Long-term follow-up of autoimmune thrombocytopenic purpura (ATP) patients submitted to splenectomy

We studied the general outcome in 94 adult patients with autoimmune thrombocytopenic purpura (ATP) submitted to splenectomy. Of 84/94 patients who presented a complete or partial response 30 d after splenectomy, 16 (19%) showed one or more relapses. The clinical situation of the 81 patients still under observation is as follows: 13 unresponsive, 60 completely or partially responsive, without relapses during the follow-up, 8 completely or partially responsive after one or more relapses. No correlation was found between the favourable splenectomy outcome and age at splenectomy, the diagnosis-splenectomy interval and initial response to corticosteroids. The probability of disease-free survival is 83%, projected at 10 yr, while the overall survival is 93%, projected at 10 yr. PAIgG levels of the normal subjects and of responding patients were found to be similar, while in the groups of non-responding/relapsing patients, significantly higher values of PAIgG were detected, as compared to the control group.     

Halitosis and Helicobacter pylori: A Possible Relationship

With the aim of investigating a possiblerelationship between objective halitosis(established by sulfide levels in the breath) andHelicobacter pylori, we performed a study in 58dyspeptic patients reported to suffer from "badbreath." Furthermore, we evaluated the effects onhalitosis of eradication therapy (only for H.pylori-positive patients) and chlorhexidine antisepticmouth rinses (in all patients). Sulfide compoundassay indicated objective halitosis in 52/58 patients,30 of whom were positive and 22 negative for H. pylori.In 19/30 eradication by double therapy provoked a decrease to below the cutoff value of sulfidelevels in 15. In the other 11 of the 30 subjects, inwhom H. pylori positivity persisted, halitosisparameters did not change. Chlorexidine reduced sulfides to below the cutoff value in 16/22 H.pylori-negative patients, but did not provoke any changein the 11 unsuccessfully treated H. pylori-positivesubjects. In these, objective halitosis disappeared only after a successful eradication by tripletherapy (9/11). Our results show a possible associationbetween halitosis and H. pylori since bacterialeradication may resolve the symptom. Antisepticmouthwashes may be effective only in absence of H. pylori,when halitosis may be due to oral putrefactive microbialactivity. In a small number of subjects the cause andtreatment of halitosis need to be clarified.     

Mycophenolate mofetil in the treatment of autoimmune HCV-associated haematological disorders showing steroid resistance or dependence

Summary. We report two cases of hepatitis C virus (HCV) associated autoimmune haematological disorders successfully treated with an unusual protocol (mycophenolate mofetil: MMF). The first case was a male patient with chronic HCV infection who developed, during interferon (IFN)/ribavirin therapy, severe autoimmune thrombocytopenia unresponsive to steroids. MMF was then administered and, simultaneously, the steroid dose was gradually reduced until withdrawal. Following this strategy, a progressive increase in platelet count and complete negativity of anti-PLT antibodies were achieved without changes in HCV-RNA quantitative determination. The second case was a woman with HCV liver cirrhosis with severe anaemia and Coombs test positivity partially responsive to continuous administration of steroid high doses. However, this treatment unmasked a severely painful vertebral osteoporosis. For this reason we introduced MMF and simultaneously steroid therapy was progressively reduced until withdrawal. Haemoglobin reached a normal value and the Coombs test became negative within 60 days. These case reports suggest that MMF may represent an interesting therapeutic approach for autoimmune HCV associated haematological disorders.     

Blood endothelin-1 levels before and after carotid endoarterectomy for atherosclerotic stenosis

