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Biomedical subjects

R Troiano

Publications and source records attributed to R Troiano.

At least 37 records · Page 2Linked to original sources
PubMed1989

MHC-restricted autoantigen-reactive T cell clones in multiple sclerosis.

Multiple sclerosis is a demyelinating disease of the central nervous system with genetic, viral and autoimmune characteristics. Myelin basic protein (MBP) is a suspected target autoantigen since it induces experimental autoimmune encephalomyelitis, an animal model closely resembling multiple sclerosis. The disease is mediated by Class II restricted, MBP-reactive T cells possessing the T helper/inducer phenotype. In the present study, we have isolated MBP-reactive T cell clones from the peripheral blood of a chronic progressive multiple sclerosis patient. The clones displayed blastogenic memory responses when rechallenged with the autoantigen and irradiated autologous lymphocytes. MBP recognition by the autoantigen-reactive T lymphocytes was restricted by major histocompatibility complex Class II antigens. Both CD4+8- and CD4-8+ MBP-reactive T cell clones were obtained.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Total lymphoid irradiation for multiple sclerosis.

Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one. Our data suggest that this modified TLI regimen has clinical efficacy and sufficiently low toxicity to make it suitable for investigative immunosuppressive treatment of patients with progressive MS or other non-malignant conditions.

Adult↗
PubMed1988

T cell subsets and disease progression after total lymphoid irradiation in chronic progressive multiple sclerosis.

T lymphocyte subset percentages were determined in 16 total lymphoid irradiation (TLI) treated and 18 sham treated control patients with chronic progressive multiple sclerosis. During the first year after treatment, the ratio of T helper/inducer to T suppressor/cytotoxic cells (Th/Ts ratio) was significantly higher in sham treated multiple sclerosis patients who worsened clinically compared with TLI treated and sham treated multiple sclerosis patients who remained clinically stable. TLI caused a fall in the percentage of T helper cells in treated patients, while the percentage of T suppressor cells remained stable during the first year after treatment. In contrast, the percentage of T suppressor cells fell in sham treated multiple sclerosis patients who worsened clinically.

Follow-Up Studies↗
PubMed1988

Effect of total lymphoid irradiation on functional status in chronic multiple sclerosis: importance of lymphopenia early after treatment--the pros.

To determine whether immunosuppression by total lymphoid irradiation (TLI) slowed deterioration of chronic progressive multiple sclerosis (MS), functional impairment score and blood lymphocyte counts were compared at 6-month intervals through 4 years following treatment of MS patients by either TLI (n = 27) or sham irradiation (n = 21). At each interval, 20 to 30% fewer TLI-treated patients had deteriorated (p less than 0.05 at 6, 12, and 18 months), and the difference in mean functional impairment score between groups became progressively greater (p less than 0.01 at 42 and 48 months). Benefit accrued principally to the 17 TLI-treated patients with absolute blood lymphocyte counts less than 900/mm3 3 months after treatment, whose mean functional impairment score remained within 0.6 units of baseline (p = NS), whereas the ten TLI patients with higher post-treatment lymphocyte counts had progressive deterioration (p less than 0.05 to p less than 0.001 versus TLI-treated patients with lower lymphocyte counts at all intervals except 30 months) and had deteriorated by more than 5 functional scale units by 42 and 48 months. Side effects were minor and complications rare in TLI-treated patients, but one TLI-treated patient developed staphylococcal sepsis. Thus, TLI slows deterioration of chronic progressive MS, with what appears to be enduring benefit through 4 years compartmented to patients with greater induced lymphopenia. Modification of lymphoid irradiation regimens to increase the proportion of MS patients who achieve a favorable degree of lymphopenia and to avert functional hyposplenism may further improve the benefit/risk ratio.

Adult↗
PubMed1987

Steroid therapy in multiple sclerosis. Point of view.

A number of studies have demonstrated that high-dose corticosteroid treatment improves the rate of recovery from acute exacerbations of multiple sclerosis. The beneficial effect is more rapidly and consistently produced by high-dose corticosteroid administration than with adrenocorticotropic hormone. The most rapid improvement in clinical condition and cerebrospinal fluid parameters of patients has been observed with short courses of very high-dose intravenous therapy. This form of treatment would be most advantageous for patients with severe and rapidly progressive exacerbations. Ultimately, the duration of treatment will depend on the patient's response to treatment, tolerance of corticosteroid withdrawal, and the occurrence of significant complications of therapy. However, in our experience, a three- to four-month slowly tapered course of oral therapy is often needed, and is usually well tolerated, with few serious side effects when given once daily in the morning.

