The impact of the factor V Leiden mutation on pregnancy

A resistance to the anticoagulant activity of activated protein C (APC), most frequently due to a point mutation in the Factor V gene (the Leiden mutation), represents the most common genetic cause of thrombophilia. The Leiden mutation has been significantly related to pregnancy complications associated with hypercoagulation, e.g. deep vein thrombosis during pregnancy (8-fold increased risk), pre-eclampsia (prevalence of the mutation up to 26%), placental infarction extending to > 10% of the placenta (10-fold increased risk), abruptio placentae (prevalence of the mutation up to 29.6%), and second- and third-trimester pregnancy failure (prevalence of the mutation up to 31.3%). An association of the maternal mutation with recurrent first-trimester miscarriage does not emerge from the literature, although fetal mutation (frequency higher than twice compared with that of the general population) has been related to early spontaneous miscarriage. Although some evidence suggests an association between APC resistance and intrauterine growth retardation, no significant relationship emerges currently from the literature. Screening for the Leiden mutation would seem advisable in women with previous pregnancy complications amongst those associated with APC resistance. Carriers of the mutation should be given appropriate counselling. The screening of asymptomatic women is not recommended at present.     

Nociceptin inhibits non-adrenergic non-cholinergic contraction in guinea-pig airway

1. Electrical field stimulation (EFS) of guinea-pig isolated main bronchi induced a non-adrenergic non-cholinergic (NANC) contractile response. Nociceptin (0.01–1 μM) significantly inhibited the contractile response to EFS (P<0.01), but not to capsaicin (P>0.05).
2. The μ-, δ- and κ-opioid receptor antagonists, naloxone (0.3 μM), naltrindole (3 μM) and nor-binaltorphimine (1 μM), respectively, did not significantly affect the inhibitory effect of nociceptin (0.03 μM; P>0.05).
3. The novel nociceptin antagonist, [Phe¹ψ(CH₂-NH)Gly²]nociceptin(1–13)NH₂ (0.03–1 μM); the σ ligands, carbetapentane (30 μM), 3-phenylpiperidine (30–100 μM) and (+)-cyclazocine (10–100 μM) significantly reversed the inhibitory effect of nociceptin (0.03 μM, P<0.05). In contrast, rimcazole, did not significantly reverse the inhibitory effect of nociceptin (0.03 μM) at any concentration tested (P>0.05).
4. EFS of guinea-pig bronchial preparations significantly increased SP-LI release above basal SP-LI (P<0.05). In the presence of nociceptin (1 μM), EFS induced a significant increase in SP-LI release above basal SP-LI release (P<0.05). Nociceptin caused a 59±11% (n=5) inhibition of EFS-induced release of SP-LI.
5. Nociceptin reduces the release of sensory neuropeptides induced by EFS, but not capsaicin, from guinea-pig airways. These experiments provide further evidence for a role for nociceptin in regulating the release of sensory neuropeptides in response to EFS.

     

Stimulation of airway sensory nerves by cyclosporin A and FK506 in guinea-pig isolated bronchus

1. We have investigated the contractile property of cyclosporin A and FK506 in guinea-pig isolated bronchus.
2. Cyclosporin A (10 μM) failed to significantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) and cholinergic contractile response (per cent methacholine E_max) induced by electrical field stimulation (EFS). In contrast, eNANC responses were significantly attenuated by both the neurokinin (NK)-1 and (NK)-2 receptor antagonists, N-acetyl-L-tryptophan 3,5-bis (trifluoromethyl)-benzyl and SR48968, respectively.
3. Cyclosporin A and FK506 caused a concentration-dependent contraction in guinea-pig isolated bronchus, which was significantly attenuated by NK-1 and NK-2 receptor antagonists. The capsaicin receptor antagonist, capsazepine (10 μM) significantly reduced the contractile response to cyclosporin A and capsaicin, but not to FK506.
4. The N-type calcium channel blocker, ω-Conotoxin (ωCTX: 10 nM), significantly reduced the contractile response to FK506 and the eNANC response following EFS. In contrast, ω-CTX failed to significantly reduce the contractile potency to capsaicin or cyclosporin A.
5. In bronchial preparations desensitized by repeated application of capsaicin (1 μM), the contractile responses to both cyclosporin A (100 μM) and FK506 (100 μM), were significantly reduced. In contrast, the contractile responses to substance P and neurokinin A (10 μM) were not altered. Furthermore, repeated application of cyclosporin A (100 μM) significantly inhibited the contractile response to capsaicin (1 μM).
6. The findings from this study would indicate that cyclosporin A and FK506 mediate contraction of guinea-pig isolated bronchus secondary to the release of neuropeptides from airway sensory nerves. However, the release of sensory neuropeptides appears to be mediated via different mechanisms for cyclosporin A and FK506, the former by stimulation of the vanilloid receptor and the latter via opening of N-type calcium channels.

