Structural and functional abnormalities at 11p15 are associated with the malignant phenotype in sporadic adrenocortical tumors: study on a series of 82 tumors

Abnormalities of the 11p15 region with overexpression of the normally imprinted insulin-like growth factor II (IGF-II) gene have been implicated in the pathogenesis of adrenocortical tumors. We evaluated the frequency and distribution of 11p15 loss of heterozygosity (LOH) and IGF-II gene overexpression in a series of 82 sporadic adrenocortical tumors, screened for pathological functional imprinting of the 11p15 region in tumors not exhibiting LOH and evaluated the expression of H19 gene in these tumors. Abnormalities of the 11p15 region as LOH (loss of the maternal allele and duplication of the paternal allele) and/or IGF-II gene overexpression are frequent features of the malignant state and were found in 27 of 29 (93.1%) of the malignant tumors and in only 3 of 35 (8.6%) of the benign tumors. Tumors without abnormality of the 11p15 region (mainly benign tumors) did not exhibit pathological functional imprinting. In tumors with mosaicism for 11p15 LOH, biallelic expression of the IGF-II gene was constant in the tumor cell contingent not undergoing LOH. Abrogation of H19 expression correlated with the loss of the maternal allele (LOH or pathological imprinting), but did not always correlate with overexpression of the IGF-II gene. These data indicate the involvement of dysregulation of the 11p15 region in late steps of adrenocortical tumorigenesis and provide us with new molecular markers for a better diagnostic and prognostic evaluation of adrenocortical tumors.     

Exertional compartment syndrome of the upper extremity

Exertional compartment syndrome is characterized by intracompartmental pressures that rise transiently following repetitive motion or exercise, thereby producing temporary, reversible ischemia, pain, weakness, and, occasionally, neurologic deficits. The exact cause or pathogenesis remains unclear; a disturbance of microvascular flow caused by elevated intramuscular pressure leads to tissue ischemia, depletion of high-energy phosphate stores, and cellular acidosis. Anatomic contributing factors may include a limited compartment size, increased intracompartmental volume, constricted fascia, loss of compartment elasticity, poor venous return, or increased muscle bulk. The diagnosis is suspected based on history and confirmed with physical examination and intramuscular pressure evaluation before and after exercise (stress test). Differential diagnosis includes claudication or other vascular abnormalities, myositis, tendinitis, periostitis, chronic strains or sprains, stress fracture, other compression or systemic neuropathies, and cardiac abnormalities with angina or referred extremity pain. Initial treatment includes activity modification; refractory symptoms can be managed with elective fasciotomy.     

Comparison of the in vitro and in vivo effects of meropenem and ciprofloxacin on the morphology of Escherichia coli and Staphylococcus aureus

Second-semester ultrasonography of a female fetus documented short femora and humeri and dislocation of the radii. Based on the clinical and postmortem radiological findings, autosomal-recessive omodysplasia was diagnosed. The physeal plates of the long tubular bones were assessed by computer-assisted image analysis. The dimensions and orientation of the chondrocytic lacunae in the physeal plates of the omodysplastic fetus were compared with those in the physeal plates of fetuses without gross limb abnormalities (oligohydramnios, n = 2; hydrocephalus, n = 2; Down syndrome, n = 1). The pathological characteristics of the omodysplastic physeal plates were an expanded zone of proliferating cartilage and an increased number of closely packed, small chondrocytes. We propose that a genetic, functional deficiency of the physeal cells, underlying the short-limbed dwarfism of autosomal-recessive omodysplasia, is partially compensated, albeit ineffectively, by an increased number of small chondrocytes in the proliferating zone of the physeal plate.     

Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice

BACKGROUND: The efficacy of omeprazole, 20 mg once daily, in the treatment of reflux oesophagitis and the therapeutic advantages over the histamine H2 receptor antagonists are well documented. This study assessed 20 mg omeprazole daily (OM20), 10 mg omeprazole daily (OM10), and 150 mg ranitidine (RAN) twice daily for symptom relief in gastro-oesophageal reflux disease (GORD). METHODS: Patients (n = 994) presenting with heartburn to their general practitioner underwent endoscopy to exclude peptic ulcer disease and were randomized into a UK, multicentre, parallel-group, double-blind comparison of the three treatments for 4 weeks. Symptoms were assessed at clinic visits after 2 and 4 weeks. RESULTS: Symptom relief after 4 weeks was achieved by 61% (OM20), 49% (OM10), and 40% (RAN) patients (OM20 versus OM10, P < 0.0167; OM20 versus RAN, P < 0.0001; OM10 versus RAN, P < 0.01). Among the patients (32%) with erosive reflux oesophagitis, symptom relief was achieved in 79% (OM20), 48% (OM10), and 33% (RAN) (OM20 versus OM10, P < 0.0001; OM20 versus RAN, P < 0.0001; OM1O versus RAN, NS). CONCLUSION: Omeprazole, 20 mg, is the most effective initial therapy for relief of GORD symptoms.     

Research of psychosocial issues of children with craniofacial anomalies: progress and challenges

Benign intracranial hypertension and communicating hydrocephalus are uncommon but important disorders that affect cerebrospinal fluid dynamics. They have clinical similarities but their management is usually different. The factors determining which of the two disorders will develop include brain compliance, the state of the cranial sutures, the nature of the insult and its magnitude. I propose that the time course of the pathological events leading to presentation may be a further factor to consider in the pathogenesis and management of these disorders.     

