Crazy days around the world

I’ve almost forgot that I have this website around. As I (and you) can see, i didn’t wrote anything here for about half a year and that mostly because I went around Europe with conferences and wanting to learn more and more about humans pathology.

My roads got me through Prague, Villnius, Salonic, Bucharest, Viena and Dubrovnik. I’ve saw some amazing places, I’ve stayed in some nice places in this towns.

I had the pleasure of staying on a college doctor in Prague in town center. Although is an old town, is quite vibrant and full of people working around all day, just like in an European capital. In Salonic I was in summer, when the temperatures where high. Two weeks after that I went to Bucharest and I had a horrific weather, with heavy rains and nothing to do. Good thing that the aparthotel Bucharest service that I’ve searched game me a nice apartment in town center and could go around the town when the rain would calm for a little bit.

In Villnius it was quite hot, which was a little bit surprising, knowing that in September rains quite a lot. I’ve ended this “tournament” in Dubrovnik, on an international conference about gastrointestinal diseases. Many many new things have been discovered in this domains, as in others and I can’t wait to start posting about those many discoveries.

Until then, I’ll just sip some tea from my cup and watch some London news on BBC. To relax a little. And then, back to work. It’s a new year and we have a lot of interesting things to discover.

Recycling Plastics, The Challenges & Opportunities Faced By Today’s Society

Plastics are cheap, lightweight and durable materials, which can be readily made into a variety of products which can be used in a wide range of applications. As a result, the production of plastics has increased hugely over the last 40 years.

However, with these current levels of usage the disposal generates several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture.

 These two observations would indicate that our current use of plastics is un-sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide.

Recycling is one of the most important methods currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal.

Here in Ireland, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through down grading or product reuse, the use of alternative biodegradable materials and energy recovery as fuel. And it’s not that hard to do it, because you can hire a skip dublin service, so you don’t have to worry about the logistics in this operation.

While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen massive expansion over the last few decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities to recycle it, and with the combined actions of the public, industry and governments it might be possible to divert the majority of plastic waste from landfills to recycling over the next 20 years.

Articular manifestations of Rheumatoid arthritis

RA can affect any of the synovial joints. Most commonly, the disease starts in the MCP, PIP, and MTP joints followed by the wrists, knees, elbows, ankles, hips, and shoulders in roughly that order. Early treatment helps limit the number of joints involved. Of particular importance, RA almost always spares the distal interphalangeal (DIP) joints (in contrast, these joints are often involved in osteoarthritis and psoriatic arthritis).

Less commonly, and usually only in more advanced cases, RA may involve the temporomandibular, cricoarytenoid and sternoclavicular joints. RA may involve the upper part of the cervical spine, particularly the C1–C2 articulation, but unlike the spondyloarthropathies, rarely if ever involves the rest of the spine. Patients with RA are, however, at an increased risk for osteoporosis, and this risk should be considered and dealt with early.

The hands are a major site of involvement in almost all patients with RA; hand involvement is responsible for a significant portion of the disabilities caused by RA. Typical early disease is with the swelling of the PIP joints easily seen.

The DIP joints are almost always spared unless the patient also has osteoarthritis; both diseases are common and can coexist, particularly in elderly patients. Radiographs can detect evidence of articular damage early in the course of disease and long before the appearance of joint deformities. Late established disease all too commonly causes ulnar deviation of the fingers at the MCPs and swan-neck deformities (hyperextension of the PIP joints; Figure 15–2B). Boutonnière (or buttonhole) deformities of the fingers result from hyperextension of the MCP joints. If the clinical disease remains active, hand function will slowly deteriorate.

Wrists are involved in most patients with RA. Early in the course of the disease, synovial proliferation in and around the wrists can compress the median nerve, causing carpal tunnel syndrome. Chronic synovitis can lead to radial deviation of the wrist, and in severe cases, to volar subluxation. Synovial proliferation of the wrist can invade extensor tendons, leading to rupture and abrupt loss of function of individual fingers.

The feet, particularly the MTP joints, are involved early in almost all cases of RA and are second only to hand involvement in terms of the problems they cause. Radiographic erosions occur at least as early in the feet as in the hands. Subluxation of the toes at the MTP joints is common and leads to the dual problem of skin ulceration on the top of the toes and painful ambulation because of loss of the cushioning pads that protect the heads of the metatarsals. Symptoms from MTP subluxation can respond to orthotics but may require surgery.

