Overexpression of human lecithin:cholesterol acyltransferase in cholesterol-fed rabbits: LDL metabolism and HDL metabolism are affected in a gene dose-dependent manner

Lecithin:cholesterol acyltransferase (LCAT) is an enzyme well known for its involvement in the intravascular metabolism of high density lipoproteins; however, its role in the regulation of apolipoprotein (apo) B-containing lipoproteins remains elusive. The present study was designed to investigate the metabolic mechanisms responsible for the differential lipoprotein response observed between cholesterol-fed hLCAT transgenic and control rabbits. 131I-labeled HDL apoA-I and 125I-labeled LDL kinetics were assessed in age- and sex-matched groups of rabbits with high (HE), low (LE), or no hLCAT expression after 6 weeks on a 0.3% cholesterol diet. In HE, the mean total cholesterol concentration on this diet, mg/dl (230 +/- 50), was not significantly different from that of either LE (313 +/- 46) or controls (332 +/- 52) due to the elevated level of HDL-C observed in HE (127 +/- 19), as compared with both LE (100 +/- 33) and controls (31 +/- 4). In contrast, the mean nonHDL-C concentration for HE (103 +/- 33) was much lower than that for either LE (213 +/- 39) or controls (301 +/- 55). FPLC analysis of plasma confirmed that HDL was the predominant lipoprotein class in HE on the cholesterol diet, whereas cholesteryl ester-rich, apoB-containing lipoproteins characterized the plasma of LE and, most notably, of controls. In vivo kinetic experiments demonstrated that the differences in HDL levels noted between the three groups were attributable to distinctive rates of apoA-I catabolism, with the mean fractional catabolic rate (FCR, d-1) of apoA-I slowest in HE (0.282 +/- 0.03), followed by LE (0.340 +/- 0.01) and controls (0.496 +/- 0.04). A similar, but opposite, pattern was observed for nonHDL-C levels and LDL metabolism (h-1), such that HE had the lowest nonHDL-C levels with the fastest rate of clearance (0.131 +/- 0.027), followed by LE (0.057 +/- 0.009) and controls (0.031 +/- 0.001). Strong correlations were noted between LCAT activity and both apoA-I (r= -0.868, P < 0.01) and LDL (r = 0.670, P = 0.06) FCR, indicating that LCAT activity played a major role in the mediation of lipoprotein metabolism. In summary, these data are the first to show that LCAT overexpression can regulate both LDL and HDL metabolism in cholesterol-fed rabbits and provide a potential explanation for the prevention of diet-induced atherosclerosis observed in our previous study.     

Contact allergy to cocamidopropyl betaine

Cocamidopropyl betaine is an amphoteric surfactant used increasingly in cosmetic products. We describe 20 cases of cosmetic allergy to cocamidopropyl betaine; all were caused by shampoo or shower gel. 8 patients were hairdressers, who had occupational allergic contact dermatitis from shampoos. We recommend patch testing cocamidopropyl betaine 1% aq. routinely in hairdressers with dermatitis of the hands, and in all patients suspected of suffering from cosmetic allergy.     

Cementless implant composition and femoral stress. A finite element analysis

Proximal atrophy and thigh pain are recognized problems with some cementless femoral stems in total hip arthroplasty. It is thought that reduced femoral stress from alterations in load transfer caused by an intramedullary stem contributes to proximal femoral atrophy. An increase in flexural rigidity and bone stress near the stem tip is thought to contribute to thigh pain. A three-dimensional finite element analysis study was performed to calculate stresses in the proximal femur and bone near the stem tip before and after implantation of a collared, proximally coated, cementless femoral prosthesis. The influence of prosthetic material was examined by changing implant composition from cobalt chrome to titanium alloy and leaving all other parameters constant. Femoral stress was increased twofold immediately below the collar with the titanium implant compared with the cobalt chrome. However, the proximal femoral stress in the titanium implanted model was still 1/10 that in the corresponding region of the unimplanted femur model. At the stem tip, as much as a 30% reduction in femoral stress was seen with the titanium stem compared with the cobalt chrome. These findings suggest biomechanical evidence of an advantage for titanium as an implant material compared with cobalt chrome for cementless femoral stems.     

Serum carcinoembryonic antigen as an adjunct to preoperative staging of lung cancer

AIMS AND BACKGROUND: The authors report the case of a 23-year-old woman affected by intra-abdominal desmoplastic small round cell tumor (DSRCT) who obtained a complete response to multiagent chemotherapy. DSRCT is a rare, highly aggressive neoplasm generally arising in young people and seldom in females (about 20 cases described in the literature). METHODS: The patient underwent surgical resection of a large 15 x 15 cm mass located in the right lower abdominal quadrant, but after only 2 months later, two liver metastasis were noted. Thus, she was subjected to an aggressive antineoplastic treatment consisting of three groups of alternating non-cross resistant multiagent regimens administered every 21 days (cis-platin-etoposide-adriamycin-bleomicin; gemcitabine-ifosfamide-dacarbazine; methotrexate-5-fluorouracil-folinic acid) for a total of 9 administrations. RESULTS: After one cycle of treatment including the administration of all the three alternated schemes of chemotherapy, a complete disappearance of liver disease was noted. The treatment was relatively well-tolerated and the toxicity was acceptable. At present, after 15 months from diagnosis and 12 months after starting chemotherapy, the patient is disease-free and in good health. CONCLUSIONS: Even though this study regards only a single patient, it is noteworthy because of the rarity of this neoplasm and because of the infrequent complete responses reported in the literature. The efficacy and manageability of the treatment, suggests that both the timing and schedule used could constitute an important therapeutical option for this aggressive and poorly chemo-responsive tumor.     

