INHB) requiring phototherapy, yet with no identifiable causes. We searched for an association between abnormal thyroid levels after birth and INHB.

Methods

Of 5188 neonates, 1681 (32.4%) were excluded due to one or more risk factors for hyperbilirubinemia. Total thyroxine (TT4) and thyroid stimulating hormone values were sampled routinely at 40–48 hours of age and measured in the National Newborn Screening Program.

Results

Of the 3507 neonates without known causes for hyperbilirubinemia, 61 (1.7%) developed INHB and received phototherapy. Univariate analyses found no significant association between mode of delivery and INHB (vacuum-delivered neonates were a priori excluded). Nonetheless, in cesarean-delivered (CD) neonates, two variables had significant association with INHB: TT4 ≥ 13 µg/dL and birth at 38–38.6 weeks. In vaginally delivered (VD) born neonates, INHB was associated with weight loss > 7.5% up to 48 hours of age. Multivariate logistic regression analysis showed a strong effect of mode of delivery on possible significant association with INHB. In CD neonates, such variables included: TT4 ≥ 13 µg/dL [P = 0.025, odds ratio (OR) 5.49, 95% confidence interval (CI) 1.23–24.4] and birth at 38–38.6 weeks (P = 0.023, OR 3.44, 95% CI 1.19–9.97). In VD neonates, weight loss > 7.5% (P = 0.019, OR 2.1, 95% CI 1.13–3.83) and 1-min Apgar score < 9 (P < 0.001, OR 3.8, 95% CI 1.83–7.9), but not TT4, showed such an association.

Conclusions

INHB was significantly associated with birth on 38–38.6 week and TT4 (≥ 13 µg/dL) in CD neonates, and with a weight loss > 7.5% in VD neonates. We herein highlight some acknowledged risk factors for neonatal hyperbilirubinemia, and thus minimize the rate of INHB.

     

Ibuprofen versus continuous indomethacin in premature neonates with patent ductus arteriosus: is the difference in the mode of administration?

Ibuprofen has been proposed as a preferential alternative to indomethacin in treating patent ductus arteriosus (PDA), because it is purported to have less renal, mesenteric, and cerebral vasoconstrictive effects. However, short and long-term safety concerns regarding ibuprofen remain. Continuous slow infusion of indomethacin also eliminates peripheral vasoconstriction and may thus offer similar benefits to ibuprofen without safety concerns. In this study, our objective was to show that treating a PDA with continuous indomethacin is similar to ibuprofen in its effect on urine output, renal function, and blood flow velocities in the renal, superior mesenteric, and anterior cerebral arteries. Sixty four prematures with PDA were randomly, prospectively assigned to either treatment. PDA closure rates were similar (74 versus 59%; p = 0.123). Nine indomethacin-treated babies (29%) versus twelve ibuprofen babies (38%) underwent repeated therapy (p = 0.656). Two indomethacin and four ibuprofen infants required surgical ligation (p = 0.672). Serum creatinine, oliguria, estimated glomerular filtration rate, and fractional excretion of sodium were similar in both groups, as were blood flow velocity parameters in the vessels studied. There were no differences in necrotizing enterocolitis, BPD, intraventricular hemorrhage, and/or retinopathy of prematurity. In conclusion, PDA treatment with either continuous indomethacin infusion or ibuprofen was equally devoid of adverse renal effects and/or peripheral vasoconstrictive effects.     

The P300 Event-Related Potential Technique for Libido Assessment in Women with Hypoactive Sexual Desire Disorder

IntroductionThere is a need for an objective technique to assess the degree of hypoactive sexual desire disorder (HSDD). Recently, we described such a methodology (event-related potential technique [ERP]) based on recording of p300 electroencephalography (EEG) waves elicited by auditory stimuli during synchronous exposure to erotic films.AimsTo compare sexual interest of sexually healthy women to females with sexual dysfunction (FSD) using ERP, and to explore whether FSD women with and without HSDD would respond differently to two different types of erotic stimuli—films containing (I) or not containing (NI) sexual intercourse scenes.MethodsTwenty-two women with FSD, of which nine had HSDD only, and 30 sexually healthy women were assessed by the Female Sexual Functioning Index. ERP methodology was performed applying erotic NI or I films.Main Outcome MeasuresSignificant differences in percent of auditory p300 amplitude reduction (PR) in response to erotic stimuli within and between all three groups for each film type.ResultsPRs to each film type were similar in sexually healthy women (60.6% ± 40.3 (NI) and 51.7% ± 32.3 [I]), while in women with FSD, reduction was greater when viewing the NI vs. I erotic films (71.4% ± 41.0 vs. 37.7% ± 45.7; P = 0.0099). This difference was mainly due to the greater PR of the subgroup with HSDD in response to NI vs. I films (77.7% ± 46.7 vs. 17.0% ± 50.3) than in the FSD women without HSDD group or the sexually healthy women (67.5% ± 38.7 vs. 50.4% ± 39.4 respectively), P = 0.0084. For comparisons, we used the mixed-model one-way analysis of variance.ConclusionsDifferences in neurophysiological response patterns between sexually healthy vs. sexually dysfunctional females may point to a specific inverse discrimination ability for sexually relevant information in the subgroup of women with HSDD. These findings suggest that the p300 ERP technique could be used as an objective quantitative tool for libido assessment in sexually dysfunctional women. Vardi Y, Sprecher E, Gruenwald I, Yarnitsky D, Gartman I, and Granovsky Y. The P300 event-related potential technique for libido assessment in women with hypoactive sexual desire disorder. J Sex Med 2009;6:1688–1695.     

