[Efficacy of intravenous drug information management system on the improvement of anemia in maintenance hemodialysis patients].

Objective: To investigate the effect of information management of intravenous drugs on anemia in maintenance hemodialysis patients. Methods: The information management of intravenous drugs was a management system developed by the Hemodialysis Center of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital in April 2020. The parameters six months before and after the use of the information management system were retrospectively collected and compared, including the rate of reaching the standard of hemoglobin, ferritin, transferrin saturation rate and the incidence of cardiovascular events. Specifically, the control stage was from October 2019 to March 2020, which was before the use of information management, and the study stage was from April to September 2020, which was after the use of information management. Results: There were 285 patients (190 males and 95 females) included in the control stage, with an average age of (62.4±13.2) years, while 278 patients (193 males and 85 females) were included in the study stage, with an average age of (62.8±13.2) years. Compared with the control stage, the rate of reaching the standard of hemoglobin [47.8% (797/1 668) vs 40.2% (687/1 710), P<0.001], ferritin [39.0% (217/556) vs 31.2% (178/570), P=0.006], and transferrin saturation [64.7% (360/556) vs 58.6% (334/570), P=0.034] increased in the study stage. The incidence of cardiovascular events in the study stage was 11.2% (31/278), which was significantly lower than that in the control stage [16.5% (47/285)] (P=0.043). Conclusion: The information management of intravenous drugs in the hemodialysis center may help improve the anemia status in maintenance hemodialysis patients.

The single nucleotide polymorphism rs11643718 in SLC12A3 is associated with the development of diabetic kidney disease in Chinese people with type 2 diabetes.

AIMS: To examine the association between 24 literature-based single nucleotide polymorphisms and diabetic kidney disease in Chinese people with type 2 diabetes. METHODS AND RESULTS: Twenty-four candidate diabetic kidney disease-susceptible single nucleotide polymorphisms were genotyped in 208 participants with type 2 diabetes and diabetic kidney disease and 200 participants with type 2 diabetes without diabetic kidney disease (case and control groups, respectively), together with 206 healthy participants using MassARRAY. Rs11643718 in the SLC12A3 gene was associated with diabetic kidney disease in the recessive model after adjusting for confounding factors, such as age and gender (adjusted odds ratio 2.056, 95% CI 1.120-3.776; P = 0.020). Meta-analyses further confirmed the association (P = 0.002). In addition, participants with the GG genotype had worse renal function and more albuminuria than those with the AA+AG genotype (P < 0.05). Renal section immunohistochemistry was conducted in participants with type 2 diabetes, diabetic kidney disease and AA+AG or GG genotypes and in participants with glomerular minor lesions. Together with data from the Nephroseq database, it was shown that the abundance of SLC12A3 was reduced in patients with the GG genotype, while elevated expression of SLC12A3 was associated with better renal function. In addition, rs10951509 and rs1345365 in ELMO1, which were determined to be in high linkage disequilibrium by SHEsis software, were also associated with diabetic kidney disease (adjusted P = 0.010 and 0.015, respectively). CONCLUSIONS: The G allele and GG genotype of SLC12A3 rs11643718 are associated with the development of diabetic kidney disease in a Chinese population with type 2 diabetes.

Etanercept therapy-associated acute uveitis: a case report and literature review.

A female patient diagnosed with ankylosing spondylitis experienced a new onset acute iritis following the initiation of etanercept therapy and recurrent episodes of iritis continues during the treatment of etanercept. Etanercept-associated iritis was suspected. Anti-TNF therapies can alleviate uveitis in some studies, but in some other anecdotal reports etanercept is considered as the main cause of uveitis. A literature review is presented below. For clinicians, more attention must be paid to the potential association between uveitis or iritis and etanercept, and more careful surveillance of patients under etanercept treatment is necessary.

Secretagogue-induced changes in membrane calcium permeability in chicken and chinchilla ileal mucosa. Selective inhibition by loperamide.

