Sporadic visceral myopathy with inclusion bodies. A light-microscopic and ultrastructural study

We report the clinical and pathologic findings of two patients with sporadic visceral myopathy. Both presented with chronic intestinal pseudo-obstruction that necessitated colectomy. Microscopically, typical changes of primary visceral myopathy were present, including variable fibrous replacement of the muscularis externa and vacuolar degeneration of myocytes. In addition, the muscle cells contained cytoplasmic inclusions that have only been recently reported in visceral myopathy. These inclusions were numerous and easily visible in routine hematoxylin-eosin-stained sections but greatly enhanced by periodic acid-Schiff staining. They were reactive immunohistochemically at their periphery and were seen to be myofibrils at various stages of degeneration on electron microscopy. Inclusions were present in both muscularis externae and muscularis mucosae and were identified in mucosal biopsy specimens, providing a means of diagnosing this type of myopathic change on endoscopic biopsies.     

Clonidine therapy for comorbid attention deficit hyperactivity disorder and conduct disorder: preliminary findings in a children's inpatient unit

This retrospective study examined the clinical course of 18 prepubertal boys (aged 6 to 12) who had dual diagnoses of attention deficit hyperactivity disorder and conduct disorder and who received clonidine on an inpatient basis after failed trials of conventional drug therapy, consisting predominantly of psychostimulants. The effects of clonidine were assessed during inpatient treatment and after discharge at intervals of 1 to 2 months. Eleven (61%) of the children had marked improvement as measured by clinical impression. Transient sedation lasting 2 to 3 days occurred after initial administration or dosage increase; otherwise, clonidine was well tolerated. Our findings suggest that clonidine may prove to be an alternative treatment of comorbid attention deficit hyperactivity disorder and conduct disorder.     

Excess mortality in general hospital patients with delirium: a 5-year follow-up of 519 patients seen in psychiatric consultation

Mortality was determined in 519 patients with delirium who were seen in psychiatric consultation in two general hospitals. Among 419 patients with simple delirium (DSM-III: 293.00) in-hospital mortality was 26%. As compared to average hospital patients the age adjusted in-hospital excess mortality ratio varied from 6.2 for patients with malignancies to 2.1 for patients with motor system disease. After hospital discharge the 5-yr cumulative mortality was 51%. As compared to the general population excess mortality was noted in most, but not in all diagnostic subgroups. The age and sex adjusted excess mortality ratio varied from 14.1 for malignancies to 1.3 for motor system disease. The figures underline a general notion that delirium may be an indicator of disorders of grave prognosis, but mortality appears to depend more on the medical condition than on the presence of delirium.     

Structure of d(GT)n.d(GA)n sequences: formation of parallel stranded duplex DNA

Alternating polypurine sequences exhibit remarkable polymorphism. In this study, we report that dGA.dGT sequences form parallel stranded duplex DNA at neutral pH. Using two model hairpins, 3'-d(GT)3-5'5'-T4(AG)3-3' (I) and 3'-d(GT)4-5'5'-T4(AG)4-3' (II), containing 5'5' linkages which direct parallel strand formation, we systematically explored the spectroscopic and thermodynamic properties of parallel stranded d(GA)n.d(GT)n. The parallel stranded hairpins are remarkably stable structures with TM's of 41.5 and 47.5 degreesC (in 0.4 M NaCl) for the shorter and longer hairpins, respectively. The van't Hoff enthalpies of 80.7 and 114 kJ mol-1 are relatively low but are comparable to a parallel stranded d(GA)n duplex. On the basis of the spectroscopic and electrophoretic characteristics, we conclude that parallel strand formation is not restricted to hairpin systems, but also readily occurs in unconstrained dimeric duplexes with the appropriate sequence homologies. Both melting curves and electrophoretic analyses of parallel stranded heteroduplexes in which the sequence enforces specific base pairing demonstrate that G-G and A-T base pairs are formed in d(GA)n.d(GT)n segments.     

Perioperative specific management of blood volume loss in craniosynostosis surgery

Accurate assessment and replacement of blood loss and fluid-electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg(-1) h(-1) except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis.     

Immunological mimicry between retinal S-antigen and group A streptococcal M proteins

Immunological mimicry between host and microbial proteins has been suggested as a potential mechanism in the development of uveitis in humans. In this study immunological crossreactivity between anti-streptococcal monoclonal antibodies (MAbs) and the human eye was investigated. In indirect immunofluorescence, we demonstrated novel immunological crossreactivity of two anti-streptococcal MAbs (27 and 112) with the rod outer (and inner) segments of the retina of the human eye. In further studies, retinal S-Ag, a uveitogenic protein in the rod outer (and inner) segments, was found to react with the anti-streptococcal MAbs. In addition, several uveitogenic peptides of S-Ag were recognized by the anti-streptococcal MAbs. In the ELISA and Western immunoblot, anti-S-Ag MAbs crossreacted with group A streptococci and the streptococcal M protein further demonstrating sites of antigenic similarity. Homology between the retinal S-Ag and streptococcal M protein was observed in amino acid sequences repeated in the B repeat region of the streptococcal M5 protein. These data show that retinal S-antigen has immunological similarities with streptococcal M protein, a major virulence determinant and strong bacterial cell surface antigen.     

Medical conditions of the puerperium

The puerperium is a time of continued, dramatic pregnancy-associated adaptation. Although much less common than in the early part of the century, maternal death can still occur from common postpartum problems such as infection, hemorrhage, and disease. This article reviews the physiologic and emotional changes as well as the clinical management of common problems in the puerperium.     

Retinoic acid and interferon alpha act synergistically as antiangiogenic and antitumor agents against human head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy in which multiple independent lesions develop over time throughout the mucosa of the upper aerodigestive tract. Therefore, the comprehensive treatment of this neoplasm must include a chemopreventive arm to hold premalignant lesions in check, a role well-suited to antiangiogenic agents. Retinoic acid (RA) and interferon alpha (IFN-alpha), drugs with known biological activity against HNSCC when used individually, are also inhibitors of angiogenesis. Here we show that they are remarkably synergistic antiangiogenic agents able to inhibit both the growth and the neovascularization of HNSCC injected into the floor of the mouth of nude mice. The mechanism of action of these drugs as antiangiogenic agents was 2-fold. They decreased the angiogenic activity of the tumor cells, and they caused the endothelial cells to become refractory to inducers of angiogenesis. When tumor cells were treated in vitro with IFN-alpha A/D, there was a dramatic drop in their secretion of interleukin-8, the major angiogenic factor produced by these tumors. When combined with RA, which causes tumor cells to secrete an inhibitor of angiogenesis, there was a synergistic inhibition of both tumor cell growth and secreted angiogenic activity. The combination of RA and IFN-alpha also acted synergistically on endothelial cells by reducing their responsiveness to both interleukin-8 and tumor conditioned media. Doses of each drug could be reduced by two logs without loss of activity. When animals bearing human HNSCC tumor cells were treated systemically with a combination of RA and IFN-alpha A/D at doses that were ineffective when used alone, dramatic decreases in both tumor growth and tumor angiogenesis were seen. These data suggest that the use of antiangiogenic mixtures may be a particularly effective way to design future chemoprevention protocols against HNSCC.