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Biomedical subjects

C A Koch

Publications and source records attributed to C A Koch.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice.

Expression of human lecithin cholesterol acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high cholesterol diets, expression of CETP in LCAT-Tg mice reduced total cholesterol (-39% and -13%, respectively; p < 0.05), reflecting a decrease in HDL cholesterol levels. CETP normalized both the plasma clearance of [(3)H]cholesteryl esters ([(3)H]CE) from HDL (fractional catabolic rate in days(-1): LCAT-Tg = 3.7 +/- 0.34, LCATxCETP-Tg = 6.1 +/- 0.16, and controls = 6.4 +/- 0.16) as well as the liver uptake of [(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 +/- 2.0 micrometer(2) x 10(3)) compared with LCAT-Tg mice (35.7 +/- 2.0 micrometer(2) x 10(3); p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [(3)H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse cholesterol transport.

Animals↗
PubMed1999

Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix.

Neuroendocrine tumors of the cervix are rare and are often under- or misdiagnosed. Because these tumors are very aggressive, early diagnosis and subsequent treatment are warranted. We describe a 46-yr-old woman with carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. At age 44, she had dysplasia on Pap smear and underwent total abdominal hysterectomy with the diagnosis of adenocarcinoma. Fourteen months postoperatively, she developed the carcinoid syndrome and was found to have numerous liver metastases. Histological and immunohistochemical investigations of biopsy specimens from the patient's liver lesions and original cervical lesion ("adenocarcinoma") suggested that this woman had a primary atypical carcinoid of the uterine cervix with metastases to the liver. Treatment with octreotide and alkylating agents decreased the episodes of flushing and diarrhea within 8 weeks. If an adenocarcinoma of the uterine cervix is diagnosed, atypical carcinoid should be in the differential diagnosis. Symptoms of the carcinoid syndrome should be pursued and, if present, a urinary 5-hydroxyindolacetic acid level should be obtained. Timely diagnosis of a neuroendocrine tumor of the cervix may improve survival.

Adenocarcinoma↗
PubMed1999

Cushing's disease presenting with avascular necrosis of the hip: an orthopedic emergency.

Nontraumatic avascular necrosis (AVN) of the hip is commonly caused by exogenous glucocorticoid administration, whereas it has rarely been associated with endogenous hypercortisolism. We report a 30-yr-old woman with Cushing's disease whose presenting manifestation was early AVN of the hip. Although plain x-ray was negative, magnetic resonance imaging (MRI) of the hip showed stage 2 AVN. Her orthopedic disease was considered an emergency, and thus, it was treated with core decompression before the diagnosis of Cushing's syndrome (CS) was pursued further. The femur recovered fully, as demonstrated by her improved clinical picture and a subsequent MRI. AVN carries a poor prognosis, if not treated early. The diagnostic procedure of choice is MRI, because plain radiographs are falsely negative in early stages. This case illustrates that AVN can be the presenting manifestation of CS; to prevent irreversible effects on the femoral head, core decompression should not be delayed for the purpose of evaluation and treatment of CS.

Adult↗
PubMed1998

Arachnoid cysts: how do postsurgical cyst size and seizure outcome correlate?

Arachnoid cysts (ACs) are congenital cystic brain malformations associated with epilepsy. The purpose of this study was to determine the effect of surgical intervention of ACs on cyst size and seizure outcome. We reviewed the world's medical literature dealing with surgically treated ACs in epilepsy patients. Our study included only cases, in which the relationship between pre-and postoperative CT-size of the AC and seizure outcome was described. We also included six patients with ACs and epilepsy treated surgically at the University of Mainz. We analyzed postoperative AC size and seizure outcome with respect to mode of operation, cyst location, and patients' age. A total of 76 patients was reviewed. Sixty (79%) patients had a smaller AC postoperatively. Forty-six of those 60 (76.6%) experienced seizure improvement. Thirteen patients (21.6%) remained unchanged and one patient (1.8%) worsened. In 16 of the 76 patients (21%) the postoperative AC size was unchanged. Eight of those 16 patients improved. Six patients (37.5%) remained unchanged and two (12.5%) worsened. A positive correlation between postoperative AC size and seizure outcome was well demonstrated among patients treated by cyst fenestration, needle aspiration, or internal shunting. Among patients treated by cystoperitoneal shunting this direct correlation was less clear. Seizure outcome correlates directly with postoperative AC size. Seizure reduction is associated with decreased AC size postoperatively and depends on the mode of operation. Based on these data we would expect that patients with epilepsy secondary to ACs would demonstrate improved seizure control with lower AC volume. Conversely, we might expect increasing AC size to correlate with worse seizure control. This relationship may guide physicians in efficacy and timely patient management.

