Biomedical subjects
Publications and source records attributed to M Pasqualini.
NAD analogs modified at the ribose adenylyl moiety, named N-2'-MeAD and Na-2'-MeAD, were synthesized as ligands of pyridine nucleotide (NMN/NaMN) adenylyltransferase (NMNAT). Both dinucleotides resulted selective inhibitors against human NMNAT-3 isoenzyme.
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AIM: Patients who have a fracture of the hip, usually are considered at a risk of fracturing the contralateral hip. This risk, not sufficiently addressed to in literature, becomes increasingly important in the light of increasing longevity of the population. In this retrospective study, we present some of our epidemiological and post-operative data on limb function in a group of our patients. METHODS: We examined the database of our patients over 50 years of age, admitted at our hospital in the last 9 years for fracture of the proximal third part of the femur bone. These patients did not have a history of neoplasms or severe multitrauma. The variables considered were: unilateral or bilateral fracture, age, sex, the level of physical activity before trauma (MET scale), the severity of the trauma, fracture site (cervical or trochanteric), the type of surgery and the level of functional autonomy (FIM scale) at time of discharge. RESULTS: A total of 2 771 patients were identified. Bilateral fractures were present in 7.58% (n=210). Among bilateral fractures, the female to male ratio was 1 to 7.08 and the site of the contralateral fracture remained similar to the original site. In more than 48%, the second fracture occurred in patients over 85 years of age. The most common causes of both bilateral and mono lateral fractures, were either a moderate trauma or a fall in domestic premises. Cervical fractures were treated with cemented endoprothesis of the hip while for trochanteric fractures osteosyntesis with endomedullar nails were used. After the second fracture, the level of functional autonomy was found to be significantly reduced (FIM score mean difference +/-SD of 16.77+/-10.72) and the number of non deambulatory patients were tripled. Furthermore, these patients were found to be more sedentary, before the second fracture, as compared to the ones with only one fracture. CONCLUSIONS: Bilateral fractures of the femur neck bone is still considered to be a rare event. The second fracture seems to be more frequent in sedentary women over 85 years of age. More often, the second fracture is caused by a simple domestic accident. Due the increasing age of the population, in future this event might become statistically relevant. The drastic decrease in post-operative functional autonomy in such patients might become a serious socio-economic and welfare policy problem. It is advisable to render domestic premises less hazardous and intense and prolonged postoperative physical rehabilitation treatment must be continued after discharge.
BACKGROUND: Pringle's manoeuvre controls excessive bleeding, but results in ischaemia-reperfusion injury during liver surgery. Activation of the heat-shock protein system of cell defense has been demonstrated after ischaemia-reperfusion injury in animal tissues. The aim of the present study was to determine whether the ischaemia-reperfusion accompanying hepatic surgery induces heat-shock protein 70 (HSP70) in human liver and whether the induction of HSP70 is related to the recovery of liver function. METHODS: Heat-shock protein 70 and gamma-actin mRNAs were assayed in the liver biopsies of 10 subjects undergoing partial hepatectomy for localized lesions. Measurements were performed before the Pringle's manoeuvre and at the end of the surgery. Transaminases and fibrinogen were measured before and at 12, 24 and 36 h following hepatectomy. RESULTS: After an average 40 +/- 8-min period of warm ischaemia, a significant increase of HSP70 mRNA (187 +/- 67%, 2P < 0.05) was observed. The acute increase of HSP70 mRNA correlates with the decrease of transaminases (AST: rs -0.964, ALT: rs -0.891, P < 0.002) and the increase of fibrinogen (rs -0.7, P < 0.02) observed between 12 and 24 h following surgery. CONCLUSIONS: Heat-shock protein 70 is induced by ischaemia-reperfusion injury in human liver. Its induction seems to have beneficial effects, including a prompt reduction of transaminases and a rapid recovery of fibrinogen synthesis.
The Authors present a case of an insidious onset of Crohn Disease (CD) in an elderly patient. Diagnosis complicated by extraintestinal manifestation properly of old age could be delayed and often made after surgery on the histological specimen as in our case. CD is uncommon as primary manifestation in old age, often unsuspected, incorrectly diagnosed and in many case the clinical features may lead to late diagnosis. Differential diagnosis of CD in elder people with fever, diarrhoea and abdominal pain is difficult and other symptoms affecting intestinal tract can closely mimic CD symptoms, although the pattern of clinical presentation in older patient resemble those in younger.
