Value of body mass index in the detection of severe malnutrition: influence of the pathology and changes in anthropometric parameters.

BACKGROUND & AIMS: We have estimated the prevalence of severe malnutrition in groups of patients hospitalized for different medical causes and assessed the sensitivity of BMI in the diagnosis of severe malnutrition. DESIGN: A prospective study enrolled 1052 patients: 396 patients with liver cirrhosis including 165 non-ascitic patients (NAP), 124 patients with mild ascites (MAP), 107 patients with tense ascites (TAP), 251 patients after cardiac surgery (SCP), 81 patients with cardiac diseases (MCP), 85 patients with stroke (SP), 36 patients with degenerative neurological diseases (DNP), 68 patients after surgery of a hip fracture (HFP), 91 patients with palliative care for cancer (CP) and 44 elderly patients with medical affections (EP). BMI, mid-arm muscular circumference (MAMC) and triceps skinfold thickness (TST) were measured within 48 h after admission. Patients with MAMC and TST below the 5th percentile of a reference population when aged < or = 74 or the 10th percentile when aged > or = 75 were defined as severely malnourished. Sensitivity of BMI < 20 to detect malnutrition was assessed. RESULTS: The prevalence of severe malnutrition was the highest in TAP (39.1%) HFP (25.6%) and MAP (24.3%) and the lowest in SCP (4%), SP (4.8%), DNP (5.7%) and MCP (7.4%) (P < 10(-4)). In multivariate analysis, low TST was associated with female gender (P < 10(-4)) mild and tense ascites (P = 0.038, P = 0.0004), low MAMC with male gender (P < 10(-4)), low BMI with female gender (P = 0.0082), hip fracture (P = 0.0407) and cancer (P = 0.0059). The sensitivity of BMI to detect severe malnutrition was the highest in HFP, CP and EP (100%, 80% and 100% respectively) and the lowest in TAP, MCP and SP (40%, 33.3% and 50% respectively). After exclusion of TAP, sensitivity of BMI to detect malnutrition correlated significantly with the coefficient of correlation between MAMC and TST observed in each group (r = 0.821, P = 0.0066). CONCLUSION: Ascitic cirrhotic patients and elderly patients after surgery of hip fracture had the highest prevalence of severe malnutrition. BMI had the highest sensitivity when both TST and MAMC were damaged to the same extent. BMI < 20 has a high sensitivity in the diagnosis of severe malnutrition in elderly and cancer patients but not in cirrhotic patients with tense ascites, cardiovascular and neurological patients.

Altered balance between matrix gelatinases (MMP-2 and MMP-9) and their tissue inhibitors in human dilated cardiomyopathy: potential role of MMP-9 in myosin-heavy chain degradation.

BACKGROUND: End-stage of human dilated cardiomyopathy (DCM) is characterized by myocyte loss and fibrosis, and associated with ventricular dilatation and reduced cardiac function. Matrix metalloproteinases (MMPs) and their natural tissue inhibitors (TIMPs) have been involved in the myocardial remodeling. AIMS: To evaluate the potential role of matrix gelatinases (MMP-2 and MMP-9) in DCM, the balance between gelatinases and TIMPs and the gelatinase localization were investigated in left free wall ventricles from six normal donors and six patients with DCM at the transplantation time. METHODS: TIMP-(1, 2, 3 and 4) mRNAs were analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). TIMP-1 and -2 protein content was assessed by ELISA. MMP-2 and MMP-9 expression were examined by zymography and immunological techniques. RESULTS: All TIMPs were down-regulated in DCM hearts, especially TIMP-1 (reduced by 80%). Gel zymography revealed similar activity of MMP-2 and MMP-9 in both tissues. By in situ zymography and immunohistochemistry, active and immunoreactive gelatinases were pericardiomyocyte in control hearts and intracardiomyocyte in DCM hearts. Intracellular MMPs were associated with sarcomeric structure in DCM. To estimate a putative role of these gelatinases, several sarcomeric contractile proteins were digested in vitro by purified active MMP-9. Only myosin-heavy chain was cleaved in vitro giving 180-, 120-, 80- and 20-kDa proteolytic fragments. In vivo, two major myosin-heavy chain proteolytic fragments (80 and 20 kDa) were detected by specific monoclonal antibody against myosin-heavy chain in DCM left ventricular homogenates, only. CONCLUSIONS: Taken together, these data highly suggest that MMP-2 and MMP-9 may be involved in the disorganization of the contractile apparatus in DCM hearts.

Protein kinase C isoform expression in normal and failing rabbit hearts.

