Gastric Transit and Pharmacodynamics of a Two-Millimeter Enteric-Coated Pancreatin Microsphere Preparation in Patients with Chronic Pancreatitis

It has been suggested that enteric-coatedpancreatin microsphere (ECPM) preparations with spheresizes larger than 1.7 mm pass through the stomach at aslower rate than a meal and therefore may be less efficacious in restoring pancreatic enzymeactivity than preparations with smaller sphere sizes.The aim of this study was to investigate the gastrictransit profile of a 2-mm ECPM preparation in relation to that of a solid meal and to simultaneouslymeasure enzyme activities in eight patients withpancreatic exocrine insufficiency due to chronicpancreatitis. Gastric transit was assessed bydouble-isotope scintigraphy. A pancake was labeled with^99mTc. A 2-mm ECPM preparation was labeledwith ¹⁷¹Er. Intraluminal pancreatic enzymeactivities were assessed during a 6-hr period with thecholesteryl-[¹⁴C]octanoate breath test (for carboxyl ester lipaseactivity) and the N -benzoyl-L-tyrosyl-p aminobenzoicacid/p-aminosalicylic acid (NBT-PABA/PAS) test (forchymotrypsin activity). The ECPM preparation passedthrough the stomach more rapidly (median 24 min) thanthe pancake (median 52 min, P < 0.05). During ECPMtherapy, mean cumulative ¹⁴CO₂outputs rose significantly from 30% to 70% (P <0.05), but remained below outcomes in healthy volunteers. Mean cumulative plasmaPABA concentrations rose significantly from 46% to 87%(P < 0.05) and were not significantly different fromoutcomes in healthy volunteers. In chronic pancreatitis, a 2-mm ECPM preparation does not pass throughthe stomach more slowly than a solid meal, but in factfaster. Digestion of ester lipids and proteins showed animprovement to subnormal and normal levels,respectively.     

Short and Long-Term Outcomes of Diabetes Mellitus in Patients with Autoimmune Pancreatitis after Steroid Therapy

Background/Aims

Autoimmune pancreatitis (AIP) is frequently associated with diabetes mellitus (DM). This study evaluated the effect of steroid therapy on the course of DM in AIP.

Methods

Glucose tolerance was examined in 69 patients with AIP. DM onset was classified as either a simultaneous onset with AIP or an exacerbation of pre-existing DM. Based on the changes in the HbA1c levels and insulin dose, the responses of DM to steroids were classified as improved, no change, or worsened.

Results

Thirty (46%) patients were diagnosed as having DM (simultaneous onset, n=17; pre-existing, n=13). Three months after starting the steroid treatment, the DM improved in 13 (54%) of 24 DM patients. The DM improved in 55%, had no change in 36%, and worsened in 9% of the 11 simultaneous onset DM patients, and it improved in 54%, had no change in 31%, and worsened in 15% of the 13 pre-existing DM patients. At approximately 3 years after starting the steroid treatment, the DM improved in 10 (63%) of 16 patients. The pancreatic exocrine function improved in parallel with the changes in the DM in seven patients.

Conclusions

Because approximately 60% of DM associated with AIP is responsive to steroids in the short- and long-terms, marked DM associated with AIP appears to be an indication for steroid therapy.     

Morphological Aspects of Necrosis as a Guideline for Treatment of Necrotizing Pancreatitis (A Brief Report About 50 Patients)

In a retrospective study, 50 patients withobvious necrotizing pancreatitis (NP) were allocated infour groups according to the morphological aspects ofthe necrosis. Appearance of ascite (N1), extrapancreatic spread of necrosis towards neighboring organs(N2), a large amount of necrosis (N3), and infectednecrosis (N4), appears to be an easy and usefulguideline for the management of NP patients. Organfailures (72%) and mortality rate (36%) are higher whenthe process is infected. In the other groups, organicdysfunctions were frequent, but all the patients exceptone survived. The majority (80%) of patients were operated on. Only 20% of patients hadsuccessful nonsurgical treatment and they were in N3group. This percentage may increase through amorphological approach to treating necrosis, with theuse of endoscopic treatment for the disruption ofpancreatic duct, and better accuracy in the managementof patients with noninfected necrosis, whenever organfailures are present.     