Monocyte-derived macrophages (M/M) are considered important in vivo reservoirs for different kinds of viruses, including HIV. Hence, therapeutic strategies are urgently needed to protect these cells from virus infection or to control viral replication. In this paper, we report the synthesis, target delivery and in vitro efficacy of a new heterodinucleotide (AZTpPMPA), able to inhibit HIV-1 production in human macrophages. AZTpPMPA consists of two established anti-HIV drugs [zidovudine (AZT) and tenofovir (PMPA)] chemically coupled together by a phosphate bridge. This drug is not able to prevent p24 production when administered for 18 h to M/M experimentally infected with HIV-1 Bal (inhibition 27%), but can almost completely suppress virus production when given encapsulated into autologous erythrocytes (inhibition of p24 production 97%). AZTpPMPA is slowly converted to PMPA, AZT monophosphate and AZT (36 h half-life at 37 degrees C) by cell-resident enzymes. Thus AZTpPMPA should be considered a new prodrug of AZT and PMPA that is able to provide stechiometric amounts of both nucleoside analogues to macrophage cells and to overcome the low phosphorylating activity of M/M for AZT and the modest permeability of PMPA.
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OBJECTIVES: We sought to obtain a noninvasive estimation of mean pulmonary wedge pressure (MPWP) in patients with chronic atrial fibrillation (AF). BACKGROUND: It has previously been demonstrated that MPWP can be reliably estimated from Doppler indexes of mitral and pulmonary venous flow (PVF) in patients with sinus rhythm. Doppler estimation of MPWP has not been validated in patients with AF. METHODS: MPWP was correlated with variables of mitral and pulmonary venous flow velocity as assessed by Doppler transthoracic echocardiography in 35 consecutive patients. The derived algorithm was prospectively tested in 23 additional patients. RESULTS: In all patients the mitral flow pattern showed only a diastolic forward component. A significant but relatively weak correlation (r = -0.50) was observed between MPWP and mitral deceleration time. In 12 (34%) of 35 patients, the pulmonary vein flow tracing demonstrated only a diastolic forward component; a diastolic and late systolic forward flow was noted in the remaining 23 patients (66%). A strong negative correlation was observed between MPWP and the normalized duration of the diastolic flow (r = -0.80) and its initial deceleration slope time (r = -0.91). Deceleration time > 220 ms predicted MPWP < or = 12 mm Hg with 100% sensitivity and 100% specificity. When estimating MPWP by using the equation MPWP = -94.261 PVF deceleration time -9.831 Interval QRS to onset of diastolic PVF -16.337 Duration of PVF + 44.261, the measured and predicted MPWP closely agreed with a mean difference of -0.85 mm Hg. The 95% confidence limits were 4.8 and -6.1 mm Hg. CONCLUSIONS: In patients with chronic AF, MPWP can be estimated from transthoracic Doppler study of PVF velocity signals.
Barrett's esophagus is defined as a disorder in which the normal stratified squamous mucosa of the esophagus is replaced by columnar epithelium. Patients with Barrett's esophagus are at risk to develop an adenocarcinoma of the esophagus. Pathologic gastroesophageal reflux is correlated to the disease and therapeutical options must aim to stop this noxa in order to prevent columnar metaplasia, and subsequent dysplasia and/or neoplasia. The Authors report the case of a patient in whom the complete regression of the metaplasia was observed after medical therapy.
Hypertrophic cardiomyopathy (HCM) is a typical primary cardiac disease characterized by diastolic abnormal function due to both prolonged relaxation and decreased compliance (Sanderson et al., 1977; Spirito & Maron, 1990). Since the contribution of the atrial systole to ventricular filling is usually increased, the appearance of a fourth heart sound (S4) is a common finding in HCM. This sound is related to the ventricular compliance and to the atrial contractility. It is generated during the rapid setting into vibration of the left ventricular walls that results from the rapid rush of the blood due to the atrial contraction (Nishimura et al., 1989; Tavel, 1978). The aim of this study is to look for relationships between the frequency peak of S4 and various mono- and two-dimensional echocardiographic parameters in order to identify those cardiac structures involved in its genesis and obtaining an estimation of the stiffness of the acoustic vibrating system with a simply vibratory model (Baracca et al., 1991).
