Pathogenicity of Candida albicans isolates from bloodstream and mucosal candidiasis assessed in mice and Galleria mellonella.

The working hypothesis of this study was to elucidate a possible association between the pathogenic potential of Candida albicans strains with a clinical entity, systemic versus superficial candidiasis. Specifically, we assessed the pathogenicity of two groups of clinical C. albicans isolates: isolates from bloodstream infection (S) versus isolates from vaginitis patients (M), in two experimental in vivo systems - mice and Galleria melonella, in comparison to a control strain (CBS 562). Mice and G. mellonella larvae were inoculated with CBS 562 and the different S and M isolates, and followed up for survival rate and survival time during 30 and 7 days, respectively. Candida kidney colonization of mice was assessed by histopathology and colony-forming units' enumeration. The results revealed: (1) S and M isolates had different behavior patterns in the two models and varied in different parameters; (2) no statistically significant difference in pathogenicity between S and M isolates as whole groups was noted; (3) S14 was the most virulent isolate and close to the standard strain CBS 562 in both models. This study is distinctive in its outline combining two different groups of C. albicans clinical isolates originating from two different clinical entities that were assessed in vivo concurrently in two models.

Prediction of morbidly adherent placenta using a scoring system.

OBJECTIVE: To evaluate the accuracy of an ultrasound-based scoring system for diagnosing morbidly adherent placenta (MAP). METHODS: This study included pregnant women referred to our ultrasound unit during 2013-2015 because of suspected MAP on a previous ultrasound examination or because they had at least one previous Cesarean delivery. All women were assessed using a scoring system based on the following: number and size of placental lacunae; obliteration of the demarcation between the uterus and placenta; placental location; color Doppler signals within placental lacunae; hypervascularity of the placenta-bladder and/or uteroplacental interface zone; and number of previous Cesarean deliveries. Each criterion was assigned 0, 1 or 2 points and the sum of points yielded the final score. Patients were classified into low, moderate or high probability for MAP based on the final score. The presence of MAP was determined by the surgeon at delivery and clinical descriptions were documented in the electronic patient file. Pathological diagnoses were available only in cases that underwent hysterectomy. RESULTS: In total, 258 pregnant women were included in the study, of whom 23 (8.9%) were diagnosed with MAP. There was a statistically significant difference in the prevalence of MAP when women were grouped according to the scoring system, with 0.9%, 29.4% and 84.2% in the low, moderate and high probability groups, respectively (P < 0.0001). All sonographic criteria of the scoring system were significantly associated with MAP (P < 0.0001). Receiver-operating characteristics (ROC) curves for prediction of MAP using the number of placental lacunae and obliteration of the uteroplacental demarcation yielded an area under the ROC curve of 0.94 (95% CI, 0.86-1.00). CONCLUSIONS: Our proposed scoring system is highly predictive of MAP in patients at risk. This allows an adequate multidisciplinary team approach for the planning and timing of delivery in such cases. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal diagnosis of testicular torsion: what shall we tell the parents?

OBJECTIVES: The objectives of this study are to present our collective experience with the prenatal diagnosis of testicular torsion and to propose a possible prenatal management scheme. METHODS: We retrospectively collected and reviewed all medical records of cases that were diagnosed with perinatal testicular torsion in our medical center between the years 2002 and 2013. Prenatal torsion was categorized as torsion diagnosed in utero or on immediate newborn examination. RESULTS: A total of five unilateral prenatal torsions were diagnosed. Two fetuses were diagnosed in the third trimester of pregnancy. In both cases, cesarean section was performed immediately upon diagnosis. One newborn underwent immediate orchiectomy with contralateral orchiopexy. Torsion was confirmed by pathological examination. The other was managed conservatively, just as the three newborns who were diagnosed immediately after birth. On follow-up scan, the affected testicle was found atrophied with lack of blood flow on color Doppler examination. The unaffected contralateral testicle remained within the normal size with good blood flow. CONCLUSIONS: Prenatal diagnosis of unilateral testicular torsion is a coincidental rare finding. Because the twisted testicle cannot be salvaged, induced delivery and prompt surgery are not recommended.

Activity of an Intralipid formulation of nystatin in murine systemic candidiasis.

