Non-insulin-dependent diabetes mellitus and hypertriglyceridemia impair lipoprotein metabolism in chronic hemodialysis patients

Patients with diabetes mellitus undergoing chronic hemodialysis treatment have the worst outcome on dialysis due to an increased rate of cardiovascular complications. Nearly all patients present with dyslipidemia, a prominent vascular risk factor, probably responsible for the high rate of vascular injury. Since both uremia and diabetes predispose to hypertriglyceridemia, the present study was conducted to investigate the influence of diabetes mellitus and/or hypertriglyceridemia on lipoprotein metabolism in hemodialysis patients. LDL was isolated and characterized from hyper- and normotriglyceridemic diabetic and nondiabetic hemodialysis patients (n = 40; 10 in each group); also, LDL-receptor-dependent uptake and intracellular cholesterol metabolism were studied in HepG2 cells. In addition, scavenger-receptor-mediated uptake was examined in mouse peritoneal macrophages. LDL isolated from nondiabetic normotriglyceridemic hemodialysis patients exhibited impaired cellular uptake via the LDL receptor. Additionally, intracellular sterol synthesis was less inhibited and cholesterol esterification was reduced compared with LDL from healthy control subjects. Reduction of catabolic capacities was more marked in hemodialysis patients who were either diabetic or hypertriglyceridemic and even more pronounced in patients presenting with a combination of both diabetes and hypertriglyceridemia. Hypertriglyceridemic and diabetic patients showed reduced lipase activity and increased LDL oxidation. Furthermore, they accumulated a fraction of small, dense LDL, and LDL was predominantly taken up via the scavenger-receptor pathway in peritoneal macrophages. This study elucidates the distinct influence of diabetes and/or hypertriglyceridemia in hemodialysis patients on cellular LDL metabolism via specific and nonspecific metabolic pathways. Furthermore, it underscores the cumulative impact of these pathologic entities on impairment of lipoprotein metabolism and increase of cardiovascular risk.     

Why does postpsychotic IQ decline in childhood-onset schizophrenia?

OBJECTIVE: The authors' goal was to examine whether the postpsychotic decline in full scale IQ during adolescence for patients with childhood-onset schizophrenia is due to a dementing process or simply failure to acquire new information and skills. METHOD: Linear regression was used to determine the rate of change for scaled and raw scores on subtests of 31 patients with childhood-onset schizophrenia. The resulting slopes were examined and related to changes in the patients' brains determined by magnetic resonance imaging. RESULTS: Three postpsychotic subtest scaled scores declined significantly: picture arrangement, information, and block design. In contrast, there was no decline in the non-age-corrected (raw) scores for any subtest. A significant correlation was found between decrease in hippocampal volume and a smaller increase in raw score on the information subtest. CONCLUSIONS: The decline during adolescence in the full-scale IQ of patients with childhood-onset schizophrenia does not reflect dementia but, rather, an inability to acquire new information and abilities.     

Association of IGF-I and IGF-II with myofiber regeneration in vivo

This study examined expression of insulinlike growth factor (IGF) in the myofibers and nonmyofibrillar structures of murine soleus muscle following contraction-induced damage. Identifying the cellular sources of this myogenic growth factor could improve muscle rehabilitation strategies. Immunohistochemical analysis of muscle sections indicated that the number of myofibers expressing both IGF-I and IGF-II increased significantly at 4, 7, and 10 days following injury, compared with control. Muscle spindles and vascular tissue expressed only IGF-II, and staining intensity did not change following injury. The number of fibers expressing developmental myosin heavy chain increased significantly at 7 and 10 days postinjury, and these usually coexpressed IGF. No IGF-specific staining of interstitial/inflammatory cells was observed. Therefore, expression of IGF after mechanically induced fiber damage occurs exclusively within regenerating fibers without supplemental delivery of IGF to the tissue by inflammatory cells or changes in constitutive expression of IGF-II in vascular tissue.     

MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

Hirayama’s disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama’s disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4–C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama’s disease is an intrinsic motor neuron disease. Received: 15 March 1999 Received in revised form: 25 May 1999 Accepted: 1 June 1999     

Individualized drug dosage in patients treated with continuous hemofiltration

BACKGROUND: Subtherapeutic drug dosing may be even more dangerous than overdosage, especially for intensive care patients requiring hemofiltration. PROPOSAL: According to Dettli's fundamental equation, body clearance of any drug (Cl) is a linear function of creatinine clearance (Cl = Cl anur + a x C(Cr)), with [a = (Cl norm - Cl anur)/C(Cr), norm]. We propose to individualize drug dosage during high-flux hemofiltration by basing it on Dettli's equation and on total C(Cr) (C(Cr) tot = C(Cr) ren + C(Cr) filt). Using this approach, drug clearance will eventually be overestimated for drugs with substantial tubular secretion and for high-efficiency hemofiltration (C(Cr) tot > 30 ml/min). CONCLUSION: In patients undergoing hemofiltration, the total C(Cr) approach might be a practical alternative to standardized dosing schemes for deriving an individualized dosage from published pharmacokinetic data and functions.     

The "point of no return" and the rate of progression in the natural history of IgA nephritis

BACKGROUND: Based on the observation of 7 patients with chronic IgA nephritis and on a course to end-stage renal failure after several years, D'Amico et al. [1993] reported on a "point of no return" at 2.5 to 3 mg/dl serum creatinine. After exceeding this limit all 7 patients exhibited an irreversible progressive renal failure. PATIENTS AND METHODS: Therefore, 115 patients with IgA nephritis from the "German Glomerulonephritis Therapy Study" were examined in order to look for the existence of such a "point of no return". RESULTS: Three different courses could be distinguished: a stable chronic course with constantly normal or only minor elevated serum creatinine lasting for years (91 patients), a progressive course with continuously increasing serum creatinine (22 patients), and a rare (only 2 patients) early acute course with a short-term increase of serum creatinine followed by a rapid return to the normal range. After exceeding 3 mg/dl serum creatinine no remissions were observed in the progressive cases. Sixteen patients showed a rapid, continuously progressive course until end-stage renal failure with exactly the same progression as the 7 patients of D'Amico et al. Six patients of the 22 progressors were not observed long enough. The serum creatinine level doubled on average from 3 to 6 mg/dl within 10 months. CONCLUSION: Our study confirmed the existence of a "point of no return" at 3 mg/dl (265 micromol/l) during the natural course of chronic IgA nephritis.     

An update of antidote availability in veterinary medicine.

Lack of commercially available antidotes for animals is an issue of significant concern to the American Board of Veterinary Toxicology. A few antidotes are available for food animals through extra-label use, regulatory discretion and compounding. However, regulatory restrictions arising from human food, safety concerns have limited the availability of food animal antidotes. Use of some antidotes in food animals requires establishment of an investigational new animal drug application. Antidotes are generally more available for non-food animals from several sources: approved animal drugs, extra-label use of approved animal and human drugs, regulatory discretion and compounding. Present alternatives are discussed as well as the need for legislation to increase antidote availability. Human food safety will always be an issue for food animal antidotes. Future availability of non-food animal and food animal antidotes will depend on several mechanisms and may include the establishment of veterinary antidote depots. Stakeholders are encouraged to participate in identifying and implementing these mechanisms.     

Cerebrovascular doppler examination and cerebral angiography-alternative or complementary?

Summary Obstructions in the extracranial cerebral arteries can be detected noninvasively by directional Doppler ultrasound technique using indirect and direct criteria. The indirect criteria are based on measurement of flow in the common carotid and in the terminal branches of the ophthalmic artery before and after the common carotid artery and branches of the external carotid artery are compressed. With the direct criteria, internal and external carotid artery are differentiated by diastolic flow, and local inhomogeneities of flow (turbulence) are detected. Flow in the vertebral artery is picked up transorally in the oropharynx. The Doppler examination was used in 2230 patients of whom 436 underwent angiography. The results of Doppler and angiography correlated in more than 90% of the cases.