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Biomedical subjects

P Kieffer

Publications and source records attributed to P Kieffer.

At least 19 recordsLinked to original sources

[A young woman with granulomatous mastitis: a corynebacteria may be involved in the pathogenesis of these disease].

INTRODUCTION: The granulomatous mastitis is an inflammatory pseudotumor of the breast of which evolution benign but likely to generate important morphological after-effects among young women. This anatomoclinic entity of dubious etiology until these last years poses a problem of differential diagnosis with other etiologies of granulomatosis and especially with inflammatory carcinoma of the breast. The infectious theory is actually based on solid arguments and mainly explains the physiopathology of this affection. INTERPRETATION: A 26 years old young woman developed an inflammatory tumor of the left breast of which the catch of load by surgery and an antibiotherapy had shown trailing local continuations and of the esthetic after-effects. One year later, a very inflammatory repetition on the level of the right breast was dealt with in a different way: by steroids and immunomodulating drugs associated with iterative punctures with the purulent collections, the objective being to be less dilapidating that left side. The initial answer was rather favorable and encouraging but the purulent reappearance bulky granulomas with sinus way made reconsider the therapeutic attitude and antibiotics were undertaken after description of a lipophilic corynebactery in the material of puncture (Corynebacteria kroppenstedtii). The effectiveness of the amoxicilline introduced on the data of the antibiogram was undeniable. CONCLUSION: This observation illustrates the therapeutic and diagnostic difficulties of an exceptional affection. Potentially accessible to antibiotics it generally requires a joint surgical assumption of responsibility, at the same time to ensure the histological diagnosis but also with a therapeutic aim. The interest of steroids and the immunomodulation by methotrexate is debatable, these treatments cannot however be conceived without antibiotherapy and sometimes surgery.

Adult↗

Withdrawal reveals lack of effect of prolonged antihypertensive treatment on intrinsic aortic wall stiffness in senescent spontaneously hypertensive rats.

1. Chronic antihypertensive treatment lowers cardiovascular morbidity and mortality. The beneficial effect on the blood vessel wall may be due to the lowering of blood pressure (BP) and, hence, wall stress (WS), or to a treatment-induced change in wall structure. 2. We have previously shown that, when evaluated at the same level of BP and WS, the stiffness of the aortic wall of old spontaneously hypertensive rats (SHR) is higher than that of young and adult SHR and that of age-matched Wistar-Kyoto (WKY) rats. In the present study, we tested the hypothesis that the intrinsic changes in wall composition and mechanics in old SHR can be modulated by long-term treatment with an angiotensin I-converting enzyme inhibitor (captopril; 40 mg/kg per day) combined with a diuretic (hydrochlorothiazide; 20 mg/kg per day) and that treatment withdrawal would reveal whether such changes are maintained when BP and WS return to pretreatment levels. 3. We evaluated aortic structure and mechanics in SHR following 1 week withdrawal of oral antihypertensive treatment from 3 to 15 months of age (n = 8). Results were compared with age-matched SHR that were maintained on treatment (n = 12) or were not treated (n = 13) and with WKY rats (no treatment n = 11; maintained n = 11; withdrawn n = 10). 4. Isobaric aortic wall stiffness was estimated from the ratio of baseline aortic pulse wave velocity (PWV) to BP and the slope relating aortic PWV to BP following sodium nitroprusside-induced hypotension. Relative wall stiffening was estimated as the ratio of elastic modulus (EM) to WS. We argued that if treatment produced a change in wall elastin or collagen content, with a subsequent decrease in isobaric wall stiffness, then this would be maintained when BP increased following withdrawal of treatment. 5. In old SHR, treatment lowered isobaric wall stiffness (baseline PWV/BP 4.6 +/- 0.3 cm/s per mmHg; slope relating PWV to BP 6.7 +/- 0.4 x 10-3 cm/s per mmHg and EM/WS 4.1 +/- 0.4 vs 6.1 +/- 0.4 cm/s per mmHg, 9.7 +/- 0.9 x 10-3 cm/s per mmHg and 8.9 +/- 1.1, respectively, without treatment; all P < 0.05). After 1 weeks treatment withdrawal, the indices (5.7 +/- 0.2 cm/s per mmHg, 9.1 +/- 0.2 x 10-3 cm/s per mmHg and 7.2 +/- 0.6) increased in parallel with the increase in WS to levels similar to those observed in untreated SHR. There were no significant differences among the WKY rat groups. 6. Treatment increased the elastin and collagen contents of the aortic wall in both SHR (196 +/- 13 and 128 +/- 5 vs 111 +/- 9 and 86 +/- 4 mg/g wet weight, respectively, in untreated; P < 0.05) and WKY rats (190 +/- 19 and 135 +/- 4 vs 115 +/- 7 and 114 +/- 5 mg/g wet weight, respectively, in untreated; P < 0.05). This increase remained following withdrawal (213 +/- 26 and 118 +/- 4 vs 161 +/- 14 and 127 +/- 4 mg/g wet weight in SHR and WKY rats, respectively). 7. In summary, 1 year of treatment with captopril plus hydrochlorothiazide increases wall elastin content and reduces WS and stiffness in old SHR. Following withdrawal, elastin content remains high, but wall stiffness parallels WS in a manner similar to that in untreated SHR.

