Effects of antiretroviral therapy on proprotein convertase subtilisin/kexin 9: focus on lipids, inflammation and immunovirological parameters.

OBJECTIVES: Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of cholesterol metabolism, have been reported to have an increasing trend in people living with HIV (PLWH) compared with controls. We assessed the impact of different antiretroviral (ARV) regimens on plasma PCSK9 levels as well as plasma lipids, systemic inflammation and immunovirological parameters. METHODS: Eighty HIV-positive ARV therapy (ART)-naïve PLWH and 40 uninfected controls were retrospectively enrolled. At baseline and 3, 6 and 12 months after ART initiation, plasma PCSK9 levels, lipids, high-sensitivity C-reactive protein (hs-CRP), HIV-1 RNA levels and CD4 T-cell count were measured. RESULTS: Baseline PCSK9 levels were significantly more elevated in PLWH and were associated with HIV-1 RNA levels (P < 0.001), CD4 T-cell counts (P < 0.001), triglycerides (P < 0.001) and high-density lipoprotein (HDL) cholesterol (P < 0.001), but not with total cholesterol, low-density lipoprotein (LDL) cholesterol and lipoprotein(a) levels. The prescription of ART was paralleled by significant decreases in plasma PCSK9 and hs-CRP levels, and increases in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and lipoprotein(a), independent of regimen. CONCLUSIONS: PCSK9 levels, along with systemic inflammation, were progressively reduced following the initiation of an effective ART. However, at the end of the study PCSK9 levels remained higher than in controls and did not correlate with any of the lipid variables.

Radiofrequency resection of bronchial tumours in combination with cryotherapy: evaluation of a new technique.

BACKGROUND: A number of treatments, including Nd-YAG laser therapy, brachytherapy, cryotherapy, electrocautery, and photodynamic therapy, can re-open the obstructed bronchial lumen in patients with inoperable obstructive bronchial tumours. None of these is considered to be a "gold standard". METHODS: The results of a retrospective study of 98 patients treated by radiofrequency tissue ablation and subsequent cryotherapy between January 1994 and June 1995 are reported. The patients were divided in two groups according to whether they were treated either after (group 1, n = 50) or before (group 2, n = 48) radiotherapy and/or chemotherapy. Bronchoscopic follow up was performed. The intervention was considered successful if the lumen was opened by > 80% and partially successful if it was opened by > 50%. RESULTS: In group 1 treatment was successful in 60%, partially successful in 32%, and unsuccessful in 8%. The median survival time was five months from the time of bronchoscopic surgery. In group 2 treatment was successful in 66%, partially successful in 21.5%, and unsuccessful in 12.5%, with a median survival time of 14 months from the time of bronchoscopic treatment. Forty patients (24 in group 1 and 16 in group 2) received a Dumon stent. CONCLUSIONS: Radiofrequency bronchoscopic surgery with cryotherapy appears to be a useful technique in the treatment of tracheobronchial obstruction.

Therapeutic delivery of calcitonin to inhibit external inflammatory root resorption. I. Diffusion kinetics of calcitonin through the dental root.

Insertion of calcitonin into root canals of monkey teeth has been shown to inhibit external inflammatory root resorption and suppress inflammation. Regulation of this therapeutic event depends upon the rate of arrival (diffusion) of the hormone at sites of resorptive activity. In the present study, the diffusion characteristics of calcitonin through the dental root in an extracted human-tooth model are described, and the role of cementum in the diffusion process is also addressed. Root-canals were endodontically prepared to form a reservoir for [125I]-calcitonin, and macerated to remove organic material from dentinal tubules. In teeth with intact cementum, an initial period of delay (4-5 h) prior to the detection of calcitonin at the external tooth-root surface was followed by a rapid release of the calcitonin during the first 10.5 h (rate peaks at 6 h). Slower, sustained releases of calcitonin through intact cementum were measured for the following 9 days. Removal of cementum, to expose "smear-free" dentine, resulted in an earlier efflux of calcitonin (2 h) at external tooth surfaces and increased amounts of calcitonin release over 9 days. Biphasic delivery of calcitonin by such internal diffusion mechanisms suggests that loss of cementum will enhance therapeutic availability, while prolonged delivery to intact external dental-root surfaces following early intra-canal placement may also be useful for the therapeutic prevention of external inflammatory root resorption.

