Genome-wide transcriptional profiling linked to social class in asthma.

OBJECTIVES: Low socioeconomic status (SES) is one of the most robust social factors associated with disease morbidity, including more severe asthma in childhood. However, our understanding of the biological processes that explain this link is limited. This study tested whether the social environment could get "under the skin" to alter genomic activity in children with asthma. DESIGN AND PARTICIPANTS: Two group design of children with physician diagnosed asthma who came from low or high SES families. OUTCOMES: Genome-wide transcriptional profiles from T lymphocytes of children with asthma. RESULTS: Children with asthma from a low SES background showed overexpression of genes regulating inflammatory processes, including those involved in chemokine activity, stress responses and wound responses, compared with children with asthma from a high SES background. Bioinformatic analysis suggested that decreased activity of cyclic AMP response element binding protein and nuclear factor Y and increased nuclear factor kappaB transcriptional signalling mediated these effects. These pathways are known to regulate catecholamine and inflammatory signalling in immune cells. CONCLUSIONS: This study provides the first evidence in a sample of paediatric patients diagnosed with asthma that the larger social environment can affect processes at the genomic level. Specifically, gene transcription control pathways that regulate inflammation and catecholamine signalling were found to vary by SES in children with asthma. Because these pathways are the primary targets of many asthma medications, these findings suggest that the larger social environment may alter molecular mechanisms that have implications for the efficacy of asthma therapeutics.

Late CT manifestations in spontaneous lobar hematoma.

PURPOSE: The purpose of this work was to determine the late CT manifestations of spontaneous lobar hematoma. METHOD: Serial CT studies were performed in 75 cases. The initial study was done during the acute stage of stroke, and the subsequent one was performed at least 6 months later. RESULTS: There were 20 cases (27%) with no trace of previous hemorrhage, 14 (19%) with a slit cavity, 11 (15%) with a small round cavity, 20 (27%) with pseudoinfarct, 8 (11%) with ventricular deformity but no residual cavity, and 2 (3%) with only calcification at the site of the hemorrhage. CONCLUSION: Our data show that the typical residual slit was relatively uncommon in lobar hematomas and that, depending on their size, hematomas would disappear, reduce to a small cavity, or form a pseudoinfarct.

Serial magnetic resonance imaging in patients with Balò's concentric sclerosis: natural history of lesion development.

We reviewed the magnetic resonance imaging scans from 22 serial studies of 5 patients with Balò's concentric sclerosis collected during the past 3 years. The data showed the concentric lesions did not occur simultaneously but developed step by step in a centrifugal direction. The development of lesions was preceded by an enhancing ring relatively devoid of demyelination and was followed by progressive demyelination occurring mainly at the inner aspect of the enhancement. The same process recurred on the edge of the previous enhanced zone. Thus, an appearance of concentric rings with alternating demyelinated and relatively myelin-preserved bands was formed.

Case report: Pontine haemorrhage following iohexol lumbar myelography.

A case of pontine haemorrhage following lumbar myelography using iohexol is described. Stress, inducing transient hypertension during the procedure, with superimposed neurotoxicity from contrast medium (iohexol) is suggested as a possible mechanism. No brain stem lesion was seen on the initial brain CT scan, possibly because of the high attenuation of the contrast medium in the subarachnoid space. A delayed CT brain scan demonstrated the pontine haemorrhage and was necessary to confirm the diagnosis.

A positive residue in the hydrophobic core of the Escherichia coli lipoprotein signal peptide suppresses the secretion defect caused by an acidic amino terminus.

The signal peptide of secretory proteins requires a basic amino terminus followed by a stretch of hydrophobic residues to effect efficient translocation of precursor proteins. Replacement of the positively charged amino-terminal residues of prolipoprotein by acidic amino acids decreased the rate of precursor translocation (Inouye, S., Soberon, X., Franceschini, T., Nakamura, K., Itakura, K., and Inouye, M. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 3438-3441; Vlasuk, G. P., Inouye, S., Ito, H., Itakura, K., and Inouye, M. (1983) J. Biol. Chem. 258, 7141-7148). We demonstrate here that an arginine residue, but not an aspartate, when localized at position 9 of the hydrophobic region of the lipoprotein signal peptide, is able to suppress intramolecularly the processing defect caused by an acidic amino terminus. Furthermore, when present at position 14 of the signal peptide, this positive residue, but not aspartate, was able to support efficient translocation of unmodified prolipoprotein. This demonstrates that a positive residue can restore the function of a severely defective signal peptide and need not be localized at the amino terminus to do so. Both aspartate and arginine substitution at position 14 of the lipoprotein signal peptide stimulated prolipoprotein synthesis. This effect was position-specific, did not require precursor translocation, and was dominant to the inhibition of synthesis caused by an acidic amino terminus.

Late CT manifestations in spontaneous putaminal haemorrhage.

Serial CT studies were performed on 61 patients with putaminal haemorrhage, to determine outcome. The average duration of the follow-up was 2 years and 5 months. Several types of late CT change were identified, including disappearance of the haematoma without a trace of haemorrhage, a residual cavity, deformity of the lateral ventricle, atrophy of the head of the caudate, white matter degeneration and linear pseudocalcification around the cavity. Small haematomas, comma-shaped and less than 2 cm wide might disappear without leaving any trace. A slit or small rounded residual cavity was a frequent result of elliptical or irregular haematomas with little mass effect. With prominent ventricular compression, there were distortion and dilatation of the lateral ventricle and atrophy of the head of the caudate nucleus, which might be accompanied by white matter degeneration and pseudocalcification around the cavity. Five cases (8%) were left with no trace of previous haemorrhage, 32 (52%) with a slit cavity, 10 (16%) with a small round cavity, 8 (13%) with a large cavity, 5 (8%) with no residual cavity but with ventricular deformity, and 1 (3%) with only pseudocalcification at the site of the haemorrhage.

