[The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain].

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians' awareness of opportunistic virus reactivation during anti-tumor treatment.

[Distribution and reference intervals of daytime intraocular pressure in the eye health screening population of Handan].

Objective: To describe the distribution and establish reference intervals (RI) of daytime intraocular pressure (IOP) in the eye health screening population of Handan. Methods: This cross-sectional study included subjects who participated in eye health screening at the Physical Examination Center of Handan First Hospital from May 2021 to June 2022. A complete general and ocular examination was performed, including measurements of visual acuity and IOP (using Goldmann tonometry), slit lamp microscopy, fundus photography, and anterior and posterior segment optical coherence tomography. Subjects with factors that could cause significant changes in IOP or affect the accuracy of IOP measurement, or with an inability to measure IOP were excluded. Simple random sampling was used to select participants, who were grouped by gender and age (18 to <30, 30 to <40, 40 to <50, 50 to <60, 60 to <70, and ≥70 years). Central corneal thickness and IOP at 8 to 11 o'clock in one eye of each participant were recorded. The independent sample t test and ANOVA were used for statistical analysis, and the RI of IOP values was calculated by x¯±1.96s. Results: A total of 9 310 subjects had their IOP measured, and 3 491 participants (3 491 eyes) were randomly selected from 7 886 healthy subjects. The age of the participants was (47.74±14.47) years old, ranging from 18 to 90 years old. There were 1 694 males and 1 797 females. The central corneal thickness of all participants was (525.56±49.39) µm. The daytime IOP of all participants was (15.40±2.54) mmHg (1 mmHg=0.133 kPa), and the RI was 10.42 to 20.39 mmHg. The IOP was (15.49±2.58) mmHg for males and (15.29±2.49) mmHg for females, and the gender difference was statistically significant (P<0.05). The RI of daytime IOP values was 10.43 to 20.54 mmHg for males and 10.41 to 20.18 mmHg for females. There were significant differences in daytime IOP [(15.13±2.58), (15.33±2.53), (15.49±2.50), (15.53±2.55), (15.39±2.62), and (15.28±2.52) mmHg] among 6 age groups (P<0.05). Conclusions: The distribution of daytime IOP in different gender and age groups in the eye health screening population of Handan and the RIs derived from the distribution were roughly the same as the international normal IOP RI (10 to 21 mmHg). It is recommended to refer to the RI of daytime IOP values of different genders and ages for clinical decision.

[Clinical characteristics and prognosis of patients with anti-glutamic acid decarboxylase antibody-related cerebellar ataxia].

The clinical data, diagnosis, treatment, and prognosis of 10 patients with anti-glutamic acid decarboxylase (GAD) antibody-related cerebellar ataxia in Department of Neurology, Peking Union Medical College Hospital, from May 2015 to November 2021 were retrospectively analyzed. There were 8 female patients with a median age of 55 years old. Patients mainly presented with gait ataxia (10/10), dizziness (8/10), diplopia (6/10), and dysarthria (5/10). Four of them were complicated with other autoimmune disease, including vitiligo (3/4), Hashimoto thyroiditis (1/4), thrombocytopenia (1/4), and small cell lung cancer (1/4). All patients received immunotherapy, 6 out of 10 exhibited a good response, and half of them had satisfied functional prognosis. Patients of anti-GAD antibody-related cerebellar ataxia may be complicated with other autoimmune diseases, but underlying tumor is rare. More than half of patients have a good response to immunotherapy and satisfied prognosis.

[Association of thrombocytopenia with mortality after surgery in patients with Standford type A aortic dissection].