Since nystatin (NYT) is used only topically owing to its toxicity upon systemic administration, a study was initiated aiming to develop a formulation of NYT that could be used systemically against invasive mycoses. The present research is a continuation of previous in vitro investigation of the antifungal effect of nystatin-Intralipid (NYT-IL) against Candida, exploring its in vivo activity. NYT-IL was tested in murine systemic candidiasis induced in naïve as well as cyclophosphamide-immunosuppressed female ICR mice. The infection was assessed by survival rate (SR), mean survival time (MST) and qualitative and quantitative fungal organ colonisation. Mice were treated by intravenous administration of various doses of NYT-IL for 5 consecutive days starting either 24h or 48 h after the initiation of infection. The experiments showed that NYT-IL is therapeutically effective in the murine candidiasis model. NYT-IL was found to be less toxic in vivo than NYT and therefore higher doses of NYT-IL could be used. The efficacy of NYT-IL was expressed in treated naïve and immunosuppressed mice by increased SR, prolonged MST and reduced fungal organ colonisation. Early initiation of treatment increased efficacy. In summary, the Intralipid formulation of NYT can be administered parenterally and is effective against systemic experimental Candida infection.

The effect of Ondansetron on memory in schizophrenic patients.

It has been well established that patients with schizophrenia have impaired cognitive function on neuropsychological tasks related to memory. Previous studies also suggest serotonin's central role in memory. This double-blind crossover study aimed to explore the effect of Ondansetron, a selective serotonin 3 receptor (5-HT(3)) antagonist, on a variety of memory tasks in schizophrenic patients. Clozapine-treated schizophrenic patients in remission (N=21) were randomly treated with Ondansetron or placebo and then evaluated at three consecutive points. These evaluations included clinical measures (including Positive and Negative Syndrome Scale for Schizophrenia, Clinical Global Impression and Extrapyramidal Symptoms Rating Scale) and neuropsychological measures (including Digit Span, Paired Association, Rey-Osterich Complex Figure Test, Digit Symbol and the Rivermead Behavioral Memory Tests). Ondansetron, when compared with placebo, did not affect the above clinical measures and most of the neuropsychological tests. Short-term administration of Ondansetron, however, was associated with significantly improved visuo-spatial memory as measured by the Rey-Osterich Complex Figure Test. These preliminary results suggest Ondansetron's possible role in enhancement of memory function in schizophrenia.

Ectopic pregnancies in a Caesarean scar: review of the medical approach to an iatrogenic complication.

Implantation of a pregnancy within a Caesarean fibrous tissue scar is considered to be the rarest form of ectopic pregnancy and a life-threatening condition. We conducted a computer search of the English literature of all studies since 2002 to gather updated data on the outcome of such pregnancies. Sixty-six new cases were reported since 2002, possibly reflecting the increasing number of Caesareans currently being performed as well as the more widespread use of the transvaginal scan allowing their earlier detection. Analysis of these women's obstetric history revealed that those at risk for pregnancy in a Caesarean scar appear to have a history of dilatation and curettage, placental pathology, ectopic pregnancy, and IVF. Twenty-one out of 39 for which this information was available (54%) had undergone multiple (> or =2) Caesareans and 13 had previous dilatation and curettage, which might also be an associated factor. We review and discuss the features of contemporary work-ups, including a high index of awareness, a detailed history and a skillful ultrasound examination for an early and accurate diagnosis. Healthcare professionals should be familiar with the possibility of untoward sequelae and how a modern work-up can help in guiding conservative options, thus reducing morbidity and preserving fertility.

Ectopic pregnancies in Caesarean section scars: the 8 year experience of one medical centre.

