Epidermolysis bullosa: radiographic findings in 16 cases

Epidermolysis bullosa is a group of dermatologic disorders with varied inheritance patterns having the common manifestation of blister or bulla formation after minor trauma. Sixteen patients with the disease had the following radiographic manifestations: esophageal stricture (16), fecal impaction (six), vaginal stenosis (one), epithelial bridging and fusion of the digits (six), and aspiration changes in the lungs (two). Esophageal strictures involved the pharynx or cervical esophagus in eight cases and were multiple in five; they ranged in length from 2 mm to 15 cm and tended to progress over time. The findings of esophageal stricture, particularly when multiple and involving the proximal esophagus, and/or the presence of distal phalangeal atrophy with soft-tissue webbing suggest the diagnosis of epidermolysis bullosa.     

Pigmentary retinal dystrophy associated with pigmentary glaucoma

Two young brothers were bilaterally affected by pigmentary glaucoma and extensive symmetrical changes of the retinal pigment epithelium (RPE). Fundus changes consisted in widespread salt-and-pepper RPE mottling and pigment clumping, sparing only the peripapillary and foveal areas. During the course of 4 years, one of the two patients suffered multiple, recurrent, exudative and hemorrhagic detachments of the RPE that involved the midperiphery and posterior pole. No exudative lesions appeared in the brother. The medical history and systemic laboratory tests were noncontributory in both patients. The ERG was normal and the EOG subnormal. Dark adaptation was delayed and showed an elevation of the scotopic threshold. These cases seem to support the hypothesis that the RPE is also involved in the pigmentary dispersion syndrome. An inherited defect could affect the pigment epithelium in both the anterior and posterior segments of the eye. The multifocal subretinal exudative pattern that occurred in one of our patients has not been previously observed in hereditary disorders of the RPE.Presented at the XVIth Meeting of the Club Jules Gonin, Bruges, 4–8 September 1988     

A comparision of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients

Twenty patients with AIDS who had intracranial lesions underwent both brain biopsy and cerebro-spinal fluid (CSF) examination to compare histological diagnosis with the polymerase chain reaction (CSF-PCR) for the identification of infectious agents. CSF-PCR was performed for herpes simplex virus, varicella zoster virus, cytomegalovirus (CMV), JC virus (JCV), Epstein-Barr virus (EBV), Toxoplasma gondii and Mycobacterium tuberculosis. A definitive diagnosis was obtained by brain biopsy in 14 patients (2 with astrocytoma, 12 with brain infection). CSF-PCR was positive for EBV DNA in 3 of 3 cases of primary cerebral lymphoma, positive for JCV DNA in 6 of 7 biopsy-proven (and one autopsy-proven) cases of progressive multifocal leukoencephalopathy (PML). CSF-PCR was positive for CMV DNA in one biopsy-proven and one autopsy-proven case of CMV encephalitis (the former also had PML) and positive for M. tuberculosis DNA in one case of tuberculous encephalitis. None of the five toxoplasmic encephalitis cases (one definite, four presumptive) were T. gondii DNA positive. There was close correlation between histology and CSF-PCR for CMV encephalitis, PML and PCL. Antitoxoplasma therapy affected the sensitivity of both histological and CSF-PCR methods. Received: 8 November 1995 Received in revised form: 9 July 1996 Accepted: 19 July 1996     

Successful management of laryngotracheosophageal cleft through an anterior approach

Laryngotracheoesophageal cleft is an uncommon disease that is difficult to diagnose and treat. Repair of the cleft depends on length and localization of the defect as well as the associated anomalies. A successful repair of a type II cleft is reported in this paper. An anterior split of the larynx and trachea was used and provided excellent exposure and safe repair without injury to the neurovascular structures. This is the best approach and should be used to correct all type II defects.     

The vascular response to tumor infiltration in malignant gliomas

Summary Neo-vascularization and endothelial hyperplasia have been shown to be very active in malignant gliomas. In this contribution the vascularization of the cortex infiltrated by malignant gliomas is morphometrically studied and the endothelial proliferations are immunohistochemically investigated and reconstructed by a three-dimensional computer-assisted procedure. Vessel density increases after tumor infiltration in some cases only. The diameter of vessels increases and so does the number of nuclei/vessel after the complete invasion of the cortex when vascular glomeruli develop. In completely infiltrated cortex with development of glomeruli and circumscribed necroses, vessel density is very low. No neoformation of vessels takes place before the complete infiltration of the cortex by the tumor. The hyperplastic formations, usually arranged parallel to the deep or outer cortical layers, take origin from the radially penetrating vessels from the meninges and their lateral branching. The hyperplasia deforms the vascular network, making it often inadequate to supply tumor cells. Immunohistochemically, the cells composing the hyperplastic structures are variably positive for factor VIII/RAg and, at a lesser extent, for -smooth muscle actin. The poorness of the vascular network in many instances of completely infiltrated cortex is responsible for the development of circumscribed necroses.Supported by Grant 87.01446.44 CNR, Rome and by A. I. R. C., Milan. Presented in part at the 63rd Annual Meeting of the American Association of Neuropathologists, Seattle, Washington, June 11–14, 1987     

Metabolism and pharmacokinetics of p-(3,3-dimethyl-1-triazeno) benzoic acid in M5076 sarcoma-bearing mice

