Sexual needs and sexual function of patients with Parkinson's disease.

BACKGROUND: Sexual dysfunction (SD) is a frequent non-motor symptom in Parkinson's disease (PD) that is rarely addressed, and sexual counseling is sporadic. OBJECTIVES: To investigate PD patients' SD and sexual counseling motivation and to propose an interventional strategy for movement disorder specialists. METHODS: All consecutive PD patients who presented to a movement disorder unit between 2018 and 2019 completed anonymous questionnaires containing the Female Sexual Function Index, the International Index of Erectile Function, and a questionnaire on sexual needs and motivation to receive sexual counseling. RESULTS: The age range of the 100 recruited patients (78 men) was 40-80 years, and the mean disease duration was 8.64 ± 6.84 years. SD appeared at all PD stages. The presence of SD pre-PD diagnosis significantly predicted SD post-diagnosis in men. Erectile dysfunction was the most common male SD (70%). Women reported frequent SD before PD diagnosis and currently. More than half of the responders (74% of the men and 40% of the women) were motivated to receive sexual counseling. Most of them (77.4%) were in a relationship. CONCLUSIONS: The findings of this analysis revealed that most PD patients had experienced SD before being diagnosed with PD and were interested in receiving sexual counseling. We propose a six-step intervention strategy for the management of SD in PD designed for application in a movement disorder unit. We also recommend that neurologists and other healthcare providers undergo training to provide basic sexual counseling tailored to the needs of PD patients.

Modeling the spread of polio in an IPV-vaccinated population: lessons learned from the 2013 silent outbreak in southern Israel.

BACKGROUND: Polio eradication is an extraordinary globally coordinated health program in terms of its magnitude and reach, leading to the elimination of wild poliovirus (WPV) in most parts of the world. In 2013, a silent outbreak of WPV was detected in Israel, a country using an inactivated polio vaccine (IPV) exclusively since 2005. The outbreak was detected using environmental surveillance (ES) of sewage reservoirs. Stool surveys indicated the outbreak to be restricted mainly to children under the age of 10 in the Bedouin population of southern Israel. In order to curtail the outbreak, a nationwide vaccination campaign using oral polio vaccine (OPV) was conducted, targeting all children under 10. METHODS: A transmission model, fitted to the results of the stool surveys, with additional conditions set by the ES measurements, was used to evaluate the prevalence of WPV in Bedouin children and the effectiveness of the vaccination campaign. Employing the parameter estimates of the model fitting, the model was used to investigate the effect of alternative timings, coverages and dosages of the OPV campaign on the outcome of the outbreak. RESULTS: The mean estimate for the mean reproductive number was 1.77 (95 % credible interval, 1.46-2.30). With seasonal variation, the reproductive number maximum range was between zero and six. The mean estimate for the mean infectious periods was 16.8 (8.6-24.9) days. The modeling indicates the OPV campaign was effective in curtailing the outbreak. The mean estimate for the attack rate in Bedouin children under 10 at the end of 2014 was 42 % (22-65 %), whereas without the campaign the mean projected attack rate was 57 % (35-74 %). The campaign also likely shortened the duration of the outbreak by a mean estimate of 309 (2-846) days. A faster initiation of the OPV campaign could have reduced the incidence of WPV even if a lower coverage was reached, at the risk of prolonging the outbreak. CONCLUSIONS: OPV campaigns are essential for interrupting WPV transmission, even in a developed country setting with a high coverage of IPV. In this setting, establishing ES of WPV circulation is particularly crucial for early detection and containment of an outbreak.

Development and validation of a real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay for investigation of wild poliovirus type 1-South Asian (SOAS) strain reintroduced into Israel, 2013 to 2014.