Objective: To evaluate the association of thromboytopenia with mortality of Standford type A aortic dissection after cardiopulmonary bypass surgery. Methods: Total of 498 patients with Standford type A aortic dissection after surgery in Fuwai Hospital of the Chinese Academy of Medical Sciences from May 2017 to December 2018 were collected retrospectively. There were 350 males and 148 females, with a mean age of (51.7±12.0) years. The patients were divided into thrombocytopenia group (platelet count<75×1015/L, n=178) and normal platelet group (platelet count≥75×1015/L, n=320) according to the lowest platelet count within 72 hours after surgery. The perioperative in-hospital mortality and related complications were calculated by univariate and multivariate logistic regression analysis. The primary endpoint was in-hospital mortality, and the secondary endpoints included secondary thoracotomy, pneumonia, postoperative continuous renal replacement therapy, paraplegia, heart failure, length of hospital stay and intensive care unit (ICU) stay time. Results: The morbidity of thrombocytopenia after Standford type A aortic dissection surgery was 35.7% (178/498). Univariate logistic regression analysis showed that postoperative thrombocytopenia was significantly associated with in-hospital mortality and 7 secondary endpoints (P<0.05). Multivariate logistic regression analysis showed thrombocytopenia after aortic dissection surgery was significantly associated with increased postoperative mortality (OR=12.57, 95%CI: 2.26-69.93, P=0.004), secondary thoracotomy (OR=6.21, 95%CI: 1.31-29.46, P=0.022), continuous renal replacement therapy (OR=7.51, 95%CI: 2.53-22.34, P<0.001), paraplegia (OR=23.99, 95%CI: 1.47-392.21, P=0.026), heart failure (OR=4.71, 95%CI: 1.19-18.62, P=0.027) and longer ICU stay time (OR=1.86, 95%CI: 1.11-3.12, P=0.019). Conclusions: Thrombocytopenia after Standford type A aortic dissection after cardiopulmonary bypass surgery (the lowest platelet count within 72 hours) is strongly associated with postoperative in-hospital mortality. Trying to avoid the factors related to thrombocytopenia can prevent more complications at the same time.

[Current status and quality analysis of interventional therapy for patients with atrial fibrillation in China].

Objective: To define the current status and analyze the medical quality of interventional therapy for patients with atrial fibrillation (AF) in China. Methods: This survey was performed in all seven large regions of China, one to three regional major medical centers were selected from each region. Medical records of patients underwent interventional therapy for AF in the year 2017 were randomly inspected. CHA2DS2-VASc score, prescribed anticoagulant after ablation, indication of left atrial appendage occlusion (LAAO), and complications in the medical records were analyzed. Results: A total of 10 800 AF catheter ablations and 447 LAAOs were performed in 17 regional medical centers in 2017. There were 10/17 centers performing AF catheter ablation<500 cases and 7/17 centers performing LAAO<20 cases. A total of 1 347 cases of catheter ablation and 160 cases of LAAO were selected for further analysis. Among all selected cases, 15.8% (238/1 505) non-valvar AF cases recorded CHA2DS2-VASc scores. The anticoagulation rate after AF catheter ablation was 98.6% (1 328/1 347), anticoagulation rate was higher than 90% in 16 out of 17 centers. The complication and severe complication rates of AF catheter ablation were 0.9% (12/1 347) and 0.4% (5/1 347), respectively. The differences of complication and severe complication rates in AF catheter ablation were similar between centers performing<500 cases and centers performing ≥500 cases (0.5% (2/413) vs. 1.1% (10/934), P>0.05; 0.5% (2/413) vs. 0.3% (3/934), P>0.05). The coincidence rate of LAAO indication was 81.3% (130/160), and the rate was higher in center performing ≥20 cases than in centers performing<20 cases (84.8% (106/125) vs. 68.6% (24/35), P<0.05). The complication and severe complication rates of LAAO were 3.1% (5/160) and 1.9% (3/160). The rate of complications in LAAO was higher in center performing<20 cases than in centers performing ≥20 cases (8.6% (3/35) vs. 1.6% (2/125), P<0.05), and there was no significant difference in severe complication rate (5.7% (2/35) vs. 0.8% (1/125), P>0.05). Conclusions: Interventional therapy for AF in China is generally standardized and safe. The overall incidence of complications post AF interventional ablation is low, the anticoagulation rate after AF catheter ablation is high, and the adherence rate of LAAO indication is fair. The indicators mentioned above vary widely among centers.

[Neuropsychiatric symptoms and caregivers' distress in anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To explore the characteristics of psychiatric symptoms and caregivers' distress in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Seventy-two patients with anti-NMDAR encephalitis were investigated in Peking Union Medical College Hospital from 2011 to 2018. The Chinese version of the Neuropsychiatric Inventory-Questionnaire (NPI-Q) was used to assess the severity of neuropsychiatric symptoms and caregivers' distress around the treatment. Results: A highly positive correlation existed between severity scores of neuropsychiatric symptoms and caregiver distress, and pre- and post-treatment correlation coefficients was 0.872 and 0.947, respectively (all P<0.001). The frequency of 12 symptom domains was higher than 45% before treatment, however, it significantly reduced to below 45% after treatment. Irritability/lability, agitation/aggression were the most common neuropsychiatric symptoms. Irritability/lability, agitation/aggression, and nighttime behavioral disturbances occurred concurrently. Patients with severe symptoms tended to be administrated antipsychotics (Z=-2.581, P=0.01). Neuropsychiatric symptoms significantly improved after immunotherapy (Z=-6.611, P<0.001). There was no significant difference in the symptom severity and distress subscale scores between the first episode and relapse around the therapy (P>0.05). Conclusion: Patients with anti NMDAR encephalitis often present severe neuropsychiatric symptoms, which aggravate the burden on caregivers. Immunotherapy significantly improves neuropsychiatric symptoms, and thus reduces the distress of caregivers.

