Heart rate variability: a diagnostic and prognostic tool in anesthesia and intensive care.

The autonomic nervous system (ANS) plays an important role in the human response to various internal and external stimuli, which can modify homeostasis, and exerts a tight control on essential functions such as circulation, respiration, thermoregulation and hormonal secretion. ANS dysfunction may complicate the perioperative course in the surgical patient undergoing anesthesia, increasing morbidity and mortality, and, therefore, it should be considered as an additional risk factor during pre-operative evaluation. Furthermore, ANS dysfunction may complicate the clinical course of critically ill patients admitted to intensive care units, in the case of trauma, sepsis, neurologic disorders and cardiovascular diseases, and its occurrence adversely affects the outcome. In the care of these patients, the assessment of autonomic function may provide useful information concerning pathophysiology, risk stratification, early prognosis prediction and treatment strategies. Given the role of ANS in the maintenance of systemic homeostasis, anesthesiologists and intensivists should recognize as critical the evaluation of ANS function. Measurement of heart rate variability (HRV) is an easily accessible window into autonomic activity. It is a low-cost, non-invasive and simple to perform method reflecting the balance of the ANS regulation of the heart rate and offers the opportunity to detect the presence of autonomic neuropathy complicating several illnesses. The present review provides anesthesiologists and intensivists with a comprehensive summary of the possible clinical implications of HRV measurements, suggesting that autonomic dysfunction testing could potentially represent a diagnostic and prognostic tool in the care of patients both in the perioperative setting as well as in the critical care arena.

Risk factors, atrial fibrillation and thromboembolic events.

AIM: The aim of this study was to evaluate the relation between risk factors for atrial fibrillation (AF) and thromboembolic complications. METHODS: We studied 480 patients (mean age: 71.2+/-11.6 years): 240 with paroxysmal AF, 240 with permanent AF. The association between AF and the presence of risk factors, cardiac and systemic disease was observed and the correlation with the occurrence of complications analyzed. RESULTS: Patients with AF had a high prevalence of the following conditions: hypertension, hypertensive heart disease (HHD), coronary artery disease, hyperthyroidism. Thromboembolism was observed in 26.6% of the patients. A correlation between the occurrence of a thromboembolic complication and the presence of one of the following risk factors for thromboembolism was observed: older age, diabetes mellitus, HHD and hyperfibrinogenemia. No correlation was detected between: female sex, arterial hypertension, hypercholesterolemia, smoking, and obesity. Exitus was observed in 7 patients with permanent AF. CONCLUSION: Older age, diabetes mellitus, HHD and hyperfibrinogenemia were strongly associated with the occurrence of thromboembolic complications. Patients with effectively pharmacologically controlled hypertension had not more frequently thromboembolic complications. A strict blood pressure control may prevent thromboembolic complications of AF.

Charcot-Marie-Tooth type X: unusual phenotype of a novel CX32 mutation.

BACKGROUND: X-linked Charcot-Marie-Tooth disease (CMTX), caused by mutations in the gene encoding connexin32, is the second most common form of inherited demyelinating neuropathy, next to CMT 1A, and accounts for 10-20% of all hereditary demyelinating neuropathies. AIMS OF THE STUDY: To describe clinical and electrophysiological data of an Italian family carrying a novel mutation in the Cx32 gene. PATIENTS AND METHODS: Clinical, electrophysiological, and genetic findings of three patients carrying the Ser128Leu mutation in the intracellular domain of the Cx32 gene were reported. Brain MRI studies were also performed. RESULTS: In our family the disease was characterized by a moderate-to-severe polyneuropathy affecting similarly males as well females. In the proband the phenotype was quite unusual in terms of late-onset, rapidity of evolution and severity. Abnormal brain MRI in association with CNS symptoms were also observed. Both sons had also clinical evidence of CNS involvement. CONCLUSIONS: The Ser128Leu mutation in the Cx-32 gene is a novel substitution, which has not been reported so far. This novel mutation could be added to the group of Cx-32 mutations with CNS phenotypes. The identification of new CMTX causing mutations is a crucial step for carrier detection and pre-symptomatic diagnosis.

Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers.

BACKGROUND: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown an interesting activity as single agents in this group of patients. PATIENTS AND METHODS: We carried out a multicenter phase II study to evaluate the efficacy and safety of combined oxaliplatin and gemcitabine in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included oxaliplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8, every 21 days. RESULTS: All the 24 patients were evaluable for response and toxicity. According to RECIST criteria we observed one complete response and 11 partial responses for an overall response rate of 50%. Overall survival for all the patients on study was 12 months (range 2-30). According to WHO criteria, three patients (12.5%) suffered grade 3 neutropenia and three patients (12.5%) grade 3 thrombocytopenia. Only two patients (8%) suffered grade 3 neuropathy. CONCLUSIONS: Oxaliplatin and gemcitabine chemotherapy seems to be effective with a favorable safety profile in first-line chemotherapy of advanced biliary tract cancers.

Upper body venous thrombosis associated with ovarian stimulation: case report and review of the literature.

Thromboembolic events are a serious complication of assisted conception treatment. Thrombosis may be either arterial or venous but the latter is far more common. This phenomenon is more frequent in the lower limb, but several cases of upper extremity thrombosis have been described in the literature. Although the aetiology of these thromboembolic disorders is not fully understood, the mechanism is thought to be due to a hypercoagulable state associated with haemostasis and thrombophilia. Predisposing factors seem to be hyperoestrogenism, ovarian hyperstimulation syndrome, a hereditary hypercoagulable state and multifoetal pregnancy. We report a case of superior sagittal sinus thrombosis that developed in a patient following successful assisted conception in the absence of evident risk factors. In the current literature, the site of thrombosis, possible predisposing factors, oestrogen levels, number of foetuses, maternal and foetal outcomes, and management of thrombosis were analysed.

