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Plasma and Muscle Carnitine Levels in Haemodialysis Patients with Morphological-Ultrastructural Examination of Muscle Samples

The present study investigates 14 patients on intermittent haemodialysis. Pre-dialysis blood and muscle samples taken for determining plasma free- and acetylcarnitine levels. The tissue fragments were used for light and electron microscopy studies. Our results support the findings of other investigators that patients on haemodialysis generally display decreased free- and acetylcarnitine levels both in plasma and skeletal muscle when compared with control values. Muscle carnitine deficiency was apparently more severe in the longer-term haemodialysis patients. Moreover, a significant correlation (p less than 0.05) between plasma and muscle free-carnitine values was found. Morphologically no pathological alterations were observed in the muscle fibres in 13 of the patients. Light and electron microscopic studies of the muscle fibre of the 14th patient showed a typical nemaline myopathy with rod bodies in the cytoplasm. The muscle free-carnitine concentration in this patient was among the lowest of the group.

Increased serum thyroglobulin concentrations and impaired thyrotropin response to thyrotropin-releasing hormone in euthyroid subjects with endemic goiter in Sicily: their relation to goiter size and nodularity

Serum thyroglobulin (Tg), T4, T3, FT4, FT3, TSH concentrations and TSH response to iv TRH (ΔTSH) were measured in 56 consecutive patients with (multi) nodular goiter from a severily iodine-deficient endemic goiter area in Northeastern Sicily and in 11 non goitrous euthyroid individuals living in the same area. Serum Tg concentrations were sharply increased in goitrous subjects (453 ± 476 ng/ml) and related to thyroid size and the presence of nodules (χ2 = 43.5, p < 0.0005). Serum TSH levels measured in goitrous patients (2.1 ± 0.9 μU/ml) were significantly lower than those measured in nongoitrous iodine deficient subjects (3.1 ± 0.9 μU/ml, p <0.001) and decreased with increasing goiter size and nodularity (χ2 = 27.3, p<0.05). A similar pattern was shown by the analysis of the Δ TSH (χ2 = 43.1, p<0.0005). These results suggest that at least a part of the largest and multinodular goiters become autonomously functioning with duration and growing in size. In 13 goitrous patients with absent or impaired response to TRH, a significant direct relation was apparent between log-Tg and goiter size and nodularity (r = 0.64) with an inverse relationship between serum FT3 and Δ TSH (r = 0.73). A computed program analysis based on the combination of different independent variables (x) including age, thyroid size and nodularity, serum TSH, log-Tg and FT3, indicated the existence of a significant negative relationship between these variablesand the TSH response to TRH (r = 0.75, p = 0). This confirms the limited clinical significance of the impaired TSH response to TRH in patients with multinodular goiters and gives an explanation for the not infrequently observed ineffectiveness of suppressive treatment with thyroid hormones.

Circulating immunoglobulin E (IgE) antibodies to L-thyroxine in a euthyroid patient with multinodular goiter and allergic rhinitis

A 30-yr-old woman with allergie rhinitis and multinodular goiter developed atopic manifestations on different desiccated thyroid extract treatment. U rticaria was observed when the patient was on L-T4 treatment; no atopy was experienced during L-T3 regimen. Serum total immunoglobulin E (IgE) concentration was 390 ± 7kU/liter (mean ± SD) prior to any treatment and rose to 850 ± 7.5 kU/liter when the patient developed urticaria, but declined to baseline figures while she was on L-T3. Intracutaneous testing was positive for desiccated pork thyroid powder, L-T4 and D-T4, but negative for L-T3, DIT and L-tyrosine. I mmunoradioligand analyses of mixtures of patient’s serum or precipitated immunoglobulin fraction and of 125I-T4 or of 125I-T3 revealed binding of radiolabeled thyroxine to the patient’s serum IgE, in turn bound to anti-human-lgE serum covalently coupled to paper discs. This binding was completely inhibited by the preincubation of immunoglobulin fraction with excess unlabeled L-T4 and D-T4, but not with excess nonradioactive L-T3, thus proving the specificity of the binding. Preadsorption experiments performed with desiccated pork thyroid powder solution mixed with the patient’s immunoglobulin fraction suggested binding of some unknown component(s) of desiccated thyroid which was apparently not thyroglobulin. This study provides evidence of IgE antibodies to L-T4 cross reacting with D-T4 and capable of binding 125I-T4 in serum. It also suggests a model for the detection of circulating IgE antibodies to thyroid hormones.

Nosography and Immunopathogenesis of Viral Hepatitis

Five viruses are responsible for the vast majority of cases of viral related hepatitis. They have been named hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV). The more recent literature concerning the viral structure, the epidemiology, the serological identification, the clinical course and the prevention of each type of hepatitis is reviewed. HBV is not directly cytopathic. Hepatitis is a consequence of the destruction of the virus-infected cells. The efficient elimination of the virus relies on the viral antigenic determinants (HBs, pre-S1, pre-S2, HBc, HBe) and on the immune system of the host. The viral persistence may be caused by defect of the host immunity (interferon production, T and B lymphocyte function) or by factors related to the virus such as a genome mutation (lack of HBe formation). Some evidence suggesting an immunopathogenetic mechanism also for HCV, HDV and HAV is reported.