Protein kinase C (PKC) is activated by alpha-adrenergic stimulation. Molecular analysis showed that PKC consists of a family of at least 12 isozymes. Studies of their distribution in the heart showed conflicting results. The first goal of our study was thus to characterize cardiac PKC in normal rabbits. PKC plays an important role in gene expression, cell growth, and differentiation and is involved in the hypertrophy phase of cardiac overload, but since its expression has never been evaluated in heart failure, the second goal of our study was to evaluate PKC activity and isoform expression in rabbits with heart failure induced by a double hemodynamic overload (aortic insufficiency followed by an aortic stenosis). In the first part of the study, PKC isoform expression analyzed in normal rabbits by immunoblotting showed that isoforms alpha, beta, epsilon, and zeta were expressed along with PKC gamma, which had never been detected in the heart. PKC gamma expression was also identified by polymerase chain reaction, and immunofluorescence techniques showed a localization on intercalated disks associated with the membrane localization observed with the other isoforms. In the second part of the study, PKC activity, content, and isoform expression showed a decrease of 37% in the failing group. PKC immunodetection with a monoclonal antibody (Mab 1.9) recognizing the catalytic domain of all PKC isoforms revealed a 20% decrease in the failing ventricles compared with normal left ventricles. Expressed PKC isoforms quantified by Western blot showed, in the failing heart group compared with the control group, a decrease of 27%, 32%, 16%, and 9% of PKC alpha, PKC beta 1, PKC gamma, and PKC epsilon, respectively, whereas PKC zeta was not significantly modified. These results show that, in heart failure, PKC activity and expression of Ca(2+)-dependent PKC isoforms are decreased. This may lead to alterations of PKC-induced phosphorylations.

Hydroxocobalamin vs cobalt toxicity on rat cardiac and diaphragmatic muscles.

BACKGROUND: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles. METHODS: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect. RESULTS: During the study period, no significant increase in body weight was noted in the cobalt-treated group (-4 +/- 1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and the saline-treated group (22 +/- 2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/- 16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P < 0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs cobalt-treated group). CONCLUSION: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning.

In vivo comparative study of two lactobionate based solutions for prolonged heart preservation.

The duration of safe heart preservation must be improved. Using a heterotopic heart transplantation model, we compared in vivo the recovery of rabbits hearts preserved with a K+Lactobionate based fluid (UW: University of Wisconsin solution) or with a Na+Lactobionate based fluid. In the "preservation" group, hearts were cold stored (4 degrees C) for 6 hours with UW (n = 9) or Na+Lactobionate solution (n = 9). In the "transplantation" group, cold storage was followed by 3 hours of reperfusion (UW: n = 8, Na+Lactobionate solution: n = 7). Functional recovery, adenine nucleotide pool, circulating blood cardiac enzymes, circulating blood and tissue malondialdehyde (MDA) were measured. Left ventricular end-diastolic and developed pressures at different preload levels were better after preservation with UW than with Na+Lactobionate solution (p < 0.05). Also with UW, adenosine diphosphate and total adenine nucleotide content were significantly higher than with Na+Lactobionate solution (p < 0.05) whereas adenosine triphosphate, monophosphate and energy charges were similar. Cardiac enzymes and tissue MDA were similar with UW and Na+Lactobionate solution. In circulating blood, MDA was not detected. These results enhance the superiority of UW solution over a Na+Lactobionate based solution for long term heart preservation.

Sarcoplasmic reticulum function abnormalities in rabbit failing hearts.

In a model of heart failure induced in rabbits by a double volume plus pressure overload, sarcoplasmic reticulum (SR) function was measured by Ca uptake and ryanodine receptor analysis. When expressed per mg of proteins, Ca uptake was decreased by 20% in failing hearts (FH) and ryanodine receptor density was similar in control hearts (CH) and in FH. However Ca uptake and ryanodine receptor density were significantly increased when expressed per total left ventricle suggesting SR hypertrophy. On electron microscopic examination, SR morphology not directly examined but large hypertrophied T tubules were observed suggesting a change in the relationship between membranes and contractile apparatus which may lead to alterations in excitation-contraction-relaxation coupling in spite of minimal biochemical alterations of SR.

Cardiac ultrastructural abnormalities in Syrian hamsters with spontaneous cardiomyopathy or subjected to cardiac overloads.

Ultrastructural and morphometric abnormalities of Syrian hamster cardiomyopathy were compared to those observed in two different models of cardiac hypertrophy produced by mechanical overload (abdominal aortic stenosis, 60-day duration) or by isoproterenol injection during 15 days in normal Syrian hamsters of the same strain. Aspects of increased protein synthesis were observed in all three groups of animals. This was the only abnormality observed in the aortic stenosis group. Cardiomyopathy was different from the two other types of overload by the existence of large calcium deposits inside of the myocytes, by the presence of thin filaments and amorphous material accumulation suggesting abnormal synthesis and by a significant reduction of myofibrils at the heart-failure phase. Nuclear abnormalities with nuclear constrictions suggesting a division process and an increased number of myocytes with two nuclei were present in both spontaneous cardiomyopathy and isoproterenol-induced cardiopathy. Therefore, Syrian hamster cardiomyopathy appears to be different from cardiopathy induced by hemodynamic overload but, in spite of specific aspects, resembles that induced by isoproterenol injections, strengthening the hypothesis of a pathogenic role of catecholamines in the Syrian hamster cardiomyopathy.

