Star formation inside a galactic outflow.

Recent observations have revealed massive galactic molecular outflows that may have the physical conditions (high gas densities) required to form stars. Indeed, several recent models predict that such massive outflows may ignite star formation within the outflow itself. This star-formation mode, in which stars form with high radial velocities, could contribute to the morphological evolution of galaxies, to the evolution in size and velocity dispersion of the spheroidal component of galaxies, and would contribute to the population of high-velocity stars, which could even escape the galaxy. Such star formation could provide in situ chemical enrichment of the circumgalactic and intergalactic medium (through supernova explosions of young stars on large orbits), and some models also predict it to contribute substantially to the star-formation rate observed in distant galaxies. Although there exists observational evidence for star formation triggered by outflows or jets into their host galaxy, as a consequence of gas compression, evidence for star formation occurring within galactic outflows is still missing. Here we report spectroscopic observations that unambiguously reveal star formation occurring in a galactic outflow at a redshift of 0.0448. The inferred star-formation rate in the outflow is larger than 15 solar masses per year. Star formation may also be occurring in other galactic outflows, but may have been missed by previous observations owing to the lack of adequate diagnostics.

Age-dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene.

Idiopathic achalasia is a rare disorder of the oesophagus of unknown aetio-pathogenesis characterized by a myenteric inflammation, aperistalsis and insufficient lower oesophageal sphincter relaxation. Vasoactive intestinal peptide (VIP), present in the myenteric plexus, is involved in smooth muscle relaxation and acts as an anti-inflammatory cytokine. The human VIP receptor 1 gene (VIPR1) is highly polymorphic and may play a role in idiopathic achalasia. One hundred and four consecutive patients and 300 random controls from the same geographic area were typed for five SNPs mapping in the VIPR1 gene. Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype distribution of SNP rs437876 mapping in intron 4. This association, however, was almost entirely due to the group of patients with late disease onset (P = 0.0005). These results strongly suggest that idiopathic achalasia is a heterogeneous disease with a different aetiology in cases with early or late disease onset.

A functional polymorphism of the vasoactive intestinal peptide receptor 1 gene correlates with the presence of HLA-B*2705 in Sardinia.

The association of HLA-B27 with ankylosing spondylitis (AS) is the strongest among all inflammatory diseases. However, the exact role of these molecules in disease pathogenesis is still unknown. The existence of HLA-B27 variants rarely found in patients introduces a further level of complexity. It is now accepted that other genes of minor impact contribute to modify disease susceptibility and these genes might be diverse in different populations depending on the genetic background. We report here a study performed in Sardinia, an outlier population in which two major HLA-B27 subtypes are present, B (*)2705 strongly associated with AS and B (*)2709 which is not, and show the co-occurrence of the B (*)2705 allele with a single nucleotide polymorphism (SNP) mapping at 3'-UTR of the receptor 1 (VIPR1) for the vasoactive intestinal peptide (VIP), a neuropeptide with anti-inflammatory properties. This same SNP is associated with a different kinetics of down-modulation of the VIPR1 mRNA in monocytes after exposure to lipopolysaccharide (P=0.004). This particular setting, HLA-B (*)2705 and a functional polymorphism in VIPR1 gene, might be due to a founder effect or might be the result of a selective pressure. Irrespectively, the consequent downregulation of this receptor in the presence of a 'danger' signal might influence susceptibility to AS.

Animal and human tissue Na,K-ATPase in normal and insulin-resistant states: regulation, behaviour and interpretative hypothesis on NEFA effects.