Substance P (SP), neurotensin (NT), bombesin (BB), serotonin (5HT), and carbamylcholine (CCH) transiently increase electrogenic anion secretion in chinchilla and chicken ileum. SP and CCH also transiently inhibit amiloride-sensitive Na/H exchange in isolated chicken enterocytes. Loperamide (LP) inhibits the short-circuit current responses caused by SP, NT, and BB, but not those caused by CCH, 5HT, Ca ionophore, or cyclic nucleotides. Similarly, LP inhibits the effects of SP, but not those of CCH, on Na/H exchange. LP inhibition of the SP effects was further studied in isolated chicken enterocytes. CCH and SP transiently increased cytosolic Ca activity by 20-50 nmol/liter, but only the response to SP was inhibited by LP (10(-5) M) and by the absence of extracellular Ca. We conclude SP and CCH effects on intestinal electrolyte transport are mediated by increasing enterocyte Ca activity and LP specifically inhibits peptide hormone-activated Ca entry by an opiate receptor-independent mechanism.

Polyomavirus large T-antigen expression in heart of transgenic mice causes cardiomyopathy.

One of the early genes of polyomavirus, large T-antigen (PVLT), has been classified in vitro as an immortalizing gene. In order to determine the ability of PVLT to cause the formation of hyperplasia or tumors in vivo, we generated transgenic mice harboring the cDNA for PVLT linked to the heavy-metal responsive metallothionein-1 promoter (MT). The transgene was primarily expressed in testes and seminal vesicles, but expression was also detected in heart of a single transgenic line. The expression of the transgene in the heart of MT-PVLT line 8 mice was correlated with cardiomyopathy and atrial thrombus formation leading to premature death at approximately 160 days due to cardiac failure. The heart of affected animals was from 1.5 to 5.2 fold greater in weight and 2 fold greater in dimensions than normal nontransgenic mice. Affected hearts fell short of frank tumor phenotype and no macroscopic nor microscopic focal growth was found. Histologically the heart has a heterogenous cardiomyocyte population with markedly enlarged cells mixed with relatively normal cells. Both cell types express PVLT protein. The primary cell type affected is the cardiomyocyte however, as heart proportions are maintained, interstitial and non-myocyte cells must be affected either directly or indirectly. Expression of PVLT has upset normal strict control of cell growth in these hearts to result in a new model of congestive cardiomyopathy.

Pathogenesis of pulmonary infarction.

Pulmonary embolism discovered at autopsy is still as prevalent as previously reported in the last three to four decades. Only a certain percentage of pulmonary emboli result in pulmonary infarction. Recently published studies have suggested that importance of the size of the occluded pulmonary artery in the occurrence of infarction. Our study of 45 autopsy subjects in which there were pulmonary emboli shows a 31 percent incidence of pulmonary artery branches of 3 mm in diameter or less, but emboli in larger arteries may show frequent extensions into their smaller distal branches without producing infarct. Pulmonary infarction also occurs more commonly in patients dying of cardiovascular or malignant diseases than it does in those dying of other diseases, and the combination of shock and congestive left heart failure appears to be the most significant hemodynamic risk factor in the development of pulmonary infarction. However, the increased risk of pulmonary infarction in patients with malignancy may not be accounted for by the existence of these two hemodynamic risk factors alone.

Ultrastructural localization of a breast tumor-associated antigen.

We used a monoclonal antibody to a high molecular weight glycoprotein of the milk fat globule membrane to study at the ultrastructural level the sites of accumulation of immunoreactive material in breast tumors. By light microscopy, the antigen was found only on the luminal membrane of normal resting or lactating breast cells. In tumors, antigen could be found in the cytoplasm. We used the avidin-biotin-peroxidase complex immunoperoxidase technique to localize the site of cytoplasmic accumulation of immunoreactive material in breast tumors. This technique showed that antigen is found on the membrane of cytoplasmic vesicles. Some of these vesicles were collapsed and gave rise to what appeared to be clumps of free cytoplasmic immunoreactive material. We have also documented that in some tumors the entire cytoplasmic membrane bears antigen, whereas in other tumors only areas of cytoplasmic membrane that form microscopic lumina express antigen.

