Post-infantile giant cell hepatitis: histological and immunohistochemical study.

AIM--To determine the composition of the inflammatory infiltrate and to check for the presence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in nine cases of post-infantile giant cell hepatitis. METHODS--The clinical, serological, and histological features of the nine cases were reviewed. Immunohistochemistry was used on liver biopsy specimens from six cases to: (i) characterise the lymphocytic infiltrate; (ii) assess the monocyte/macrophage response; (iii) detect "activated" perisinusoidal cells; and (iv) detect CMV and EBV antigens. Electron microscopic examination was carried out in two cases. RESULTS--Four patients had serological features suggestive of autoimmune chronic active hepatitis; in the other five cases the aetiology was obscure. Two patients presented with neurological symptoms. Hepatitis resolved completely in one patient; two patients showed clinical improvement; and one remained stable. Cirrhosis developed in three patients, one of whom proceeded to liver transplantation, and three patients died. Portal inflammation was present in all cases and lymphocytic piecemeal necrosis in eight cases, but intra-acinar inflammation associated with hepatocyte necrosis was observed in only five cases. The inflammatory infiltrate was composed predominantly of T lymphocytes; an increase in monocyte/macrophage cells was also observed. Mallory bodies, often with associated neutrophilic infiltrate, were present in four cases, and bilirubinostasis was a feature in four cases. "Activated" perisinusoidal cells were present, especially in relation to areas of inflammation, necrosis, and fibrosis. There was severe fibrosis or cirrhosis in five cases. Paramyxoviral nucleocapsids were not seen in the two cases examined ultrastructurally. CONCLUSIONS--Post-infantile giant cell hepatitis should be viewed as a heterogeneous clinical and aetiological entity encompassing cases of hepatitis with extensive giant cell hepatocyte transformation.     

SCREENING PROCEDURES IN PEDIATRICS

Pediatric health screening procedures, both prenatal and postnatal, have a tremendous potential in improving the health status of children and in turn reducing the resource burden on the parents and the State. The existing recommendations, inherent problems and different screening procedures are discussed. The need for suitable mass screening pediatric procedures in the Indian context is stressed.KEY WORDS: Pediatric screening procedures     

Polymeric micellar paclitaxel phosphorylates Bcl-2 and induces apoptotic regression of androgen-independent LNCaP prostate tumors

BACKGROUND: Paclitaxel has been difficult to evaluate in preclinical tumor model systems because its poor solubility requires a Cremophor EL formulation, which results in lethal anaphylaxis. We tested the effectiveness of a novel polymeric micellar paclitaxel on androgen-independent tumor growth in the LNCaP tumor model. METHODS: Athymic male mice bearing LNCaP tumors were castrated and allowed to grow until their PSA levels increased to three times above precastration levels. The animals were then treated with 0.5 mg intravenous polymeric micellar paclitaxel once daily for the first 5 days of a 3-week cycle. In total, three cycles were given. Tumor volume and serum PSA levels were measured weekly to monitor tumor progression. RESULTS: In vitro mitogenic assays demonstrated that polymeric micellar paclitaxel was effective in inhibiting LNCaP cell growth with an IC(50) of 5 nM. Paclitaxel precipitated apoptosis in vitro at a concentration of 1 nm and higher, confirmed by DNA laddering. Western blotting demonstrated that paclitaxel treatment phosphorylated and inactivated Bcl-2. In mice bearing LNCaP tumors treated with micellar paclitaxel, tumors regressed rapidly with the commencement of micellar paclitaxel treatment. Tumor size decreased 91% and PSA level decreased 96% after three cycles of treatment. TUNEL immunostaining of the tumor treated with micellar paclitaxel showed marked apoptosis when compared with the control. No significant side effects or mortality was observed in the micellar paclitaxel group (n = 7). In contrast, all (n = 7) mice treated with conventional Cremophor EL paclitaxel died within 1 day of injection. CONCLUSIONS: The polymeric micellar paclitaxel formulation is water-soluble and capable of inducing complete response in mice bearing androgen-independent LNCaP tumors. The lack of toxicity of polymeric micellar paclitaxel permits in vivo preclinical testing of paclitaxel-based combination regimens.     