Aging↗

[Von Recklinghausen's disease associated with pancreatic somatostatinoma].

INTRODUCTION: Pancreatic somatostatinoma is a rare entity and its association with Von Recklinghausen's disease has only been described on two occasions. We report a new observation, with clinical and evolving status differing from those described in isolated cases of somatostatinoma. OBSERVATION: A 28 year-old man presenting with familial Von Recklinghausen's disease, had suffered for 10 years from paroxysmic abdominal pain. He was hospitalized for intense pain. Imaging revealed a retroperineal tumoral formation. Following duodenopancreatectomy, somatostatinoma was diagnosed. Diffuse metastatic miliary was revealed and multiple glandular metastases. DISCUSSION: Other than the rarity of the morbid association (pancreatic somatostatinoma and Von Recklinghausen's disease) described, this case is particular in that the patient was very young, symptomatology was unapparent and tumoral evolution was minimal.

Adult↗

Improving survival of vulnerable infants increases neonatal intensive care unit nosocomial infection rate.

OBJECTIVE: To determine the factors associated with an increasing rate of nosocomial infections in infants with very low birth weights. METHODS: Retrospective review of clinical and nosocomial infection databases for all infants with birth weights of 1500 g or less admitted to an academic neonatal intensive care unit between January 1, 1991, and December 31, 1997 (N = 1184). Two study periods were compared: 1991-1995 and 1996-1997. RESULTS: Among the 1085 infants who survived beyond 48 hours, the proportion who developed nosocomial infections increased from 22% to 31% (P =.001) and the infection rate increased from 0.5 to 0.8 per 100 patient-days (P<.001) during the period from 1996 to 1997. In that same period, the median duration of indwelling vascular access increased from 10 to 16 days (P<.001), and the median duration of mechanical ventilation increased from 7 to 12 days (P<.001). Although the device-specific rate of bloodstream or respiratory infections did not change, the increase in infections was directly attributable to the increasing proportion of infants who required these devices. In both study periods, the peak incidence of initial infection occurred between 10 and 20 days of age. For the entire sample, proportional hazard models identified birth weight, duration of vascular access, and postnatal corticosteroid exposure as significant contributors to the risk of infection. CONCLUSIONS: The increasing number of technology-dependent infants was the primary determinant in the increase of nosocomial infections. Because these infections occur in a small proportion of infants, understanding the host factors that contribute to this vulnerability is necessary to decrease nosocomial infections in neonatal intensive care units.

Catheterization, Central Venous↗

Activation of metalloproteinase-2, loss of matrix scleroprotein content and coronary artery calcification.

Plaques from the coronary arteries of explanted hearts showed massive calcification (15-fold increase) with a loss of scleroproteins (-36%), an increase in the collagen to elastin ratio (twofold) and activation (+15%) of matrix metalloproteinase-2 (MMP-2). Plaque-free portions of the coronary artery gave results similar to those obtained with the internal mammary artery. There was a significant correlation between plaque calcification and MMP-2 activation, suggesting that the two processes may be linked.