BACKGROUND: Our aim was to supplement the mostly individual case reports on the rarely occurring and life-threatening condition of ectopic pregnancy developing in a Caesarean section scar. METHODS AND RESULTS: Eight of all the patients treated in our department between 1995 and 2002 had been diagnosed for ectopic pregnancy that developed in a Caesarean section scar. They comprised this case series group. Four of them underwent methotrexate treatment; one had expectant management, one transcervical aspiration of the gestational sac and two by open surgery. All the non-surgically treated women had an uneventful outcome. One underwent a term Caesarean hysterectomy and the other first trimester hysterotomy and excision of the pregnancy located in the scarred uterus. Analysis of all these women's obstetric history revealed that five of them (63%) had been previously operated because of breech presentation, one had a cervical pregnancy and one had placenta previa. Four of them (50%) had multiple (> or = 2) Caesarean sections. CONCLUSIONS: The women at risk for pregnancy in a Caesarean section scar appear to be those with a history of placental pathology, ectopic pregnancy, multiple Caesarean sections and Caesarean breech delivery. Heightened awareness of this possibility and early diagnosis by means of transvaginal sonography can improve outcome and minimize the need for emergency extended surgery.

Electroconvulsive therapy in adolescents: similarities to and differences from adults.

OBJECTIVE: Information on the indications, technique, and effectiveness of electroconvulsive therapy (ECT) in adolescent patients is scarce. The recommendations for the use of ECT in this age group are similar to those in adults. This study compares the experience with ECT in the two age groups in the same community psychiatric institution, which adheres to the accepted protocols for diagnosis and treatment. METHOD: The files of 24 consecutive adolescent patients treated in an ECT unit located in the center of Israel in the years 1991-1995 were retrospectively examined, and the findings were compared with those in 33 adult patients who started their ECT course on the same day. The technique for applying ECT was essentially the same in the two age groups. RESULTS: ECT was equally effective for adolescents and adults (58% in each group achieved remission). The main difference was the diagnosis for which patients were referred: most of the adolescents were in the "psychotic spectrum, whereas most of the adults were in the "affective spectrum." CONCLUSIONS: The findings support the current medical recommendations for the use of ECT in adolescents. Possible explanations for the differences in diagnosis between the two age groups are discussed.

Injections of depot antipsychotic medications in patients suffering from schizophrenia: do they hurt?

INTRODUCTION: Long-acting depot injections of antipsychotic medications are an important way to monitor treatment noncompliance in patients suffering from schizophrenia. Pain and discomfort at the injection site may result in patients' refusal of depot injections. The present study is a pilot study that attempts a systematic characterization of injection site pain. METHOD: Thirty-four consecutive outpatients suffering from DSM-IV-defined schizophrenia or schizoaffective disorder and treated with depot antipsychotic medications were evaluated. The pain they suffered from the injections was quantified using a visual analog scale. This evaluation was made 5 minutes before the injection, 5 minutes after. 2 days after, 10 days after, and before the next injection. Patients were also administered a modified version of the Rating of Medication Influences scale that included a specific question on the possible relationship between injection-associated pain and future compliance to depot treatment. RESULTS: The depot injections cause pain, which is maximal immediately after the injection, declines substantially 2 days after, and disappears by the tenth day after the injection. A correlation exists between reported injection site pain and the effect it has on patients' attitude toward the depot injection as reported by the patients. Zuclopenthixol depot injection is more painful than other depot medications. CONCLUSION: Depot injections are painful. The pain they inflict has a typical course, and medication type is among the factors that influence this pain. This pain might have an effect on patients' attitude toward depot injections and thus is of importance in the management of patients suffering from schizophrenia.

Increased apoptosis in patients with major depression: A preliminary study.

Apoptosis is a programmed cell death that can be observed in normal cells. Major depression poses a combination of a depressed and destructive autoimmune reaction. We measured apoptosis in the PBLs of seven patients with major depression and in age- and sex-matched controls. We observed significantly increased apoptosis in the PBLs of depressive patients (p < 0.05). These preliminary results could contribute to an understanding of the interactions of the CNS with the immune system, which could lead to the increased vulnerability of the CNS in depressive disorders. Further studies are needed to establish these results.

Immune activation in non-treated suicidal major depression.

In the following study we have analyzed cytokine secretion of T-cells of suicidal and non-suicidal depressed patients and healthy controls. It was found that T-cells of suicidal depressed patients have Th1 characteristics, while T-cells of non-suicidal depressed patients have Th2 characteristics. Th1 environment is associated with most of autoimmune diseases. It is thus speculated that Th1 activation in suicidal depression may reflect a unique form of autoimmune suicide.

