By Y. Trano. Florida Southern College.
In the extreme purchase 20 mg fluoxetine with amex menstrual 3 times a month, so little flow gets into the pulmonary vascular bed that the patient cannot survive proven 10 mg fluoxetine women's health center walnut creek. In the early stages of the Eisenmenger reaction 20 mg fluoxetine fast delivery generations women's health center boca raton, the pulmonary vascular changes are related to smooth muscle hypertrophy and vasoconstriction and are reversible if the extra flow is removed by surgical ligation of the ductus purchase fluoxetine 10 mg on line breast cancer knee high socks, which is usually an easy procedure. However, if the condition is allowed to progress to the point where ductal right-to-left shunting Fetal Circulation & Congenital Heart Disease - Daniel Bernstein, M. While it may take years for irreversible pulmonary vascular resistance changes to occur with a patent ductus arteriosus, this phenomenon can occur in many other congenital cardiac defects, and can progress at a fast rate, sometimes within the first year of life. Thus it is very important that children with cardiac defects be evaluated early in life, in order to prevent this complication. Calculate pulmonary and systemic blood flows and flow indices, and pulmonary vascular resistance for each age. Artery(s/d,m) Aorta (s/d,m) 60/45,50 85/40,55 95/40,60 100/65,70 110/70,80 110/70,82 Left 5 15 12 8 7 5 Atrium(mean) Right 3 7 7 5 4 5 Atrium(mean) Fetal Circulation & Congenital Heart Disease - Daniel Bernstein, M. As we have seen, there are several important anatomic and physiologic differences between the fetal circulatory pathways, the newborn, and the adult circulation. The fetus adapts to this environment with specialized hemodynamic, metabolic, and hematologic adaptations. For example, increased levels of hemoglobin, increased affinity of fetal hemoglobin for oxygen, and a preferential distribution of blood to different parts of the body: the fetal organs with the highest metabolic demands (brain and heart) receive blood which has a higher concentration of oxygen and other nutrients than the blood which flows to the fetal lower body, placenta and abdominal viscera. The anatomic structures which are unique to the fetus (ductus arteriosus, ductus venosus, foremen ovale) normally close or are lost at the time of birth. Physiologically, pulmonary blood flow is low in the fetus, while pulmonary pressure is at systemic levels; at birth, pulmonary blood flow increases as pulmonary resistance and pressure falls. It is hoped that the student will be able to discuss the locations and functions of the various fetal structures, the composition of venous return to the heart, the distribution of venous return between the right and left ventricles, and the distribution of ventricular output from the heart. Examples are also provided to illustrate 1) one situation in which persistence of a fetal pathway may actually be beneficial (pulmonary atresia), and 2) what can happen if complete transition from the fetal circulation does not occur (patent ductus arteriosus). Congenital cardiac defects can be classified into two major groups based on the presence or absence of cyanosis (Figure 1). Congenital Heart Disease Observation Acyanotic Cyanotic Chest X-Ray Increased Normal Decreased Increased Pulmonary Pulmonary Pulmonary Pulmonary Blood Flow Blood Flow Blood Flow Blood Flow 1. Physiologic classification of congenital heart disease based on presence or absence of cyanosis and pattern of pulmonary blood flow. The chest X-ray can then be used to further refine the diagnosis based on whether the pulmonary vascular markings show evidence of increased, normal or decreased pulmonary circulation (Figure 2). Top Left: Normal heart size and pulmonary vascular markings in a patient without congenital heart disease. Top Right: Increased heart size and increased pulmonary vascular markings in an acyanotic patient with a ventricular septal defect. Bottom: “Boot” shaped heart and decreased pulmonary vascular markings in a cyanotic patient with tetralogy of Fallot. This group of congenital lesions can be divided by physiological principles into those that induce a volume load on the heart (most commonly due to a left-to-right shunt but also due to atrioventricular valve regurgitation or to abnormalities of the myocardium itself-the cardiomyopathies) and those that induce a pressure load on the heart (subvalvar, valvar or great vessel stenoses). The chest X-ray is a useful tool for differentiating between these two major categories, since heart size and pulmonary vascular markings