Rifabutin for treating tuberculosis in solid organ transplant recipients: A retrospective observational study and literature review.

BACKGROUND: The treatment of tuberculosis (TB) in solid organ transplant (SOT) recipients is challenging owing to interactions between rifampin and immunosuppressive drugs. Rifabutin, a rifamycin with excellent activity against Mycobacterium tuberculosis and that induces cytochrome p450 less, may facilitate treatment. We report our experience with rifabutin for treating TB in SOT recipients and review the available literature. METHODS: A retrospective observational study of all SOT recipients with TB between January 2000 and December 2019. The clinical characteristics and outcomes of patients treated with and without rifabutin-containing regimens were compared and a literature review was conducted. RESULTS: We included 31 SOT recipients with TB, among whom 22 (71%) were men and the median age was 62 years (interquartile range 50-20). There were no significant differences between patients treated with rifabutin (n = 12), rifampin (n = 14), and non-rifamycins (n = 5) in clinical cure rates (83.3%, 64.3%, and 100%, respectively; P = .21), side effects (25%, 37.5%, and 20%, respectively; P = .74), or mortality (16.7%, 35.7%, and 0%, respectively; P = .21). Only one patient, treated with rifampin, suffered graft rejection. The literature review identified 59 SOT recipients with TB treated with rifabutin-containing regimens from 8 publications. Overall, the clinical cure, graft rejection, and mortality rates were 93.2%, 5.1%, and 6.8%, respectively. CONCLUSIONS: Rifabutin-containing regimens offer a reliable alternative to rifampin when treating TB in SOT recipients.

18F-FDG uptake and calcifications on positron emission tomography/computed tomography in octogenarians with severe aortic stenosis.

AIM: The degree of inflammation within the atherosclerotic plaque can be detected non-invasively by positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG). The incidence of aortic plaques with 18F-FDG increased uptake in octogenarians with aortic stenosis is unknown. Aim of this study was to evaluate the frequency of inflamed aortic atherosclerotic plaques in octogenarians with or without severe aortic stenosis and their correlations with calcifications. METHODS: The study group comprised 27 patients older than 80 years who underwent a 18FDG PET/CT. Nine patients with severe symptomatic aortic stenosis, eligible to TAVI procedure (TAVI Group), and 18 patients age and sex matched, without clinical evidence of aortic stenosis (No TAVI Group), were selected and analysed. RESULTS: In the whole population 4/27 patients (9.3%) had a significant focal aortic vessel wall 18F-FDG increased uptake: 1 patient (11.1%) in TAVI group and 3 in non-TAVI Group (16.7%). Overall 81 aortic segments were analysed. 18F-FDG uptake rates were similar in the two groups (1/27, 3.7% in TAVI Group and 3/54, 5.5% in No TAVI Group, P=0.7). At CT scan calcifications were significantly more frequent in the TAVI Group compared to non-TAVI Group (23/27, 85.2% and 28/54, 51.8% P=0.005). None of the sites of arterial calcification had an increased focal 18F-FDG uptake. CONCLUSION: Irrespectively to the presence of aortic stenosis, a significant FDG plaque uptake in octogenarians is rare while calcifications are extremely frequent.

Chronic migraine in women is associated with insulin resistance: a cross-sectional study.

BACKGROUND AND PURPOSE: Migraine is a common neurological disorder. It can be divided into episodic migraine (EM) and chronic migraine (CM), based on headache frequency. Some studies have shown that insulin sensitivity is impaired in migraine; moreover, hypertension, diabetes and obesity are common in patients with CM. The aim of this study was to assess serum glucose, insulin levels and insulin resistance (IR) in a sample of episodic migraineurs, chronic migraineurs and non-pain healthy controls. METHODS: Eighty-three women with EM, 83 with CM and 83 healthy controls were recruited. Headache was diagnosed according to the latest International Classification of Headache Disorders 2 criteria. Waist circumference, body mass index (BMI) and blood pressure were measured. Checked metabolic parameters included fasting glucose, the 2 h 75 g oral glucose tolerance test (2 h OGTT), serum HbA1c, blood lipid profile, C-reactive protein and prolactin. The homeostasis model assessment formula was used to calculate IR. RESULTS: A significant prevalence of IR in CM was observed (P = 0.002). No significant associations were found with fasting glycaemia, the 2 h OGTT, HbA1c, blood lipid profile, C-reactive protein, prolactin and waist circumference. Obesity (BMI >30 kg/m(2)) was associated with an increased risk of CM [odds ratio (OR) 2.4]. When the outcome of interest was the association between IR and obesity, the OR was significantly increased compared with IR alone (OR = 13.2). CONCLUSION: This may suggest that CM is associated with IR status, particularly when it is in partnership with obesity.