Involvement of large joints (knees, ankles, elbows, hips, and shoulders) is common but generally occurs somewhat later than small joint involvement. Characteristically, the entire joint surface is involved in a symmetric fashion. Therefore RA is not only symmetric from one side of the body to the other, but is also symmetric within the individual joint. In the case of the knee the medial and lateral compartments are both severely narrowed in RA, whereas osteoarthritis usually involves only one compartment.

Total joint replacements of hips and knees can dramatically improve function and quality of life and should be considered in patients with severe mechanical damage.

Synovial cysts present as fluctuant masses around involved joints (large or small). Synovial cysts from the knee are perhaps the best examples of this phenomenon. The inflamed knee produces excess synovial fluid that can accumulate posteriorly because of a one-way valve effect between the knee joint and the popliteal space (popliteal or Baker cyst).

Baker cysts cause problems by compressing the popliteal nerve, artery, or veins; by dissecting into the tissues of the calf (usually posteriorly); and by rupturing into the calf. Dissection usually produces only minor symptoms such as a feeling of fullness. Rupture of a Baker cyst, however, leads to extravasation of the inflammatory contents into the calf, producing significant pain and swelling that may be confused with thrombophlebitis (the so-called pseudothrombophlebitis syndrome).

Ultrasonography of the popliteal fossa and calf is useful to confirm the diagnosis and to rule out thrombophlebitis, which may be precipitated by popliteal cysts. Short-term treatment of popliteal cysts usually involves injecting the knee with glucocorticoids to interrupt the inflammatory process.

Although most of the spine is spared in RA, the cervical spine (especially the C1–C2 articulation) is not. As with RA elsewhere, bony erosions and ligament damage can occur in this area and can lead to subluxation. Most often, subluxation is minor, and patients and caregivers need only be cautious and avoid forcing the neck into positions of flexion. Occasionally, C1–C2 subluxation is severe and requires complex surgical intervention in an attempt to prevent compromise of the cervical cord, and in some cases, death.

Wherever synovial tissue exists, RA may cause problems; the temporomandibular, cricoarytenoid, and sternoclavicular joints are examples. The cricoarytenoid joint is responsible for abduction and adduction of the vocal cords. Involvement of this joint may lead to a feeling of fullness in the throat, to hoarseness, or rarely to a syndrome of acute respiratory distress with or without stridor when the cords are essentially frozen in a closed position. In this latter situation, emergent tracheotomy may be life-saving.

Rheumatoid arthritis – general considerations

Rheumatoid arthritis (RA) is the second most common form of chronic arthritis and affects approximately 1% of the adult population worldwide. This potentially crippling disease shortens survival, and most importantly, significantly compromises quality of life in most affected patients. RA is an inflammatory disease of unknown etiology, and most patients have systemic features such as fatigue, low-grade fevers (up to 38°C), anemia, and elevations of acute phase reactants (erythrocyte sedimentation rates and C-reactive protein levels).

Despite these systemic features, the primary target of this disease is the synovium. Some clinicians have likened RA to a cancer of the synovial tissues because these proliferate in an uncontrolled fashion, resulting in excess fluid production, erosion of surrounding bone, and damage to tendons and ligaments.

Swelling – definition

The hallmark of inflammation is swelling, which, when present in a joint, indicates that arthralgia has become arthritis. An increase in synovial fluid causes generalized joint swelling unless fluid accumulates in a contiguous synovial pouch (eg, suprapatellar space) or bursa (eg, gastrocnemius-semimembranous popliteal bursa [Baker cyst). Inflammation of a tendon sheath may cause soft, localized para-articular swelling. Soft tissue edema tends to be more diffuse.

Well-defined swelling over a bony prominence such as the olecranon process or patella may represent an inflamed subcutaneous bursa, a rheumatoid nodule, a gouty tophus, or rarely, a xanthoma or an amyloid deposit. Bony enlargements (osteophytes) adjacent to joints are typical of osteoarthritis and occur as a result of cartilage damage. Occasionally, such overgrowths are a product of chronic inflammation. Osteophytes may be palpable and visible at the distal interphalangeal and proximal interphalangeal (PIP) joints, where they are called Heberden and Bouchard nodes, respectively.

