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.

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.

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.

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".

Thyroid function and prolactin levels in insulin-dependent diabetic children and adolescents.

We evaluated serum thyroid hormones, TSH, and prolactin before and after induction of TRH and thyroid microsomal autoantibodies in 91 diabetic children and adolescents (mean age 11.11 +/- 4.13 yr), with illness ranging from a few days to 14.25 yr, and in 127 "short-normal" subjects (mean age 10.32 +/- 3.18 yr). All were clinically euthyroid. The control pubertal subjects showed T4, rT3, TBG, and rT3/T3 ratio values that were significantly lower than those of prepubertal subjects. The PRL area was significantly higher in pubertal than in prepubertal females. In diabetic patients, differences between pubertal and prepubertal subjects were similar to those of controls regarding T4 levels and PRL area only. T3, T4, and fT3 appeared to be significantly lower than in controls, while the rT3/T3 ratio was higher. A negative correlation (r = -0.277, P = 0.009) between T3 and HbA1 levels was demonstrated. Furthermore, thyroid function was not different in subjects with or without retinal changes or in subjects with or without residual B-cell function. Microsomal autoantibodies were observed in 6.25% of the subjects examined, though none showed any clinical or humoral sign of impaired thyroid function. In conclusion, the lower T4 and rT3 values detected in pubertal controls suggest an increased efficacy of peripheral thyroid activity in this particular life span. Considering the fact that, in diabetic children, such a decrease in rT3 at puberty is not present and that the T3 value in diabetic children is persistently lower than in controls, it would seem that even diabetic children show a "low T3 syndrome," as in adult diabetic subjects.

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.

Histological behaviour of chronic hepatitis in patients treated with alpha interferon.

To evaluate the histological effects of alpha Interferon (IFN) therapy, serial liver biopsy specimens from 30 patients with chronic hepatitis were studied. The biopsies were examined using a scoring system. After 12 mths of IFN therapy responders were 8 out of 11 HBV infected patients, 10 out of 12 HCV infected patients and only 1 out of 7 patients with cryptogenetic hepatitis. As spontaneous improvement of hepatic changes is infrequent, our data indicate that in terms of histological patterns interferon therapy is effective in chronic viral hepatitis.

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 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.

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.

Class I HLA antigens hepatic display and beta-2-microglobulin serum values in chronic hepatitis C: effect of treatment with recombinant alpha interferon.

BACKGROUND/AIMS: Enhanced hepatocellular display of class I HLA antigens together with rising serum beta-2-microglobulin (a subunit of class I HLA molecule) and transaminases is reported in patients with chronic hepatitis B during treatment with interferon as an index of immune lysis of virus infected cells. METHODOLOGY: We studied class I HLA antigens and beta-2-microglobulin display in the livers of 23 patients with chronic hepatitis C before and after a 12 month treatment with recombinant alpha interferon. Beta-2-microglobulin serum values were monitored. In all the patients before treatment, class I HLA antigens and beta-2-microglobulin were diffusely displayed in the bile duct epithelium, in the sinusoidal lining cells, in approximately 50% of the inflammatory cells and in the hepatocyte membrane with marked staining in the areas of periportal and lobular necrosis. RESULTS: At the end of the treatment, class I HLA antigens and beta-2-microglobulin were no longer or only faintly detectable in the hepatocytes of 12 patients who showed clinical and histological improvement. The immunohistochemical pattern was unchanged in the 11 patients who did not respond to the therapy. Baseline serum beta-2-microglobulin values were high in all the patients and decreased significantly only in the group of responders. No peaks of transaminases were registered. CONCLUSIONS: The disappearance or reduction of HLA hepatocellular display without acute increase of serum beta-2-microglobulin values and transaminases during successful treatment with interferon in chronic hepatitis C suggests a clearance of the virus due to direct antiviral rather than immunologically mediated mechanism.

Therapeutic association for nasopharyngeal cancer.

The authors studied retrospectively 16 cases of malignant epithelial nasopharyngeal tumors which were treated at the Head and Neck Service of the Heliópolis Hospital, São Paulo, Brasil, from December 1977 to December 1983. The treatment was intra-arterial chemotherapy (IAC) followed by radiotherapy. The chemotherapeutic schedules were: methotrexate and vincristine, methotrexate, bleomycin and vincristine (2 different schedules) and methotrexate, bleomycin, vincristine and cisplatinum. Objective responses to IAC were observed in 18.6% of the cases. Only 3 patients are alive at 26, 37 and 53 months; 2 of them had exhibited response to IAC. The authors analyze the results and suggest randomized trials in order to determine the exact effects of this method of treatment.

