Giant basal cell carcinomas: a result of neglect?

Although the occurrence of giant basal cell carcinoma in clinical practice is quite rare, there are some references to these malignancies in the literature. Our study includes 12 patients without previous treatment who had giant basal cell carcinoma with no evidence of metastatic dissemination. Depending on the anatomic region, we used a primary suture, local flap and split-thickness skin grafts for the reconstruction of the defect after the wide excision of the carcinoma. All patients have been followed up and no recurrence has been detected to date. Nine lesions diagnosed on the face (69%) were obvious, and therefore they should have been diagnosed at their early stage. In our series most of the patients had had tumors for more than 3 years (except 2 cases) with no history of radiation exposure or recurrence after previous treatment. Therefore our findings suggest to us that the primary reason for a tumor to achieve this giant size was neglect.     

The organization and connections of anterior and posterior parietal cortex in titi monkeys: do New World monkeys have an area 2?

We used multiunit electrophysiological recording techniques to examine the topographic organization of somatosensory area 3b and cortex posterior to area 3b, including area 1 and the presumptive area 5, in the New World titi monkey, Callicebus moloch. We also examined the ipsilateral and contralateral connections of these fields, as well as those in a region of cortex that appeared to be similar to both area 7b and the anterior intraparietal area (7b/AIP) described in macaque monkeys. All data were combined with architectonic analysis to generate comprehensive reconstructions. These studies led to several observations. First, area 1 in titi monkeys is not as precisely organized in terms of topographic order and receptive field size as is area 1 in macaque monkeys and a few New World monkeys. Second, cortex caudal to area 1 in titi monkeys is dominated by the representation of the hand and forelimb, and contains neurons that are often responsive to visual stimulation as well as somatic stimulation. This organization is more like area 5 described in macaque monkeys than like area 2. Third, ipsilateral and contralateral cortical connections become more broadly distributed away from area 3b towards the posterior parietal cortex. Specifically, area 3b has a relatively restricted pattern of connectivity with adjacent somatosensory fields 3a, 1, S2 and PV; area 1 has more broadly distributed connections than area 3b; and the presumptive areas 5 and 7b/AIP have highly diverse connections, including connections with motor and premotor cortex, extrastriate visual areas, auditory areas and somatosensory areas of the lateral sulcus. Fourth, the hand representation of the presumptive area 5 has dense callosal connections. Our results, together with previous studies in other primates, suggest that anterior parietal cortex has expanded in some primate lineages, perhaps in relation to manual abilities, and that the region of cortex we term area 5 is involved in integrating somatic inputs with the motor system and across hemispheres. Such connections could form the substrate for intentional reaching, grasping and intermanual transfer of information necessary for bilateral coordination of the hands.     

Spatial clustering of remodeling osteons in the femoral neck cortex: a cause of weakness in hip fracture?

Intracapsular femoral neck fractures are associated with decreased cortical width and increased proportions of Haversian canals with diameters greater than the normal mean plus 3 SD (i.e., >385 microm). Such canals might be formed if closely associated resorbing osteons merge; a cortical event analogous with the loss of cancellous connectivity. To test this, we investigated the pattern of osteon distribution in the aging femoral neck to determine if remodeling osteons were distributed in anatomical clusters. Femoral neck biopsies from female patients with intracapsular hip fractures (n = 13) were compared with age/gender-matched cadaveric controls (n = 13). Solochrome-stained sections were analyzed for Haversian canal location, canal diameter, and the presence of an osteoid surface. Clustering was investigated using statistical software with a cluster defined as two or more osteoid-bearing osteon centers within 0.75 mm of each other. Clusters occurred more frequently than would be expected by chance (p < 0.001). Fracture cases had more clusters per unit area (3.14 +/- 0.31 clusters/25 mm2 of cortical bone) than controls (1.89 +/- 0.22) (p = 0.002). In fracture cases, the antero-inferior, antero-superior, and infero-anterior regions had more clusters per 25 mm2 than comparable control regions (ant/inf: 4.12 +/- 0.79, 1.70 +/- 0.60,p = 0.025; ant/sup: 5.31 +/- 1.1, 1.80 +/- 0.59,p = 0.013; inf/ant: 3.15 +/- 0.49, 1.27 +/-0.29, p = 0.004). The mean number of clusters per 25 mm2 per region correlated with the mean porosity per region (adjusted r2 = 0.60;p = 0.014), and the total number of giant canals per region correlated with the total number of clusters per region (adjusted r2 = 0.58; p = 0.011). In conclusion, remodeling osteons are clustered or grouped anatomically, and fracture cases have more clusters than controls. Our data suggest that merging of adjacent, clustered osteons during resorption could lead to the rapid development of canals with excessive diameters and focal weakness. Clustering is greatest in those regions that we have previously shown to have the largest relative reductions in bone strength compared with controls and known to be maximally loaded during a sideways fall. This implicates the remodeling process underlying clustering of remodeling osteons in the aetiology of hip fracture.     

