Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH)

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.     

Repetitive transcranial magnetic stimulation transiently reduces punding in Parkinson’s disease: a preliminary study

Amongst the impulse-control disorders (ICDs) associated with dopamine-replacement therapy in patients with Parkinson’s disease (PD) is a repetitive, complex, stereotyped behaviour called punding. Disruption of the reciprocal loops between the striatum and structures in the prefrontal cortex (PFC) following dopamine depletion may predispose patients with PD to these behavioural disorders. The purpose of the present study was to assess the effects of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral PFC (DLPFC) on punding in PD. We used low-frequency (LF) rTMS in four PD patients presenting with punding. Punding was transiently reversed by LF-rTMS over the DLPFC without enhancing motor impairment. The effect was more sustained after right DLPFC rTMS. Therefore, LF-rTMS produced a transient beneficial effect in PD patients with punding, similar to that reported in PD patients with levodopa-induced dyskinesias. rTMS might have therapeutic potential for the treatment of punding and perhaps other ICDs in PD.     

Palliative treatment of bone metastases with samarium-153 EDTMP at onset of pain

We evaluated the pain response and daily discomfort in patients suffering from a borderline degree of bone pain due to breast or lung cancer bone metastases, who had undergone early palliative radionuclide treatment. The results were compared with those from patients who had received standard analgesic therapy. Twenty-one patients (65.7 ± 3 years; 17 women) with metastatic bone cancer underwent samarium-153 (Sm-153) ethylene diamine tetramethylene phosphonate (EDTMP) administration (group A) and 18 patients (64.3 ± 8 years; 16 women) continued to receive standard analgesics (group B; control group). The patients kept a daily pain diary assessing both their discomfort and the pain at specific sites by means of a visual analog scale, rating from 0 (no discomfort–no pain) to 10 (worst discomfort–pain). These diaries were reviewed weekly for 2 months and three physicians rated the pain response on a scale from ?2 (considerable deterioration) to +2 (considerable improvement). Baseline characteristics were similar in both groups. The reduction of total discomfort and of bone pain in group A was significantly greater compared to group B (p < 0.0001). A significant improvement of clinical conditions was observed in group A, where the physician rate changed from ?1 to 1, compared to group B in which the rate changed from ?1 to 0. Sm-153 EDTMP therapy can be considered for patients with bone pain from breast and lung cancer in advance, i.e., before the establishment of severe pain syndrome.     

Severe form of Freeman-Sheldon syndrome associated with brain anomalies and hearing loss

We describe a child with whistling face and multiple contractures, including ulnar deviation of fingers, compatible with a diagnosis of Freeman-Sheldon syndrome (FSS). This patient also presented severe hypertonicity, multiple episodes of pneumonia, difficulty in swallowing, and poor weight gain, which are characteristic of the most severe cases of FSS. A brain CT scan showed cerebellar and brainstem atrophy. Auditory brainstem responses were absent. The child died at 5 months of respiratory failure. This case suggests the possibility that, especially in the most severe forms, brain abnormalities may be responsible for some of the clinical manifestations of this syndrome, i.e., respiratory problems, difficulty in swallowing and severe hypertonicity. We assume that there is more than one pathogenetic mechanism (muscular, skeletal, and neurological) underlying FSS, which, together with the genetic heterogeneity and the wide range of clinical symptoms leads us to suggest that it is more appropriate to speak of a Freeman-Sheldon spectrum rather than syndrome and that thorough investigation for CNS and auditory abnormalities should be part of the initial work-up of these patients. © 1996 Wiley-Liss, Inc.     

Major congenital malformations in Down syndrome

We studied major malformations in 5,581 infants with Down syndrome (DS) from three registers of congenital malformations. The prevalence at birth of 23 different malformations was compared with the program-specific rates for each malformation in non-DS infants. An about 300 times risk increase was seen for annular pancreas, cataracts and duodenal atresia and an about 100 times risk increase for megacolon and choanal atresia. Esophageal, anal and small bowel atresia, preaxial polydactyly, and omphalocele all showed risk increases between 10 and 30 times. Statistically significantly elevated risk ratios around 3–5 were seen for cleft palate, cleft lip/palate, and limb deficiencies. No increased risk was seen for neural tube defects, hydrocephaly, microtia, renal agenesis or severe dysgenesis, hypospadias or polydactyly other than preaxial. Oral clefts were more often present in DS in the Swedish material than in the other two materials. Cardiac defects were registered in 26% of all cases (varying between programs) but 28% of the cardiac defects were unspecified. DS infants born to women younger than 25 years had a significantly increased risk for megacolon and there was a trend of increasing risk for esophageal or anal atresia with maternal age. A decreased risk for cardiac defect in DS infants born to teenage mothers was found, quite pronounced for endocardial cushion defects and ventricular septum defects. There were no statistically significant differences in the sex distribution of specific malformations in infants with DS and in non-DS infants. © 1996 Wiley-Liss, Inc.     

First-line carboplatin/nab-paclitaxel in advanced ovarian cancer patients,after hypersensitivity reaction to solvent-based taxanes: a single-institution experience

One of the major challenges related to solvent-based taxanes administration in clinical practice is the high rate of hypersensitivity reactions (HSRs). Nab-paclitaxel is a solvent-free, albumin-bound, paclitaxel, which minimize the risk of HSR occurrence. In this single-institution, retrospective analysis, we evaluated stage IIIc–IV epithelial ovarian cancer (EOC) patients, treated with first-line carboplatin/nab-paclitaxel (± bevacizumab), after the occurrence of an HSR with solvent-based paclitaxel (and/or docetaxel). Between April 2012 and December 2018, ten patients (20.8%) received carboplatin/nab-paclitaxel (± bevacizumab) after the occurrence of an HSR to solvent-based taxanes. Among the evaluable patients, ORR was 100%. At median follow-up of 28.5 months, median PFS was 16.7 months, and median OS was 65.4 months, respectively. Median received dose intensity (DI) was 86% and 80% of the projected DI for nab-paclitaxel and carboplatin, respectively. There were no treatment-related grade 4 adverse events. Most relevant treatment-related grade 3 adverse events were: asthenia (10%), hypertransaminasemia (10%), neutropenia (20%), thrombocytopenia (20%), and anemia (10%). No HSR recurrence was observed. The high rate of HSR occurrence could limit first-line treatment options in clinical practice. Carboplatin/nab-paclitaxel association could represent a valid treatment option in this setting.