Characteristics of patients with schizophrenia successive to childhood attention deficit hyperactivity disorder (ADHD).

The goal of this study was to investigate the characteristics of schizophrenic patients with a history of childhood attention deficit hyperactivity disorder (ADHD). The study was performed on 37 adolescent patients meeting the DSM-III-R criteria for schizophrenia and ADHD and 40 controls with schizophrenia only. Schizophrenic patients who were diagnosed in childhood as suffering from ADHD had more prominent developmental disturbances in infancy, more insidious course of schizophrenia, failed to respond to neuroleptics and had poorer outcome as compared to patients with schizophrenia only. The results of this study indicate that schizophrenia subsequent to childhood ADHD has a poor prognosis as compared to schizophrenia only.

Short note: can depressive patients exploit the immune system for suicide?

It is suggested that patients with depression can exploit their immune system for suicide. This could be done passively by reducing the ability of the immune system to overcome factors threatening the integrity of the body, or actively by directing the immune system towards self constituents.

The role of the 16/6 idiotype network in the induction and manifestations of systemic lupus erythematosus.

Experimental systemic lupus erythematosus (SLE) has been induced in mice by immunization with either a human anti-DNA mAb bearing a common idiotype (Id) designated 16/6 Id (antibody 1, Ab1) or with a murine anti-16/6 Id mAb (Ab2). In the present study a murine mAb (5G12-4, Ab3) that bears the 16/6 Id and binds to DNA was produced and was found to bind rabbit anti-16/6 Id sera and murine anti-16/6 Id mAb similarly to the human mAb 16/6 Id (Ab1). Moreover, mAb 5G12-4 was shown to share T cell epitopes with the human 16/6 Id mAb, since lymph node cells of mice immunized with the mAb 5G12-4 proliferated significantly to the human 16/6 mAb and vice versa. Following immunization of mice with the murine mAb bearing the 16/6 Id, antibodies to dsDNA, ssDNA, 16/6 Id, anti-16/6 Id, and to HeLa nuclear extract proteins were detected, similarly to those observed previously upon immunization with Ab1 or Ab2. Six months following the immunization, the mice exhibited leukopenia, increased erythrocyte sedimentation rates, and proteinuria. Examination of the kidneys of the mice disclosed immune complex deposits, thickening of the Bowman's capsule and glomerular necrosis. These results show the importance of the 16/6 Id network in the induction and progression of SLE in mice.

Induction of systemic lupus erythematosus in naive mice with T-cell lines specific for human anti-DNA antibody SA-1 (16/6 Id+) and for mouse tuberculosis antibody TB/68 (16/6 Id+).

Previously we have shown the ability to induce experimental systemic lupus erythematosus (SLE) in naive mice with pathogenic antibodies carrying the 16/6 idiotype (Id) and with the T-cell line specific for the 16/6 Id. In the present study we established and characterized a series of T-cell clones that react against diverse autoantibodies carrying the 16/6 Id and show that they are capable of inducing a SLE-like disease in mice. The T-cell clones were generated from BALB/c mice immunized with the human mAb anti-DNA antibody (SA-1) and the mouse monoclonal anti-tuberculous Ab (TB/68), both carrying the 16/6 Id. The T-cell clones proliferated only in the presence of either human or mouse mAb carrying the 16/6 Id. All the T-cell clones were found to be of the helper type (L3T4) and were H-2 restricted in their function. The injection of the clones to BALB/c mice resulted in serological findings (e.g., anti-DNA, anti-Sm), clinical manifestations (e.g., proteinuria, low white blood cell counts, increased erythrocyte sedimentation rate), and renal insult typical of SLE disease. Our data support the role attributed to pathogenic idiotypes in SLE on the one hand and that played by cellular immunity on the other. The mechanism by which Id-specific T-helper cells may induce SLE is currently not clear. The immunogenicity of the T-cell receptor (anti-16/6) and the cells themselves acting as effector/helper cells, thus leading to damage, may play a role in initiating a chain of events that ends in the production of a panoply of autoantibodies, some of which may also have a regulatory function.

Idiotype specific T-cell lines inducing experimental systemic lupus erythematosus in mice.

