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Saturday, September 26, 2015

Dosing Blood Pressure Control Medicines at Bed Time Reduces the risk of Stroke and T2 Diabetes Mellitus

Posted by Prahallad Panda on 9:12 PM Comments

We all prescribe medications for control of Hypertension. Most common among those are the ACE (Angiotensin Converting Enzyme) inhibitors, ARBs (Angiotensin Receptor Blocker) and Third generation β-Blocker like Nebivolol. But, seldom we advise the patients which is the preferred time to take these groups of medications. Most of the patients, conventionally, take these medicines after awakening, in the morning.
It has been observed that most susceptible people get heart attack towards dawn or early morning. One of the factors can possibly be due to the fact that blood pressure starts rising from 03 to 04 AM and gradually rises till 12 Noon.
Normally, there is a fall of systolic blood pressure more than 10% of mean day time BP reaching the zenith from 12 Mid-Night to 03-04 AM, regulated by circadian rhythm. This phenomenon is called as “Dipping.”
Alterations in these intrinsic circadian rhythms can result in the absence of the nocturnal BP decline (non-dipping). This altered pattern is commonly seen in patients with essential hypertension, several forms of secondary hypertension and disorders of the autonomic nervous system.
The clinical relevance of this phenomenon lies in the fact that non-dipping has been associated with increased frequency of hypertensive target organ damage (brain, heart and kidney), as well as cerebrovascular and cardiovascular events in hypertensive patients.
Circadian rhythms typically originate in “master oscillators” located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. How this hypothalamic rhythm is translated into changes in blood pressure is not entirely known, but the autonomic nervous system is suspected to play a role; sympathetic activity is also modulated by hypothalamic centers, and follows a circadian pattern similar to that of blood pressure.
Patients are categorized, usually based on systolic blood pressure, as extreme dippers (night–day blood pressure ratio ≤ 0.8), dippers (0.8 < ratio ≤ 0.9), non-dippers (0.9 < ratio ≤ 1.0) and reverse dippers or risers (ratio > 1.0). Reverse dipper are particularly in the risk of developing end organ damages.
A new research article published in The Diabetologia by Ramón C. Hermida, Diana E. Ayala, Artemio Mojón and José R. Fernández of University of Vigo, Campus Universitario, Vigo, Pontevedra 36310, Spain, titled as”Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial” has concluded that in hypertensive patients without diabetes, ingestion of 1 BP-lowering medications at bedtime, mainly those modulating or blocking the effects of angiotensin-II, compared with ingestion of all such medications upon awakening, results in improved ambulatory BP (ABP) control (significant further decrease of asleep BP) and reduced risk of new-onset diabetes.
Renin angiotensin pathway or RAAS.
Renin angiotensin pathway or RAAS. (Photo credit: Wikipedia)
Drugs that target angiotensin include angiotensin receptor blockers (ARBs), ACE inhibitors and beta blockers. These medications act through blockade of the RAAS (Rennin-Angiotensin-Aldosterone System) in kidney that causes blood vessels to constrict and blood pressure to rise. 
Angiotensin, Aldosterone and adrenaline also contribute to increased glucose (sugar) release from the liver and decreased insulin sensitivity. These factors can lead to Type 2 diabetes.
 The researchers conducted a prospective, randomised, open-label, blinded endpoint trial of 2,012 hypertensive patients without diabetes, 976 men and 1,036 women, 52.7±13.6 years of age. Patients were randomised, using a computer-generated allocation table, to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of 1 of them at bedtime.
During a median follow-up of 5.9 years, 171 participants developed type 2 diabetes. Patients in the bedtime, compared with the morning-treatment group, showed a significantly lower asleep mean BP and a greater sleep-time relative BP decline.
In the bedtime treated group, there was a lower-prevalence of a phenomenon known as 'non-dipping' -- in which patients' night time BP falls by less than 10% compared to daytime BP. Non-dipping occurred in 32% of bedtime-treated patients and 52% of those getting their treatment in the morning.
There was also a 57% decrease in the risk of developing new-onset type 2 diabetes in the bedtime-treated group after adjustment for the potential confounders of fasting glucose, waist circumference, mean asleep systolic BP, dipping classification and chronic kidney disease.
Specifically, the odds of type 2 diabetes dropped 61 percent for people taking angiotensin receptor blockers at bedtime compared to morning. For those on ACE inhibitors at night, the odds went down 69 percent. People on beta blockers reduced their odds of the blood sugar disease by 65 percent when they took their medicine at night, the researchers reported.
All three classes of medication were associated with a reduced risk of type 2 diabetes when taken at bedtime as the effect will be much more on liver/kidney in comparison to the waning effect at night when taken in the morning.
Let us remember to advise our hypertensive patients to take their anti-hypertensive medications at bed time, especially ARBs, ACE-Inhibitors and Nebovolol for better effect and delaying development of T2DM.


Monday, September 14, 2015

Can we call a Tract from Anus without External Opening as Fistula-in-Ano?