In PCOS patients the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism than metformin alone.

BACKGROUND & AIMS: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism and by insulin resistance and related metabolic alterations. Both metformin and anti-androgens, such as spironolactone, are used to ameliorate the different aspects of this disorder. We investigated whether therapy with metformin plus low-dose spironolactone is more effective than metformin alone in PCOS patients. METHODS AND RESULTS: Fifty-six PCOS patients were randomized in two groups: group A (28 patients) was treated with metformin (1700 mg/die) and group B (28 patients) was treated with metformin (1700 mg/die) plus low-dose spironolactone (25 mg/die). Anthropometric, hormonal and metabolic parameters were evaluated at baseline and after six months of treatment. After therapy regular menses were restored in approximately 82% of group A patients (P < 0.001) and in 68% of group B patients (P < 0.001). Circulating testosterone, Δ-4-androstenedione and Hirsutism Score (HS) significantly decreased in both groups. However, dehydro-epiandrosterone sulphate significantly decreased only in group B, and HS underwent a stronger reduction in group B (P < 0.001). At baseline, 39/56 (69.6%) patients met the diagnostic criteria for metabolic syndrome, but only one patient met these criteria after treatment. CONCLUSIONS: This study confirms the beneficial effects of metformin in PCOS patients. It also indicates that the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism as compared to metformin alone.

[Pain assessment in terminally-ill cancer patients on admission in hospice and its modification after the first three days of care. A monocentric experience]. / Il dolore nel paziente oncologico terminale: valutazione del sintomo all'ingresso in hospice e delle sue modifi cazioni nei primi tre giorni di assistenza. Esperienza monocentrica.

AIMS: Pain is among the most frequent and distressing symptoms in terminally-ill cancer and, to date, many patients still experience uncontrolled pain. In this paper we evaluated prevalence and intensity of pain on admission in our palliative care center and during the first three days of care. PATIENTS AND METHODS: From September 2009 to October 2009 we consecutively recruited 96 terminally-ill cancer patients : on admission more than 50% had severe pain and only 4% referred to be pain-free. 54% of patients was on treatment with strong opioids. RESULTS: After three days from admission in our palliative care unit only 7% of patients experienced severe pain, 25% reported absence of pain and 80% of patients was on treatment with strong opioids. CONCLUSIONS: The beginning of palliative care led to a meaningful and rapid reduction of pain in the vast majority of terminally-ill cancer patients evaluated in this study.

Daily motor performance after switching levodopa to melevodopa: an open-label on advanced Parkinson's disease with "delayed-on" and/or"wearing-off".

AIM: Aim of the present study was to evaluate the clinical efficacy, tolerability and quality-of-life measures to melevodopa in advanced Parkinson's disease (PD) with motor fluctuations (MFs). METHODS: A total of 37 patients with advanced PD and MFs participated in the study. Patients were switched from standard l-dopa/carbidopa to melevodopa and were treated for 10 weeks. RESULTS: Assessment of "On-Day" time demonstrated improvement to about 0.7 hour in the melevodopa treatment. The benefit was greater in patients with "delayed-on" (P=0.002) and especially in those with both "delayed-on" and "wearing-off" (P<0.001). Most patients showed a significant improvement in PDQ-39 total score (P=0.002) and PSI distress domain (P<0.001). Instead, not significant difference was observed in patients with only wearing-off. CONCLUSION: These data show that melevodopa is an effective agent for improving daily motor performance and quality-of-life in PD with "delayed-on", also in association with "wearing-off".

Bell's palsy: a manifestation of prediabetes?

