Complete mutism after midbrain periaqueductal gray lesion.

Several neurophysiological studies have highlighted the role of the midbrain periaqueductal gray matter (PAG) in the initiation of vocalization in various animal species, from frogs to primates. With regard to humans, only two cases of complete mutism following a lesion to the PAG have been reported so far. This article describes a new case of a patient (GM) who, following an ischemic lesion to the periaqueductal gray region of the midbrain, presented with complete and irreversible mutism, though her language comprehension functions and her non-verbal expression capacity were preserved. This clinical case provides evidence that in humans the PAG also acts as a link between different vocalization-eliciting external and internal stimuli (which reach the PAG from sensory and emotional structures) and the vocal-motor coordinating mechanisms in the lower brain stem.

Intravenous immunoglobulin versus corticosteroid in treatment of Graves' ophthalmopathy.

We compared the effectiveness of systemic corticosteroids with the use of high-dose intravenous immunoglobulin (IVIG) in the treatment of Graves' ophthalmopathy. This was performed as a prospective, nonrandomized study including a blinded ophthalmological and orbital computed tomographic (CT) evaluation. The two groups of patients were not significantly different in relation to sex composition, age distribution, duration of Graves' disease, and ophthalmopathy and previous hyperthyroidism. All patients were followed up by endocrinologic evaluation and blinded ophthalmological (before therapy = B, at the end of therapy = E, and 6 months after the end = 6M) and orbital CT (B and E) evaluations. Twenty-seven patients treated with IVIG were followed up after the end of treatment for an average of 21 months (range 12 to 48 months). Soft tissue involvement (NOSPECS) improved or disappeared in 32 of 35 (90%) patients treated with IVIG and in 25 of 27 (92.5%) patients treated with corticosteroids. Diplopia improved or disappeared in 22 of 29 (75%) patients treated with IVIG and in 16 of 20 (80%) patients treated with corticosteroids. The results observed by clinical evaluation were confirmed with orbital CT score in 30 IVIG patients and in the corticosteroid-treated patients; a significant reduction of extraocular muscle thickness was observed after treatment in both groups. Proptosis improved or disappeared in 20 of 31 (65%) patients treated with IVIG and in 15 of 24 (62%) patients treated with corticosteroids. Mean values of proptosis evaluated by Hertel's exophthalmometer showed a slight reduction both in IVIG as well as in corticosteroid-treated patients. It is interesting to observe that in 28 IVIG-treated patients in whom it was possible to evaluate soft tissue involvement, proptosis and diplopia in the period between the fifth and sixth month from the start of therapy, the most important part of the amelioration (if responders) was already obtained at that time. Responder patients were defined in relation to the decrease in the highest NOSPECS class or grade. Among IVIG-treated patients 26 of 34 (76%) responded; while in the corticosteroid group 18 of 27 (66%) responded to treatment. The prevalences of patients who responded to the treatments were not significantly different in the two groups (Chi-square). The initial values of the subjective eye score were similar in the two groups, and a significant reduction was observed in both. Major side effects requiring discontinuation of the corticosteroid therapy were observed in two patients with hemorrhagic gastritis and in one patient with manic-depressive psychosis. Among 15 patients submitted to the evaluation of bone mineral content before and after corti-costeroid therapy, 4 presented signs of osteoporosis and 3 a reduction of bone mineral content. Moderate and minor side effects were more frequently noted in steroid-treated patients than in the IVIG group. These data suggest that IVIG is safe and effective in reducing the eye changes in patients with Graves' ophthalmopathy.

Role of neck ultrasonography in the follow-up of patients operated on for thyroid cancer.

The aim of the study was to evaluate the role of neck ultrasonography in follow-up of patients with differentiated thyroid cancer. Sixty-three patients had total thyroidectomy and 131I ablation for differentiated thyroid cancer and had a negative whole body scan during follow-up. They were admitted for a high resolution neck ultrasound examination. Sixteen of 63 patients presented images suspicious for lymph node metastasis and/or for local recurrences (4 cases). Fine needle aspiration confirmed the suspicion of malignancy in 12 patients: only lymph node metastasis in 8 cases, local recurrence and lymph node metastasis in 3 cases, and in one case only local recurrence. Fine needle aspiration was suspicious for lymphadenitis in 4 cases. Thyroglobulin levels were very high in all patients with local recurrence and/or lymph node metastasis but undetectable in 2 cases presenting node metastasis and in 4 cases with lymphadenitis. All but one patient were admitted for surgery and the cytological diagnosis was confirmed. Early identification of a pathologic mass in the neck is a desirable goal; high resolution echography can play an important role in the follow-up of these patients and can detect local recurrences even when there is a negative whole body scan or undetectable thyroglobulin level.

