Frequent clones of p53-mutated keratinocytes in normal human skin

The multiple genetic hit model of cancer predicts that normal individuals should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated keratinocytes, arising from the dermal-epidermal junction and from hair follicles. These clones, 60-3000 cells in size, are present at frequencies exceeding 40 cells per cm2 and together involve as much as 4% of the epidermis. In sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin. We conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells. These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to cancer.     

Orbital venous approach to the cavernous sinus: an analysis of the facial and orbital venous system

Carotid-cavernous fistulas are abnormal communications between the internal carotid artery and the cavernous sinus produced by a rupture of the wall of the carotid artery or one of its branches into the sinus. Extradural branches of the internal or external carotid arteries may communicate with the cavernous sinus, producing proptosis, progressive glaucoma, and ocular vascular engorgement. Various approaches to obliterate these fistulas have evolved, many of which carry high morbidity or are precluded by anatomical considerations. Analysis of the venous anatomy of the orbit and face, including human cadaver dissections, reveals a new and safe approach to the cavernous sinus, requiring microsurgical isolation and cannulation of the superior ophthalmic vein through an anterior orbital approach. Selective embolization of a carotid-cavernous fistula can be performed successfully through this route. We present pertinent anatomy and technical considerations and the successful clinical application of these principles. Surgeons familiar with craniofacial anatomy and microvascular techniques can apply these principles and play an active role in the treatment of these complex problems.     

Measurement of neonatal responses to painful stimuli: a research review

The measurement of neonatal responses to painful stimuli remains a significant clinical problem. Although numerous measures have been evaluated, instruments that are valid, reliable, and clinically feasible are not yet available. The purpose of this paper is to critique the studies that have been done using biochemical, physiological, and behavioral measures to evaluate neonatal responses to painful stimuli. Specific issues regarding measurement in premature and critically ill neonates are emphasized. The intent of this review and critique of the literature is to stimulate additional research into the assessment of neonatal pain.     

Effects of size and orientation change on hippocampal activation during episodic recognition: a PET study

To determine whether physical match between studied and tested items influences blood flow increases in the hippocampal formation associated with recognition memory, positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while healthy volunteers made old/new judgements about line drawings of objects. Some objects were tested in the same size and orientation as they had appeared earlier during the study phase of the experiment; other objects were tested in a different size or orientation than when they were studied. Blood flow increases in the vicinity of the hippocampal formation were observed in the same object condition compared with the size change and the orientation change conditions, even though recognition accuracy was affected significantly only by orientation change. Results add to previous findings suggesting that physical similarity between studied items and test cues may contribute to hippocampal activation during episodic retrieval.     

Scabies associated with a bullous pemphigoid-like eruption

Intramuscular phenol neurolysis is a well-known procedure used to decrease spasticity and improve function in patients who have failed to respond to more conservative forms of intervention. Traditionally, this approach has been limited to spasticity reduction in limb muscles, and its use in managing spasticity of the facial muscles has not been described in the literature. This case report describes a new and previously unreported application of intramuscular neurolysis for managing severe unrelenting facial muscle spasticity in a postanoxic encephalopathic patient. Prior to the procedure, hypertonicity in the orbicularis oris muscle was so profound that it limited speech and affected cosmetic, hygienic, and nutritional status. After intramuscular phenol neurolysis of the orbicularis oris muscle, the patient's level of functioning improved.     

Reduced dosage of genes encoding ribosomal protein S18 suppresses a mitochondrial initiation codon mutation in Saccharomyces cerevisiae

A yeast mitochondrial translation initiation codon mutation affecting the gene for cytochrome oxidase subunit III (COX3) was partially suppressed by a spontaneous nuclear mutation. The suppressor mutation also caused cold-sensitive fermentative growth on glucose medium. Suppression and cold sensitivity resulted from inactivation of the gene product of RPS18A, one of two unlinked genes that code the essential cytoplasmic small subunit ribosomal protein termed S18 in yeast. The two S18 genes differ only by 21 silent substitutions in their exons; both are interrupted by a single intron after the 15th codon. Yeast S18 is homologous to the human S11 (70% identical) and the Escherichia coli S17 (35% identical) ribosomal proteins. This highly conserved family of ribosomal proteins has been implicated in maintenance of translational accuracy and is essential for assembly of the small ribosomal subunit. Characterization of the original rps18a-1 missense mutant and rps18a delta and rps18b delta null mutants revealed that levels of suppression, cold sensitivity and paromomycin sensitivity all varied directly with a limitation of small ribosomal subunits. The rps18a-1 mutant was most affected, followed by rps18a delta then rps18b delta. Mitochondrial mutations that decreased COX3 expression without altering the initiation codon were not suppressed. This allele specificity implicates mitochondrial translation in the mechanism of suppression. We could not detect an epitope-tagged variant of S18 in mitochondria. Thus, it appears that suppression of the mitochondrial translation initiation defect is caused indirectly by reduced levels of cytoplasmic small ribosomal subunits, leading to changes in either cytoplasmic translational accuracy or the relative levels of cytoplasmic translation products.     

The incidence and characteristics of the clinical picture of recurrent myocardial infarct in the rural population

As many as 3033 patients with myocardial infarction residing in rural areas were kept under observation. In this population, myocardial reinfarction (MRI) was diagnosed in 411 subjects, with 78.8% having had it for 4 years. Those MRI patients ranging between 51 to 60 years showed the greatest prevalence (44.3%). The ratio of micro- to macrofocal (through-and-through) MRI was 1:3, that of males to females 9:1. Microfocal MRI was commonly associated with a pain-free variant of the disease (23.5%) with low frequency of thromboembolic complications (3.1%). Every fifth patient with macrofocal (through-and-through) renecrosis presented with aneurysm of the heart. In a 10-year and longer follow-up, mortality from MRI was 43.6 percent among patients with macrofocal MRI, while deaths attributable to microfocal MRI were estimated to be 28.9 percent. High mortality rates suggest great severity of illness and low efficacy of the drug therapy adopted.     

Independent common-mode and differential-mode design of fully differential analog filters

Fully differential filter design is usually made departing from a single-ended prototype. This procedure guarantees the desired differential-mode response, but does not take into account common-mode dynamics, which could present nonacceptable transient responses or stability problems. A state-space design technique, which provides control of both differential and common-mode responses, is proposed. It is based on a feedback topology that allows independent assignment of differential and common-mode eigenvalues. This technique ensures circuit stability and also provides a high common-mode rejection ratio, which is independent of component unbalances. Experimental results on a first-order state-space filter are presented.