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1.
J Cyst Fibros ; 18(5): 606-613, 2019 09.
Article in English | MEDLINE | ID: mdl-30803905

ABSTRACT

BACKGROUND: Cell-based studies have shown that W1282X generates a truncated protein that can be functionally augmented by modulators. However, modulator treatment of primary cells from individuals who carry two copies of W1282X generates no functional CFTR. To understand the lack of response to modulators, we investigated the effect of W1282X on CFTR RNA transcript levels. METHODS: qRT-PCR and RNA-seq were performed on primary nasal epithelial (NE) cells of a previously studied individual who is homozygous for W1282X, her carrier parents and control individuals without nonsense variants in CFTR. RESULTS: CFTR RNA bearing W1282X in NE cells shows a steady-state level of 4.2 ±â€¯0.9% of wild-type (WT) CFTR RNA in the mother and 12.4 ±â€¯1.3% in the father. NMDI14, an inhibitor of nonsense-mediated mRNA decay (NMD), restored W1282X mRNA to almost 50% of WT levels in the parental NE cells. RNA-seq of the NE cells homozygous for W1282X showed that CFTR transcript level was reduced to 1.7% of WT (p-value: 4.6e-3). Negligible truncated CFTR protein was generated by Flp-In 293 cells stably expressing the W1282X EMG even though CFTR transcript was well above levels observed in the parents and proband. Finally, we demonstrated that NMD inhibition improved the stability and response to correctors of W1282X-CFTR protein expressed in the Flp-In-293 cells. CONCLUSION: These results show that W1282X can cause substantial degradation of CFTR mRNA that has to be addressed before efforts aimed at augmenting CFTR protein function can be effective.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis , Membrane Transport Modulators/pharmacology , RNA, Messenger , Cells, Cultured , Codon, Nonsense , Cystic Fibrosis/drug therapy , Cystic Fibrosis/genetics , Cystic Fibrosis/metabolism , Gene Expression Profiling , Homozygote , Humans , Mutation , Nasal Mucosa/metabolism , Protein Stability/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism
2.
Am J Transplant ; 17(1): 227-238, 2017 01.
Article in English | MEDLINE | ID: mdl-27321167

ABSTRACT

Risk factors for non-skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow-up time was 1086 days (interquartile range 436-2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95-3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04-8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45-22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02-1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02-1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37-0.97, p = 0.04) and single-lung transplantation (HR 1.64, 95% CI: 1.34-2.01, p < 0.001). Significant interactions between donor or recipient smoking and single-lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10-1.88, p = 0.009).


Subject(s)
Carcinoma, Squamous Cell/etiology , Graft Rejection/etiology , Lung Transplantation/adverse effects , Skin Neoplasms/etiology , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Graft Rejection/pathology , Graft Survival , Humans , Male , Middle Aged , Prognosis , Risk Factors , Skin Neoplasms/pathology , Survival Rate
3.
Anat Histol Embryol ; 46(1): 73-84, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27457370

ABSTRACT

The morphological variations and the androgen receptor (AR) expression were studied in viscacha epididymis in relation to sexual maturity. The animals were divided into immature, pre-pubertal and adult, according to their corporal weight and testicular histology. The epididymides were studied by light microscopy, immunohistochemistry for AR and morphometric analysis. In pre-pubertal and adult animals, four well-differentiated segments (initial, caput, corpus and cauda) were observed, while in immature animals, three segments were identified (initial-caput segment, corpus and cauda). In each segment, the structural parameters and the relative cell distribution were different between the groups. The serum testosterone levels of pre-pubertal and adults showed a very significant increase related to sexual maturity. The AR expression in epithelial and fibromuscular stromal cells was different between the groups. In conclusion, the present work demonstrates that the morphological characteristics of the viscacha epididymis vary while sexual maturity is reached, the development of initial and caput is subsequent to corpus and cauda development and the androgens might play an important role during this process.