Differential Induction of HSP60 and HSP72 by Different Stress Situations in Rats (Correlation with Cerulein-Induced Pancreatitis)

We previously reported that water-immersionstress specifically induced the synthesis of a 60-kDaheat-shock protein (HSP60, chaperonin homolog) inpancreatic cells and preinduction of HSP60 completely prevented development of cerulein-inducedpancreatitis in the rat in an HSP60 quantitativelydependent manner. In order to study the cytoprotectivefunction of a 72-kDa heat-shock protein (HSP72,stress-inducible hsp70), the effect of specific preinduction ofHSP72 by hyperthermia on cerulein-induced pancreatitiswas investigated and compared with the effect ofpreinduction of HSP60 in this study. Expression of HSP60 and HSP72 in the pancreas wasinvestigated by immunoblot before and after waterimmersion or hyperthermia. Following pretreatment withwater-immersion stress or hyperthermia, the rats wereinjected with cerulein (40 g/kg, intraperitoneally).The pancreas wet weight and serum amylase concentrationwere measured before and after cerulein injection.Hyperthermia (42.5°C, 20 min) specifically induced HSP72 in the pancreas. The synthesis of HSP60was specifically induced by water-immersion stress inthe pancreas. Cerulein-induced pancreatitis was clearlyprevented by specific preinduction of HSP60 by water-immersion stress. However, preinductionof HSP72 by hyperthermia had no preventive effect oncerulein-induced pancreatitis. Our findings suggest thatHSP60 and HSP72 have distinct functions in the pancreas, and their induction mechanisms arealso different in vivo. These results could be importantfor understanding the mechanism of adaptivecytoprotection in the pancreas mediated byheat-shock proteins.     

Clinical challenge: heparin-induced thrombocytopenia type II (HIT II) or pseudo-HIT in a patient with antiphospholipid syndrome

Treatment of patients with heparin-induced thrombocytopenia type II (HIT II) and thrombosis in some cases that represents a clinical challenge, which, if unrecognized, may lead to treatment delay or disease progression with potentially lethal outcome. We present a case of a 19-year-old patient with antiphospholipid syndrome, factor V (FV) Leiden mutation in heterozygous state, and venous thromboembolism. The patient was subjected to intravenous infusions of unfractionated heparin (UFH), and 16 days after the beginning of the treatment, his condition worsened, with thrombocytopenia and extension of thrombosis. Whereas the patient had a high clinical score for HIT II, functional and antigenic assays for the presence of HIT antibodies were negative. After repeated negative functional and antigenic assays, pseudo-HIT was suspected and nadroparin was introduced, which resulted in further worsening of the clinical presentation. Disease remission, along with complete normalization of platelet count, was finally accomplished with the introduction of lepirudin. The presence of multiple comorbid states, such as antiphospholipid syndrome, can potentially make laboratory confirmation of disease more difficult in patients with HIT II. In our opinion, it is of great importance that HIT II diagnosis be primarily clinical and that laboratory test results are carefully interpreted, especially when HIT is indicated by high clinical score values.     

Identification of New Fas Mutations in a Patient with Autoimmune Lymphoproliferative Syndrome (ALPS) and Eosinophilia

ABSTRACT: Autoimmune lymphoproliferative syndrome (ALPS) is a rare, newly recognized, chronic lymphoproliferative disorder in children and is characterized by lymphadenopathy, splenomegaly, pancytopenia, autoimmune phenomena and expansion of double-negative (DN) T lymphocytes (TCRαβ⁺, CD4⁻, CD8⁻). Defective lymphocyte apoptosis caused by mutations of the Fas (CD95) gene has been linked in the pathogenesis of ALPS, as binding of Fas-ligand to Fas can trigger apoptosis. Of the ALPS cases reported to date, point mutations, frameshifts and silent mutations in Fas all have been identified. We report two new point mutations in Fas in a child with ALPS and eosinophilia; studies on other family members established the pattern of inheritance for these mutations. Flow cytometric analysis of blood and tissues (spleen, lymph node, bone marrow) revealed abnormally expanded populations of DN T lymphocytes. Furthermore, activated lymphocytes and IFNγ-activated eosinophils were resistant to Fas-mediated apoptosis. Eosinophil resistance to Fas-mediated apoptosis has not been previously described in ALPS. Sequencing of Fas revealed two separate mutations not previously reported. One mutation, a C to T change at base 836, was a silent mutation inherited from the mother, while the second mutation, a C to A change at base 916, caused a non-conservative amino acid substitution in the death domain of Fas, changing a threonine to a lysine. This mutation is associated with a predicted change in the structure of a part of the death domain from a β-pleated sheet to an α-helix. We speculate that the mutation in the death domain prevents the interaction of Fas with intracellular mediators of apoptosis and is responsible for the autoimmune manifestations of ALPS and the abnormal lymphocytosis and eosinophilia in this patient.     