will usually both be increased in the left-to-right shunt lesions. Classification of acyanotic congenital heart defects based on physiologic perturbation. The common pathophysiologic denominator in this group of lesions is a communication between the left and right sides of the circulation and the shunting of fully oxygenated blood back into the lungs. Although pulmonary Fetal Circulation & Congenital Heart Disease - Daniel Bernstein, M. As pulmonary resistance drops over the first month of life, the left-to-right shunt increases, and so does the intensity of the murmur and the symptoms. The increased volume of blood in the lungs is quantitated by pediatric cardiologists as the pulmonary to systemic blood flow ratio or Qp:Qs. This increase in pulmonary blood flow decreases pulmonary compliance and increases the work of breathing. Fluid leaks into the interstitium or alveoli causing pulmonary edema and the common symptoms: tachypnea, chest retractions, nasal flaring, poor feeding and wheezing (Table 1). In order to maintain a left ventricular output which is now several times normal (although most of this output is ineffective, since it returns to the lungs) heart rate and stroke volume must increase, mediated by an increase in sympathetic stimulation. The increased work of breathing and the increase in circulating catecholamines lead to an elevation in total body oxygen requirements, taxing the oxygen delivery capability of the circulation. Thus, the common symptoms of tachycardia, sweating, irritability and failure to thrive. The combination of left-to-right shunt and valve regurgitation increases the volume load on the heart and usually leads to earlier presentation and more severe symptomatology. As opposed to the left-to-right shunts, the cardiomyopathies (see below) cause heart failure directly due to diminished cardiac muscle function, leading to increased atrial and ventricular filling pressures, and to pulmonary edema secondary to increased capillary pressure. The common pathophysiologic denominator of these lesions is that, unless the stenosis is severe, cardiac output is maintained, thus, in children, symptoms of heart failure are often not present. This compensation is accomplished by a marked increase in cardiac wall thickness (hypertrophy). If the ductus arteriosus is still open, the oxygen saturation may be Fetal Circulation & Congenital Heart Disease - Daniel Bernstein, M. Coarctation of the aorta may present solely with a systolic murmur and with diminished pulses in the lower compared with the upper extremities. Thus, it is important to always palpate both the femoral and either the brachial or radial pulses simultaneously during a routine screening examination of any infant or child. A coarctation may be localized to the area of the descending aorta immediately opposite the ductus arteriosus (juxtaductal coarctation). In these patients, in the first few days or weeks of life the ductus arteriosus may remain partially patent and will serve as a conduit for blood flow to partially bypass the obstruction at the level of the coarctation. In more severe forms, coarctation involves hypoplasia of the transverse aortic arch, in which case it presents with a more significant obstruction to blood flow and usually causes heart failure and signs of poor perfusion in the neonatal period. This group of congenital heart lesions can be divided by physiological principles into those associated with decreased pulmonary blood flow (e. The chest X-ray is again an important primary initial diagnostic tool for differentiating between these two major categories. There are two basic pathophysiologic elements which underlie all of these lesions: First, is an obstruction to pulmonary blood flow at some level (tricuspid valve, sub- pulmonary muscle bundles, pulmonary valve, main or branch pulmonary arteries). It is important to remember that even with severe pulmonic stenosis, systemic desaturation will not occur unless there is right-to-left shunting at some level. Classification of cyanotic congenital heart lesions based on physiologic perturbation. In these lesions, the degree of clinical cyanosis will depend on the degree of obstruction to pulmonary blood flow. If the obstruction is mild, cyanosis may not be present at rest, but only with stress (these hypercyanotic episodes are known as "Tet spells"). If the obstruction is severe, pulmonary flow may be totally dependent on the patency of the ductus arteriosus. These infants present with profound cyanosis in the newborn period and require pharmacologic manipulation (prostaglandin E1) to maintain ductal patency until surgical intervention. Unlike the previous group of lesions, pulmonary blood flow is more than adequate in this group, yet because of the defect only a small portion of this oxygenated blood can enter the systemic circulation. Deoxygenated blood from the body returns to the right side of the heart and is pumped directly back to the body again.