Reuse of Ilizarov frame components: a potential cost savings?

Although there is a potential hospital cost savings in reusing Ilizarov frame components, such reuse must be carefully considered in view of the deterioration of the parts during clinical use. A study is presented that addresses this issue through examination of clinically removed frames, laboratory testing, and engineering calculations.     

Are there excitability changes in the hand motor cortex during speech in left-handed subjects?

Hemispheric dominance was investigated in left-handed subjects using single transcranial magnetic stimulation to assess the possible effect of forced change in the dominant hand. Single transcranial magnetic stimuli were delivered randomly over the hand area of the left or right motor cortex of 8 Japanese self-declared left-handed adult volunteers. Electromyographic responses were recorded in the relaxed first dorsal interosseous muscle while the subjects read aloud. Laterality quotient calculated by the Edinburgh Inventory ranged from -100 to -5.26 and laterality index calculated from motor evoked potentials ranged from -86.2 to 38.8. There was no significant correlation between laterality quotient and laterality index. Mean data values across all 8 subjects indicated significant increases only in the left hand. Our ratio analysis of facilitation of the hand motor potentials showed that 2 each of the 8 self-declared left-handers were right- and left-hand dominant and the other 4 were bilateral-hand dominant. Speech dominancy was localized primarily in the right cerebral hemisphere in left-handed subjects, but some individuals exhibited bilateral or left dominance, possibly attributable to the forced change of hand preference for writing in childhood. Our findings suggest changes in the connections between the speech and hand motor areas.     

Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage?

OBJECT: The pathogenesis of delayed ischemic neurological deficits after subarachnoid hemorrhage has been related to products of hemolysis. Topical brain superfusion of artificial cerebrospinal fluid (ACSF) containing the hemolysis products K+ and hemoglobin (Hb) was previously shown to induce ischemia in rats. Superimposed on a slow vasospastic reaction, the ischemic events represent spreading depolarizations of the neuronal-glial network that trigger acute vasoconstriction. The purpose of the present study was to investigate whether such spreading ischemias in the cortex lead to brain damage. METHODS: A cranial window was implanted in 31 rats. Cerebral blood flow (CBF) was measured using laser Doppler flowmetry, and direct current (DC) potentials were recorded. The ACSF was superfused topically over the brain. Rats were assigned to five groups representing different ACSF compositions. Analyses included classic histochemical and immunohistochemical studies (glial fibrillary acidic protein and ionized calcium binding adaptor molecule) as well as a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Superfusion of ACSF containing Hb combined with either a high concentration of K+ (35 mmol/L, 16 animals) or a low concentration of glucose (0.8 mmol/L, four animals) reduced CBF gradually. Spreading ischemia in the cortex appeared when CBF reached 40 to 70% compared with baseline (which was deemed 100%). This spreading ischemia was characterized by a sharp negative shift in DC, which preceded a steep CBF decrease that was followed by a slow recovery (average duration 60 minutes). In 12 of the surviving 14 animals widespread cortical infarction was observed at the site of the cranial window and neighboring areas in contrast to findings in the three control groups (11 animals). CONCLUSIONS: The authors conclude that subarachnoid Hb combined with either a high K+ or a low glucose concentration leads to widespread necrosis of the cortex.     

The role of ventromedial prefrontal cortex in decision making: judgment under uncertainty or judgment per se?

Ventromedial prefrontal cortex (VMF) is thought to be important in human decision making, but studies to date have focused on decision making under conditions of uncertainty, including risky or ambiguous decisions. Other lines of evidence suggest that this area of the brain represents quite basic information about the relative "economic" value of options, predicting a role for this region in value-based decision making even in the absence of uncertainty. We tested this prediction in human subjects with VMF damage. Preference judgment is a simple form of value-based decision making under certainty. We asked whether VMF damage in humans would lead to inconsistent preference judgments in a simple pairwise choice task. Twenty-one participants with focal damage to the frontal lobes were compared with 19 age- and education-matched control subjects. Subjects with VMF damage were significantly more inconsistent in their preferences than controls, whereas those with frontal damage that spared the VMF performed normally. These results argue that VMF plays a necessary role in certain as well as uncertain decision making in humans.     

The once-daily formulation of tacrolimus: a step forward in kidney transplantation?

Nonadherence is a critical issue in transplantation. Recently, Astellas designed a once-daily-extended release formulation of tacrolimus (Tac). Despite initial reports showing bioequivalence of Tac once-daily (Advagraf) with the original formulation requiring twice-daily intake (Tac twice-daily, Prograf), several groups have now shown a sustained decrease in Tac exposure upon conversion from Prograf to Advagraf. Here, we discuss the possible reasons for this observation and how it could affect the expected benefits of Advagraf, and we comment on the fact that a similar lack of bioequivalence might prevail with generic immunosuppressive drugs.     