BACKGROUND: Idiopathic peripheral facial nerve palsy or Bell's palsy (BP) is the most common cause of facial nerve palsy. OBJECTIVE: To evaluate the role of glucose metabolism abnormalities in BP. METHODS: We identified 148 patients with unilateral BP and 128 control subjects. In all we evaluated glucose level at fasting and after a 2-h oral glucose tolerance test (2h-OGTT). In addition we determined insulin resistance (IR), by HOMA-index. Patients and controls were divided in to two groups, according to their Body Mass Index (BMI). RESULTS: Following a 2h-OGTT, the prevalence of glucose metabolism abnormalities was significantly higher in patients with BP than in controls (P < 0.001). Impaired glucose tolerance (IGT) was found in 57 (38%) patients and in 23 (18%) controls, while a new-diagnosed DM (NDDM) was found in 29 (19%) patients and in 8 (6%) controls. The IR was significantly increased only in BP patients with BMI ≥ 24.9 (P = 0.005). BMI, waist circumference, blood pressure, tryglicerides, serum lipid, drugs use were not significantly different between patients and controls. CONCLUSIONS: In this study we found that prediabetes is frequently associated with facial palsy. We propose to perform a 2h-OGTT in patients with peripheral facial palsy and normal fasting glycaemia. HOMA-index should be evaluated in obese facial palsy patients.

Expression and localization of ATP binding cassette transporter A1 (ABCA1) in first trimester and term human placenta.

ATP binding cassette transporter A1 (ABCA1) is a membrane transporter which performs cellular efflux of cholesterol and phospholipid. ABCA1's cholesterol transporting role in human placenta appears to be crucial for normal fetal development. Despite the critical importance of cholesterol in fetal development, expression of ABCA1 in the human placenta throughout gestation and its specific cellular localization have not been known yet. We therefore investigated ABCA1 expression in human placenta at first trimester and term by western blot and quantitative real-time PCR (qRT-PCR) analysis. Furthermore, its localization was investigated by immunohistochemistry and confocal microscopy. Expression of ABCA1 did not differ significantly between first trimester and term placenta at both protein and mRNA levels. Immunohistochemical data demonstrated that ABCA1 was widely localized in the villous and extravillous cytotrophoblast as well as in some stromal and endothelial cells. Confocal microscopy imaging data showed that ABCA1 was localized largely at the basolateral and to some extent at the apical side of first trimester villous cytotrophoblast cell membranes. Placental expression of ABCA1 throughout the gestation and its specific cellular localization indicate that this transporter may play an important role in materno-fetal cholesterol transfer.

Relationship between high prolactin levels and migraine attacks in patients with microprolactinoma.

The pathophysiology of pituitary-associated headache is unknown, although structural and functional features of the tumour are proposed mechanisms. The objective of this study was to evaluate whether headache in a population with pituitary micro-adenomas was related to hyperprolactinemia. We recruited 29 patients with microprolactinoma and headache: 16 with migraine (group A) and 13 with tension-type-headache (group B). The prolactin (PRL) levels measured during attacks of headache were significantly higher in nine patients (56%) of group A and in one patient (8%) of group B. In four of the nine patients of group A, PRL increased after thyrotropin-releasing-hormone (TRH) test and induced severe attacks. After dopamine-agonist (DA) treatment, the headache improved in seven (44%) patients of the group A and in two (15%) patients of the group B. Three of the four patients in whom the TRH-test induced headache attacks, improved after DA treatment. We suggest that hyperprolactinemia may contribute to development of pain in migraine subgroups and further TRH-test could be used to predict which patients could benefit by DA therapy.

Umbilical endometriosis in pregnancy: a case report.

To our knowledge, this is the first case reported in the literature of umbilical endometriosis in a pregnant woman. We report a case of umbilical endometriosis in a pregnant woman at 16 weeks of gestation. The patient revealed a reddish-brown polypoid nodule within the umbilical depression, with the typical history of monthly bleeding from the umbilicus. A nodule biopsy, testing of serum levels of CA-125 and a transabdominal ultrasound examination were performed. The diagnosis of endometriosis was confirmed by pathological examination. Serum levels of CA-125 were slightly increased and the pelvic ultrasound examination did not identify ovarian cysts of a possible endometriotic nature. The patient was also examined at 24 weeks' gestation, after delivery and in the late postpartum period. No therapy was given and the lesion resolved spontaneously 2 months after the biopsy was taken.

