Skin cancer in the North Solomons

The Melanesians of the North Solomons are exposed to intense equatorial sunlight and yet have a very low incidence of skin cancer. This study reveals no proven cases of basal cell carcinoma in these people, and demonstrates the rarity of squamous cell carcinoma and melanoma arising in normal pigmented skin. Most, if not all squamous cell carcinomas, arise in skin damaged by tropical ulceration, burns or osteomyelitis. Melanoma arises from the unpigmented skin of the sole of the foot. North Solomon Islanders are very deeply pigmented. Presumably, dense cutaneous melanin in normal undamaged skin provides the highly effective protection against solar carcinogenesis which these people enjoy. Chronic or recurrent skin ulceration with subsequent repair, scarring and loss of pigment is the precursor to almost all non-melanoma skin cancer in these people. Most of these cancers could be prevented by split thickness skin grafting of chronic ulcers, and protection of ulcerated, depigmented and scarred skin from solar radiation.     

Selective management of abdominal stab wounds. Importance of the physical examination

The treatment of patients with anterior abdominal stab wounds remains controversial. We reserve celiotomy for patients who have clinical findings of peritonitis or hemorrhage. Repeated physical examination is the most important element of observation. Recently, 330 patients with stable abdominal stab wounds presented over a 12-month period. These patients were followed up with serial physical examinations and laboratory measurements. Of the 330 patients, 107 patients (32%) required celiotomy for the repair of a life-threatening injury (group 1); 28 patients (8%) underwent nontherapeutic celiotomies (group 2); 19 patients (6%) had negative explorations (group 3); and 176 patients (53%) were observed and discharged (group 4). There were three missed injuries in group 4. Serial physical examination can be a reliable technique in the management of abdominal stab wounds and is comparable to other approaches.     

Growth factor pre-treatment differentially regulates phosphoinositide turnover downstream of lysophospholipid receptor and metabotropic glutamate receptors in cultured rat cerebrocortical astrocytes

Reactive gliosis is an aspect of neural plasticity and growth factor (GF) stimulation of astrocytes in vitro is widely regarded as a model system to study astrocyte plasticity. Astrocytes express receptors for several ligands including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), agonists for the G-protein-coupled lysophospholipid receptors (lpRs). Activation of lpRs by LPA or S1P leads to multiple pharmacological effects including the influx of calcium, phosphoinositide (PI) hydrolysis, phosphorylation of extracellular receptor regulated kinase (ERK), release of arachidonic acid, and induces mitogenesis. Treatment of astrocytes in vitro with a growth factor cocktail (containing epidermal growth factor [EGF], basic fibroblast growth factor [bFGF] and insulin) led to a marked attenuation of lpR-induced PI hydrolysis. In contrast, under identical conditions, GF treatment led to marked potentiation of PI hydrolysis downstream of activation of another abundantly expressed G-protein coupled receptor, mGluR5. Quantitative gene expression analysis of GF-treated or control astrocytes by TaqMan RT-PCR indicated that GF treatment did not change gene expression of lpa1 and s1p1, but increased gene expression of s1p5 which is expressed at very low levels in basal conditions. These results suggest that GF differentially affected PLC activation downstream of mGluR5 versus lpR activation and that the changes in mRNA levels of lpRs do not account for marked attenuation of agonist-induced phosphoinositide turnover.     

Fatal esophageal-arterial fistula 17 years following tetralogy of Fallot repair.

Blalock-Taussig shunts (subclavian to pulmonary anastomoses) have remained the most effective palliation in cyanotic heart disease. Late complications are rare but can be devastating. The case of a 26-year-old female with tetralogy and an original Blalock shunt constructed at age four years is reported. Despite subsequent primary repair of the tetralogy and presumed ligation of the Blalock shunt, the patient succumbed to a fatal hemorrhage due to esophageal-arterial fistula involving the Blalock shunt. The circumstances leading to this dramatic outcome are outlined and discussed. It is important for cardiologists caring for congenital heart disease patients to be aware of the late complications of congenital heart surgery, and carry out the proper follow-up investigations.     