Adolescent↗
PubMed1998

Fenestration of porencephalic cysts to the lateral ventricle: experience with a new technique for treatment of seizures.

BACKGROUND: Porencephalic cysts are brain cavities resulting from perinatal vascular occlusion and are commonly associated with severe neurological deficits and medically intractable epilepsy. Thirty-seven children presenting to the University of Münster with intractable seizures because of a porencephalic cyst were treated by uncapping and fenestration of these cysts to the lateral ventricle between 1978 and 1992. We conducted the following study to determine the efficacy and safety of the uncapping and fenestration procedure for the treatment of seizures. METHODS: We reviewed all cases retrospectively and assessed the outcome of these patients with regard to seizures, paresis, and perioperative complications. RESULTS: Of 37 children, 23 (62%) were seizure-free postoperatively. Nine patients (24%) had a reduction of seizures and five children (14%) remained unchanged. Of 30 patients with preoperative hemiparesis, 11 (30%) improved after the operation. The leading postoperative problem was a subcutaneous/subgaleal cushion of CSF, which affected 12 children (12 of 37). A dural patch covering the iatrogenic dural defect could not prevent or reduce postoperative CSF leakage, but prolonged the postoperative fever period. Postoperative fever occurred in 36 children (36 of 37) and was caused by an aseptic meningitis. CONCLUSIONS: Children with intractable seizures and porencephalic cysts benefit from uncapping and cyst fenestration to the lateral ventricle. Concomitant perioperative complications are mild and are easily treated.

Adolescent↗
PubMed1997

Targeted disruption of the mouse lecithin:cholesterol acyltransferase (LCAT) gene. Generation of a new animal model for human LCAT deficiency.

We have established a mouse model for human LCAT deficiency by performing targeted disruption of the LCAT gene in mouse embryonic stem cells. Homozygous LCAT-deficient mice were healthy at birth and fertile. Compared with age-matched wild-type littermates, the LCAT activity in heterozygous and homozygous knockout mice was reduced by 30 and 99%, respectively. LCAT deficiency resulted in significant reductions in the plasma concentrations of total cholesterol, HDL cholesterol, and apoA-I in both LCAT -/- mice (25, 7, and 12%; p < 0. 001 of normal) and LCAT +/- mice (65 and 59%; p < 0.001 and 81%; not significant, p = 0.17 of normal). In addition, plasma triglycerides were significantly higher (212% of normal; p < 0.01) in male homozygous knockout mice compared with wild-type animals but remained normal in female knockout LCAT mice. Analyses of plasma lipoproteins by fast protein liquid chromatography and two-dimensional gel electrophoresis demonstrated the presence of heterogenous prebeta-migrating HDL, as well as triglyceride-enriched very low density lipoprotein. After 3 weeks on a high-fat high-cholesterol diet, LCAT -/- mice had significantly lower plasma concentrations of total cholesterol, reflecting reduced levels of both proatherogenic apoB-containing lipoproteins as well as HDL, compared with controls. Thus, we demonstrate for the first time that the absence of LCAT attenuates the rise of apoB-containing lipoproteins in response to dietary cholesterol. No evidence of corneal opacities or renal insufficiency was detected in 4-month-old homozygous knockout mice. The availability of a homozygous animal model for human LCAT deficiency states will permit further evaluation of the role that LCAT plays in atherosclerosis as well as the feasibility of performing gene transfer in human LCAT deficiency states.

Animals↗