Breast cancer

Breast cancer

Incidence

Carcinoma of the breast is the most common cancer in women in the United States (32%) and is second only to lung cancer as a cause of cancer death in women (15%).
Estimated new cases and deaths from breast cancer (women only) in the United States in 2005:

• New cases: 211,240.
• Deaths: 40,410.

The lifetime risk for women of being diagnosed with breast cancer is currently about 1 in 8.

Gender

Breast cancer is relatively uncommon in men; the female-to-male ratio is approximately 100:1.

Age

The risk of developing breast cancer increases with age. Only about 0.8% of breast cancers occur in women < 30 years old and approximately 6.5% develop in women between 30 and 40 years old. Most cases occur in patients over 40 years of age.

Race and ethnicity

White women have a higher overall rate of breast cancer than African-American women; however, this difference is not apparent until after menopause. American Asian and Hispanic women have approximately half the incidence of American Caucasian women. Native-American women extremely low risk of developing breast cancer.

Geography

The incidence of breast cancer is significantly higher in the United States and European countries such as the United Kingdom, Denmark, the Netherlands, New Zealand and Switzerland than in India, Japan, Thailand, Nigeria. It has been suggested that these trends in breast cancer incidence may be related to dietary fat consumption.

Nephrotic syndrome and Treatment

Nephrotic syndrome and Treatment 


Nephrotic syndrome and Treatment 

Definition

Nephrotic syndrome Is a clinical syndrome associated with proteinuria in the nephrotic range (3.5mg/m2/24hrs), edema and hyperlipidemia.

Nephrotic syndrome is not due to inflammatory processes but due to direct action of the membrane attack unit of complement on the glomerulus.

Clinical suspicion

It should be suspected when a patient presents with generalized oedema, protein detected in urine, hypoalbuminemia.

Diagnosis

The diagnosis maybe established with proteinuria in the nephrotic range alone without the other criteria.

1.  Proteinuria > 3.5 g/m2/day:
On detection of protein in urine a 24 hour urinary protein test is in order. There are two cut off values for this test: 1. increased urinary protein <1.5g/day; this is refered to as isolated proteinuria. 2. >3.5g/day; this establishes nephrotic syndrome.

2.  Hypoalbuminaemia

3.  Hyperlipidaemia:
As albumen in serum is lost through the kidneys, the liver increases its production of albumen and concomitantly increases the production of cholesterol.

4.  Oedema: resulting from loss of intravascular fluid to the extravascular space due decreased intravascular oncotic pressure (decreased albumen).

However, the presence of proteinuria in the nephrotic range (3.5g/day) establishes the diagnosis.

Differential diagnosis: proteinuria

Causes

Once the diagnosis of nephrotic syndrome is established the cause of the syndrome is sought in order to treat accordingly.

Nephrotic syndrome with active sediment (mixed nephrotic/ nephritic)

This denotes the presence of RBC casts (active sediment). Causes include:

1ry glomerular diseases as MPGN (main cause), and 2ry glomerular diseases as SLE (most common presentation of SLE), vasculitis such as Henoch Schonlein purpura, mixed essential cryoglobulinemia.

Nephrotic syndrome with bland sediment (Pure nephrotic)

1ry glomerular diseases such as MCNS, Membranous glomerulonephritis, Focal glomerulosclerosis. As well as 2ry glomerular diseases that result from Diabetes (Klemelsteli-Wilson syndrome) and amyloidosis.

Treatment

Treatment of nephrotic syndrome depends primarily on the cause, however, it frequently involves the use the glucorticoids given over long periods of time. Especially in cases of minimal change disease. Here the role of steroids is to suppress the autoimmune basis for this disease. The use of cytotoxic agents maybe required in some cases (e.g. cyclophosphamide).
Dietary salt control, treatment of hypertension and hypercholestrolemia is also recommended. ACE inhibitors, in addition to controlling blood pressure have also been found to decrease the protein loss. Diuretics may help control the edema and the hypertension.