Peptic ulcer disorder

Burning epigastric pain exacerbated by fasting and improved with meals is a symptom complex associated with peptic ulcer disease (PUD). An ulcer is defined as disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation. Ulcers occur within the stomach and/or duodenum and are often chronic in nature. Acid peptic disorders are very common in the United States, with 4 million individuals (new cases and recurrences) affected per year.

Lifetime prevalence of PUD in the United States is ~12% in men and 10% in women. Moreover, an estimated 15,000 deaths per year occur as a consequence of complicated PUD. The financial impact of these common disorders has been substantial, with an estimated burden on direct and indirect health care costs of ~$10 billion per year in the United States.

Gastric anatomy – short description

The gastric epithelial lining consists of rugae that contain microscopic gastric pits, each branching into four or five gastric glands made up of highly specialized epithelial cells. The makeup of gastric glands varies with their anatomic location. Glands within the gastric cardia comprise <5% of the gastric gland area and contain mucous and endocrine cells. The majority of gastric glands (75%) are found within the oxyntic mucosa and contain mucous neck, parietal, chief, endocrine, and enterochromaffin cells. Pyloric glands contain mucous and endocrine cells (including gastrin cells) and are found in the antrum.

The parietal cell, also known as the oxyntic cell, is usually found in the neck, or isthmus, or the oxyntic gland. The resting, or unstimulated, parietal cell has prominent cytoplasmic tubulovesicles and intracellular canaliculi containing short microvilli along its apical surface. H+, K+-ATPase is expressed in the tubulovesicle membrane; upon cell stimulation, this membrane, along with apical membranes, transforms into a dense network of apical intracellular canaliculi containing long microvilli. Acid secretion, a process requiring high energy, occurs at the apical canalicular surface. Numerous mitochondria (30 to 40% of total cell volume) generate the energy required for secretion.

Physiology of Gastric Secretion

Hydrochloric acid and pepsinogen are the two principal gastric secretory products capable of inducing mucosal injury. Acid
secretion should be viewed as occurring under basal and stimulated conditions. Basal acid production occurs in a circadian pattern, with highest levels occurring during the night and lowest levels during the morning hours. Cholinergic input via the vagus nerve and histaminergic input from local gastric sources are the principal contributors to basal acid secretion. Stimulated gastric acid secretion occurs primarily in three phases based on the site where the signal originates (cephalic, gastric and intestinal).

Sight, smell, and taste of food are the components of the cephalic phase, which stimulates gastric secretion via the vagus nerve. The gastric phase is activated once food enters the stomach. This component of secretion is driven by nutrients (amino acids and amines) that directly stimulate the G cell to release gastrin, which in turn activates the parietal cell via direct and indirect mechanisms. Distention of the stomach wall also leads to gastrin release and acid production.

The last phase of gastric acid secretion is initiated as food enters the intestine and is mediated by luminal distention and nutrient assimilation. A series of pathways that inhibit gastric acid production are also set into motion during these phases. The gastrointestinal hormone somatostatin is released from endocrine cells found in the gastric mucosa (D cells) in response to HCl.

Somatostatin can inhibit acid production by both direct (parietal cell) and indirect mechanisms [decreased histamine release from enterochromaffin-like (ECL) cells and gastrin release from G cells. Additional neural (central and peripheral) and hormonal (secretin, cholecystokinin) factors play a role in counterbalancing acid secretion. Under physiologic circumstances, these phases are occurring simultaneously.

The acid-secreting parietal cell is located in the oxyntic gland, adjacent to other cellular elements ( ECL1 cell, D cell) important in the gastric secretory process. This unique cell also secretes intrinsic factor (IF). The parietal cell expresses receptors for several stimulants of acid secretion including histamine (H 2), gastrin (cholecystokinin B/gastrin receptor), and acetylcholine (muscarinic, M 3). Each of these are G protein-linked, seven transmembrane-spanning receptors.