Immunization of mice with either antibodies bearing the 16/6 idiotype (16/6 Id) or anti-idiotypic antibodies against the 16/6 Id induces experimental systemic lupus erythematosus (SLE). We report here the establishment and characterization of 16/6 Id-specific T-cell lines from C3H.SW (H-2b) and BALB/c (H-2d) mice. Both lines proliferate specifically in response to the 16/6 Id in an H-2-restricted manner. The injection of 16/6 Id-specific T cells into syngeneic mice led to the development of experimental SLE. Furthermore, inoculation of the 16/6 Id-specific T-cell line derived from C3H.SW mice into the H-2 compatible C57BL/6 mice, which are non-responders to the 16/6 Id, induced experimental SLE. This report provides direct evidence for the role of idiotype-specific T cells in the induction of experimental SLE.

Effects of aging on the induction of experimental systemic lupus erythematosus (SLE) in mice.

The study was designed to determine whether manifestations of autoimmunity are altered with age, using an experimental model in which systemic lupus erythematosus (SLE) is induced in mice. Young (2-month-old), and aging (18-month-old) BALB/c female mice were immunized with a human monoclonal anti-DNA antibody that bears a common idiotype (16/6 Id). Control groups were either left untreated or were injected with human IgM (HIgM). Anti-16/6 Id levels were found to be significantly lower in the old mice than in the young. Similarly, anti-anti-16/6 Id (murine 16/6 Id+) values were lower in the old. Mice injected with the 16/6 Id also produced various autoantibodies, including anti-dsDNA, anti-RNP, anti-Sm and anti-histones antibodies. The levels of these antibodies were lower in the old mice than in the young, yet the differences were not statistically significant. Levels of autoantibodies examined in control animals were either similar in both age groups (anti-RNP and histones) or lower in the old (anti-dsDNA and Sm). Four months after a booster injection of 16/6 Id, the young mice developed clinical manifestations of SLE, including proteinuria and leukopenia, which were seen, in milder form, in the aged mice. Immune complex depositions examined by immunohistology on kidney sections suggested similar differences based on the age of the animals. Our results suggest that aging might actually be associated with a decline in the capacity to produce autoimmune responses.

Specific proliferative responses following the induction of experimental SLE in mice.

We have previously reported the induction of experimental systematic lupus erythematosus (SLE) in mice by immunization with a human monoclonal antibody that expresses a common anti-DNA idiotype (16/6 Id). Following immunization, antibodies directed against various nuclear autoantigens could be detected in the sera of the mice. In the present study, we investigated the proliferative responses of lymph node cells to one particular autoantigen (DNA) following the induction of experimental SLE. Cells reactive with ssDNA could be detected following immunization of BALB/c mice with the 16/6 Id. The appearance of these DNA-reactive cells succeeded the appearance of 16/6 Id-specific cells. The activation of this subset of autoreactive cells could be achieved only by the immunization of the mice with the 16/6 Id, but not by their immunization with DNA, thus suggesting that the induction of experimental SLE is associated with the alteration of the low responsive potential of the mice to DNA.

Anti-DNA idiotype- and anti-idiotype-specific T cell responses in patients with systemic lupus erythematosus and their first-degree relatives.

We examined the proliferative responses of T cells of patients with systemic lupus erythematosus (SLE), their first-degree relatives, and healthy donors, to a human monoclonal antibody that bears a common anti-DNA idiotype, 16/6 Id, and to a murine, 16/6 Id-specific, monoclonal antibody. Both 16/6 Id+ and 16/6 Id-specific antibodies were previously shown to be involved in the induction of experimental SLE in mice. Here we show that T cells of fewer SLE patients, as compared with healthy donors, could proliferate to both antibodies. The difference between T cell responses of patients and controls to the 16/6 was found to be significant. The proliferative responses of T cells of first degree relatives of SLE patients to the anti-16/6 Id were found to be significantly lower compared with the responses detected in healthy donors and in SLE patients. The responses of T cells of SLE relatives to the 16/6 Id were found to be lower than those of healthy donors, but this difference was not significant. The present study suggests a possible involvement of T cells, and specifically of idiotype and anti-idiotype specific T cells, in SLE.