Coronary heart disease and depression in the elderly--a population- based study

BACKGROUND: Growing interest is nowadays focused on the quality of life of elderly people who survive with chronic diseases. Coronary heart disease (CHD) is one of the most common diseases among the elderly and may have an unfavourable impact on the patient's emotional well-being. OBJECTIVES: We aimed to describe the prevalence of depression and the occurrence of depressive symptoms among elderly CHD patients, with a special emphasis on the relations between depression and the severity of CHD, and to find out the possible association between CHD and depression. METHODS: The study was carried out at the health centre of the municipality of Lieto, in south-west Finland. The study population consisted of 488 community-dwelling men and 708 women, over 64 years old, from among whom the participants with CHD (89 men and 73 women) were selected, and for whom 178 male and 146 female sex- and age- matched controls (free of CHD) were drawn from the population. CHD patients were selected on the basis of the presence of angina pectoris or a past myocardial infarction. Depressive symptoms were measured with the Zung Self-rating Depression Scale. Depression was described in relation to the severity of dyspnoea and chest pain among patients. The associations between depression and age, health, health behaviour, drugs, functional ability and social, psychosocial and environmental factors were analysed by logistic regression analyses. RESULTS: The prevalence of depression was 29% among male patients and 20% among female patients. Depression was significantly more common among male CHD patients than among male controls (P = 0.011). Among women, depression was not associated with CHD. Earlier, depression had gone undiagnosed among many CHD patients and controls, especially male patients. Among male CHD patients, depression was associated with more severe dyspnoea, but no similar association was found among female CHD patients. Among men the occurrence of CHD, physical disability, widowhood or divorce, and among women previous clinical depression, physical disability and the use of angiotensin-converting enzyme (ACE) inhibitors, were associated with depression. CONCLUSION: Depression is common among patients with CHD. It seems that CHD is not an independent factor in the aetiology of depression among the elderly. The association of CHD with depression among men is explained by the acute or chronic psychic stress caused by CHD. It may be that the more complicated the patient's CHD, the more probable is the presence of depression.      

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.     

Necrosectomy and postoperative local lavage in patients with necrotizing pancreatitis: Results of a prospective clinical trial

Seventy-four patients with necrotizing pancreatitis were included in a prospective clinical trial of a surgical management protocol comprising necrosectomy and postoperative local lavage of the lesser sac and of the necrosis cavity. Fifty-eight patients showed preoperative organ failures such as pulmonary dysfunctions (57%), renal dysfunctions (37%), shock (12%), and sepsis (26%) in spite of intensive care treatment. The median value of the early prognostic signs was 4.5 points. Intraoperatively, 62% of the patients revealed extensive intrapancreatic parenchymal necrosis, 69% had extrapancreatic necrosis, and 39% showed bacterial contamination of the necrotic material. Following the necrosectomy, postoperative local lavage was performed for an average period of 25 days with 7 liters (median) of lavage fluid per 24 hours. In each of 18 studied patients, a considerable release of immunoreactive trypsin was demonstrated and, in each of 20 studied patients, a high concentration of immunoreactive phospholipase A₂ was demonstrated in the lavage fluid up to the 12th/14th postoperative day. The intensive care period averaged 6 1/2 days, the hospital stay averaged 54 days. The hospital mortality rate was 8.1%. It is concluded that restricted necrosectomy and postoperative local lavage treatment correspond in particular to the pathomorphologic conditions and to the local release of biologically active compounds such as bacteria, endotoxin, trypsin, and phospholipase A₂ in patients with necrotizing pancreatitis.

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Resumen Setenta y cuatro pacientes con pancreatitis necrotizante fueron incluídos en un ensayo clínico prospectivo aplicando un protocolo de manejo quirÚrgico que comprende necrosectomía y lavado peritoneal postoperatorio de la transcavidad de los epiplones y de la cavidad necrótica. Cincuenta y ocho pacientes exhibierion fallas orgánicas postoperatorias tales como disfunción pulmonar (57%), disfunción renal (37%), shock (12%), y sepsis (26%) a pesar de cuidado intensivo. El valor promedio de los signos précoces pronóstico (Ranson), con exclusión de la retención de líquido fue de 4.5 puntos. Los hallazgos intraoperatorios revelaron necrosis pancreática extensa en 62% de los pacientes, necrosis extrapancreática en 69%, y contaminación bacteriana del material necrótico en 39%. Realizada la necrosectomía se instauró lavado peritoneal postoperatorio por un período promedio de 25 días con 7 litros (promedio) de líquido por cada 24 horas. En cada uno de los 18 pacientes estudiados se demostró liberación considerable de tripsina inmunorreactiva, así como una elevada concentración de fosfolipasa A₂ inmunorreactiva, en el líquido de lavado hasta el 12/14 días postoperatorios. El período de cuidado intensivo fue de 6 1/2 días, y la hospitalización de 54 días en promedio. La mortalidad hospitalaria fue de 8.1%. En conclusión, se plantea que el tratamiento mediante la necrosectomía restringida y el lavado peritoneal local postoperatorio está indicado en pacientes con las condiciones patomorfológicas de pancreatitis necrotizante que resultan en la liberación local de compuestos biológicamente activos tales como bacterias, endotoxina, tripsina, y fosfolipasa A₂. Serán necesarios ulteriores estudios clínicos controlados para confirmar los resultados favorables que hemos obtenido con la necrosectomía y el lavado peritoneal postoperatorio en pacientes con pancreatitis necrotizante y extensa e infectada necrosis pancreática.