Comparison between ethanol sclerotherapy and emptying with injection of saline in treatment of thyroid cysts.

We compared the results of ethanol sclerotherapy in thyroid cysts with emptying of cysts and instillation of saline. Twenty-six patients with recurrent thyroid cysts were treated with cyst aspiration and subsequent ethanol sclerotherapy. A control group of 44 patients was submitted to cyst aspiration and subsequent injection with isotonic saline; among them 20 had previously been treated with repeated aspirations of the cyst fluid. The patients were followed up clinically and ultrasonically 1 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion or an ultrasonic cyst volume less than 50% of basal after 12 months from the start of treatment. Cytological study showed all of the lesions to be benign. Of the 44 patients in the saline group 16 (36%) were cured, among whom 6 of 20 had previously been submitted to repeated aspirations. Among the 26 patients treated with ethanol sclerotherapy 20 (77%) were cured. Statistical analysis revealed a significantly higher effectiveness of treatment with ethanol than that with emptying and saline instillation (chi-square, P = 0.002) or with repeated aspiration and saline instillation (chi-square, P = 0.003). Slight pain was observed in two patients treated with saline and five treated with ethanol sclerotherapy. Three patients treated with ethanol sclerotherapy presented severe pain and one transitory hyperthyroidism. We conclude that ethanol sclerotherapy is effective and safe in the treatment of thyroid cysts.

[Review of a case series of cervical cysts and evaluation of the efficacy of sclerotherapy with tetracycline hydrochloride in thyroid cystic lesions]. / Revisione di una casistica di cisti della regione cervicale e valutazione dell'efficacia del trattamento sclerosante con tetraciclina cloridrato nelle lesioni cistiche tiroidee.

We have reexamined a series of 1119 patients consecutively submitted to fine needle aspiration of nodules of the neck. Among these in 166 cases ultrasonography combined with aspiration suggested the presence of cysts. 60 patients were submitted to cyst aspiration and 34 were aspirated and submitted to cyst injection with tetracycline hydrochloride. The patients were followed up clinically and ultrasonically 3 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion and an ultrasonic cyst volume less than 50% with respect to basal after 12 months from the start of treatment. 18 of the 60 (30%) patients only aspirated and 24 of the 34 patients (70%) in the tetracycline group were cured (statistically significant; p < 0.005). We conclude that tetracycline seems an effective sclerotherapy in treatment of thyroid cysts.

Pretibial myxedema and high-dose intravenous immunoglobulin treatment.

Seven patients affected by Graves' ophthalmopathy and pretibial myxedema (four patients with nodular form, two with diffuse, and one with elephanthiasic form) have been treated with high-dose intravenous immunoglobulins. We have observed (a) clinical improvement of pretibial myxedema and Graves' ophthalmopathy in all patients, (b) a reduction of pretibial skin thickness, by ultrasonography evaluation, in four patients, (c) a reduction of mucopolysaccharide skin content in three patients, (d) disappearance of lymphocytic skin infiltration and IgG deposition in two patients, and (e) a parallel reduction of the titer of circulating autoantibodies as antithyroglobulin, antimicrosomal, anti-TSH receptor, and of non-organ-specific antibodies as antinuclear, anti-smooth muscle cells, and anti-mitochondrial. In comparison two patients with Graves' ophthalmopathy and pretibial myxedema treated with systemic corticosteroids did not present any improvement of the cutaneous ailment. Therefore, this study suggests that intravenous immunoglobulins are effective in the treatment of pretibial myxedema and may have an immunomodulant action in patients with Graves' disease and related disorders.

Prospective, randomized, double-blind study about effectiveness of levothyroxine suppressive therapy in prevention of recurrence after operation: result at the third year of follow-up.