In February 2013, wild poliovirus type 1 (WPV1) was reintroduced into southern Israel and resulted in continuous silent circulation in the highly immune population. As a part of the public health emergency response, a novel real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was developed, to allow for the sensitive and specific detection of the circulatingWPV1-South Asian (SOAS) strain. Specific primers and probes derived from the VP-1 region were designed, based on sequenced sewage isolates, and used to simultaneously amplify this WPV1-SOAS sequence together with bacteriophage MS-2 as internal control. High titre WPV1-SOAS stock virus was used for assay optimisation and 50 processed sewage samples collected from southern Israel and tested by reference culture based methods were used for analytical validation of the assay's performance. The limit of detection of the multiplex qRT-PCR (SOAS/MS-2) assay was 0.1 plaque-forming unit (pfu)/reaction (20 pfu/mL) for WPV1-SOAS RNA with 100% sensitivity, specificity, positive and negative predictive values when compared to the culture based method. The turnaround time was rapid, providing results for environmental samples within 24 to 48 hours from completion of sewage processing, instead of five to seven days by culture-based analysis. Direct sewage testing by qRT-PCR assay proved to be a useful tool for rapid detection and environmental surveillance of WPV1-SOAS circulating strain during emergency response. Application of the approach for detection of WPV1-SOAS in stool samples obtained during acute flaccid paralysis (AFP) surveillance or field surveys should be further evaluated.

Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013.

An emergency response was triggered by recovery of wild poliovirus type 1 (WPV1) of the South Asia (SOAS) lineage from sewage in southern Israel in April 2013 during routine environmental surveillance. Public health risk assessment necessitated intensification of environmental surveillance in order to facilitate countrywide monitoring of WPV1-SOAS circulation. This involved increasing sampling frequency and broadening the geographical area, for better coverage of the population at risk, as well as modifying sewage testing algorithms to accommodate a newly developed WPV1-SOAS-specific quantitative real-time RT-PCR assay for screening of RNA extracted directly from sewage concentrates, in addition to standard virus isolation. Intensified surveillance in 74 sites across Israel between 1 February and 31 August 2013 documented a sustained high viral load of WPV1-SOAS in sewage samples from six Bedouin settlements and two cities with Jewish and Arab populations in the South district. Lower viral loads and intermittent detection were documented in sampling sites representing 14 mixed communities in three of the five health districts in central and northern Israel. Environmental surveillance plays a fundamental role in routine monitoring of WPV circulation in polio-free countries. The rapid assay specific for the circulating strain facilitated implementation of intensified surveillance and informed the public health response and decision-making.

Molecular epidemiology of silent introduction and sustained transmission of wild poliovirus type 1, Israel, 2013.

Poliovirus vaccine coverage in Israel is over 90%. The last nine birth cohorts have been vaccinated exclusively with inactivated polio vaccine (IPV). However, between February and July 2013 type 1 wild poliovirus (WPV1) was detected persistently in 10 and intermittently in 8 of 47 environmental surveillance sites in southern and central Israel and in 30 stool samples collected during July from healthy individuals in southern Israel. We report results of sequence and phylogenetic analyses of genes encoding capsid proteins to determine the source and transmission mode of the virus. WPV1 capsid protein 1 nucleotide sequences were most closely related to South Asia (SOAS) cluster R3A polioviruses circulating in Pakistan in 2012 and isolated from Egyptian sewage in December 2012. There was no noticeable geographical clustering within WPV1-positive sites. Uniform codon usage among isolates from Pakistan, Egypt and Israel showed no signs of optimisation or deoptimisation. Bayesian phylogenetic time clock analysis of the entire capsid coding region (2,643 nt) with a 1.1% evolutionary rate indicated that Israeli and Egyptian WPV1-SOAS lineages diverged in September 2012, while Israeli isolates split into two sub-branches after January 2013. This suggests one or more introduction events into Israel with subsequent silent circulation despite high population immunity.

Insidious reintroduction of wild poliovirus into Israel, 2013.

Israel was certified as polio-free country in June 2002, along with the rest of the World Health Organization European Region. Some 11 years later, wild-type polio virus 1 (WPV1) was isolated initially from routine sewage samples collected between 7 and 13 April 2013 in two cities in the Southern district. WPV1-specific analysis of samples indicated WPV1 introduction into that area in early February 2013. National supplementary immunisation with oral polio vaccine has been ongoing since August 2013.

Juvenile onset of primary low-grade cutaneous B-cell lymphoma.