Therapeutic delivery of calcitonin to inhibit external inflammatory root resorption. II. Influence of calcitonin binding to root mineral.

Experimentally-induced external inflammatory tooth-root resorption can be inhibited by therapeutic doses of calcitonin. Such doses can be delivered by an intrinsically slow diffusion pathway, from a reservoir in endodontically-debrided root canals, via the dentinal tubules. While the kinetics of this journey have been followed in an earlier report, the binding characteristics of calcitonin to the tooth mineral, which will be responsible, in part, for these kinetics, have not been reported before. The current study examines the binding potential of calcitonin to root mineral and addresses the potential role of non-specific binding proteins. A modified Scatchard plot indicated that a simple non-reactive type of ligand binding exists between calcitonin and root mineral, represented by a small number of identical binding sites. This interaction is both strong and reversible. Furthermore, it appears to be time-dependent with more time being required for the residual ligands to interact with the diminishing numbers of free calcitonin-binding sites. While preloaded [125I]-calcitonin could be incompletely (75-91%) displaced from dental-root material by non-radioactive calcitonin, its release was slow over 23 h. Calcitonin was four times as effective as bovine-serum albumin in competing for common "calcitonin binding sites" on macerated dental-root material. Thus, even in the presence of extraneous protein, calcitonin will bind tightly but reversibly to tooth-root material, making it a good candidate for therapeutically protracted delivery to external root surfaces from root canals.

[A case of secondary misplacement of the selective bronchial tube in thoraco-pulmonary surgery]. / Su di un caso di malposizionamento secondario del tubo bronchiale selettivo in chirurgia toraco-polmonare.

The authors, after a short synthesis of the causes of secondary misplacement of the selective bronchial tube in thoracic surgery, describe a clinical case. A patient, after the induction of anaesthesia and selective intubation with Carlens tube, undergoes a surgical procedure of right upper lobectomy. During this procedure, a very serious O2 desaturation stands out and only at the end of the procedure, after X-ray examination, it is possible to understand. The cause of the O2 desaturation is a secondary movement of the bronchial tube. The authors come to the conclusion that to diagnose the secondary misplacement of the bronchial tube during the surgical procedure it should be useful perioperative fiberoptic bronchoscopy.

[Dieulafoy ulcer associated with acute drug-induced gastritis: a rare case]. / Ulcera di Dieulafoy associata a gastrite acuta da farmaci: un raro caso.

The lesion in Dieulafoy's disease consists of an unusually large and tortuous artery in the base of an ulcer. The disease is underdiagnosed rather than truly rare and often presents with a massive and potentially fatal, usually repeated, haematemesis. The authors describe a case of Dieulafoy's disease associated with acute drug-induced gastritis whose gravity required, in the case reported, a very serious emergency treatment.

[Pancreatic encephalopathy. Description of an unusual case]. / Encefalopatia pancreatica. Descrizione di un raro caso.

The authors describe a case of pancreatic encephalopathy. This uncommon condition, rarely described in the literature, occurs with neuropsychiatric signs 3-4 days after the onset of acute pancreatitis. Diagnosis is due to clinical and biochemical findings and to post mortem examinations revealing also amylase in CSF.

An SEM study of the effects of different irrigation sequences and ultrasonics.