BACKGROUND: Levothyroxine has often been given to patients operated on for nodular goiter to prevent recurrence. The rationale is that suppression of thyroid-stimulating hormone (TSH), considered to be the main growth factor in this disease, can be obtained by administration of levothyroxine. METHODS: Sixty patients undergoing operation for nontoxic nodular goiter were randomized in two groups: (1) thirty-two were administered levothyroxine at substitutive dosage (100 micrograms) or placebo and (2) twenty-eight were given levothyroxine at suppressive dosage (2.2 to 3 micrograms/kg/day). Levels of thyroid hormones and TSH were evaluated every 6 months. Recurrences detected by echography were then considered. RESULTS: After a 3-year follow-up we observed 25 of 32 recurrences in group 1 and 6 of 28 in group 2 (p < 0.005). Subjects with endemic goiter problems responded better to therapy. Patients with a multinodular goiter responded better than patients with a uninodular goiter. No difference was found regarding the type of surgical treatment (subtotal thyroidectomy vs lobectomy). CONCLUSIONS: The results confirmed suppressive therapy as actually being effective in preventing recurrences at least in iodine-deficient regions like Italy. Thus for these patients it may be suggested as a prophylactic treatment after operation.

Demeclocycline-induced phosphate diabetes in a patient with inappropriate ADH secretion and systemic sarcoidosis.

We report a case of phosphate diabetes in a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with sarcoidosis. Our patient was affected by systemic sarcoidosis and he fits the criteria of Schwartz for the diagnosis of SIADH. He presented with phosphate diabetes which appeared during demeclocycline (DMC) therapy and persisted for about 1 month from the end of DMC. It constitutes the fourth case of phosphate diabetes induced by tetracycline described in the literature and it is the third case of SIADH associated with sarcoidosis.

Inappropriate antidiuretic hormone secretion in a patient with systemic sarcoidosis.

A 59 year old man presenting fever, serum hyponatremia and hypoosmolality in association with hyperosmotic urine was hospitalized in our unit in February 1988. We demonstrated evidence of systemic sarcoidosis and inappropriate secretion of antidiuretic hormone (ADH). The patient was treated with corticosteroid therapy for a period of about 1 year, with regression of signs of the inappropriate vasopressin secretion as well as the symptomatology related to systemic sarcoidosis. This study identified systemic sarcoidosis as a definite cause of "syndrome of inappropriate ADH secretion".

[Changes in markers of autoimmunity in patients with Hashimoto thyroiditis treated with intravenous immunoglobulins. Preliminary results]. / Modificazioni dei markers di autoimmunità in pazienti affetti da tiroide di Hashimoto trattati con immunoglobuline per via endovenosa. Risultati preliminari.

We have evaluated the variations of thyroid function, of thyroid autoantibodies titer, of non-organ specific autoantibodies and of other autoimmunity indices in 3 patients affected with Hashimoto's thyroiditis treated with "high dose intravenous gammaglobulin" (IVIG) (400 mg/Kg/day for 3 cycles of 5 days and subsequently 9-12 cycles of 1 day every 21 days). Before the starting of IVIG treatment patient 1 presented clinically evident hypothyroidism while patients 2 and 3 presented a preclinical form of hypothyroidism. At the end of IVIG treatment patients presented no variation of thyroid function, while patients 2 and 3 presented a normalization of T3, T4 and TSH circulating levels. Before the starting of IVIG treatment thyroglobulin antibodies (TgAb) were positive in 3/3 patients, microsomal antibodies (MAb) were positive in 3/3 patients adt TRAb were positive in 2/3 patients and MAb titre was decreased or negative in 0/3 patients. At the end of IVIG treatment Tg Ab titre was decreased or negative in 2/3 patients and MAb titre was decreased or negative in 2/3 patients. Anti-nuclear antibodies (ANA) 1/3 patients before the titre and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA), anti-mitochondrial antibodies (AMA), C3, C4, CH50 and rheumatoid factors were negative or in the normal range in all the patients. In conclusion these data suggest that IVIG is effective in the treatment of preclinical hypothyroidism in patients with Hashimoto's thyroiditis and determine a stable immunosuppressive action on circulating thyroid and non organ specific autoantibodies.

