Clinical evaluation of atypical glandular cells of undetermined significance upon cervical cytologic examination in Israeli Jewish women

The adjusted incidence of cervical carcinoma among Israeli Jewish women is approximately 5 out of 100 000. This retrospective study sought to determine the clinical implications of finding atypical glandular cells of undetermined significance (AGUS) in cervical cytologic specimens in this population. Cervical cytologic examinations during January 2001-June 2003 diagnosed as AGUS were identified by a computerised database. Medical records were reviewed to determine the presence or absence of associated significant pathologic conditions of the cervix and identified 45 out of 11 800 patients (0.38%) with AGUS. AGUS was the only cytologic diagnosis in 14 patients, while 31 patients had both AGUS and an additional atypical squamous cell of undetermined significance (ASCUS). All subjects underwent colposcopy, endocervical curettage, and cervical biopsy. A clinically significant diagnosis (cervical intraepithelial neoplasia (CIN) II, CIN III, or carcinoma) was made in 24 patients (53.3%), including cancer in three (6.7%): one had microinvasive adenocarcinoma and two had microinvasive squamous cell carcinoma. Squamous carcinoma coexisting with a clinically significant lesion carried a risk of 61.3%, compared with a risk of 35.7% for AGUS alone (P=0.20). Detection of AGUS during cervical cytologic screening, especially with a coexisting ASCUS, indicates the existence of serious pathologic processes; management by cervical colposcopy, endocervical curettage, and cervical biopsy is recommended.     

Bone strength in multiple sclerosis: cortical midtibial speed-of-sound assessment

It has been previously suggested that multiple sclerosis (MS) patients are at increased risk for osteoporosis due to reduced mobility, decreased exposure to sunlight and recurrent steroid treatment. In order to systematically evaluate bone strength we assessed 256 MS patients (171 females, 75 males) through quantitative ultrasound measurement of cortical bone. Tibial speed of sound (SOS, m/sec) was measured at midpoint of the tibial shaft using a Soundscan 2000 (Myriad Ultrasound Systems, Rehovot, Israel) and results were compared to age- and gender-matched population norms. T-score distribution in male MS patients was similar to normal population. In contrast, for female MS patients T-score distribution was significantly different from population norms, reflected by increased SOS in 30.4% (T-score intervals 1-2 and >2 above normal values; P=0.001), compared with 7.4% in controls. These findings held true for both female patients younger and older than 45 years of age. Increased neurological disability and specifically motor involvement were more frequent in female patients with increased SOS (P<0.05). Bone strength was preserved in MS patients. In a subgroup of female patients increased SOS was conceivably related to spasticity.     

Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial

BACKGROUND: Intravenous immunoglobulin (IVIg) has been reported to reduce disease activity in patients with relapsing-remitting multiple sclerosis. We assessed the effect of IVIg treatment in patients after the first neurological event suggestive of demyelinative disease and evaluated the occurrence of a second attack and dissemination in time demonstrated by brain magnetic resonance imaging within the first year from onset. METHODS: We conducted a randomized, placebo-controlled, double-blind study in 91 eligible patients enrolled within the first 6 weeks of neurological symptoms. Patients were randomly assigned to receive IVIg treatment (2-g/kg loading dose) or placebo, with boosters (0.4 g/kg) given once every 6 weeks for 1 year. Neurological and clinical assessments were done every 3 months, and brain magnetic resonance imaging was performed at baseline and the end of the study. RESULTS: The cumulative probability of developing clinically definite multiple sclerosis was significantly lower in the IVIg treatment group compared with the placebo group (rate ratio, 0.36 [95% confidence interval, 0.15-0.88]; P = .03). Patients in the IVIg treatment group had a significant reduction in the volume and number of T2-weighted lesions and in the volume of gadolinium-enhancing lesions as compared with the placebo group (P = .01, P = .01, and P = .03, respectively). Treatment was well tolerated, compliance was high, and incidence of adverse effects did not differ significantly between groups. CONCLUSIONS: Intravenous immunoglobulin treatment for the first year from onset of the first neurological event suggestive of demyelinative disease significantly lowers the incidence of a second attack and reduces disease activity as measured by brain magnetic resonance imaging.     

