Medicine Updates

·         There are six stages of behavior change in addicted personalities:

1.       Precontemplation = Denies problem; no intention of changing

2.       Contemplation = Acknowledges problem; seriously thinks about solving it

3.       Preparation = Committed to action; needs to plan

4.       Action = Modifies behavior and surroundings

5.       Maintenance = At risk for relapse if not committed

6.       Termination = No continuing effort needed; addiction no longer a threat

·         The SAFE questionnaire may be used to screen for domestic violence:

S = Do you feel Safe or Stressed in a relationship?

A = Have you ever been Abused or Afraid in a relationship?

F = Are your Friends and Family aware of your relationship problem?

E = Do you have an Emergency plan if needed?

·         CRAFFT Mnemonic Tool: SCREENING FOR SUBSTANCE ABUSE DISORDERS.

·         Hand held echocardiography has recently been developed that allows for echocardiographic images to be displayed on devices not much larger than a pocket-sized personal digital assistant (PDA). These may evolve into useful tools to document structural heart disease at the bedside

·         two additional entities have been added to the list: a transient cardiomyopathy due to high catecholamine discharge (Tako-Tsubo cardiomyopathy) and an embryologic defect resulting in massive trabeculation in the LV (ventricular noncompaction).

·         Cardiomyopathy of Pregnancy (Peripartum Cardiomyopathy)

In approximately one of 4000–15,000 patients, dilated cardiomyopathy develops in the final month of pregnancy or within 6 months after delivery. The cause is unclear, but immune and viral causes have been postulated. More recently, it has been noted that the disease may be related to a cathepsin-D cleavage product of the hormone prolactin- suggesting blockage of prolactin may be a potential therapeutic strategy if proven in clinical trials using bromocriptine. The disease occurs more frequently in women over age 30 years, is generally related to the first or second pregnancy, and is associated with gestational hypertension and drugs used to stop uterine contractions. The course of the disease is variable; many cases improve or resolve completely over several months, but others progress to refractory heart failure. About 60% of patients make a complete recovery. Immunosuppressive therapy has been advocated, but few supportive data are available. Recently, -blockers have been administered judiciously to these patients, with at least anecdotal success. Some advocate anticoagulation because of an increased risk for thrombotic events. Recurrence in subsequent pregnancies is common, particularly if cardiac function has not recovered

·         Recently, a predictive rule has been developed that allows a clinician to exclude a lower extremity DVT in patients without an ultrasound if the patient has low pretest probability for DVT and has a negative sensitive D-dimer test (the "Wells rule").

·         A recent multivariate analysis found that the Model for End-stage Liver Disease (MELD) score (which incorporates bilirubin and creatinine levels, and the prothrombin time expressed as the International Normalized Ratio) was the strongest predictor of postoperative mortality and outperformed the Child-Turcotte-Pugh classification. Patients with a MELD score above the median score of 8 had a 30-day mortality risk exceeding 10%. A conservative approach would be to avoid elective surgery in patients with Child-Turcotte-Pugh class C cirrhosis or in patients with a MELD score greater than 8. In addition, when surgery is elective, it is prudent to attempt to reduce the severity of ascites, encephalopathy, and coagulopathy preoperatively.

·         Recently, the lymphocyte-white blood cell count ratio has been reported to efficiently and specifically differentiate tonsillitis from infectious mononucleosis. With about 90% sensitivity, lymphocyte ratios of greater than 35% suggest EBV infection.

·         Since renin cleavage of angiotensinogen is the rate-limiting step in the renin-angiotensin cascade, the most efficient inactivation of this system would be expected with renin inhibition, but this option has only recently become available. Conventional ACE inhibitors and ARBs probably offer incomplete blockade, even in combination. Aliskiren, a renin inhibitor, was recently approved by the FDA for use as monotherapy or combination therapy of hypertension. This drug binds the proteolytic site of renin, thereby preventing cleavage of angiotensinogen. As a consequence, levels of angiotensins I and II are reduced and renin concentration is increased. Aliskiren is synergistic with diuretics, ACE inhibitors, and ARBs in lowering blood pressure. Whether renin inhibition offers real advantages over conventional drugs remains to be demonstrated