Is there a relationship between somatic and autonomic neuropathies in chronic alcoholics?

We investigated the relationship between somatic and autonomic neuropathy in 40 chronic alcoholics. Electromyographic and neurographic studies of upper and lower limbs and a battery of six cardiovascular reflex tests were carried out. A score for somatic or autonomic neuropathy was calculated. All parameters were investigated for possible relationship with total life dose (TLD) of alcohol intake. Somatic neuropathy was detected in 25 patients (62.5%) and autonomic neuropathy in 13 patients (32.5%). Nineteen patients (47.5%) presented only a somatic neuropathy, six patients (15%) had only an autonomic neuropathy, and seven (17.5%) had a combined somatic and autonomic neuropathy. TLD was significantly higher in the group of patients with combined neuropathy than in the group with isolated somatic neuropathy. There was no significant correlation between laboratory parameters of somatic and autonomic neuropathy. Our findings do not support the existence of a parallel involvement of peripheral somatic and autonomic cardiovascular nerve fibers in chronic alcoholism.

Autonomic dysfunction in uremia.

Autonomic nervous system dysfunction is a common feature in uremia and may have a number of clinical sequelae. Simple cardiovascular reflex screening can be performed in patients during conservative treatment, on periodic dialysis therapy, or after kidney transplantation to diagnose and follow up autonomic function impairment. Other approaches, such as heart-rate variability studies in the frequency domain by power spectral analysis, can provide a more accurate investigation of the disease.

Peripheral neuropathy as the presenting feature of multiple system atrophy.

The authors report a case of multiple system atrophy (MSA) with an onset as a peripheral nerve involvement. Their patient, a 55-year-old man, had a 3-year history of distal weakness and atrophy in upper limbs with dysesthesia in the feet. Other identifiable causes of peripheral neuropathy were ruled out. The authors postulate that peripheral nervous system impairment can anticipate the typical appearance of MSA, and they suggest that, in peripheral neuropathies with autonomic system dysfunction, after excluding main causes of autonomic neuropathy, MSA may need to be suspected.

Cardiovascular autonomic control in Becker muscular dystrophy.

Although autonomic symptoms are not prominent in dystrophinopathies, a reduced vagal activity and an enhanced sympathetic tone have been found in Duchenne muscular dystrophy. Twenty patients with Becker muscular dystrophy (BMD) were investigated by a battery of six cardiovascular autonomic tests (beat-to-beat variability during quiet breathing and deep breathing, heart rate responses to Valsalva maneuver and standing, blood pressure responses to standing and sustained handgrip) and power spectral analysis (PSA) of heart rate variability. Although 11 patients revealed abnormal findings at some cardiovascular tests, none of them had a definite autonomic damage, as indicated by two or more abnormal tests. The mean results of the single tests did not differ from normal controls, except for the beat-to-beat variability during quiet breathing, which was significantly higher in BMD (p<0.05). Such finding was confirmed by a significantly higher total variance (p<0.05), indicating an increased parasympathetic activity. Spectral components were not significantly different from normal controls. PSA values were not influenced by age, functional ability score or presence of heart abnormalities. Our data suggest that autonomic involvement does not represent a major finding in BMD.

Biliary tract cancer: our experience with gemcitabine treatment.

Biliary tract cancers are uncommon tumors, with a poor prognosis because most patients present an invasive cancer at diagnosis that makes them inoperable. Chemotherapy is a palliative treatment, but single drugs or combination schedules have demonstrated a response rate of 14-18%, with a duration of response of 8.5 months. We report a single center experience with gemcitabine in the treatment of patients with advanced biliary tract cancers. We report on four cases of chemonaive patients with advanced biliary tract cancers treated with gemcitabine 1 g/m q days 1, 8 and 15. After three cycles of treatment we observed one partial response and three stable disease (according to WHO criteria), with an increase in performance status and a complete relief of pain in all patients. The median time to progression observed was 10.7 months. Although this experience is limited to a small number of patients, it shows that gemcitabine appears to be worthy of clinical research in this neoplastic pathology and makes the drug a particularly interesting agent for investigation in patients with biliary tract malignancies.

Sickle cell anemia and beta-gene cluster haplotypes in Cuba.

We have studied 91 patients with SS genotype, 44 children and 47 adults. Excluding the Cameroon and atypical haplotypes, the distribution in the children's sample exhibited 43% Benin, 38% Bantu, and 3% Senegal. In adults, the sample exhibited 46% Benin, 30% Bantu, and 9% Senegal (chi 2: 13.511, 2 df, P = 0.001). When the whole sample of 198 chromosomes (SS, SC, and S/beta thal) is considered, we find that the beta s chromosome is linked 51% to the Benin haplotype, 41% with the Bantu, and 8% with the Senegal. After adjusting for the different frequencies of beta s in Africa, these numbers would predict the port of origin to be 16% from Atlantic West Africa, 37.3% from Central West Africa, and 46% from Bantu-speaking Africa. This is in direct contradiction with the historical record that establishes a higher percentage from Bantu-speaking Africa (55%) and a much lower percentage from Senegal (3.4%). The overall conclusions from these findings is that there is a loss of Bantu haplotypes in sickle cell syndromes in Cuba, particularly among adults, and that there is an excess of Senegal haplotype, also among adults. These differences might reflect the differential survival and severity of the sickle cell disease linked to these haplotypes.