Accuracy of GFR Estimation in Obese Patients; Lemoine S, Guebre-Egziabher F, Sens F, Nguyen-Tu M, Juillard L, Dubourg L, Hadj-Aissa A; Clinical Journal of the American Society Nephrology, CJASN (Jan 2014)

BACKGROUND AND OBJECTIVES Adequate estimation of renal function in obese patients is essential for the classification of patients in CKD category as well as the dose adjustment of drugs. However, the body size descriptor for GFR indexation is still debatable, and formulas are not validated in patients with extreme variations of weight.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study included 209 stages 1-5 CKD obese patients referred to the Department of Renal Function Study at the University Hospital in Lyon between 2010 and 2013 because of suspected renal dysfunction. GFR was estimated with the Chronic Kidney Disease and Epidemiology equation (CKD-EPI) and measured with a gold standard method (inulin or iohexol) not indexed (mGFR) or indexed to body surface area determined by the Dubois and Dubois formula with either real (mGFRr) or ideal (mGFRi) body weight. Mean bias (eGFR-mGFR), precision, and accuracy of mGFR were compared with the results obtained for nonobese participants (body mass index between 18.5 and 24.9) who had a GFR measurement during the same period of time.
RESULTS Mean mGFRr (51.6±24.2 ml/min per 1.73 m(2)) was significantly lower than mGFR, mGFRi, and eGFRCKD-EPI. eGFRCKD-EPI had less bias with mGFR (0.29; -1.7 to 2.3) and mGFRi (1.62; -3.1 to 0.45) compared with mGFRr (8.7; 7 to 10). This result was confirmed with better accuracy for the whole cohort (78% for mGFR, 84% for mGFRi, and 72% for mGFRr) and participants with CKD stages 3-5. Moreover, the Bland Altman plot showed better agreement between mGFR and eGFRCKD-EPI. The bias between eGFRCKD-EPI and mGFRr was greater in obese than nonobese participants (8.7 versus 0.58, P<0.001).
CONCLUSIONS This study shows that, in obese CKD patients, the performance of eGFRCKD-EPI is good for GFR≤60 ml/min per 1.73 m(2). Indexation of mGFR with body surface area using ideal body weight gives less bias than mGFR scaled with body surface area using real body weight.

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Efficacy of Levofloxacin in the Treatment of BK Viremia: A Multicenter, Double-Blinded, Randomized, Placebo-Controlled Trial; Lee B, Gabardi S, Grafals M, Hofmann R, Akalin E, Aljanabi A, Mandelbrot D, Adey D, Heher E, Fan P, Conte S, Dyer-Ward C, Chandraker A; Clinical Journal of the American Society Nephrology, CJASN (Jan 2014)

BACKGROUND AND OBJECTIVES BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months.
RESULTS At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period.
CONCLUSIONS A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed. The BK virus was first isolated in 1971 from the urine of a renal transplant patient, initials B.K.[1] The BK virus is similar to another virus called the JC virus (JCV), since their genomes share 75% sequence similarity. Both of these viruses can be identified and differentiated from each other by carrying out serological tests using specific antibodies or by using a PCR based genotyping approach.