·         Posttransfusion purpura (PTP) is a rare disorder that features sudden-onset thrombocytopenia in an individual who recently has received transfusion of red cells, platelets, or plasma within 1 week prior to detection of thrombocytopenia. Antibodies against the human platelet antigen Pl^A1 are detected in most individuals with PTP. Patients with PTP almost universally are either multiparous women or persons who have received transfusions previously. Severe thrombocytopenia and bleeding is typical. Initial treatment consists of administration of IVIG (1 g/kg/d for 2 days) should be administered as soon as the diagnosis is suspected. Platelets are not indicated unless severe bleeding is present, but if they are to be administered, HLA-matched platelets are preferred. A second course or IVIG, plasma exchange, corticosteroids, or splenectomy may be used in case of refractoriness. Pl^A1-negative or washed blood products are preferred for subsequent transfusions

·         Recently, a randomized, placebo-controlled study has demonstrated efficacy of the novel prokinetic agent itopride in the treatment of functional dyspepsia. This agent enhances the release of gastric acetylcholine through dual inhibition of D₂ receptors and acetylcholinesterase

·         The FDA has recently approved a bipolar probe (HALO) for Barrett’s esophagus that uses radiofrequency wave energy for thermal ablative therapy. Preliminary studies with this probe demonstrate complete eradication of Barrett epithelium in up to 70% of patients without significant complications. Further long-term studies are needed to establish the role of ablative therapy in patients with Barrett esophagus without dysplasia.

·         Recent studies suggest that proton pump inhibitors that are metabolized by CYP2C19 may inhibit activation of clopidogrel, reducing its antiplatelet effects.

·         Recently, mutations in the MYH gene, a gene involved with base excision repair, have been identified in patients with the classic and attenuated forms of FAP who do not have mutations of the APC gene. FAP due to MYH mutation is inherited in an autosomal recessive fashion, hence a family history of colorectal cancer may not be evident. Of patients with classic FAP, approximately 90% have a mutation in the APC gene and 8% in the MYH gene

·         Etravirine is the most recently approved NNRTI for the treatment of patients with prior NNRTI intolerance or resistance. The DUET trials demonstrated potent and durable antiviral activity in patients with NNRTI resistance to "first-generation" NNRTIs

·         Recent studies, however, suggest that rasagiline, 1 mg daily, slows progression of Parkinson disease

·         There have been recent reports of juvenile spinal muscular atrophy due to hexosaminidase deficiency, with abnormal findings on rectal biopsy and reduced hexosaminidase A in serum and leukocytes.

·         D-cycloserine (DCS), an antituberculosis drug, has recently been investigated as an augmenting agent in exposure treatment in Phobia. As a partial agonist at the NMDA receptor in the amygdala, DCS may be useful in reducing fear responses. Importantly, such medications must be used in combination with cognitive behavioral exposure strategies

·         Recently, experimental work has suggested a role for deep brain stimulation in OCD.

·         Most patients with type 1 diabetes mellitus have circulating antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GAD65), and tyrosine phosphatases (IA-2 and IA2-) at the time the diagnosis is made. These antibodies facilitate screening for an autoimmune cause of diabetes, particularly screening siblings of affected children, as well as adults with atypical features of type 2 diabetes. An additional autoantibody to a zinc transporter ZnT8 (Slc30A8) was recently found to be present in about 28% of type 1 diabetes patients who were negative for the other antibodies. Screening with zinc transporter, GAD65, IA2 and IAA autoantibodies may identify about 98% of people who have an autoimmune basis for their beta cell loss. Antibody levels decline with increasing duration of disease. Also, low levels of anti-insulin antibodies develop in almost all patients once they are treated with insulin

·         Serum fructosamine is formed by nonenzymatic glycosylation of serum proteins (predominantly albumin). Since serum albumin has a much shorter half-life than hemoglobin, serum fructosamine generally reflects the state of glycemic control for only the preceding 1–2 weeks. Reductions in serum albumin (eg, nephrotic state or hepatic disease) will lower the serum fructosamine value. When abnormal hemoglobins or hemolytic states affect the interpretation of glycohemoglobin or when a narrower time frame is required, such as for ascertaining glycemic control at the time of conception in a diabetic woman who has recently become pregnant, serum fructosamine assays offer some advantage. Normal values vary in relation to the serum albumin concentration and are 1.5–2.4 mmol/L when the serum albumin level is 5 g/dL

·         Persistent Islet Hyperplasia (Noninsulinoma Pancreatogenous Hypoglycemia Syndrome)

