Immunolocalization of pS2, a putative growth factor, in pancreatic carcinoma

pS2 is a 60 amino acid secretory polypeptide which belongs to a newly described family of trefoil-shaped growth factors. It is widely distributed throughout the gastrointestinal tract, particularly adjacent to damaged mucosa, and is also expressed by some epithelial tumours such as breast carcinoma. The aim of this study was to examine the expression of pS2 in pancreatic cancer. The presence of pS2 was analysed immunohistochemically using two antibodies, a polyclonal (pNR-2) and a monoclonal (pS2^TM) in 42 cases of pancreatic adenocarcinoma and 10 cases of ampullary carcinoma. The findings were compared with chronic pancreatitis and normal pancreas. No immunostaining was seen in normal pancreas, with the exception of one area of ductular proliferation, and although 8/10 cases of chronic pancreatitis expressed pS2, it was focal and confined to the occasional duct. In contrast, a significant proportion of malignant cells in 23/42 (55%) of pancreatic adenocarcinoma and 8/10 (80%) of ampullary tumours expressed immunoreactive pS2. The finding of pS2 expression in more than 50% of pancreatic and ampullary carcinomas in contrast to the findings seen in chronic pancreatitis and normal pancreas suggests that pS2 may play an important role in the growth of these highly malignant tumours.     

Effects of disease and corticosteroids on appendicular bone mass in postmenopausal women with rheumatoid arthritis: comparison with axial measurements

The potential value of measurements of peripheral bone mass in rheumatoid arthritis (RA) as an assessment of long-term disease activity has recently received renewed attention. This study examines the effects of RA and corticosteroid therapy on newer methods of measuring peripheral bone mass, comparing the results with dual-energy X-ray absorptiometry (DXA) at axial sites. Peripheral quantitative computed tomography of the radius, ultrasound of the calcaneus, and DXA of the hip and spine were compared between 29 controls and 46 women with RA of whom 25 were receiving low-dose corticosteroid therapy. Bone mass was significantly reduced in the RA groups for: (i) radial trabecular (36.1%) and total (15.6%) measurement sites; (ii) calcaneal ultrasound attenuation (31.7%) and velocity (6.6%); and (iii) femoral neck (15.4%) bone mineral density. Lumbar spine and radial cortical measurements were not significantly affected. There were no significant differences between the RA groups. Disease activity and physical activity did appear to be responsible for much of the reduction in bone mass. These results demonstrate that RA is associated with significant bone loss at the hip, radius and calcaneus, but not at the lumbar spine. In this small study, low-dose corticosteroids had little additional deleterious effect.      

Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy

Activated killer cells, unrestricted by major histocompatibility (MHC) antigens circulate in the peripheral blood of patients who have undergone autologous and allogeneic bone marrow transplant (BMT) and may contribute to the reduced risk of leukemic relapse observed after these procedures. Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used therapeutically might thereby promote the eradication of minimal residual disease. In order to assess whether these effects on cytotoxicity can be reproduced in vivo, we studied changes in number, phenotype, and MHC unrestricted cytotoxicity of peripheral blood mononuclear cells obtained from patients with hematologic malignancy receiving IL-2 infusions. Patients with acute myeloid leukemia and multiple myeloma were treated after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an initial lymphopenia, followed by a progressive recovery in mononuclear cell numbers and a rebound lymphocytosis after the termination of treatment. This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor) positive cell numbers rose sevenfold. Cells with the ability to kill a natural killer (NK)-resistant, lymphokine activated killer cell (LAK)-sensitive target appeared in the circulation during 16 of 19 infusions and mean LAK activity rose from 5.9% to 15.5% during infusion (E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in the peripheral blood inhibited the growth of myeloid leukemia blasts in agar after overnight co-culture. Depletion experiments showed that LAK activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+ CD16- (T derived) subsets. LAK precursor activity in peripheral blood also significantly increased during IL-2 infusion. Increases in major histocompatibility complex (MHC) unrestricted cytotoxicity can be produced by IL-2 infusions in vivo and may result in improved relapse-free survival following chemotherapy or BMT.     

Patient-oriented education and visual-aid intervention are inadequate to identify patients with potential capsule retention: a prospective randomized study

Background/aims: The key procedure-related risk with video capsule endoscopy (VCE) is capsule retention, which should be suspected in patients who have not reported capsule passage. The study aims were to determine the frequency of capsule passage visualization and the difference in self-reporting of capsule passage between patients who receive patient-oriented education (POE) and patients who receive POE and a visual aid intervention in the form of a wrist band (WB).

Methods: This was a prospective randomized study that enrolled patients undergoing VCE. Patients were randomly assigned to a POE group versus a POE and WB group. POE consisted of verbal education and an information booklet. Both groups received instructions to notify the study team regarding capsule passage.

