BACKGROUND Hypergonadotropic hypoestrogenic infertility is the most burdensome complication for females suffering from classic galactosemia. In contrast, male gonadal function seems less affected. ...The underlying mechanism is not understood and several pathogenic mechanisms have been proposed. Timing of the lesion, prenatal or chronic post-natal, or a combination of both are not yet clear. METHODS This review focuses on gonadal function in males and females, ovarian imaging and histology in this disease. It is based on the literature known to the authors and a Pubmed search using the keywords galactosemia, GALT deficiency, (premature) ovarian failure/insufficiency/dysfunction, testicular function, gonadotrophins, FSH, LH (published between January 1971 and April 2009). RESULTS Male gonads are less affected, boys spontaneously reach puberty, although onset can be delayed. Semen quality has not been extensively studied. Several affected males are known to have fathered a child. Female gonads are invariably affected, although to a varied extent (hypergonadotropic hypoestrogenic ovarian dysfunction). Intriguingly, FSH is often already increased in infancy. Imaging usually shows hypoplastic and streak-like ovaries. Histological findings in some cases reveal the presence of morphologically normal but decreased numbers of primordial follicles, with the absence of intermediate and Graafian follicles. CONCLUSION Gonads in males seem less affected than in females who exhibit hypergonadotropic hypoestrogenic subfertility. FSH can be elevated in infancy, and ovarian histology sometimes shows the presence of normal primordial follicles with absence of intermediate and Graafian follicles. These findings are similar to other genetic diseases primarily affecting the ovary.
The Netherlands Pharmacovigilance Centre Lareb has received two reports of cholesterol crystal embolisms associated with the use of a direct oral anticoagulant (DOAC). The European pharmacovigilance ...database contains several other cases concerning this association, and one report was published in the scientific literature. Cholesterol crystal embolisms were described in association with the use of several other antithrombotic drugs, although the role as an independent risk factor is not conclusive. The case series described in this article, indicates the possibility of an adverse drug reaction when a patient develops cholesterol crystal embolisms while using a DOAC.
Purpose: Image Guided Radiotherapy (IGRT) is a necessity for accurate radiotherapy. Ultrasound (US) imaging is a frequently used diagnostic technique for qualitative imaging of soft tissues. ...Recently, a quantitative 3D US system was introduced (Clarity system, Resonant Medical, Canada) which can assess the position of soft tissue in absolute space. Before introducing the device into daily practice, user variability, during both image acquisition and matching procedures must be determined. In this study we determined the inter‐ and intra‐operator variability of 3D US matching in prostate cancer patients. Moreover, we studied the influence of the scan variability on patient setup corrections, and the influence of probe pressure on the prostate position while using a strict bladder filling protocol. Methods: For 12 prostate patients multiple US scans are acquired by one or two operators during treatment. The repeated scans are matched to the reference US‐scan by a single user (variability for scanning). The remaining scans are matched three times by different users, and for each patient one single scan is matched five times by the same user (variability for matching). Results: In all three directions the mean intra‐operator difference ranges from 1.5 to 2.4 mm, with a standard deviation of approximately 1.7 mm. The mean inter‐operator difference is of the same order, 1.7 to 2.3 ± 1.8 mm. The prostate displacement due to the probe pressure varies from patient to patient and is not limited to one direction. Only the superior/inferior displacement seemed significant for high pressure, which was not needed to obtain good image quality with our bladder filling protocol. The total uncertainty is conservatively estimated to be 4 mm. Conclusions: The uncertainty of the 3D US IGRT system is comparable to the uncertainty of the current standard IGRT for prostate: electronic portal imager in combination with fiducial markers.
OBJECTIVETo study whether the circulatory changes of human septic shock are mediated in part by nitric oxide.
DESIGNOpen-label, nonrandomized clinical trial on the effects of methylene blue, an ...inhibitor of nitric oxide action.
SETTINGIntensive care unit of a teaching hospital.
PATIENTSNine consecutive patients with documented septic shock and a pulmonary artery catheter in place, after initial resuscitation with fluids, sympathomimetics, and mechanical ventilation.
INTERVENTIONSHemodynamic and metabolic variables were measured before and then 15, 30, 60, and 120 mins after the start of a 20-min infusion of 2 mg/kg of methylene blue.