BACKGROUND: Cutaneous lymphomas rarely occur in children and adolescents, and are mostly of the T-cell lineage. Low-grade primary cutaneous B-cell lymphoma (CBCL) is extremely rare in individuals under 18 years old. Only 11 patients under 20 years old have been reported in the literature. OBJECTIVES: To evaluate the number of patients younger than 18 years with primary CBCL diagnosed at our centre and to investigate its clinicopathological features, treatment and course in this age group. METHODS: We reviewed the files of all 90 patients with primary CBCL who attended the Department of Dermatology of our tertiary care university-affiliated centre from 1992 to 2007. RESULTS: Four patients who met study criteria were identified: three girls and one boy. Mean age at diagnosis was 16.6 years (range 16-17). Three patients had cutaneous marginal zone lymphoma (CMZL), and one had a spindle-cell (sarcomatoid) lymphoma, most probably follicular centre cell type. All were treated with the standard regimen used in adults. The mean duration of follow up was 45 months. No extracutaneous progression was noted. At present two of the four patients are in complete clinical remission. CONCLUSIONS: In Israel, primary CBCL apparently occurs more often in young patients than reported in the literature. CMZL is the most frequent type. Long follow up is mandatory to assess the biological behaviour of CBCL in the paediatric/adolescent age group.

The role of short-term synaptic dynamics in motor control.

During the past few years, much attention has been given to the role of short-term synaptic plasticity, in particular depression and facilitation, in sculpting network activity. A recent study shows that synaptic depression in rhythmic motor networks could switch the control of network frequency from intrinsic neuronal properties to the synaptic dynamics. Short-term synaptic plasticity is also involved in the stabilization and reconfiguration of motor circuits and in the initiation, maintenance and modulation of motor programs.

[Fiberoptic endoscopic evaluation of swallowing--the Tel Aviv Voice and Swallowing Disorders Clinic].

Fiberoptic endoscopic evaluation of swallowing (FEES) involves passing a fiberoptic laryngoscope transnasally to visualize the hypopharynx, larynx, and proximal trachea in order to assess swallowing disorders. FEES has been compared with the modified barium swallow (MBS) (the presumed "gold standard"). To date, reports have demonstrated that FEES is as sensitive as, or even more sensitive, for use as a tool in swallowing assessment compared with the MBS. FEES provides the clinician with a safe, portable, effective, and valid means of evaluating individuals with swallowing disturbances. FEES allows the examiner to identify swallowing physiology, determine the safest and least restrictive level of oral intake, implement appropriate compensatory techniques, and identify a dysphagia rehabilitation plan. In this article we present the Tel-Aviv Voice and Swallowing Disorders Center experience. Out of 100 patients that were referred to our center for swallowing evaluation 97 patients underwent 102 FEES examinations. Three patients couldn't tolerate the examination. In 63% of the patients swallowing pathology was found. FEES were performed by teamwork involving a speech-language pathologist and otolaryngologist collaborating together thus optimally managing the individual with dysphagia safely and efficiently.

Synaptic depression mediates bistability in neuronal networks with recurrent inhibitory connectivity.

When depressing synapses are embedded in a circuit composed of a pacemaker neuron and a neuron with no autorhythmic properties, the network can show two modes of oscillation. In one mode the synapses are mostly depressed, and the oscillations are dominated by the properties of the oscillating neuron. In the other mode, the synapses recover from depression, and the oscillations are primarily controlled by the synapses. We demonstrate the two modes of oscillation in a hybrid circuit consisting of a biological pacemaker and a model neuron, reciprocally coupled via model depressing synapses. We show that across a wide range of parameter values this network shows robust bistability of the oscillation mode and that it is possible to switch the network from one mode to the other by injection of a brief current pulse in either neuron. The underlying mechanism for bistability may be present in many types of circuits with reciprocal connections and synaptic depression.

Transition from T cell protection to T cell enhancement during tumor growth in an allogeneic host.