The sodium(Na)- and potassium(K)-activated adenosine-triphosphatase (Na,K-ATPase) is a membrane enzyme that energizes the Na-pump by hydrolysing adenosine triphosphate and wasting energy as heat, so playing a role in thermogenesis and energy balance. Na,K-ATPase regulation by insulin is controversial; in tissue of hyperglycemic-hyperinsulinemic ob/ob mice, we reported a reduction, whereas in streptozotocin-treated hypoinsulinemic-diabetic Swiss and ob/ob mice we found an increased activity, which is against a genetic defect and suggests a regulation by hyperinsulinemia. In human adipose tissue from obese patients, Na,K-ATPase activity was reduced and negatively correlated with body mass index, oral glucose tolerance test-insulinemic area and blood pressure. We hypothesized that obesity is associated with tissue Na,K-ATPase reduction, apparently linked to hyperinsulinemia, which may repress or inactivate the enzyme, thus opposing thyroid hormones and influencing thermogenesis and obesity development. Insulin action on Na,K-ATPase, in vivo, might be mediated by the high level of non-esterified fatty acids, which are circulating enzyme inhibitors and increase in obesity, diabetes and hypertension. In this paper, we analyse animal and human tissue Na,K-ATPase, its level, and its regulation and behaviour in some hyperinsulinemic and insulin-resistant states; moreover, we discuss the link of the enzyme with non-esterified fatty acids and attempt to interpret and organize in a coherent view the whole body of the exhaustive literature on this complicated topic.

Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acids.

AIM: Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short-term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT). METHODS: Insulin sensitivity was investigated before and after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal glucose tolerance and without FHD and 13 obese patients with diabetes (n=7) or FHD (n=6). By using specifically designed formulae, we calculated four insulin-sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT) of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)-b, ISI (gly)-a, ISI (ffa)-b and ISI (ffa)-a. RESULTS: In patients with diabetes or FHD, MET improved ISI (gly)-b (0.79 +/- 0.06 vs. 0.59 +/- 0.07, p<0.001) and ISI (gly)-a (0.69 +/- 0.09 vs. 0.51 +/- 0.07, p<0.05), whereas only minor changes occurred for ISI (ffa)-b and ISI (ffa)-a. In contrast, in simple obese subjects, MET induced further deterioration of both ISI (gly)-a (0.47 +/- 0.07 vs. 0.64 +/- 0.10, p<0.01) and ISI (ffa)-a (0.43 +/- 0.07 vs. 0.55 +/- 0.08, p<0.05). Fasting level and total area of lactate were high in the obese patients and were not affected by MET. A statistically significant increase (p<0.01), however, was observed for the 'decremental' area of lactate in obese subjects with diabetes or FHD, which might probably contribute to the reduction of insulin resistance induced by the drug in these patients. CONCLUSIONS: Although the low number of subjects studied precludes absolute conclusions, data would suggest that MET improved ISI towards glucose but not towards FFA, in the diabetic and 'prediabetic' obese patients, whereas worsened it in the obese subjects without FHD. Therefore, the effects of MET would not be secondary to changes of FFA but rather to a primary action of MET on glucose metabolism. Thus, utilization of MET to treat the insulin resistance in obesity is indicated only in the presence of alterations of glucose metabolism or FHD.

A review of the literature of Bardet-Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty.

Bardet-Biedl syndrome (BBS) is a genetic autosomal-recessive disease (formerly grouped with Laurence-Moon-Biedl syndrome but considered today as a separate entity) characterized by abdominal obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism or hypogenitalism (limited to male patients) and kidney structural abnormalities or functional impairment. The expression and severity of the various clinical BBS features show inter- and intrafamilial variability. This study focuses on three cases of familial BBS--two sisters and one brother (66, 64 and 51 years of age, respectively)--with the main cardinal findings of the disease plus a classic 'metabolic syndrome' (characterized by abdominal obesity, atherogenic dyslipidaemia, raised blood pressure, insulin resistance with or without glucose intolerance, and prothrombotic risk and proinflammatory states). One female patient (not affected by reproductive dysfunction) had three healthy offspring, while the other two patients were unmarried. Another severely affected brother died at 70 years of age; two other brothers are lean but affected by nephropathy, retinopathy, slight mental retardation, polydactyly, hypertension and thrombotic diseases, and had healthy offspring. BBS is a rather rare but severe syndrome that is often mis- or undiagnosed. Ophthalmologists, endocrinologists and nephrologists should be aware of BBS because of its adverse prognosis--early onset of blindness, associated findings of metabolic syndrome and increased vascular risk, and severe renal impairment (the most frequent cause of reduced survival and death early in life).