The cognitive-orientation theory of anorexia nervosa

The major goal was to explore the cognitive-motivational dynamics of anorexia in terms of the cognitive-orientation (CO) theory (Kreitler & Kreitler, 1982). CO is a comprehensive theory of behavior that assumes that behavior is a function of a cognitively shaped motivational disposition and performance. The study deals with the motivational disposition for anorexia. It focused on examining whether beliefs of four types (about self, goals, norms, and reality) concerning themes relevant for anorexia (defined in pretests) identify correctly anorectics. All participants were women 15 to 18 years old: 58 anorectics (35 restricting, 23 binge eating/purging) and 59 matched healthy controls. All were administered a background-information questionnaire and the CO-Anorexia questionnaire assessing beliefs about 30 themes. The results showed that the themes formed 5 clusters defined by foci, such as dissociation from reality, the body, drives or emotionality, and identified significantly the anorectics of each type and the healthy controls. A brief CO questionnaire was developed. Discussion centered on the similarity of the identified themes to some of those discussed by others, on the pathogeneity of the CO of anorexia, and on outlining a blueprint of a theory of anorexia.     

Monitoring indirect presentation of alloantigens by utilizing the autologous processing machinery of dendritic cells in-vitro

BACKGROUND: Judicious individualization of immunosuppression protocols requires the ability to monitor the recipients' specific immune response towards the allograft. While several indirect presentation studies have been reported, currently there are no consistently reliable means to assess the state of transplant acceptance. A potential explanation might be the lack of established kinetics for in-vitro indirect presentation assays. METHODS: Dendritic cell (DCs) were used as self-specific "processing machinery" for the generation of allogeneic peptide repertoire tailored by the individual's capacity to process antigens via the indirect pathway. The kinetics of antigen processing and presentation of newly acquired antigens was then assessed to define the following: (1) Optimal time to introduce apoptotic-allogeneic cells to DCs; (2) optimal time for processing before induction of DC maturation; and (3) optimal time for stimulation of autologous T cells by the pulsed DCs. RESULTS: Altering kinetic parameters associated with time allotted for antigen processing; antigen presentation and DCs maturation, showed substantial variations in the level of T cell activation, as was documented by mixed lymphocyte reaction (MLR)-like proliferation assays. Further experiments using allogeneic cellular extracts showed similar variations in T cell stimulation by monitoring T cell precursor frequencies and interferon (IFN)-gamma secretion ELISPOT assays. Using the appropriate kinetic parameters, we have also shown difference in T-cell-subsets (CD4, CD8) precursor frequencies and cytokine secretion in response to different antigenic sources. CONCLUSIONS: The ability to construct an in-vitro, recipient-tailored, donor-specific, indirect presentation assay is dependent on essential kinetic parameters associated with antigen processing and presentation, as described in this report. Moreover, the use of this approach may circumvent the need for identifying specific immunogenic peptides for cancer-related or other vaccine-development studies.     

From caring to managing and beyond: an examination of the head nurse's role

AIM: The aim of this study was to depict the essence of what head nurses do, and how they perform their managerial role. METHODS: To achieve this, the work behaviour of 48 head nurses was examined by a semi-structured observation technique for 6 hours each. RESULTS: Results demonstrated that head nurses spent a large proportion of their time in clinical practice, followed by co-ordinating care, operating the unit's functions, and leading staff. Personnel management and quality improvement occupied only a marginal share of head nurses' time. CONCLUSIONS: These results implied that head nurses exhibited a management style orientated to maintenance rather than to re-creation, focusing more on the 'doing' and the 'here and now' aspects of the job than on leading, planning, and proactive problem solving.     