Adult↗

Aortic wall mechanics and composition in a transgenic mouse model of Marfan syndrome.

In Marfan syndrome, mutations of the fibrillin gene (FBN1) lead to aneurysm of the thoracic aorta, making the aortic wall more susceptible to dissection, but the precise sequence of events underlying aneurysm formation is unknown. We used a rodent model of Marfan syndrome, the mgR/mgR mouse (with mgR: hypomorphic FBN1 mutation), which underexpresses FBN1, to distinguish between a defect in the early formation of elastic fibers and the later disruption of elastic fibers. The content of desmosine plus isodesmosine was used as an index of early elastogenesis; disruption of elastic fibers was analyzed by histomorphometry. Because disruption of the medial elastic fibers may produce aortic stiffening, so amplifying the aneurysmal process, we measured thoracoabdominal pulse wave velocity as an indicator of aortic wall stiffness. Both mgR/mgR and wild-type (C57BL/6J-129SV) strains were normotensive, and wall stress was not significantly modified because the increase in internal diameter (0.80+/-0.06 vs 0.63+/-0.03 mm in wild type, P<0.05) was accompanied by increased medial cross-sectional area. The aortic wall stiffened (4-fold increase in the elastic modulus-to-wall stress ratio). Desmosine content was not modified (mgR/mgR 432+/-31 vs wild type 492+/-42 microg/mg wet weight, P>0.05). Elastic fibers showed severe fragmentation: the percentage of the media occupied by elastic fibers was 18+/-3% in mgR/mgR mice vs 30+/-1% in wild-type mice, with the number of elastic segments being 1.9+/-0.2 vs 1.4+/-0.1x10(-6)/mm(2) in the wild type (both P<0.05). In conclusion, underexpression of FBN1 in mice leads to severe elastic network fragmentation but no change in cross-linking, together with aortic dilatation. This result suggests that fragmentation of the medial elastic network and not a defect in early elastogenesis is 1 of the determinants of aortic dilatation in Marfan syndrome.

Animals↗

Aminoguanidine and aortic wall mechanics, structure, and composition in aged rats.

With aging, the aortic wall becomes stiffer. This could be because of changes in wall stress or composition. We investigated whether a specific change in wall composition, ie, accumulation of advanced glycation end products (AGEs) on the extracellular matrix, is a major factor. We measured aortic mechanics, geometry, and composition in 3-, 10-, 15-, 20-, and 30-month-old inbred normotensive Wistar-Glaxo/Rijswick rats and in a group of 30-month-old rats treated from 20 months onward with aminoguanidine (AG, 42 mg/kg per day), an inhibitor of AGE formation. Thoracoabdominal aortic (pressure) pulse-wave velocity (PWV) increased progressively with age (44% from 3 to 30 months). This age-related increase in aortic PWV was not related to changes in wall stress. For all ages, central (and peripheral) aortic mean blood pressures were not statistically different. Dilatation occurred (18% increase in internal diameter from 3 to 30 months), but this was accompanied by outward hypertrophic remodeling, with an increase in the medial cross-sectional area of 95% and in the ratio of medial thickness to internal diameter of 29%. Wall stress decreased with age (-34%). There was an increase in the ratio of elastic modulus (calculated from the Moens-Korteweg equation) to wall stress (calculated from the Lamé equation, 117% from 3 to 30 months), suggesting that a change in the composition of the wall is responsible for the age-linked increase in wall stiffness. Dry weight decreased slightly but significantly (-14%) with age. Total protein, elastin, collagen, and nonscleroprotein protein [total-(elastin+collagen)] contents did not change with age, but calculated densities of all 4 were halved (as the medial cross-sectional area doubled). The elastin/collagen ratio was statistically similar at all ages. The only significant effect of AG treatment was a fall in PWV (-20%), leading to a fall in the elastic modulus/wall stress ratio (-27% at 10 months of AG treatment versus 30 months of no treatment). In conclusion, the age-related increase in aortic wall stiffness is prevented by 10 months of treatment with AG, which has no effect on wall stress or composition, suggesting that AG may improve aortic wall stiffness by lowering the degree of AGE-induced cross-linking of the extracellular matrix scleroproteins, such as collagen.