Rheumatoid syndrome associated with lung interstitial disorder in a dental technician exposed to ceramic silica dust. A case report and critical literature review.

Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler-Rose reaction, increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid syndrome with lung interstitial disorder, associated with silica exposure from dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51-B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune disease susceptibility. A 6-month follow-up, with adequate protection and without treatment, showed disappearance of the symptomatology and negative tests for Waaler-Rose reaction and rheumatoid factor. Exposure to silica should, therefore, be sought in the history of any patient with autoimmune or lupus-like syndrome and pulmonary changes. Symptoms associated with silica dust exposure from dental ceramic products should be recognised as being due potentially to an occupational disease, and dental technicians should be protected as workers at risk.

Hypomagnesemia. A review of pathophysiological, clinical and therapeutical aspects.

The aim of this paper is to discuss, on the basis of an extensive literature review, the role of magnesium (Mg) in health and disease. Mg is an essential cation playing a crucial role in many enzyme systems. Quantitative Mg body stores are regulated by metabolic and hormonal effects on gastrointestinal absorption and renal excretion. Mg is a smooth muscle relaxant, dilates coronary arteries and peripheral vessels, exerts antiarrhythmic effects, may have a permissive effect on catecholamine actions and can play a role in various thrombogenic conditions. Today, hypomagnesemia has become a recognized medical occurrence which may be associated with many different diseases, either genetic or acquired. Mg deficiency is one of the most frequent electrolyte abnormalities in clinical practice, but it is probably the most underdiagnosed one. Clinical manifestations of hypomagnesemia may begin insidiously or dramatically sudden. A large part of the population (especially aged subjects) may have an inadequate Mg intake and a chronic latent Mg deficiency. Routine inclusion of serum Mg analysis in the electrolyte panel represents a continued need to recognize hypomagnesemia and to treat Mg-depleted patients. New clinical studies on Mg deficiency are necessary to ascertain the usefulness and cost-effectiveness of Mg replacement therapy.

Multiple factor indices of protection or risk towards disease.

In order to combine several factors entailing protection or risk towards disease and to calculate a Protection Multiple Factor Index (PMFI) or, conversely, a Risk Multiple Factor Index (RMFI), we propose the following formulae: (1) PMFI = 2/[(mF)2 + 1] and (2) RMFI = 2/[(imF)2 + 1], where mF is the mean value of the factors considered and imF is the inverse (or reciprocal) of mF. In calculating mF, the value of each 'risk factor' observed in the patient under study (Vp) is expressed by taking the mean normal value (Vmn) as the unit, i.e. by calculating the ratio Vp/Vmn, whereas each 'protection factor' is expressed as the reciprocal of this ratio, i.e. as Vmn/Vp. The 'weight' of the various factors can be changed through multiplication by a number > 1 or < 1. Values of both PMFI and RMFI are always close to 1 in normal subjects, with extreme variations among patients between 0 and 2. The sum of the values of PMFI and RMFI is always equal to 2, so that one index can be deduced from the other. When factors are only two (F1 and F2), the formulae may be simplified as follows: PMFI = 2/[F1 x F2) + 1] and RMFI = 2/[(iF1 x iF2) + 1], where iF = 1/F, with only minimal changes in results.

[Hyperkeratotic Kaposi sarcoma with leg lymphoedema after prolonged corticosteroid therapy for SLE. Case report and review of the literature]. / Sarcoma di Kaposi i ipercheratosico con linfedema della gamba dopo prolungata terapia corticosteroidea per LES. Caso clinico e rassegna della letteratura.