Subject(s)
Chinchilla/anatomy & histology , Chinchilla/growth & development , Epididymis/growth & development , Immunohistochemistry/veterinary , Receptors, Androgen/biosynthesis , Animals , Epididymis/metabolism , Epithelial Cells/metabolism , Male , Muscle Fibers, Skeletal/metabolism , Testosterone/blood
4.
Am J Transplant ; 17(2): 485-495, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27618731

ABSTRACT

We simulated the impact of regionalization of isolated heart and lung transplantation within United Network for Organ Sharing (UNOS) regions. Overall, 12 594 orthotopic heart transplantation (OHT) patients across 135 centers and 12 300 orthotopic lung transplantation (OLT) patients across 67 centers were included in the study. An algorithm was constructed that "closed" the lowest volume center in a region and referred its patients to the highest volume center. In the unadjusted analysis, referred patients were assigned the highest volume center's 1-year mortality rate, and the difference in deaths per region before and after closure was computed. An adjusted analysis was performed using multivariable logistic regression using recipient and donor variables. The primary outcome was the potential number of lives saved at 1 year after transplant. In adjusted OHT analysis, 10 lives were saved (95% confidence interval [CI] 9-11) after one center closure and 240 lives were saved (95% CI 209-272) after up to five center closures per region, with the latter resulting in 1624 total patient referrals (13.2% of OHT patients). For OLT, lives saved ranged from 29 (95% CI 26-32) after one center closure per region to 240 (95% CI 224-256) after up to five regional closures, but the latter resulted in 2999 referrals (24.4% of OLT patients). Increased referral distances would severely limit access to care for rural and resource-limited populations.


Subject(s)
Algorithms , Graft Rejection/mortality , Heart Transplantation/mortality , Hospitals, High-Volume/standards , Hospitals, Low-Volume/standards , Lung Transplantation/mortality , Regional Health Planning , Adult , Computer Simulation , Female , Follow-Up Studies , Graft Survival , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Registries , Risk Factors , Survival Rate , United States
5.
Am J Transplant ; 15(7): 1948-57, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25809545

ABSTRACT

Successful lung transplantation (LTx) depends on multiple components of healthcare delivery and performance. Therefore, we conducted an international registry analysis to compare post-LTx outcomes for cystic fibrosis (CF) patients using the UNOS registry in the United States and the National Health Service (NHS) Transplant Registry in the United Kingdom. Patients with CF who underwent lung or heart-lung transplantation in the United States or United Kingdom between January 1, 2000 and December 31, 2011 were included. The primary outcome was all-cause mortality. Kaplan-Meier analysis and Cox proportional hazards regression evaluated the effect of healthcare system and insurance on mortality after LTx. 2,307 US LTx recipients and 451 individuals in the United Kingdom were included. 894 (38.8%) US LTx recipients had publically funded Medicare/Medicaid insurance. US private insurance and UK patients had improved median predicted survival compared with US Medicare/Medicaid recipients (p < 0.001). In multivariable Cox regression, US Medicare/Medicaid insurance was associated with worse survival after LTx (US private: HR0.78,0.68-0.90,p = 0.001 and UK: HR0.63,0.41-0.97, p = 0.03). This study in CF patients is the largest comparison of LTx in two unique health systems. Both the United States and United Kingdom have similar early survival outcomes, suggesting important dissemination of best practices internationally. However, the performance of US public insurance is significantly worse and may put patients at risk.


Subject(s)
Cystic Fibrosis/mortality , Cystic Fibrosis/surgery , Delivery of Health Care, Integrated/organization & administration , Graft Rejection/mortality , Lung Transplantation/mortality , National Health Programs/organization & administration , Postoperative Complications , Adult , Cohort Studies , Delivery of Health Care, Integrated/standards , Female , Follow-Up Studies , Humans , International Agencies , Male , National Health Programs/standards , Prognosis , Quality of Health Care , Registries , Risk Factors , Survival Rate , United Kingdom , United States
6.
ISRN Anat ; 2013: 128921, 2013.
Article in English | MEDLINE | ID: mdl-25969823