Management of sexual dysfunctions in women.

The deeper understanding of female physiology changed the perspective used to evaluate sexual difficulties. Systems like: vascular, neurological, biochemical, and endocrine are investigated as their modifications for aging or medical conditions may alter the sexual responsivity of women. New data imply that pharmacological interventions may become suitable for women. Gonadal steroids influence mood, wellbeing, and genital physiology but evidence of actions is controversial. Hormone imbalance provokes symptoms that may also derive from other conditions. Clinicians must exclude dismetabolism, depression and family crisis before diagnosing gonadal problems. The female androgen insufficiency syndrome was defined in July 2001 as altered mood, memory and wellbeing, and loss of desire. Estrogen maintains wellbeing and healthy genitals, influencing mood and sexuality. Progesterone provokes tension and nervousness, causing premenstrual syndrome. Hormone replacement is indicated in the treatment of endocrine deficiency. In research projects women receiving one preparation containing androgen reported improvement of mood, and arousal. Sildenafil cures approximately 25% of sexually dysfunctional, menopausal patients; being more effective with hormone replacement therapy (HRT) and consistently active against the block of antidepressants on orgasm. Added to psychiatric regimens, sildenafil ameliorates excitement. Sex therapy helps patients change behavior, overcome anger, communicate needs and redefine sex. We strongly believe that such crucial aspects must be addressed in therapy, even when the etiology is organic.

[Clinical and epidemiological characteristics of squamous cell carcinoma of the oral cavity in women]. / Características clínico-epidemológicas do carcinoma epidermóide de cavidade oral no sexo feminino.

BACKGROUND: Squamous cell carcinoma (SCC) of the oral cavity occurs mainly in the male population. The objective of the study is to identify the main clinical and epidemiological differences of the oral SCC between men and women. METHODS: Retrospective analysis of the charts of 228 cases of SCC of the oral cavity in women treated at the Head & Neck Surgery Service, Heliopolis Hospital, São Paulo, Brazil from 1977 to 1996. The clinical and epidemiological characteristics of these cases were compared with those of 849 male patients. RESULTS: The mean age of women was 60.7 years (ranging 2 to 100 years) and in the male group was 55.6 years (p<0.00001). In cases where the alcohol intake and tobacco use were absent, the tumors ocurred in older patients. The isolated tobacco use didn't affect the distribuction by age but for the alcohol intake (alone or combined with tobacco) the patients were younger. On the alcohol intake, 71% of the women and 8% of the man used no alcohol. The most common sites of tumors were tongue and floor of the mouth but in the women group the incidence of tumors in these sites were 43% compared with 61% in the men. CONCLUSIONS: The highest incidence of SCC the of oral cavity occurs later in women, than in men. This could be explained by a lesser exposure to alcohol and tobacco in women. Other factors seem to be involved in this issue.

Características clínico-epidemológicas do carcinoma epidermóide de cavidade oral no sexo feminino / Clinical and epidemiological characteristics of squamous cell carcinoma of oral cavity in women

OBJETIVO: Este trabalho tem como objetivo identificar as principais diferenças clínico-epidemiológicas do carcinoma epidermóide de cavidade oral no sexo feminino quando comparado ao sexo masculino. MÉTODOS: Foram estudados retrospectivamente os prontuários de 228 pacientes do sexo feminino portadoras de carcinoma epidermóide de cavidade oral, atendidos no Serviço de Cirurgia de Cabeça e Pescoço do Hospital Heliópolis, no período entre 1977 e 1996. As características clínico-epidemiológicas destas pacientes foram comparadas com aquelas de 849 pacientes do sexo masculino. RESULTADOS: A idade das pacientes das mulheres variou de 2 a 100 anos, com uma média de 60,7 anos. Nos homens encontramos idade entre 17 e 88 anos com uma média de 55,6 (p<0,00001). Quando o etilismo e o tabagismo estavam ausentes, a incidência do carcinoma epidermóide de boca ocorreu em uma faixa etária mais tardia. A presença do tabaco isoladamente näo afetou a distribuiçäo por faixa etária, enquanto que o álcool isoladamente ou em associaçäo com o tabaco leva a uma incidência mais precoce do câncer de boca. Os dois principais sítios de incidência säo a língua e o soalho. As mulheres têm uma menor incidência de lesöes de língua e soalho (43 por cento) quando comparado aos homens (61 por cento). Aproximadamente 50 por cento das mulheres eram estadio III e IV no momento do diagnóstico. Entre os homens este índice atinge 53 por cento. CONCLUSÖES: O carcinoma epidermóide de cavidade oral nas mulheres tem características clínico-epidemiológicas peculiares que justificam o desenvolvimento de protocolos de diagnóstico e tratamento específico para ele

