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Biomedical subjects

M Morbin

Publications and source records attributed to M Morbin.

24 records · Page 2Linked to original sources

Delayed spongiform leukoencephalopathy after heroin abuse.

Here we report the clinical and pathological findings in a 30-year-old drug addict in whom an intravenous injection of heroin led to reversible coma with respiratory depression and heart failure. On regaining consciousness, the patient was found to have rhabdomyolysis with renal failure requiring dialysis and peripheral neuropathy. Three weeks later his neurological condition suddenly deteriorated and delayed encephalopathy developed, leading to death 20 days later. The neuropathological study of the brain disclosed pale, spongy myelin with diffuse reactive astrogliosis and microglial proliferation, without hypoxic necrotic lesions. The cerebral and cerebellar cortices were unchanged. The absence of typical hypoxic lesions and the presence of spongiosis with massive astrocytosis distinguished this case from the previously reported cases of delayed leukoencephalopathy following severe hypoxia. An immunocytochemical study designed to exclude an underlying alteration of the metabolic oxidative pathway detected normal expression of the respiratory chain complexes IV, III and V. Despite the absence of an oxidative chain alteration in our patient, we cannot exclude the possibility that an individual predisposition played a pathogenetic role in this delayed leukoencephalopathy.

Adult↗

Stereotactic brain biopsy in human immunodeficiency virus-infected patients.

OBJECTIVE: To evaluate prospectively the diagnostic efficacy and safety of stereotactic brain biopsy and its impact on treatment, outcome, and survival in human immunodeficiency virus-infected patients with focal brain lesions. METHODS: Computed tomography-guided stereotactic brain biopsy was performed in 26 patients, of whom 17 failed to respond to a 2- to 3-week anti- Toxoplasma regimen. Exclusion criteria for biopsy were overt acquired immunodeficiency syndrome for 2 years or longer, Karnofsky score less than 50, and severe coagulopathies. RESULTS: A definitive diagnosis was obtained in 24 patients (92%), of whom 12 (46%) had primary brain lymphoma, six (23%) had progressive multifocal leukoencephalopathy, and four (15%) had Toxoplasma encephalitis. Two thirds of contrast-enhancing lesions on computed tomography were lymphoma and three fourths of contrast-negative lesions were leukoencephalopathy. Three patients had biopsy-related cerebral hemorrhages (morbidity, 11.5%). Median follow-up and survival for the entire group were 24 weeks (range, 6 to 135 weeks). Twenty patients (77%) received specific therapy and 13 (50%) responded to treatment. Of 11 patients with lymphoma undergoing irradiation treatment (whole-brain radiotherapy in seven and gamma-knife treatment in four), nine (82%) had clinical and radiologic response, with a median survival of 34 weeks (range, 13 to 57 weeks). CONCLUSIONS: Stereotactic brain biopsy has high diagnostic efficacy and clinical benefit in carefully selected human immunodeficiency virus-infected patients. The procedure should be performed essentially in patients with contrast-enhancing lesions on computed tomography who have a high frequency of treatable cerebral diseases.

Adult↗

Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy.

We report the results of a clinical, electrophysiological and pathological study conducted in 18 AIDS patients presenting a distal symmetrical predominantly sensory polyneuropathy (DSPN) characterized by painful dysesthesias as main complaint. Onset of the neuropathy was at CDC (Center for Disease Control) stage II in 2 patients, at CDC stage III in 5 patients and at CDC stage IV in the remainder. Electrophysiological investigation confirmed the presence of an axonal alteration in the sensory nerves, but also revealed motor involvement in all cases. The neuropathological features of sensory nerves were fiber loss and axonal degeneration with macrophagic activation. The expression of monocyte-macrophage markers and of major histocompatibility complex class II antigens appeared up-regulated in endoneurial ramified cells, while expression of CR3, a complement receptor involved in the process of phagocytosis, was down-regulated. In six nerve biopsy samples and in two out of five DSPN dorsal root ganglia we found HIV-related mRNA and protein located in scattered cells of the endoneurium which we presume to be macrophages. These data suggest that: (a) DSPN may occur early in the course of the disease and is not limited to later stages; (b) DSPN is not a ganglionitis but is actually a sensory-motor neuropathy; (c) the virus enters the peripheral nervous system and induces changes in the immunocompetent cell population with activation of macrophages. Storage of the virus inside macrophages may act both as a reservoir for the virus and as a putative cause of nerve damage, probably through release of cytotoxins and/or interaction with trophic factors.

Acquired Immunodeficiency Syndrome↗

IDPN impairs post-traumatic regeneration of rat sciatic nerve.

The role played by cytoskeletal proteins in nerve regeneration was investigated in a model in which the axonal transport of neurofilaments (NF) is almost selectively impaired. The administration of beta, beta'-iminodipropionitrile (IDPN), a synthetic lathyrogenic compound, induces an axonopathy characterized by proximal axonal enlargements, due to NF accumulation, and by diffuse atrophic changes associated with spatial segregation of NF from microtubules (MT). We investigated post-axotomy regeneration of rat sciatic nerve following IDPN administration. Changes induced by IDPN, as examined in the proximal and distal nerve stump at 15 and 30 days after lesion, consisted of a statistically significant reduction of the mean axonal diameter (P < 0.0001) as compared to control rats. In addition, the number of regenerating myelinated fibres was smaller in dosed rats (P < 0.001) 15 days after crush, whereas at the later stage the number of axons approached that of control animals. Electrophysiological investigation revealed a delay in target reinnervation in dosed rats. Regenerating IDPN axons, both 15 and 30 days after crush contained fewer NF (P < 0.001), while the number of MT was slightly increased as compared to controls. Taken together, our results suggest that severe alteration of NF transport, coupled with mild alteration of other components of cytoskeletal proteins, impairs the longitudinal and radial growth of regenerating myelinated axons and confirm that the number of NF is the major determinant of the cross-sectional area of each segment of the axon.

Animals↗

Subunit A of factor XIII regulates subunit B plasma concentration.

Subunit a of Factor XIII is found absent in homozygotes and reduced in heterozygotes. Since a concomitant reduction of subunit b occurs in these cases, an interaction between the loci controlling the synthesis of the two subunits was suggested. However in the present study we have shown that the administration of subunit a in two totally devoid homozygotes produced an increase of subunit b, reaching the maximum concentration five days after infusion. This strongly suggests that subunit b plasma level is regulated on the subunit a plasma amount.

Biological Availability↗

Failure to measure plasma activated factor XIII during disseminated intravascular coagulation.

The search for activated products of coagulation factors in blood is of considerable clinical interest because its detection would indicate activation of the clotting system. Factor XIII circulates as inactive zymogen and becomes enzymatically active after thrombin or factor Xa activation. Employing an amine-incorporating system, activated factor XIII was measured in normal and pathological plasma from leukemic patients with overt laboratory signs of disseminated intravascular coagulation (DIC). Only traces of the activated factor were detected in both normal and DIC plasma. The method, sensitive and specific, as shown by the results of measurements on the plasma of 8 patients with congenital deficiency and on normal serum, did not prove to be useful for detecting pathological in vivo thrombin generation.

Acute Disease↗