ABSTRACT

The viscacha (Lagostomus maximus maximus) is a seasonal South American wild rodent. The adult males exhibit an annual reproductive cycle with periods of maximum and minimum gonadal activity. Four segments have been identified in the epididymis of this species: initial, caput, corpus, and cauda. The main objective of this work was to relate the seasonal morphological changes observed in the epididymal duct with the data from epididymal sperm during periods of activity and gonadal regression using light and scanning electron microscopy (SEM). Under light and electron microscopy, epididymal corpus and cauda showed marked seasonal variations in structural parameters and in the distribution of different cellular populations of epithelium. Initial and caput segments showed mild morphological variations between the two periods. Changes in epididymal sperm morphology were observed in the periods analyzed and an increased number of abnormal gametes were found during the regression period. During this period, anomalies were found mainly in the head, midpiece, and neck, while in the activity period, defects were found only in the head. Our results confirm that the morphological characteristics of the epididymal segments, as well as sperm morphology, undergo significant changes during the reproductive cycle of Lagostomus.

7.
Praxis (Bern 1994) ; 101(22): 1417-22, 2012 Oct 31.
Article in German | MEDLINE | ID: mdl-23117961

ABSTRACT

In 776 primary care patients serum vitamin D level was measured in month of september showing deficiency (<50 nmol/l) in 45,1%, severe deficiency (<30 nmol/l) in 9,8% and serum levels below the recommended target level of 75 nmol/l in 88,9% of cases. Three possible symptoms of vitamin D deficiency were assessed by a visual analogue scale (0-10): fatigue, muscle weakness, and muscle and joint pain. A significant correlation between muscle weakness and degree of vitamin D deficiency was shown (p=0,04), whereas there was no correlation in the two other symptoms. However, patients with vitamin D deficiency more frequently reported fatigue (p=0,02) and muscle weakness (p=0,009) than patients without deficiency did, and no difference was seen concerning muscle and joint pain.


Subject(s)
Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Calcifediol/blood , Cross-Sectional Studies , Female , General Practice/statistics & numerical data , Health Surveys , Humans , Male , Middle Aged , Reference Values , Switzerland , Vitamin D Deficiency/blood , Young Adult
8.
Sci Total Environ ; 409(23): 5034-45, 2011 Nov 01.
Article in English | MEDLINE | ID: mdl-21925711

ABSTRACT

The Suquía River lower-middle basin (Córdoba, Argentina) is subject to a strong anthropic impact because it receives pollutants from different sources (industries, wastewaters, heavy traffic, agricultural land use, etc.) We have assessed the degree of watershed degradation of Suquía River lower-middle sections through the analysis of different ecosystem compartments (air, water, riparian soil, sediments and biota), in order to provide useful data to be considered in future river restoration programs. Four study sites were selected along the river (La Calera city, Córdoba city, Corazón de María village and Río Primero city) which were sampled during the low- and high-water flow periods. We analyzed: a) chemical and physical characteristics of water, sediments, and riparian soil; b) heavy metal content of water and sediments, and c) semi-volatile organic compounds in air. Besides, pollutant bioindicators such as fish assemblages, lichens (Usnea amblyoclada), vascular plants (Tradescantia pallida), and microorganisms (fecal coliform and Escherichia coli) were used to further assess the status of the river. All analyzed ecological compartments were affected by water pollution, particularly, fish assemblages, sediments and riparian soils by heavy metal and coliform bacteria. Moreover, we detected a possible contribution of sulfur and a high pollutant content in air that merit further research about other air-water exchanges. Accordingly, we strongly suggest that an action to restore or remediate the anthropic effect on the Suquía River be extended to all possible compartments along the river.


Subject(s)
Air Pollutants/analysis , Ecosystem , Environmental Monitoring/statistics & numerical data , Geologic Sediments/analysis , Rivers/chemistry , Soil/analysis , Water Pollutants, Chemical/analysis , Argentina , Enterobacteriaceae/chemistry , Environmental Monitoring/methods , Environmental Restoration and Remediation/methods , Lichens/chemistry , Metals, Heavy/analysis , Plants/chemistry , Volatile Organic Compounds/analysis
9.
Anat Histol Embryol ; 40(1): 11-20, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20809916