Pork brains from the grocery store may be dissected to give you the different parts of the brain generic 10mg fluoxetine with amex menstrual exercises. Chicken livers often have an attached gallbladder or piece of bile duct purchase fluoxetine 20 mg mastercard breast cancer jackets, giving you that extra organ order fluoxetine 20 mg without prescription uc davis women's health center. To make a specimen of skin buy 20mg fluoxetine overnight delivery breast cancer 80s, use hangnail bits and skin peeled from a callous, not a wart. Making a Complete Set of Tissue Samples My original complete set was made from a frozen fish. As it thawed, different organs were cut away and small pieces placed in bottles for preserving in filtered water and grain alcohol. The piece of intestine closest to the anus corresponds to our colon, the part closest to the stomach corresponds to our duodenum. The 2 layers of the stomach and different layers of the eye, the optic nerve and spinal cord were obtained this way. Another complete set of tissue samples were obtained from a freshly killed steer at a slaughter house. In this way the 4 chambers of the heart were obtained, the lung, trachea, aorta, vein, pancreas, and so forth. Purchasing a Complete Set of Tissue Samples Slides of tissues, unstained or stained in a variety of ways for microscope study give identical results to the preparations made by yourself in the ways already described. You now have a set of organ samples, either fresh, frozen, preserved or on slides. You also have a set of test substances, whether chemical compounds, or elements, or products. Your goal is to search in your own organs and body tissues for the substances that may be robbing you of health. Body Fluid Specimens Each of these fluids should be prepared by putting about ¼ tsp. Undiluted specimens do not work for reasons that are technical and beyond the scope of this book. Label your speci- mens Urine A (child), Urine B (woman), Urine C (mine), and so forth. Electronically, a dead specimen is equivalent to a live specimen, so that pasteurization of the milk does not help. Use your own, if you have deparasitized yourself and test negative to various fluke stages. When you test with a substance on one plate and nothing on the other, you are searching your entire body for that substance. By putting a tissue sample on the other plate you are testing for the substance specifically in that tissue, and this is much more sensitive. To find mercury in your kidneys you would use a mercury sample on one plate, and a kidney sample on the other. If you put a substance on each plate, a resonating circuit means the two samples have something in common. For example, if you have mercury on one plate and some dental floss on the other, a positive result indicates mercury in the floss. Materials: Prepare a pint of brown sugar solution (white sugar has propyl alcohol pollution) using filtered water. Test your skin for the presence of brown sugar, using the newly made sample bottle and your skin specimen. Prepare a paper applicator by tearing the corner from a white unfragranced paper towel. Dip the paper wick in the pint of sugar water and apply it to the skin of your inner arm where you can rub freely. Leave the shredded wick on the skin and tape it down with a piece of clear tape about 4 inches long (this increases the time you have to work). Place your skin tissue specimen on one plate and the sugar specimen bottle on the other plate. As soon as you hear resonance, implying that the skin has absorbed the sugar solution (which may take a full minute), replace the skin specimen with one of liver and listen for resonance again. After five to ten minutes the sugar will be gone from all of these tissues and your experiment is ended. Notice that you have only a few minutes to get all your testing done after the skin has absorbed the test substances. Assemble the products named in the propyl alcohol list (page 335) and benzene list (page 354)... Place the propyl alcohol test substance on one plate and your products, in turn, on the other. This is such a global tragedy that people must protect themselves by using their own tests. Rather than assurances, regulatory agencies should provide the consumer with cheap and simple tests (dip