Acute Disease↗
PubMed1987

Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course.

We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases.

Adult↗
PubMed1986

Effect of total lymphoid irradiation in chronic progressive multiple sclerosis.

Total lymphoid irradiation (TLI; 1980 cGy) or sham irradiation was given to 40 patients with chronic progressive multiple sclerosis (MS) in a prospective, randomised, double-blind study. During mean follow-up of 21 months, MS patients treated with TLI had less functional decline than sham-irradiated MS patients (p less than 0.01). A significant relation was noted between absolute blood lymphocyte counts in the first year after TLI and subsequent course, patients with higher lymphocyte counts generally having a worse prognosis (p less than 0.01). TLI was well tolerated and associated with only mild short-term, and to date, long-term side-effects.

Adult↗
PubMed1984

Effect of high-dose intravenous steroid administration on contrast-enhancing computed tomographic scan lesions in multiple sclerosis.

Six consecutive patients with multiple sclerosis and lesions contrast enhancing on computed tomographic scan were treated with high-dose intravenous infusions of methylprednisolone. Double-dose delayed computed tomographic scans were repeated at varying intervals during corticosteroid treatment. Contrast enhancement of sclerotic plaques was reduced or eliminated within as little as 8 hours after the first infusion. Rapid associated partial clinical improvement was noted in four patients with recent exacerbations of disease activity. Similar attenuation of contrast-enhancing plaques and clinical improvement were less predictable following oral corticosteroid therapy in conventional dosage. These studies suggest that the dose, route of administration, and duration of corticosteroid therapy in multiple sclerosis may partially determine the effect of treatment.

Adult↗
PubMed1982

A 14C-2-deoxyglucose analysis of the neural pathways of the limbic forebrain in the rat: II. The hypothalamus.

An attempt was made to characterize the nature of the functional organization of the hypothalamus by observing the patterns of uptake of 14C-2-deoxyglucose (2DG) following electrical stimulation of different regions within the preoptico-hypothalamus in the rat. The experimental paradigm consisted of electrical brain stimulation delivered continuously for periods of 30 sec on and 30 sec off for 45 minutes following injection of 2DG. Brains were removed and processed for autoradiography. Activation of the medial forebrain bundle was noted following stimulation of the nucleus accumbens and lateral preoptico-hypothalamus. Activated fibers could be followed only in a caudal direction through the medial forebrain bundle and into the ventral tegmental area as a result of nucleus accumbens stimulation. Stimulation of the lateral preoptic region or of the anterior half of lateral hypothalamus produced activation of the lateral septal nucleus, lateral habenular nucleus, perifornical region, midline thalamus and ventral tegmental area. Since stimulation of the perifornical hypothalamus significantly activated the rostro-caudal extent of the midbrain cental gray, it is suggested that impulses from the lateral hypothalamus reach the lower brainstem via its connections with the perifornical hypothalamus. Ventromedial hypothalamic stimulation activated only the lateral septal nucleus, cortico-medial amygdala and medial preoptico-hypothalamus, while medial preoptico-hypothalamic stimulation resulted in increased 2DG uptake in the midbrain central gray, thus suggesting that medial hypothalamic impulses reach the brainstem by first ascending to the level of the preoptico-hypothalamus. Mammillary body stimulation orthodromically activated fibers in the mammillothalamic and mammillotegmental tracts and antidromically fibers in the fornix for a short distance.

Amygdala↗
PubMed1975

Effect of stimulation of prefrontal cortex and amygdala on diencephalic neurons.

Extracellular unit recordings were obtained from the nucleus medialis dorsalis (MD) and adjacent thalamic nuclei and from the hypothalamus of anesthetized cats. Electrical stimulation of the prefrontal cortex produces suppression of unit activity and rebound excitation in MD. In addition antidromic and short latency excitation was found which was followed by prolonged suppression of firing. This suppression was also followed by a strong postinihibitory activation of unit firing which was, in some cases, again followed by a second phase of inhibition. Amygdala stimulation produced similar results except that antidromic responses were found only in the intralaminar nuclei, and short-latency transynaptic excitation occurred somewhat later. The results are in consonance with the hypothesis that the same interneuronal mechanism is engaged by both afferent sources to MD. In the hypothalamus, fewer units responded to cortical and amygdalar stimulation and alternating sequences of excitation-inhibition-excitation were not found.

Amygdala↗