ABSTRACT

The anatomy, histology and androgen receptor immunohistochemistry of the prostate (P), seminal vesicles (SV), bulbourethral and coagulant gland (CG) were studied in male viscacha, a seasonally reproductive wild rodent. Two histologically well-defined zones, peripheral and central, were identified in the prostate, according to their relationship with the urethra. The epithelial cells were periodic acid-Schiff (PAS)-positive in the central zone and alcian blue negative in the two zones. The SV are a paired gland, tubular, of tortuous aspect and formed by radial layers. The bulbourethral glands were paired, formed by tubuloalveolar acini and surrounded by a thick layer of skeletal muscle. The CG was multilobulated. The large adenomers showed PAS-positive epithelium and were negative to alcian blue. Androgen receptors in the P, SV and coagulating gland showed variations in their distribution with immunohistochemistry heterogeneous pattern. Finally, the reproductive system accessory glands of male viscacha may be considered as a novel and interesting model for the study of seasonal reproduction in photoperiod-dependent animals.


Subject(s)
Bulbourethral Glands/anatomy & histology , Prostate/anatomy & histology , Receptors, Androgen/analysis , Rodentia/anatomy & histology , Seminal Vesicles/anatomy & histology , Urogenital System/anatomy & histology , Animals , Bulbourethral Glands/chemistry , Epithelial Cells , Fluorescent Antibody Technique , Male , Photoperiod , Prostate/chemistry , Receptors, Androgen/immunology , Seminal Vesicles/chemistry , Staining and Labeling , Urethra/anatomy & histology , Urogenital System/chemistry
10.
Praxis (Bern 1994) ; 98(4): 191-9, 2009 Feb 18.
Article in German | MEDLINE | ID: mdl-19224487

ABSTRACT

Anemia is a common problem in family medicine and therefore frequently investigated in general practice. Anemias are classified according to mean corpuscular volume (MCV) and reticulocyte count. An algorithm for the evaluation of the cause contains patients history and laboratory analysis including reticulocyte count, serum ferritin and CRP, serum vitamin B12, serum or erythrocyte folate and serum creatinine. Therewith most anemias in general practice can be explained. The most important types of anemia, e.g. iron deficiency anemia, are discussed as well as aspects of diagnosis and therapy. Iron deficiency anemia is often diagnosed together with other types of anemia, such as e.g. anemia of chronic disease. Particular aspects of anemia in the elderly as well as renal anemia are discussed.


Subject(s)
Anemia/etiology , Algorithms , Anemia/classification , Anemia/diagnosis , Anemia/therapy , Diagnosis, Differential , Family Practice , Humans
11.
Reproduction ; 124(5): 691-702, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12417008

ABSTRACT

This study investigated the influence of chronic hyperthyroidism on mammary function in lactating rats and the effects on their pups. Thyroxine-treated (10 microg per 100 g body weight per day; hyperthyroid (HT)) or vehicle-treated rats were mated 2 weeks after the start of treatment and killed with their litters on days 7, 14 and 21 of lactation. Serum concentrations of triiodothyronine (T(3)) and tetraiodothyronine (T(4)) increased in thyroxine-treated rats. In HT mothers, serum prolactin decreased on day 7 and day 14 of lactation, whereas insulin-like growth factor I (IGF-I) and progesterone concentrations decreased, and corticosterone increased on day 7 of lactation. In HT pups, T(4) concentration increased on day 7 and day 14 of lactation, whereas T(3) increased only on day 14 of lactation, and growth hormone increased on day 7 of lactation. Mammary prolactin binding sites did not vary, but there was an increase in the binding sites in the liver on day 14 of lactation in thyroxine-treated rats. In an acute suckling experiment, thyroxine-treated rats released less oxytocin, growth hormone and prolactin and excreted less milk than did control rats. Mammary casein, lactose and total lipid concentrations in thyroxine-treated rats were similar to those of control rats on day 14 of lactation. Histological studies of the mammary glands showed an increased proportion of alveoli showing reduced or no lumina and cells with condensed nuclei on day 14 and day 21 of lactation; the TdT-mediated dUTP nick-end labelling (TUNEL) test revealed an increase in apoptosis in alveolar cells on day 21 of lactation in thyroxine-treated rats. Expression of SGP-2, a gene expressed during mammary involution, increased in thyroxine-treated rats on day 14 and day 21 of lactation, whereas expression of insulin-like growth factor binding protein 5, a proapoptotic signal, was unchanged. Bcl-2, which promotes survival of mammary gland epithelial cells was unchanged, whereas expression of IGF-I, which also promotes survival of mammary gland epithelial cells, increased on day 21 of lactation in thyroxine-treated rats. These results indicate that thyroxine treatment produces some milk stasis as a result of impairments in suckling induced release of oxytocin that may initiate the first stage of mammary involution, increasing apoptosis in a gland that is otherwise actively producing and secreting milk.