In a very small number of patients with organic hyperinsulinism, islet hyperplasia rather than an adenoma is present. These patients typically have documented hyperinsulinemic hypoglycemia after meals but not with fasting up to 72 hours. The patients have a positive response to calcium-stimulated angiography. A gradient-guided partial pancreatectomy leads to clinical remission, and the pathology of the pancreas shows evidence of islet hyperplasia and nesidioblastosis. These patients do not have mutations in the Kir 6.2 and SUR1 genes, which has been reported in children with familial hyperinsulinemic hypoglycemia

·         In adult patients, however, a recent unintentional change in body weight is usually a better index of undernutrition than a low BMI. This change is best expressed as a percentage of usual weight lost per unit of time. A weight loss of 10% or more of usual weight within a period of 1–2 months is generally considered to be predictive of a poor clinical outcome

·         Bocavirus, another parvovirus, was recently uncovered as a cause of winter acute respiratory disease in children and adults

·         A recent study found that HIV-positive patients with a nontreponemal antibody titer 1:32 had a sixfold increased risk of having neurosyphilis, and if the CD4 count was 350/mcL, there was a threefold increased risk of neurosyphilis, suggesting that these subgroups should also undergo lumbar puncture

·         Recent studies indicate that intravenous artesunate has superior efficacy and better tolerability than intravenous quinine for severe malaria. Intravenous artesunate became available in the United States in 2007 on an investigational basis through the CDC (for enrollment call 770-488-7788); if approved, the drug is provided emergently from CDC Quarantine Stations. The drug is administered in four doses of 2.4 mg/kg over 3 days, every 12 hours on day 1, and then daily. If artesunate cannot be obtained promptly, severe malaria should be treated with intravenous quinidine. In endemic regions, if parenteral therapy is not available, intrarectal administration of artemether or artesunate is also effective

·         For P vivax and P ovale infections, chloroquine is used to eradicate erythrocytic forms, and if the G6PD level is normal, a 14-day course of primaquine is initiated to eradicate liver hypnozoites and prevent a subsequent relapse. Some strains of P vivax, particularly in New Guinea and Southeast Asia, are relatively resistant to primaquine. For this reason, the CDC has recently doubled the recommended dosage for primaquine to eradicate liver forms (to 52.6 mg primaquine phosphate, or 30 mg base/day), but it remains possible that liver forms may not be eradicated by a single treatment

·         No specific treatments have been developed for Fragile X Syndrome. Attention-deficit and hyperactivity symptoms can respond to standard therapy, and a recent trial of L-acetylcarnitine showed promise.

·         Melatonin is believed to have antioxidant, antineoplastic, and immunomodulatory activity, but there are insufficient clinical trial data to support its use for conditions other than insomnia and jet lag. Of interest, melatonin receptors have recently been demonstrated on pancreatic islet cells, which may help explain a link between disturbed sleep and glucose intolerance

·         Recent reviews have also concluded that acupuncture is not effective (or that data were inconclusive for) treating hypertension, hot flashes, epilepsy, insomnia, allergic rhinitis, Parkinson disease, restless leg syndrome, and dyspnea. What follows is a selection of some conditions for which patients commonly seek acupuncture care

·         Also noteworthy in recent years is research on respiratory biofeedback training, in contrast to traditional thermal or electrodermal biofeedback methods for blood pressure reduction. A particular pattern of device-assisted respiration practiced for 15 minutes daily has been shown in seven of eight small studies to lower ambulatory blood pressure. In 2002, the FDA approved a simple device (RESPeRATE) to enable respiratory training for home use

·         Mindfulness meditation originated 2500 years ago in northern India from the tradition of Buddhism. It is a deliberate, sustained, nonjudgmental way of paying attention to one's experience that is said to enhance self-awareness, change maladaptive thinking, increase the capacity for skillful response to challenges, and reduce suffering. In 1979, mindfulness meditation practice was first introduced into American medical settings with the development of the MBSR program by Dr. Jon Kabat-Zinn. MBSR is an intensive 8-week program that introduces mindfulness practice in a secular, practical form to participants in the context of their life circumstances. There are now over 250 MBSR programs throughout the United States and many in other countries throughout the world. More recently, a close derivative of MBSR, mindfulness-based cognitive therapy (MBCT), has been developed exclusively for people with recurrent major depression. Mindfulness has also been adapted for use in programs for borderline personality disorder (Dialectical Behavior Therapy), eating disorders, substance abuse, and childbirth preparation