[Autoimmune polyendocrine syndrome. Treatment with intravenous immunoglobulins]. / Sindrome poliendocrina autoimmune. Trattamento con immunoglobuline endovena.

We report the effect of "intravenous gamma-globulin treatment" (IVIG) in a patient with autoimmune polyglandular syndrome type II, with circulating organ specific autoantibodies, preclinical hypothyroidism, amenorrhea and Addison syndrome. During IVIG treatment we observed a normalization of thyroid function, the appearance of some non ovulatory menses, reduction of thyroglobulin, thyroidal microsomal, anti-parietal cell, adrenal and ovary antibodies. These data confirm that intravenous immunoglobulin may represent a new tool for treatment of autoimmune disorders and show, for the first time, an immunosuppressive effect of intravenous gammaglobulin treatment in immunological phenomena direct against ovary, adrenal and gastric mucosa.

[Parameters of organ-specific and non-specific autoimmunity in patients with Basedow's disease and Basedow's ophthalmopathy. Changes induced by IVIG treatment]. / Indici di autoimmunità organospecifica e non in pazienti affetti da morbo di Basedow ed oftalmopatia basedowiana. Variazioni indotte dal trattamento con IVIG.

The aim of this study was to evaluate the variations of thyroid autoantibodies titre in a group of 15 patients affected with "Graves' disease" (G. D.) during the treatment with antithyroid drug (ATD) and "high dose intravenous immunoglobulin" (IVIG) for "Graves' ophthalmopathy". Before the starting of treatment thyroglobulin antibodies (TgAb) were positive in 10/15 patients, microsomal antibodies (MAb) were positive in 13/15 patients and TRAb were positive in 5/9 patients. At the end of treatment TgAb titre was decreased or negative in 7/10 patients, MAb titre was decreased or negative in 7/13 patients, TRAb titre was diminished or negativized in 5/5 patients. Anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were positive in 3/15 and 3/15 patients before the treatment and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA)m anti-mitochondrial antibodies (AMA) and rheumatoid factors were negative in all the patients. Also in the 3 patients not treated with ATD we have observed a reduction or a negativization of circulating thyroid autoantibodies. In conclusion these data suggest that the reduction of thyroid and non organ specific autoantibodies might be due to a stable immunosuppressive action of IVIG treatment in patients with Graves' disease.

[Liver function tests, hepatitis A, B, C markers and HIV antibodies in patients with Basedow's ophthalmopathy treated with intravenous immunoglobulins]. / Monitoraggio delle prove di funzione epatica, dei markers dell'epatite A, B, C e degli anticorpi anti HIV nei pazienti trattati con immunoglobuline endovena (IVIG) per oftalmopatia basedowiana.

Recent reports of transmission by intravenous gamma-globulin preparations of A, B, C and non-A non-B hepatitis (NANBH), including several cases that progressed to severe liver damage and death, have raised concerns about the safety of intravenous gamma-globulins. To assess this issue 15 patients treated with high-dose "intravenous immunoglobulin" (IVIG) for Graves' Ophthalmopathy had serial determination of glutamic pyruvic transaminase (GPT), glutamic oxalacetic transaminase (GOT), gamma glutamyltranspeptidase (gamma-GT), alkaline phosphatase and bilirubin that were performed regularly at interval of 3 weeks during IVIG treatment and 6 months after the end of the treatment. Hepatitis A, B, C and HIV markers were determined before, during and 6 months after the end of the treatment. The standard dosage was 400 mg per Kg body weight IVIG (3 cycles of 5 days and 12 of 1 day, every 21 days). Transient minor elevations were observed for GPT, for GOT, for gamma-GT and alkaline phosphatase. None of the elevations were considered indicative of NANBH or of any chronic hepatic disease. Transient presence of hepatitis A, B and C antibodies were observed in 6 patients. All patients remained negative for hepatitis B antigens throughout the study. HIV antibodies resulted always negative in all patients. In conclusion this study suggests the hepatitis and HIV safety of IVIG.