Subject(s)
Animals, Suckling/blood , Hyperthyroidism/physiopathology , Mammary Glands, Animal/physiopathology , Pregnancy Complications/physiopathology , Animals , Animals, Suckling/growth & development , Apoptosis , Binding Sites , Chronic Disease , Clusterin , Female , Glycoproteins/genetics , Growth Hormone/blood , Hyperthyroidism/metabolism , Hyperthyroidism/pathology , In Situ Nick-End Labeling , Insulin-Like Growth Factor Binding Protein 5/genetics , Insulin-Like Growth Factor I/analysis , Liver/metabolism , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/pathology , Microscopy, Fluorescence , Milk Ejection , Molecular Chaperones/genetics , Oxytocin/blood , Pregnancy , Pregnancy Complications/metabolism , Pregnancy Complications/pathology , Progesterone/blood , Prolactin/metabolism , RNA, Messenger/analysis , Rats , Reverse Transcriptase Polymerase Chain Reaction , Thyroxine/blood , Triiodothyronine/blood
12.
J Cardiovasc Surg (Torino) ; 42(6): 713-7, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11698934

ABSTRACT

BACKGROUND: Coronary artery reoperation represents about 20% of coronary artery operations. In this study we compared mortality and morbidity of first intervention and redo operation. EXPERIMENTAL DESIGN: a retrospective study. SETTINGS: patients who underwent coronary artery reoperations in a University Cardiac Surgery Division in 1991-1994. PATIENTS: our clinical survey was composed of two groups: group A included 44 consecutive patients (mean age 60+/-7 years, males/females=41/3) who underwent a coronary artery reoperation in the years 1991-1994 at the University Cardiac Surgery Division of Turin; group B included 344 patients (mean age 58+/-8 years, males/females=289/55) randomly selected among those who underwent a first coronary operation in the above indicated period of time and centre. All patients had angina pectoris refractory to maximal medical therapy. INTERVENTIONS: all patients underwent a coronary artery operation in extracorporeal circulation (ECC), under mild hypothermia (30-32 degrees C), during a single aortic clamp period, with antegrade cold crystalloid cardioplegia (St. Thomas). MEASURES: comparison of clinical preoperative features, risk factors and postoperative mortality and morbidity between the two groups. RESULTS: In reoperated patients we observed a greater mean akinesis score (p<0.001) and severe left ventricular dysfunction presence (p=0.014). Reoperation mortality was 11.4% against first operation mortality of 3.2% (p=0.03). Female gender (p=0.03), intra-aortic balloon counterpulsation need (p=0.002), adrenaline use (p=0.004) and low cardiac output syndrome (p=0.007) were all perioperative risk factors in group A. CONCLUSIONS: Coronary artery reoperation involves a higher mortality and morbidity compared to the first operation, especially related to the reduced left ventricular function which characterises the population that undergoes reoperation.


Subject(s)
Coronary Artery Bypass/mortality , Reoperation/mortality , Ventricular Dysfunction, Left , Extracorporeal Circulation , Female , Humans , Italy/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Sex Factors
13.
Schweiz Med Wochenschr ; 129(25): 961-5, 1999 Jun 26.
Article in German | MEDLINE | ID: mdl-10422192

ABSTRACT

A 44-year-old patient was referred with weight loss of some 6 kg in two months, weakness and diarrhoea. According to the criteria of the American College of Rheumatology (ACR), systemic lupus erythematosus (SLE) was diagnosed: photodermatosis, nephropathy, and pancytopenia with positive antinuclear antibodies and antibodies against native DNA. In addition, adrenal failure was diagnosed with hyponatraemia, relapsing fever, low baseline cortisol and impaired response to ACTH stimulation. Clinical features of SLE may obscure signs of adrenal insufficiency, and hence, diagnosis is jeopardized. SLE combined with Addition's disease is rare. In some patients with both disorders, antiphospholipid antibodies, as found in our patient, are considered responsible for the development of Addison's disease. Possible pathogenetic mechanisms such as adrenal haemorrhage or (micro)thrombosis are discussed. The patient's condition significantly improved under steroid therapy. The progression of renal insufficiency (histology: mesangioproliferative glomerulonephritis), however, required additional immunosuppression with cyclophosphamide.


Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Adult , Cyclophosphamide/therapeutic use , Diagnosis, Differential , Humans , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/diagnosis , Male , Steroids/therapeutic use
14.
Schweiz Med Wochenschr ; 127(15): 631-5, 1997 Apr 12.
Article in German | MEDLINE | ID: mdl-9198889

ABSTRACT

A 46-year-old male patient was referred from a peripheral hospital with a 5 days history of high fever, dyspnea and respiratory deterioration. Direct immunofluorescence examination of bronchoalveolar fluid repeatedly showed clusters of Pneumocystis carinii. High-dose sulfamethoxazole-trimethoprim therapy was initiated and the patient recovered promptly during the following days. This otherwise healthy patient's past history was unremarkable in terms of prior infectious diseases. There was no evidence of immunodeficiency and he was not taking medication. Antibodies against HIV-1 were repeatedly negative, as were the assay for p24-antigen, PCR for HIV-DNA and HIV culture. Subpopulations of lymphocytes showed normal values. Analysis of the IgG fractions revealed a decreased subclass 2 fraction. Functional assays showed decreased biological binding capacity of this subclass 2 IgG to polysaccharide antigens. A four-fold increase of cytomegalovirus (CMV) IgG titer suggested a concomitant CMV infection or reactivation. As CMV infection is known to cause transient cellular immunodeficiency, reactivated CMV infection, in concert with IgG subclass 2 deficiency, could be a predisposing factor for P. carinii infection in this patient.


Subject(s)
HIV Seronegativity , Pneumocystis/isolation & purification , Pneumonia, Pneumocystis/microbiology , Antibodies, Viral/isolation & purification , Cytomegalovirus/immunology , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/immunology , DNA, Viral/isolation & purification , HIV Antibodies/isolation & purification , Humans , Immunologic Deficiency Syndromes/immunology , Male , Middle Aged , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/immunology
15.
Arterioscler Thromb Vasc Biol ; 17(1): 114-8, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9012645

ABSTRACT

Many studies have shown alterations of the hemostatic and fibrinolytic systems in patients with atherosclerotic disease, principally in levels of plasminogen activator inhibitor-1. However, in a large prospective study only fibrinogen, von Willebrand factor antigen, and tissue plasminogen activator antigen were found to be independent risk markers for acute coronary events. The present study evaluated the fibrinolytic system in coronary artery disease, paying particular attention to another inhibitor of fibrinolysis, plasminogen activator inhibitor-3, also called protein C inhibitor (PCI). One hundred fifteen nonanticoagulated male survivors of myocardial infarction were investigated for a range of hemostatic and fibrinolytic parameters that were compared with values in 87 age-matched healthy control male subjects. PCI active antigen was significantly (P < .03) elevated in the myocardial infarction group compared with the control group and was associated with the number of acute coronary events suffered (P = .005) but not with the severity of disease as determined by coronary angiography. Elevated PCI plasma levels can be considered as a risk marker for acute coronary events and might be of particular importance in the pathogenesis of this disease due to the interference of PCI in both the anticoagulant and fibrinolytic systems.


Subject(s)
Myocardial Infarction/blood , Protein C Inhibitor/blood , Adult , Aged , Fibrinolysis , Humans , Male , Middle Aged , Risk Factors
16.
Blood Coagul Fibrinolysis ; 6(5): 456-9, 1995 Jul.
Article in English | MEDLINE | ID: mdl-8589213

ABSTRACT

Resistance to activated protein C (APC resistance) due to the factor V mutation 506 Arg-->Gln (factor V Leiden) is the most prevalent inherited risk factor for venous thromboembolism. Its association with arterial thromboembolic disease, however, is still controversial. In the present study we found no difference between the prevalence of APC resistance (assessed by the ratio of the aPTT with and without added APC) in 134 non-anticoagulated survivors of myocardial infarction and that in 100 controls of similar age and sex distribution (2.2% and 2.0%, respectively). Patients showed a significantly higher median value for the aPTT ratio than controls (2.85 and 2.66, respectively), a fact we could not explain by our data.


