Hemodynamic differences between carvedilol and labetalol in the cutaneous circulation

The effects of labetalol and carvedilol on local cutaneous microvascular perfusion and calculated local cutaneous microvascular resistance were investigated in anesthetized rats at submaximal doses that produced equivalent reductions in blood pressure and heart rate. Labetalol decreased cutaneous perfusion (– 25% ± 3%) without significantly affecting cutaneous vascular resistance ( – 6% ± 3%). In marked contrast, carvedilol dramatically increased cutaneous perfusion ( + 64% ± 9%) and significantly reduced cutaneous vascular resistance ( – 57% ± 3%). These results suggest that carvedilol and labetalol possess differences in the mechanisms by which they produce vasodilation in vivo.     

Association of apolipoprotein ɛ4 allele and neuropathologic findings in patients with dementia

Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE 4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE 4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.     

Symptomatic compression of the optic nerve by the carotid artery: clinical profile of 18 patients with 24 affected eyes identified by magnetic resonance imaging.

OBJECTIVE: To characterize the clinical features and course of patients with magnetic resonance imaging (MRI)-defined optic nerve compression by the supraclinoid carotid artery. DESIGN: Retrospective, observational case series. PARTICIPANTS: Eighteen patients with 24 affected eyes were identified by reviewing case records from the author's referral-based neuro-ophthalmology practice. Predetermined inclusion and exclusion criteria were applied to potential participants. MAIN OUTCOME MEASURES: The following variables were abstracted from the medical record: age, gender, presenting symptoms, past medical problems, visual acuity, color vision, visual field, pupillary reactions, optic disc appearance, other neurologic signs, and previously documented and follow-up examinations. RESULTS: There were eight women and ten men ranging in age from 28 to 86 years (median age, 72 years) at the time of diagnosis. Ten (56%) of 18 patients had hypertension. Twelve patients had unilateral optic neuropathy, whereas 6 patients had bilateral optic neuropathy. One patient presented with subacute superior orbital fissure syndrome due to mass effect of a dolichoectatic carotid artery. Another patient had oculomotor nerve palsy with signs of aberrant regeneration due to intracavernous mass effect of a dolichoectatic carotid artery. One patient had a bitemporal hemianopia associated with bilateral compression of the immediate prechiasmatic optic nerves by dolichoectatic carotid arteries. The predominant pattern of visual field loss in most patients reflected nerve fiber bundle injury. A central scotoma or absolute central visual field loss was noted in only 6 (25%) of 24 affected eyes. Most patients demonstrated saucerlike excavation of the optic disc. Progression of visual acuity loss occurred at a relatively slow rate. CONCLUSIONS: Although uncommon, intracranial compression of the optic nerve by the carotid artery should be considered in a patient with unexplained or progressive unilateral or bilateral optic neuropathy. This entity can be diagnosed using clinical skills to exclude more common causes of optic nerve injury and coronal-oriented MRI to confirm anatomic compression of the symptomatic optic nerve. Although many affected patients have excavation of the optic disc and nerve fiber bundle visual field defects, most have additional signs atypical for glaucoma, minimizing the potential for diagnostic confusion between the two disorders.     

Comparative surface thrombogenicity of implanted vascular grafts.

In order to study the comparative thrombogenicity of neointimal surfaces that develop with three types of vascular graft materials (ultralightweight knitted dacron, knitted dacron external velour, and expanded Teflon), 36 female mongrel dogs had their infrarenal aortas alternately replaced with one of the three grafts. At the end of 3 or 6 months, the grafts were removed and the surface thrombogenicity of the neointimal surface was determined. Each graft was examined visually and microscopically for evidence of “healing.” At 6 months the external velour graft is lined more frequently than the other two grafts. The external velour graft has a markedly better incidence of cellular healing noted microscopically than the other two grafts at both time intervals. While the expanded Teflon has an initially lower surface thrombogenicity (probably due to the characteristics of Teflon surface), at 6 months, the velour graft has the lowest surface thrombogenicity. This is most likely due to cellular healing. Of all the completely lined grafts at both time intervals, the surface thrombogenicity of the velour grafts was most like that of the normal aorta. The velour graft appears to develop the least thrombogenic neointimal surface while becoming most frequently healed with a cellular neointimal surface.     

