Cardiovascular sequelae and risks of obesity

Obesity is a well documented separate risk factor for metabolic and vascular diseases which may reduce life expectancy for overweight people. This is expected to create soon a major health economic problem in more or less all western countries because the numbers of morbidly obese people increase steadily. It is a type of visceral android fat deposition which bears a high risk to develop vascular remodelling processes causing coronary and cerebral artery disease with all its consequences. The various biochemical processes which may contribute to cause these vascular lesions in obesity are discussed by the author and the various resulting clinical findings are described. Further the chance is emphasized to reduce by weight reduction the risks of obesity since regression of vascular changes may result by an even moderate loss of weight.     

Chromosome abnormalities associated with recurrent abortion

A continuous flow analysis system for the preconcentration of Cu2+ and/or Cd2+ in water was developed. Trace copper or cadmium in water could be concentrated on activated carbon particles packed in micro column at pH > or = 9.0. The adsorbed analyte was eluted with 0.5 ml 2.5% nitric acid and determined by flame atomic absorption spectrometry. A sample size of 10-25 ml sufficed for the determination of copper2+ or cadmium at a level as low as microgram/L. The relative standard deviation of 6 parallel determinations was 4.3% for copper and 11% for cadmium. The proposed method was applied to the determination of copper and cadmium in natural water with a recovery of 84.4%-118%.     

Cardiovascular malformations associated with choanal atresia

In this study, cardiovascular malformations were present in 11 of 63 (17.5%) patients with choanal atresia. The most frequently encountered cardiac lesions were ventricular septal defect and patent ductus arteriosus, while cyanotic heart disease was uncommon.     

Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease

It is known that adults with autosomal dominant polycystic kidney disease (ADPKD) have an increased incidence of cardiovascular abnormalities, including mitral valve prolapse. The cardiac manifestations of ADPKD in the pediatric population have not been well established. To determine the cardiac manifestations of children with ADPKD, echocardiography was performed in 154 children of 66 families in which one parent has ADPKD. Eighty-six affected children and 68 unaffected children were evaluated in a prospective, single-blinded manner by echocardiography. Affected children were defined as those with any cysts on a concurrent renal ultrasound or those predicted to be gene carriers by gene linkage analysis. A 12% incidence of mitral valve prolapse was found in the affected children compared with only 3% of the unaffected children (P < 0.05). ADPKD children, but not their unaffected siblings, demonstrate a significant correlation between left ventricular mass index and systolic blood pressure. Moreover, hypertensive ADPKD children have significantly larger left ventricular mass index than do normotensive ADPKD children. A 3.5% incidence of congenital heart disease was found in the affected group, whereas 2.9% of the unaffected children had congenital heart disease. It was concluded that systemic manifestations of ADPKD, particularly cardiovascular abnormalities, are present even in childhood and these warrant the clinician's attention.     

Prader-Willi and other syndromes associated with obesity and mental retardation

Constitutional obesity and mental retardation cooccur in several multiple congenital anomaly syndromes, including Prader-Willi syndrome, Bardet-Biedl syndrome, Cohen syndrome, Albright hereditary osteodystrophy, and Borjeson-Forssman-Lehmann syndrome as well as some rarer disorders. Although hypothalamic-pituitary axis abnormalities are thought to be a possible causative mechanism in some of these disorders, current knowledge is insufficient to explain the pathophysiologic mechanism of obesity in most multiple congenital anomaly/mental retardation syndromes. The chromosomal location of many of these syndromes is known, and studies are ongoing to identify the causative genes. Further delineation of the functions of the underlying genes will likely be instructive regarding mechanisms of appetite, satiety, and obesity in the general population. This review details current knowledge of the clinical and molecular genetic findings of multiple congenital anomaly/mental retardation syndromes associated with intrinsic obesity in an effort to delineate causative mechanisms and genetic abnormalities contributing to obesity.     

Unsuspected pulmonary vascular abnormalities associated with diaphragmatic hernia

The pulmonary vasculature of 12 newborn infants who died with unilateral diaphragmatic hernias was studied. Four developed severe ventilatory insufficiency after birth and promptly died. Their lungs were both hypoplastic and airless dur to compression by displaced abdominal viscera and mediastinal shift. Corrective surgery permitted lung expansion and adequate ventilation for one to two hours in five infants. Subsequently, ventilatory insufficiency supervened and they died. Postoperative blood gases revealed a right-to-left ductus arteriosus shunt in one infant. Ten of the infants with hernias had a significantly greater mass of muscle in pulmonary arteries than did matched controls. This may partially explain the fetal-type circulatory infants.     

