Flow-independent angiography for peripheral vascular disease: Initial in-vivo results

Flow-independent angiography (FIA), an approach that isolates arterial blood using MR relaxation characteristics rather than flow effects, was evaluated for application in peripheral vascular disease (PVD). First, pilot studies were conducted in which FIA coronal projection images were obtained from controls and symptomatic patients with PVD to assess clinical utility. All control images corresponded to the expected leg arterial anatomy with little interference from deep veins (one of five) and muscle (zero of five). Superficial venous signal was less well suppressed in comparison to deep veins (four of five). Images of symptomatic patients were less consistent with difficulty suppressing muscle and deep venous signal in some cases and edema when present. We then compared T2 values for muscle (T2_m, tibialis anterior), arterial blood (femoral and popliteal arteries), and venous blood (femoral, popliteal, and saphenous veins) in controls (n = 8) and symptomatic patients with intermittent claudication (n = 5) or ischemic rest pain (n = 7). Changes in T2 measurements of various tissues accounted for poorer contrast in symptomatic patients. Patients with ischemic rest pain had significantly higher T2_m compared with controls (T2_m = 39.3 ± 2.1 (1 standard error of the mean [SEM]) versus 30.9 ± .4, P < .01). For all measurements, other than saphenous vein, variances were greater in symptomatic patients. To realize the inherent advantages of FIA for this clinical application, additional work on suppression of signals from muscle, veins, and edema is required. One promising approach involves shifting from projection images to three-dimensional acquisitions for improved tissue suppression.     

Morphologic and histochemical characteristics of skeletal muscle after long-term intramuscular electrical stimulation.

The purpose of this investigation was to examine the morphologic and histochemical characteristics of paraspinal muscles in patients with scoliosis after long-term electrical stimulation. Thirty-six children with idiopathic scoliosis, who had been treated with implantable muscle stimulators, had paraspinal muscle biopsies at the time of implantable muscle stimulator removal. Group A patients whose curve did not progress, had 2.9 years of stimulation stopped at skeletal maturity, with a further 1.5 years of nonstimulation before implant removal and biopsy. In group B patients, who had an average of 2.3 years of stimulation, the curve progressed and stimulation was continued until fusion and biopsy. Neither group showed any increase in the frequency of pathologic changes of paraspinal muscles contrasted with values reported in the literature for scoliotic muscle. In group A patients there was an increased proportion of type 1 fibers on the convex side of the curve compared to the concavity. Despite this finding the curves did not require fusion, suggesting that the increased percentage of type 1 fibers was not the cause of the scoliosis. In group B patients there was an even higher type 1 concentration on the convex side contrasted to the convex side of group A patients.     

Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

Natural killer cell regulation of implantation and early lung growth of H-ras-transformed 10T1/2 fibroblasts in mice

We examined the relative role of the natural killer (NK) cell and H-ras gene in controlling metastasis formation using a novel assay for quantitating viable tumor cells entering and surviving in the lung for up to 13 days following i.v. tumor inoculation. This assay utilized the resistance to G418 sulfate conferred by transfection of the neoR gene into 10T1/2 fibroblasts along with activated H-ras. We had previously shown that the metastatic efficiency of T-24-H-ras-transformed 10T1/2 fibroblasts correlated with H-ras expression at the RNA level. In this paper we show that the NK cell could recognize H-ras-transformed fibroblasts in vivo and control experimental metastasis formation using NK-suppressed and -activated syngeneic C3H recipients. Evaluation of NK sensitivity in vitro of individual lines did not predict metastatic ability. However, NK susceptibility in vitro did inversely correlate with the ability of tumor cells to arrest and survive in the lung for the first 48 h after i.v. inoculation. Although the level of H-ras RNA correlated with the ultimate metastatic potential, it did not correlate with the initial rate of tumor cell pulmonary retention or clearing. Over the next 10 to 12 days, however, we detected a preferential survival and outgrowth of high H-ras-expressing variants, which correlated well with the ultimate metastatic ability but not NK susceptibility. These observations argue that the NK cell has its major effect early in the course of the disease, while subsequent tumor growth occurs preferentially in high H-ras-expressing cell lines.     

Horner syndrome

Horner syndrome is an uncommon but important clinical entity, representing interruption of the sympathetic pathway to the eye and face. Horner syndrome is almost always diagnosed clinically, though pharmacological testing can be used to confirm the diagnosis. Imaging modalities such as PET, CT and MRI are important components of work‐up for patients presenting with acquired Horner syndrome. Our patient’s presentation with Horner syndrome unmasked the causative superior sulcus squamous cell carcinoma and a coincidental lower lobe adenocarcinoma. Successful radical treatment of these cancers resulted in complete resolution of the syndrome and disease‐free survival at 18 months. We review the anatomy and pathophysiology underlying this and other causes of Horner syndrome.     

Urinary monoamine metabolites as indices of mental stress in healthy males and females

Concentrations of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), the dopamine metabolite homovanillic acid (HVA) and the noradrenaline metabolite 4-hydroxy-3-methoxyphenyl glycol (HMPG) were determined in urine samples from healthy male and female students by mass fragmentography. Urine samples were obtained after a demanding examination (mental stress) and a day of ordinary school work (control condition). Self-ratings were obtained of feelings induced by the examination, and of habitual psychosomatic symptoms. The results for both sexes showed that the examination stress induced a significant increase of HVA and HMPG excretion, but not of 5-HIAA. The males excreted significantly more of each of the metabolites than the females. The pattern of correlations between metabolite levels and psychological and psychosomatic variables were strikingly different for the two sexes.     

Alpha-tocopherol and beta-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Idiopathic Parkinson's disease (PD) may possibly be caused by one or more unidentified neurotoxins present in the environment, or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in humans, lower primates and mice that closely resemble those found in PD. Because the mechanisms of neuronal damage in both idiopathic PD and in the MPTP model of PD may involve free radical formation in the substantia nigra, antioxidants might protect dopaminergic neurons. Previously, we found that both alpha-tocopherol and beta-carotene partially protected mice against MPTP. However, in the experiments described in this paper, neither alpha-tocopherol nor beta-carotene, each administered in massive doses, had any demonstrable protective effect for dopaminergic nigrostriatal neurons in marmosets injected with low doses of MPTP. Without more knowledge about the identity of the neurotoxin(s) causing idiopathic PD, and their mechanism of action, it is not possible at this time to predict whether these 2 antioxidants might be clinically useful in preventing or ameliorating PD.