·         Telbivudine, the most recently approved agent, is also active against both lamivudine-susceptible and lamivudine-resistant isolates and comparative trials demonstrate clear superiority over lamivudine. The advantages over lamivudine include both viral suppression as well as normalization of ALT. Combination therapy with telbivudine and lamivudine does not offer any advantages over monotherapy with telbivudine. It is well absorbed by the oral route and food has no impact upon bioavailability. Telbivudine is administered once daily and patients with moderate to severe kidney disease require dosage adjustment. The adverse effect profile is comparable to that observed with other nucleoside analogs

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·         BENIGN RECURRENT INTRAHEPATIC CHOLESTASIS (BRIC)

This rare disorder is characterized by recurrent attacks of pruritus and jaundice. The typical episode begins with mild malaise and elevations in serum aminotransferase levels, followed rapidly by rises in alkaline phosphatase and conjugated bilirubin and onset of jaundice and itching. The first one or two episodes may be misdiagnosed as acute viral hepatitis. The disorder is familial and has an autosomal recessive pattern of inheritance. BRIC is considered a benign disorder in that it does not lead to cirrhosis or end-stage liver disease.

A gene termed FIC1 was recently identified and found to be mutated in patients with BRIC. Curiously, this gene is expressed strongly in the small intestine but only weakly in the liver. The protein encoded by FIC1 shows little similarity to genes that have been shown to play a role in bile canalicular excretion of various compounds. Rather, it appears to be a member of a P-type ATPase family that transports aminophospholipids from the outer to the inner leaflet of a variety of cell membranes. Its relationship to the pathobiology of this disorder remains unclear. A second phenotypically identical form of BRIC, termed BRIC type 2, has been described resulting from mutations in the bile salt excretory protein (BSEP), the protein that is defective in progressive familial intrahepatic cholestasis type 2.

·         PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS (FIC)

Progressive FIC type 1 (Byler diseas) presents in early infancy as cholestasis that may be initially episodic. However, in contrast to BRIC, Byler disease progresses to malnutrition, growth retardation, and end-stage liver disease during childhood. This disorder is also a consequence of a FIC1 mutation. The functional relationship of the FIC1 protein to the pathogenesis of cholestasis in these disorders is unknown. Progressive FIC type 2 is associated with a mutation in the protein named sister of p-glycoprotein, which is the major bile canalicular exporter of bile acids and is also known as bile salt excretory protein (BSEP). As noted above, some mutations of this protein are associated with BRIC type 2, rather than the progressive FIC type 2 phenotype. Progressive FIC type 3 has been associated with a mutation of MDR3, a protein that is essential for normal hepatocellular excretion of phospholipids across the bile canaliculus. Although all three types of progressive FIC have similar clinical phenotypes, only type 3 is associated with high serum levels of g-glutamyltransferase activity. In contrast, activity of this enzyme is normal or only mildly elevated in symptomatic BRIC and progressive FIC types 1 and 2.

·         Hypocupric Myelopathy: This recently described myelopathy is virtually identical to subacute combined degeneration and probably explains many cases previously described with normal serum levels of B12. Low levels of serum copper are found and often there is also a low level of serum ceruloplasmin. Some cases follow gastrointestinal procedures that result in impaired copper absorption, but many others are idiopathic. Improvement or at least stabilization may be expected with reconstitution of copper stores by oral supplementation. The pathophysiology and pathology are not known.

·         Chiropractic manipulation has been touted as a treatment for a number of conditions, including hypertension, asthma, menstrual pain, and fibromyalgia. However, very little data support its use for these conditions. Much of the current use of chiropractic care stems from its utility in cases of low back pain. A number of controlled trials on chiropractic treatment for low back pain have been done, with conflicting results. A meta-analysis suggested that research was insufficient to prove a benefit for acute or chronic low back pain. In general, however, patient satisfaction is high with chiropractic therapy. Patients with coagulopathy, osteoporosis, rheumatoid arthritis, spinal neoplasms, or spinal infections should be advised against such treatments. Serious complications have been reported as a result of cervical manipulation, including brain stem or cerebellar infarction, vertebral fracture, tracheal rupture, internal carotid artery dissection, and diaphragmatic paralysis. It is therefore difficult to advocate routine use of cervical manipulation for treatment of head and neck disorders.

·         Assessment of heart fatty acid-binding protein (H-FABP) identifies AMI less than 4hrs, with a sensitivity more than cardiac TrT, the lack of specificityin detecting AMI is obviously a major disadvantage of using H-FABP in this setting. H-FABP is also compared with several other biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP), d-dimer, high sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9), which gave no additional information to cTnT regarding early sensitivity.