原发性肺隐球菌病临床与病理对照观察

目的探讨原发性隐球菌病（PC）的临床表现与病理变化特点。方法对23例肺原发性肺隐球菌病临床及病理资料进行对比分析,组织化学染色及光镜观察。结果23例中8例术前经肺穿刺活检明确诊断,15例开胸探查,病理证实为此真菌病,病理诊断5例为粘液胶样病变,炎性肉芽肿病变12例,结节状纤维肉芽肿病变6例,所有病例均检出新型隐球菌并行手术病灶切除,粘液卡红（Mc）,过碘酸雪夫染色（PAS）及六胺银（GMS）组织化学染色隐球菌呈阳性。术后3例并发隐球菌性脑膜炎,占本组病例13％（3／23）,本组病例术后经6周～3个月不同疗程的抗真菌治疗,术后随诊3个月～1年,均无隐脑及肺部复发。结论PC的临床与影像学表现均无特异性,肺穿刺活检病理检查有助于此病的诊断,术后应常规抗真菌治疗,以防发生隐脑与肺部复发。     

Impact of High Lipoprotein(a) Levels on Clinical Outcomes Following Peripheral Endovascular Therapy

BackgroundElevated lipoprotein(a) (Lp[a]) levels are an independent risk factor for the development of atherosclerotic diseases, including peripheral artery disease (PAD). However, their prognostic impact in patients with PAD remains unknown.ObjectivesThe aim of this study was to examine the prognostic impact of elevated Lp(a) levels in patients with PAD undergoing endovascular therapy (EVT).MethodsIn total, 1,169 patients who underwent successful EVT for symptomatic PAD between September 2016 and August 2021 were included in this study. High Lp(a) levels were defined as >30 mg/dL. The associations of high Lp(a) levels with incident major adverse cardiovascular events (MACE) (all-cause death, myocardial infarction, and stroke) and major adverse limb events (MALE) (repeat revascularization for target limb and major amputation) were analyzed.ResultsDuring a median follow-up period of 1.7 years (IQR: 0.6-3.0 years), 230 MACE (210 deaths, 15 myocardial infarctions, and 22 strokes) and 263 MALE (219 reinterventions and 36 major amputations) were observed. The cumulative incidence rate of MACE (48.1% vs 27.3%) and MALE (67.9% vs 27.2%) was significantly higher in patients with high Lp(a) levels (P < 0.001 for both). The adjusted HR were 1.93 (95% CI: 1.44-2.59; P < 0.001) for MACE and 4.15 (95% CI: 3.14-5.50; P < 0.001) for MALE. These associations were not influenced by low-density lipoprotein cholesterol levels or statin administration (P for interaction >0.05 for all).ConclusionsElevated Lp(a) levels were independently associated with incident MACE and MALE in patients with PAD treated with revascularization irrespective of low-density lipoprotein cholesterol level and statin administration.     

Self-Expandable Metal Stents (SEMS) Can Serve as a Bridge to Surgery or as a Definitive Therapy in Patients with an Advanced Stage of Cancer: Clinical Experience of a Tertiary Cancer Center

Background  

Self-expandable metal stents (SEMS) can be used to relieve benign and malignant colorectal obstruction.     

Highly Effective Adsorption Process of Ni(II) Ions with the Use of Sewage Sludge Fly Ash Generated by Circulating Fluidized Bed Combustion (CFBC) Technology

Recently, more and more attention has been paid to the removal of nickel ions due to their negative effects on the environment and human health. In this research, fly ash obtained as a result of incineration of municipal sewage sludge with the use of circulating fluidized bed combustion (CFBC) technology was used to analyze the possibility of removing Ni(II) ions in adsorption processes. The properties of the material were determined using analytical methods, such as SEM-EDS, XRD, BET, BJH, thermogravimetry, zeta potential, SEM, and FT-IR. Several factors were analyzed, such as adsorbent dose, initial pH, initial concentration, and contact time. As a result of the conducted research, the maximum sorption efficiency was obtained at the level of 99.9%. The kinetics analysis and isotherms showed that the pseudo-second order equation model and the Freundlich isotherm model best suited this process. In conclusion, sewage sludge fly ash may be a suitable material for the effective removal of nickel from wastewater and the improvement of water quality. This research is in line with current trends in the concepts of circular economy and sustainable development.     