Sex-related differences in patients with severe head injury: greater susceptibility to brain swelling in female patients 50 years of age and younger

OBJECT: The goal of this study was to study the influence of sex and age on factors affecting patient outcome in severe head injury. METHODS: Data from the prospectively conducted international trial of tirilazad mesylate in patients with head injury were analyzed retrospectively. Included were 957 patients, 23% of whom were female and all of whom were between the ages of 15 and 79 years. All patients presented with Glasgow Coma Scale (GCS) scores between 3 and 8 and evidence of structural brain damage and/or subarachnoid hemorrhage (SAH) on the initial CT scan. Frequencies of recognized risk factors, including brain swelling, intracranial hypertension, systemic hypotension, advanced age, SAH, and injury severity (based on GCS scores), as well as dichotomized Glasgow Outcome Scale (GOS) scores (good recovery or moderate disability compared with severe disability, persistent vegetative state, or death) obtained 6 months postinjury were compared between male and female patients. CONCLUSIONS: Overall significantly greater frequencies of brain swelling and intracranial hypertension were found in female compared with male patients (35% compared with 24% [p < 0.0008] and 39 compared with 31% [p < 0.03], respectively). The highest rates were found in female patients younger than 51 years old (38% compared with 24% [p < 0.002] and 40% compared with 30% [p < 0.02], respectively, in male patients younger than 51 years of age). This effect was independent of injury severity (GCS) scores, which were not different in male and female patients. Female patients younger than 50 years tended to have worse outcomes, but the difference was not statistically significant. Thus, female patients who sustain severe head injury, especially (presumably) premenopausal ones aged 50 years and younger, are significantly more likely to experience brain swelling and intracranial hypertension than male patients with a comparable injury severity, suggesting that younger women may benefit from more aggressive monitoring and treatment of intracranial hypertension.     

Replacing the Amsler grid: a new method for monitoring patients with age-related macular degeneration

PURPOSE: To investigate a method that uses hyperacuity, the Macular Computerized Psychophysical Test (MCPT), to evaluate the central macular visual field in patients with age-related macular degeneration (AMD). DESIGN: Prospective case-control study of a diagnostic test. PARTICIPANTS AND CONTROLS: One hundred eight eyes of 108 Patients with AMD and 51 eyes of 51 age-matched patients with no retinal disease. Patients with AMD included 32 (30%) patients with choroidal neovascularization (CNV), 23 (21%) with geographic atrophy (GA), 35 (32%) with AMD with high-risk characteristics (HRC), and 18 (17%) with early AMD with non-HRC. TESTING: Each subject underwent the MCPT, in which a virtual line composed of dots (white dots on a black background, maximal contrast) is flashed across different macular loci to a perifoveal radius of 7 degrees. Patients' responses were recorded and automatically analyzed using a specific algorithm developed before the onset of the study. All patients also underwent a supervised Amsler grid examination on the encounter before or after the MCPT in random order. MAIN OUTCOME MEASURES: Distortion, scotoma, or blurring perceived by the patient after a swift change of fixation was considered positive on the MCPT. Any perception of distortion, scotoma, or blurring was considered positive on the Amsler grid. RESULTS: Of the 32 patients with CNV, 30 (94%) were found positive on the MCPT and 11 (34%) were found positive on the Amsler grid. Of the 23 GA patients, 21 (91%) were found positive on the MCPT and 7 (30%) were found positive on the Amsler grid. Of the 35 HRC patients, 28 (80%) were found positive on the MCPT and 3 (9%) were found positive on the Amsler grid, and of the 18 early AMD with non-HRC patients, 8 (44%) were found positive on the MCPT and 3 (17%) were found positive on the Amsler grid. Of the 51 controls, 3 (6%) were positive on the MCPT and 1 (2%) was positive on the Amsler grid. CONCLUSIONS: The MCPT was superior to the Amsler grid in detecting AMD-related lesions in this cohort. Studies are underway to determine whether the MCPT is feasible for home monitoring to provide early detection of progression to CNV.