Factor IX Chongqing: a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B.

A Chinese patient with sporadic, severe hemophilia B was found to have a low level of total factor IX antigen (3.5 U/dl), but less apparent antigen in an assay using a calcium-dependent antibody fraction (1.1 U/dl). This suggested a defect in the factor IX Gla domain coded mainly by exon 2 of the factor IX gene. Exon 2 was therefore amplified and sequenced. An A to T substitution was found at nucleotide 6455 of the patient's factor IX gene. This transversion changes the codon for Glu 27 in normal factor IX to a codon for Val. Since Glu 27 becomes an essential Gla residue, the defect should result in altered calcium-binding or calcium-dependent conformation of the patient's factor IX. The introduction of a hydrophobic side chain also appears to affect the hemophilic protein's stability. In leukocyte DNA from the patient's mother, the nucleotide sequence of exon 2 was entirely normal. Thus, barring somatic mosaicism within her germ cells, the new mutation occurred in oogenesis of her ovary.

Point mutations in four hemophilia B patients from China.

Point mutations in factor IX genes of four unrelated Chinese patients with hemophilia B have been identified by direct sequencing of amplified genomic DNA fragments. These four mutations occur in exon 8 of the factor IX gene. A C to T transition at nucleotide 30,863 changes codon 248 from Arg (CGA) to a new Stop codon (TGA), described in a previous family as factor IXMalmo3 (Green P M et al., EMBO J 1989; 8: 1067). A G to A transition at nucleotide 31,051 changes codon 310 from Trp (TGG) to a nonsense or Stop codon (TGA; factor IXChongquing2). A G to A transition at nucleotide 31,119 changes codon 333 which is for Arg (CGA) in normal factor IX, to one for Gln (CAA) in the variant previously described as factor IXLondon2 (Tsang T C et al., EMBO J 1988; 7: 3009) in a patient with moderately severe hemophilia B. The fourth patient has a novel C to A transversion at nucleotide 31,290, which corresponds to replacement of codon 390 which is for Ala (GCA) in normal factor IX, to one for Glu (GAA) in a patient with moderately severe hemophilia B (factor IXChongquing3). DNA sequences of amplified fragments from mothers of three showed both their son's variant and a normal nucleotide at the appropriate position, indicating that they are carriers. The fourth patient's (factor IXMalmo3) mother, whose DNA was not evaluable, was most probably a carrier because of her low plasma factor IX levels.

A distinct type of hidrotic ectodermal dysplasia.

Four individuals from 2 generations of a family had a hidrotic type of ectodermal dysplasia (ED). Males and females were similarly affected. They had trichodysplasia, with absent eyebrows and eyelashes; normal teeth, onychodysplasia; normal sweating; mild retrognathia; abnormal dermatoglyphics; and mental retardation. Additional variable manifestations included irregular menses, high implanted or prominent ears, café-au-lait spot, keratosis pilaris, supernumerary nipple, and mild hearing loss. Their previously undescribed condition could be classified as an ED of 1-3 (trichoonychial) subgroup of group A according to Freire-Maia's classification and is inherited as an autosomal recessive trait.

Applications of electron microscopy to diagnostic pulmonary pathology.

Viruses and other possible causative agents should be sought light and electron microscopically in all cases of ill-defined diseases including "sarcoid." Ideally, tissue should be prepared for electron microscopic examination as soon as a specimen is obtained; however, when this has not been done, tissue preserved in formalin solution can be used. Viruses, some bacteria, and other agents suspected on the basis of light microscopic findings can be verified electron microscopically by reprocessing paraffin-embedded tissue from areas that show smudge cells, focal necrosis with atypical cellular proliferation, and nuclear inclusions. Electron microscopically, all dying cells show swelling and rupture of cellular organelles and membranes; reactive changes include proliferation of branching tubules and paracrystalline and other types of proteinaceous precipitates (inclusions) in both the nucleus and cytoplasm. Qualitative and quantitative changes of cellular organelles, fibrils, microvilli, and intercellular junctions reflect hyperplasia, metaplasia, or dysplasia of the cell and may enable identification of the diseases, e.g., desquamative interstitial pneumonia. In various conditions, basal laminae become irregular, disruptive, or reduplicated following epithelial necrosis and regeneration. Electron microscopic evidence of immunologic damage to basal lamina and cells and immuno-electron-microscopic features of the lung in general require further studies. Electron microscopic features of transbronchial biopsy specimens may be diagnostic in cases of alveolar proteinosis, histiocytosis X, and amyloidosis. Ultrastructural abnormalities of cilia are common; primary ciliary defects are rare. Finally, light microscopic, scanning electron microscopic, and x-ray energy-dispersive spectrometric examinations of paraffin-embedded sections appear most practical for the pathologic evaluation of cases of pneumoconiosis.