Focal segmental membranous glomerulonephropathy associated with other glomerular diseases

In four patients with the nephrotic syndrome, renal biopsy revealed focal segmental membranous glomerulonephropathy (FSMGN) associated with the histologic patterns of "nil" disease (two cases), hereditary nephritis and diffuse diabetic glomerulosclerosis. The occurrence of FSMGN in association with other glomerular diseases, presumably unrelated to immune complex deposition, is infrequent in our experience. Rather than necessarily representing an early stage or milder form of membranous glomerulonephropathy, it may be an epiphenomenon. This interpretation has prognostic and therapeutic implications and raises important pathogenetic questions. In particular, this study suggests that in some instances, preexisting functional and structural abnormalities may play a role either in the deposition of preformed circulating immune complexes or in the local formation of immune complexes.     

Long-term survival of patients with multiple myeloma and acute renal failure at presentation

Eight patients presented with simultaneous multiple myeloma and acute renal failure requiring hemodialysis. Patients had no known pre-existing renal disease nor exposure to nephrotoxic agents or x-ray contrast dye. Renal failure was attributed to light chain nephropathy in all cases. In 4 of these patients the diagnosis of myeloma was initially unsuspected. Renal biopsies in 3 of these patients, and post-mortem material in a fourth revealed the changes of "myeloma kidney." No patient regained renal function and all required chronic hemodialysis. Among these eight patients, three survived for periods greater than 21 months.     

The effect of arachidonic acid on the M current of NG108-15 neuroblastoma × glioma hybrid cells

The M current, I _M, a voltage-dependent non-inactivating K⁺ current, was recorded in NG108-15 neuroblastoma × glioma hybrid cells, using the whole-cell mode of the patch-clamp technique. We studied the effect of arachidonic acid, other fatty acids and inhibitors of the arachidonic acid metabolism. In relatively high concentrations (25–50 M) arachidonic acid first increased and later decreased the current, I _h, which holds the membrane potential at –30 mV and mainly flows through open M channels. It shifted the midpoint potential, V _o, of the relation between M conductance, g _M, and membrane potential, V, to more negative values and decreased the maximum conductance ¯g _M and the time constant _M. In smaller concentrations (5–10 M) arachidonic acid merely decreased I _h and ¯g _M with little effect on V _o and _M. Eicosatetraynoic acid and docosa-hexaenoic acid acted similarly to arachidonic acid whereas stearic acid had no effect. Of the three enzyme inhibitors studied, nordihydroguaiaretic acid acted similarly to arachidonic acid. i. e. caused a biphasic change in I _h. Indomethacin and quinacrine caused, respectively, a pure increase and a pure decrease of I _h and ¯g _M. Possible explanations are build-up of internally produced arachidonic acid, depletion of eicosanoid products or an inhibitory effect unrelated to arachidonic acid metabolism.     

Experimental vascularized total joint autografts--a primate study

Autogenous vascularized and nonvascularized total joint transfers were studied in the hands of Macaca fascicularis monkeys. Nine second toe proximal interphalangeal joints were transferred as a vascularized free graft to the hand, and the excised finger joints were transferred to the foot as a nonvascularized free graft. The grafts were examined clinically and histopathologically at 16 weeks to 10 months. Two of the nonvascularized free grafts were amputated because of infection and necrosis. Three had chronic infections. The four surviving nonvascularized grafts demonstrated necrosis of the hyaline cartilage and degenerative changes. Of the nine vascularized joints, one developed a wound infection that required amputation, another failed at 2 weeks because of wound dehiscence, and the remaining seven survived with preservation of the hyaline articular surfaces. The experimental technique was designed to be easily applied to clinical use. A skin island is provided as a "patency/viability monitor." The extensor mechanism is included in the graft for early function.