The traditional marker of early myocardial injury, myoglobin, is not compared with H-FABP in the study, but was reported as less reliable than H-FABP in a previous study.

·         In fact, the intervention that has most consistently prolonged life span in most species is calorie restriction. Recently, it has been proposed that calorie restriction imposes a level of stress that activates proteins of the Sirtuin family, such as Sir2, that function as histone deacetylases. These proteins may deacetylate and thereby activate DNA repair enzymes, thus stabilizing the DNA; in the absence of these proteins, DNA is prone to damage.Decreased cellular replication. All normal cells have a limited capacity for replication, and after a fixed number of divisions cells become arrested in a terminally nondividing state, known as replicative senescence. Aging is associated with progressive replicative senescence of cells. Cells from children have the capacity to undergo more rounds of replication than do cells from older people. In contrast, cells from patients with Werner syndrome, a rare disease characterized by premature aging, have a markedly reduced in vitro life span.

·         Normally, glucocorticoid treatment does not suppress aldosterone secretion. However, an interesting recently described syndrome is glucocorticoid-remediable aldosteronism (GRA). This is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient. The hypersecretion of aldosterone and the accompanying hypertension are remedied when ACTH secretion is suppressed by administering glucocorticoids. The genes encoding aldosterone synthase and 11b-hydroxylase are 95% identical and are close together on chromosome 8. In individuals with GRA, there is unequal crossing over so that the 5 regulatory region of the 11b-hydroxylase gene is fused to the coding region of the aldosterone synthase. The product of this hybrid gene is an ACTH-sensitive aldosterone synthase.

·         An "anti-aging" protein called a-Klotho (named after Klotho, a daughter of Zeus in Greek mythology who spins the thread of life) has also recently been discovered to play important roles in calcium and phosphate homeostasis, in part by reciprocal effects on 1,25-dihydroxycholecalciferol levels. Mice deficient in a-Klotho displayed accelerated aging, decreased bone mineral density, calcifications, and hypercalcemia and hyperphosphatemia. a-Klotho plays an important role in stabilizing the membrane localization of proteins important in calcium and phosphate (re)absorption, such as TRPV5 and Na, K ATPase. Likewise, it enhances the activity of another factor, fibroblast growth factor 23 (FGF23), at its receptor. FGF23 thereby decreases renal NaPi-IIa and NaPi-IIc expression and inhibits the production of 1a-hydroxylase, reducing levels of 1,25-dihydroxycholecalciferol.

·         miRNAs target mRNAs for degradation as well. Much of this mRNA metabolism occurs in specific cytoplasmic structures termed P-bodies.

·         The MERCI (Mechanical Embolus Removal in Cerebral Ischemia) single-arm trial investigated the ability of a novel endovascular thrombectomy device to restore patency of occluded intracranial vessels within 8 h of ischemic stroke symptoms.

·         Interstitial cells of Cajal (ICCs) play an important role in the control of gut motility. ICCs have also been identified in the upper urinary tract of animals where they may both trigger motility and be responsible for pacemaker activity in this tissue. A recent study has investigated whether ICCs exist in the human upper urinary tract by analyzing the localization and distribution of the c-kit CD117 receptor, which is found in the ICC cell membrane.

·         use of the oral hypoglycemic agent glyburide has become popular for managing gestational diabetes refractory to nutritional management.

·         Activation of cells in the trigeminal nucleus results in the release of vasoactive neuropeptides, particularly calcitonin gene-related peptide (CGRP), at vascular terminations of the trigeminal nerve. Recently, antagonists of CGRP have shown some early promise in the therapy of migraine.

·         Familial forms of PPA with tau-negative ubiquinated inclusions have recently been linked to mutations of the progranulin gene on chromosome 17.

·         A newly characterized neuropeptide, hypocretin (orexin), has recently been implicated in the pathophysiology of narcolepsy (see below), but its role in normal sleep regulation remains to be defined.

·         FIFTH Taste identified more recently "umami" (monosodium glutamate, disodium gluanylate, disodium inosinate). This taste has actually been known for almost 100 years, and it became established once its receptor was identified. It is triggered by glutamate and particularly by the monosodium glutamate (MSG) used so extensively in Asian cooking. The taste is pleasant and sweet but differs from the standard sweet taste.

·         Binge eating disorder (BED) is a more recently described syndrome characterized by repeated episodes of binge eating, similar to those of BN, in the absence of inappropriate compensatory behavior.