Kaposi sarcoma (KS) is a malignant vascular neoplasia with a viral etiology, characterized by development of multiple hyperpigmentate lesions, primarily at cutaneous level with associated edema and ulcerations, but frequently involving also the mucous membranes and/or visceral organs. In this study, we describe (in the light of the relevant literature) the clinical case of an elderly (78 yrs-old) woman, who developed red-blues multiple hyperkeratotic nodules in the right leg and foot with marked lymphoedema, blushing and pain, after a long period of a low-dose corticosteroid therapy for LES (at least 10 years of continuous treatment). The diagnosis of KS was made on the basis of histologic findings. The patient HLA-typing showed the haplotypes HLA-A2-10, -B21-35, -Bw4-6, -Cw4 and HLA-DR11-13 (some of which are known to predispose to LES, but not to KS). The KS, first described by Moritz Kaposi in 1872, has been a very rare pathology until the 80s, afterwards its frequency has steadly increased, favored by immunosuppressive therapy for autoimmune diseases or tranplants and by immunodepression of AIDS. Concerning the pathogenesis, it is crucial the role of HHV-8 of the herpesvirus family (found in the lesions and in the circulating cells of all KS patients), for which a prevailing sexual transmission is postulated. General physicians and specialists of internal medicine and angiology should know this disease, which can be undiagnosed because of the low incidence in the general population and the consequent poor knowledge of this vascular neoplastic disease, which is now reported with increasing frequency.

Insulin sensitivity of blood glucose versus insulin sensitivity of blood free fatty acids in normal, obese, and obese-diabetic subjects.

We calculated insulin sensitivity indices (ISI) concerning the insulin effect on both glycemia and blood free fatty acids (FFA), named ISI(gly) and ISI(ffa), respectively, in 34 normal, 27 obese, and 11 obese-diabetic subjects by using the following formulas: ISI(gly)= 2/[(INSp x GLYp) +1], and ISI(ffa)= 2/[(INSp x FFAp)+1], in which INSp, GLYp, and FFAp = insulinemic, glycemic, and FFA areas during oral glucose tolerance test (OGTT) (75 g glucose, suggested sampling time: 0, 1, and 2 hours) of the person studied. A slight modification of these formulas allows the calculation of insulin resistance indices (IRI), ie, IRI(gly) and IRI(ffa). ISI and IRI are complementary, as their sum is always equal to 2, so that IRI can be deduced from ISI and vice versa. By using basal levels instead of areas, insulin sensitivity (or resistance) in the basal state can also be measured. Basal levels and areas are expressed by taking the mean normal value as 1, so that in normal subjects ISI(gly) and ISI(ffa), as well as IRI(gly) and IRI(ffa), are always around 1, with maximal variations comprised between 0 and 2. ISI(ffa) was markedly reduced in both the obese (mean, 0.47 +/- 0.04) and the obese-diabetic (mean, 0.41 +/- 0.06) subjects, whereas ISI(gly) was less reduced in the obese (mean, 0.57 +/- 0.04) than in the obese-diabetic (mean, 0.40 +/- 0.03) subjects. ISI(gly)-basal was less affected than ISI(ffa)-basal in both groups. Multiple regression showed that ISI(gly) and ISI(ffa) were significantly inversely correlated with age, body mass index (BMI), and diastolic (but not systolic) blood pressure. Meta-analysis of data from the literature showed that ISI(gly) was significantly correlated with the hyperinsulinemic-euglycemic clamp data. However, the "clamp" is performed under artificial, persistent hyperinsulinemia (which entails FFA suppression) as never occurs in the life of patients, whereas our indices are performed under physiologic conditions, and represent simple tools suitable for clinical or epidemiologic studies, allowing assessment of whole-body insulin sensitivity with regard to both glycemia and blood FFA.

[Bilateral sclerosing lipogranuloma of the gluteal region with calcification. Report of a clinical case and review of the literature]. / Lipogranuloma sclerosante bilaterale delle regioni glutee con calcificazioni. Descrizione di un caso clinico e revisione della letteratura.