Aging↗

[Budd-Chiari syndrome with inferior vena cava stenosis].

BACKGROUND: Stenosis of the inferior vena cava is a rare cause of Budd-Chiari's syndrome. We report on such a case related to a specific cause with a dramatic improvement after endovascular treatment. CASE REPORT: A 53-year old woman was admitted to hospital because she demonstrated circulatory collapse, inferior limbs edema and post-prandial epigastralgia. These signs were related to the occurrence of a stenosis of the sus-hepatic segment of the inferior vena cava related to the presence of the distal part of a catheter. An angioplasty with the insertion of a stent was followed by a total recovery with a one-year survey. CONCLUSION: Angioplasty with the insertion of a stent should be considered in a Budd-Chiari syndrome related to the stenosis of the inferior vena cava. This option should be evaluated with reference to classic surgical techniques.

Angioplasty, Balloon↗

Age-related arterial calcification in rats.

In man, i) arteries calcify with age and ii) age-linked arterial calcification is amplified by vascular pathology such as hypertension or arteriosclerosis. Age-linked arterial calcification has a bad prognosis but drugs to prevent it are lacking. This is partially due to the lack of appropriate animal models. This paper looks at the extent to which arteries calcify with age in the rat and whether hypertension or arteriosclerosis amplifies such calcification. Total calcium levels were determined by acid digestion and flame spectrophotometry and intracellular calcium levels ([Ca2+]i) by the intracellular calcium-sensitive dye, fura-2. Arteries contained up to 5 times more calcium than other soft tissues. Arteries progressively calcified with age whereas other soft tissues did not. Accumulation of calcium with age was essentially extracellular. Hypertension had no effect on age-related arterial calcification. Calcification of the same order as in man was produced in a rat model of arteriosclerosis (vitamin D plus nicotine treatment). In conclusion, as in man, age-linked, organ-specific arterial calcification does occur in rats but its intensity is far less. Arterial calcification of a similar degree to that observed in man can be obtained in rats by hypervitaminosis D plus nicotine.

Aging↗

Physical exercise, aortic blood pressure, and aortic wall elasticity and composition in rats.

With a training schedule (8 weeks' treadmill running at 30 m/min up a 10% incline 5 d/wk for 90 min/day), we investigated whether exercise modifies aortic wall dimensions, composition (calcium and elastin content), or stiffness in normotensive 6-month-old male Wistar WAG/Rij rats. Maximal oxygen uptake was measured in half of the rats (n=10 per group). Wall stiffness was evaluated in the other half (9 trained and 10 untrained) on the basis of changes in thoracoabdominal pressure pulse wave velocity and differences in amplitude between the peripheral and central aortic pressure signals. Experiments were performed in nonanesthetized, unrestrained rats and then after pithing. The impact of exercise on the oxidative capacity of the plantaris muscles was evaluated with the measurement of citrate synthase activity. Training increased maximal oxygen uptake by 34% and citrate synthase activity by 40%. Mean peripheral aortic pressure increased by 6% and 19% in trained rats, under awake and pithed conditions, whereas mean central aortic pressure increased by 16%, after pithing only. All indexes of aortic stiffness were similar in trained and control rats, as were aortic wall dimensions, composition, cardiac mass, and heart rate. In conclusion, physical exercise in young rats appears to have no effect on aortic stiffness.

Animals↗

[Acute disulfiram intoxication with severe neurological sequaelae and presenting misleading psychiatric deficiency].

Disulfiram self poisoning is exceptional. The authors report on the case of such an intoxication related to the ingestion of a potentially lethal dose of this drug (30 g) and draw the attention on the following points: 1) The initial signs may be misleading because they include both psychiatrics and neurological signs such as phonation abnormalities, myoclonias and tetraparesia. 2) The evolution is unforseeable with the possible occurrence of severe psychological and motricity sequaelae, associated with bilateral and symetric injuries of the putamen, the palladium and the basal nuclei on CT-scan (or MRI). The pathophysiologic al mechanisms of theses signs are discussed, and the need for disulfiram in the care of alcoholic patients seeking for withdrawal as well.

Adult↗