Quality of life, patient satisfaction and cosmetic outcome after breast reconstruction using DIEP flap or expandable breast implant.

In a cross-sectional postal survey, we compared patient-reported outcomes in patients undergoing breast reconstruction with the deep inferior epigastric perforator (DIEP) flap or an expandable breast implant (EBI). We included 34 consecutive patients who had breast reconstruction with DIEP flap and 30 patients with EBI. Outcomes were assessed using the Short Form 36 (SF-36) quality of life questionnaire, two study-specific patient satisfaction questionnaires and a visual analogue scale (VAS) on cosmetic result. There were no significant differences in SF-36 subscale scores between the two groups. On the study-specific questionnaire, more patients in the DIEP group were satisfied with the appearance of their breast (P<0.0005) and reported an improved social relationship (P=0.02), and fewer patients were sad about their body image (P=0.01) after reconstruction than in the EBI group. On the other study-specific items, satisfaction was similar in the two groups. On all five VAS items, DIEP patients reported better cosmetic results than EBI patients. We conclude that patient satisfaction and cosmetic outcome were better after breast reconstruction with the DIEP flap compared with EBI, while there was no difference in health-related quality of life.

Cyclic AMP stimulates efflux of intracellular sterol from cholesterol-loaded cells.

The interaction of high density lipoprotein with its putative receptor stimulates translocation and efflux of intracellular sterols by a process involving activation of protein kinase C. This study shows that activation of cAMP-dependent protein kinase also stimulates efflux of intracellular sterols. When intracellular sterol pools of cholesterol-loaded cultured human skin fibroblasts and bovine aortic endothelial cells were radiolabeled with the biosynthetic precursor [3H]mevalonolactone, high density lipoprotein3 (HDL3)-mediated 3H-sterol efflux was enhanced by addition of the adenylylcyclase activator forskolin, the phosphodiesterase inhibitors theophylline and 3-isobutyl-1-methylxanthine, and the cAMP analogues N6-benzoyl-cAMP (N6-cAMP) and 8-thiomethyl-cAMP. The effect of N6-cAMP was abolished by an inhibitor of cAMP-dependent protein kinase (H8). The enhanced sterol efflux was independent of receptor binding of HDL3, as similar effects were observed in the presence of tetranitromethane-modified HDL3, which lacks receptor binding activity. N6-cAMP stimulated efflux of several subspecies of newly synthesized sterols, including cholesterol. Elevation of cAMP levels increased the proportion of radiosterols that were accessible to treatment of cells with the enzyme cholesterol oxidase, suggesting that activation of cAMP-dependent protein kinase stimulates translocation of sterols from intracellular compartments to the plasma membrane where they desorb from the cell surface. Thus, at least two distinct protein kinase signalling pathways modulate transport of intracellular sterols in cholesterol-loaded cells.

[Eosinophilic gastroenteritis]. / Eosinofil gastroenteritt.

We describe the case of a 33 year-old woman who was hospitalized for ascites, abdominal pain and food allergy. Blood samples and histologic examination of a jejunal specimen removed by laparotomy revealed that the patient suffered from eosinophilic gastroenteritis. This disease is classified among the hypereosinophilic syndromes, and food allergy may be of etiologic importance. Clinically eosinophilic gastroenteritis may present with ascites, malabsorption or gut obstruction. The eosinophilic blood cell count is usually elevated and the erythrocyte sedimentation rate is usually normal or slightly increased. Polyarteritis nodosa, Crohn's disease and nematodal infections of the gut must be excluded. Most patients respond well to corticosteroid therapy and the long-term prognosis is good, even though the disease is chronic in nature.

The effect of adaptation on the metabolism of dodecylthioacetic acid (a 3-thia fatty acid) in rat tissues.

Dodecylthioacetic acid (DTA) was both omega-hydroxylated and sulfur-oxygenated at about equal rates by the microsomal fraction from liver and kidney. Feeding tetradecylthioacetic acid (TTA) for 4 days increased omega-hydroxylation 4-fold only in the liver. The sulfur oxygenation rate was similar in liver, kidney and lung, barely detectable in heart and absent in intestinal mucosa. In isolated hepatocytes from normal rats the major metabolite from dodecylthioacetic acid was carboxypropylsulfoxyacetic acid. In hepatocytes from adapted rats, the main product was identified as bis(carboxymethyl)sulfide. In kidney perfusion experiments dodecylthioacetic acid was metabolized to carboxypropyl-sulfoxyacetic acid and preferentially excreted in the urine. In hindquarter perfusion experiments no oxidative metabolites were detected. These experiments show that only liver and kidney can metabolize dodecylthioacetic acid completely and that omega-hydroxylation in the liver is the only inducible activity, in addition to the beta-oxidation.

Formation and excretion of branched-chain acylcarnitines and branched-chain hydroxy acids in the perfused rat kidney.

alpha-Keto[U-14C]isovalerate, alpha-keto[U-14C]isocaproate and alpha-keto[U-14C]beta-methylvalerate are metabolized in the perfused kidney. Labelled 3-hydroxyisobutyrate, 3-hydroxyisovalerate, 2-methyl-3-hydroxybutyrate, branched-chain amino acids, branched-chain acylcarnitines and lactate are formed. Hydroxy acids and acylcarnitines are excreted preferentially in the urine, whereas the branched-chain amino acids are preferentially excreted in the perfusate. There is no accumulation of (U-14C)-labelled alpha-keto acids or labelled metabolites in the kidney during perfusion. (-)-Carnitine accumulates rapidly in the kidney when it is added to the perfusate. A high kidney carnitine level enhances the excretion of carnitine esters in the urine.

