Laboratory animals: NIH to lay down the law.
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Biomedical subjects
Publications and source records attributed to P David.
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A case of cystic schwannoma that presented as an intraaxial lesion on CT is reported. Magnetic resonance was able to detect the extraaxial origin of the tumor.
Twelve patients, eleven with a carotid obstruction and one with an occlusion of the middle cerebral artery, were studied before and after a successful unilateral extra-intracranial arterial by-pass, (EIAB) using PET and the 15-0 steady-state technique to measure regional cerebral blood flow (CBF), oxygen extraction fraction and oxygen metabolic rate (CMRO2). In the whole group of patients, both CBF and CMRO2 increased significantly on both cerebral hemispheres after EIAB, returning toward control levels defined in age-matched subjects. Mean oxygen extraction fraction, on the other hand, was not affected. Individually, three different effects of EIAB emerged: 1) Alleviation of a state of long standing unilateral "misery-perfusion", as reported earlier; 2) parallel increase of CBF and CMRO2 bilaterally, which appeared due to improvement of a hemodynamic depression of metabolism, the precise mechanism of which remains obscure; 3) Complex, unexpected changes in the CBF-CMRO2 couple again resulting in increases in CMRO2. This metabolic improvement afforded by EIAB in our patients has not been reported before; it suggests that long-standing hemodynamic failure may induce a metabolic depression that is still potentially reversible by surgical revascularization.
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Banking of cryopreserved hepatocytes is a prerequisite for large-scale hepatocyte transplantation in the clinic. We compared the efficacy of intrasplenic transplantation into Nagase analbuminemic rats (NAR) of freshly isolated (FIH) and cryopreserved (CH) hepatocytes. Hepatocytes were cryopreserved using a controlled rate freezing protocol. Albumin production of thawed CH and FIH was measured in vitro in culture by ELISA and by Western blot. After in vivo intrasplenic transplantation of NAR with either FIH or CH we assessed 1) albumin in the serum of recipients by ELISA and by Western blotting analysis at different time intervals, and 2) hepatocyte engraftment by albumin immunohistochemical staining into spleens and livers at euthanasia. In vitro, albumin was produced up to day 4 of culture in both CH and FIH. In vivo, no intrasplenic engraftment of hepatocytes occurred. Intrahepatic engraftment of CH (cell number/mm2) was significantly (twofold) lower than that of FIH and appeared only as isolated cells and small (<10 cells) clusters, while bigger clusters (>10 cells) were observed with FIH. In the FIH group, serum albumin production was observed up to 32-49 days posttransplantation while in the CH group no serum albumin production was detected. Our results emphasize the need to improve 1) hepatocyte transplantation procedures either by repeated hepatocytes injections and/or by transplantation under a regeneration response, and 2) the freeze/thaw protocols of hepatocytes.
BACKGROUND: Polyoma virus (PV) is a double-stranded DNA virus, member of the Papovaviridae family. BKV and JCV are the most studied in human pathology, whereas simian virus 40 (SV40) is pathogenic in the monkey and has been implicated in human carcinogenesis. PV is associated with renal and urinary tract pathology. The initial infection by PV occurs in childhood, probably by airways, and is usually asymptomatic. Subsequently, it remains latent in kidneys, tonsils and CNS and may reactivate in concomitance with significant T-cell dysfunction. Infection in immunocompromised patients can be clinically relevant. However, asymptomatic viruria may be detected in 0.3 % of individuals without a known history of immunodeficiency. CASE REPORT: We describe the case of a male patient, aged 31, admitted to our Unit for arterial hypertension and urinary abnormalities. He had a history of hemorrhagic cystitis in 1996 and persistent microscopic hematuria thereafter. Renal function was normal, arterial pressure well controlled with an ACE-inhibitor; urine culture was negative and most of the immunologic and rheumatologic tests were normal, with the exception of slightly reduced levels of C3 and an inverted CD4/CD8 ratio. Serology for HCV, HBV, HIV and screening for tumor markers were negative. Renal ultrasonography displayed an increased reflectivity, as seen in medical nephropathies; no nephrolithiasis was found. Urinary cytology showed "decoy cells", as typically found in PV infection, whose presence was confirmed by n-PCR. Diagnosis at discharge from the hospital was primary arterial hypertension and urinary JCV infection. Currently, no treatment of proven efficacy against PV is available. CONCLUSIONS: We think that there is an increasing amount of evidence to include screening for PV in the diagnosis of urinary tract abnormalities of unknown origin, even in apparently immunocompetent patients. Urinary cytology, in experienced hands, may be a useful and relatively inexpensive first step diagnostic tool.
A 72-year-old woman was admitted for the work-up of an abdominal pseudomyxoma. A brain CT was performed and revealed the presence of a tumorlike lesion in the left temporal lobe. The diagnosis of focal heterotopy was suggested and confirmed by MRI. Careful clinical history revealed Grand Mal epilepsy during infancy that was well controlled by antiepileptic drugs. No imaging studies had ever been performed. This case illustrates that the diagnosis of idiopathic epilepsy should be established only after having ruled out brain disorders including heterotopy, which can be demonstrated by MRI.
We describe the case of an adult patient with a benign congenital esophagobronchial fistula. The different types of congenital fistula without atresia or in H form are discussed. We formulate some hypotheses explaining the late occurrence of symptoms in a lesion present since the patient's birth.
A new case of subacute sclerosing panencephalitis with onset in adult life is reported. Clinical picture was characterized by a maculopathy, followed two years after by behavioural disturbances, psychomotor impairment, pyramidal signs and left-side myelonic jerks synchronously with the typical periodic R-complex in the EEG. CT-scan and MRI showed a wide demyelinative lesion in the right temporo-occipital area of the brain. Elevated antibody titers to measles virus in serum and CSF were present. Death occurred within 6 months while in coma. The neuropathologic findings confirmed the diagnosis of SSPE revealing widespread inflammatory lesions in the grey and white matter areas of demyelinization more evident in the right temporo-occipital regions and several Cowdry type A inclusions in glial cells and neurons.
The aim of this work was to study the neuropathological picture of the sural nerve in the pseudopolyneuropathic form of amyotrophic lateral sclerosis (ALS). Five patients were considered: in all cases the clinical and electromyographic follow-up excluded other diseases. EMG-studies were repeatedly performed: they showed the progressive evolution of the spinal anterior horn cell pathology from lower spinal to cervical levels. The sural nerve was removed and immediately fixed in phosphate-buffered 2.5% glutaraldehyde and processed according to the procedure used in our laboratory for light and ultrastructural microscopy. Quantitative analysis of myelinated fiber density was carried out on photographic enlargements of 1 micron semithin sections and recorded on histograms. The light and ultrastructural findings revealed a severe loss of myelinated fibers, the decrease affecting all types of fibers, but predominantly the largest ones. In the teased fibers, Wallerian-like degeneration was observed. In the axons there was an increase of mitochondria, dilatation of the small vesicles, and an increase in the number of neurofilaments. It can be assumed from the histopathologic data that the neuropathologic pattern in the pseudopolyneuropathic form of ALS shows an axonal degeneration. It is our opinion that the histopathologic data obtained in the sural nerve biopsy in this form of ALS reveals a clear involvement of the sensory neurons of the spinal ganglia, and the results can be useful for the study of precocious lesions in ALS.
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