BACKGROUND: Elevated plasma levels of endothelin-1 (ET-1) have been reported in advanced atherosclerosis. Further in vivo demonstration of cause-effect relationship between atherosclerotic lesion and high levels of ET-1 needs to be carried out. The aim of this study was to determine whether circulating levels of ET-1 are influenced by removing haemodynamically significant atherosclerotic stenosis in selected patients with mono or bilateral carotid atherosclerotic stenosis. METHODS: Cubital venous ET-1-immunoreactive (IR) levels were measured in 20 patients: 11 (mean age+/-S.D. 63.1+/-5.36 years; range 53-70 years) were affected by monolateral, and nine patients (mean age+/-S.D. 64.7+/-9.8 years; range 52-78 years) by bilateral extracranial carotid artery atherosclerotic stenosis. ET-1-IR levels were evaluated before and 7 days after monolateral surgical endoarterectomy. Pre-surgery levels of ET-1-IR were compared with those obtained from 18 healthy younger volunteers (mean age+/-S.D. 27.8+/-2.7 years; range 20-50 years). FINDINGS: The mean cubital venous levels of ET-1-IR in the atherosclerotic patients before endoarterectomy (mean+/-S.D. 4.50+/-3.35 pg/ml; range 1.28-10.66 pg/ml) were significantly higher than those observed in healthy subjects (mean+/-S.D. 0.641+/-0.137 pg/ml; range 0.36-1.02 pg/ml) (P=0.000). The mean ET-1-IR level decreased significantly after endoarterectomy in the group of patients with monolateral stenosis (pre-surgery: mean+/-S.D. 4.35+/-3.11 pg/ml; range 1.28-10.66 pg/ml; post-surgery: mean+/-S.D. 3.05+/-2.94 pg/ml, range 0.28-8.86 pg/ml) (P=0.005), but not in patients with bilateral extracranial carotid stenosis submitted to monolateral endoarterectomy (pre-surgery: mean+/-S.D. 4.77+/-3.79 pg/ml; range 2.18-10.3 pg/ml; post-surgery: mean+/-S.D. 4.60+/-3.70 pg/ml; range 2.20-11.10 pg/ml). INTERPRETATION: The removal of a haemodynamically significant atherosclerotic vascular stenosis is associated with a decrease in the circulating ET-1-IR levels 7 days after surgery when haemodynamically significant atherosclerotic lesions are absent.     

Ontogenesis of the nuclear 3,5,3'-triiodothyronine receptor in the rat testis

The aim of this study was to investigate the ontogenesis of the nuclear T3 receptor among the different cell types in the rat testis from fetuses at the 19th day of gestation and animals 1, 5, 15, 20, and 60 days after birth. Whole testis, tubular fraction, nontubular fractions, and Sertoli cells cultured in vitro or enriched in vivo by irradiation were used. The results demonstrate that high affinity, low capacity T3-binding sites are localized only in Sertoli cells; the binding specificity and affinity (Kd ranges from 0.8 +/- 0.2 to 2.6 +/- 0.4 nM) do not change significantly with the age of the animals and are comparable to those observed for T3 receptors in other mammalian tissues. In the whole testis, the concentration of receptors changes during gonadal development, being maximally expressed in the fetus (154.3 +/- 8.1 fg T3 bound/10(6) nuclei) and from 1 (203.4 +/- 10.9 fg T3 bound/10(6) nuclei) to 5 (185.3 +/- 15.1 fg T3 bound/10(6) nuclei) days of postnatal life, decreasing significantly at 15 and 20 days (65.4 +/- 2.0 and 57.9 +/- 1.9 fg T3 bound/10(6) nuclei, respectively) and being virtually absent in the adult. The same change in receptor concentration was found in Sertoli cells obtained by different techniques. This ontogenetic profile coincides with the pattern of Sertoli cell proliferation and differentiation, thus suggesting a role of thyroid hormones in the regulation of growth and maturation of the somatic cells of the seminiferous epithelium.     

Low birth weight and later development of insulin resistance and biochemical/clinical features of polycystic ovary syndrome

Reduced insulin sensitivity in adult life has been reported in subjects born at term small for gestational age (SGA) and in those born prematurely with very low birth weight (LBW) (<1,500 g). We assessed whether LBW (<2,500 g) young women, irrespective of whether they were born SGA or adequate for gestational age (premature AGA), exhibited a reduction in insulin sensitivity through a prospective historical design. The risk of developing biochemical and clinical features of polycystic ovary syndrome was also investigated. The study population included 35 LBW women (19 SGA [BW range, 1,000-2,400 g] and 16 premature AGA [BW range, 1,700-2,440 g]) aged 21.8 +/- 1.8 years and 35 term AGA controls, of similar age, recruited from a neonatal registry. All women underwent clinical, ultrasonographic, hormonal, and metabolic evaluations, including the composite insulin sensitivity index. Women under hormonal contraception (21.4%) were excluded from hormonal and metabolic analyses. Composite insulin sensitivity index was significantly lower in LBW women even when the 2 LBW subgroups, SGA and premature AGA, were analyzed separately (4.4 +/- 2.2 and 4.0 +/- 1.7, respectively) than in controls (6.9 +/- 4.4). The LBW women showed a significantly higher incidence proportion of irregular menses (14/35 [40%] vs 2/35 [5.7%]) and a significantly higher free androgen index (5.8 +/- 3.5 vs 3.9 +/- 3.2). They also showed a nonsignificantly higher proportion of hirsutism, acne, and polycystic ovaries. In conclusion, LBW (<2,500 g) young women, irrespective of whether they were SGA and premature AGA, exhibited a reduction in insulin sensitivity as compared with born at term AGA women. Furthermore, they exhibited an increased risk of developing clinical and biochemical features of polycystic ovary syndrome.     