A rare case of large bilateral sclerosing lipogranuloma with multiple calcifications of gluteal region is described in an old female patient affected by a cerebrovascular disease. The lesions appeared as firm, nontender, plaques, 9-10 cm in diameter, covered with hyperpigmented skin. This uncommon disorder is discussed on the basis of data obtained from an extensive literature review. The term "sclerosing lipogranuloma" was coined in 1950, and it defines a disease of the subcutaneous fat, which for a trauma or unknown reasons undergoes necrosis of fat cells with the release of fat droplets into intercellular spaces and a peculiar local sclerosing granulomatous reaction of fatty tissue. The cytosteatonecrosis and sclerosing lipogranuloma, post-traumatic or secondary to injection of exogenous oily substances, usually localized in the breast of women and in genitalia of men, are relatively well known. Sclerosing lipogranulomatosis of the orbita and eyelides, an infrequent but severe complication after endonasal surgery, has also been reported. Rarely, the lipogranuloma can be spontaneous or idiopathic or primitive. A particular form of genetic diffuse lipogranulomatosis is the Farber's syndrome, firstly described on 1947. In our patient, the absence of trauma seems to indicate a primitive lipogranuloma. The presence of an acute rheumatic syndrome responsive to corticosteroids, and the positivity of antimitochondrial autoantibodies are in accordance with the report of sclerosing multiple lipogranulomatosis associated with a lupus-like syndrome. Because of the long duration and the absence of acute local symptoms, this syndrome can be considered benign with favorable prognosis, but the physician should know it.

[Psoriasis complicated with severe mutilating psoriatic osteoarthropathy. Clinical case and review of the literature]. / Psoriasi complicata da grave osteoartropatia psoriasica mutilante. Caso clinico e rassegna della letteratura.

Aim of this paper is to discuss, on the basis of an extensive critical review of the recent literature, the case of a 56-yr-old male patient who suffered from cutaneous psoriasis and psoriatic arthritis mutilans (PA) (polyarticular, symmetric, destruent and erosive) with involvement of the hands, feet and spine, associated with android obesity and mild type 2 diabetes mellitus. HLA typing of the patient showed the HLA-A3-Ax, B14-B63 and Cw4-Cw6 haplotypes, some of which are associated or correlated with susceptibility to PA. Cutaneous psoriasis is a chronic inflammatory dermatitis, with onset at any age and affecting approximately 2% of the western populations. In 5-7% of patients, it is associated with articular manifestations or true arthritis. PA is a chronic, inflammatory, seronegative arthropathy which may develop in some psoriasis patients, may involve peripheral and axial (spondarthritis) joints and may lead to severe joint destruction. Genetic, immunologic and environmental (i.e., infectious agents or trauma) factors seem to play an important role in the onset and clinical appearance of PA. Although PA is a clinically monomorphic disease, it may show different heterogenous subgroups with differences in their etiopathogenesis. When PA is suspected, it is mandatory to analyze carefully the patient's familiar history, search attentively for the specific skin features, exclude a septic arthritis (especially if the involvement is monoarticular) and, in the cases of fulminant disease, consider always the possible coexistence of an acquired immunodeficiency syndrome. PA can occasionally be an aggressive, disfigurating and disabling disease and the treatment (incisive and precocious) should be similar to that for rheumatoid arthritis. At present, a definitive therapy does not yet exist, but the majority of PA patients can lead a fairly normal life and they do not show increased mortality rates (excluding the severe cases of erythrodermic or pustulosis psoriasis). However, as a result of the various problems of occupation and morbidity it causes, PA is a disease with great social involvement.

In vitro inhibition of glucose phosphorylation by an aldose-reductase inhibitor (Tolrestat) in some non-insulin-sensitive rabbit tissues.