Because analysis of pulmonary venous flow (PVF) will be extensively used in comprehensive Doppler assessment of left ventricular diastolic function, this study was designed to (1) evaluate the feasibility of PVF measurement in 116 consecutive patients with various cardiac abnormalities by using precordial pulsed Doppler echocardiography; (2) Estimate mean pulmonary capillary pressure (MPCP) and left ventricular end-diastolic pressure (LVEDP) from Doppler variables of PVF and mitral inflow; and (3) evaluate the influence of clinical and hemodynamic variables on PVF Doppler patterns. We adequately recorded anterograde PVF in 96 (82.7%) patients and retrograde PVF in 45 (38.7%) patients. The strongest correlation between MPCP and Doppler variables of PVF was found with systolic fraction (the systolic velocity time integral expressed as a fraction of total anterograde PVF) (r = -0.88; p < 0.001). Age influenced this relation, with progressive increase of the systolic fraction in older patients. A good correlation (r = 0.72; p < 0.001) was found between LVEDP and the difference in duration of the reversal PVF and the mitral a wave. In conclusion, (1) PVF can be recorded adequately in most patients with precordial Doppler echocardiography; (2) left ventricular diastolic pressures can be estimated reliably by precordial Doppler echocardiography; and (3) the clinical meaning of Doppler-derived indexes of left ventricular diastolic performance is age-related.
This study was aimed at investigating the role of US in the newborn with a clinical suspicion of hemoperitoneum. Hemoperitoneum is a dramatic clinical event which may be caused by some obstetrical and fetal factors--breech or complicated delivery, hepatomegaly, macrosomy, anoxic liver congestion being the most frequent causes. Direct or indirect trauma of an abdominal organ during delivery represents the major pathogenetic factor. Clinical symptoms are correlated with the appearance of shock whose intensity is proportional to trauma severity: symptoms may appear even 48 hours after delivery. The authors report their experience with 4 consecutive cases of neonatal hemoperitoneum which underwent US of the abdomen 24 to 72 hours after birth. In the first 3 newborns, US was performed on the basis of a clinical picture of bleeding shock, while in the extant newborn US was performed after a sudden increase in blood transaminase level associated with an obstetrical paralysis of the left arm. The US examinations were performed using a 7.5-MHz sectorial probe unit (Siemens). In all patients, US demonstrated the presence of a liquid effusion in the abdomen which could be referred to hemoperitoneum. In two patients, it was associated with a traumatic focal alteration of the liver parenchyma, in the third with a diffuse subcapsular liver hematoma and, finally in the fourth patient with a disconnected splenic vascular pedicle which was at surgery demonstrated. In conclusion, US is indicated as the most reliable and valuable diagnostic technique in the study of neonatal hemoperitoneum. The authors believe abdominal US to be essential in all the neonatal cases where hemoperitoneum is suspected and in selected cases presenting specific risk factors, to allow a rapid diagnosis and better treatment planning.
The radial forearm flaps is ideal for intra-oral reconstruction. In that it offers thin, pliable, hairless skin to replace oral mucosa removed during wide resection in surgical treatment of cancer. The vascularity of the area allows considerable variation in design and size of the flap and offers the possibility of covering structures on different levels and, when bone is included, of carrying out immediate reconstruction of the mandible. The Authors used this flap in 24 patients for intra-oral reconstruction. The ages of the subjects ranged from 30 to 70 years. The arteries and the veins of the flap used for microsurgical anastomosis were radial arteries and superficial veins of the elbow. Neck vessels were superior arteries of the thyroid and jugularis externa vein. Operating time was slightly prolonged when compared to repair employing a myocutaneous island flap. This reconstruction method was completely successful in all 24 patients; in one patient a DIC partially compromised the vascularity of the flap on day 8. Morbidity was observed, resouled, however, with minor surgical procedures. Our results support the choice of this method for intraoral reconstruction.
Liver and spleen are the organs most frequently involved in the blunt abdominal trauma. Prognosis is severe in those cases classified as IV or V according to the More score. The imaging techniques, particularly CT scan, offer today a possibility in the nonoperative management of a selected group of haemodynamically stable patients, therefore reducing the need of surgery. The authors' experience in 125 patients observed from 1983 to 1991 is reported.
The paper reports a case of cholestatic icterus caused by a large calculus in the infundibulum of the gallbladder with a cholecysto-choledochal fistula and hepato-choledochal block (Mirizzi's type II syndrome). The diagnostic iter complicated the evolution, raising questions regarding the therapeutic strategy.
The authors describe their experience with allograft in 23 cases of revised hip replacements, paying particular attention to the clinical results and the X-ray appearance. They conclude by emphasizing the particularity of the surgical technique and the various factors involved in the use of bone grafts in such elective surgery as hip replacement.
Interlocked nailing is a routine method that yields excellent results even in complex fractures of the lower limb. A series of 25 femoral and 29 tibial fractures is reviewed, and both advantages and technical difficulties are discussed. The authors point out that, in very special cases, interlocking nails may be used together with other methods of internal and external fixation.