MEASUREMENTS AND MAIN RESULTSPatients had a hyperdynamic circulation, and methylene blue increased (p < .01) mean arterial pressure from 84 +/- 18 to 109 +/- 31 mm Hg and cardiac index from 4.7 +/- 0.9 to 5.6 +/- 1.2 L/min/m, before and 30 mins after starting the methylene blue infusion, respectively. Cardiac filling pressures did not change. In the same time interval, the subnormal systemic vascular resistance index increased (p = .09) and arterial compliance decreased (p < .05). Oxygen delivery and oxygen uptake increased (p <.05) from 714 +/- 188 to 865 +/- 250 mL/min/m and from 160 +/- 39 to 186 +/- 44 mL/min/m, respectively. Except for heart rate, which increased by 11 +/- 8 beats/min (p < .01), variables returned to baseline values at time = 120 mins.
CONCLUSIONSAfter initial resuscitation from human septic shock, a single dose of methylene blue transiently increases mean arterial pressure and oxygen uptake, associated with a decrease in arterial compliance and increases in myocardial function and oxygen delivery. Hence, nitric oxide may be a mediator of the circulatory changes of human septic shock.(Crit Care Med 1995; 23:1363-1370)
In order to cope with the occupancy and radiation doses expected at the High-Luminosity LHC, the ATLAS experiment will replace its Inner Detector with an all-silicon Inner Tracker (ITk), consisting ...of pixel and strip subsystems.
In the last two years, several prototype ITk strip modules have been tested using beams of high energy electrons produced at the DESY-II testbeam facility. Tracking was provided by EUDET telescopes. The modules tested are built from two sensor types: the rectangular ATLAS17LS, which will be used in the outer layers of the central barrel region of the detector, and the annular ATLAS12EC, which will be used in the innermost ring (R0) of the forward region. Additionally, a structure with two R0 modules positioned back-to-back has been measured, demonstrating space point reconstruction using the stereo angle of the strips. Finally, one barrel and one R0 module have been measured after irradiation to 40% beyond the expected end-of-lifetime fluence. The data obtained allow for thorough tests of the module performance, including charge collection, noise occupancy, detection efficiency, and tracking performance. The results give confidence that the ITk strip detector will meet the requirements of the ATLAS experiment.
This study investigated both professional caregiver workload as well as the patients' and caregivers' satisfaction with a transmural home care program. Seventy-nine patients were included in the ...intervention program. The specialist nurse coordinator, general practitioner, community nurse providing 'intensive' community care, community nurses providing 'standard' community care, and the home helper spent in total an average of 7.5, 4.4, 55.6, 55.0, and 112.3 h, respectively, on each patient during the care process (mean survival of the 79 patients was 101.2 days). The 24 h telephone service and transmural home team were contacted in total 100 and 8 times, respectively. Patient and caregiver satisfaction with the care provided scored (very) high. Considering this acceptable workload and given that the program did not interfere with existing standard health care structures, it can be concluded that such care may easily be introduced by other hospitals and related primary care teams.
MUC16 is a cell surface mucin expressed at high levels by epithelial ovarian tumors. Following proteolytic cleavage, cell surface MUC16 (csMUC16) is shed in the extracellular milieu and is detected ...in the serum of cancer patients as the tumor marker CA125. csMUC16 acts as an adhesion molecule and facilitates peritoneal metastasis of ovarian tumors. Both sMUC16 and csMUC16 also protect cancer cells from cytotoxic responses of natural killer (NK) cells. In a previous study we demonstrated that sMUC16 binds to specific subset of NK cells. Here, we identify the csMUC16/sMUC16 binding partner expressed on immune cells.
Analysis of immune cells from the peripheral blood and peritoneal fluid of ovarian cancer patients indicates that in addition to NK cells, sMUC16 also binds to B cells and monocytes isolated from the peripheral blood and peritoneal fluid. I-type lectin, Siglec-9, is identified as the sMUC16 receptor on these immune cells. Siglec-9 is expressed on approximately 30-40% of CD16pos/CD56dim NK cells, 20-30% of B cells and >95% of monocytes. sMUC16 binds to the majority of the Siglec-9pos NK cells, B cells and monocytes. sMUC16 is released from the immune cells following neuraminidase treatment. Siglec-9 transfected Jurkat cells and monocytes isolated from healthy donors bind to ovarian tumor cells via Siglec-9-csMUC16 interaction.