Chorioretinal vascular abnormalities associated with angioid streaks and pseudoxanthoma elasticum

OBJECTIVE: To analyze the retinal and choroidal vascular abnormalities in eyes with angioid streaks (AS) associated with pseudoxanthoma elasticum (PXE). METHODS: Color photographs and fluorescein angiograms of 54 eyes of 27 consecutive patients with AS and PXE were examined retrospectively. RESULTS: Four (7%) of the 54 eyes had a major vascular abnormality at the level of the disc; this took the form of a large vascular loop corresponding to an arteriovenous communication between retina and choroid in 3 eyes (6%) and an anastomosis between 2 retinal arteries in 1 eye (2%). CONCLUSION: Analysis of the vascular network in these eyes showed several vascular abnormalities, among which chorioretinal arteriovenous communications appear to be the most dramatic.     

Duration of breastfeeding associated with obesity during adolescence

The relationship between duration of breastfeeding and obesity (body mass index > or = 85 percentile) at adolescence was investigated in a white, rural population (n = 136) in which confounding by race was absent and confounding by socioeconomic status was expected to be minimal. Relevant data were abstracted from hospital charts. When examined independently, minimal (< or = 2 months) or no breastfeeding was positively associated with adolescent obesity (p < 0.03). This association was present in the lower but not the higher socioeconomic status group. However, when sex, birthweight, and socioeconomic status were included in a multiple regression model, duration of breastfeeding was no longer significantly associated with obesity during adolescence.     

Cardiovascular changes associated with aging: the anesthetic implications

PURPOSE: Elevated arterial lactate concentrations in patients with sepsis have been interpreted as evidence of peripheral, nonpulmonary tissue hypoxia. These patients often develop pulmonary failure manifested by the acute respiratory distress syndrome (ARDS). As the result of tissue hypoxia or inflammation, the lungs of patients with sepsis and ARDS may become a source of lactate release into the circulation. MATERIALS AND METHODS: Pulmonary lactate release was measured in 19 patients with sepsis, arterial lactate > or = 2.2 mm, and gastric mucosal pH > 7.30. A normal gastric mucosal pH served as a marker of adequate splanchnic oxygenation. Pulmonary lactate release was computed as the product of the cardiac index and the difference in plasma L-lactate concentration in simultaneously obtained arterial and mixed venous blood samples. Lung injury was graded with the Lung Injury Score using radiographic and physiologic data. RESULTS: The lungs of patients with minimal or no lung injury (lung injury score <1) produced significantly less lactate than those with moderate or severe lung injury (lung injury score > or = 1) (P < .005). The Lung Injury Score correlated with pulmonary lactate release (r2 = .73; P < .0001). This relationship resulted primarily from increases in mixed venous-arterial lactate differences (r2 = .59). The Lung Injury Score correlated weakly with the cardiac index (r2 = .32). Arterial lactate concentration did not correlate with pulmonary lactate release, systemic oxygen transport, or systemic oxygen consumption. CONCLUSIONS: The lungs of patients with sepsis and ARDS may produce lactate. Pulmonary lactate release correlates with the severity of lung injury. The contribution of pulmonary lactate release should be considered when interpreting arterial lactate concentration as an index of systemic hypoxia.     

Absence of linkage of obesity and energy metabolism to markers flanking homologues of rodent obesity genes in Pima Indians

The homologues of single genes that cause obesity in rodents are suggested as candidate genes for modulation of body composition in humans. Among these genes are the four mouse mutations-diabetes (db), obesity (ob), tubby (tub), and yellow agouti (Ay). Variation in the human counterparts to these genes (OB, DB, TUB, and ASP, respectively) may contribute to human obesity, which is thought to have a substantial genetic component. To initially assess the potential contribution of these genes to human obesity, we examined polymorphic DNA markers that, by virtue of syntenic relationships to appropriate regions of the mouse genome, should be closely linked to the human counterparts of these genes. Using combined data from 716 Pima Indians comprising 217 nuclear families, we have tested a number of polymorphic microsatellite markers (three at DB, two at OB, five at TUB, and three at ASP) for sib-pair linkage to BMI, percentage body fat, resting metabolic rate, 24-h energy expenditure, and 24-h respiratory quotient. No significant linkages were found in an analysis of all sibships or in an analysis restricted to discordant sib pairs.     