Acute Renal Failure

Definition-Causes-Diagnosis

Definition

Renal failure depicts a group of diseases that may be associated with decreased GFR and manifested by retention of BUN and creatinine. Acute renal failure is defined as a rapidly (over a period of days) increasing creatinine level or decreasing urine output.

Causes

Causes of acute renal failure is caused by failure of the kidneys to perform their normal functions due to:

• Prerenal - Problems affecting the flow of blood before it reaches the kidneys
• Postrenal - Problems affecting the movement of urine out of the kidneys
• Renal - Problems with the kidney itself that prevent proper filtration of blood or production of urine 

Prerenal failure

This is by far the most common type of acute renal failure. Your kidneys do not receive enough blood to filter. Prerenal failure can be caused by the following conditions:

• Dehydration - From vomiting, diarrhea, water pills, or blood loss
• Disruption of blood flow to the kidneys - From a variety of causes
  • Drastic drop in blood pressure - From major surgery, severe injury or burns, or infection in the bloodstream (sepsis)
  • Blockage or narrowing of a blood vessel leading to the kidneys
  • Heart failure or heart attacks
  • Liver failure

There is no actual damage to the kidneys with prerenal failure. With appropriate treatment, it usually can be reversed. 

Postrenal failure

Postrenal renal failure is sometimes referred to as obstructive renal failure, since it is often caused by something blocking elimination of urine produced by the kidneys. This problem also can be reversed.
At the ureter level, this condition can be caused by the following:

• Kidney stone
• Cancer
• Medications

At the bladder level, the following conditions can cause obstruction:

• Kidney stone
• Enlarged prostate (the most common cause)
• Blood clot
• Bladder cancer
• Neurologic disorders of the bladder

Treatment consists of relieving the obstruction. Once the blockage is removed, the kidneys usually recover in 1-2 weeks if there is no infection or other problem.

Renal damage

Primary renal damage is the most complicated cause of renal failure. Renal causes of acute kidney failure can be subdivided into those affecting the filtering system of the kidney, those affecting the blood supply in the kidney, and those affecting kidney tissue.
Some of the kidney problems that can cause kidney failure include the following:

• Blood vessel diseases
• Blood clot in a vessel in the kidneys 
• Injury to kidney tissue and cells
• Glomerulonephritis
• Acute interstitial nephritis
• Acute tubular necrosis

Clinical manifestations

ARF passes through two phases 1. Destructive phase: oliguric and non-oliguric 2. Reconstructive phase: could be polyuric.

ARF due to pre-renal or renal causes (esp. ATN) usually presents as oliguric renal failure passing through the 3 phases of pathology:

1. Intitiation phase: due to the initiating insult on the kidney.
2. Maintenance phase: maintenance of oliguria (1-2 weeks).
3. Recovery phase: due to recovery of renal function (polyuria).

ARF due to other causes as partial obstruction may present as polyuria.
ARF due to postrenal obstruction may present as anuria.

Diagnosis

Renal failure is manifested by the rise of serum creatinine. The next step is to identify if chronic or acute renal failure. Then exclude if postrenal then identify if pre-renal or renal. If renal identify what type of intrisic renal disease ? if no diagnosis is reached then by exclusion the diagnosis is ATN.

1. Prerenal azotemia

• Urine/plasma creatinine ratio > 40
• Urinary Na decreased < 20
• Fractional excretion of Na is <1%
• Urine osmolarity is > 500

2. Renal azotemia

• Urine/plasma creatinine ratio < 20
• Urinary Na decreased > 40
• Fractional excretion of Na is >1%
• Urine osmolarity is > 350

?        These findings can be altered by diuretic use and urine sample should be taken before institution of diuretic use.

