先天性肠闭锁166例临床分析

目的分析先天性肠闭锁病例的诊断及治疗,以提高治愈率及术后生活质量。方法回顾性分析166例先天性肠闭锁的临床资料。结果治愈142例,治愈率85.5%(142/166),其中包括18例二期手术治愈者;术中10例、术后8例放弃治疗;术后死亡6例。结论早期诊断和选择合理的术式是提高肠闭锁治愈率的关键,基础支持及手术技术改进能促进病情的恢复,改善预后。     

Chronic colitis due to an epithelial barrier defect: the role of kindlin-1 isoforms

Kindlin-1 is an epithelium-specific phosphoprotein and focal adhesion adaptor component. Mutations in the corresponding gene (KIND1) cause Kindler syndrome (KS), which is manifested by skin blistering, poikiloderma, photosensitivity and carcinogenesis. Some patients also exhibit gastrointestinal symptoms, but it has remained unclear whether these represent a feature of Kindler syndrome or a coincidence. We examined kindlin-1 in human gastrointestinal epithelia and showed that it is involved in the aetiopathology of Kindler syndrome-associated colitis. Kindlin-1 expression was assessed by indirect immunofluorescence, western blot and RT-PCR. Kindlin-1 is expressed in oral mucosa, colon and rectum. Both the full-length 74 kDa kindlin-1 protein and a 43 kDa isoform were detected in CaCo2 cells, the latter resulting from alternative splicing. In the first months of life, patients (homozygous for null mutations) had severe intestinal involvement with haemorrhagic diarrhoea and showed morphological features of severe ulcerative colitis. Later in childhood, histopathology demonstrated focal detachment of the epithelium in all segments of the colon, chronic inflammation and mucosal atrophy. These findings define an intestinal phenotype for Kindler syndrome as a consequence of a primary epithelial barrier defect. The different clinical intestinal manifestations in Kindler syndrome patients may be explained by partial functional compensation of kindlin-1 deficiency by the intestinal isoform or by the presence of truncated mutant kindlin-1.     

Dephosphorylation of myo-inositol phosphates in the in vitro intestinal Caco-2 cell model

Plant and microbial phytases present in raw materials can cause a dephosphorylation of phytate (myo-inositol hexakisphosphate) (InsP₆)) during food processing resulting in a broad range of different myo-inositol phosphates such as pentakisphosphate (InsP₅) and tetrakisphosphate (InsP₄) in foods. Here, we investigated whether the human intestinal epithelium is able to dephosphorylate myo-inositol phosphates (InsP₆, InsP₅-, InsP₄-, InsP₃-isomers) using an in vitro model with differentiated human Caco-2 cells cultured on semipermeable inserts. Incubation of InsP₆ and an InsP₅-isomer with cells for 3?h showed no dephosphorylation of both InsPs. Treatment of cells with a mixture of different InsP₄-isomers, however, caused a formation of about 3.5% of an InsP₃-isomer (Ins(1,5,6)P₃) and treatment with a mixture of different InsP₃-isomers caused about 20% formation of InsP₂-isomers, respectively. Thus, human intestinal cells can contribute to the dephosphorylation of myo-inositol phosphates of partly dephosphorylated forms such as InsP₃ and InsP₄.     

Valuation of EuroQol Five-Dimensional Questionnaire,Youth Version (EQ-5D-Y) and EuroQol Five-Dimensional Questionnaire,Three-Level Version (EQ-5D-3L) Health States: The Impact of Wording and Perspective

Background

Valuations of health states were affected by the wording of the two instruments (EQ-5D-3L and EQ-5D-Y) and by the perspective taken (child or adult).

Overtreatment and Deintensification of Diabetic Therapy among Medicare Beneficiaries

Background

Deintensification of diabetic therapy is often clinically appropriate for older adults, because the benefit of aggressive diabetes treatment declines with age, while the risks increase.

Objective

We examined rates of overtreatment and deintensification of therapy for older adults with diabetes, and whether these rates differed by medical, demographic, and socioeconomic characteristics.

Design, Subjects, and Main Measures

We analyzed Medicare claims data from 10 states, linked to outpatient laboratory values to identify patients potentially overtreated for diabetes (HbA1c < 6.5% with fills for any diabetes medications beyond metformin, 1/1/2011–6/30/2011). We examined characteristics associated with deintensification for potentially overtreated diabetic patients. We used multinomial logistic regression to examine whether patient characteristics associated with overtreatment of diabetes differed from those associated with undertreatment (i.e. HbA1c > 9.0%).

Key Results

Of 78,792 Medicare recipients with diabetes, 8560 (10.9%) were potentially overtreated. Overtreatment of diabetes was more common among those who were over 75 years of age and enrolled in Medicaid (p < 0.001), and was less common among Hispanics (p = 0.009). Therapy was deintensified for 14% of overtreated diabetics. Appropriate deintensification of diabetic therapy was more common for patients with six or more chronic conditions, more outpatient visits, or living in urban areas; deintensification was less common for those over age 75. Only 6.9% of Medicare recipients with diabetes were potentially undertreated. Variables associated with overtreatment of diabetes differed from those associated with undertreatment.

Conclusions

Medicare recipients are more frequently overtreated than undertreated for diabetes. Medicare recipients who are overtreated for diabetes rarely have their regimens deintensified.

     

MODES OF INACTIVATION OF NEUROHYPOPHYSIAL HORMONES: SIGNIFICANCE OF PLASMA DISAPPEARANCE RATE FOR THEIR PHYSIOLOGICAL RESPONSES

Analogues of oxytocin and deaminooxytocin with 4-glutamine replaced by 4-glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4-glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the 'oil-bath'technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Its in situ/in vitro ratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the persistence of the uterotonic effect in situ is slightly less than that of deaminooxytocin. The results with these 'rapidly inactivated'analogues can be used as proof of some predictions of the three-compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtained are discussed.     

Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.