[Laparoscopic appendectomy as first choice intervention in the treatment of inflammatory diseases of the appendix. Analysis of 397 laparoscopic interventions]. / L'appendicectomia laparoscopica come intervento di scelta nel trattamento delle malattie infiammatorie dell'appendice. Analisi di 397 interventi laparoscopici.

Despite the increasingly widespread use of laparoscopy, especially for gallbladder diseases, laparoscopic appendectomy has not yet met with universal acceptance. The aim of the present retrospective study was to illustrate the technical aspects and the results of 397 laparoscopic appendectomies carried out at the Surgical Department of the San Giovanni Battista Hospital in Zagarolo, Rome, from January 1993 to December 2000. The patients included 260 females with a mean age of 35.5 years and 137 males with a mean age of 38.5 years. All the appendectomies were carried out laparoscopically, with a conversion index of 0%, by two surgeons, utilising only three trocars and the Veress needle technique. Mean operating time was 22.5 min (range: 15-30 min). The mean postoperative hospital stay was 1.5 days. Morbidity was 1.76% (7 cases) and mortality nil. The authors emphasise the numerous advantages of laparoscopic techniques in their experience, including the excellent cosmetic results, reduced postoperative pain, rapid functional recovery, and lower incidences of adhesions, wound infections and laparocele, and believe that laparoscopic appendectomy is a reliable operation for treating all inflammatory diseases of the appendix.

[Videolaparoscopic treatment of varicocele: retrospective study of 165 cases]. / Trattamento videolaparoscopico del varicocele: studio retrospettivo su 165 casi.

Idiopathic varicocele is a common condition that is present in approximately 15% of the general male population. The mechanism by which varicocele exerts a deleterious effect on testicular function and semen quality remains unknown. Nevertheless, it is generally regarded as a significant factor in male infertility. Varicocelectomy is accomplished with a variety of approaches: the inguinal and high retroperitoneal procedures are still commonly accepted methods, but laparoscopic varicocelectomy is currently proving an increasingly popular procedure. The authors report the results of a retrospective study of 165 laparoscopic varicocelectomies performed from 1993 to 2000 and conclude that this approach is simple, safe and effective and should be recommended as the treatment of choice.

Pyrite suspended in artificial sea water catalyzes hydrolysis of adsorbed ATP: enhancing effect of acetate.

Minerals have been implicated in different catalytic processes during chemical evolution. It has been proposed that exergonic synthesis of pyrite (FeS2) could have served to promote the endergonic synthesis of biomonomers in early stages of life formation on Earth. The present study was aimed to investigate whether pyrite can adsorb nucleotides and oxo acids in the potentially mild prebiotic conditions found away from the hot hydrothermal vents. It is shown that pyrite strongly adsorbs adenosine 5'-triphosphate in an artificial medium that simulates primordial aqueous environments, and that adsorption is enhanced in the presence of acetate and in an oxygen-free atmosphere. Moreover, the mineral catalyzes the sequential hydrolysis of the gamma and beta phosphoanhydride bonds of the nucleotide.

Perioperative frozen section examination in parotid gland tumors.