The influence of reverse-thread screw femoral fixation on laxity measurements after anterior cruciate ligament reconstruction with hamstring tendon

In arthroscopically assisted anterior cruciate ligament reconstruction using hamstring tendon graft, the graft rotates slightly as the femoral screw is inserted. Its final position tends to be in the anterior half of the tunnel in right knees, resulting in clinical laxity. To perform identical procedures on left and right knees, a reverse-thread screw was designed for femoral fixation in right knees. We prospectively studied 80 patients undergoing right-knee anterior cruciate ligament reconstruction with hamstring tendon autograft. Thirty-six patients underwent reconstruction with a standard screw and 44 underwent reconstruction with a reverse-thread screw. The same technique, performed by the same surgeon, was used on all patients. At 12 months' follow-up, the average side-to-side differences on arthrometry testing were 2.00 mm for the standard screw group and 0.95 mm for the reverse-thread screw group using a manual maximum test, and 1.66 mm and 1.00 mm, respectively, using the 20-pound test. Both differences were statistically significant. Of the standard group, 23% had a manual maximum difference of 3 mm or more, compared with 8% of the reverse-thread group. A significant difference was found between these two groups for Lachman test (77% with grade 0 for the standard group compared with 92% for the reverse group) but pivot shift and Lysholm knee score were not significantly different. The use of a reverse-thread screw for femoral fixation in right-knee anterior cruciate ligament reconstructions in men significantly decreased laxity at 12 months after surgery compared with standard screw fixation.     

Strategic,feasibility, economic,and cultural aspects of phase 0 approaches: Is it time to change the drug development process in order to increase productivity?

Research conducted over the past 2 decades has enhanced the validity and expanded the applications of microdosing and other phase 0 approaches in drug development. Phase 0 approaches can accelerate drug development timelines and reduce attrition in clinical development by increasing the quality of candidates entering clinical development and by reducing the time to “go‐no‐go” decisions. This can be done by adding clinical trial data (both healthy volunteers and patients) to preclinical candidate selection, and by applying methodological and operational advantages that phase 0 have over traditional approaches. The main feature of phase 0 approaches is the limited, subtherapeutic exposure to the test article. This means a reduced risk to research volunteers, and reduced regulatory requirements, timelines, and costs of first‐in‐human (FIH) testing. Whereas many operational aspects of phase 0 approaches are similar to those of other early phase clinical development programs, they have some unique strategic, regulatory, ethical, feasibility, economic, and cultural aspects. Here, we provide a guidance to these operational aspects and include case studies to highlight their potential impact in a range of clinical development scenarios.     

术中胆道造影在腹腔镜胆囊切除术中发现胆道损伤的作用

目的：评估术中胆道造影（IOC）在早期发现腹腔镜胆囊切除术（LC）术中胆道损伤的作用。方法：回顾分析31例LC术后胆道损伤的部位，机理，诊断时间，治疗方法及结果，并对是否行IOC进行评估。结果：胆道错认引起胆道损伤共19例，其中12例IOC显示胆道错认，致胆道部分切开损伤，腹腔镜下行I期修复或开腹修复，T管引流，但无并发症。19例中3例IOC误读及4例未行IOC患者中发生迷走胆管损伤2例，胆总管完全离断1例，胆总管完全离断合并胆道缺损2例，本组有2例损伤发生于IOC后，结论：行IOC并正确阅读可及时发现腹腔镜胆囊切除术中胆道错认所致的胆道损伤，从而防止随之可能发生的严重并发症。     

Traumatic lumbar hernia: report of cases and comprehensive review of the literature

BACKGROUND: Acute lumbar hernia secondary to blunt trauma is an uncommon injury of the abdominal wall and, when encountered, is a difficult challenge for the trauma surgeon. METHODS: Three cases of lumbar hernia secondary to blunt trauma are described and a review of the literature was conducted for other such cases. Clinical, anatomic, and demographic data were extracted from these reports and analyzed. RESULTS: Sixty-three cases of lumbar hernia secondary to blunt trauma were found in the English literature and three cases are described here. Hernias occurred most commonly in the inferior lumbar triangle (70%) and were most frequently a result of a motor vehicle collision (71%). Physical examination findings were variable and reported in only a minority of cases (palpable hernia, 33%; flank hematoma, 27%) and associated intra-abdominal injuries were common (61%). Most traumatic lumbar hernias were diagnosed immediately, and computed tomography was 98% sensitive for diagnosis. Fifty-eight percent of patients were managed initially with exploratory laparotomy. Timing of hernia repair was variable. CONCLUSION: Traumatic lumbar hernias are associated with a high incidence of intra-abdominal injury and should be considered in all cases of severe blunt abdominal trauma. Computed tomography should be implemented when the diagnosis is suspected in a hemodynamically stable patient. Repair should be performed by mesh patching techniques at a time based on clinical correlation.