Evidence that host size determines liver size: studies in dogs receiving orthotopic liver transplants

Orthotopic liver transplantation was performed in two groups of dogs; Group I animals consisted of large dogs that served as recipients of livers obtained from smaller dogs while Group II animals consisted of dogs that received liver from donor dogs of nearly the same size. The small-for-size livers transplanted into the Group I dogs rapidly increased in size over the course of 2 weeks until they achieved a size equal to that originally present in the larger recipient dogs. In contrast, the livers transplanted into dogs of the same size as the donors underwent some degree of atrophy. In both groups of animals, plasma levels of insulin and glucagon and hepatic (graft) activities of thymidine kinase and ornithine decarboxylase were followed serially. The only difference between the two groups of animals for these measures was that the ornithine decarboxylase activity rose to a greater degree in the liver that underwent graft enlargement. These data suggest that recipient size determines, at least in part, liver graft size once it is transplanted. These data also suggest that of the parameters followed, only ornithine decarboxylase activity parallels the finding of growth of the transplanted liver.     

Energetic metabolism and human sperm motility: impact of CB₁ receptor activation

It has been reported that the endocannabinoid anandamide (AEA) exerts an adverse effect on human sperm motility, which has been ascribed to inhibition of mitochondrial activity. This seems to be at variance with evidence suggesting a major role of glycolysis in supplying ATP for sperm motility; furthermore, the role of AEA-binding receptors in mediating mitochondrial inhibition has not yet been explored. In this study, human sperm exposure to Met-AEA (methanandamide, nonhydrolyzable analog of AEA) in the micromolar range significantly decreased mitochondrial transmembrane potential (ΔΨm), similarly to rotenone, mitochondrial complex I inhibitor. The effect of Met-AEA (1 μm) was prevented by SR141716, CB(1) cannabinoid receptor antagonist, but not by SR144528, CB(2) antagonist, nor by iodoresiniferatoxin, vanilloid receptor antagonist. The effect of Met-AEA did not involve activation of caspase-9 or caspase-3 and was reverted by washing. In the presence of glucose, sperm exposure either to Met-AEA up to 1 μm or to rotenone for up to 18 h did not affect sperm motility. At higher doses Met-AEA produced a CB(1)-independent poisoning of spermatozoa, reducing their viability. Under glycolysis blockage, 1 μm Met-AEA, similarly to rotenone, dramatically abolished sperm motility, an effect that was prevented by SR1 and reverted by washing. In conclusion, CB(1) activation induced a nonapoptotic decrease of ΔΨm, the detrimental reflection on sperm motility of which could be revealed only under glycolysis blockage, unless very high doses of Met-AEA, producing CB(1)-independent sperm toxicity, were used. The effects of CB(1) activation reported here contribute to elucidate the relationship between energetic metabolism and human sperm motility.     

Audio-visual communication and its use in palliative care

The technology of telemedicine has been used for over 20 years, involving different areas of medicine, providing medical care for the geographically isolated patients, and uniting geographically isolated clinicians. Today audio-visual technology may be useful in palliative care for the patients lacking access to medical services due to the medical condition rather than geographic isolation. We report results of a three-month trial of using audio-visual communications as a complementary tool in care for a complex palliative care patient. Benefits of this system to the patient included 1) a daily limited physical examination, 2) screening for a need for a clinical visit or admission, 3) lip reading by the deaf patient, 4) satisfaction by the patient and the caregivers with this form of communication as a complement to telephone communication. A brief overview of the historical prospective on telemedicine and a listing of applied telemedicine programs are provided.