Relationship of myocardial morphometry in aortic valve regurgitation to myocardial function and post-operative results.

In 24 patients with aortic insufficiency undergoing aortic valve replacement, a clinical and hemodynamic study was performed pre-operatively. Left ventricular biopsies were obtained perioperatively for morphometric study. No significant relations were found when morphometric data were compared to functional class, cardiothoracic radio and ECG findings. The percentage of interstitial fibrosis was not correlated with any of the measured hemodynamic parameters. Myocardial cell diameter was weakly correlated with left ventricular systolic function parameters. A decrease in the percentage of contractile material was strongly correlated with an impaired left ventricular function, assessed pre-operatively. During clinical follow-up, patients were divided into two groups: Group A (17 patients) included patients who were in class I or II of NYHA after surgery. Group B (seven patients) included patients who died or were in functional class III or IV. As compared with Group A, Group B patients had a significantly lower ejection fraction; their myocardial cell diameter was larger and the percentage of myofibrils, and the content of contractile material were significantly lower. This suggests that, in aortic regurgitation, left ventricular dysfunction is correlated with contractile material loss and not with interstitial fibrosis, and that morphometric changes are good predictors of follow-up after surgery.

Reduced coronary flow and resistance reserve in primary scleroderma myocardial disease.

The maximum coronary vasodilator capacity after intravenous dipyridamole (0.14 mg X kg-1 X min-1 X 4 minutes) was studied in seven patients with primary scleroderma myocardial disease and compared to that of seven control subjects. Hemodynamic data and left ventricular angiographic data were not different in the two groups. The coronary flow reserve was evaluated by the dipyridamole/basal coronary sinus blood flow ratio (D/B CSBF) and the coronary resistance reserve by the dipyridamole/basal coronary resistance ratio (D/B CR). Coronary reserve was greatly impaired in the group with primary scleroderma myocardial disease: D/B CSBF was lower than in the control group (2.54 +/- 1.37 vs 4.01 +/- 0.56, respectively; p less than 0.05) and D/B CR was higher than in the control group (0.47 +/- 0.25 vs 0.23 +/- 0.04, respectively; p less than 0.05). Such a decreased coronary flow and resistance reserve in patients with primary scleroderma myocardial disease was not explained by an alteration of left ventricular function. It may be an important contributing factor in the pathogenesis of primary scleroderma myocardial disease.

Decreased coronary reserve in primary scleroderma myocardial disease.

We assessed coronary reserve, by measuring the increase in coronary sinus blood flow (CSBF) after intravenous administration of dipyridamole (0.14 mg/kg/minute for 4 minutes), in 7 patients with primary scleroderma myocardial disease (PSMD) and in 7 control subjects. Coronary reserve was greatly impaired in PSMD: before administration of dipyridamole, CSBF was similar in patients with PSMD (89 +/- 32 ml/minute/100 gm, mean +/- SD) and in controls (100 +/- 15 ml/minute/100 gm); after dipyridamole infusion, CSBF was significantly lower in patients with PSMD (191 +/- 45 ml/minute/100 gm) than in controls (399 +/- 58 ml/minute/100 gm) (P less than 0.01). Six of the 7 patients with PSMD had angiographically normal epicardial coronary arteries and normal left ventricular function. Decreased coronary reserve may be an important contributor to the pathogenesis of primary scleroderma myocardial disease.

Myocardial cell nucleus in cardiac overloading in the rat.

The myocardial cell nucleus was studied in the rat during its normal growth and under different types of heart overloading. Under overloading of short duration, a disappearance of condensed chromatin and an increase in the nucleolus and nucleolonema were interpreted as representing cell overactivity. With isoproterenol overloading, a first stage of cell necrosis and of its consequences on chromatin and nucleolus was followed by the process of cell repair and overactivity. With overloading of long duration, several different nuclear aspects were encountered: (a) enlarged and distorted nuclei as possible supports of polyploidy; (b) a partial coupling between two adjacent nuclei, interpreted either as nuclear fusion or amitosis; (c) segregation of different proteins, probably due to cell damage. The number of nuclei per myocyte was high (90%) in the adult. It decreased (80%) two days after isoproterenol overloading, as well as in heart hypertrophy of 6-9-months duration. Nuclear size increased under isoproterenol overdosage of 48-h duration. The amount of nuclear DNA also increased two days after isoproterenol overdosage, particularly in mononucleated cells.