The cell-mediated immune response of mice toward a lethal allogeneic tumor was investigated during tumor development. The activity of spleen cells from the tumor-bearing mice was studied by transferring them together with 3LL tumor cells into normal C3H/eb recipient mice. The activity depended upon the time interval between inoculation of the tumor and transfer. Spleen cells taken relatively early, 1 week after tumor inoculation, mediated protection against tumor growth. In contrast, spleen cells taken 4 weeks after tumor inoculation markedly enhanced tumor growth. The tumor-enhancing cells, like the tumor-protecting cells, appeared to be T lymphocytes. The enhancing activity could be transferred by extra cellular medium prepared by incubating the enhancing T cells. Protecting activity could not be transferred by cell-free medium prepared from the protecting T cells. Both activities were found to exist to a relatively slight degree in populations of spleen cells from normal mice. The transition from T cell protection to T cell enhancement might be a determining factor in the outcome of the host-tumor relationship.

Autologous mixed lymphocyte reaction in man: further characterization of responding cells.

Experiments were performed to determine the type of cells undergoing thymidine incorporation in 7-day autologous mixed lymphocyte reactions (AMLR). Peripheral blood mononuclear cells (PBM) were separated into B cells, T cells, B + Null cells and T + Null cell-enriched populations. Cells were cultured in various combinations. Monocytes were removed to determine their influence on AMLR. The main thymidine-incorporating cells in cultures were shown to be Null cells and to a lesser extent T cells. Monocytes were found to have a more pronounced suppressor effect on stimulation of T cells by non-T cell populations in younger individuals than in the elderly. Whether Null cells undergo a spontaneous blastogenesis in culture or are stimulated by T or B cells, could not be answered by the present investigation.

Acute renal failure in a neonate caused by the transplacental transfer of a nephrotoxic paraprotein: successful resolution by exchange transfusion.

Acute renal failure was diagnosed within 6 days of birth in a full-term neonate. The mother was known to have a monoclonal gammopathy, immunoglobulin G (IgG) lambda, discovered a year before pregnancy on being investigated for hematuria and proteinuria. Her renal function was intact. Maternal renal biopsy performed at the time showed a focal proliferative glomerulonephritis with nonfibrillary homogeneous mesangial and intramembranous electron-dense deposits. Immunoperoxidase staining was positive for IgG and lambda and kappa light chains along the glomerular and tubular basement membranes. Pregnancy was uneventful. Protein electrophoresis and immunofixation of the infant girl's serum and urine samples showed the presence of a paraprotein electrophoretically identical to that found in the mother. Exchange transfusion resulted in a rapid improvement of renal function in parallel to the disappearance of the monoclonal component.

Placental isoferritin as a marker of early abortion in pregnancies induced by in vitro fertilization.

The relatively high rate of early pregnancy loss in artificial reproductive technology-induced conceptions has driven researchers to seek for an efficient diagnostic tool for estimating the gestational risk in these cases. Monitoring early gestation normalcy using serial beta-human chorionic gonadotrophin (beta hCG) measurements requires several days before diagnosis can be established. The objective of this study was to determine whether placental isoferritin (PLF) can be used as a predictive marker of normal pregnancy development during early stages of in vitro fertilization (IVF)-induced pregnancy. Ninety-three consecutive IVF cycles were investigated. Blood samples for PLF (enzyme linked immunosorbent assay; ELISA) and beta hCG (radio-immunoassay; RIA) determination were obtained from all women on days 11, 13 and 15 following embryo transfer. Placental isoferritin was detectable in the serum 11 days after embryo transfer in IVF conception cycles. These levels were significantly higher in normally developing pregnancies (n = 18) than in cases which eventually aborted spontaneously (n = 9) during the first trimester (mean +/- s.d.; 33 +/- 28 U/mL as compared with 1 +/- 2 U/mL; P = 0.0004; Wilcoxon test; sensitivity 94.5 per cent, specificity 88.9 per cent, positive predictive value 89.9 per cent, negative predictive value 94.5 per cent). Moreover, in those patients who later aborted, lower than normal PLF levels were detected long before the decline in beta hCG titres was evident. Considering its suppressor activity, it is expected that PLF levels would be high at the initiation of normal pregnancy. This may explain the present finding of low PLF levels in abnormally developing IVF-induced pregnancies. These preliminary data suggest that PLF can be used as a sensitive marker for detecting those cases destined to abort at a very early stage. However, further studies are still required on spontaneous conceptions, before this test can be recommended for routine clinical application.