Cardiovascular abnormalities in Kawasaki disease. An Italian prospective study

We report a prospective study performed over a 9 year period in 96 children with Kawasaki disease (mean age 35 +/- 29 months), 84 of whom < 5 years of age. The male/female ratio was 1.5 (57/39). A total of 38 patients had cardiac involvement, including flattened T waves in the ECG (10 patients), pericardial effusion (6 patients), myocarditis (1 patient), and coronary artery aneurysms (25 patients; frequency of aneurysms: 26%). All patients were evaluated during the acute phase (first month) of the illness. The first echocardiographic examination was performed 15 days (range 4.30 days) from the appearance of fever, and coronary aneurysms were observed in 23 patients; in 2 patients, however, aneurysms appeared later (2 and 6 months). Aneurysms were small (< or = 4.5 mm) in 12, medium (4.5-7 mm) in 11, and large (> 7 mm) in 12 patients. Male sex (p = 0.02), age < 12 months (p = 0.005), ESR (p = 0.001), platelet count (p = 0.009), and pericardial effusion (p = 0.02) were significantly related to the presence of aneurysm. Among females, incidence of aneurysms was significantly higher in infants < 12 months than in older patients (60 vs 6%, p < 0.001). Intravenous immunoglobulin treatment was started early (within 10 days) in 61 patients and late (> 10 days) in 22. Compared to late treatment, early i.v. immunoglobulin treatment was associated with smaller aneurysms and higher regression rate (67 vs 28%, p < 0.05). No difference was observed concerning frequency and number of dilated vessels as related to therapeutical regimens. Total i.v. immunoglobulin dose (2 g/kg) was administered over 1-2 days in 26 patients (scheme I) or over 4-5 days in 58 (scheme II). Frequency of aneurysms was significantly lower in patients treated early (p = 0.02). No myocardial infarctions or deaths occurred at short- or long-term follow-up.     

Analysing human developmental abnormalities

About one in forty babies is born with a recognisable congenital anomaly at birth. Rapid progress is being made in recognising the genetic contribution to these defects. From over 2000 likely single gene malformation syndromes in humans the gene has been isolated or mapped in about 10%. Despite the availability of animal models, the study of malformations in humans continues to reveal novel genes and unpredicted functions for known genes. The importance of the study of clinical malformations to the understanding of embryological development in humans and other organisms is discussed and reviewed.     

Congenital perilymphatic fistula and associated middle ear abnormalities

An analysis of central microbial keratitis with respect to etiology, recovery, complications and visual outcome was carried out in Gothenburg, Sweden, during a 3-year period. Gram positive bacteria were found in 22 out of 48 cases; Staphylococcus aureus and Staphylococcus epidermidis accounted for more than 50% of these Gram positive cases. Pseudomonas was the most common Gram negative bacterium. No case with etiology of fungus was found. The contact lens wearers showed mainly the same bacterial spectrum as non-wearers. The initial 'shotgun' therapy with cefuroxime and gentamycin seemed adequate for this bacterial spectrum. Seventy percent of the eyes healed within 3 weeks. Contact lens wear and trauma were found to be the two major predisposing factors in the cases with microbial keratitis. The lens wearers had shorter recovery times than the non wearers. The visual results after one month were good in 50% of the eyes, and another 12% attained useful vision.     

Intracoronary ultrasound assessment of morphological and functional abnormalities associated with cardiac allograft vasculopathy