·         NO-1 (CDC nonoxidizer group 1) is a recently identified bacterium associated with dog- and cat-bite wounds. Infections in which NO-1 has been isolated have tended to manifest locally (i.e., as abscess and cellulitis). These infections have occurred in healthy persons with no underlying illness and in some instances have progressed from localized to systemic illnesses. The phenotypic characteristics of NO-1 are similar to those of asaccharolytic Acinetobacter species; i.e., NO-1 is oxidase-, indole-, and urease-negative. To date, all strains identified have been shown to be susceptible to aminoglycosides, b-lactam antibiotics, tetracyclines, quinolones, and sulfonamides.

·         IGRAS: IFN –gamma Release Assays: Recently, two in vitro assays that measure T cell release of IFN-gamma  in response to stimulation with the highly tuberculosis-specific antigens ESAT-6 and CFP-10 have become commercially available. QuantiFERON-TB Gold® (Cellestis Ltd., Carnegie, Australia) is a whole-blood enzyme-linked immunosorbent assay (ELISA) for measurement of IFN-gamma, and T-SPOT.TB® (Oxford Immunotec, Oxford, UK) is an enzyme-linked immunospot (ELISpot) assay.

·         DC-SIGN :certain dendritic cells express a diversity of C-type lectin receptors on their surface, one of which is called DC-SIGN, that also binds with high affinity to the HIV gp120 envelope protein, allowing dendritic cell to facilitate the binding of HIV virus to the CD4+ T cell upon engagement of dendritic cells with CD4+ T cells .

·         TRIM5-ALPHA : It is a cytoplasmic protein found in rhesus macaque cells which blocks SIV simian immunodeficiency virus replication at a point shortly after the virus fuses with the host cell.

·         The term Ondine curse has been used to describe the syndrome of sleep apnea as a result of reduced respiratory drive, although the term central hypoventilation syndrome (CHS) is used more correctly. This rare condition is often associated with other abnormalities of brain-stem function. CHS can be idiopathic, or it can be a complication of an earlier insult to the developing brain. In some families, it is genetic. Children with CHS are initially treated by tracheostomy and mechanical ventilati on during sleep. Results with phrenic nerve pacing have been good in older infants and children.

·         The ketogenic diet is effective for the treatment of all seizure types, particularly in children with myoclonic forms of epilepsy. The diet involves supplying the majority of calories through fats with concurrent limitation of carbohydrates and protein. The mechanism of seizure control is unclear, but it is perhaps related to a switch in the cerebral metabolism from the use of glucose to the use of beta-hydroxybutyrate. After 24 hours of fasting, the child is placed on a high-fat diet in which the ratio of fats to carbohydrates and protein combined is 3-4:1. Anticonvulsant drugs may be reduced or eliminated entirely if the diet is effective. The regimen must be followed closely, and parents must understand the demands of close adherence to the diet. A skilled dietitian is instrumental for providing variety and palatability to the diet. It is important to recall that the diet may have adverse effects, including serious, potentially life-threatening complications such as hypoproteinemia, lipemia, and hemolytic anemia.

·         A skin condition called nephrogenic fibrosing dermopathy has recently been reported in which progressive subcutaneous induration, especially on the arms and legs, is described. The condition is similar to scleromyxedema and is seen in patients with CKD, most commonly on dialysis. Recent reports suggest that exposure to the magnetic resonance contrast agent, gadolinium, may precipitate this syndrome.

·         Nephrogenic Syndrome of Inappropriate Antidiuresis: Activating mutations of the V2R were recently described in two boys who presented with irritability and seizures within the first three months of life. Laboratory evaluation was significant for hyponatremia with inappropriately elevated urinary osmolality and undetectable vasopressin levels. Genomic analysis revealed missense mutations of AVPR2 causing constitutive activation of V2R and inappropriate water reabsorption.

·         Proton-pump inhibitors are an increasingly recognized culprit and have recently been implicated in up to half of cases of biopsy-proven acute tubulointerstitial nephritis.

·         ADAMTS 13 is a member of the recently recognized ADAMTS (a disintegrin with thrombospondin type 1 motifs) zinc metalloproteinase family that cleaves vWF complexes and prevents vWF-platelet interaction. A severe deficiency of ADAMTS 13 has been described in patients with TTP. Two forms have been identified: (1) In sporadic TTP, the deficiency appears to be autoimmune suppression of ADAMTS 13 by circulating IgG antibodies to the protein. (2) Schulman-Upshaw syndrome (a hereditary deficiency) is characterized by thrombocytopenia and microangiopathic hemolysis soon after birth, responding to plasma infusion.