3. Postrenal azotemia

Post-renal azotemia develops only if the obstruction is bilateral or affects a solitary functioning kidney. During the early stages of obstruction, continued glomerular filtration leads to increased intra-luminal pressure proximal to the site of obstruction. As a result, there is gradual distension of the proximal ureters, renal pelvis and calyces and fall in glomerular filtration which will be evident by renal ultrasound.
N.B.: the level of creatinine in serum has nothing to do with whether the ARF is oliguric, anuric or non-oliguric: it is an indication that tubular function is lost as creatinine is not filtered- it is secreted. K+ and H+ are retained even in nonoliguric renal failure due to the same principal (they are both secreted and not filtered).

Treatment  

Treatment of acute renal failure usually should be conservative and largely supportive. It requires careful and precise management. All patients will require close monitoring, many of them within intensive care settings.
Supportive care includes stabilizing the patient, monitoring input and output strictly, weighing daily, determining electrolyte values frequently, preventing sepsis via reducing the number of intravenous lines and removing an indwelling urinary.

Therapy for prerenal failure

Rapid volume replacement and treatment of the underlying condition that resulted in prerenal failure are the cornerstones of therapy. Initial fluid administration of isotonic saline (0.9%) or 5% albumin (10 to 20 mL/kg per dose) should be used to restore intravascular volume. This can be both a diagnostic and a therapeutic trial. Fluid administration also can convert oliguric to nonoliguric renal failure in its early stage.

Therapy for postrenal failure

Therapy for postrenal failure includes removal of obstruction by decompression or diversion of the urinary tract, stabilization of electrolyte abnormalities, management of postobstructive diuresis, and therapy for voiding dysfunction and for urinary tract infection. Surgical intervention will require urologic consultation. The site of the obstruction will determine the approach: placement of a Foley catheter, vesicostomy, ureteral catheters (stents), or nephrostomy tubes.

Therapy for established renal failure

Maintaining Balance of Fluid and Electrolytes

In a euvolemic state, fluid intake, including water generated from endogenous metabolism (insensible fluid gain), is balanced by fluid output.

Treating Hypertension

Kidney failure in any form can present as hypertension and hypertensive encephalopathy. It is essential to lower the blood pressure quickly and safely. The blood pressure should be reduced by at least 25% within 1 hour with an antihypertensive medicine whose onset of action is rapid. It is advisable to start with one antihypertensive medicine and increase the dose to its maximum recommended level. Therapy is individualized and needs titration. In most cases, hypertension is the result of sodium and fluid retention, but other factors, such as activation of the renin-aldosterone-angiotensin II and/or the alpha-adrenergic system, may have roles in kidney failure.

Improved survival in AML with higher anthracycline doses

Improved survival in AML with higher anthracycline doses



Younger patients with acute myeloid leukemia (AML) that receive higher doses of anthracyclines during induction chemotherapy are reported to have better complete remission rates in most studies. As of yet, studies have failed to show an improved surivival when compared to the standard doses of the “7 and 3” regimen. This article reviews the results of a new randomized controlled trial exploring the effects of higher doses of anthracyclines on overall survival.

With the exception of the use of all trans-retinoic acid (ATRA) for patients with acute pro-myelocytic leukemia (APL), relatively few changes in the therapy of acute myeloid leukemia (AML) have been made since the introduction of the so-called “7 and 3” regimen in 1973.^{1, 2} The regimen is made up of 3 daily doses of daunorubicin at a dose of 45 mg/m2 combined with cytarabine for seven continuous daily doses at 100 mg/m2.^{1, 2}

The outcome to current therapy is suboptimal with only 60-70% of patients achieving their first complete remission. The median survival of patients who achieve remission is 12-24 months and the five year survival is achieved in only 20% of those patients.³ Attempts to find a superior alternative or improve the 7 and 3 induction regimen have been disappointing.^{4, 5} Both, the intensification of cytarabine dose^6-8 and the addition of other drugs, have failed to improve outcome when compared to “7 and 3”.⁹