Subject(s)
Drug Resistance , Myocardial Infarction/blood , Protein C/pharmacology , Adult , Aged , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Factor V/analysis , Factor V/genetics , Factor VII/analysis , Female , Humans , Male , Middle Aged , Mutation , Partial Thromboplastin Time , Reference Values
17.
Acta Haematol ; 90(1): 13-8, 1993.
Article in English | MEDLINE | ID: mdl-8237268

ABSTRACT

In order to study the relationship between erythropoiesis and serum ferritin (SF) during erythropoietin (rHuEPO) therapy in the anaemia of end-stage renal disease (ESRD), 19 patients were followed without iron supplementation and at a fixed dose of the drug (40 U/kg). Twelve patients failed to attain the target haemoglobin (Hb) value, 7 of whom due to the appearance of iron deficiency. Erythropoiesis, as measured by the serum transferrin receptor concentration, increased from 12 to 120% of the basal value. This increment was not constantly associated with a proportional rise of Hb or reticulocyte count. SF decreased exponentially from a median value of 221 micrograms/dl (range 42-470) to a median value of 54 micrograms/dl (range 20-172). Halving of the basal SF value (SF-T50) was reached at the 18th-95th day of therapy (median = 43), representing a iron shift of 3.4-11.6 mg/day (median = 5.4). SF-T50 was not correlated with the Hb increase, but with that of erythropoiesis (r = 0.78; p = 0.003). The minimum SF (MSF) value attained was not correlated with the appearance of iron deficiency. The conclusion is that the rate of SF decrease during rHuEPO in ESRD is a reliable measure of iron mobilisation for erythropoiesis, but not for haematologic response. The MSF value reached during therapy is not representative of available iron for erythropoiesis.


Subject(s)
Anemia/blood , Anemia/drug therapy , Erythropoiesis/drug effects , Erythropoietin/therapeutic use , Ferritins/blood , Ferritins/drug effects , Kidney Failure, Chronic/blood , Adolescent , Adult , Aged , Anemia/etiology , Combined Modality Therapy , Female , Hemoglobins/analysis , Hemoglobins/drug effects , Humans , Iron/blood , Iron Deficiencies , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , Receptors, Transferrin/analysis , Receptors, Transferrin/drug effects , Recombinant Proteins/therapeutic use , Renal Dialysis , Time Factors , Treatment Failure
19.
Schweiz Med Wochenschr ; 122(43): 1622-6, 1992 Oct 24.
Article in German | MEDLINE | ID: mdl-1439683

ABSTRACT

We report the case of a 78-year-old patient with recurrent attacks of severe fasting and late postprandial hypoglycemia, whose plasma showed highly elevated concentrations of immunoreactive insulin evidenced by high titers of spontaneous insulin and proinsulin-binding antibodies. Insulin autoimmune syndrome was diagnosed. Further investigations revealed a multiple myeloma of the kappa-light chain type. The monoclonal insulin-binding antibodies were characterized as IgG2-subclass and were identical with the paraprotein, thereby confirming that the insulin-binding antibodies were in fact produced by the myeloma. Together with initial symptomatic treatment, plasmapheresis was performed repeatedly to reduce the antibody pool. Subsequently octreotide therapy proved successful. The underlying myeloma was treated by chemotherapy.


Subject(s)
Hypoglycemia/etiology , Insulin Antibodies/biosynthesis , Multiple Myeloma/complications , Aged , Autoimmune Diseases/immunology , Humans , Hypoglycemia/immunology , Hypoglycemia/therapy , Immunoglobulin kappa-Chains , Male , Multiple Myeloma/immunology , Octreotide/therapeutic use , Plasmapheresis , Proinsulin/immunology
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