sticks and papers so we need not lug our Syncrometers around). Even if some test should fail, not all tests would fail to find an important pollutant like benzene. If your aluminum specimen actually has cadmium or copper in it, you are also testing for these in your brain. Leave your purest aluminum test substance on one plate, and replace the brain sample with these items, testing them one at a time. Choose tissues like kidney, nerves, brain, liver, in addition to white blood cells. I have never dissected human tissues and subjected them to confirmatory laboratory tests. It seems reasonable that because skin and tongue are directly provable, that other tissues work similarly. Testing the Air Fine particles and gas molecules that are in the air stick to the dust and eventually fall down onto the table, kitchen counter, and other places. Wipe the kitchen table and counter with a dampened piece of paper towel, two inches by two inches square. Do not get old dust, like from the top of the refrigerator or back shelves, because it does not represent the current air quality. Testing Someone Else Seat the person comfortably with their hand resting near you. Choose the first knuckle from the middle or first finger just like you do for yourself. Since you are touching this person, you are putting yourself in the circuit with the subject. A coil of about 10 microhenrys, worn next to the skin, works well and is easily made. Obtain insulated wire and wrap 24 turns around a ball point pen (or something about that size), closely spaced. Nevertheless, Salmonella in your liver, mercury in your kidneys, aluminum in the brain all show up in the saliva, too. This test is not as sensitive as having the person present in the circuit, though. Materials: A saliva specimen from the person being tested; they may be thousands of miles away. The whole thing, towel and all, can be pushed into a glass bottle for pre- serving.
Contra-indications discount 20 mg fluoxetine fast delivery women's health center utexas, adverse effects 20mg fluoxetine fast delivery pregnancy 0 thru 40 wks, precautions – Do not administer to patients with cardiac disorders (cardiac failure discount fluoxetine 20 mg with visa menstruation on depo provera, recent myocardial infarction cheap fluoxetine 20 mg otc women's health group tallmadge ohio, conduction disorders, bradycardia, etc. Remarks – Haloperidol decanoate is a long-acting form used in the long-term management of psychotic disorders in patients stabilised on oral treatment (100 mg every 3 to 4 weeks). Start with an initial dose of 250 Iu/kg and adjust dosage according to coagulation tests. Contra-indications, adverse effects, precautions – Do not administer if: • haemorrhage or risk of haemorrhage: haemophilia, active peptic ulcer, acute bacterial endocarditis, severe hypertension; in postoperative period after neurosurgery or ophtalmic surgery; • thrombocytopenia or history of heparin-induced thrombocytopenia. Reduce doses of protamine if more than 15 minutes has elapsed since heparin administration. Contra-indications, adverse effects, precautions – Administer with caution to patients with heart failure, coronary insufficiency, recent myocardial infarction, severe tachycardia, history of stroke. Contra-indications, adverse effects, precautions – Avoid prolonged administration in patients with peptic ulcer, diabetes mellitus or cirrhosis. Contra-indications, adverse effects, precautions – Do not administer to patients with benign prostatic hyperplasia, urinary retention, closed-angle glaucoma, tachycardia. For each preparation, onset and duration vary greatly according to the patient and route of administration. Indications – Insulin-dependent diabetes – Diabetes during pregnancy – Degenerative complications of diabetes : retinopathy, neuropathy, etc. Duration – Insulin-dependent diabetics: life-time treatment – Other cases: according to clinical response and laboratory tests Contra-indications, adverse effects, precautions – Do not administer in patients with allergy to insulin (rare). Rotate injection sites systematically and use all available sites (upper arm, thighs, abdomen, upper back). Diabetes is controlled when: • there are no glucose and ketones in urine; • before-meal blood glucose levels are < 1. Treatment includes: insulin administration, specific diet, education and counselling under medical supervision (self-monitoring of blood glucose, self-administration of insulin, knowledge about signs of hypoglycaemia and hyperglycaemia). Also comes in solution containing 100 Iu/ml, administered only with calibrated syringe for Iu-100 insulin. Dosage – 20 to 40 Iu/day divided in 2 injections for intermediate-acting insulin, in 1 or 2 injections for long-acting insulin. Short-acting insulin is often administered in combination with an intermediate-acting or long-acting insulin. Examples of regimens: Insulin Administration • Short-acting insulin • 2 times/day before breakfast and lunch • Intermediate-acting insulin •at bedtime • Short-acting insulin • 3 times/day before breakfast, lunch and dinner • Long-acting insulin • at bedtime or before breakfast • Intermediate-acting with or without short- • 2 times/day before breakfast and dinner acting insulin Contra-indications, adverse effects, precautions – See "insulin: general information". Remove from the refrigerator 1 hour before administration or roll the vial between hands. Remarks – Storage: to be kept refrigerated (2°C to 8°C) – • do not freeze; discard if freezing occurs. Indications – As for insulin in general, particularly in cases of diabetic ketoacidosis and diabetic coma. Dosage – Emergency treatment of ketoacidosis and diabetic coma • Child: initial dose 0. Correct cautiously acidosis with isotonic solution of bicarbonate and, if necessary, post-insulinic hypokalaemia. When hyperglycemia is controlled, an intermediate-acting insulin may be substituted in order to limit injections. Short-acting insulin may be mixed with intermediate-acting insulin in the proportion of 10 to 50%. Contra-indications, adverse effects, precautions – See "Insulin: general information". Remarks – The terms "cristalline insulin" and "neutral insulin" are used either for soluble insulin or intermediate and long-acting insulin. If hypertension remains uncontrolled 5 and 10 minutes after injection, administer another dose of 20 mg (4 ml). Administer additional doses of 40 mg (8 ml) then 80 mg (16 ml) at 10 minute intervals as long as hypertension is not controlled (max. If the implant is inserted later (in the absence of pregnancy), it is recommended to use condoms during the first 7 days after the insertion. Contra-indications, adverse effects, precautions – Do not administer to patients with breast cancer, severe or recent liver disease, unexplained vaginal bleeding, current thromboembolic disorders. Use a copper intrauterine device or condoms or injectable medroxyprogesterone or an oral contraceptive containing 50 micrograms ethinylestradiol (however there is still a risk of oral contraceptive failure and the risk of adverse effects is increased). Remarks – Implants provide long term contraception, their efficacy is not conditioned by observance. However, the etonogestrel implant (one rod) is easier to insert and remove than the levonorgestrel implant (2 rods). Contra-indications, adverse effects, precautions – Do not administer if known allergy to lidocaine, impaired cardiac conduction. Contra-indications, adverse effects, precautions – Reduce the dose in patients with renal impairment; do not administer to patients with severe renal impairment. In the event of decreased urine output (< 30 ml/hour or 100 ml/4 hour), stop magnesium sulfate and perform delivery as soon as possible. If delivery cannot be performed immediately in a woman with eclampsia, stop magnesium sulfate for one hour then resume magnesium sulfate perfusion until delivery. The following injections may be administered within the 2 weeks before the scheduled date and up to 2 weeks after, without the need for additional contraception. In post-partum period, it is better to wait until the 5th day if possible, as the risk of bleeding is increased if the injection is administered between D0 and D4. If the injection is given later (in the absence of pregnancy), it is recommended to use condoms during the first 7 days after injection. Contra-indications, adverse effects, precautions – Do not administer to patients with breast cancer, uncontrolled hypertension, current thromboembolic disorders, non-equilibrated or complicated diabetes, severe or recent liver disease, unexplained vaginal bleeding. Remarks – It may take as long as a year for fertility to return to normal after stopping injections. Dosage and duration – Patients must be treated in hospital, under close medical supervision. As propylene glycol can dissolve plastic, the drug should preferably be administered using a glass syringe (only if sterilisation is reliable), otherwise inject immediately (but slowly) using a plastic syringe. Duration – According to clinical response Contra-indications, adverse effects, precautions – Do not administer in gastric ulcer. Do not freeze – • Expiry date indicated on the label is only valid if stored under