Cystic fibrosis and neonatal calcified scrotal masses

We report a case of an infant who presented with failure to thrive and in whom the identification of calcified scrotal masses led us to the diagnosis of cystic fibrosis.     

Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan

The serotonergic system has been implicated in both the aetiology and pharmacological treatment of obsessive compulsive disorder. In pharmacological challenge tests, mCPP, a 5-HT agonist, with an affinity for 5HT_2C as well as 5HT_1A and 5HT_1D, receptors, was associated with a transient exacerbation of obsessive compulsive symptoms. Chronic administration of mCPP was found to bring about some relief of these symptoms. Sumatriptan is an antimigraine agent, which interacts most potently with 5HT_1D receptors. In the cases to be presented, we report the effects of chronic administration of Sumatriptan to three severe, treatment resistant, OCD patients. Following chronic administration of sumatriptan, these patients, who have been resistant to any former pharmacological treatment, responded with an improvement in their depression and a modest reduction in their obsessive compulsive symptoms.     

Haemodialysis activates phospholipase A2 enzyme

BACKGROUND: Clinical and experimental evidence suggest that haemodialysis(HD) procedure is an inflammatory process. For the productionof proinflammatory lipid mediators in many inflammatory reactions,the release of arachidonic acid by phospholipase A₂ (PLA₂ enzymeis a prerequisite. Therefore, the purpose of the present investigationwas to establish whether the activity of PLA₂ increases duringHD and whether the increase depends on the type of dialyserused. METHODS: We performed dialysis in eight chronic HD patients. Blood samplesentering and leaving the dialyser were obtained before and at15, 60, 120 and 180 min after the dialysis was started, on oneoccasion using a cuprophane and on another occasion a cellulosetriacetate dialyser. PLA₂ activity was assessed in crude plasmaand in plasma extract. RESULTS: PLA₂ activity in plasma extract exhibited similar biochemicalproperties to that of inflammatory human synovial fluid PLA₂enzyme which is of group II PLA₂. PLA₂ activity in crude plasmarepresents a type of PLA₂ other than the synovial type. In HDpatients, baseline PLA₂ activities in crude plasma and plasmaextract were significantly increased when compared to normalsubjects. An increase in PLA₂ activity was observed in crudeplasma with a peak appearing at 15 min when the patients weredialysed with cuprophane and cellulose triacetate membranes.This increase was observed in both arterial and venous bloodsamples and was more pronounced when the patients were dialysedwith cuprophane than with cellulose triacetate membranes. WhenPLA₂ was assessed in plasma extract, the activity increasedonly with cuprophane but not with cellulose triacetate membranes. CONCLUSIONS: PLA₂ activity in plasma is increased in HD patients and increasesduring the dialysis procedure to a greater extent with a lessbiocompatible membrane. Continuous activation of PLA₂ mightbe relevant for long-term deleterious consequences of HD.     

Adjustment to breast cancer: the contribution of resources and causal attributions regarding the illness

The study examined personal resources (sense of coherence and social support) and attributions concerning the causes of illness, and their relationship to adjustment to breast cancer. The research sample included 60 Israeli women with breast cancer, who responded to questionnaires at two stages of their illness: the stage of initial discovery (after first learning of the illness) and approximately six months later (the stage of mitigation and accommodation). The overall level of adjustment to the illness was moderate. While the patients adjusted relatively well in the family and domestic environments, their adjustment in the dimensions of health care, psychological distress, and sexual relations was relatively low. The most frequent causal attributions were psychological factors and family history of illness. The patients' subjective state of health, sense of coherence, and levels of social support were related to most of the adjustment dimensions examined, although both internal and external causal attributions correlated negatively with adjustment in every dimension.     

Role of biofilms in neurosurgical device-related infections

Bacterial biofilms have recently been shown to be important in neurosurgical device-related infections. Because the concept of biofilms is novel to most practitioners, it is important to understand that both traditional pharmaceutical therapies and host defense mechanisms that are aimed at treating or overcoming free-swimming bacteria are largely ineffective against the sessile bacteria in a biofilm. Bacterial biofilms are complex surface-attached structures that are composed of an extruded extracellular matrix in which the individual bacteria are embedded. Superimposed on this physical architecture is a complex system of intercellular signaling, termed quorum sensing. These complex organizational features endow biofilms with numerous microenvironments and a concomitant number of distinct bacterial phenotypes. Each of the bacterial phenotypes within the biofilm displays a unique gene expression pattern tied to nutrient availability and waste transport. Such diversity provides the biofilm as a whole with an enormous survival advantage when compared to the individual component bacterial cells. Thus, it is appropriate to view the biofilm as a multicellular organism, akin to metazoan eukaryotic life. Bacterial biofilms are much hardier than free floating or planktonic bacteria and are primarily responsible for device-related infections. Now that basic research has demonstrated that the vast majority of bacteria exist in biofilms, the paradigm of biofilm-associated chronic infections is spreading to the clinical world. Understanding how these biofilm infections affect patients with neurosurgical devices is a prerequisite to developing strategies for their treatment and prevention.     