Epileptic seizures in thrombotic stroke.

Epileptic seizures due to thrombotic cerebral infarction were studied in 118 patients. The occurrence of seizures had a bimodal distribution with one peak period within 2 weeks and another peak period from 6 to 12 months after stroke. Four patients had seizures preceding stroke, while 23 patients without a history of previous stroke had "silent infarct" on the CT scan. Fifteen patients (13%) had status epilepticus. Simple partial seizures occurred in 56% of patients, complex partial seizures in 24% and generalized tonic-clonic seizures in 4%. Epilepsy developed in 35% of patients with early seizures and in 90% of patients with late seizures.

Epileptic seizures in elderly people: aetiology and seizure type.

We have studied 342 patients who had their first seizures after the age of 60 years. The causes of seizures were identified in 305 patients (89%) with cerebrovascular disease accounting for 39%, head injury 21%, brain tumours 11%, metabolic disorders 7%, multifactorial aetiology 6%, and CNS infection 4%. The majority of patients (80%) had focal onset seizures that were secondarily generalized in 50%.

Epileptic seizures in intracerebral haemorrhage.

Among 1402 patients with intracerebral haemorrhage (ICH), seizures occurred in 64 (4.6%) and epilepsy in 35 (2.5%). Seizure was the first manifestation of ICH in 19 patients (30%). Status epilepticus occurred in 11 patients (17%) and it was the initial presentation of ICH in six (9%). The majority had simple partial seizures that were predominantly focal and motor. There were 38 patients with early seizure and 26 patients with late seizure. Ninety per cent of seizures occurred within one year after ICH. Eleven patients (29%) with early seizure developed epilepsy, whereas 24 patients (93%) with late seizure developed recurrent seizures. The incidence of seizure was 32% for lobar haematoma, 2% respectively for putaminal, thalamic and pontine haemorrhages and 1% for cerebellar haemorrhage. Twenty-six (62%) out of 42 patients with lobar haematomas developed epilepsy. Thirteen patients (34%) with early seizure died within three months after the onset of seizures whereas three patients (12%) with late seizure died within the same period. The majority of patients who died had deep-seated haematomas.

Reconstruction of the esophagus with the left colon.

This report reviews our experience with 96 patients with benign or malignant stricture of the esophagus who underwent interposition of the left colon with or without esophageal resection from July 1982 to June 1987. There were 67 male and 29 female patients ranging in age from 8 to 80 years. Thirty-seven patients had fibrotic stricture secondary to corrosive injury of the esophagus, 42 had cancer of the esophagus, and 17 had cancer of the gastric cardia. The incidence of postoperative complications and surgical mortality, respectively, was 16.2% and 2.7% for patients with corrosive stricture of the esophagus, 35.7% and 11.9% for patients with cancer of the esophagus, and 35.2% and 5.8% for patients with cancer of the gastric cardia. Reconstruction resulted in good function in 75.6% of the patients with corrosive stricture of the esophagus, 66.6% of the patients with cancer of the esophagus, and 70.5% of patients with cancer of the gastric cardia. The morbidity and mortality were higher in the group with malignant esophageal strictures because of advanced age, poor general condition of the patient, and extent of the surgical procedure needed. Cervical anastomotic leakage was the most frequently encountered complication (13.5%), and all the poor-function results were caused by this complication. In our experience, reconstruction of the esophagus with left colon is a satisfactory method that can be accomplished with acceptable morbidity and mortality. The left colon is a durable and functional substitute.

Status epilepticus in the elderly: etiology, seizure type and outcome.

We have studied status epilepticus among 342 patients who had their first seizures after the age of 60 years. One hundred and two patients (30%) had status epilepticus. Cerebrovascular disease (35%) was the leading cause of status, followed by head trauma (21%), multifactorial etiology (11%), metabolic disorders (10%), brain tumors (8%) and CNS infection (2%). The etiology of status remained undetermined in 13 patients (13%). The majority (80%) had partial status or generalized status with focal onset. Overall mortality was 35%.

Epithelioid granulomas of the bone marrow in non-Hodgkin's lymphoproliferative malignancies.

Ten cases of epithelioid granulomas in the bone marrow of patients with various non-Hodgkin's lymphoproliferative malignancies have been encountered. These included six with non-Hodgkin's lymphoma (three histiocytic and three poorly differentiated lymphocytic types), three with multiple myeloma, and one with acute lymphoblastic leukemia. The bone marrow was not involved by the primary disease in two of the six patients with lymphoma, whereas three with lymphoma showed both granulomatous and lymphomatous lesions in the same marrow specimens, and in one, these lesions were seen in the marrow at different times. The three myeloma patients showed evidence of both myeloma and granulomas in their marrow. In the case of acute lymphoblastic leukemia, the bone marrow showed only granulomas, the leukemic process being in complete remission. Although small numbers of similar cases have been reported before, the authors were unable to find a previous report of acute lymphoblastic leukemia associated with bone marrow granulomas. Although the pathogenesis and the clinical significance of the granulomatous lesion of the bone marrow in non-Hodgkin's lymphoproliferative malignancies are unknown, this lesion should be differentiated from infectious or lipid granulomas as well as from involvement by the primary disease.