Recent studies indicate that csMUC16 can act as an anti-adhesive agent that blocks tumor-immune cell interactions. Our results demonstrate that similar to other mucins, csMUC16 can also facilitate cell adhesion by interacting with a suitable binding partner such as mesothelin or Siglec-9. Siglec-9 is an inhibitory receptor that attenuates T cell and NK cell function. sMUC16/csMUC16-Siglec-9 binding likely mediates inhibition of anti-tumor immune responses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective This update of a 2008 guideline from the American Academy of Otolaryngology-Head and Neck Surgery Foundation provides evidence-based recommendations to benign paroxysmal positional vertigo ...(BPPV), defined as a disorder of the inner ear characterized by repeated episodes of positional vertigo. Changes from the prior guideline include a consumer advocate added to the update group; new evidence from 2 clinical practice guidelines, 20 systematic reviews, and 27 randomized controlled trials; enhanced emphasis on patient education and shared decision making; a new algorithm to clarify action statement relationships; and new and expanded recommendations for the diagnosis and management of BPPV. Purpose The primary purposes of this guideline are to improve the quality of care and outcomes for BPPV by improving the accurate and efficient diagnosis of BPPV, reducing the inappropriate use of vestibular suppressant medications, decreasing the inappropriate use of ancillary testing such as radiographic imaging, and increasing the use of appropriate therapeutic repositioning maneuvers. The guideline is intended for all clinicians who are likely to diagnose and manage patients with BPPV, and it applies to any setting in which BPPV would be identified, monitored, or managed. The target patient for the guideline is aged ≥18 years with a suspected or potential diagnosis of BPPV. The primary outcome considered in this guideline is the resolution of the symptoms associated with BPPV. Secondary outcomes considered include an increased rate of accurate diagnoses of BPPV, a more efficient return to regular activities and work, decreased use of inappropriate medications and unnecessary diagnostic tests, reduction in recurrence of BPPV, and reduction in adverse events associated with undiagnosed or untreated BPPV. Other outcomes considered include minimizing costs in the diagnosis and treatment of BPPV, minimizing potentially unnecessary return physician visits, and maximizing the health-related quality of life of individuals afflicted with BPPV. Action Statements The update group made strong recommendations that clinicians should (1) diagnose posterior semicircular canal BPPV when vertigo associated with torsional, upbeating nystagmus is provoked by the Dix-Hallpike maneuver, performed by bringing the patient from an upright to supine position with the head turned 45° to one side and neck extended 20° with the affected ear down, and (2) treat, or refer to a clinician who can treat, patients with posterior canal BPPV with a canalith repositioning procedure. The update group made a strong recommendation against postprocedural postural restrictions after canalith repositioning procedure for posterior canal BPPV. The update group made recommendations that the clinician should (1) perform, or refer to a clinician who can perform, a supine roll test to assess for lateral semicircular canal BPPV if the patient has a history compatible with BPPV and the Dix-Hallpike test exhibits horizontal or no nystagmus; (2) differentiate, or refer to a clinician who can differentiate, BPPV from other causes of imbalance, dizziness, and vertigo; (3) assess patients with BPPV for factors that modify management, including impaired mobility or balance, central nervous system disorders, a lack of home support, and/or increased risk for falling; (4) reassess patients within 1 month after an initial period of observation or treatment to document resolution or persistence of symptoms; (5) evaluate, or refer to a clinician who can evaluate, patients with persistent symptoms for unresolved BPPV and/or underlying peripheral vestibular or central nervous system disorders; and (6) educate patients regarding the impact of BPPV on their safety, the potential for disease recurrence, and the importance of follow-up. The update group made recommendations against (1) radiographic imaging for a patient who meets diagnostic criteria for BPPV in the absence of additional signs and/or symptoms inconsistent with BPPV that warrant imaging, (2) vestibular testing for a patient who meets diagnostic criteria for BPPV in the absence of additional vestibular signs and/or symptoms inconsistent with BPPV that warrant testing, and (3) routinely treating BPPV with vestibular suppressant medications such as antihistamines and/or benzodiazepines. The guideline update group provided the options that clinicians may offer (1) observation with follow-up as initial management for patients with BPPV and (2) vestibular rehabilitation, either self-administered or with a clinician, in the treatment of BPPV.
PDF