Post-translational modifications of alpha5beta1 integrin by glycosaminoglycan chains. The alpha5beta1 integrin is a facultative proteoglycan

Cell-fibronectin interactions, mediated through several different receptors, have been implicated in a wide variety of cellular properties. Among the cell surface receptors for fibronectin, integrins are the best characterized, particularly the prototype alpha5beta1 integrin. Using [125I]iodine cell surface labeling or metabolic radiolabeling with sodium [35S]sulfate, we identified alpha5beta1 integrin as the only sulfated integrin among beta1 integrin heterodimers expressed by the human melanoma cell line Mel-85. This facultative sulfation was confirmed not only by immunoprecipitation reactions using specific monoclonal antibodies but also by fibronectin affinity chromatography, two-dimensional electrophoresis, and chemical reduction. The covalent nature of alpha5beta1 integrin sulfation was evidenced by its resistance to treatments with high ionic, chaotrophic, and denaturing agents such as 4 M NaCl, 4 M MgCl2, 8 M urea, and 6 M guanidine HCl. Based on deglycosylation procedures as chemical beta-elimination, proteinase K digestion, and susceptibility to glycosaminoglycan lyases (chondroitinase ABC and heparitinases I and II), it was demonstrated that the alpha5beta1 heterodimer and alpha5 and beta1 integrin subunits were proteoglycans. The importance of alpha5beta1 sulfation was strengthened by the finding that this molecule is also sulfated in MG-63 (human osteosarcoma) and HCT-8 (human colon adenocarcinoma) cells.     

Clinical effects of childbirth with median episiotomy and anal sphincter injury on fecal incontinence of primiparous women

Obstetric damage of the anorectal continence organ can lead to impaired anal continence. To assess the effect of birth, either with or without direct injury of the anal sphincter, 123 primiparae were studied. 41 patients with a midline episiotomy and 82 patients with an additional injury of the anal sphincter were assessed at a median of 21 weeks postpartum and compared with 18 healthy volunteers. Anorectal manometry as well as a standardized questionnaire were employed. Patients with an additional injury of the anal sphincter reported persistent flatus incontinence significantly more often (p = 0.0069) than patients with a midline episiotomy only. Incontinence of solid or liquid stool occurred only transiently. Compared to nulliparae in all primiparae a significant shortening of anal canal and a decreased squeeze pressure were observed. In addition, a significantly reduced resting pressure was seen in patients with an anal sphincter injury. The rectoanal inhibitory reflex was absent significantly more often following anal sphincter tear (p = 0.0023). Vaginal delivery, both with and without anal sphincter injury, leads to early detectable changes in anorectal sphincter function.     

Distressed or relieved? Psychological side effects of breast cancer screening in The Netherlands

PURPOSE: To compare three methods of combined cataract extraction and glaucoma surgery. METHODS: Retrospective review of 35 eyes of patients who had extracapsular cataract extraction and trabeculectomy using a corneoscleral incision (SAME), 54 eyes undergoing extracapsular cataract extraction and trabeculectomy using a separated corneal incision for cataract extraction and 43 eyes undergoing phacoemulsification and trabeculectomy. RESULTS: Ninety-one percent of the eyes in the SAME group, 85% of the SEPARATE group and 97% of the phacoemulsification and trabeculectomy group had an IOP < 22 mmHg at 6 months with or without medication (NS). Postoperative visual acuity and astigmatism were not significantly different between the groups. The number of eyes requiring YAG laser capsulotomy was significantly greater in the extracapsular cataract extraction and trabeculectomy (same and separated incision) as compared to the phacoemulsification and trabeculectomy group (P < 0.001). CONCLUSION: Phacoemulsification and trabeculectomy was not significantly more successful than the other methods of combined surgery. Although complication rates were similar, visual rehabilitation was faster and there was a reduced incidence of early posterior capsule opacification.     

Ticlopidine induced cholestatic jaundice

Ticlopidine hydrochloride (Ticlid) has been increasingly used as an antiplatelet agent. Some studies showed that it has higher efficacy in reducing stroke recurrence when compared to conventional aspirin. Side effects like gastrointestinal disturbances and blood dyscrasias are common but ticlopidine-induced cholestatic jaundice has been reported only rarely. We present a case report on a patient who has ticlopidine-induced cholestatic jaundice.