The formaldehyde-fixed and paraffin-embedded tissues for diagnostic transmission electron microscopy: a retrospective and prospective study.

The fine structures of tissues processed routinely for light microscopy were studied retrospectively in 44 tissues and tumors and prospectively in 13 tissues and tumors. In the prospective study, we fixed tissues in an ample amount of fixatives, carefully avoiding crushed and air-dried portions, and processed them by five methods. The fine structures of the retrospective cases were mostly poor or passable, whereas those of the prospective cases were generally good. All formaldehyde-fixed tissues showed varied degrees of tissue extraction, notably of lipids, membranous structures, ribosomes, glycogen, and other loose cellular and intercellular matrix materials, that was related to the status and type of tissue as well as the kind and duration of fixation, dehydration, and tissue clearance. Paraffin embedding per se appeared to cause little alteration of the fine structure. Transmission electron microscopy of the paraffin-embedded tissue appeared most useful to identify infective agents, foreign particles, and densely packed organelles or structures, usually in the differential diagnosis of neoplasms. Although many factors are difficult to control, initial careful thin slicing, judicious selection, and fixation of the tissue (even by regular phosphate-buffered formaldehyde solution) can improve the fine structure of paraffin-embedded tissues and be useful in the direct correlation of light and electron microscopic findings.

The pattern of goblet cell hyperplasia in human airways.

Three types of mucosal alterations were found in the large and small airways in eight surgically resected human lungs. These changes were linear depressions and the formation of furrows and diverticula. Goblet cell hyperplasia, mucus retention, and macrophages were frequently associated with these surface deformities, and inflammatory cells were found both in the mucosa and in the underlying bronchial wall. Linear depressions, furrows, and diverticula may be sequential and may persist in the lungs of a patient with or without causing symptoms.

Leukotic spread: an unusual tumor transition.

This report concerns a case of lung cancer, which is of interest because it proves that an epithelial tumor is capable of spreading in a manner morphologically identical to that of a malignant lymphoreticular tumor.

Endobronchial plasma cell granuloma (xanthomatous pseudotumor); a light and electron microscopic study.

Plasma cell granuloma (xanthomatous pseudotumor) is polymorphic at light as well as electron microscopic examination. At light microscopy the endobronchial variant of this entity was rich in plasma cells and interwoven, whorl-like, or concentrically arranged spindle cells. Foamy histiocytes and macrophages usually abundant in the intrapulmonary variant were rare. At electron microscopy particles 20 to 50 nm. in size were found at the bronchial mucosal surface but not elsewhere in the lesion. Plasma cells near the bronchial surface contained cytoplasmic fibrils, mitochondria with concentric cristae, and inclusions that bore a close resemblance to adjacent extracellular crystallized hemoglobin. Those in the center of the lesion ordinary round inclusions and none of the other changes. Spindle cells in the interlaced areas were mostly fibroblasts or myofibroblasts, whereas those whorled around capillaries resembled pericytes with basement membranes and nuxes-like intercellular junctions. Year rings like multilayered basal laminae were frequently present between the pericyte-like cells and the endothelial cells of the capillaries. The ultrastructure of plasma cell granuloma, like the histologic and clinical aspects, differs from that of sclerosing hemangioma, pseudolymphoma, and malignant plasma cell tumor affecting the lung.