[Clinical featuers of adult patients with post-viral-encephalitis autoimmune encephalitis].

Objective: To explore the clinical features of post-viral-encephalitis autoimmune encephalitis (PVEAE). Methods: Ten cases of PVEAE, who were hospitalized in the Neurology Department of Peking Union Medical College Hospital (PUMCH) between November 2014 and October 2019, were retrospectively reviewed. Clinical manifestation, immunology, neuroradiology, treatment and outcomes were analyzed. Results: There were 5 males and 5 females, with a median age of 44 (18, 66) years. Of 9 cases, the median interval between the two onsets of encephalitis was 37 (24, 60) days, and there was no obvious interval in case 7. In viral encephalitis phase, the peak modified Rankin scale (mRS) was 4.5 (4.0, 5.0) and the remission mRS was 2.0 (1.0, 3.0). In autoimmune encephalitis (AE) phase, the peak mRS was 4.0 (3.0, 5.0). Symptoms of AE included mental and behavioral abnormalities (10/10), amnesia (10/10), motor disorders (5/10), autonomic dysfunction (5/10), speech disorders (4/10), seizures (2/10) and consciousness disturbance (2/10). On average, each case presented with 4 (2, 6) symptoms. In AE phase, the positive rate of anti-N-methyl-D-aspartate (anti-NMDA) receptor antibody in cerebrospinal fluid (CSF) was 80% (8/10), while in serum it was only 20% (2/10). Neuroimaging showed that in AE phase, the lesions expanded in 8 cases, remained unchanged in 1 case and shrank in 1 case. In AE phase, 10 cases received first line treatments, and 2 cases accepted long-course immunotherapy. After treatment, symptoms of 9 cases were obviously relieved. The mRS for short-term and long-term outcomes was 2.0 (1.0, 4.0) and 1.0 (0, 2.0), respectively. Conclusions: PVEAE might present with either typical biphasic course or monophasic/pseudo-monophasic course. In AE phase, anti-NMDA receptor antibody turned positive in most cases. Much importance should be attached to the recognition and diagnosis of PVEAE and treat it actively thereafter.

[Clinical approach and prognosis of continuous neurological care after intensive care for the patients with severe and refractory anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To study the clinical features, continuous care and prognosis of the patients with severe and refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis after intensive care unit (ICU). Methods: Clinical data of patients with severe and refractory anti-NMDAR encephalitis, who were transferred from ICU to general ward of neurology between December 2015 and October 2019, were retrospectively reviewed and analyzed in the study. Results: Twenty patients (11 females and 9 males) were enrolled in the study. The median course of disease when patients were transferred to general ward was 4.4 (2.0, 6.0) months. Six cases were alert, 6 cases were in a coma, 5 were in the early recovery phase and 3 were in the late recovery phase. Severe malnutrition, pneumonia, urinary tract infections, bedsores and leukocytopenia were common complications. Seven out of 18 patients were tested positive for cerebrospinal fluid anti-NMDAR antibodies with high titers (≥1∶100). During this continuous therapy stage,10 patients were treated with intravenous immunoglobulin (IVIg), 1 with methylprednisolone, 2 with rituximab, 1 with intrathecal methotrexate and 1 received intravenous cyclophosphamide. All Patients were prescribed a long-term immunotherapy (mycophenolate mofetil 1.5-3.0 g/d). Sixteen patients (80%) had good prognosis (modified Rankin Scale (mRS)≤2), and the mortality was 10%, with follow-up time of 17.0 (8.0, 27.0) months. Conclusions: Patients with anti-NMDAR encephalitis, who are transferred from ICU, have severely impaired neurologic function. These patients need long-term individualized immunotherapy and continuous neurological care. Good outcomes can be achieved in most patients.

[Clinical experience and next-generation sequencing analysis of encephalitis caused by pseudorabies virus].