Risk factors and management of patients with upper limb deep vein thrombosis.

STUDY OBJECTIVES: To determine the prevalence of endogenous and exogenous risk factors for venous thrombosis in patients with upper limb deep vein thrombosis (DVT), and to evaluate the risk of clinically detectable pulmonary embolus, recurrent DVT, and postphlebitic symptoms in these patients. DESIGN: A combined prospective and retrospective descriptive analysis of a cohort of patients with upper limb DVT compared with age- and sex-matched patients with lower limb DVT. SETTING: Internal medicine departments, and hematology and vascular surgery outpatient clinics at a tertiary-care university hospital. PATIENTS: Consecutive patients with "spontaneous" upper limb DVT diagnosed between 1989 and 1997 were studied. Twenty age- and sex-matched patients with lower limb DVT admitted to the hospital via the emergency department served as control patients. RESULTS: Eighteen patients with upper limb DVT were studied. An endogenous risk factor (thrombophilia) was present in 11 of 18 patients vs 8 of 20 control patients (p = not significant). In the upper limb group, nine patients had activated protein C resistance, four patients had anticardiolipin antibodies, and two patients had both forms of thrombophilia. Furthermore, 14 of the upper limb DVT patients were found to have an exogenous risk factor for thrombosis compared with 7 of the patients with lower limb DVT (p = 0.01), and 66.6% of patients with upper limb DVT had both an exogenous and an endogenous risk factor for thrombosis vs 15% of patients with lower limb DVT (p < 0.002). No clinically detectable pulmonary emboli occurred among the upper limb DVT patients. Three patients have minor postphlebitic symptoms. Two patients experienced recurrent DVT. CONCLUSION: In the majority of patients with upper limb DVT that we studied in this relatively small study, exogenous (environmental) or endogenous risk factors for venous thrombosis, or a combination of both, were found. Furthermore, in our patients, these thromboses had a low propensity to cause clinically significant pulmonary embolus and did not cause significant postphlebitic symptoms. Finally, we suggest that anticoagulant therapy for these thromboses may be adequate and that thrombolytic agents and surgical intervention are not routinely indicated.

A clinical approach to "idiopathic" normocytic-normochromic anemia.

OBJECTIVES: Normocytic-normochromic anemia is frequently found in patients with chronic disorders. The pathogenesis, epidemiological and clinical characteristics of normocytic normochromic anemia of unknown cause are not well established. We evaluated the role of bone marrow examination and the clinical course of patients with "idiopathic" normocytic-normochromic anemia. DESIGN: Patients with normocytic-normochromic anemia underwent a noninvasive evaluation according to a predetermined protocol. Bone marrow aspiration and biopsy were performed in those patients in whom no explanation for the anemia was found. They were later followed at 3 to 6 month intervals. RESULTS: Thirty-one patients (23 females and 8 males) with "idiopathic" normocytic-normochromic anemia (mean hemoglobin concentration was 10.0 + 0.6 g/dL) were detected. No patient had symptoms related to the anemia. Twenty-nine bone marrow aspirations and 21 biopsies were performed. Iron deficiency and mild myelofibrosis were found in one patient each. The rest of the bone marrow examinations were normal. During 15.5 +/- 10.3 months of follow-up, the hemoglobin level rose marginally to 10.9 + 1.0 g/dL (P < .0002). No changes in clinical or laboratory variables that could be ascribed to anemia were detected. CONCLUSION: Normocytic-normochromic anemia of unknown cause is encountered infrequently in clinical practice and is found mainly in older patients. The evaluation should be noninvasive to exclude correctable causes of the anemia. Bone marrow examination is only rarely contributive in this setting. The prognosis of these patients is excellent.

Monoclonal antibodies against native ovarian tumor cells: specificity and characterization of the antigen. A preliminary report.