Giant cell carcinoma of the lung. A light and electron microscopic study.

Three cases of giant cell carcinoma of lung and six other lung carcinomas with large atypical cell formation were studied by both light and electron microscopy. The giant cell carcinomas showed unique light and electron microscopic features, whereas large atypical cells from other lung carcinomas usually retained some ultrastructural characteristics of their cellular origin. The giant cell carcinoma is characterized by abundant mitochondria, a concentric whorl of tonofilament-like fibrils, and aggregates of several pairs of centrioles. The "phagocytic activity" of the giant cell carcinoma is more likely attributable to the so-called tumor cell-tumor cell or leukocyte-tumor cell emperipolesis. Giant cell carcinoma of lung may originate from a primitive multipotential cell in the distal bronchiole or be associated with a squamous, glandular, or clear cell pattern. Whether in pure or mixed form, this tumor should still be considered a specific entity because of its unique light and electron microscopic features and the fulminant clinical course it follows despite rate reported exceptions.

Small cell malignant tumors of the thyroid. A light and electron microscopic study.

Three small cell malignant tumors involving the thyroid gland were examined by light and electron microscopy. In each, numerous similarities were presented on light microscopic analysis rendering interpretation difficult. In the first patient the small cells were identified on electron microscopy as moderately well differentiated lymphocytes. This tumor occurred in an elderly woman as a locally invasive thyroid tumor, subsequently involving distant sites, including the liver, spleen, lymph nodes, and soft tissue. The tumor repeatedly regressed following radiotherapy. The patients eventually died with disseminated lymphocytic lymphoma. In the second patient the thyroid tumor, also locally invasive, was composed principally of neoplastic epithelial cells when studied on electron microscopy. This patient responded poorly to radiation and died within a year after diagnosis. The third patient presented with an enlarging thyroid mass, which ultrastructurally was found to be composed principally of well differentiated lymphocytes. Subsequent clinical evaluation established a diagnosis of chronic lymphocytic leukemia. Small cell malignant tumors of the thyroid represent a difficult diagnosis problem for surgical pathologists. Ultrastructural study, we believe, is a useful adjunct in the differentiation of these tumors.

Morphogenesis of human bronchial diverticulum. A scanning electron microscopic study.

Diverticulosis of the bronchial wall was found in patients not only with, but also without, chronic obstructive lung disease; it appeared to start as submicroscopic depressions and dilatations of the ducts of the bronchial gland on the mucosal surface. Multiple depressions and dilatations fused to form a diverticulum which herniated between and through the smooth-muscle cellular bundles. Rupture of the latter resulted in large diverticula. Cough and a weakened bronchial wall, from whatever causes, likely lead to bronchial diverticulosis. Exaggerated but unequal formations of bronchial diverticula at the sites of dichotomy suggest either that the effect of cough could be different between segments or subsegments, or that there are local differences in connective-tissue atrophy, inflammation, and structural defects. Mucous plugs, macrophages, red blood cells, inhaled particles, and probably carcinogens are accumulated at the bronchial diverticula, which apparently interfere with airway cleansing and also cause continuous local irritation. The relationship between bronchial diverticulosis and small-airway disease or lung cancer needs further clarification.

Recurrent endobronchial soft tissue tumors.

Two benign appearing endobronchial soft tissue lesions in two young patients (ages 33 and 26) were incompletely excised to conserve normal lung. Both tumors recurred four and seven years later. The first tumor had abundant small vessels in a myxomatous background (angiomyxoma); myofibroblasts formed the invasive component of the second tumor. To the best of our knowledge these two types of tumor have not been reported in the endobronchial location. Endobronchial lipoma, epithelial papilloma, inflammatory polyps, nodular sarcoid or amyloid and lymph nodes should be managed endoscopically. The potentially recurring and locally invasive endobronchial tumors such as granular cell myoblastoma, pleomorphic adenoma, angiomyxoma, and tumors of myofibroblast, and probably all other sessile benign tumors should be excised completely with part of the bronchial wall. The maximum preservation of normal lung usually does not conflict with this type of radical procedure.