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Résumé Un essai prospectif d'une méthode de traitement chirurgical consistant en nécrosectomie associée au lavage de l'arrière cavité des épiploons et de la cavité nécrotique a concerné 74 malades présentant une pancréatite nécrotique. Malgrè le traitement intensif 58 d'entre eux ont accusé des complications telles que troubles pulmonaires (57%), rénaux (37%), choc (12%), et infection (26%). La valeur moyenne des signes de pronostic précoce fut de 4.5 points. A l'intervention 62% des opérés présentaient une nécrose pancréatique étendue, 69% des opérés une nécrose extra-pancréatique, 39% une surinfection du tissu pancréatique. Après l'exèrése de la nécrose le lavage fut pratiqué quotidiennement avec en moyenne 7 litres de liquide pendant une période de 25 jours. Chez 18 malades fut constaté une libération importante de trypsine immunoactive et chez 20 malades un taux élevé de phospholipase cA dans le liquide de lavage pendant 12/14 jours après l'intervention. La durée des soins intensifs fut en moyenne de 6.5 jours et celle de l'hospitalisation de 54 jours. Le taux de mortalité opératoire fut de 8.1%. On peut conclure de ces faits que la nécrosectomie limitée, associée au lavage local constitue un traitement adapté aux lésions et à la libération locale d'éléments biologiques pathologiques: bactérie, endotoxine, trypsine, et phospholipase A au cours de la pancréatite nécrotique.

     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Nasal congestion as a side effect of cromolyn sodium

Cromolyn sodium, a recently introduced antiasthmatic medication, is known occasionally to produce maculopapular and urticarial rashes, and increased bronchospasm. A patient is reported with a previously unpublished side effect of this medication, i.e., severe nasal congestion.     

Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion

Submicroscopic deletions of the Y chromosome and polymorphisms of the androgen receptor (AR) gene in the X chromosome have been observed in men with defective spermatogenesis. To further define the subregions/genes in the Y chromosome causing male infertility and its relationship to polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of 202 subfertile males and 101 healthy fertile controls of predominantly Chinese ethnic origin. Y microdeletions were examined with 16 sequence-tagged site (STS) probes, including the RBM and DAZ genes, spanning the AZFb and AZFc subregions of Yq11, and related to the size of trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions were detected and confirmed in three out of 44 (6.8%) of azoospermic and three out of 86 (3.5%) severely oligozoospermic patients. No deletions were detected in any of the patients with sperm counts of >0.5 x 10(6)/ml, nor in any of the 101 fertile controls. All six affected patients had almost contiguous Y microdeletions spanning the entire AZFc region including the DAZ gene. The AZFb region, containing the RBM1 gene, was intact in five of the six subjects. Y deletions were not found in those with long AR polyglutamine tracts. Our study, the first in a Chinese population, suggest a cause and effect relationship between Y microdeletions in the AZFc region (possibly DAZ), and azoospermia or near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear to be independent contributors to male infertility.      

High level expression of apoptosis inhibitor in hepatoma cell line expressing Hepatitis B virus

The serious result of hepatitis B (HBV) virus infection is development of hepatocellular carcinoma (HCC). However, the reason of development of HCC in HBV infected patients is still unclear. Recently, the suppression of cell apoptosis is found to relate with the development of cell carcinogenesis, therefore, the expression of apoptosis inhibitor in the virus related cancer line such as hepatoma cell line HepG2.215 was investigated. There are at least six Human apoptosis inhibitors (IAP) have been identified now. They are cIAP1, cIAP2, XIAP, NAPI, survivin and pIAP. Using gene-assay technology, we have recently compared the expression of IAPs in the HepG2.215 cells that persistently expresses Hepatitis B virus by integrated HBV genome with its parent cell line HepG2. The results suggest that there was obviously increase of cIAP2 and cIAP1 in the HepG2.215 cells versus HepG2 cells. Those observations imply a possibility of long time HBV infection could induce the over-expressing apoptosis inhibitors, furthermore, causing the liver cancer. The high expression of cIAP1 and cIAP2 in HBV expressing cells was confirmed by RT-PCR and Northern blot analysis. However, we did not find the change of NIAP and suvivin in HepG2.215 cells. In contrast, the expression of XIAP was down in the HepG2.215 cells comparing with HepG2 cells. How HBV triggers the over-expression of apoptosis inhibitor is unclear. Transient transfection of HepG2 cells with the plasmids expressing different HBV proteins such as S, M, L, X and core proteins did not give a decisive conclusion. Further study is going on now.     