老年醫學: 維生素D可預防跌倒
(Geriatrics Society Guidelines: Vitamin D May Prevent Falls)
Older patients should receive sufficient vitamin D intake from all sources to lower their risk for falls and fractures, according to a new consensus statement published online December 18 in the Journal of the American Geriatrics Society. Dietary sources, sunlight, and supplements can all contribute to vitamin D levels of around 30 ng/mL (75 nmol/L), which appears to protect against fall-related injuries.
"In studies that achieved average serum levels greater than 25 ng/mL, falls and fracture rates were significantly reduced," James Judge, MD, chair of the American Geriatrics Society's (AGS's) Consensus Statement on Vitamin D Supplementation for Older Adults Work Group, told Medscape Medical News. "The impact on fractures is most likely due to the reduction in falls. In older adults, the impact of vitamin D on bone density is very small, while the impact on falls is measurable."
The consensus statement targets primary healthcare providers, aiming to help them ensure that community-dwelling and institutionalized older adults receive adequate vitamin D from all available sources. In addition to incorporating evidence from recent high-quality research, the statement is based on input from several medical organizations.
The health and well-being of older adults depends on fall and fracture prevention. Previously independent older adults often have to enter long-term care institutions because of repeated falls, and half of all nursing home residents older than 65 years have at least a single fall annually. Hip fracture is one of the most serious consequences of an elderly person falling, as it typically leads to long-term disability, untimely nursing home admission, and premature mortality.
Calcium absorption, healthy bone density, and physical function all require adequate vitamin D levels, and calcium is also vital for bone health. In addition, low Vitamin D levels are linked to muscle weakness, loss of bone strength, and falls and fractures.
Sources of vitamin D include fortified milk and other fortified foods, supplements, and production by the skin when exposed to sunlight (which becomes significantly less efficient with advancing age). In addition, sunlight exposure can cause skin cancer and excess exposure should be avoided. Therefore, the elderly are especially likely to need vitamin D supplementation.
The AGS workgroup agreed with the Endocrine Society (2011), the Osteoporosis Canada Statement (2010), and the majority opinion of the International Osteoporosis Foundation (2010) that a vitamin D [25(OH)D] serum concentration of 30 ng/mL (75 nmol/L) was safe and would ensure the full benefit of vitamin D for older adults.
"For the population of older adults, a total average daily intake from all sources (diet, supplement, and sunlight) of 4000 IU will ensure that 90% of the population will achieve serum 25(OD) D levels of 30 ng/mL," said Dr. Judge, who is also a member of the AGS Clinical Practice Committee, associate clinical professor of medicine at the University of Connecticut School of Medicine in Farmington, and senior medical director of Optum in Eden Prairie, Minnesota.
"This is the serum level that will maximize the protection from falls and fractures that vitamin D can provide," Dr. Judge continued. "The Institute of Medicine (IOM) determined that [a] 4000 IU daily supplement is safe and can be given without risk of toxicity."
The committee used dose–response calculations included in the 2011 IOM report to determine the total vitamin D intake that would achieve recommended serum levels in 92% or more of older adults.
Recommendations for Clinicians to Ensure Adequate Vitamin D Levels in Older Adults

• Review the report and the vitamin D dose–response curve indicating that 1000 IU daily will achieve recommended vitamin D levels in only half of older adults and that substantially higher doses are needed to achieve these levels in 90% of patients.
• Review older patients' vitamin D intake from dietary, sunlight, and supplement sources and discuss strategies to achieve a total vitamin D input of 4000 IU/day.
• Discuss strategies for adequate vitamin D and calcium supplementation with older adults and their caregivers. Available evidence does not support a recommendation for increased vitamin D supplementation without calcium for older people. Supplemental calcium doses in most studies range between 500 and 1200 mg daily.
• Help older adults and their caregivers choose the vitamin D and calcium supplementation schedule they are most likely to follow. Various vitamin D supplements may be taken daily, weekly, or monthly, and different combinations of calcium and vitamin D supplements are available.

"Vitamin D supplementation weekly, biweekly, monthly and up to every 3 months is OK," Dr. Judge said. "To maximize absorption, the vitamin D supplements should be taken with meals that provide some fat or oils. Understanding your patient's preferences will help you provide a dosing strategy that they can sustain."
Dr. Judge added that clinicians generally do not need to measure vitamin D levels in patients receiving adequate supplementation. The exceptions are patients with obesity, defined as a body mass index (BMI) higher than 30 kg/m² or body mass higher than 90 kg; malabsorption syndromes; and/or use of medications that either bind vitamin D in the gut or accelerate the breakdown of vitamin D. These medications include cholestyramine and inducers of the cytochrome P450 pathway, such as phenytoin and phenobarbital.
A table included in the AGS statement can help clinicians determine which patients are in need of higher supplement doses and how they can easily determine how much they need based on dietary, sunlight, and supplement exposure.
"We know that in populations, vitamin D levels in the late summer/fall are higher...and our best estimate is that the seasonal variation in total vitamin D generation from sunlight is roughly 1000 IU [a] day," Dr. Judge said. "We know that obese persons have lower vitamin D levels and will need more supplementation. Deeper pigmentation is associated with lower vitamin D levels, but there is evolving information (not available when the statement was completed) that vitamin D levels in African-Americans may not reflect the bioavailability of vitamin D."
Dr. Judge pointed out that most Americans report dietary intake of 150 to 225 vitamin D units daily, with the majority coming from fortified dairy products. Salmon, tuna, mackerel, sardines, and shitake mushrooms provide about 200 IU per serving. Milk products and fortified yogurts provide about 100 IU per 8-ounce (240 cc) serving.
When asked about the need for additional research, Dr. Judge commented that the recommendations of the AGS are based on limited evidence.
"It would be very helpful to clinicians if there were more accurate dosing algorithms than the one presented in this statement," he concluded. "There is limited evidence that 90% of normal-weight older adults (BMI < 25) will achieve recommended serum levels with 1600 to 2000 IU daily supplements. Overweight and obese adults require higher daily supplements — up to 4000 IU daily to achieve serum levels of 30 ng/mL."
Dr. Judge has disclosed no relevant financial relationships.
J Am Geriat Soc. Published online December 18, 2013. Full text