Abnormal daily periodicity of serum thyrotropin (TSH) and evidence for defective TSH suppression in a case of non-neoplastic syndrome of inappropriate TSH secretion

A non-neoplastic syndrome of inappropriate secretion of TSH (ITSHS) was diagnosed in a hemithyroidectomized and clinically euthyroid 44-yr-old man, who also exhibited limping (Perthes’ disease), genu valgum, pes supinatus and lateral nystagmus. Computed tomography demonstrated an enlarged sella turcica due to empty sella. Baseline serum T3, T4, free T3, free T4 and TSH fluctuated between 179 and 274 ng/dl, 6.0 and 13.2 µg/dl, 4.2 and 6.0 pg/ml, 7.6 and 15.3 pg/ml, and 4.3 and 33.0 µU/ml, respectively. Serum alpha-TSH subunit was repeatedly normal (0.36–0.69 ng/ml) over the follow-up period (> 3 yr). No changes in serum liver enzymes and lipids were observed after thyroid hormone administration, whereas red blood cell glucose-6-phosphate dehydrogenase (G-6-PD) and urinary OH-proline were sligthly enhanced during 120 µg/day L-T3 regimen. This also resulted in an inappropriately normal glucagon-stimulated cAMP levels. Tachycardia was experienced only during L-T3 and very high L-T4 dose treatments. Therefore, the patient showed some evidence for thyroid hormone peripheral refractoriness. Patient’s TSH was physiologically responsive to agents (thyrotropin releasing hormone, methimazole, the dopamine antagonists domperidone and sulpiride) known to elicit its release into circulation, while it responded paradoxically to those which normally inhibit TSH secretion. In fact, the infusion of somatostatin (320 µg/h) or dopamine (4 µg/Kg/min), and the oral administration of bromocriptine or nomifensine (two dopamine agonists) or corticosteroids (dexamethasone) provoked an unexpected elevation of both unstimulated and TRH-stimulated TSH levels. Serum TSH also showed an abnormal daily periodicity, reaching the zenith in the daytime, after awakening- a finding confirmed on 4 different occasions. The above findings suggest that the underlying disturbance in our patient was a defective supression of TSH secretion. In this view, the present case is the first one in whom multiple defects of the inhibitory control of TSH secretion have been documented.

Long-term therapy with slow-release nifedipine in essential hypertension

SummaryThe purpose of this study, designed as an open multicenter trial, was to test the antihypertensive efficacy, patient acceptability, and side effects of long-term treatment with slow-release nifedipine in alarge population. The drug was studied in 330 outpatients with essential hypertension, WHO stage 1–2, recruited in 20 hospital centers. After washout period was completed, nifedipine (20 mg bid) was given for 1 month (phase 1). Then, the treatment was extended for 4 months (phase 2) with variable doses (rang 20–80 mg daily). No other antihypertensive drugs were administered during phase 1. However diuretics, beta blockers, or captorpril were added to nifedipine during phase 2 in 11 patients. Seventy patients did not meet ciiteria for inclusion at washout. During phase 1 and 2, 66 additional patients were excluded due to side effects, the need of other antihyperftnsive drugs, or noncomplicance. Systolic blood pressure significantly lowered (10% or more) in 84% patients in phase 1 and in 76% in phase 2. No responders were 6.1% and 3.6%, respectively. Diastolic blood pressure was normalized in 60% of patients after 5 months of therapy. Effects on blood pressure were equal in young patients and in the elderly, but a minimal rise in heart rate was recroded in younger patients.At least one side effect occurred in 46.6% patients, mainly headeche (15.4%), hot flashes (13.3%), ankle edema (12.8%), or palpitation (6.6%). Sixteen patients (8.2%) were obliged to stop nifedipine treatment due to the severity of the side effects. This trial confirms the efficacy of nifedipine in hypertension, both in young and in aged patients. The adherence of patients to the twice-daily regimen was very good, without the development of tolerance in long-term treatment. The drug does not affect the physiologic cardiovacscuolar response to standing, but induces several relatively common, very seldom severe, adverse reactions.

Concealed ventricular hexageminy

The authors report a case of concealed ventricular hexageminy in which, with a few exceptions, extrasystoles were separated by sinus beats conforming to the formula 6n - 1. Whenever an exception to this formula occurs, the intervening beats are not all of sinus origin, but include also a ventricular extrasystole that is different from those occurring in hexageminal distribution. The pattern is explained by a parasystolic rhythm modulated by sinus impulses, assuming a 3:1 ratio between the parasystolic cycle and the sinus cycle. Such a ratio would have to be associated with a trigeminal or concealed trigeminal distribution. There is, however, a 2:1 ectopic-ventricular block, leading to a change of the ectopic distributional pattern from the expected concealed trigeminy to that of the concealed hesageminy.

Parasystolic ventricular tachycardia with variable exit block

This case is an example of ventricular parasystolic tachycardia associated with variable expressions of ectopic-ventricular (E-V) exit block. The exit block manifested with 2:1, 3:2, 4:3 and higher ratios of E-V conductions, interspaced with periods of 1:1 conduction. Concealed E-V conduction of the ectopic impulse could also be deduced.