     

Iron balance and iron nutrition in infancy

At birth, the total body iron content is approximately 75 mg/kg, twice that of an adult man in relation to weight. During the first 6 mo of life, total iron body content increases slightly and exclusive breastfeeding is sufficient to maintain an optimal iron balance. Thereafter, iron body content substantially increases and the infant becomes critically dependent on dietary iron, provided by complementary foods. Numerous factors may contribute to nutritional iron deficiency in infancy, the most important being low body iron content at birth, blood loss, high postnatal growth rate, and a low amount and/or bioavailability of dietary iron. We have documented that the prevalence of iron deficiency declined in Italy as iron nutrition improved and that early feeding on fresh cow's milk is the single most important determinant of iron deficiency in infancy. Healthy full-term infants should maintain optimal iron balance by consuming a good diet, which can be summarized as follows: breastfeeding should be continued exclusively for at least 5 mo and then together with complementary foods containing highly bioavailable iron; infants who are not breastfed or are partially breastfed should receive an iron-fortified formula, containing between 4.0 and 8.0mg/L iron, from birth to 12 mo of age; fresh cow's milk should be avoided before 12 mo of age.     

Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study.

PURPOSE: To describe the clinical features and outcome of HIV-associated primary effusion lymphoma (PEL) and to compare them with those of the other HIV-associated non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS: From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated in our institution. Clinical features and outcome of PEL patients were compared with the features and outcomes of 162 patients belonging to the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75). RESULTS: Among the 277 NHL patients, PEL was diagnosed in 11 patients (4%). Eight of 11 patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimen. Complete remission was reached in 42% of patients, with a median survival time of 6 months. When the clinical features and outcome of 11 PEL patients were compared with the other three groups of patients affected by NHL, at the onset of the disease, no statistically significant differences were observed in demographic data, CD4 absolute number, HIV viremia plasma levels, and clinical characteristics. When we compared the outcome of PEL patients with the CBCL group, a statistically significant worse outcome was observed; however, the clinical outcome of PEL patients was not significantly different from the outcome observed in the other two groups (PBLOC and IBL groups). CONCLUSION: PEL is a rare HIV-associated NHL type occurring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients.     

High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy.

PURPOSE: High-dose therapy (HDT) and peripheral-blood stem-cell transplantation (PBSCT) in HIV-associated lymphoma (HIV-Ly) has been recently reported in selected patients. We describe the results of a multi-institutional program of HDT and PBSCT as salvage therapy in HIV-Ly responsive to highly active antiretroviral therapy (HAART) in unselected patients. PATIENTS AND METHODS: Patients with resistant or relapsed HIV-Ly after first-line chemotherapy (CT) underwent PBSC collection after a course of second-line CT or cyclophosphamide and granulocyte colony-stimulating factor. Patients with chemotherapy-sensitive disease received carmustine, etoposide, cytarabine, and melphalan (BEAM regimen) and PBSC reinfusion. Effective HAART was maintained during the entire program. RESULTS: Sixteen consecutive patients entered the program. Adequate collection of PBSC was obtained in 80% of patients (median CD34+ cells 6.8 x 106/kg). Three patients had early progression. Ten patients (62%) received PBSCT with prompt engraftment in all patients (neutrophils and platelet engraftment after a median of 10 days [range, 8 to 10 days] and 13 days [range, 8 to 18 days], respectively). No patients died as a result of opportunistic or other infections or treatment-related complications. Eight of nine assessable patients achieved complete remission (one patient after radiotherapy for residual disease) and one patient achieved partial remission. Two patients experienced relapse and died at +10 and +14 months. Six patients are alive and disease free at a median of 8 months after transplantation. CONCLUSION: Our data confirm that HDT plus PBSCT is feasible and active as salvage therapy in HIV-Ly on a multi-institutional basis and in unselected HAART-responding patients. HIV infection should no longer preclude the opportunity of HDT in patients with lymphoma.     