Hyperkalemia  (Serum K > 5.0 mEq/L or 5 mmol/L)
Signs & Symptoms of Hyperkalemia:
The symptoms of hyperkalemia are related to impaired neuromuscular transmission (nonspecific Sx).
The earliest findings are paresthesias and weakness, which can progress to paralysis affecting respiratory muscles. 鉀多感弱麻痺呼吸肌中樞無恙
These symptoms are similar to those seen with hypokalemia; cranial nerve function, however, characteristically remains unaffected.
EKG changes: increase T, S ,PR interval, QRS interval; decreased P, R, ST segment; 2-3 AV block; atrial or vent. arrhythmia

• Serum K 5.5 - 6.5 mEq/L: peaked T waves; prolonged PR segment
• Serum K 6.5 - 8.0 mEq/L: loss of P wave, prolonged QRS complex, ST-segment elevation, ectopic beats and escape rhythms
• Serum K > 8.0 mEq/L: progressive widening of QRS complex, sine wave, ventricular fibrillation, asystole, axis deviations, bundle branch blocks, fascicular

• Hyperkalemia ECG

  Hyperkalemia can cause life-threatening arrhythmia and thus recognizing hyperkalemia on the ECG is crucial. The ECG findings of hyperkalemia change as the potassium level increases. From slightly high levels to very high levels, ECG findings include:
  1.  Peaked T waves best seen in the precordial leads, shortened QT interval, and sometimes ST segment depression.
  

  

  2.  Widening of the QRS complex (usually potassium level is 6.5 or greater). This frequently appears as in "non-specific intraventricular conduction delay" or IVCD which is characterized by a widened QRS complex of > 120 ms that does not meet the criteria for a left or right bundle branch block. Frequently an IVCD will look like a left bundle branch block in lead V1 with a rS complex or monomorphic S wave and it appears like a right bundle branch block in leads I and V6 with a broad, slurred S wave.
  CLINICAL PEARL: If you see an IVCD, think of hyperkalemia.
  3.  Decreased amplitude of the P waves, an increase in the PR interval, and bradycardia in the form of AV blocks occur as the potassium level exceeds 7.0.
  CLINICAL PEARL: Supportive measurements like fluids, pacing, and pressors do not work in the setting of hyperkalemia. You must treat the hyperkalemia first.
  4.  Absence of the P waves and eventually a "sine wave" pattern (see below) which is frequently a fatal rhythm.
  

  

  CLINICAL PEARL: Giving intravenous calcium is "cardioprotective" in the setting of hyperkalemia. Frequently instant reversal of all hyperkalemic ECG changes within seconds of administration. Calcium does not decrease the potassium levels, so other therapy like bicarbonate or insulin is needed to do this. Calcium administration can be fatal when digoxin toxicity is causing hyperkalemia and should be avoided.
• Treatment of Hyperkalelmia   Discontinuance of all medications that adversely affect potassium balance is mandatory in true hyperkalemia, particularly when it is severe (plasma [K+] > 6.0 mEq/L).
  These medications include nonselective beta blockers, ACE inhibitors, potassium-sparing diuretics, NSAIDs, and trimethoprim. Salt substitutes, which contain potassium chloride, should also be avoided. Persons with mild hyperkalemia (plasma [K+] < 6.0 mEq/L) can usually be treated conservatively with reduction of daily intake to less than 2 g and, if indicated, with the addition of a loop diuretic. Algorithmic management of Hyperkalemia Is life-threatening hyperkalemia present? (ECG changes?  Serum K > 6.5 mEq/L? High-risk as renal failure, receiving dialysis, causative medications?) A.  If No (Life-threatening hyperkalemia is not present) --> Resin exchange with laxative, loop diuretic as furosemide, dialysis
  • Kayexalate (Na Polystyrene Sulfonate) 30 gm in 100 cc 20% sorbitol PO q3-4h. Kayexalate 50 gm in 200 cc 20% sorbitol retention enema 30- 60 min q 4- 6h (decreased 0.5-1 meqK)
  • Furosemide (Lasix) 40-80-160 mg IV
  • Dialysis
  B.  If Yes (life-threatening hyperkalemia is present)--> Step 1: Stabilize the myocardium: (IV Calcium infusion) 
  • IV Calcium Chloride (27.2 mg/dL calcium) or Calcium gluconate  (8.8 mg/dL calcium) 10 mL (1 amp) of 10% solution (500-1000 mg)
    IV infusion over 2-3 minutes.
    * Be extra careful when using calcium infusion in patients with concurrent digitalis toxicity, it could worsen brady-arrhythmia and potentially cause cardiac arrest; use EKG monitor.
    - for slow infusion, may give the calcium solution in 250 mL D5W and given over 30 minutes.
  Step 2: Shift potassium into cells:  (IV glucose +/- insulin +/- Na bicarbonate; Albuterol nebulizer Rx or IV infusion)
  • IV 25 - 50 gm of glucose (25-50 g = 1-2 ampules of 50% dextrose D50W or 250-500 mL of D10W solution) +/- IV Regular insulin 10 units
    - may add Na HCO3 7.5% 50 cc amp 1 -2 amp in the setting of substandial metabolic acidosis (bicarbonate <22 mEq/L)
    
