[Acute liver failure due to human herpesvirus 6 in an infant]. / Insufficienza epatica acuta da Human Herpesvirus 6 in un lattante.

We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

[Celiac disease and "gluten sensitivity"]. / Malattia celiaca e "gluten sensitivity".

It is known that celiac disease is characterized by a huge variety of clinical forms ranging from classical ones to silent forms, potential ones and to an increased number of cases of gluten-sensitivity. The latter is an abnormal non-allergic sensibility to gluten. Clinical manifestations can be very different without a severe intestinal damage (Marsh/Oberhuber 0-I) and this condition seems to benefit from a gluten free diet. Cases of gluten-sensitivity appear very interesting in the search of histological markers with elevated specificity, which are able to identify slight and early gluten dependent enteropathy, especially in at risk patients for celiac disease even before classical autoantibodies appear: for instance, this is the case of intraepithelial lymphocytes T-cell receptor gamma delta and mucosal deposits of class IgA anti transglutaminase antibodies. Other studies are investigating transglutaminase isoenzimes (different from tissue one), that can be identified in patients with gluten dependent symptoms without classical autoantibodies. Forms of gluten allergy have a different pathogenesis from celiac disease and are represented by "backer's asthma" or by classical allergy to wheat proteins. Clinical manifestations can vary from anaphylactic reactions to dermatological, respiratory and intestinal symptoms. Also in these cases the therapeutic approach is based on gluten free diet.

Novel pyrimidine and 1,3,5-triazine hypolipidemic agents.

New compounds were synthesized by changing the substituents of a trisubstituted pyrimidine, i.e., [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio] acetic acid, a potent hypolipidemic agent, impaired, however, by a marked hepatomegaly-inducing effect. The structural variations led to the subsidence (14b, i.e., 4-chloro-2-(dimethylamino)-6-[(2,3-dimethylphenyl)amino]pyrimidine) or to the reduction (18b, [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]amino] acetic acid) of said untoward effect but still maintained the hypolipidemic effect that, although markedly decreased, still proves significant for serum cholesterol and triglycerides (18b) or for serum triglycerides only (14b).

Synthesis of 2-carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one and related compounds.

A series of 2-carboxy-1, 4-androstadien-3-one derivatives and their alkyl esters, were prepared by high-yield syntheses. The compounds were structurally identified by physical methods. All these steroids are characterized by a marked antiglucocorticoid activity that proved long-acting in the case of the ester derivatives. 2-Carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one or roxibolone, and its n-decylester or decylroxibolone, are the most promising derivatives in consideration of their pharmacological properties.

[Bacteriological study at the vaginal level in sexually active women]. / Ricerca batteriologica a livello vaginale in donne sessualmente attive.

We have studied the microbiological environment of the vagina in 202 sexually active women when they came into an outpatient gynecological hospital. By some specific bacterioscopic and cultural examinations we have tried to understand the pathological role of some microrganism in sexually transmitted diseases. An elevated incidence of mycoplasm in asymptomatic subjects has shed light on the probable saprophytic behaviour of these microrganisms.

Inhibition of puerperal lactation by metergoline: interactions with methylergobasine maleate.

Metergoline, a prolactin (PRL) lowering drug, is used in the puerperal period to inhibit lactation. Methylergobasine maleate (MEM), widely employed in the puerperium to promote uterine contractions, has also been reported to decrease PRL release and to reduce lactation. To evaluate the possible interactions of the two drugs, groups of 6-11 puerperae each received no treatment, metergoline alone (8 or 12 mg/day for 5 days), MEM alone (0.2 mg i.v. at delivery followed by 0.5 mg/day p.o. for 5 days) and metergoline plus MEM. Metergoline fully prevented lactation and significantly reduced PRL release, the higher dose inducing effects faster. MEM was without effect on PRL release and lactation, and did not modify the effect of metergoline.

Spontaneous preterm delivery in pregnant diabetics: a high risk hitherto "unrecognized".

Preterm delivery (PD)--before the 259th day from the beginning of the last menstrual period--is very frequent in pregnant diabetics (from 50% to 80% or more, personal investigation in progress). In these patients a policy is generally followed of a systematically controlled early delivery. Therefore, one is inclined to think that the high frequency of PD is mainly the consequence of this policy. However, it has been recently pointed out [5] that spontaneous labor accounts for half or more of PD in pregnant diabetics. Moreover in pregnant women with gestational diabetes PD rate due to spontaneous labor is three times higher than in the general obstetric population [5]. A different result emerges from our case study, 1963-1975. Insulin was administered to the maximal tolerated dose both in case of gestational and clinical diabetes [1, 6, 7, 8, 9, 10, 11, 12]. The incidence of PD due to spontaneous labor is 6.7% (7.1% in gestational and 6.1% in clinical diabetes), i.e. no difference from PD rate in general. Since 1974 M. Chartier, Paris, has been adopting the same therapeutic criteria [2]. His results seem to confirm that the risk of PD due to spontaneous labor drastically reduces in pregnant diabetics strictly controlled.

Metergoline versus bromocriptine in the prevention of puerperal lactation. A double-blind clinical trial.

In a double blind study of the prevention of puerperal lactation, the clinical efficacy of two antiprolactin drugs was compared: metergoline 4 mg tid and bromocriptine 2.5 mg bid were both given for 7 days. An additional 7 days of treatment was administered to 16 patients in whom mammary activity was still present or appeared in the following 3 days. The first 7 day period of treatment was effective in 16/20 women receiving metergoline and in 7/20 on bromocriptine (p less than 0.02); the second period of treatment was effective in all remaining patients. These data indicate that metergoline acts rapidly to arrest puerperal lactation, possibly by a mechanism different from that of bromocriptine.

Pharmacological profile of BR-931, a new hypolipidemic agent that increases high-density lipoproteins.

BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-acetamide], a new hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and hyperlipidemia in rats, and in the cholesterol-induced atherosclerosis in rabbits. Significant hypolipidemic activity was observed in rats with doses of the agent at 12.5--50 mg/kg. In the Triton-induced hyperlipidemia, 50 mg BR-931 per kg was equieffective as 200 mg of clofibrate (CPIB) per kg. In contrast with CPIB, BR-931 exerted a powerful antilipolytic activity against epinephrine, ACTH, nicotine and cold exposure. BR-931 was particularly effective in diet-induced hyperlipidemias. Ethanol lipemia was totally prevented by the agent at 100 mg/kg. With Nath's diet, doses as low as 25 mg/kg significantly reduced hypercholesterolemia and hypertriglyceridemia. In these last two tests, the distribution of lipoprotein cholesterol was also determined. CPIB did not affect HDL cholesterol levels that had been decreased by the diets; in contrast, BR-931, already at doses of 50 mg/kg, brought the HDL/total cholesterol ratio back toward normal. A significant HDL cholesterol increase, together with some reduction of atheromatosis, was also observed in cholesterol-fed rabbits. BR-931, a potent inducer of liver peroxisones and of mitochondrial carmitine acetyltransferase, appears to be a hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of hyperlipidemias and atherosclerosis.