[Histological and ultrastructural study of the left ventricular myocardium in mitral stenosis. Correlations with angiocardiographic indices of left ventricular function. Eleven cases]. / Etude histologique et ultrastructurale du myocarde ventriculaire gauche dans le rétrécissement mitral. Corrélations avec les indices angiocardiographiques de fonction ventriculaire gauche à propos de 11 observations.

Left ventricular myocardial biopsy was carried out at operation in 11 patients with pure, isolated mitral stenosis after preoperative angiocardiographical assessment of left ventricular function. The biopsy specimens were examined by light and electron microscopy. The diameter of the myocytes was normal (20 +/- 1.6 mu). The changes observed were probably of a degenerative type with anarchy and irregularities in the sarcomeres, modification of the Z bands, as seen in Nemaline myopathies, and changes in the intercalatory discs. Moderate interstitial fibrosis with scanty histiocytes was also observed. A quantitative assessment by two dimensional planimetry showed a significant increase in the interstitial space (37 +/- 5.5%) compared to a control group without fibrosis (22 +/- 1.1%). The angiocardiographical indices of left ventricular function were all decreased. The amplitude of circumferential fibre shortening was reduced: 25 +/- 6% the ejection fraction by 52 +/- 9% and the average speed of circumferential fibre shortening by 1.0 +/- 0.3 circ/s. Only four patients had normal left ventricular function (ejection fraction > 55%). However, it was not possible to establish a significant correlation between the degree of fibrosis and the reduction in left ventricular function. Left ventricular fibrosis may be one of the factors responsible for the reduction of myocardial function, but it does not in itself explain all the changes in left ventricular function observed in mitral stenosis.

Ultrastructural and histological study of left ventricular myocardium in mitral stenosis. Correlations with angiocardiographic indices of left ventricular function (in 11 observations).

Left ventricular myocardial biopsies were performed during surgery in 11 patients with pure and isolated mitral stenosis. Patients had undergone a preoperative angiocardiographic study of left ventricular function. Biopsy specimens were examined with the light and electron microscope. Myocyte cell diameter was normal (20 +/- 1.6 mu). Lesions existed which were probably degenerative, including anarchy and irregularities of sarcomeres, Nemaline Myopathy-type Z line changes and alterations of intercalated discs. A moderate fibrosis was found in the interstitial spaces with very few histiocytes. The coincidence planimetry study of the interstitial spaces showed a 37 +/- 5.5% increase compared to a control group with no fibrosis (23 +/- 1.5%, p less than 0.01). The angiocardiographic indices of left ventricular function were all decreased. Only four subjects had normal left ventricular function (EF greater than or equal to 55%). Nevertheless, it was not possible to establish a significant correlation between the extent of fibrosis and the decrease of left ventricular function. Although left ventricular fibrosis could be one of the factors responsible for decreased myocardial function, it is not sufficient to explain the changes of left ventricular function which are rather frequently observed in mitral stenosis.

[Endomyocardial biopsy results and left ventricular function in primary myocardiopathies (author's transl)]. / Résultats de la biopsie endomyocardique et fonction ventriculaire gauche dans les myocardiopathies primitives.

Endomyocardial biopsies (EMB) of the left ventricle (LV) were performed during cardiac catheterization in 27 patients with apparently primary myocardiopathies (PMC). The results of optical and electron microscopy were compared with ventricular performance indices calculated from hemodynamic and cinematographic data from the left ventricle. The telediastolic pressure of the LV increases with the spread of fibrosis (r = 0.68) suggesting that it disturbs the filling of this cavity. Systolic effort is reduced as this fibrosis increases (r = 0.56), and it contributes to the changes in the pumping function of the LV, but the contractile power of the LV is altered in a less evident and less constant manner. The association of cell and fibro-elastic tissue degeneration is always accompanied by a drop in ventricular performance (p less than 0.0001). Apart from its diagnostic role, which is limited but may be of great value, the EMB can help to clarify the physiopathology of PMC and to formulate a prognosis based on more solid grounds.

Development and reversal of pressure-induced cardiac hypertrophy. Light and electron microscopic study in the rat under temporary aortic constriction.

Light and electron microscopy, combined with morphometry, were utilized to study myocardial cell modifications induced by a temporary abdominal aortic constriction in the rat. During the early stage of active hypertrophy, cell enlargement in the subendocardial layers of the left ventricle was predominant. This enlargement may be partly due to intracellular edema, characteristic of cell damage. Degenerative foci leading to fibrous scars were found primarily in the subendocardium and midwall layers. The times taken by the different cell structures to adapt to modifications of the load were rather different; some adapted very rapidly (nucleoli, intercalated discs), while others were much slower (cell diameter, mitochondria).