Early cardiac abnormalities and increased C-reactive protein levels in a cohort of children with sleep disordered breathing.

BACKGROUND: This study aims to evaluate left ventricular (LV) structure and function and inflammation in a paediatric population with sleep disordered breathing (SDB) and in control subjects. METHODS: Forty-nine children with SDB and 21 healthy, age-matched subjects were enrolled. The diagnosis of obstructive sleep apnoea syndrome (OSAS) was confirmed by the laboratory polysomnography, showing an obstructive apnoea/hypopnoea index of more than one per hour, according to the criteria of the American Academy of Sleep Medicine and modified for paediatric population. Fasting blood samples for the biochemical evaluation (including high-sensitivity C-reactive protein (hsCRP) were drawn in the morning, after the polysomnographic examination in all patients with SDB and in the control group. All children underwent a two-dimensional colour Doppler cardiac examination with LV mass assessment and systolic and diastolic function evaluation. RESULTS: Higher hsCRP levels were observed in subjects with OSAS than in children with primary snoring and in controls (0.8 ± 0.7 vs 0.3 ± 0.1 ng/dl, p = 0.001, and 0.4 ± 0.2 ng/dl, p = 0.01, respectively). The LV diastolic dysfunction was significantly more frequent in patients with severe OSAS and higher hsCRP levels than in control group. CONCLUSIONS: This study shows that OSAS in children is associated with higher LV mass, early LV diastolic dysfunction and a pro-inflammatory state (high CRP levels). These findings might help to explain the higher incidence of cardiovascular morbidity in patients with OSAS.

Intrabiliary rupture of a hydatid liver cyst: a case report.

Intrabiliary rupture of a hydatid liver cyst is a rare occurrence which may result in the development of obstructive jaundice and cholangitis. In this report we discuss the diagnostic and therapeutic management of a patient in whom the parasitic nature of cholangitis was underestimated due to the small size and site of the cyst, and to the misleading concomitant presence of cholelithiasis.

Y chromosomal haplogroup J as a signature of the post-neolithic colonization of Europe.

In order to attain a finer reconstruction of the peopling of southern and central-eastern Europe from the Levant, we determined the frequencies of eight lineages internal to the Y chromosomal haplogroup J, defined by biallelic markers, in 22 population samples obtained with a fine-grained sampling scheme. Our results partially resolve a major multifurcation of lineages within the haplogroup. Analyses of molecular variance show that the area covered by haplogroup J dispersal is characterized by a significant degree of molecular radiation for unique event polymorphisms within the haplogroup, with a higher incidence of the most derived sub-haplogroups on the northern Mediterranean coast, from Turkey westward; here, J diversity is not simply a subset of that present in the area in which this haplogroup first originated. Dating estimates, based on simple tandem repeat loci (STR) diversity within each lineage, confirmed the presence of a major population structuring at the time of spread of haplogroup J in Europe and a punctuation in the peopling of this continent in the post-Neolithic, compatible with the expansion of the Greek world. We also present here, for the first time, a novel method for comparative dating of lineages, free of assumptions of STR mutation rates.

Clinal patterns of human Y chromosomal diversity in continental Italy and Greece are dominated by drift and founder effects.

We explored the spatial distribution of human Y chromosomal diversity on a microgeographic scale, by typing 30 population samples from closely spaced locations in Italy and Greece for 9 haplogroups and their internal microsatellite variation. We confirm a significant difference in the composition of the Y chromosomal gene pools of the two countries. However, within each country, heterogeneity is not organized along the lines of clinal variation deduced from studies on larger spatial scales. Microsatellite data indicate that local increases of haplogroup frequencies can be often explained by a limited number of founders. We conclude that local founder or drift effects are the main determinants in shaping the microgeographic Y chromosomal diversity.

A multistep process for the dispersal of a Y chromosomal lineage in the Mediterranean area.

In this work we focus on a microsatellite-defined Y-chromosomal lineage (network 1.2) identified by us and reported in previous studies, whose geographic distribution and antiquity appear to be compatible with the Neolithic spread of farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it with respect to other lineages associated with the same movements by other authors, examine its diversity by means of tri- and tetranucleotide loci and discuss the implications in reconstructing the spread of this group of chromosomes in the Mediterranean area. Our results define a tripartite phylogeny within HG 9 (Rosser et al. 2000), with the deepest branching defined by alleles T (Haplogroup Eu10) or G (Haplogroup Eu9) at M172 (Semino et al. 2000), and a subsequent branching within Eu9 defined by network 1.2. Population distributions of HG 9 and network 1.2 show that their occurrence in the surveyed area is not due to the spread of people from a single parental population but, rather, to a process punctuated by at least two phases. Our data identify the wide area of the Balkans, Aegean and Anatolia as the possible homeland harbouring the largest variation within network 1.2. The use of recently proposed tests based on the stepwise mutation model suggests that its spread was associated to a population expansion, with a high rate of male gene flow in the Turkish-Greek area.