Binding of histamine to the H2 receptor leads to activation of adenylate cyclase and an increase in cyclic AMP. Activation of the gastrin and muscarinic receptors results in activation of the protein kinase C/phosphoinositide signaling pathway. Each of these signaling pathways in turn regulates a series of downstream kinase cascades, which control the acid-secreting pump, H+, K+-ATPase. The discovery that different ligands and their corresponding receptors lead to activation of different signaling pathways explains the potentiation of acid secretion that occurs when histamine and gastrin or acetylcholine are combined. More importantly, this observation explains why blocking one receptor type (H 2) decreases acid secretion stimulated by agents that activate a different pathway (gastrin, acetylcholine).

Parietal cells also express receptors for ligands that inhibit acid production (prostaglandins, somatostatin, and EGF2). The enzyme H+, K+-ATPase is responsible for generating the large concentration of H +. It is a membrane-bound protein that consists of two subunits, a and ß. The active catalytic site is found within the a subunit; the function of the ß subunit is unclear. This enzyme uses the chemical energy of ATP to transfer H + ions from parietal cell cytoplasm to the secretory canaliculi in exchange for K +. The H+,K+-ATPase is located within the secretory canaliculus and in nonsecretory cytoplasmic tubulovesicles. The tubulovesicles are impermeable to K +, which leads to an inactive pump in this location. The distribution of pumps between the nonsecretory vesicles and the secretory canaliculus varies according to parietal cell activity. Under resting conditions, only 5% of pumps are within the secretory canaliculus, whereas upon parietal cell stimulation, tubulovesicles are immediately transferred to the secretory canalicular membrane, where 60 to 70% of the pumps are activated. Proton pumps are recycled back to the inactive state in cytoplasmic vesicles once parietal cell activation ceases.

The chief cell, found primarily in the gastric fundus, synthesizes and secretes pepsinogen, the inactive precursor of the proteolytic enzyme pepsin. The acid environment within the stomach leads to cleavage of the inactive precursor to pepsin and provides the low pH (<2.0) required for pepsin activity. Pepsin activity is significantly diminished at a pH of 4 and irreversibly inactivated and denatured at a pH of =7. Many of the secretagogues that stimulate acid secretion also stimulate pepsinogen release. The precise role of pepsin in the pathogenesis of PUD3 remains to be established.

Sinus node disfunction

The SA node is normally the dominant cardiac pacemaker because its intrinsic discharge rate is the highest of all potential cardiac pacemakers. Its responsiveness to alterations in autonomic nervous system tone is responsible for the normal acceleration of heart rate during exercise and the slowing that occurs during rest and sleep. Increases in sinus rate normally result from an increase in parasympathetic tone acting via muscarinic receptors and/or an increase in sympathetic tone acting via ß-adrenergic receptors.

Slowing of the heart rate is normally due to opposite alterations. In adults, the normal sinus rate under basal conditions is 60 to 100
beats/min. Sinus bradycardia is said to exist when the sinus rate is <60 beats/min, and sinus tachycardia when it is >100 beats/min.

However, there is wide variation among individuals, and rates <60 beats/min do not necessarily indicate pathologic states. For example, trained athletes often exhibit resting rates <50 beats/min due to increases in vagal tone. Normal elderly individuals may also show marked sinus bradycardia at rest.

Polyarteritis Nodosa – Treatment

In patients with idiopathic PAN, glucocorticoids and cytotoxic agents remain the cornerstones of treatment. Approximately half of patients with PAN achieve remissions or cures with high doses of glucocorticoids alone. Cyclophosphamide (eg, 2 mg/kg/d orally or 0.6 g/m2/mo intravenously, decreased in the setting of renal dysfunction) is indicated for patients whose disease is refractory to corticosteroids or who have serious involvement of major organs. Prophylaxis against Pneumocystis jiroveci pneumonia is an important consideration in patients treated with these medications.

Treatment of HBV-associated PAN with immunosuppressive agents has deleterious long-term effects on the liver. Fortunately, the availability of effective antiviral agents has revolutionized the treatment of HBV-associated cases in recent years. One effective strategy involves the initial use of prednisone (1 mg/kg/d) to suppress the inflammation. Patients begin 6-week courses of plasma exchange (approximately three exchanges per week) simultaneously with the start of prednisone. The doses of glucocorticoids are tapered rapidly (over approximately 2 weeks), followed by the initiation of antiviral therapy (eg, lamivudine 100 mg/d).