CONTEXT: The minimal recommended surgical approach to parotid tumors is partial parotidectomy with resection of the superficial lobe of the gland. Histologic diagnosis prior to surgery is not possible, as incisional biopsies are contraindicated due to the possibility of facial nerve injury or incomplete tumor resection. Thus, the biopsies tend to be perioperative. OBJECTIVE: To compare the results of frozen section examination with the definitive pathological diagnosis. DESIGN: Accuracy study by retrospective analysis. SETTING: Head and Neck Surgery Service of Heliópolis Hospital, São Paulo, Brazil. SAMPLE: 153 cases of parotid gland tumors treated between 1977 and 1994. DIAGNOSTIC TEST: Frozen section and pathological diagnosis. MAIN MEASUREMENTS: Sensibility and specificity of the frozen section examination. RESULTS: Frozen section study diagnosed 19 (12.4%) malignant and 127 (83.7%) benign tumors. Sensitivity of the frozen sections for malignancy was 61.5% (95% CI 54 to 69%) and specificity was 98% (95% CI 94 to 100%), and this result is comparable to the literature. CONCLUSIONS: We consider that frozen section examination for salivary gland tumors is not sufficient on its own for deciding on the best management. Their interpretation must be correlated with clinical and intraoperative findings, in association with the surgeon's experience.

Peripherally injected IL-1 induces anorexia and increases brain tryptophan concentrations.

Interleukin-1 is an anorexigenic cytokine, and is involved in the pathogenesis of cancer anorexia. Interleukin-1 induced anorexia is mediated by direct action within the hypothalamus, and by peripheral mechanism(s) yet to be determined. Here we present evidence showing that in an animal model the peripheral injection of interleukin-1 is followed by a significant rise in brain tryptophan concentrations. Tryptophan is the precursor of the neurotransmitter serotonin, known to mediate the onset of satiety under normal and pathological conditions. By inference, we conclude that interleukin-1 induced anorexia is mediated by at least two different mechanism: i) interleukin-1 direct action within the hypothalamus; ii) increased brain serotonergic activity, secondary to interleukin-1 induced increased brain availability of the serotonin precursor, tryptophan.

Effect of cisplatin and paclitaxel on plasma free tryptophan levels. An in vitro study.

UNLABELLED: Emesis is a common side effect of some antineoplastic drugs. Cisplatin (CP) induces a biphasic pattern of emesis referred to as acute (AE) and delayed (DE) emesis. The serotonergic system plays a major role in the pathogenesis of CP-induced AE, as suggested by the therapeutic efficacy of 5HT3 receptor antagonists. The pathogenesis of CP-induced DE are not clear. To date, there are no pharmacological agents which satisfactorily control DE. We hypothesize that increased availability of tryptophan (TRP) for the synthesis of brain serotonin (5-HT) could, at least in part, contribute to CP-induced DE. In fact, within 2-4 hrs of administration, CP is largely bound to albumin (ALB) with consequent possible displacement of TRP which circulates in plasma mostly (90% of total plasma TRP) bound to its natural carrier, ALB. To test this hypothesis, we studied in vitro the effect of increasing doses of cisplatin on F-TRP in plasma obtained from healthy volunteers. We also tested the effects of therapeutic amounts of paclitaxel, an antineoplastc agent which does not cause emesis. RESULTS: F-TRP concentrations increased in a dose-dependent manner following incubation with cisplatin, in contrast to paclitaxel (PTX). CONCLUSIONS: The preliminary data obtained suggest that CP, but not PTX, at therapeutic doses, increases plasma F-TRP concentrations. This increase has likely negligible relevance in CP-induced AE, which is induced by the 5-HT released by the enterochromaffin cell system, while it might play a role in the pathogenesis of CP-induced DE. In fact, CP binding to ALB is stable for 4-5 days following administration, thus suggesting long-term TRP displacement from ALB and enhanced brain 5-HT synthesis and release. Whether increased TRP availability for 5-HT synthesis might be the pathogenic mechanism for CP-induced DE in vivo, is currently being tested.

Effect of kynurenine on tryptophan-albumin binding in human plasma.

Increased plasma free tryptophan levels have been reported in cancer patients and causally associated to the presence of anorexia. The pathogenesis of this occurrence is yet to be completely understood. Kynurenine is a metabolite of tryptophan, and has been reported increased in plasma during tumor growth. Because of the similarities between tryptophan and kynurenine we speculate that their rise in the presence of a tumor might be causally related. To test this hypothesis, we performed a series of in-vitro studies, showing that kynurenine supplementation reduces the amount of tryptophan bound to albumin, and thus, by competition, increases free tryptophan levels. The likely clinical consequences of these findings are discussed.