Desmoplastic infantile astrocytoma with metastases at presentation

In the process of health planning and of the evaluation of health care, there is growing interest in assessing the quality of medical care. Traditionally, quality indexes are divided into three groups: structure, process and outcome. The first two indexes can be measured more easily and quickly, but outcome indexes are more appropriate care indicators for both health planners and patients. The introduction of quality assessment means that physicians work in order to achieve the required standards even if it does not increase the real quality of care, that data are systematically biased in order to increase the quality score and, lastly, that physicians do not rely on case-mix statistical adjustment of results. All these problems have already been evaluated by the Health Department of New York State. Since 1989, outcome data of open-heart surgery have been monitored in all cardiac surgery centers in the state. It is still open to debate whether the decreased mortality in New York State is due to the quality assessment program, to the migration of sicker patients to nearby states, or to the refusal of heart surgeons to operate on high-risk patients. In Italy as well, new rules have been introduced into health legislation in order to assess the quality of health care. Even if methodological and legislative instruments to assess quality of care are still not completely reliable in terms of assessing the quality of care with simple and effective methods, this does not exclude the need to proceed in assessing the quality of health care.     

Decreased expression of bcl-2 (p26) in CD8(+) lymphocytes of patients with T-cell lymphoproliferative disorders of large granular lymphocytes

The objective of the present study was to identify the polychlorinated biphenyl congeners of Aroclor 1254 that are responsible for the induction of the cytosolic bioactivation of aromatic amines. Various chlorobiphenyls, ranging from di- to hexa-substituted, were administered to rats and the ability of the hepatic cytosol to bioactivate 2-aminoanthracene and 2-aminofluorene was investigated. These studies revealed that the induction of the cytosolic activation of aromatic amines increased with the increasing extent of chlorination; moreover, planar congeners were more effective inducers of this activity compared to their non-planar isomers. This observation prompted us to investigate whether the cytosolic activation of aromatic amines is associated with the Ah receptor. Treatment of mice with Aroclor 1254 stimulated the cytosolic activation of aromatic amines in C57BL6 mice, an Ah-responsive strain, whereas it had no effect in DBA2 mice, a non-responsive strain. These findings indicate that the bioactivation of aromatic amines by the liver cytosol is linked to the Ah receptor.     

Increased saturated triacylglycerol levels in plasma membranes of human neutrophils stimulated by lipopolysaccharide

Neutrophils isolated from patients with bacterial infections or stimulated in vitro with lipopolysaccharide (LPS) produce a high resolution, lipid-dominated spectrum on 1H-NMR spectroscopy (May et al, 1993. J. Infect. Dis. 168: 386-392). We have investigated the origin of this lipid signal using NMR and chemical analyses of both whole neutrophils and purified plasma membranes. Plasma membranes from neutrophils that had been stimulated with 50 microg/ml LPS exhibited the high resolution 1H-NMR signal, and contained double the triacylglycerol (TAG) content of plasma membranes isolated from resting cells. Chemical analysis of the whole cells indicated that the TAG also increased at the cellular level (1.7-fold) after stimulation with LPS. Diradylglycerol increased 2- to 3-fold in both whole cells and plasma membranes after stimulation, but was only a minor component compared with TAG. The plasma membrane protein/phospholipid ratio increased 2.6-fold, whereas cholesterol (free and esterified) was unchanged. The membranes from LPS-stimulated neutrophils exhibited increased fluidity, as judged by increased merocyanine 540 binding, consistent with a 2-fold reduction in cholesterol/phospholipid ratio. LPS induced a shift in fatty acid content of whole cell polar lipids towards more oleic acid and less palmitic acid, whereas the neutral lipid fraction contained increased amounts of palmitic and stearic acids. The TAG fraction of plasma membrane lipids contained increased amounts of palmitic acid when prepared from cells stimulated with LPS. We conclude that the 1H-NMR signal in LPS-stimulated neutrophils arises from increased amounts of plasma membrane TAG with an elevated content of palmitic acid.     

Vaccination of pregnant macaques protects newborns against mucosal simian immunodeficiency virus infection

Simian immunodeficiency virus (SIV) infection of newborn rhesus macaques is a rapid, sensitive animal model of human pediatric AIDS. Newborn macaques were readily infected by uncloned SIVmac following oral-conjunctival exposure and had persistently high viremia and rapid development of AIDS. In contrast, when 3 pregnant macaques were vaccinated against SIV, 2 of the newborns that had transplacentally acquired antiviral antibodies were protected against mucosal SIV infection at birth. These results suggest that intervention strategies such as active immunization of human immunodeficiency virus (HIV)-infected pregnant women and anti-HIV immunoglobulin administration may decrease the rate of perinatal HIV infection.     

Tumour suppressor gene mutations in humans and mice: parallels and contrasts

Tumour suppressor genes prevent cancer development. They can be identified by studying humans, but a full understanding of the mechanisms of their action requires the production of animal models. Mice with mutations in tumour suppressor genes can be produced by gene targeting. The phenotypic consequences of tumour suppressor gene mutations in mice and humans show parallels and contrasts, and both can contribute to the elucidation of disease processes.