Objective: To detect potential pathogens including pseudorabies virus in patients with encephalitis of unknown etiology in China and describe novel encephalitic entities. Methods: Patients with clinically suspected infectious encephalitis were enrolled in a multicenter study to identify the pathogens in PUMCH Encephalitis Program.Next-generation sequencing(NGS) of cerebrospinal fluid (CSF) was used in patients with encephalitis of unknown etiology enrolled from 2016 to 2017.The patients diagnosed as PRV encephalitis were studied to describe this novel entity. Results: The four patients(3 male, 1 male, 38-54 years old) had occupational exposure to raw park when working in the production or marketing of pork and at least one got injured during pork-cutting.Two of them were confirmed with NGS of CSF, and anti-PRV antibodies were positive in 3 patients whose serum was available for serological analysis.They all presented with an acute onset of fever, convulsion, loss of consciousness and respiratory failure within 1 to 4 days and rapidly deteriorated even on extensive treatment.All the patients needed ICU admission and 3 needed mechanical ventilation.Two patients also had bilateral retinitis.Neuroimaging revealed symmetric gray matter lesions including limbic system, basal ganglia and midbrain without obvious hemorrhage.Lumbar puncture revealed elevated intracranial pressure and lymphocytic pleocytosis [(6-64)×10(6)/L] of CSF.The patients failed to response to the treatment of acyclovir combined with intravenous immunoglobulin and steroids.Modified Rankin Score was 3, 5, 5 and 6 (died) for the 4 patients respectively on last follow-up. Conclusions: PRV could be a cause of severe encephalitis.The patients with suspected pseudorabies encephalitis (PRE) need to be tested for PRV DNA timely.Severe encephalitis with bilateral involvement of limbic system, basal ganglion, thalamus and midbrain in patient with occupational exposure indicate this emerging infectious encephalitis.

[A clinical analysis of 20 patients with neurobrucellosis].

Objective: To investigate the epidemiological and clinical features of 20 patients with neurobrucellosis (NB) . Methods: The epidemiological, clinical, laboratory and treatment data of patients diagnosed with NB from 2010 to 2016 in Peking Union Medical College Hospital were retrospectively analyzed. Results: Twelve (60%) patients reported the history of contact with infected animals and intake of raw milk product. The common manifestations included headache (85%, 17/20), fatigue (85%, 17/20), fever (80%, 16/20), weight loss (70%, 15/20), the signs included pathological reflection (70%, 15/20), decreased muscle strength(45%, 9/20). The mean time to diagnosis was 7.9 months. All patients were diagnosed by positive serum antibody against Brucella. Body fluid culture revealed positive blood Brucella in 5 (31.2%, 5/16) patients and positive cerebrospinal fluid in 3 (16.7%, 3/18) patients. The medication consisted of rifampicin and minocycline based regimens or combined with ceftriaxone, fluroquinolone, streptomycin or trimethoprim-sulfamethoxazole (TMP-SMX). Ninety percent(18/20) patients obtained clinical improvement, whereas mild sequelae were observed in 5 patients. Conclusions: Clinical features of NB are heterogeneous. Carefully seek for epidemiological clues and early tests for Brucella may lead to well outcome. Combination therapy with two or more active antimicrobial agents is suggested.

AKT2 expression in histopathologic grading and recurrence of meningiomas.

BACKGROUND: AKT2 (protein kinase B), an important protein in PI3K signaling pathway, is overexpressed in a variety of malignant tumors. However, in patients with meningiomas, the potential correlation between AKT2 and clinical outcome remains unknown. METHODS: The expression of AKT2 and Ki-67 in meningioma tissues were evaluated immunohistochemically in 94 patients with meningiomas. The correlation of AKT2 immunoreactivity with clinicopathological features and the prognostic value of AKT2 in patients were also analyzed. RESULTS: In this study, we examined the expression of AKT2 in meningiomas and unveiled its possible relationship with the clinical outcome. Immunohistochemical analysis revealed high AKT2 expression in 46 patients (46/94, 48.9%) and low AKT2 expression in the remaining 48 patients (48/94, 51.1%). There was a positive correlation between AKT2 and Ki-67 immunoreactivity (r = 0.35, P = 0.01). Clinicopathological evaluation suggested that AKT2 expression was associated with pathological grade and recurrence (P < 0.05). Univariate and Cox analysis indicated a significant correlation between high levels of AKT2 immunoreactivity and high rates of tumor recurrence (P < 0.05). CONCLUSIONS: We conclude that AKT2 may play an important role in the development of meningioma. High AKT2 labeling index indicates higher grade of meningioma, and therefore AKT2 may be a useful molecular marker for predicting the prognosis of meningioma.

