Human apolipoprotein B. Evidence for its immunochemical heterogeneity using monoclonal antibodies and an immunoenzymometric assay

Predefined monoclonal antibodies (Mabs) were used in an immunoenzymometric assay to study the immunochemical heterogeneity of lipoproteins and to search for potential epitopes with pathological importance. By measuring apolipoprotein B (apo B) epitopes in patients with and without angiographically documented coronary artery disease and in patients with type IIa hyperlipoproteinemia, we have found that both types of patients have a significant increase in Apo B-containing particles specifically recognized by one Mab (BL3). We have also observed that the effects of fenofibrate on type IIa patients vary greatly depending on the plasma concentrations of various Apo B-containing lipoproteins. The greatest effects occurred in patients with epitopes recognized by BL3. Lastly, by sequential precipitation of specific epitopes by BL3, we have obtained evidence that the residual epitope(s) may be related to one or more lipoprotein particles.     

Delayed presentation of traumatic popliteal artery pseudoaneurysms: a review of seven cases.

OBJECTIVES: to examine the management and outcome of patients with traumatic popliteal artery pseudoaneurysms with delayed presentation. MATERIALS: over a 2-year period 7 patients with traumatic popliteal pseudoaneurysms presenting to a tertiary referral unit after a delay of 1 month were reviewed. METHODS: a retrospective review of clinical records. RESULTS: the median interval between injury and presentation was 1.5 months (range 1-24 months). Penetrating trauma from gunshot wounds was the cause of the initial vascular injury in 6 patients and a stab wound in one. All patients had large pseudoaneurysms of more than 8 cm filling the popliteal fossa with variable degrees of fixed flexion deformity (FFD) of the knee. Severe FFD of more than 40 degrees was noted in 2 patients and 3 others had mild flexion deformities of 10 to 20 degrees. Six patients underwent repair of the pseudoaneurysm. One patient required an above knee amputation due to an infected false aneurysm. There were no deaths or graft related complications. Despite aggressive post-operative physiotherapy only 2 patients were able to completely straighten the leg at the time of discharge. CONCLUSIONS: in patients with neglected popliteal artery pseudoaneurysms, morbidity is associated with the pre-operative degree of fixed flexion deformity of the knee.     

Freezing of gait in postmortem-confirmed atypical parkinsonism.

The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.     

Determination of 3,4-dihydroxyphenylalanine (DOPA) in plasma and cerebrospinal fluid by high performance liquid chromatography with electrochemical detection

We report a reliable method for determining DOPA levels in plasma and cerebrospinal fluid. The method is based on complete conversion of DOPA to dopamine and quantification by HPLC-ECD of the dopamine formed. Lower limit of detection was 0.5 nmol/l. No differences in plasma DOPA levels were found between normal children (0-15 yr, n = 60), normal adults (n = 39) and patients with essential hypertension (n = 40) or Parkinson's disease (no DOPA therapy, n = 30). In normal individuals and in patients with essential hypertension venous plasma levels were higher than arterial levels (10.2 vs 9.3 nmol/l, p less than 0.001, V/A ratio 1.11 (SD 0.08), n = 15). Sympathetic stimuli (standing, tilting, bicycle exercise, tyramine) did not influence DOPA levels. In untreated depressed patients (n = 10) and in non-parkinsonian neurological patients (n = 12) cerebrospinal fluid levels of DOPA were 4.5 (SD 2.4) and 5.2 (SD 1.3) nmol/l respectively. A direct method for the measurement of DOPA by HPLC-ECD after deproteinization of plasma is also described and compared with the conversion method. Good agreement was found when plasma DOPA levels exceeded 0.25 mumol/l (y(conversion method) = 0.943x (direct method) + 0.118; n = 60; r = 0.985). The direct method, because of greater simplicity and the possibility of simultaneous measurement of the DOPA metabolite 3-O-methyldopa, is the method of choice with plasma samples from DOPA-treated patients. In non-DOPA treated individuals the conversion method is superior and has proved to be an accurate and sensitive method for the determination of DOPA levels in plasma and cerebrospinal fluid.     

Brachial artery hemodynamic response to acute converting enzyme inhibition by enalaprilat in essential hypertension

To assess the vascular involvement of renin-angiotensin system inhibition in human hypertension, acute effects of intravenous enalaprilat on brachial artery diameter, blood flow, and blood velocity were investigated in hypertensive patients by pulsed Doppler technique and compared with effects of saline vehicle. Compared with saline vehicle, enalaprilat reduced blood pressure (P less than 0.001) and increased brachial arterial diameter (P less than 0.01) and brachial blood flow (P less than 0.01). Enalaprilat effect on arterial pulse pressure was dependent on preinjection pulse pressure (r = -0.76; P less than 0.001), but its effect on mean blood pressure was not dependent on preinjection mean blood pressure. On the other hand, enalaprilat effect on arterial blood flow was negatively correlated with preinjection blood pressure (r = -0.64; P less than 0.02). The findings point to different responses of large and small arteries to intravenous enalaprilat.     

Androgen receptors in colorectal adenomas

Summary To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17–2.7x10^-9 M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P=0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24–3.1x10^-9 M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.