That all changed this week, with the publication of the first conclusive evidence for better overall survival in patients receiving higher doses of daunorubicin (90 mg/m2) compared to the conventional dose (45 mg/m2) regimen. The Eastern Cooperative Oncology Group (ECOG) study, which appears this week in the New England Journal of Medicine,¹⁰ assigned 657 patients between the ages of 17 and 60 years with newly diagnosed AML to receive either the 7 and 3 induction regimen with conventional dose of  daunorubicin versus the higher dose. Those that achieved a complete remission were then given post remission therapy according to their risk stratification as well as the availability of an HLA matched sibling. Patients with unfavorable or intermediate risk profile were offered allogeneic transplant if they had an HLA matched sibling.^{11, 12} The remainder were offered high dose cytarabine with or without gemtuzumab ozgamicin, followed by an autologous transplant.¹³

An intention to treat analysis, with a median follow up of 25.2 months, revealed that 90 mg/m2 daunorubicin resulted in higher complete remission rates (70.6% vs. 57.3%, P=0.001) as well as improved median survival (23.7 vs. 15.7 months, P=0.003).

Interestingly, the rates of serious (grade 3 to 5) adverse events were similar in the two groups. Serious cardiac toxicity was observed in 7.2% in the standard dose arm compared to 7.9% in the high dose arm. A reduced left ventricular ejection fraction was observed in 1.3% of patients in the high dose group and none of the standard regimen group. The rate of treatment related mortality was 4.5% in the standard arm compared to 5.5% in the high dose arm (P=0.60). The most common cause of death was from infections and pulmonary failure.

Results

For those patients with a favorable cytogenetic profile that received the high dose, the median survival had not been reached at the time of the final analysis (median follow up of 25.2 months); thus, exceeding the current median survival of 12-24 months in patients who achieve remission.³ The largest difference was seen in those with intermediate risk who received the daunorubicin 90 mg/m2. Patients with unfavorable cytogenetic profile, however, did not experience any benefit from higher doses.

Conclusion

Patients with low and intermediate risk de novo AML should be offered 7 and 3 induction therapy with daunorubicin dose intensification at 90 mg/m2. This is both safe and effective in these patients but not associated with any benefit in patients with poor prognostic features. However, as the authors note, it is not yet clear what the optimal dose of intensification is. Whether 90 mg/m2 is better than 60 mg/m2, requires further study.

Conflict of interest statement

No financial conflicts or disclosures to report.

CITE THIS ARTICLE:
Tamer M. Fouad, M.D.. Improved survival in AML with higher anthracycline doses. Doctors Lounge Website. Available at: http://www.doctorslounge.com/index.php/articles/page/300. Accessed April 01 2012.

Iron deficiency anemia in pregnancy

Iron deficiency anemia in pregnancy

Anemia in pregnancy is defined as hemoglobin concentration < 10 g/dl during pregnancy and puerperium.  

Introduction

The pregnant woman needs 1000 mg iron all through pregnancy i.e. a daily amount of 3.5 mg to maintain iron balance. The iron requirement in the latter half of pregnancy and for several weeks after delivery increases to about 6-7 mg/day.
It is the most common form of anemia encountered during pregnancy. The incidence is higher in poorly nourished women of low socioeconomic standard.

Causes

• Depletion of iron stores as occurs in non-supplementation of diet.
• Multifetal pregnancy
• Deficient absorption e.g. achlorhydria
• Bleeding with pregnancy or ankylostoma infestation 

Diagnosis

Symptoms

• Weakness, loss of concentration
• Headache and loss of appetite
• Dyspnea and palpitations 

Examination

• Pallor (nails, lips, conjunctiva)
• Pulse: tachycardia and waterhammer pulse
• Cardiac examination: systolic murmurs
• Abdominal examination: splenomegaly 

Investigations

Complete blood picture shows a picture of hypochromic microcytic anemia:

• Low RBC count and hemoglobin 
• Color index and MCHC are decreased
• WBC and platelets are normal

Serum iron is decreased

New cause of sexual dysfunction in women revealed

New cause of sexual dysfunction in women revealed

Researchers at Yale School of Medicine and the Albert Einstein College of Medicine have found that female sexual dysfunction (FSD) affects 48.2 percent of women in a new study and that these women had decreased sensation in the clitoris, which increased the risk of sexual dysfunction.