Posted by Prahallad Panda on 7:48 PM Comments

Fistula-in-Ano is a completely or incompletely epithelised tract that connects the internal opening in anus to an external opening in the perianal skin.
In most of the cases, external opening can be identified; whereas in minority of cases, external opining is absent.
It happens that a firm to hard tract is palpable, ending blindly in the perineum. This is a situation, when the perineal abscess has not broken the skin, though pus can be seen coming from anal opening, on pressing from the exterior.
Hence, whether the condition can be called as Fistula-in-ano, in true sense of the term?
English: Cassia-fistula
English: Cassia-fistula (Photo credit: Wikipedia)
In one case, a cystic swelling was noted in the posterior aspect of the scrotum, not attached to the testis; attached to it is a firm to hard tract that leads to the anal canal. A raw area can be felt in the superficial plane, in the anal canal; presumed to the internal opening of the tract. The tract could be probed.
The tract was dissected from near the base of the scrotum till the anal canal is reached, it is probed from inside and excision was completed.
The biopsy report of the tract comes as “Non-specific Chronic Inflammation.” No malignancy or Tuberculosis is seen.
Should we call it, “Anal-perineal Sinus” or “Anal-perineal blind Tract.”

Tuesday, June 30, 2015

Importance of Debridement and Total Contact Cast in Trophic Ulcer Healing

Posted by Prahallad Panda on 7:35 PM Comments

An ulcer refusing to heal may be due to various diseases. Among all, diabetes, leprosy and cancer are most important. Those due to diabetes and leprosy are called Trophic Ulcers; Trophe=Nutrition. There is impaired nutrition to the place due to lack or less blood supply; neuropathy i.e. damage to the nerve fibre.

Deutsch: Geschwür am diabetischen Fuß
Deutsch: Geschwür am diabetischen Fuß (Photo credit: Wikipedia)
Lack of pain sensation, mostly in the foot, makes it vulnerable to repeated trauma; pain makes the person cautious, to use foot carefully and draws attention.
Apart from the specific disease oriented treatment, offloading of foot after debridement plays a major role in healing the ulcer.
Offloading can be achieved in various ways, among the available methods, non-removable ones are more helpful; Total Contact Cast (TCC) or plaster boot.
After through debridement of the infected and dead tissue, excision of the callous and hypertrophied skin, either TCC or plaster boot is to be applied for 21 days. After this period, the ulcer can be inspected for healing and if required, can be kept offloaded for a further period of 21 days.
Debridement of the wound helps healing by migration of platelets and thereby the growth factor; Offloading helps by saving from repetitive trauma and pressure to the part.

Thursday, April 2, 2015

Formation and Accumulation of Ketone Bodies In Diabetic Ketoacidosis

Posted by Prahallad Panda on 8:51 PM Comments

Finding Ketone bodies in blood and urine are hallmark of Diabetic Ketoacidosis along with clinical features.

These are three in number, namely, acetoacetate (AcAc), 3-beta-hydroxybutyrate (3HB) and the third,least abundant, acetone.

Ketones are always present in the blood in some amount and their levels increase during fasting and prolonged exercise.

Diabetes is the most common pathological cause leading to elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counter-regulatory hormones.
Acyl CoA is produced from break down of fatty acid, when cannot enter the Citric Acid Cycle (Cycle is down) due to lack of insulin sensitivity, get converted & accumulate in the form of ketone bodies. 
In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels.

The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results.

Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples.
These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies.


Sunday, March 22, 2015

A Novel Host Immune Protein for Differentiating between Acute Bacterial and Viral Infection

Posted by Prahallad Panda on 11:04 AM Comments

Can we doctors definitely say in the acute phase, whether an infectious disease is due to bacteria, virus or mixed? Is there any blood test to know it?
Answer will be no to a larger extent. Diagnosis, largely depends on the epidemiology; most of upper respiratory infections are due to viral infection. Such types of assumptions and uncertainties lead to misuse of antibiotics, antibiotic resistance and adverse effect due to antibiotic use; nontheless, the financial burden on the family.
Several bio-markers like CRP (C-Reactive Protein), procalcitonin and Interleukin-6 are used to support the diagnosis of bacterial infection. But, take the case of CRP, it is increased in cases of bacterial infection and non-infectious inflammatory diseases as well.
Recently, in a research article published in PLOS One, the researchers claim to have successfully tested for a novel Host Immune Protein that is mostly elevated in viral infection and least in bacterial infection.
In the PLOS One study, the ImmunoXpert immune signature was developed and independently validated on a cohort of 1002 patients with acute infections and yielded highly accurate results, with sensitivity and specificity greater than 90%. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) to diagnose viral infection.

MeMed, Ltd., announced publication of the results of this large multicenter prospective clinical study that validates the ability of its ImmunoXpertTM in-vitro diagnostic blood test, enrolling over 1000 patients between 2009 and 2013.
Reportedly, three host proteins are tested in ImmunoXpert kit; CRP, IP 10 and TRAIL; from swing of results, the most probable cause of infection i.e. bacterial or viral can be distinguished. TRAIL (member of the tumor necrosis factor family implicated in programmed cell death), IP-10 (IFN-gamma-inducible protein 10) small cytokine implicated in multiple cellular processes including chemotaxis and cell growth inhibition, and CRP (acute phase protein with diverse roles in tissue injury, infection and other inflammation processes).
This test will perhaps be a boon to mankind and handy to the doctors for near accurate diagnosis. 


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