We have previously demonstrated that in some non-insulin-sensitive tissues (capillaries of eel swimbladder Rete mirabile, and rabbit eye choroidocapillary lamina, optic nerve, retina, and lens) glucose phosphorylation increases with the increase in the concentration of glucose, a characteristic relevant to the hyperglycemia of diabetes. In the present research we demonstrate an effect of the aldose reductase inhibitor, Tolrestat, on the glucose-phosphorylating activity of rabbit lens and optic nerve, by assaying the enzyme activity of tissue homogenates (in the presence of 10 mmol/L glucose) without or with 10 min preincubation with increasing concentrations of Tolrestat (2, 4, and 8 micromol/L). In the lens, a 18% inhibition (p < 0.01) was observed in the presence of 8 micromol/L Tolrestat. In the optic nerve, a 12% (p < 0.05) and a 21% (p < 0.01) reduction was recorded at 4 and 8 micromol/L Tolrestat, respectively. Significant inverse correlations existed between the concentration of Tolrestat and the phosphorylation rate of glucose of rabbit lens and optic nerve. The dose-dependent inhibition of glucose phosphorylation observed by us suggests that the inhibitory action of Tolrestat on glucose metabolism extends beyond the well-known effects of this compound on the polyol pathway, and might contribute to the refraining action of Tolrestat on the development and progression of late diabetic complications in non-insulin-sensitive tissues.

Controlled oral glucose tolerance test: evaluation of insulin resistance with an insulin infusion algorithm that forces the OGTT glycaemic curve within the normal range. A feasibility study.

This is a technical study to show the feasibility of a computer-controlled oral glucose tolerance test (OGTT) using a specific algorithm, consisting of an OGTT carried out while insulin is infused as required to keep glycaemia within the normal range (National Diabetes Data Group 1979 criteria). This technique allows (a) the amount of insulin (insulin area) required to maintain a normal glycaemic curve to be assessed, a parameter indicating the degree of insulin resistance; and (b) the unique parameter consisting of the insulin secretory response (C-peptide) to a normal glycaemic curve under the inhibitory feedback exerted by the insulin levels required to maintain normal glycaemia to be obtained. Preliminary results confirmed the feasibility of this approach by showing that during the test while the glycaemic area was kept normal the insulinaemic area (endogenous + infused insulin) increased markedly in obese (n = 8) and obese diabetic (n = 5) subjects compared with normal subjects (n = 6), with values of 145.10 +/- 26.71, 204.75 +/- 20.77 and 68.25 +/- 5.93 nmol l-1 min-1 respectively (P < 0.01 in both instances). In contrast, endogenous insulin secretion (C-peptide levels) remained almost unchanged. Compared with data in normal subjects, free fatty acid (FFA) values were basally elevated in the obese and obese diabetic patients, and underwent a smaller decrease during the test. The FFA areas were greater than normal in both groups of patients, suggesting that FFAs were not fully suppressible despite the highest possible insulin levels (higher insulin levels would produce hypoglycaemia). The computer-controlled OGTT might be useful for the metabolic study of patients in the clinical setting.

A large spontaneous splenorenal shunt in a patient with liver cirrhosis and uncomplicated portal hypertension.

The aim of this paper is to describe and discuss, on the basis of a thorough review of the literature, the case of a 70-year-old woman with probable cirrhosis secondary to chronic hepatitis B and C, uncomplicated portal hypertension (without ascites, encephalopathy or bleeding varices), splenomegaly and hypersplenism, and an unusual, spontaneous, large splenorenal shunt and recanalization of the umbilical vein. The tortuous and varicose splenorenal shunt was diagnosed by abdominal ultrasound and CT investigations. A duplex Doppler ultrasonography evaluation was performed to study shunt flow direction and velocity. No gastroesophageal varices were identified on endoscopic examination. The clinical relevance of spontaneous splenorenal shunt, often associated with fundic gastric varices, is discussed.

Genetic deficiency of factor VII and hemorrhagic diathesis. A case report and literature review.