  • Albuterol  nebulizer Rx can be administered at a dosage of 10 to 20 mg in 4 ml of saline by nasal inhalation over 10 minutes or by a 0.5 mg I.V. infusion.
    - Beta-agonists decrease plasma potassium levels.  Albuterol can be given via a nebulizer (10-20 mg in 4 mL of saline) or via IV infusion (0.5mg).  The dosages of B-agonists administered in this setting are relatively high, ranging from 4 to 8 times that recommended for Rx of an acute asthma exacerbation).  The major adverse effects are tremor, tachycardia, anxiety, and flushing.
  Step 3:  Enhance elimination of potassium:  (Kayexalte, Lasix, Dialysis)
  • Resin exchange with laxative: Kayexalate (Na Polystyrene Sulfonate) 30 gm in 100 cc 20% sorbitol PO q3-4h. Kayexalate 50 gm in 200 cc 20% sorbitol retention enema 30- 60 min q 4- 6h (decreased 0.5-1 meqK)
  • Loop diuretic as furosemide (Lasix) 40-80-160 mg IV
  • Hemodialysis - It is the Rx of choice for life-threatening hyperkalemia that is refractory to medical management.  It may decrease the serum K level by 1.0 - 1.5 mEq/L for each hour of dialysis.
  REF: Mayo Clinic Proceedings Dec 2007   * If aldosterone deficiency has been documented in cases of chronic hyperkalemia that are inadequately controlled by diet or diuretics, aldosterone replacement with fludrocortisone acetate may be useful. The combination of fludrocortisone and a loop diuretic may limit the development of hypertension or edema. However, because its onset of action may take several days or longer, this therapy is not sufficiently effective to be used in the treatment of acute, life-threatening hyperkalemia.
• Diff. Dx:A. Pseudohyperkalemia (Factitious hyperkalemia)
  1. Improper blood collection (lab error)
  2. Hematologic disorder with increased WBC or platelets B. Exogenous potassium load
  1. Oral or IV potassium supplement intake
  2. Potassium containing drugs
  3. Transfusion C. Decreased renal potassium excreation
  1. Renal failure: acute or chronic
  2. Potassium sparing diuretics or ACE-inhibitors
  3. Mineralocorticoid deficiency
      a. Addison's disease or  Bilateral adrenalectomy
      b. Hypoaldosteronism
         (1) Hyporeninemic hypoaldosteronism
         (2) Heparin therapy
         (3) Specific enzyme defect or Tubular unresponsiveness
  4. Congenital adrenal hyperplasia or Primary defect in potassium excretion D. Cellular shift of K+
  1. Tissue damage: trauma, burns, rhabdomyolysis;   Destruction of tumor tissue
  2. Acidosis
  3. Digitalis overdose; Hyperosmolality
  4. Hyperkalemic periodic paralysis
  5. Succinylcholine, Arginin infusion

含Pioglitazone成分藥品(泌特穩錠、泌特士錠)