Distribution of variable vs fixed costs of hospital care.

CONTEXT: Most strategies proposed to control the rising cost of health care are aimed at reducing medical resource consumption rates. These approaches may be limited in effectiveness because of the relatively low variable cost of medical care. Variable costs (for medication and supplies) are saved if a facility does not provide a service while fixed costs (for salaried labor, buildings, and equipment) are not saved over the short term when a health care facility reduces service. OBJECTIVE: To determine the relative variable and fixed costs of inpatient and outpatient care for a large urban public teaching hospital. DESIGN: Cost analysis. SETTING: A large urban public teaching hospital. MAIN OUTCOME MEASURES: All expenditures for the institution during 1993 and for each service were categorized as either variable or fixed. Fixed costs included capital expenditures, employee salaries and benefits, building maintenance, and utilities. Variable costs included health care worker supplies, patient care supplies, diagnostic and therapeutic supplies, and medications. RESULTS: In 1993, the hospital had nearly 114000 emergency department visits, 40000 hospital admissions, 240000 inpatient days, and more than 500000 outpatient clinic visits. The total budget for 1993 was $429.2 million, of which $360.3 million (84%) was fixed and $68.8 million (16%) was variable. Overall, 31.5% of total costs were for support expenses such as utilities, employee benefits, and housekeeping salaries, and 52.4% included direct costs of salary for service center personnel who provide services to individual patients. CONCLUSIONS: The majority of cost in providing hospital service is related to buildings, equipment, salaried labor, and overhead, which are fixed over the short term. The high fixed costs emphasize the importance of adjusting fixed costs to patient consumption to maintain efficiency.

HLA antigens and pANCA define ulcerative colitis as a genetically heterogeneous disorder.

BACKGROUND: Several genetic and subclinical markers have been associated with ulcerative colitis. AIM: To determine whether a significant association with HLA class I and II antigens was present in Italian ulcerative colitis patients considered as a whole population or stratified according to their anti-neutrophil cytoplasmatic antibodies. METHODS: HLA class I and II antigens were studied by serological typing techniques and related to the presence of anti-neutrophil cytoplasmatic antibodies detected by means of indirect immunofluorescence. RESULTS: Patients with ulcerative colitis (n = 45) had a significantly increased frequency of DQ6 (p = 0.04) and DQ7 (p = 0.003) and a decreased frequency of DQ5 (p = 0.03) and DQ8 (p = 0.02) when compared with ethnically matched healthy controls (n = 252 for HLA class I and 173 for HLA class II). No significant difference in HLA I- and DR-antigens was observed. Anti-neutrophil cytoplasmatic antibodies were found in 27/45 (60%) ulcerative colitis patients and in 0/252 controls (p < 0.001). After stratifying ulcerative colitis patients according to their anti-neutrophil cytoplasmatic antibodies status, anti-neutrophil cytoplasmatic antibodies +ve patients had an increased frequency of A19 (p = 0.007), DR2 (p = 0.03), and DR15 (p = 0.006), and a decreased frequency of A1 (p = 0.004) compared with anti-neutrophil cytoplasmatic antibodies -ve ones. CONCLUSIONS: We suggest that specific HLA-class II loci play an important role in the susceptibility to ulcerative colitis in Italy. A subset of ulcerative colitis patients is characterised by the presence of a specific subclinical marker (anti-neutrophil cytoplasmatic antibodies) which seems to be genetically determined as shown by the increased frequencies of HLA-A19 and DR2 observed in anti-neutrophil cytoplasmatic antibodies +ve ulcerative colitis.

Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain: a randomized controlled trial.

CONTEXT: More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units. OBJECTIVE: To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain. DESIGN: Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques. SETTING: A large urban public teaching hospital serving a predominantly African American and Hispanic population. PATIENTS: A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm. MAIN OUTCOME MEASURES: Primary outcomes measured for each subject were LOS and total cost of treatment. RESULTS: The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01). CONCLUSIONS: In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACI.

Pre-Cushing's syndrome not recognized by conventional dexamethasone suppression-tests in an adrenal "incidentaloma" patient.

Pre-Cushing's syndrome has been recently diagnosed in 6-12% of patients affected with incidentally discovered adrenal masses. Some of these patients have been described to show transient hypoadrenalism after surgery, similarly to those affected with overt Cushing's syndrome. We studied a 70-year-old male patient with a large left adrenal mass, incidentally discovered, who displayed 24-h urinary free cortisol levels at the upper limit of the normal range, normal dexamethasone overnight and low-dose suppression tests and not suppressed ACTH levels, increased 17-hydroxyprogesterone response to ACTH stimulation and low upright plasma renin activity with normal serum aldosterone levels; furthermore, DHEAS level was low and 75 Selenium-cholesterol scintigraphy showed unilateral uptake concordant with the side of the mass. Soon after left adrenalectomy, he complained of acute hypoadrenalism requiring cortisol replacement therapy: ten months after surgery he is still hypoadrenal. Moreover, stimulated 17-hydroxyprogesterone and plasma renin activity in clino- and orthostatic posture have become normal. We propose that conventional dexamethasone suppression-tests may be not enough sensitive in this kind of patients and that in selected cases the absence of controlateral uptake at scintigraphy may be more reliable in predicting post-surgical hypoadrenalism.