Breathing at a rate of 5.5 breaths per minute with equal inhalation-to-exhalation ratio increases heart rate variability.

OBJECTIVES: Prior studies have found that a breathing pattern of 6 or 5.5 breaths per minute (bpm) was associated with greater heart rate variability (HRV) than that of spontaneous breathing rate. However, the effects of combining the breathing rate with the inhalation-to-exhalation ratio (I:E ratio) on HRV indices are inconsistent. This study aimed to examine the differences in HRV indices and subjective feelings of anxiety and relaxation among four different breathing patterns. METHODS: Forty-seven healthy college students were recruited for the study, and a Latin square experimental design with a counterbalance in random sequences was applied. Participants were instructed to breathe at two different breathing rates (6 and 5.5 breaths) and two different I:E ratios (5:5 and 4:6). The HRV indices as well as anxiety and relaxation levels were measured at baseline (spontaneous breathing) and for the four different breathing patterns. RESULTS: The results revealed that a pattern of 5.5 bpm with an I:E ratio of 5:5 produced a higher NN interval standard deviation and higher low frequency power than the other breathing patterns. Moreover, the four different breathing patterns were associated with significantly increased feeling of relaxation compared with baseline. CONCLUSION: The study confirmed that a breathing pattern of 5.5 bpm with an I:E ratio of 5:5 achieved greater HRV than the other breathing patterns. This finding can be applied to HRV biofeedback or breathing training in the future.

Aberrant expression of imprinted genes and their regulatory network in cloned cattle.

Domesticated animals cloned by somatic cell nuclear transfer (SCNT) generally have poor developmental competency, with many developmental abnormalities attributed to incomplete reprogramming of the nuclear genome and abnormal expression of genes important for regulation of growth and development. To investigate the molecular mechanism leading to the abnormalities of cloned animals, pathologic and histologic analyses were conducted on seven cloned cattle that were oversized at birth and had cardiac and pulmonary abnormalities. Quantitative reverse transcription (RT)-polymerase chain reaction (PCR) analysis of four imprinted genes IGF2, IGF2R, H19, and GRB10, as well as genes from related regulatory networks, were performed in liver, lung, kidney, and muscle to investigate disruption of expression. Expression of IGFBP2 was not detected in morphologically normal cloned cattle, but was detected in the liver, lung, kidney, and thymus of abnormal calves. Expression levels of IGF1 and imprinted genes IGF2 and H19 were substantially higher in these organs of abnormal cattle. In contrast, expression levels of GRB10, CTSD, and TRPV2 were substantially lower in abnormal cattle. Transcript abundance of IGFBP6 was higher in kidney, but lower in liver and lung. In conclusion, we inferred that altered expression of imprinted and related genes may be closely related to increased birth weight and pathologic changes in abnormal cloned cattle.

Orexin A-induced extracellular calcium influx in prefrontal cortex neurons involves L-type calcium channels.

Orexins, novel excitatory neuropeptides from the lateral hypothalamus, have been strongly implicated in the regulation of sleep and wakefulness. In this study, we explored the effects and mechanisms of orexin A on intracellular free Ca2+ concentration ([Ca2+]i) of freshly dissociated neurons from layers V and VI in prefrontal cortex (PFC). Changes in [Ca2+]i were measured with fluo-4/AM using confocal laser scanning microscopy. The results revealed that application of orexin A (0.1-1 microM) induced increase of [Ca2+]i in a dose-dependent manner. This elevation of [Ca2+]i was completely blocked by pretreatment with selective orexin receptor 1 antagonist SB 334867. While depletion of intracellular Ca2+ stores by the endoplasmic reticulum inhibitor thapsigargin (2 pM), [Ca2+]i in PFC neurons showed no increase in response to orexin A. Under extracellular Ca2+-free condition, orexin A failed to induce any changes of Ca2+ fluorescence intensity in these acutely dissociated cells. Our data further demonstrated that the orexin A-induced increase of [Ca2+]i was completely abolished by the inhibition of intracellular protein kinase C or phospholipase C activities using specific inhibitors, BIS II (1 microM) and D609 (10 microM), respectively. Selective blockade of L-type Ca2+ channels by nifedipine (5 microM) significantly suppressed the elevation of [Ca2+]i induced by orexin A. Therefore, these findings suggest that exposure to orexin A could induce increase of [Ca2+]i in neurons from deep layers of PFC, which depends on extracellular Ca2+ influx via L-type Ca2+ channels through activation of intracellular PLC-PKC signaling pathway by binding orexin receptor 1.