Platelet-activating factor (PAF)-dependent biochemical, morphologic, and physiologic responses of human platelets: demonstration of translocation of protein kinase C associated with protein phosphorylation

Platelet-activating factor (PAF) is a potent stimulus for platelet aggregation and secretion. PAF has been shown to stimulate the phosphatidylinositol (PI) pathway in platelets, which implies that PAF should activate protein kinase C. In this study, measurements of PI metabolites, the elevation of intracellular free calcium concentration, (Ca2+)i, the activation of protein kinase C, and the phosphorylation of platelet proteins (using a two-dimensional gel electrophoretic technique) were performed before and after the addition of 10(-8) M PAF to human platelets. These findings were correlated with morphologic changes in the platelets as determined by immunoelectron microscopic studies on the cytoskeleton and by X-ray analysis of dense bodies. The results show that PAF stimulates the production of PI metabolites and causes an increase in the membrane-associated activity of protein kinase C. These changes are accompanied by a rise in the (Ca2+)i and protein phosphorylation. The increase in protein kinase C activity reaches a maximum at approximately 60 s, a time frame that is consistent with the protein phosphorylation and the subsequent morphologic and secretory events. X-ray analysis revealed two types of dense bodies containing various amounts of calcium which appeared to be released sequentially after PAF activation. These results suggest that the protein phosphorylation that controls the physiologic events resulting from PAF activation of human platelets is catalyzed by protein kinase C.     

Hoechst staining and exposure to UV laser during flow cytometric sorting does not affect the frequency of detected endogenous DNA nicks in abnormal and normal human spermatozoa

Controlling the sex of offspring by the separation of X and Y chromosome-bearing spermatozoa using flow cytometry has been reported as a clinical technique aiding prevention of X-linked diseases. Although this technique has resulted in several hundred normal births in animals and at least one human birth, there is still concern over its genetic safety due to the involvement of two potentially mutagenic agents: UV light and the fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly those considered abnormal, may be more likely to suffer DNA damage following exposure to mutagenic agents, compared with other mammalian species. The stability of normal fresh and decondensed human spermatozoa were examined after exposure to a range of levels of UV and H33342 staining, using an assay that detects endogenous nicks in the DNA of spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed human spermatozoa was examined following UV laser, H33342 staining and flow cytometry treatments utilizing the same assay. There was an increase in the presence of endogenous nicks when spermatozoa were decondensed compared with fresh spermatozoa. There was no increase in the incidence of nicks in any group of spermatozoa after UV and fluorochrome exposure compared with controls without exposure.      

Modulation of disease severity of dystrophic epidermolysis bullosa by a splice site mutation in combination with a missense mutation in the COL7A1 gene

Dystrophic epidermolysis bullosa (EBD) is a clinically heterogeneous skin disorder, characterized by abnormal anchoring fibrils (AF) and loss of dermal-epidermal adherence. EBD has been linked to the COL7A1 gene at chromosome 3p21 which encodes collagen VII, the major component of the AF. Here we investigated two unrelated EBD families with different clinical phenotypes and novel combinations of recessive and dominant COL7A1 mutations. Both families shared the same recessive heterozygous 14 bp deletion at the exon-intron 115 boundary of the COL7A1 gene. The deletion caused in-frame skipping of exon 115 and the elimination of 29 amino acid residues from the pro-alpha1(VII) polypeptide chain. As a result, procollagen VII was not converted to collagen VII and the C-terminal NC-2 propeptide which is normally removed from the procollagen VII prior to formation of the anchoring fibrils was retained in the skin. All affected individuals also carried missense mutations in exon 73 of COL7A1 which lead to different glycine- to-arginine substitutions in the triple-helical domain of collagen VII. Combination of the deletion mutation with a G2009R substitution resulted in a mild phenotype. In contrast, combination of the deletion with a G2043R substitution led to a severe phenotype. The G2043R substitution was a de novo mutation which alone caused a mild phenotype. Thus, different combinations of dominant and recessive COL7A1 mutations can modulate disease activity of EBD and alter the clinical presentation of the patients.