The hazards of off-road motor sports: Are four wheels better than two?

BackgroundOff-road motorsports are an increasing popular activity, yet the relative safety profile of all-terrain vehicles (ATV) to off-road motorcycles (ORMC) has not been compared.Study designA retrospective review of the 2002–2006 US National Trauma Data Bank of ATV and ORMC crash victims. Patients were described according to demographic (age, sex, race and ethnicity, insurance status) and injury characteristics (Injury Severity Score, hypotension, motor component of the Glasgow Coma Score, presence of a severe head or extremity injury) known to affect trauma outcomes. Logistic regression evaluated the independent effect of an ATV vehicle on mortality, intensive care unit (ICU) admission, and placement on a ventilator relative to ORMC. The anatomic distribution of severe injuries was compared between survivors and decedents within each vehicle type.ResultsA total of 34,457 patients met inclusion criteria, of whom, 24,582 were ATV patients and 9875 were ORMC patients. ATV patients had 51% higher risk-adjusted odds of death (OR 1.51; 95% CI 1.03–2.20), 55% higher risk-adjusted odds of being admitted to an ICU (OR 1.55; 95% CI 1.42–1.70), and 42% higher risk-adjusted odds of being placed on a ventilator (OR 1.42, 95% CI 1.17–1.72) compared to ORMC crash victims. Decedents in both vehicle types were more likely to suffer severe head, thoracic, and abdominal injuries relative to their surviving counterparts.ConclusionFor injured riders, ATVs are associated with increased mortality and higher resource utilisation compared to ORMCs. Both groups suffer distinct anatomic injuries, suggesting the need for focused areas of injury prevention planning and research.     

The bispectral index: a measure of depth of sleep?

How does physiological sleep affect the Bispectral Index (BIS)? We collected electroencephalographic (EEG) data from five subjects during the early part of the night, comparing the changes in the BIS with the conventional EEG stages of sleep. We found that the BIS was a consistent marker of depth of sleep. Light sleep occurred at BIS values of 75-90, slow-wave sleep occurred at BIS values of 20-70, and rapid eye movement sleep occurred at BIS values of 75-92. The effects of natural sleep on the BIS seem to be similar to the effects of general anesthesia on the BIS. The BIS may have a role in monitoring depth of sleep. IMPLICATIONS: Electroencephalographic data were collected from five subjects during sleep. We found that the Bispectral Index decreased during increasing depth of sleep in a fashion very similar to the decrease in Bispectral Index that occurs during general anesthesia. This study further highlights the electroencephalographic similarities of states of sleep and general anesthesia.     

The cycle of the seminiferous epithelium in humans: a need to revisit?

Understanding the dynamics of spermatogenesis is central to clinical andrology or to probing environmental effects on human testes. This review considers what is known about renewal and proliferation of spermatogonia, how germ cells are organized in cellular associations constituting the cycle of the seminiferous epithelium, relative frequencies of cellular associations, durations of the cycle of the seminiferous epithelium and spermatogenesis, and measurement of daily sperm production. Daily sperm production (DSP) per testis tends to decline with advancing age. Regardless of age, there is substantial loss of potential sperm from degeneration of spermatocytes, but not spermatids. DSP per gram testis parenchyma or DSP per testis cannot be predicted on the basis of testis size or age of a man. The review shows why our 1960s data base is neither robust nor precise and suggests how deficiencies might be rectified. New cellular associations should be defined, with none representing >15% of the cycle of the seminiferous epithelium. Then determine when A(pale)-spermatogonia become committed to proliferate or how many mitotic divisions occur thereafter. Restudy the duration of spermatogenesis because the accepted value might be in error by approximately 6 days. Restudying human spermatogenesis will benefit clinicians, toxicologists, and epidemiologists probing testis function by direct evaluations or indirectly via evaluations of quantity and quality of sperm ejaculated. It also will benefit scientists interested in renewal and proliferation of spermatogonia, or a spermatogonium as a prototype stem cell.     

The pre-operative ECG in day surgery: a habit?

As the population presenting for day-case surgery and anaesthesia increases, so does the challenge of adequate pre-operative assessment. Although an electrocardiogram is frequently performed, its value in day-case surgery remains unproven. One thousand, one hundred and eighty-five patients presenting for day-case surgery were assessed. One hundred and fifty-four (13%) were referred for electrocardiogram according to well-recognised criteria for the prediction of coronary artery disease. They were read independently by the anaesthetist responsible for the case and by an experienced cardiologist. A significant abnormality was noted in 26% of electrocardiograms, most frequently in patients referred with hypertension. There was a good correlation between the reports of the anaesthetist and cardiologist. Only 20% of those patients with an abnormal electrocardiogram had their surgery postponed. No adverse events occurred in patients proceeding to surgery despite the abnormalities. We conclude that a resting electrocardiogram is of limited value in risk stratification of patients undergoing day-case surgery.