Summary The pharmacokinetics of the anticancer agent p-(3,3-dimethyl-1-triazeno) benzoic acid (pCOOH-DMT), a drug now in phase I clinical trial in Europe, was investigated in C57 Bl female mice with M5076 reticulum-cell sarcoma that were treated i.v. with 200 mg/kg pCOOH-DMT. The drug disappeared from plasma with a terminal half-life of about 2.5 h. Plasma clearance was approximately 6 ml/min per kg. Distribution studies showed some differences in drug levels in different tissues. The highest levels were found in the tumor, liver, kidney and lung; lower levels were found in the spleen and gut, and the lowest, in the brain. The N-desmethyl derivative of pCOOH-DMT was not detectable in plasma or tissues of mice treated with the drug. Therefore, the previous evidence of low N-demethylation of pCOOH-DMT was confirmed. pCOOH-DMT glucuronide was identified by mass spectrometry and quantified by high-performance liquid chromatography (HPLC) in plasma, tissues and urine samples. pCOOH-DMT glucuronide appears to be the major urinary metabolite of pCOOH-DMT in mice. Another metabolite identified by mass spectrometry and quantified by HPLC in some tissues and urine was pCOOH-DMT glycinate.Abbreviations DTIlC 5-(3,3-dimethyl-l-triazeno)imidazole-4-carboxamide - pCOOH-DMT p-(3,3-dimethyl-l-triazeno)benzoic acid - pCOOH-MMT p-(3-methyl-l-triazeno)benzoic acid - pCONH₂-DMT p-(3,3-dimethyl-l-triazeno)carboxamide - BSTFA N,O-bis(trimethylsilyl)trifluoroacetamide - TMCS trimethylchlorosilane - TLC thin-layer chromatography - FAB fast atom bombardment - EI electron impact - M5 M5076 reticulum-cell sarcoma - t_1/2 beta-half-life - C₀ concentration time 0 - AUC area under the concentration vs time curve - Cl total clearance - V volume of distribution     

A dosimetric approach to patient-specific radioiodine treatment of Graves' disease with incorporation of treatment-induced changes in thyroid mass

The traditional algorithms (Marinelli-Quimby and MIRD) used for the absorbed dose calculation in radionuclide therapy generally assume that the mass of the target organs does not change with time. In radioiodine therapy for Graves' disease this approximation may not be valid. In this paper a mathematical model of thyroid mass reduction during the clearance phase (30-35 days) after 131I administration to patients with Graves' disease is presented. A new algorithm for the absorbed dose calculation is derived, taking into account the reduction of the mass of the gland resulting from the 131I therapy. It is demonstrated that thyroid mass reduction has a considerable effect on the calculated radiation dose. Either the model of the thyroid mass reduction or the new equation for the absorbed dose calculation depend on a parameter k for each patient. This parameter can be calculated after the administration of a diagnostic amount of radioiodine activity (0.37-1.85 MBq). Thus, thyroid absorbed dose and thyroid mass reduction during the first month after therapy can be predicted before therapy administration. The absorbed dose values calculated by the new algorithm are compared to those calculated by the traditional Marinelli-Quimby and MIRD algorithms.     

Adoptive immunotherapy of feline immunodeficiency virus with autologous ex vivo-stimulated lymphoid cells modulates virus and T-cell subsets in blood

The potential of immunotherapy with autologous virus-specific T cells to affect the course of feline immunodeficiency virus (FIV) infection was explored in a group of specific-pathogen-free cats infected with FIV a minimum of 10 months earlier. Popliteal lymph node cells were stimulated by cocultivation with UV-inactivated autologous fibroblasts infected with recombinant vaccinia viruses expressing either FIV gag or env gene products, followed by expansion in interleukin-2. One or two infusions of both Gag- and Env-stimulated cells resulted in a slow increase in FIV-specific gamma interferon-secreting T cells in the circulation of cats. In the same animals, viral set points fluctuated widely during the first 2 to 3 weeks after adoptive transfer and then returned to pretreatment levels. The preexisting viral quasispecies was also found to be modulated, whereas no novel viral variants were detected. Circulating CD4(+) counts underwent a dramatic decline early after treatment. CD4/CD8 ratios remained instead essentially unchanged and eventually improved in some animals. In contrast, a single infusion of Gag-stimulated cells alone produced no apparent modulations of infection.     

Effect of interferon-alpha therapy on epitope-specific cytotoxic T lymphocyte responses in hepatitis C virus-infected individuals.

The majority of hepatitis C virus (HCV)-infected individuals fail to resolve the infection and become chronically infected despite the presence of HCV-specific CTL responses directed to different HCV-derived peptide antigens. Only a minority of individuals is able to clear the virus by mounting efficient CTL responses early after acute infection, but at present it is not clear whether viral clearance is associated with CTL responses of defined specificity. To elucidate those responses associated with improvement of the disease, we analyzed CTL responses to 16 different HLA-A2-presented, HCV-derived epitopes in 12 chronically infected patients, 14 chronically infected patients treated with interferon-alpha, and in one patient with acute symptomatic disease. We show here that the majority of chronically infected individuals present CTL responses directed to an NS4-derived peptide antigen (amino acids 1789-1797). Treated patients presented stronger HCV-specific CTL responses and therapy-induced changes in CTL target choice. In particular, 13 out of 14 individuals responded to an NS3-derived epitope (amino acids 1073-1081). By longitudinal analysis we show that five individuals responding to IFN-alpha therapy with decreases in alanine aminotransferase levels presented a strong CTL activity directed to the NS3-derived epitope. One patient that spontaneously resolved the infection presented a generally strong CTL activity specific for HCV-derived epitopes with a dominant response to the NS3-derived peptide antigen. This suggests that CTL responses directed to this NS3-derived antigen may be beneficial for the control of HCV infection. Improvement of these responses may represent a therapeutic intervention in chronic HCV infection.