Results: Sixty patients (mean age 57?±?18 years; 61% female) were included. A total of 57 patients were included in the analysis (3 lost to follow-up; 28 in POE group; 29 in WB group). Capsule passage status was reported by 68% without significant difference between POE and WB groups (72% vs. 64%; p?=?.51). Capsule passage status was obtained from all 57 patients with the addition of a proactive follow-up. Only 56% (n?=?32) reported visualizing capsule passage. Of the remaining patients who did not visualize capsule passage, 60% (n?=?15) reported on this without significant difference between the POE and WB groups (p?=?.23).

Conclusions: Lack of visualization of capsule passage is a poor indicator of retention. Self-reporting of VCE passage status is suboptimal and the addition of a visual aid did not improve this parameter.     

Monitoring antimalarial drug resistance in India via sentinel sites: outcomes and risk factors for treatment failure, 2009–2010

Objective

To describe India’s National Antimalarial Drug Resistance Monitoring System, measure the efficacy of first-line malaria treatments, and determine risk factors for treatment failure.

Methods

In 2009–2010, prospective studies with 28 days of follow-up were conducted at 25 sentinel sites. Patients infected with Plasmodium falciparum were given artesunate plus sulfadoxine-pyrimethamine (AS+SP); those infected with P. vivax were given chloroquine. Polymerase chain reaction was used to distinguish post-treatment reinfection from treatment failure. Isolates of P. falciparum were checked for dhfr and dhps mutations.

Findings

Overall, 1664 patients were enrolled. Kaplan–Meier survival analysis showed an efficacy of 98.8% for AS+SP. Most patients with P. falciparum parasitaemia cleared their parasitaemias within 24 hours of treatment initiation, but six, including four with treatment failure, remained parasitaemic after 72 hours. Double mutants in dhfr were found in 68.4% of the genotyped isolates. Triple or quadruple mutants in dhfr and mutations in dhps were rare. A daily dose of artesunate of < 3 mg per kg of body weight, age of less than 5 years, and fever at enrolment were associated with an increased risk of treatment failure. Chloroquine remained 100% efficacious and generally cleared P. vivax parasitaemias within 48 hours. Vomiting (seen in 47 patients) was the most common adverse event.

Conclusion

India’s National Antimalarial Drug Resistance Monitoring System provides wide coverage. The first-line antimalarials used in the country remain safe and efficacious. The treatment of malaria in young children and the relative benefits of age- and weight-based dosing need further exploration.     

Impact of 2013 ASCO/CAP HER2 reporting guidelines in breast cancer: An assessment study from Indian oncology centre that primarily performs HER2 IHC testing with special emphasis on IHC equivocal category

The ASCO/CAP guidelines for HER2 reporting in breast cancer published in 2007 and were updated in 2013 to assure that the right patient receives the targeted therapy. The updated guidelines have lowered the threshold for HER2 positivity criteria and altered the equivocal category for both IHC and FISH. This first study from India addresses the impact of these updated guidelines in the various reporting categories at a tertiary care centre. We compared the trend of HER2 IHC reporting 1 year before (Period A) and 1 year after (Period B) the implementation of updated 2013 ASCO/CAP guidelines. All HER2 equivocal IHC cases of post 2013 guidelines were reclassified as per 2007 guidelines to detect additional number of cases that have been put into equivocal category. Reflex FISH correlation was also assessed to detect any additional cases eligible for anti HER2 therapy with implementation of these updated guidelines. With implementation of updated 2013 guidelines, there was significant decrease in the number of cases scored as 1+ (from 30.7% to 20.6%; P value: .0001) while significant increase in number of 2+ cases (from 20.2% to 27.3%; P value: .004). Post 2013 guidelines, 39% (64 cases) of tumors were additionally put into the equivocal category which would have been considered as negative (score 1+) as per 2007 guidelines. The reflex FISH testing in these equivocal cases resulted in detection of only 1.5% of additional cases eligible for anti HER2 therapy. With implementation of updated 2013 guidelines, there is no significant increase in HER2 positivity trend. However, there is appreciable increase in IHC equivocal cases which subsequently led to increased reflex FISH testing without significantly contributing to the detection of additional eligible cases for anti HER2 therapy, but resulted in delaying of definite HER2 status along with financial implications.     

Management of nonpsychiatric medical conditions presenting with psychiatric manifestations

There is a significant dilemma when underlying medical disorders present as psychiatric conditions. It is important to identify the medical condition because treatment and management strategies need to be directed to the presenting symptoms and also to the underlying medical condition for successful treatment of the patient. Some systemic disorders present with psychiatric manifestations more often than others. The pattern of psychiatric disturbance seen may be specific for a particular medical disorder but may also be varied. Many drug formulations and medications also may produce psychiatric presentations. This article considers the management of nonpsychiatric medical conditions presenting with psychiatric manifestations.     

国产尼莫地平片和尼莫通片的生物利用度比较

国产尼莫地平片和尼莫通片的生物利用度比较施孝金王宏图韦阳张静华张莉莉钟明康（上海医科大学华山医院临床药学研究室，上海２０００４０）钙离子通道拮抗剂尼莫地平（ｎｉｍｏｄｉｐｉｎｅ，ＮＭ），临床上主要用于治疗有明显症状的老年性脑功能损伤和由于蛛网膜下腔出...