Intensification of 111In-DTPA-octreotide scintigraphy by means of pretreatment with cold octreotide in small cell lung cancer.

Small cell lung cancer (SCLC) expresses somatostatin receptors that can be traced with 111In-DTPA-octreotide scintigraphy. Although this technique is currently employed for staging and follow-up of neuroendocrine tumors of the gastrointestinal tract, its role in the clinical work-up of SCLC is at present under discussion. A better imaging contrast is desirable and recent reports suggest that this aim could be achieved by pretreatment with cold octreotide. Here we report on the results of 111In-DTPA-octreotide scintigraphy in 12 SCLC patients carried out before and after octreotide treatment. The patients were treated for 7 days with octreotide 200 micrograms three times a day s.c. Uptake was studied at 5 h with whole body planar and SPET imagings. In all cases studied, pretreatment with octreotide was followed by enhancement of tumor imaging. In one patient a better contrast of the lesions was found at the parenchymal and mediastinal levels as well as at brain level, allowing a clear definition of otherwise questionable metastases. After octreotide treatment, a decrease in background uptake in the subdiaphragmatic area was observed in most cases, allowing a better imaging of liver metastases. The enhancement effect was confirmed by semiquantitative analysis of scintigraphic uptake. Taken together, our results seem to indicate that cold octreotide enhancement can improve 111In-DTPA-octreotide imaging and optimize its clinical role in SCLC.

Genetic susceptibility to fixed drug eruption: evidence for a link with HLA-B22.

BACKGROUND: Our observation of familial cases of fixed drug eruption (FDE) prompted us to consider a genetic predisposition to this disease. OBJECTIVE: Our purpose was to determine whether there is any association between FDE and any of the major histocompatibility complex class I or II alleles. METHODS: HLA class I and II typing was performed by lymphocytotoxicity assay in 36 unrelated patients with FDE. RESULTS: Significantly higher (p < 0.0001) frequencies of the B22 and Cw1 antigens were found in the 36 patients with FDE. CONCLUSION: Our data are the first to suggest a genetic predisposition to FDE.

[Modification of the sympatho-vagal interaction in mitral valve prolapse syndrome. Evaluation of heart rate variability by spectrum analysis]. / Modificazioni del tono neurovegetativo nella sindrome del prolasso valvolare mitralico. Studio della variabilità della frequenza cardiaca mediante analisi spettrale.

To determine whether clinical manifestations in patients with mitral valve prolapse (MVP) are associated with altered sympatho-vagal tone, 46 patients (mean age 27 +/- 6, range 20-45 years; 18 males and 28 females) were studied by power spectrum analysis of RR variability. Patients were divided in 2 groups, according to echocardiographic criteria: Group A: 11 patients with classical MVP; Group B: 35 patients with non classical MVP. These patients were compared with 30 healthy subjects (Group C) well matched for age, body surface area and heart rate. Our findings indicate that at rest there is a significant difference in the high-frequency component between Group A and Group C. Similarly, during the increase in sympathetic activity induced by 70 degrees head-up tilt all groups showed an increase in the low-frequency component, that was more evident in Group A. The data generated from our laboratory suggest that mitral regurgitation (Group A) is a probable cause of vagal tone increase and that there is an adaptive long-term mechanism towards sympathetic conditions. In addition, probably the normalization, demonstrable by the effect of sympathetic activity in tilt, can mask a dysfunction that may be differently evoked.

Nocturnal headache-hypertension syndrome: a chronobiologic disorder.

The study of blood pressure (BP) monitoring in essential hypertensive patients recurrently suffering from nocturnal headache revealed a rhythmic elevation of sphygmomanometric values during the night. Such a finding was not detected in essential hypertensive patients suffering from occasional headache. The nocturnal elevation of BP was seen to be paralleled by the circadian peak of heart rate, suggesting that the disorder is a systemic phenomenon. Importantly, the headache episodes were seen to disappear after antihypertensive therapy that was adjusted to lower the nocturnal increase of BP. The therapeutic results suggested that the nocturnal headache was dependent on the phasic elevation of BP. The beneficial effects further suggested that the nocturnal headache and the nocturnal elevation of BP may represent a particular syndrome with a cause-effect relationship. The term "nocturnal headache-hypertension syndrome" is proposed.

Familial occurrence of fixed drug eruptions.

Fixed drug eruptions following the use of pyrazolone derivatives occurred in 4 members of the same family: a 12-year-old girl, her grandmother, and two of her great aunts. Although the pathophysiologic events leading to this type of reaction are unknown, these cases of familial occurrence suggest that genetic predisposition might be an important causal factor.