refrigeration and protected from light. Exposure to heat and especially light causes the deterioration of the active ingredient and thus loss of efficacy. Contra-indications, adverse effects, precautions – Do not administer to patients with allergy to metronidazole or another nitroimidazole (tinidazole, secnidazole, etc. Contra-indications, adverse effects, precautions – Do not administer to patients with severe respiratory impairment or decompensated hepatic impairment. The child may develop withdrawal symptoms, respiratory depression and drowsiness when the mother receives morphine at the end of the 3rd trimester and during breast-feeding. In these situations, administer with caution, for a short period, at the lowest effective dose, and monitor the child. Contra-indications, adverse effects, precautions – May cause: • tachycardia, fibrillation, hypertension, pulmonary oedema when given postoperatively, due to a sudden reversal of analgesia; • nausea, vomiting; • acute withdrawal syndrome in opioid-dependent patients. Contra-indications, adverse effects, precautions – May cause: headache, diarrhoea, skin rash, nausea, abdominal pain, dizziness. Initially 5 to 8 drops/minute, then increase by 5 to 8 drops/minute every 30 minutes (max. Do not freeze – • Expiry date indicated on the label is only valid if stored under refrigeration and protected from light. Exposure to light and heat causes the deterioration of the active ingredient and thus loss of efficacy.
Chitin and cellulose are the most abundant sugar polymers on the surface of the earth generic fluoxetine 10mg free shipping menstruation 35 day cycle. Yet such β-linked sugar polymers are rare in vertebrate tissues generic fluoxetine 20 mg without a prescription menstrual underwear, and require unusual reactions for their catabolic turnover purchase 20 mg fluoxetine women's health problems white discharge in hindi. There is strong evidence that an H2O bridge between the acetamide and carboxyl groups is involved in the secondary structure buy fluoxetine 20 mg fast delivery womens health magazine women diet test. The unusually stiff tertiary poly- meric structure is also stabilized by such hydrophobic interactions. Glycosaminoglycans and proteoglycans must be distinguished from ‘‘mu- cins,’’ the branch-chained sugars and their associated proteins. These occur more often on cell surfaces, though they also accumulate in the intercellular ‘‘ground substance,’’ particularly in association with malignancies. This problem has arisen in part because of the ill-deﬁned or unknown nature of histochemical color reactions. The molecular domain encompasses a large volume of water, and even at low concentrations, solutions have very high viscosity. It functions as a sieve, to exclude certain molecules, to enhance the extracellular domain of cell surfaces, particularly the lumenal surface of endothelial cells, to stabilize structures by electrostatic interactions, and also acts as a lubricant. Hyaluronan increases whenever rapid tissue proliferation, regeneration, and repair occur (14). Ele- vated levels promote cell detachment, in preparation for mitosis, as cells leave tissue organization, and enter the transient autonomy required for the mitotic event to occur. The water of hydration also opens up spaces creating a per- missive environment for cell movement. Hyaluronan is generally produced in the interstitium, in the mesenchymal connective tissue of the body, and is thought to be largely a product of ﬁbroblasts. This remaining 15% that reaches the blood stream has a rapid turnover, with a t1/2 of 2 to 5 min, being rapidly eliminated by receptors in the liver, and also, by unknown mechanisms in the kidney (15,53,54). Hyaluronan also increases in the circulation in liver disease, particularly cirrhosis, and in renal failure reﬂecting aberrant degradation (65– 67), in rheumatoid arthritis (68) and in some malignancies, resulting from in- creased tissue synthesis (69). This corresponds approximately to the time when a ‘‘switch’’ from the scar-free fetal wound healing to the adultlike wound healing with scarring occurs (71). There is also an abundance of inﬂammatory cells, a necessary component for the normal process of wound healing. Such observations are made in both the experimental fetal rabbit and sheep models, as well as clinically, in infants delivered following in utero surgery. Aspects of wound healing appear to be a strategic retreat to an embryonic situation, fol- lowed by a rapid recapitulation of ontogeny. However, overexpression of hyaluronidase also correlates with disease pro- gression, as shown recently in