FVII deficiency is a rather rare inherited hemocoagulation disorder that predisposes to hemorrhagic events, especially from mucous membranes, that are not predictable and severe as in hemophilia A. This defect produces prolonged prothrombin time (PT), reduced activity of FVII and normal activated partial thromboplastin time (aPTT). We report the case of a 43-year-old obese woman with severe deficiency of factor VII (FVII), probably genetic in nature, and meno-metrorrhagia associated with multiple fibromas of uterus. Our patient had no history of bleeding in infancy and young age, and in the past, before the disease was diagnosed, underwent major surgery operations (thyroidectomy and caesarian section) without hemorrhage. Patient's relatives with mild heterozygous deficiency of FVII (the father, a brother, a sister, a sister's daughter and the patient's son) did not show any bleeding tendency. This case report is discussed in the light of literature data ((source: Medline from 1964 to 1996). The different forms of congenital (isolated or combined with other clotting disorders) and acquired FVII deficiency, with the appropriate therapies, are reviewed. The clinician must consider FVII deficiency in cases of recurrent bleeding, and this disease, even if rather rare, should not be underestimated in clinical practice because it is potentially fatal.

Insulin resistance in obesity: metabolic mechanisms and measurement methods.

In obesity several mechanisms contribute to produce insulin resistance. Elevation of plasma FFA increases the concentration of cytoplasmic long-chain-CoA (LC-CoA) and mitochondrial acetyl-CoA. The latter inhibits pyruvate dehydrogenase (PDH) and, therefore, glucose oxidation. LC-CoA exerts an array of effects, some mediated by peroxisome proliferator-activated receptors, including modulation of gene expression of enzymes of glycolipid metabolism, thus inhibiting glucose utilization and potentiating FFA oxidation. Enhanced availability of glucose plus insulin forces glucose utilization (activation of PDH and glycogen synthase) and leads to increased production of malonyl-CoA (via citrate), which inhibits carnitine palmitoyl transferase 1 and therefore FFA beta-oxidation. In obesity there is often enhanced availability of both FFA and glucose plus insulin. The latter, by increasing malonyl-CoA, may limit FFA beta-oxidation. This, however, leads to further increases in LC-CoA, which worsens insulin resistance. All these mechanisms occur through both short-term and long-term effects. Therefore, when insulin sensitivity is measured with the hyperinsulinemic clamp, which artificially suppresses FFA levels, the FFA short-term effects are lost. More physiological methods are those utilizing OGTT data, allowing calculation of an Insulin Sensitivity Index for glycemia, or ISI(gly), through the formula: 2/((INSp x GLYp)+1), where INSp and GLYp are the measured insulin and glycemic areas expressed by taking mean normal value as 1. The corresponding Insulin Resistance Index, or IRI(gly), can be obtained through the formula: 2/((1/(INSp x GLYp))+1). Substitution of glycemic (GLYp) with FFA (FFAp) values allows the calculation of indices of insulin sensitivity and resistance for FFA, i.e., ISI(ffa) and IRI(ffa).

Hypomagnesemia and smooth muscle contractility: diffuse esophageal spasm in an old female patient.

The aim of this paper is to describe and discuss, on the basis of the available literature, the case of an old female patient, admitted to our university hospital because of a severe dysphagia for solid foods, in whom laboratory data showed a marked hypomagnesemia. She reported a long history (20 years) of allergic bronchial asthma treated with theophylline. Esophagography evidenced a disorder of esophagus motility with diffuse multiple spasm, reminiscent of the 'corkscrew esophagus'. A link with the severe hypomagnesemia (Mg 1.1 mEq/l, normal range 1.6-2.1) was suspected, and a therapy with oral pidolate of Mg (1.5 g/twice a day) was started and continued for 4 months. This was associated with a slow progressive normalization of the Mg plasma level and reverted radiographic esophageal findings with disappearance of dysphagia. Mg is an important element for health and disease, and today Mg deficiency in man has become an accepted medical problem which might complicate many diseases. Neuromuscular disorders, as laryngeal spasm, are recognized complications of hypomagnesemia, but until now only 1 case of motor esophageal disorder associated with a low Mg plasma level was briefly reported in the literature, even if dysphagia is generally included in the symptomatological pattern of hypomagnesemia. Our observation of a severe form of esophageal spasm, associated with hypomagnesemia, in an aged female patient underlines the pathophysiological meaning of the plasma Mg level and suggests the need for routine Mg determination in the clinical setting.