Female genital mutilation and legislation

This article deals with the legal aspect concerning female genital mutilations (FGM). Such a practice (a partial excision of the external genitalia) is highly widespread in Central Africa, especially in Ethiopia and Somalia, and currently involves approximately 130,000,000 women worldwide and, in Italy, about 30,000 women amongst the immigrant population. Since 1982 the World Health Organization (WHO), which condemns such a practice as injurious to women's rights and health, proposed that laws and professional codes prohibit it in all countries. Legislation, although insufficient as a sole measure, is considered indispensable for the elimination of FMG. Since a long time some western countries (Sweden, Great Britain, Belgium and Norway), involved by immigration from countries with FGM tradition, legislated with regard to FGM. In Italy, a specific law does not exist; however, FGM are not allowed by the article 5 of the Civil Code. Nevertheless, recently, several cases of mutilations took place: this led some members of the Parliament to introduce a bill in order to specifically forbid FGM. The authors believe that legislation could effectively support the job of prevention and education, which physicians may carry out in order to save little girls from the risk of familial tradition of genital mutilations.     

Early self-rehabilitation in thoracolumbar fractures (a guide for patients)

The authors report the purposes and the contents of a guide entitled "Early self-rehabilitation in thoracolumbar fractures" currently used at the Division of Orthopaedics and Traumatology in the Macerata hospital, for patients affected with somatic "benign" fractures of the thoracolumbar passage (from T10 to L3). With elementary language and the support of simple images, several indications are given as to the anatomy and function of the column and its features, and the type of treatment used for fractures, so that the patient is aware of his or her lesion; the guide then becomes an actual manual for early and independent functional rehabilitation, capable of improving the physical and psychological state of the patient, in addition to favoring and accelerating healing. According to the authors, this study is useful in perfecting the relationship between physician and patient in the field of injuries of the vertebral column, which is often characterized by confusion and fear.     

Apolipoprotein E polymorphism and breast carcinoma: correlation with cell proliferation indices and clinical outcome

There is preliminary evidence that polymorphism of apolipoprotein E (apoE, protein; APOE, gene), one of the key regulatory proteins in cholesterol metabolism, influences the pathobiology of carcinoma of the colon, prostate and breast and also primary tumours of the brain. This study was designed to determine whether APOE polymorphism is related to variation in the rate of tumour cell proliferation and clinical outcome in carcinoma of the breast. One hundred and eleven infiltrating ductal carcinomas, for which follow up data were available, were included in the study. Estrogen and progesterone receptor status (ER, PR) cell proliferation index (MIB-1) and APOE genotypes were determined from paraffin-embedded tissue by standard methods. Positive correlations were found between grade and tumour size, grade and presence of metastasis, grade and MIB-1 expression, as well as between ER and PR. Survival correlated inversely with tumour size and the presence of positive lymph nodes. Both steroid receptors correlated inversely with MIB-1 expression. PR positive status also correlated inversely with high histological grade and presence of lymph node metastases. APOE allele frequencies resembled those of the general population. No significant associations were found between possession of either APOE 2 or 4 alleles and the parameters investigated. Although there is evidence to suggest that APOE 4 may predispose to the development of carcinoma of the breast our data do not support the hypothesis that APOE genotype influences the rate of tumour cell proliferation or the clinical course.