bladder (77,78) and in breast tumor metastases (79,80). It is the probable basis of the failure to rosette in the classic sheep red blood cell rosette test, a former laboratory procedure used to diagnose malignancy (93,94). These are referred to collectively as hya- ladherins, a term coined by Toole (38,39). Such factors are presented to cells as mechanisms for growth control and modulators of cell func- tion. They also appear to be a component of the nuclear matrix in a wide variety of cells (103,104). It plays a role in cell adhesion, migration, lymphocyte activation and homing, and in cancer metastasis. In skin pathophysiology, the effect of local and systemic immune disorders on such interactions between Langerhans cells and keratinocytes awaits explication (110). This receptor is implicated in cell locomotion, focal adhesion turnover, and contact inhibition. The length of time tissue is in the formalin is a variable that may explain the conﬂicting results that are often encountered. A further incubation of 24 h in aqueous buffer further increases the disparity between the acid alcohol formalin Fig. Hyaluronan is most prominent in the upper spinous and granular layers of the epidermis, where most of it is extracellular. The most intense staining is observed in the section ﬁxed with the acid-formalin/alcohol (A), compared to the section ﬁxed with the conventional neutral- buffered formalin (B). Of particular interest is that small scattered foci of staining in the epidermal layer are comparable to the intensity of staining found in the dermis using the acid-formalin/alcohol (A). Such foci in the epidermal layer stained less intensely in conventionally ﬁxed samples (B). This increase in calcium that appears to simulate in culture the natural in situ differentiation of basal keratinocytes parallels the increasing calcium gradient observed in the epidermis. There may be intracellular stores of calcium that are released as keratinocytes mature. The lamellar bodies are thought to be modiﬁed lysosomes containing hydrolytic en- zymes, and a potential source of the hyaluronidase activity. The lamellar bodies fuse with the plasma membranes of the terminally differentiating keratinocyte, increasing the plasma membrane surface area. The lemallar bodies also acidify, and their polar lipids become partially converted to neutral lipids, thereby participat- ing in skin barrier function. And the water contained therein cannot penetrate beyond the lipid-rich stratum granulosum. And the stratum granulosum is essential for maintenance of that hydration, not only of the skin, but of the body in general. Profound dehydration is a serious clinical problem in burn patients with extensive losses of the stratum granulosum. The ﬁbroblasts of the body, the most banal of cells from a histological perspective, is probably the most diverse or all vertebrate cells with the broadest repertoire of biochemical reactions and potential pathways for differentiation. What makes the papillary dermal ﬁbroblast different from other ﬁbroblasts is not known. Each of these phenomena contribute to the apparent dehydration, atro- phy, and loss of elasticity that characterizes aged skin. But the transient sense of well being in the long run extracts a high price, particularly with prolonged exposure. The biochemical changes that distinguish photoaging and chronological aging have not been identiﬁed. These appear as ‘‘smudges’’ on H&E sections of sun-damaged skin, rather than between the collagen and elastin ﬁbers as would be observed in normal skin. Acute and Chronic Inﬂammation Chronic inﬂammation causes premature aging of the skin, as observed in patients with atopic dermatitis. The constant inﬂammatory process leads to decreased function of the skin barrier, accompanied by loss of skin moisture. The erythema, swelling, and warmth of the acute process are followed later by the characteristic dry ap- pearance and the formation of wrinkles. The precise mechanisms are unknown, but may relate to the differences between acute and chronic inﬂammatory cells and the attendant chemical mediators released by such cells. Alternatively, ini- tiation of a wound healing response, with collagen deposition, may be a mecha- nism invoked for the premature aged appearance of the skin in chronic inﬂam- mation. Hyaluronan in Skin Substitutes There is a requirement for skin substitutes in a great number of clinical situations. In patients with extensive burns, insufﬁcient skin is available for autologous split- thickness skin grafts. Resurfacing of the burned area can occur with autologous cultured epidermal cell autografts.