Uptake, metabolism and release of carnitine and acylcarnitines in the perfused rat liver.

The uptake and release of carnitine and isovalerylcarnitine have been studied in the perfused rat liver. Labelled carnitine accumulates in rat livers perfused with 50 or 500 microM [3H]carnitine. When alpha-ketoisocaproate (5 mM) is added to the perfusate after 30 min of perfusion, the net uptake of carnitine in the liver stops, and there is even a decrease in liver radioactivity. The decrease in liver carnitine can be attributed to an enhanced formation and efflux to the perfusate of short-chain acylcarnitines. Thin-layer chromatography of liver and perfusate extracts showed that efflux rates for branched-chain acylcarnitines (isovalerylcarnitine) formed are at least 2.5-fold the efflux rate for carnitine. Acetylcarnitine is released about twice as fast as carnitine from the liver. Perfusion with 50 microM [3H]isovalerylcarnitine showed that the influx rate of isovalerylcarnitine exceeds that of carnitine 1.5-fold. Since the efflux rate is still higher, a net loss of carnitine from the liver to the perfusate will result when branched-chain acylcarnitines are formed in the perfused liver. The addition of 500 microM unlabelled carnitine to the perfusate does not influence the release of labelled carnitine or acylcarnitines from the liver, showing that uptake and release are independent processes. Isovalerylcarnitine accumulates faster than carnitine does, also in the perfused rat heart. A mechanism for the development of secondary carnitine deficiencies associated with organic acidemia is proposed.

Metabolism of dicarboxylic acids in vivo and in the perfused kidney of the rat.

After intraperitoneal injection of (1-14C)-labelled suberic or dodecanedioic acid, the acids themselves and their metabolites were excreted in urine and as 14CO2. There was a striking difference in the capacity to oxidize the two dicarboxylic acids. Most of the suberic acid was excreted unchanged in the urine, and less was recovered as 14CO2. A trace was excreted as adipic acid. Dodecanedioic acid was more efficiently oxidized; 2-3-times more was expired as 14CO2, and the urine contained only a trace of the unchanged acid. Adipic acid was the main metabolite. Kidney perfusion experiments confirmed these results by showing that unmetabolized suberic acid was actively excreted by the kidneys. Dodecanedioic acid was oxidized and shorter dicarboxylic acids were excreted. The perfused hindquarter did not metabolize the dicarboxylic acids. Our results show that dodecanedioic acid can be completely oxidized both in the whole animal and in the kidneys. Dicarboxylic acids in the urine may to a significant extent be formed in the kidneys themselves.

Methionine metabolism by rat muscle and other tissues. Occurrence of a new carnitine intermediate.

Perfused rat hindquarter preparations were shown to incorporate radioactivity from [U-14C]methionine into citrate-cycle intermediates, lactate, alanine, glutamate, glutamine and CO2. During perfusion, large amounts of methionine were also oxidized to methionine sulphoxide. The capacity for transamination of methionine or its oxo analogue, 4-methylthio-2-oxobutyrate, by muscle extracts was demonstrated. Rat skeletal muscle, heart, liver and kidney mitochondria, when incubated with the latter plus radiolabelled carnitine, formed a newly identified carnitine derivative, 3-methylthiopropionylcarnitine. It is concluded that the capacity for oxidation of methionine by a trans-sulphuration-independent pathway occurs in several mammalian tissues. The extent of inter-organ handling of intermediates in this pathway(s) is discussed.

Metabolism and excretion of carnitine and acylcarnitines in the perfused rat kidney.

Rat kidneys were perfused for 30 min with a Krebs-Henseleit bicarbonate buffer with 5 mM glucose. Albumin proved superior to pluronic polyols as oncotic agent with regard to carnitine reabsorption in the perfused kidney. The reabsorption of 30 microM (-)-[methyl-3 H]carnitine was approx. 96% during the first 10 min. At 750 microM the reabsorption decreased to 40%. The tubular reabsorptive maximum (Tmax) was approx. 170 nmol/min per kidney. The fractional reabsorption and clearance of (+)-carnitine, gamma-butyrobetaine, and carnitine esters did not deviate significantly from that of (-)-carnitine. (+)-Carnitine was not metabolized by the perfused kidney. In perfusions with (-)-carnitine or (-)-carnitine plus 10 mM alpha-ketoisocaproate or alpha-ketoisovalerate increased amounts of acetylcarnitine, isovalerylcarnitine and isobutyrylcarnitine were found. Propionate (5 mM) inhibited acetylcarnitine formation. Isovalerylcarnitine, isobutyrylcarnitine and propionylcarnitine were actively degraded to free (-)-carnitine. In urine, we found a disproportionally high excretion of carnitine or carnitine esters formed in the kidney, compared to the same derivatives when ultrafiltrated. Leakage of metabolites formed in the kidney into preurine may explain this phenomenon.