·         development of K-x-ray fluorescence (KXRF) instruments for making safe in vivo measurements of lead levels in bone (which, in turn, reflect cumulative exposure over many years, as opposed to blood lead levels, which mostly reflect recent exposure). High bone lead levels measured by KXRF have been linked to increased risk of hypertension in both men and women from an urban population.

·         In the Gardner-Diamond syndrome (autoerythrocyte sensitivity), female patients develop large ecchymoses within areas of painful, warm erythema. Intradermal injections of autologous erythrocytes or phosphatidyl serine derived from the red cell membrane can reproduce the lesions in some patients; however, there are instances where a reaction is seen at an injection site of the forearm but not in the midback region. The latter has led some observers to view Gardner-Diamond syndrome as a cutaneous manifestation of severe emotional stress. More recently, the possibility of platelet dysfunction (as assessed via aggregation studies) has been raised.

·         Recently, elastrography has been proposed as a means of detecting early stages of liver fibrosis, but its reliability and reproducibility remain to be proven. Thus, at present early stages of fibrosis are detectable only by liver biopsy.

·         The nonspecific TNF inhibitor, pentoxifylline, recently demonstrated improved survival in the therapy of severe alcoholic hepatitis

·         PSTI, or SPINK1, is a 56-amino-acid peptide that specifically inhibits trypsin by physically blocking its active site. SPINK1 acts as the first line of defense against prematurely activated trypsinogen in the acinar cell. Recently, it has been shown that the frequency of SPINK1 mutations in patients with idiopathic chronic pancreatitis is markedly increased, suggesting that these mutations may be associated with pancreatitis.

·         IPEX (immunodysregulation, polyendocrinopathy, enteropathy X-linked) syndrome results from the failure to express the FOXP3 gene, which encodes a molecule critical in the differentiation of regulatory T cells.

·         A multicenter randomized phase III trial has recently been completed using eprodisate, designed to interfere with the interaction of AA amyloid protein with glycosaminoglycans in tissues and thus prevent or disrupt fibril formation. This drug is well tolerated and appears to markedly delay progression of AA renal disease, regardless of the underlying inflammatory process. Eprodisate is the first targeted inhibitor for diseases of protein misfolding and deposition to become available to patients.

·         Kenney-Caffey syndrome features hypoparathyroidism, short stature, osteosclerosis, and thick cortical bones. A defect seen in Middle Eastern patients, including Bedouin kindred, termed Sanjad-Sakati syndrome, also exhibits growth failure and other dysmorphic features. This syndrome, which is clearly autosomal recessive, involves a gene on chromosome 1q42-q43. Both syndromes apparently involve a chaperone protein, called TBCE, relevant to tubulin function.

·         Recently a splicing variant of the interleukin 7 receptor  chain, resulting in production of more soluble and less membrane-bound receptor, was found to be associated with susceptibility to multiple sclerosis (MS) in multiple different populations.

·         A recently published randomized trial found no added benefit of acyclovir (400 mg five times daily for 10 days) compared to prednisolone alone for treatment of acute Bell's palsy.

·         Two other cardiomyopathies recently classified as distinct entities include arrhythmogenic right ventricular dysplasia (ARVD) and left ventricular noncompaction.

·         The vagus nerve stimulator (VNS) is a recently developed treatment for medically intractable epilepsy. A pacemaker-like device is implanted below the clavicle on the left and attached to the left vagus nerve. A cycle of stimulation of the nerve is established (typically 30 seconds of stimulation every 5 minutes), which has an antiepileptic effect, reducing seizures by at least 50% in over half the children so treated. In addition, turning on the stimulator by the use of a magnet may interrupt a seizure (ie, an anticonvulsant effect). With current technology, the battery in the stimulator will last 7 or more years in many patients.

·         Transient myeloproliferative disorder is unique to patients with trisomy 21 or mosaicism for trisomy 21. It is characterized by uncontrolled proliferation of blasts, usually of megakaryocytic origin, during early infancy and spontaneous resolution. The pathogenesis of this process is not well understood, although mutations in the GATA1 gene have recently been implicated as initial events.

·         Recently, a new entity of low-grade tumor of childhood, the pilomyxoid astrocytoma has been recognized. Pilomyxoid astrocytomas seem to have a worse prognosis than juvenile pilocytic astrocytomas.