The effect of topical lignocaine gel in pain relief for colposcopic assessment and biopsy: is it useful?

We investigated the use of topical ligocaine gel in pain relief for colposcopy and cervical punch biopsy. Ninety women referred for colposcopy due to abnormal cervical cytology were randomised to receive 5 ml of either 2% xylocaine gel or KY jelly to the cervix and the upper part of the vagina for at least 10 minutes prior to the colposcopic procedures. Pain score was obtained at several points of the procedure. Topical lignocaine gel did not significantly relieve pain from cervical punch biopsy and alleviate the stinging sensation from application of acetic acid and Lugol's iodine to cervix and vagina. However, it may be beneficial to a subgroup of women with prior unpleasant experience towards speculum examination.

Effect of local lignocaine gel application for pain relief during suction termination of first-trimester pregnancy: a randomized controlled trial.

BACKGROUND: This study evaluated the effectiveness of local lignocaine gel application in pain control during first-trimester suction termination of pregnancy (STOP). METHODS: In this prospective randomized placebo-controlled double-blind trial, 131 women undergoing STOP between 7 and 10 weeks of gestation were studied. They were computer-randomized to receive 2% lignocaine gel or placebo (KY Jelly) locally applied to the cervix 1 min before cervical manipulation/dilatation. They all had cervical priming with misoprostol and premedication with diazepam and pethidine. Pain scores on a verbal analogue scale preoperative, at cervical manipulation/dilatation, intraoperative and 1 h post-operative, as well as the patients' satisfaction level towards pain control, were compared. RESULTS: The lignocaine gel group had significantly reduced overall intraoperative pain score compared with placebo group (P = 0.021). No significant difference in pain score between the two groups was demonstrated at other time points. Subgroup analysis revealed that the difference in overall intraoperative pain scores between the two groups was evident in the multiparous (P = 0.015) but not the nulliparous subjects. CONCLUSION: The use of local lignocaine gel application reduces overall intraoperative pain in multiparous women undergoing first-trimester STOP preceded by misoprostol cervical priming and premedication for conscious sedation.

Bone loss associated with long-term use of depot medroxyprogesterone acetate.

On 17 November 2004, the United States Food and Drug Administration issued a black box warning on the long-term use of depot medroxyprogesterone acetate stating that bone loss might be irreversible with use of more than 2 years. Despite the seriousness of such a safety warning, the Food and Drug Administration provided no clinical recommendations. Various professional bodies have made different recommendations on the management of women prescribing such long-term injections but there is no consensus on the best practice. Thus individual institutions need to revise service protocols. The Health Services Subcommittee of the Family Planning Association of Hong Kong has reviewed the scientific evidence from international and local studies and made its recommendations in a meeting held on 1 March 2005. This article aimed to share our opinion with other medical professionals in Hong Kong.

Astrocyte-derived VEGF mediates survival and tube stabilization of hypoxic brain microvascular endothelial cells in vitro.

Chronic sublethal hypoxia has been associated with changes in neurovascular behavior, mediated, in part, by induction of vascular endothelial growth factor-A (VEGF-A(165)). In this report we demonstrate that RBE4 cells (derived from rodent cerebral microvasculature), when cultured in three-dimensional collagen gels: (1) Are induced to undergo increased tube formation in response to VEGF-A(165) in a dose-dependent manner; (2) undergo apoptosis under mild hypoxic conditions; (3) are rescued from the effects of hypoxia by the addition of exogenous VEGF-A(165) in a dose-dependent and inhibitable manner or by co-culture with primary newborn rat astrocytes, which are induced to express increased amounts of VEGF-A in hypoxic conditions. Further, we demonstrate that: (4) The observed astrocyte-produced, VEGF-mediated protection from apoptosis (survival) is inhibitable with soluble recombinant VEGF receptor-1 (sFlt), and is associated with a robust induction of MAPK tyrosine phosphorylation. These findings illustrate the importance of VEGF in the process of neurovascular survival in response to injury in developing brain and provide insight into the signaling pathways involved.