Association between birth control pills and voice quality

OBJECTIVES/HYPOTHESIS: The objective was to extend our knowledge of the effect of birth control pills on voice quality in women based on various acoustic measures. STUDY DESIGN: A longitudinal comparative study of 14 healthy young women over a 36- to 45-day period. METHODS: Voices of seven women who used birth control pills and seven women who did not were recorded repeatedly approximately 20 times. Voice samples were analyzed acoustically, using an extended set of frequency perturbation parameters (jitter, relative average perturbation, pitch period perturbation quotient), amplitude perturbation parameters (shimmer, amplitude average perturbation quotient), and noise indices (noise-to-harmonics ratio, voice turbulence index). RESULTS: Voice quality and stability were found to be better among the women who used birth control pills. Lower values were found for all acoustic measures with the exception of voice turbulence index. Results also provided preliminary indication for vocal changes associated with the days preceding ovulation. CONCLUSION: In contrast to the traditional view of oral contraceptives as a risk factor for voice quality, and in keeping with the authors' previous work, the data in the present study showed that not only did oral contraceptives have no adverse effect on voice quality but, in effect, most acoustic measures showed improved voice quality among women who used the birth control pill. The differences in the noise indices between groups may also shed light on the nature of the effect of sex hormones on vocal fold activity. It was suggested that hormonal fluctuations may have more of an effect on vocal fold regulation of vibration than on glottal adduction.     

Targeting an extracellular epitope of the human multidrug resistance protein 1 (MRP1) in malignant cells with a novel recombinant single chain Fv antibody

Inherent and acquired multidrug resistance (MDR) is characterized by a simultaneous resistance to diverse anticancer drugs and is a major impediment towards curative chemotherapy of cancer. Hence one important goal is to develop strategies aimed at specific targeting of major anticancer drug efflux transporters of the ATP-binding cassette (ABC) superfamily including multidrug resistance protein 1 -MRP1 (ABCC1). To date, no monoclonal antibody has been isolated that can target an extracellular MRP1 epitope. Using a phage display approach, we have isolated a recombinant single-chain Fv (scFv) antibody that specifically reacts with the extracellular N-terminus of the human MRP1. Flow cytometric analysis revealed that this scFv fragment binds specifically to various viable human tumor cells that display variable MRP1 expression levels but not to MRP1 null cells. Furthermore, this scFv antibody failed to react with tumor cells that overexpress other members of the MRP family that have an extracellular N-terminus (MRP2 and MRP3) as well as with MRP4, MRP5, and breast cancer resistance protein. Flow cytometric analysis also showed a good correlation between the fluorescence intensity of the anti-MRP1 scFv antibody and MRP1 levels in viable tumor cells. These findings constitute the first successful isolation of a small recombinant scFv antibody directed to an extracellular epitope of the MRP1 in viable malignant cells. These novel small Fv-based recombinant antibodies that possess superior tumor penetration capabilities may possibly be used to selectively target drugs or tumor cells that express MRP-1.     

Amelioration of behavioral deficits in a rat model of Huntington's disease by an excitotoxic lesion to the globus pallidus

Four groups of rats, sustaining a striatal quinolinic acid (QA) lesion, a pallidal QA lesion, a combined striatal + pallidal lesion, or sham operation, were tested in spontaneous and amphetamine-induced activity, spatial navigation in a water maze, position discrimination and reversal in a wet T maze, and food manipulation. The striatal lesion markedly impaired rats' performance on the motor and cognitive tasks. In contrast, rats sustaining a bilateral lesion to the GP in addition to the striatal lesion performed similarly to sham-operated rats on the motor and cognitive tasks, although they showed a transient decrease in activity levels. Given that a similar dysfunction of basal ganglia circuitry is thought to subserve the behavioral alterations seen in QA-lesioned rats and Huntington's disease (HD) patients, the present results raise the possibility that manipulations of the external segment of the globus pallidus (the primate analogue of the rat GP) could ameliorate some of HD symptoms.     

Do oral contraceptives improve vocal quality? Limited trial on low-dose formulations

OBJECTIVE: To evaluate the effect of low-dose monophasic oral contraceptives on female vocal quality. METHODS: Acoustic voice parameters of six women who use oral contraceptives and six women who do not were evaluated repeatedly during the menstrual cycle. Frequency and amplitude variations were measured using a computerized voice analysis program. Repeated-measures analysis of variance was performed to test differences between groups for each acoustic voice parameter. RESULTS: Vocal stability among the women who use oral contraceptives was significantly better than among those who did not use oral contraceptives (P <.05). Specifically, amplitude and frequency variations between successive vocal cycles were smaller in women using oral contraceptives in comparison with the control group (.24 dB versus.37 dB and.86% versus 1.27% for amplitude and frequency variations, respectively). CONCLUSION: Contrary to the reports of adverse effects that high-dose pills have on voice, low-dose oral contraceptives show a favorable influence on voice in young women.