Monoclonal antibodies were prepared against native human ovarian carcinoma cells derived from the ascitic fluid of a patient (BH). One antibody, HC7R7, was selected on the basis of its binding to tumor BH cells, to other ovarian tumor cell lines (CAOV-3 and GZL-8), but not to the patient's fibroblasts. One hundred cell smears from ascitic and pleural effusions of tumor-suspected patients were immunostained with HC7R7. All serous ovarian carcinomas and half of the breast carcinomas stained positive with HC7R7; cells from noncancer ovarian aspirates were negative. Mesothelial cells were also stained with HC7R7. A correlation was noted between HC7R7 and OC-125 staining of ovarian tumor cells but not between HC7R7 and c-neu staining of breast tumor paraffin sections. The location of HC7R7-positive material in ovarian tumor cell lines (CAOV-3 and GZL-8) differed from that in the breast tumor cell line (MCF-7). CAOV-3 and GZL-8 showed membrane binding while, in MCF-7, not fully identified intracellular organelles were stained. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis and immunoblots from membrane and cytosol fractions of GZL-8 and MCF-7 showed HC7R7 binding to three protein bands in the membrane fraction and to three other bands in the cytosol, all in the 29- to 68-kDa range. Two of the bands were glycoproteins. The only band that was different in the GZL-8 and MCF-7 cells was a 43-kDa glycoprotein, which was more pronounced in the MCF-7 cells. The possible significance of the new HC7R7 antibodies for detection and survey of ovarian malignancies is discussed.

Frequency control of a slow oscillatory network by a fast rhythmic input: pyloric to gastric mill interactions in the crab stomatogastric nervous system.

The stomatogastic nervous system of the crab, Cancer borealis, produces a slow gastric mill rhythm and a fast pyloric rhythm. When the gastric mill rhythm is not active, stimulation of the modulatory commissural ganglion neuron 1 (MCN1) activates a gastric mill rhythm in which the lateral gastric (LG) neuron fires in antiphase with interneuron 1 (Int1). We present theoretical and experimental data that indicate that the period of the MCN1 activated gastric mill rhythm depends on the strength and time course of the MCN1 evoked slow excitatory synaptic potential (EPSP) in the LG neuron, and on the strength of inhibition of Int 1 by the pacemaker of the pyloric network. This work demonstrates a new mechanism by which a slow network oscillator can be controlled by a much faster oscillatory neuron or network and suggests that modulation of the slow oscillator can occur by direct action on the neurons and synapses of the slow oscillator, or indirectly by actions on the fast oscillator and its synaptic connection with the slow oscillator.

To beat or not to beat: a decision taken at the network level.

The cells of the inferior olivary nucleus, the sole source of the cerebellar climbing fibers, form a network of electrically coupled neurons. Experimental observations show that these neurons produce a large repertoire of electrical signals, among which sub-threshold oscillations of the membrane potential. Simultaneous recordings from pairs of neurons and optical imaging of voltage sensitive dyes show that sub-threshold activity occurs in synchrony throughout the network. The mechanism underlying the generation of the sub-threshold oscillations is not fully understood. Experimental observations suggest that the electrical coupling is essential but insufficient for their generation. Several theoretical mechanisms have been suggested to explain these observations. Up-to-date, the most realistic model is the heterogeneity model, that assumes a certain degree of heterogeneity among olivary neurons. The heterogeneity model proposes that sub-threshold oscillations are produced by electrical coupling of neurons with the same types of ionic conductances, but with different densities. The variability in channel densities yield neurons of different functional types. The main prediction of the model is that different functional types of neurons should be found in the inferior olive. Dynamic clamp experiments support this prediction.

Fluorescence in situ hybridization for the detection of trisomies 8 and 9 in polycythemia vera.

Trisomies 8 and 9 are the most common numerical chromosome abnormalities in polycythemia vera (PCV). Their role in the pathogenesis of the disease is unclear, however, as is their diagnostic or prognostic value. We evaluated fluorescent in situ hybridization as compared to chromosome analysis for the detection of trisomies 8 or 9 in peripheral blood cells of PCV patients. We demonstrated that FISH is a more sensitive method for the detection of the abnormalities. A positive correlation between the duration of the disease and trisomy 9 was found. FISH is a sensitive, convenient, and rapid method for the diagnosis and follow-up of chromosome aberrations in patients with PCV. The application of FISH to a larger cohort of patients may provide valuable information regarding the role of the chromosomal aberrations in the initiation and progression of this disease.