[Results of high-dose intravenous immunoglobulin treatment of patients with pretibial myxedema and Basedow's disease. Preliminary findings]. / Risultati del trattamento con immunoglobuline endovena ad alto dosaggio in pazienti affetti da mixedema pretibiale e morbo di Basedow. Osservazioni preliminari.

Three patients affected with Graves' ophthalmopathy and pretibial myxoedema have been treated with high dose intravenous immunoglobulins. We have observed in all patients clinical improvement of pretibial myxoedema and a parallel reduction or negativization of the titre of circulating thyroglobulin, microsomal, TSH receptor autoantibodies and of non organ-specific antibodies (antinuclear, anti smooth muscle cells and antimitochondrial autoantibodies). In conclusion the results of this study suggest that intravenous immunoglobulin are effective in the treatment of pretibial myxoedema and probably act by an immunomodulation of autoimmune phenomena.

[The combined therapy of Basedow's ophthalmopathy with retrobulbar radiotherapy and i.v. immunoglobulins. The preliminary results]. / Terapia combinata della oftalmopatia basedowiana con radioterapia retrobulbare e immunoglobuline e.v. Risultati preliminari.

The most frequently used medical treatment of Graves' ophthalmopathy is the combination of orbital irradiation and systemic corticosteroid. In this study the effectiveness of "high dose intravenous immunoglobulin" (IVIG) in Graves' ophthalmopathy treatment is explored. 11 patients were treated with orbital radiotherapy combined with systemic corticosteroid (Group 1), while 10 patients were treated with the combination of orbital irradiation and IVIG (Group 2). The therapeutic effect was assessed by an ophthalmopathy index based on the American Thyroid Association, classification of ocular changes of Graves' ophthalmopathy. All signs and symptoms of endocrine ophthalmopathy improved significantly in both groups. The mean ophthalmopathy index decreased from 7.0 +/- 1.3 to 3.4 +/- 1.5 in Group 1, and from 7.0 +/- 1.8 to 3.0 +/- 2.1 in Group 2. Statistical analysis showed no significant difference between Group 1 and 2 mean initial and final ophthalmopathy index, and a significant difference between initial and final ophthalmopathy index both in Group 1 and 2. While side effects were present in Group 1 treated with systemic corticosteroid, no side effect was observed in patients treated with IVIG. These preliminary results suggest that IVIG is safe and effective in the treatment of Graves' ophthalmopathy.

High-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy.

We have evaluated the efficacy of high-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy, and have carried out a prospective randomized clinical trial, including a single-blind evaluation, whereby 14 patients were assigned to two different treatment groups: 7 patients were treated with intravenous immunoglobulin and orbital radiotherapy (Group 1) and 7 patients were given intravenous immunoglobulin alone (Group 2). The results of the intravenous immunoglobulin treatment were also compared with those obtained in a Historical Control Group (12 patients) treated with systemic methylprednisolone and orbital irradiation. Degree of ocular involvement and response to treatment were assessed by ophthalmopathy index. The mean initial and final ophthalmopathy index showed no significant difference among the three groups. Comparison between the mean initial and final ophthalmopathy index showed a statistically significant reduction (p less than 0.005) in all three groups, the observed changes being confirmed by orbital computerized tomography in Groups 1 and 2. Corticosteroid treatment was associated with major and minor side effects, while no important adverse reactions were observed during intravenous immunoglobulin treatment. Even considering our results as preliminary, we conclude that intravenous immunoglobulin treatment is effective and safe in improving Graves' ophthalmopathy.

Enzymatic synthesis of formic acid from H2 and CO2 and production of hydrogen from formic acid.

Whole cells of Alcaligenes eutrophus (as well as isolated P. oxalaticus formate dehydrogenase and A. eutrophus hydrogenase coupled via NAD(+) or methyl viologen) have been shown to produce H(2) from formic acid. Immobilization of the cells in kappa-carrageenan gel greatly enhances their stability at room temperature. The rate of hydrogen production catalyzed by immobilized A. eutrophus has been studied as a function of the concentrations of the cells and formate and also pH. An inhibition by high concentrations of formate has been found. Immobilized cells were also capable of synthesizing formate from H(2) and bicarbonate. Yields of formate up to 30% have been obtained. The catalytic efficiency of immobilized A. eutrophus cells was compared with that of palladium adsorbed on activated carbon.