The work of walking: a calorimetric study

Experiments were designed to test the traditional assumption that during level walking all of the energy from oxidation of fuel appears as heat and no work is done. Work is force expressed through distance, or energy transferred from a man to the environment, but not as heat. While wearing a suit calorimeter in a respiration chamber, five women and five men walked for 70 to 90 min on a level treadmill at 2.5, 4.6, and 6.7 km.h-1 and pedalled a cycle ergometer for 70 to 90 min against 53 and 92 W loads. They also walked with a weighted backpack and against a horizontal load. During cycling, energy from fuel matched heat loss plus the power measured by the ergometer. During walking, however, energy from fuel exceeded that which appeared as heat, meaning that work was done. The power increased with walking speed; values were 14, 29, and 63 W, which represented 11, 12, and 13% of the incremental cost of fuel above the resting level. Vertical and horizontal loads increased the fuel cost and heat loss of walking but did not alter the power output. This work energy did not re-appear as thermal energy during 18 h of recovery. The most likely explanation of the work done is in the inter-action between the foot and the ground, such as compressing the heel of the shoe and bending the sole. We conclude that work is done in level walking.     

Effects of alterations in left ventricular filling, contractility, and systemic vascular resistance on the ascending aortic blood velocity waveform of normal subjects.

OBJECTIVES: To confirm the consistent effects on Doppler-measured aortic blood flow velocity waveform variables of alterations in left ventricular preload, afterload, and inotropy using pharmacologic and physiologic maneuvers. SETTING: Medical school laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Increasing infusion rates of dobutamine (1.25 to 5 micrograms/kg.min), esmolol (1.25 to 5 mg/min), phentolamine (1.25 to 5 mg/min), methoxamine (1.25 to 5 mg/min), metaraminol (1.25 to 5 mg/min), and placebo (1.25 to 5 mL of 0.9% saline/min) and increasing plasma removal (0.5 to 1 L) in awake, rested, supine subjects. MEASUREMENTS AND MAIN RESULTS: Ascending aortic blood flow was measured by the suprasternal Doppler approach allowing calculation of waveform variables of stroke distance and minute distance (linear measures of stroke volume and cardiac output), peak velocity, mean acceleration and flow time corrected for heart rate. An index of systemic vascular resistance was obtained by dividing mean systemic BP by the minute distance. Inotropic changes predominantly affected peak velocity and mean acceleration. Changes in preload mainly affected the flow time corrected for heart rate, whereas afterload changes had an intermediate effect. Unsuspected but subsequently confirmed hemodynamic effects were seen with esmolol and metaraminol. CONCLUSIONS: Aortic blood flow velocity waveform variables measured by Doppler ultrasound can be used to noninvasively follow changes in left ventricular preload, afterload, and inotropy.     

Changes in alpha 2-adrenoceptors on vascular smooth muscle and neural membranes following hypertension induced by renal ischemia.

alpha 2-Adrenoceptors were characterized on neural and vascular membranes from 2-kidney-1-clip renal hypertensive (RHT) and normotensive (NT) rats. Rats were sacrificed 6 weeks after induction of renal ischemia, and the specific binding of 3H-clonidine to smooth muscle membranes form tail arteries and neural membranes from various brain regions was examined. Additionally, isometric contractions of helically cut tail artery strips produced by various alpha-adrenoceptor agonists were measured. Scatchard analysis indicated an increased number of high-affinity binding sites on the smooth muscle membranes from RHT rats (Bmax = 43.5 +/- 1.4 fmol/mg protein) compared to that from the NT rats (25.4 +/- 3.8 fmol/mg protein). An increased contractile sensitivity to clonidine was also observed in tail artery strips from RHT rats (EC50 for RHT = 3.04 x 10(-8) M; NT = 1.52 x 10(-7) M). In neural tissue, the number of alpha 2-adrenoceptor-binding sites was significantly increased in the locus coeruleus from RHT rats, but not in the amygdala, hypothalamus, parietal cortex, hippocampus or lower brain stem. These results demonstrate that renal ischemia produces changes in both peripheral and neural alpha 2-adrenoceptor density. The increase in smooth muscle alpha 2-adrenoceptors might also provide a partial explanation for the supersensitivity to adrenergic agonists in this model of hypertension.     

Reversible and irreversible effects of chemical fixation on the NMR properties of single cells.

The effects of chemical fixation are known to alter MR parameters, such as relaxation times and the apparent diffusion coefficient (ADC) of water. It is often assumed that such changes are reversible after samples have been reimmersed in a buffer solution for a sufficient period of time. In this study we characterize the changes associated with fixation of single Xenopus laevis oocytes and their subsequent reimmersion in buffer. Substantial reductions in both T(1) and T(2) values were measured for all compartments of the cell after fixation, with the cytoplasm showing larger changes than the nucleus. After reimmersion in buffer, there were small but statistically significant differences in MR parameters between fresh and reimmersed cells. Experiments with a gadolinium (Gd) contrast agent showed evidence of irreversible changes in the permeability of cellular membranes to small molecules.