The root canals of 30 extracted human teeth with single canals were prepared biomechanically with hand instruments using a flaring technique. Three different irrigation regimes were used, with and without ultrasonic activation of a root canal file. The six irrigation sequences used in this study were as follows: Savlon, Savlon with ultrasound, EDTAC/NaOCl/EDTAC, EDTAC/NaOCl/EDTAC with ultrasound, NaOCl/EDTAC/NaOCl, and NaOCl/EDTAC/NaOCl with ultrasound. Scanning electron microscopic (SEM) examination of the prepared root canal walls showed a complete smear layer when Savlon was used. Ultrasound reduced the amount of smear with Savlon, but did not do so significantly with the other irrigation regimes. The most effective irrigation regime for removing smear layer and other debris was EDTAC/NaOCl/EDTAC. In all groups there was a significant decrease in cleaning efficiency as the apical end of the canal was approached.

[Anesthesia for pleuroscopy. Importance of intubation with the Carlens tube for a selective diagnosis of emphysematous bullae in primary spontaneous pneumothorax]. / L'anestesia per le pleuroscopie. Importanza dell'intubazione con sonda di Carlens per una diagnosi selettiva delle bolle enfisematose nel pneumotorace sponataneo primitivo.

A brief account of the origin of spontaneous pneumothorax and the indications for pleuroscopy in thoracopulmonary surgery is followed by an explanation of the advantages of this method in the selective detection of emphysematous bullae, their number and size, and the state of the lung parenchyma. The evaluation of these parameters is essential to the planning of oriented surgery. A general anaesthesia technique employing a Carlens tube in selective intubation is also illustrated. By permitting separate ventilation of the lungs this method allows a selective diagnosis to be made of emphysematous bullae (including microbullae), and prevents all forms of acute respiratory distress.

[Problems of anesthesia and resuscitation in the extraction of tracheo-bronchial foreign bodies in children]. / Problemi di anestesia e rianimazione per l'estrazione dei corpi estranei tracheo-bronchiali in età pediatrica.

After briefly considering the high incidence of foreign bodies found in the bronchi of children, and some characteristics connected with their nature, the early and late complications that may occur as a results are illustrated. Resuscitation and anaesthesia techniques are then described, stress being laid on the importance of the ketamine-TCT injection and local anaesthetic association. The latter has proved most effective in personal cases as it resolves the laryngotracheo-bronchial spasm responsible for asphyctic crisis and prevents any dangerous deepening of narcosis during bronchoscopic manoeuvres for the extraction of the foreign body.

[Problems of alimentation in massive intestinal resections]. / Problemi di alimentazione nelle resezioni intestinali massive.

Before reviewing the consequences of extensive exeresis of the small intestine, the physiology of the entero-hepatic circulation of bile salts, the absorption of triglycerides and the varying sites of absorption of foodstuffs at intestinal level are discussed. It has been found that massive (i.e. at least 2/3) removal of the small intestine is incompatible with life owing to the onset of serious metabolic disturbances due to the increase in the speed of transit of foodstuffs from stomach to colon. Malabsorption of lipides causes steatorrhoea and is often associated with choleriform diarrhoea owing to the massive losses of water and electrolytes (Na, Cl, Ca, Mg). Some surgical techniques are illustrated and the local compensation mechanisms (anatomical adaptation of the intestinal mucosa, functional adaptation) designed to prolong transit time are described. Feeding must be parenteral for the first 2--3 months and oral during the alimentary adaptation phase.

[The pancreatico-respiratory syndrome. Problems of intensive therapy and illustration of 5 clinical cases]. / La sindrome pancreatico-respiratoria. Problemi di terapia intensiva ed illustrazione di 5 casi clinici.

A short account of the mechanisms responsible for pleuropulmonary affections in the course of pancreatitis is followed by the presentation of personal cases observed over the previous four years and reference is made to the relatively high frequency of pleuropneumopathy. Lastly, mention is made of the treatment of pancreatitis. Recent criteria lay down that this should be conservative and medico-intensive in the acute stage. Surgery should be left for cases of peritonitic abdomen (exploratory laparotomy) and chronic pancreatitis.