"There is a paucity of data available on FSD and this study brings attention to the possibility of a neurological cause for the dysfunction," said lead author Kathleen Connell, M.D., assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.
Connell said previous epidemiological studies have shown that about 10 million women between the ages of 50 and 74 report abnormal sexual complaints, including decreased desire, inability to reach orgasm and increased pain with intercourse. In contrast to data on men, Connell said clinical trials evaluating the physiologic mechanisms responsible for sexual function in women are few, despite reports of other investigators, which suggest that sexual dysfunctions may be more common in women than men.
"The sexual response is complex and involves interaction between the nervous system, the vascular system and the musculoskeletal system," said Connell. "Alterations in any of these systems could potentially cause FSD."
The trial was conducted while Connell was at the Albert Einstein College of Medicine. The team studied the pudenal nerve, which provides nerve fibers to the pelvic floor muscles and is also responsible for sensation in the genital region. They evaluated the role of genital neurological integrity and sexual function in 56 women. They used a validated screening questionnaire to identify women between ages 18 and 68 with FSD and tested vibratory and pressure sensation in the genital region.
The team found that almost half of the women studied reported sexual dysfunction. Of the women with FSD, 23.2 percent had more than one form of sexual dysfunction. Those with sexual dysfunction had decreased sensation in the clitoris compared to asymptomatic women. 

Chest pain in young females Causes and diagnosis

Chest pain in young females Causes and diagnosis

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Chest pain is one of the common complaints heard in medical OPDs as well as at the GP?s clinic. Chest pain causes a lot of anxiety in the patient as it is many a time related to ?heart attack? or angina and people are quite aware of the serious consequences of the symptom. Anyone having a chest pain would first think of the heart and would like to know if he/she is having a ?heart attack?.

However not all times is a chest pain necessarily originating from or caused by diseases of the heart. There are plenty of other structures in the thoracic cavity and a systematic approach is needed to arrive at the correct diagnosis or in other words to find out the ?real culprit? causing the chest pain.
Of special importance is the issue of chest pain in women, as this group is less liable to get heart disease till menopause. Estrogen is said to confer a protective effect and prevents the development of atherosclerosis. Myocardial infarction or Coronary artery disease (CAD) is very rare in menstruating women. As menopause approaches and estrogen levels go down, the probability of development of CAD catches up with those in men.
Even then, there are lots of young to middle aged, menstruating women complaining of chest pain and quite distressed about it. Before I highlight the special features of this particular issue lets first review the differential diagnosis of chest pain.

Differential Diagnosis of Chest Pain

1. Angina Pectoris/Myocardial Infarction
2. Other Cardiovascular Causes

a. Possibly Ischemic Pain

1) Aortic Stenosis
2) Hypertrophic Cardiomyopathy
3) Severe Systemic Hypertension
4) Severe Right Ventricular Hypertension
5) Aortic Regurgitation
6) Severe Anemia/hypoxia

b. Non Ischemic in Origin

1) Aortic Dissection
2) Pericarditis
3) Mitral Valve Prolapse

3. Gastrointestinal

a. Esophageal Spasm
b. Esophageal Reflux
c. Esophageal Rupture
d. Peptic Ulcer Disease

4. Psychogenic

a. Anxiety
b. Depression
c. Cardiac Psychosis
d. Self Gain

5. Neuromusculoskeletal

a. Thoracic Outlet syndrome
b. Lesions of Cervical/Thoracic Spine
c. Costochondritis[Tietze?s Syndrome]
d. Herpes Zoster
e. Chest wall pain

6. Pulmonary

a. Pulmonary Embolus/Infarction
b. Pneumothorax
c. Pneumonia with pleural involvement

7. Pleurisy
As most patients are anxious of their chest pain being that of Heart origin, we shall first have a look at the features of Cardiac Pain.