Scopolamine impairs the response-to-change following observation of the environment but not after its exploration by the rat

The tendency to select the T-maze arm that has been changed in brightness between two successive trials (response-to-change) was investigated in rats injected with scopolamine (Sc) or saline (NaCl) 20 min before the test. In the "passive" version of the test, when in trial 1 rats could inspect the white-black arms through clear partitions blocking the entrance to the arms, a dose of when in trial 1 rats could inspect the white-black arms through clear partitions blocking the entrance to the arms, a dose of 1.0 mg/kg Sc decreased significantly the number of changed arm choices in trial 2, as compared to saline controls. A lower dose of Sc (0.5 mg/kg) was ineffective. In the "active" test version, when in trial 1 the rats were allowed to explore the white-black arms, doses of 1.0 and 2.0 mg/kg Sc did not affect the preference for the changed arm in trial 2. NaCl rats showed a significant preference for the changed arm choices in both tests. The scopolamine effects on response-to-change, i.e., impairment of performance in the passive but not in the active version, were essentially the same as those found by us previously in hippocampal rats.     

Cloning and mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome

A strategy for cloning and mutagenesis of an infectious herpesvirus genome is described. The mouse cytomegalovirus genome was cloned and maintained as a 230 kb bacterial artificial chromosome (BAC) in E. coli. Transfection of the BAC plasmid into eukaryotic cells led to a productive virus infection. The feasibility to introduce targeted mutations into the BAC cloned virus genome was shown by mutation of the immediate-early 1 gene and generation of a mutant virus. Thus, the complete construction of a mutant herpesvirus genome can now be carried out in a controlled manner prior to the reconstitution of infectious progeny. The described approach should be generally applicable to the mutagenesis of genomes of other large DNA viruses.     

Women in the early days of cytology: A personal recollection

The fight for the acceptance of the validity of cytopathology has been fought by a group of individuals associated with George N. Papanicolaou. The common effort to convince the skeptics that Papanicolaou's method of diagnosing cancer was the best way to detect its presence at an early stage became a bond linking all of us. When we taught cytology, we felt more like preaching a gospel than like teaching a subject. Those of us who became involved in original research experienced an additional excitement from expanding the frontiers of our new specialty. This uniquely stimulating experience has been shared by women and men in most of the early cytology teaching centers throughout the world. This was diffrent from the enthusiasm with which people enter the field of cytopathology today. All of us had to constantly prove the validity of what we were doing, whereas now the value of cytologic diagnosis is fully recognized and taken for granted. © 1994 Wiley-Liss, Inc.     

Patient's view of heart failure: from the understanding to the quality of life.

BACKGROUND: Non-pharmacological management is one of heart failure treatment cornerstones. Despite its importance several studies showed lack of clinical advising by medical staff as well as poor patient compliance to education and pharmacological treatment. Hospitalizations and symptoms of heart failure negatively influence patients' quality of life. In Slovenia there is a scarcity of non-pharmacological management and quality of life data in heart failure patients. AIMS: We wanted to obtain data on heart failure patient's quality of life and their satisfaction with management of the condition in Slovenia. METHODS: During 6 weeks, patients from one university and two community Slovenian hospitals were prospectively enrolled to the EuroHeart survey. We invited 415 patients (mean age 70.6+/-11.4 years, 53% men) to attend an interview 12 weeks after the discharge.Out of 415 eligible patients 25 (6%) died during follow up period and 187 (45%) attended the interview. Twenty-three percent of them were re-hospitalized. Vast majority (89%) of interviewed patients were aware of their heart condition but only 61% were satisfied with the explanation of their clinical condition given by medical staff. On average they were taking 6.3+/-2.3 drugs. General clinical advice (salt intake 65%, cholesterol or fat intake 63%) was more common than specific (daily weighing 35%, avoidance of non-steroidal anti-inflammatory drugs 17%). Patients reported high adherence as only 3% of given advice were neglected. Symptoms of heart failure were much less common at rest than during daily activity (breathlessness in 20% and 78%, fatigue in 18% and 81%, respectively). Psychological symptoms as anxiety (70%), depression (50%) and stress (48%) were common, as well as cognitive and sleep disturbances, both present in more than half of the patients. CONCLUSIONS: Patients with heart failure experienced restrictions in quality of life and psychological status. Non-pharmacological and pharmacological management and patient's satisfaction with medical care were below optimal. Educational strategies for medical staff and patients as well as organization of an out-patient setting in community hospitals are needed.