Dynamic diffusion lung capacity of carbon monoxide (DLCO) as a predictor of pulmonary microangiopathy and its association with extra pulmonary microangiopathy in patients with type II diabetes mellitus

Background and aimLung as a target end organ for microvascular disease often remains underdiagnosed. This study aims to assess occurrence of pulmonary microangiopathy among Type 2 diabetes mellitus (T2DM) using dynamic diffusion lung capacity of carbon monoxide (DLCO).MethodsA total of 120 participants aged >18 years were enrolled in this study. Group 1 comprised T2DM with microangiopathy (n = 40), group 2 include T2DM without microangiopathy (n = 40), group 3 were healthy controls (n = 40). Individuals with underlying lung disease, smoking history, heart failure, urinary tract infection, macrovascular complications of diabetes, microalbuminuria due to other causes were excluded from the study. Using electronic spirometry, Forced Expiratory Volume in first second (FEV1), Forced Vital Capacity (FVC) was measured and FEV1/FVC ratio calculated. DLCO (%predicted) using single breath method was measured in sitting position followed by supine position and delta DLCO was calculated. DLCO measured was compared between the three groups.ResultsDLCO (median [IQR]) in sitting (78 [70–82.75]) and supine position (70 [62–84]) among group one was significantly decreased when compared to other two groups (p value < 0.001, p value < 0.001 respectively). Delta DLCO (median, [IQR]) among patients with diabetic microangiopathy (?6 [-8 to ?2]) was significant on comparison with group two (4[2,6]) and control group (5[4,6]) (p < 0.001). Negative delta DLCO reflecting pulmonary microangiopathy was significantly associated with extrapulmonary microangiopathy (p value = 0.027).ConclusionPostural variation in DLCO is a useful non-invasive test for identifying pulmonary microangiopathy among T2DM patients. Presence of pulmonary microangiopathy has significant association with diabetic nephropathy and retinopathy.     

单根电极VDD起搏器的初步应用（附七例报告）

自１９９４年１～１０月共为７例（完全性房室传导阻滞６例、高度房室传导阻滞１例）病人应用了单电极ＶＤＤ起搏器。术后随诊３～１２（平均６．５±２．５）个月，动态心电图监测全部达到心房同步起搏的目的，其中１例有个别间断性Ｐ波感知差而自动转为ＶＶＩ起搏，但总的Ｐ波感知率在９８％以上。如植入病例经严格选择（窦房功能正常的房室传导阻滞），单电极ＶＤＤ起搏可代替双腔ＤＤＤ起搏。     

Plasminogen Activator Inhibitor Type-1 (Part Two): Role for Failure of Thrombolytic Therapy. PAI-1 Resistance as a Potential Benefit for New Fibrinolytic Agents

Rapid and sustained reperfusion of an occluded coronary artery is the goal of thrombolytic therapy in acute myocardial infarction. However, the clot-dissolving efficacy of fibrinolytic agents such as tissue-type plasminogen activator (t-PA) is limited, in vivo, in part by the action of plasminogen activator inhibitor type-1 (PAI-1). A new generation of fibrinolytic agents has been genetically engineered to have greater resistance to PAI-1 inhibition. This articlereviews the pathophysiologic role of PAI-1 in failureof thrombolytic therapy and describes the advantages that PAI-1-resistance may confer uponfibrinolytic agents such as TNK-t-PA, the new fibrinolytic agent with the most powerful PAI-1 resistance.     

Helicobacter pylori Stool Antigen Test (Clinical Evaluation and Cost Analysis of a New Enzyme Immunoassay)

Noninvasive tests for Helicobacter pylori areincreasingly used. Recently, an enzyme immunoassay forH. pylori detection in feces has been put on the market.Aim of this multicenter study was to evaluate the usefulness of this novel test as apredictor of H. pylori status in the pretreatmentsetting. Three hundred consecutive patients wereenrolled. None of the patients had received anyeradicating treatment in the last 12 months, and all underwentgastroscopy with biopsies of the antrum and body forhistology (H) and rapid urease test (RUT). H. pyloristatus was defined positive (or negative) if both H and RUT were positive (or negative). When H and RUTgave conflicting results, the patients were classifiedas H. pylori indeterminate. A stool specimen wascollected for each patient and tested by using a novel enzyme immunoassay for H. pylori detection(HpSAT). Sensitivity, specificity, and diagnosticaccuracy of the test were calculated, as was the cost ofeach assay. H. pylori status was positive in 159patients, negative in 131, and indeterminate in 10. HpSATgave evaluable results (positive or negative) in 293patients, and doubtful results in 7 (2.3%). Sensitivity,specificity, and diagnostic accuracy of HpSAT were 96.8%, 89.7%, and 93.6% respectively.Considering the H. pylori-indeterminate patients aspositive, the percentages were 95.8%, 98.7%, and 93.2%respectively. The cost for each assay was about US $27. These results suggest that HpSAT is anoninvasive, simple, reliable, fast, and cheap methodfor evaluating H. pylori status in the pretreatmentsetting.