·         Although CVID is typically a diagnosis of exclusion, recent research has yielded multiple specific mutations that have previous been labeled simply as CVID. One example is a mutation in a member of the tumor necrosis factor receptor family, identified as transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), which mediates isotype switching in B lymphocytes. TACI mutations were recently found in 10–15% of patients with CVID, as well as in some relatives of CVID patients with IgA deficiency. The mutations appear to be autosomal dominant with variable penetrance of clinical immunodeficiency and disease.

·         Genes mutated in Marfan syndrome can also be mutated in related disorders: Beal syndrome (FBN2), Shprintzen-Goldberg Syndrome (FBN1) and the recently described Loeys-Dietz syndrome (TGFBR1 and 2).

·         Other overgrowth syndromes include Beckwith-Wiedemann syndrome (BWS), described earlier, and two single gene disorders, Simpson-Golabi-Behmel syndrome and Bannayan-Riley-Ruvalcaba syndrome. Patients with Simpson-Golabi-Behmel syndrome exhibit a BWS-like phenotype, but with additional anomalies, including polydactyly and more severe facial dysmorphism. Unlike patients with BWS, who have normal intelligence, patients with Simpson-Golabi-Behmel syndrome often have developmental delay. It is inherited as an X-linked disorder. Patients with Bannayan-Riley-Ruvalcaba syndrome have macrosomia, macrocephaly, and unusual freckling of the penis. They have mild developmental issues and may present with autism. They may develop hemangiomatous or lymphangiomatous growths and have a predisposition to intestinal malignancies. The cause of Bannayan-Riley-Ruvalcaba syndrome was recently found to be a mutation of the PTEN gene implicated in Cowden syndrome, the association of intestinal polyposis with malignant potential.

·         Rubinstein-Taybi syndrome is a genetic disorder of unknown cause, characterized by developmental delay, growth failure, and a distinctive facial dysmorphology comprising microcephaly, prominent nose, and small chin. Feeding problems are common. About 25% of patients have been found with a microdeletion of chromosome 16 detectable by FISH, but most patients have a normal karyotype.

·         Recently, there has been greater interest in the Stewart approach to acid-base disturbances and the calculation of the "strong ion difference”.

·         Calcium stimulates insulin release from insulinomas but not normal islets, and so a step-up of insulin levels regionalizes the hyperinsulinism to the head of the pancreas for the gastroduodenal artery, to the uncinate process for the superior mesenteric artery, and to the body and tail of the pancreas for the splenic artery. This technique may also provide data that are particularly helpful when multiple insulinomas are suspected (MEN 1) and it has become a major tool in confirming the diagnosis of diffuse islet hyperplasia in the recently described noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS)

·         Recently, it has been reported that the use of gatifloxacin in diabetic patients is associated with serious hypoglycemic and hyperglycemic reactions.

·         An epidemic of a novel syndrome with features suggestive of SSc occurred in Spain in the 1980s. The outbreak, termed toxic oil syndrome and affecting over 20,000 individuals, was linked to consumption of contaminated rapeseed oils used for cooking. A similar epidemic outbreak, termed eosinophilia-myalgia syndrome (EMS), occurred a decade later in the United States. Affected individuals presented with marked peripheral blood eosinophilia and severe myalgia, followed by the development of scleroderma-like chronic skin lesions. The epidemic was linked to the consumption of imported batches of L-tryptophan used as dietary supplements. The incidence rate of new cases of EMS showed a dramatic decline following the nationwide recall of L-tryptophan products. While both of these apparently novel toxic-epidemic syndromes were characterized by scleroderma-like chronic skin changes and variable visceral organ involvement, their clinical, pathological, and laboratory features clearly distinguished them from SSc.

·         Recently, the branched DNA (bDNA) a rapid assay for direct quantification of viral nucleic acid has been developed for hepatitis B, hepatitis C, and HIV infections. Because the bDNA assay measures viral nucleic acids at physiological levels by boosting the reporter signal, rather than by amplifying target sequences, it is not subject to the errors inherent in the amplification steps of PCR-based methods. Inherently quantitative and amenable to routine use in a clinical setting, the bDNA assay may be useful in the management of patients with chronic viral diseases. Recent studies have illustrated the potential clinical utility of the bDNA assay in determining the prognosis and in therapeutic monitoring of infection. Additional nucleic acid tests include hybrid capture and nucleic acid sequence-based amplification.