什麼是Pioglitazone？

Pioglitazone是一種處方藥物，用來治療第二型糖尿病，可作為單一藥物使用，或與其他降血糖藥物合併使用。

Pioglitazone可以刺激胰島素在肝臟、肌肉組織、脂肪組織的作用，使血糖降低。

如果有下列情況，醫師應小心處方：

@對Pioglitazone或其他藥物曾發生異常過敏勿用。

@有心臟或肝臟疾病。禁忌用於重度心臟衰竭(紐約心臟協會訂定的第三級或第四級心衰竭狀態)。活動性肝疾病或肝功能ALT檢查值大於2.5倍正常上限值勿用。

@曾有膀胱癌病史。

@已知懷孕或計劃懷孕。

@正哺餵母乳或計劃哺餵母乳

@尚未進入更年期，卻已停經或經期不規律的婦女；使用Pioglitazone可能造成排卵恢復，必須考慮避孕措施。

@正在服用的所有藥物，包括處方藥和非處方藥，維生素、中草藥、健康食品。

行政院衛生署民國98年度統計資料顯示，

台灣每十萬人口的膀胱癌發生率，男性為12.19人，女性為5.09人。

此發生率統計是低於西方國家的。

膀胱癌的症狀可能有：血尿，頻尿與排尿時疼痛。

膀胱癌常發生在老年人，特別是男性。

以台灣健保資料庫分析糖尿病與膀胱癌關聯性的研究顯示，

糖尿病患者罹患膀胱癌的機率，比非糖尿病患者高；但與處方用藥使用目前尚無強烈證據證明相關。

病人如有以下症狀，請立即聯絡醫師或回診：

@低血糖。血糖濃度過低，可能會感到胸悶、頭暈、顫抖、飢餓感等。

@體液滯留造成水腫。

@體重增加。

@骨折，通常發生在女性的腳、手腕及手臂。

@黃斑部水腫，會造成視力模糊。

3-3 植物如何獲得養分

植物體獲得養分的途徑有以下二種：

（1）植物根部從土壤中吸收水分及礦物質（主要為氮、磷、鉀三類）。
（2）植物進行光合作用，自行合成的養分（剛合成時為醣類，而後再轉化為蛋白質及脂質）。



葉子的構造與功能

 葉子是植物行光合作用最主要的器官，葉子上的構造有以下幾種：
（1）上、下表皮：
    表皮細胞排列整齊，透明無色，細胞外具有角質層能夠防止水分散失。
    同時表皮亦能保護植物體避免受到病原體的感染。
（2）保衛細胞及氣孔：
    大多數植物的表皮上具有半月形的保衛細胞，保衛細胞兩兩成對，中間的部分則組成氣孔，保衛細胞藉由水分滲透進出細胞內外，來控制氣孔的開閉，而保衛細胞內亦具有葉綠體，可行光合作用。
    通常有光線的時候，氣孔會打開，植物體行光合作用所需的二氧化碳即是由氣孔進入植物細胞中，而製造出來的氧氣則從氣孔釋放到大氣之中，所以氣孔是植物體氣體進出的孔道。經觀察可以發現，陸生植物大多數的氣孔分佈於葉片的下表皮，如此可以減少水分過度的散失。
（3）葉脈：
    葉脈是由輸導組織（維管束）所組成，能將根部維管束所吸收的水分運送至葉子，提供葉子水分的來源，同時也作為光合作用中參與反應的物質。
    除此之外，葉脈中的維管束也能將光合作用所產生的養分運送至植物體全身，提供所有植物細胞利用。

（4）葉肉細胞：
    葉片中間含有綠色葉綠體的細胞，稱為葉肉細胞，是葉子進行光合作用的主要場所。

光合作用的過程
光合作用是指葉綠體中的葉綠素吸收太陽能，並將根部所吸收的水分和經由氣孔進來的二氧化碳合成為葡萄糖，並同時釋放出氧氣的過程。

整體光合作用的反應，依反應發生的先後，可分為兩個階段：第一階段為光反應、第二階段為暗反應，詳細過程敘述如下：
1、光反應（反應過程如下圖所示）：
第一階段的過程需要太陽光才能進行，所以稱為光反應。在光反應過程中葉綠素利用太陽光的能量，將水分解成氧氣、氫離子[氫]，同時並產生能量作為暗反應時的能量來源。所形成的氧氣藉由氣孔而釋放到大氣中，而氫離子[氫]及能量則繼續參與暗反應。

 2、暗反應（反應過程如上圖所示）：
第二階段因不需太陽光直接參與反應，稱為暗反應。暗反應利用光反應所產生的氫離子[氫]及能量，透過許多酵素的作用，將二氧化碳進行固定，轉換成葡萄糖和水，所產生的葡萄糖可直接提供細胞利用，來進行呼吸作用產生細胞所需的能量；除此之外，產生的葡萄糖亦可進一步合成為澱粉、蛋白質及脂質等其他養分，供植物體使用。

光合作用的生態系的重要性
1、植物行光合作用，將太陽光的光能轉化成葡萄糖的化學能，提供給大多數生物使用，使得生物體的細胞能夠得到能量而表現出生命的現象。光合作用串起了生命與環境間的橋樑，讓太陽光的能量可以提供給生物使用。
2、光合作用會吸收二氧化碳並釋放出氧氣，氧氣可以提供生物呼吸所需，所以光合作用對於維持大氣中氧氣與二氧化碳濃度的穩定具有重要的貢獻。

I introduce myself with this photograph.