Behavioral control of abnormal breathing in sleep

Behavioral control of abnormal breathing in sleep was studied to determine if an intervention procedure could reduce apnea duration and also SaO ₂ (blood oxygen) desaturation levels. Sleep apnea patients (n=11) were instructed while awake that tones would be presented in sleep whenever an apnea event occurred. They were told to breathe deeply to the tones and were given practice in doing so. Intervention and nonintervention hours alternated across 2 nights following 2 baseline nights. As expected, during the intervention hours, the duration but not the frequency of apneic events was reduced. The procedure also resulted in higher SaO ₂ levels during the intervention hours. Daytime sleepiness was not greater following intervention but sleep staging effects were observed. The results are sufficiently promising to warrant additional research.This research was supported by NIH Grants 2 HL 27149-84 and HL 34125 entitled Behavioral Control of Respiration in Sleep.     

Presymptomatic diagnosis of SMA III by genotype analysis

Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I-III SMA to region 5q12-q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR-based polymorphic markers. In one family, a 7-year-old boy affected with type III SMA and an 8-year-old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. © 1993 Wiley-Liss, Inc.     

Morphological variability of pterion in the human skull

The pterion is one of the most interesting bone meeting points in craniofacial osteology and its complex morphology derives from the fact that is the contact point of the facial skeletal elements, skull base and calvarium. Knowledge of its peculiar morphology is mandatory for the pterional approach used in microsurgery and surgery. The Authors studied 506 adult, human skulls where the pterion was accurately reconstructed on polyethylene sheets. They report their data on the morphological analysis and classify the forms. They focussed their attention on the presence of wormian bones at the level of the sphenoparietal suture, on the peculiar existing morphology and reviewed the literature on these classifications. The Authors also evaluated the length of the sphenoparietal suture, the minimum gap between the frontal and temporal, the influence of pteric bones on pterion variability and any correlations between measurements and cranial indexes.     

Blue rubber bleb nevus syndrome and pulmonary hypertension: an unusual association

INTRODUCTION: Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital systemic angiodysplasia with multiple vascular malformations in the skin, gastrointestinal tract and, less often, in other internal organs and the brain. CASE REPORT: A 36-year-old man with past history of BRBNS was admitted to our hospital for progressive dyspnea and fatigue. Primary pulmonary hypertension (PPH) was diagnosed. He then developed acute abdominal pain and dyspnea, dying in a few hours due to sudden cardiac arrest. Postmortem examination demonstrated angiomatous lesions located in the skin, small bowel, heart, lungs, liver and thyroid. The lesions were slightly raised, soft and compressible and microscopically consisted of dilated vascular channels lined by a flattened endothelium. The vascular wall was formed by several layers of smooth muscle cells, intermixed with abundant aggregates of elastic lamellae and thin collagen fibers. Luminal thrombi were a frequent finding. In the small bowel, we identified the presence of an abnormally large artery directly opening into a thin-walled venous channel. The most striking finding in the lungs was the presence of thrombi of varying age in the lumen of segmental and elastic arteries, as well as muscular arteries and arterioles. Severe medial hypertrophy of muscular arteries and muscolarization of arterioles were also present. Intimal proliferative lesions and plexiform lesions were never observed. CONCLUSION: The pulmonary findings are consistent with recurrent thromboembolic events from shunts in the visceral lesions. To our knowledge, this is the first report of BRBNS with visceral arterovenous (AV) fistulae complicated by thromboembolic pulmonary hypertension (PH).     

Clinical,immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.     

Identification, characterization and biological activity of oxytocin receptor in the developing human penis

Although abnormalities of the male external genitalia (MEG) are a relatively common problem, little is known concerning the molecular mechanisms that finely regulate penile development. We report here the expression of the oxytocin receptor (OTR) gene by real-time RT-PCR in human fetal tissues (11th-12th week of gestation), including the MEG. The developing penis expressed a very high level of OTR mRNA, only a half log(10) unit lower than fetal central nervous system, used as a positive control. The OTR protein is also highly expressed (western, immunohistochemistry and binding studies) and immunolocalized both in the mesenchymal body and in the surrounding blood capillaries, which will later constitute penile trabeculae and sinusoids. Binding studies using [125I]oxytocin antagonist ([125I]OTA) in cultured human fetal penile smooth muscle cells (hfPSMC) revealed the presence of specific OTR with a high capacity and affinity for oxytocin (OT) and for OTA. Increasing concentrations of OT dose-dependently induced intracellular Ca2+ mobilization. Furthermore, OTR mediated an increase in the proliferation and the migration of hfPSMC. In conclusion, we demonstrate that in the developing human MEG, OTR is highly expressed and might be involved in coordinating timely and appropriate proliferation and migration of the penile cells. Thus, OTR might represent an additional target for investigating human fetal MEG organogenesis.     

DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein

Fanconi anemia (FA) is a cancer-predisposition syndrome characterized by hypersensitivity to interstrand-cross-link (ICL) inducers. FA hypersensitivity to ICL has been correlated with alterations in homologous recombination, non-homologous end-joining, telomere maintenance, DNA-damage assessment and checkpoint regulation, processes in which the components of the RAD50/MRE11/NBS1 (RMN) complex are involved. To better characterize the mechanisms by which ICL are processed in human cells and to gain insight into their toxicity in FA, we examined (i). the RMN complex assembling in response to the ICL inducers mitomycin C (MMC) and photoactivated 8-methoxypsoralen and (ii). the proficiency of FA cells to perform RMN activation in response to ICL inducers. We show here that ICL activates the assembly of the RMN proteins into subnuclear foci, and that their formation proceeds independently of ICL incision, a step mainly dependent on XP-F/ERCC1 heterodimer activity. Interestingly, FA cells were unable to form RMN foci in response to either ICL inducer. Analysis by pulsed-field gel electrophoresis and single-cell gel electrophoresis of MMC-treated cells showed that FA cells from complementation group C (FA-C cells, defective in the FANCC gene) form double-strand breaks and unhook MMC-induced ICL similarly to FANCC wild-type cells. These observations imply that the absence of RMN assembly in FA-C cells is not simply due to the absence of DNA ends produced as intermediates of ICL processing, and indicates a direct role for FANCC in RMN focus assembly in response to ICL inducers. Moreover, we show that the formation of foci, including BRCA1 and/or RAD51 proteins, is significantly delayed in FA cells. These alterations in the assembly of DNA-repair proteins in FA provide an interpretation for the DNA-damage processing anomalies observed in FA cells and for the genetic instability and the cancer predisposition of the syndrome.     

In Vivo Observation of Cutaneous Larva Migrans by Fluorescence-Advanced Videodermatoscopy

Fluorescence-advanced videodermatoscopy is not a widespread diagnostic technique. Its application in dermatology can facilitate the diagnosis of diseases such as cutaneous larva migrans by enabling us to recognize the precise position of larva in vivo on the skin. Using this noninvasive technique, we detected a case of cutaneous larva migrans in a patient.     

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review

Neurosurgical Review - Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after...