Transfusion-transmitted virus (TTV) in Brazil. Preliminary report.

TTV is a recently discovered DNA virus, isolated from a patient with post-transfusion hepatitis of unknown etiology by Japanese researchers. In the present study, we evaluated the presence of TTV among chronic liver diseases patients in São Paulo and Pará states, representing two geographically distinct Brazilian regions. TTV DNA was found in 21/105 (20%) and 9/20 (45%) cases from São Paulo and Pará States, respectively. DNA sequence data confirmed the presence of TTV genotypes 1a and 2a, as well as other genotypes not yet described. In conclusion, TTV is present in chronic liver diseases cases from Southeast and North Brazil. However, further studies involving healthy populations are necessary before establishing any causal relationship among TTV and human hepatitis.

[Acupuncture therapy of hypogalactia]. / Terapia agopunturale dell'ipogalattia.

Reference is made to the current tendency to reappraise breast feeding in the light of both medical and social-cultural considerations, and attention is called to the current lack of sound treatments for hypogalactia. The physiopathological mechanisms underlying this condition are examined, and an account is given of results obtained with acupuncture reflexotherapy in this field. The conclusion is drawn that the technique is effective, innocuous and well accepted.

[Assessment of portal hypertension in hepatic cirrhosis in relation to etiologic factors]. / Valutazione dell'ipertensione portale nella cirrosi epatica in rapporto ai fattori etiologici.

Hundred-forty-one patients, 78 affected by alcoholic liver cirrhosis and 63 by posthepatitic cirrhosis were studied in order to assess the degree of portal hypertension in liver cirrhosis of different etiology taking into account the developing stages of the disease. Etiological assessment was based on anamnesis, laboratory data, needle liver biopsy and patients of each group were divided into 3 subgroups (grade A, B, C) according to Child-Turcotte classification. A > 1.3 cm diameter of portal vein and a > 13 cm spleen size evaluated by means of real-time ultrasonography together with the occurrence of esophageal varices at endoscopy were considered as signs of portal hypertension. Our study shows that such signs are more frequent in patients affected by posthepatitic cirrhosis in comparison with those affected by alcoholic cirrhosis. If the severity of the disease was considered, at the early stage (grade A) no significant difference was reported in portal diameters while splenomegaly and esophageal varices appeared more frequent in posthepatitic cirrhosis. In grade B patients the increase of portal and spleen size proved significantly greater in posthepatitic cirrhosis whereas prevalence of esophageal varices was similar in the two groups. The lack of differences in the three considered parameters at the end stage of the disease may be due to severe changes in liver morphology actually similar in the 2 groups apart from etiological factors.

[The use of vegetable fibers in the treatment of pregnancy diabetes and/or excessive wight gain during pregnancy]. / Utilizzazione delle fibre vegetali per la terapia del diabete gestazionale e/o dell'eccessivo aumento ponderale in gravidanza.

Vegetable fibres with a high viscosity reduce the levels of basal and post-prandial glycemia in both normal and diabetic subjects. The paper reports the results of a study to asses the value of glucomannan and guar in the treatment of excessive wight gain in pregnancy and gestational diabetes. Thirty-four patients were included in the study, of which 13 received glucomannan (3 g/day) and 21 guar (10 g/day). An oral glucose tolerance test was performed in all patients before and after therapy. A diminution of basal and post-OGTT glycemia values was observed in all subjects.

Leiomyoma of the ovary. Case report.

The leiomyoma of the ovary is a very rare form of ovarian neoplasia, while its uterine localization is very common and diffused. It occurs prevalently in post-menopausal women usually causing abdominal swelling and pain. Such a case occurred in our observation and we report it here.

The value of therapeutic planning and the degree of experience of the surgical team on the results of cancer treatment of the larynx and hypopharynx.

This is a prospective study supported by 170 cases of epidermoid carcinoma of the larynx or hypopharynx, treated during the period from January of 1981 to January of 1988, at the Head and Neck Surgery Service of the Heliópolis Hospital Complex, São Paulo. The objective of this project was to evaluate the importance of surgeon experience with regard to the rates of post-operative complications and the rates of relapse and survival. The results of the 8 surgical specialists who integrate the permanent staff at the institute and who different varying degrees of experience with regard to time spent exercising their specialties were compared. The results obtained did not show a significant difference among the various surgeons, and this uniformity is explained by the fact that all the therapeutic planning was elaborated through consensus of the whole group, and this could have minimized the effect of experience of a surgeon responsible for the operation. The authors emphasize the importance of pre-operative evaluation for good results and propose that it is in the direction of complete mastery of preliminary work in the area that programs for the formation of new specialists should be directed.

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.