BACKGROUND: The diffuse nature of cardiac allograft vasculopathy makes early detection of the disease by traditional noninvasive methods or coronary angiography difficult. The aim of this study was to determine if there is a relation between abnormalities in vessel wall morphology, as assessed by intracoronary ultrasound, and a decreased vasodilatory response to the endothelium-dependent vasodilator papaverine hydrochloride and if cardiac allograft vasculopathy detected by coronary angiography is associated with specific intracoronary ultrasound findings. METHODS AND RESULTS: Twenty-three heart transplant recipients underwent 25 intracoronary ultrasound studies and 24 studies of coronary vasomotor tone 10 days to 8.3 years after surgery using a 20-mHz intracoronary ultrasound catheter. The studies were divided in two groups according to the presence (n = 7, group 1) or absence (n = 18, group 2) of angiographically evident cardiac allograft vasculopathy. Qualitative assessment of vessel wall morphology and quantitative analysis of the vasodilator response to the injection of papaverine hydrochloride into the coronary artery distal to the imaging site were performed off-line, and results for the two study groups were compared. A significantly higher percentage of patients with than without angiographic evidence of cardiac allograft vasculopathy had a three-interface vessel wall morphology by intracoronary ultrasound (100% versus 11%, P < .001). In two recipients who underwent two serial studies, the appearance of three interfaces in the vessel wall or a progressive thickening of the inner interface of the vessel wall occurred in conjunction with the appearance of angiographic cardiac allograft vasculopathy. The vasodilator response to papaverine was less in patients with than in those without angiographically evident cardiac allograft vasculopathy both in terms of absolute and relative increases in lumen diameter (+0.1 +/- 0.12 mm versus +0.3 +/- 0.17 mm, P < .05, and +5.1 +/- 5.3% versus +8.2 +/- 5.3%, P = NS) and lumen cross-sectional area (+0.5 +/- 0.6 mm2 versus +1.7 +/- 1.1 mm2, P < .02, and +7.1 +/- 8.8% versus 16.6 +/- 11.0%, P = .055), respectively. CONCLUSIONS: Intracoronary ultrasound assessment of vessel wall morphology and evaluation of vascular response to endothelium-dependent vasodilators are useful techniques for detecting cardiac allograft vasculopathy.     

Abdominal obesity and associated cardiovascular comorbidities in the elderly

An abnormally high mortality from atherosclerotic cardiovascular (CV) accidents has long been reported in patients on maintenance hemodialysis (HD). However, incidence of such complications had not been so far evaluated in chronic renal failure (CRF) patients not yet on dialysis. In a cohort study bearing on 232 predialysis CRF patients, followed as out-patients at Necker hospital, incidence of first myocardial infarction (MI) was three times higher than in the French general population in every age group and in both genders, with a mean (+/- SEM) age at onset of MI of 62.9 +/- 1.2 years. In a retrospective cooperative study involving 748 patients treated in 9 hemodialysis centers in the Ile-de-France area, incidence of first MI episodes did not differ before and after start of HD therapy and was similar to that observed in the cohort study. Mean age of patients at first MI, before and after start of HD, was respectively 62.4 +/- 1.6 and 63.7 +/- 1.5 years, a not significant difference. In conclusion, two epidemiologic studies confirm the existence of accelerated atherosclerosis in CRF patients, the incidence of MI being 3 times higher in uremic patients than in the general population in every age group and in both genders. The fact that incidence of first MI episodes and age at onset was similar in predialysis and in dialyzed patients suggests that the uremic state per se is a main determinant of such accelerated atherosclerosis. It results that therapeutic measures aimed at preventing development of atherosclerosis should be initiated from the early stage of CRF, long before start of renal replacement therapy.     

p53 abnormalities in CLL are associated with excess of prolymphocytes and poor prognosis

To determine the role of the p53 gene in chronic lymphocytic leukaemia (CLL) and its possible involvement in the pathogenesis of a progressive form of CLL characterized by > 10%, prolymphocytes (CLL/PL), we selected 32 cases, 17 with typical morphology and 15 CLL/PL. The extent of inactivation of p53 was examined by assessing loss of heterozygosity (LOH) at 17p13.3, by sequencing the highly conserved region (exons 5-9) of the p53 gene and by analysing p53 protein expression. LOH was detected in 8/28 (29%) cases, p53 mutations in 5/32 (16%) cases and p53 expression in 5/27 (19%) cases. Overall 11 cases (30%) had p53 abnormalities of which eight cases had CLL/PL. There was a significant association between CLL/PL and p53 abnormalities (P=0.05); 75% of cases with LOH, 80% of p53 mutations and 80% of cases positive for p53 protein had CLL/PL. Thus, p53 inactivation is the first gene abnormality identified so far to be involved in the development of CLL/PL. All the cases with typical CLL and p53 abnormalities had only one allele affected whereas 4/6 CLL/PL had both alleles inactivated. This difference in the extent of p53 inactivation suggests that accumulation of p53 abnormalities may be associated with progression of CLL to CLL/PL. CLL cases with p53 abnormalities were characterized by a higher incidence of stage C (P<0.025), a higher proliferative rate (P=0.05), short survival (P<0.005) and resistance to first-line therapy (P<0.02) but not to nucleoside analogues. Analysis of the correlation between p53 status and incidence of trisomy 12 by fluorescence in situ hybridization (FISH) showed that trisomy 12 was more frequent in cases without p53 abnormalities, suggesting that trisomy 12 and p53 may represent different pathways of transformation in CLL.