Chronic radiographic lung changes in children with vertically transmitted HIV-1 infection

OBJECTIVE: We prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 to determine the incidence of chronic radiographic lung changes (CRC) and to correlate these changes with clinical assessments. SUBJECTS AND METHODS: Between 1990 and 1997, we scored 3050 chest radiographs using a standardized form. Group I children (n = 201) were HIV-1-infected at enrollment. Group II children (n = 512) were enrolled prenatally or before 28 days postpartum and subsequently subdivided into group IIa (n = 86), children identified as HIV-1-infected; and group IIb (n = 426), those who were HIV-1-uninfected. CRC were defined as parenchymal consolidations or nodular disease lasting 3 months or more or increased bronchovascular markings or reticular densities lasting 6 months or more. Morbidity was assessed by CD4 counts, viral load, the presence of low oxygen saturation, wheezing, tachypnea, crackles, and clubbing. RESULTS: The cumulative incidence of chronic radiographic lung changes in HIV-1-infected children was 32.8% by 4 years old, with increased bronchovascular markings or reticular densities being most common. Chronic changes were associated with lower CD4 cell counts and higher viral loads. Resolution of these chronic changes was associated with decreasing CD4 cell counts but not with lower rates of clinical findings, viral load, or difference in survival. CONCLUSION: With increased survival, CRC are becoming more common. The resolution of these changes may indicate immunologic deterioration rather than clinical improvement.     

High mobility group proteins 1 and 2 recognize chromium-damaged DNA

Chromium (Cr) is a human carcinogen and a potent DNA damaging agent. Incubation of DNA with CrCl3 resulted in dose-dependent binding of Cr to DNA and, at concentrations >20 microM, altered the electrophoretic mobility of a 100 bp oligonucleotide. We also demonstrate that high mobility group (HMG) proteins 1 and 2 bind Cr-damaged DNA (Cr-DNA). Protein binding was lesion density-dependent, with maximal binding to DNA treated with 100 microM CrCl3. HMG2 binds to Cr-DNA with a calculated Kd of approximately 10(-9) M. These proteins also bound DNA obtained from chromate-treated cells. These results suggest that the covalent attachment of Cr to DNA induces alterations in DNA structure which are recognized by HMG1 and HMG2. Therefore, these proteins may function as Cr-damaged DNA recognition proteins in vivo and as a consequence of binding, may play a role in directing the cellular response to Cr-DNA adduct formation.      

Sexual precocity: sex incidence and aetiology

The aetiology of 197 girls and 16 boys presenting with sexual precocity was reviewed. Ninety one girls and four boys had central precocious puberty (M:F 23:1); a cause was identified in all the boys but in only six girls. All boys with precocious puberty need detailed investigation; in girls investigation should be based on clinical findings, particularly the consonance of puberty.     

Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2).

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.     

Reduction of sound levels with antinoise in MR imaging

A combination of active and passive techniques was used to reduce the sound levels in magnetic resonance imagers. These techniques were integrated into an existing audio system. Measurements of sound reduction varied with the protocol being used and averaged 9.9 dB with coaxial cabling and 14.2 dB with fiberoptic conduction of the feedback signal to a controller. Patient comfort and communication were improved.     

Conformationally restricted bicyclic analogs of somatostatin.

A model for a biologically active conformation of somatostatin is proposed. This model is based primarily on the biological results obtained with novel bicyclic somatostatin analogs having a covalent bridge replacing the side chains of residues 5 and 10, 6 and 11, and 5 and 12, respectively, rather than on physical measurements on the hormone in solution. The high activity of an analog in which Phe6 and Phe11 are replaced by cystine provides evidence that these phenylalanines stabilize the biologically active conformer through "hydrophobic bonding" but do not directly interact with the receptor. The synthesis of the novel bicyclic analogs of somatostatin and the effects of these on the inhibition of secretion of insulin, glucagon, growth hormone, and gastric acid are described.     

Studies on the post-ictal rise in seizure threshold

Seizure thresholds were determined by timed infusion of a convulsant drug. Following an electroconvulsive shock (ECS) rats exhibited a raised seizure threshold to infusion of the GABA antagonist drugs, pentylenetetrazol, bicuculline and isopropyl-bicyclophosphate, but not to the glycine antagonist strychnine or the 5-HT agonist, quipazine. The increase in threshold was seen following a bicuculline-induced seizure and 30 min following the last of a course of ECS given once daily for 10 days. The rise in seizure threshold still occurred when animals were pretreated with alpha-methyl-p-tyrosine (200 mg . kg-1), p-chlorophenylalanine (200 mg . kg-2), naloxone (1 mg . kg-1) or indomethacin (20 mg . kg-1). Diazepam (2 mg . kg-1), flurazepam (10 mg . kg-1) and sodium valproate (400 mg . kg-1) elevated basal seizure threshold and a further rise followed the ECS. Phenytoin (40 mg . kg-1) and carbamazepine (40 mg . kg-1) had no effect on basal seizure threshold or the ECS-induce rise. (?Propranolol (20 mg . kg-1) did not affect basal seizure threshold but prevented the ECS-induced increase. The rise in seizure threshold following a convulsion may be an important adaptive mechanism which could be related to the reported increase in specific benzodiazepine binding following a seizure.