The role of macrophages in demyelination

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS). In particular in the CsA-induced chronic relapsing form (CREAE), pronounced demyelination occurs, in temporal association with relapses. It is still a matter of discussion which cell type ultimately is responsible for the actual process of demyelination. Macrophages, cytotoxic T lymphocytes and also astrocytes are possible candidates. In this short overview, the role of macrophages in the pathogenesis of EAE is discussed. It is shown that in particular, newly recruited macrophages play a crucial role in the generation of clinical signs. Possible mechanisms by which macrophages are involved in the pathogenesis of demyelinating diseases are presented.     

Bone disorders following total gastrectomy

Bone disorders following gastrectomy were studied by measuring absolute and relative bone mineral density of the Wards triangle, serum 1,25-(OH)₂-D, alkaline phosphatase, and total serum calcium. The subjects were 20 males who had undergone total gastrectomy not more than three months previously (group A₁). Seventeen of these patients were reviewed three years later (group A₂). Absolute and relative bone density were significantly lower in group A₂ than in A₁ (0.52 ± 0.011 g/cm² versus 0.6 ± 0.014 g/cm²,P<0.01 and 85.5 ± 1.4% age-matched control versus 95 ± 1.3%,P<0.01). 1,25-(OH)₂-D was significantly lower in group A₂ than in group A₁ (14.3 ± 0.97 pg/ml versus 20.6 ± 1.02 pg/ml,P<0.01). There was no difference in alkaline phosphatase and calcium serum concentration. The mean weight loss was 6.26 ± 0.57% over the follow-up period, and weight loss correlated with absolute and relative bone density (r=–0.74,P<0.01). There was a positive correlation between 1,25-(OH)₂-D and absolute or relative bone density (r=0.67,r=0.62 andP<0.01). These data suggest that bone density decrease has already occurred three years after total gastrectomy and is positively correlated to 1,25-(OH)₂-D deficiency. As no differences in serum alkaline phosphatase and serum calcium concentration were found, these factors are of little value for the early detection of postgastrectomy bone disorders, whereas weight loss is a valuable screening parameter.     

Establishing a cancer center data bank and biorepository for multidisciplinary research.

The establishment of a biorepository with linkage to clinical and epidemiologic data will provide an invaluable resource for cancer research, including studies of cancer etiology, progression, and prognosis, as well as development of biomarkers for early detection. Developing an infrastructure for a biorepository linked to clinical, pathologic, and epidemiologic data requires significant efforts in strategic planning for efficient means to ascertain, identify, and consent participants, as well as guidelines for blood collection, processing, and storage while maintaining participant privacy rights. In this report, we present an approach to developing a Data Bank and Biorepository at our own institution, with discussion of elements to be considered when establishing such a bank.     

Unlabeled uses of botulinum toxins: a review, part 1.

PURPOSE: Efficacy and safety data regarding the unlabeled uses of botulinum toxins are reviewed, and the pharmacology, adverse effects, and characteristics of commercially available botulinum toxins are discussed. SUMMARY: More than 300 articles have been published on the use of botulinum toxins, particularly botulinum toxin type A, to treat conditions characterized by excessive smooth or skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium botulinum and cause temporary local paralysis of the injected muscle by inhibiting acetylcholine release at the neuromuscular junction. While botulinum toxins have Food and Drug Administration-approved labeling to treat a limited number of spasticity disorders, including cervical dystonia and blepharospasm, the toxins have more than 50 reported therapeutic uses. Among these uses, the most rigorously studied indications include achalasia, essential tremors, palmar hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity. The main adverse effects of the toxins are pain and erythema at the injection site, although unintended paralysis of muscles adjacent to the site of toxin injection may also occur. CONCLUSION: Clinical studies support the use of botulinum toxins for certain conditions, although more studies are needed to establish the role of the drug relative to conventional therapies and to determine patient predictors of response. Although botulinum toxins are generally well tolerated, a patient-specific risk-benefit assessment should precede any decision to use them for unlabeled indications.     

The Changing Faces of the Nutcracker Esophagus

Although the nutcracker esophagus, characterized by high amplitude peristaltic contractions with mean distal amplitude greater than 180 mm Hg, is the most common esophageal motility disorder associated with noncardiac chest pain, little is known about its natural history. Therefore, we reviewed the manometric tracings of 23 patients with the nutcracker esophagus who had an average of 4.6 studies during a mean period of 32 months. Ten age-matched volunteers with normal baseline manometry who had undergone multiple studies (mean 5.8) over a mean time span of 32 months served as controls. In the 17 nutcracker patients with three or more motility studies, the variability of mean distal amplitudes between studies was 41.9% +/- 4.1 (+/- SE) compared to 27.0% +/- 3.3 for the control subjects (p less than 0.01). Highest distal pressures were noted during the first study in 11 of 17 patients (65%) compared to two of 10 controls (20%). The consistency of the diagnosis of nutcracker esophagus varied considerably: four patients always had high amplitude pressures, three patients only had the nutcracker diagnosis on the initial study, and 10 patients intermittently had pressures in the nutcracker range. Overall, these 17 patients had the diagnosis of the nutcracker esophagus confirmed on only 54% of subsequent studies. Changes in motility patterns were intermittently seen in six of 23 patients: one diffuse spasm and five nonspecific motility disorders. None of the control subjects developed high amplitude contractions or changed their motility pattern on serial testing. The possible pathophysiological implications of the changing faces of the nutcracker esophagus are discussed.