Acute abdomen

This is a good introductory video to understand acute abdomen either as preparation for PBL or history taking.

Punca mandul?

http://www.ncbi.nlm.nih.gov/pubmed/23142464#
Fluorochemicals used in food packaging inhibit male sex hormone synthesis.

Rosenmai AK, Nielsen FK, Pedersen M, Hadrup N, Trier X, Christensen JH, Vinggaard AM.

Source

Division of Toxicology & Risk Assessment, National Food Institute, Technical University of Denmark, DK-2860 Søborg, Denmark. akjro@food.dtu.dk

Abstract

Polyfluoroalkyl phosphate surfactants (PAPS) are widely used in food contact materials (FCMs) of paper and board and have recently been detected in 57% of investigated materials. Human exposure occurs as PAPS have been measured in blood; however knowledge is lacking on the toxicology of PAPS. The aim of this study was to elucidate the effects of six fluorochemicals on sex hormone synthesis and androgen receptor (AR) activation in vitro. Four PAPS and two metabolites, perfluorooctanoic acid (PFOA) and 8:2 fluorotelomer alcohol (8:2 FTOH) were tested. Hormone profiles, including eight steroid hormones, generally showed that 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH led to decreases in androgens (testosterone, dehydroepiandrosterone, and androstenedione) in the H295R steroidogenesis assay. Decreases were observed for progesterone and 17-OH-progesterone as well. These observations indicated that a step prior to progestagen and androgen synthesis had been affected. Gene expression analysis of StAR, Bzrp, CYP11A, CYP17, CYP21 and CYP19 mRNA showed a decrease in Bzrp mRNA levels for 8:2 monoPAPS and 8:2 FTOH indicating interference with cholesterol transport to the inner mitochondria. Cortisol, estrone and 17β-estradiol levels were in several cases increased with exposure. In accordance with these data CYP19 gene expression increased with 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH exposures indicating that this is a contributing factor to the decreased androgen and the increased estrogen levels. Overall, these results demonstrate that fluorochemicals present in food packaging materials and their metabolites can affect steroidogenesis through decreased Bzrp and increased CYP19 gene expression leading to lower androgen and higher estrogen levels.

 

Kajian in vitro ini mendapati bahan fluorochemicals yang terdapat pada pembungkus makanan boleh menyebabkan penurunan hormon androgen yang membentuk sifat lelaki dan meningkatkan aras hormon estrogen yang membentuk ciri keperempuanan. Bahan ini digunakan dalam pembungkus makanan supaya ia menjadi tidak telap air dan minyak. Pembungkus ringkas ini boleh kita dapati dengan banyak samada digunakan diindustry pempungkusan makanan, pembungkus makanan segera atau mungkin juga kertas bergris yang kita guna untuk nasi lemak, mee goreng dan nasi campur? Adakah ia menyumbang kepada peningkatan pasangan yang sukar mendapat anak? Atau mungkin kepada peningkatan lelaki lembut?

 

Rawatan Penggantian dengan Methadone (Bahagian 1)

Rawatan penggantian Methadone atau "Methadone Replacement Therapy" merupakan salah satu kaedah perawatan dadah gantian di Malaysia. Ia mula diperkenalkan pada 2005. Ia adalah satu usaha mengurangkan penularan HIV/AIDS akibat suntikan bercampur. Ia walaubagaimanapun agak bercanggah dengan hasrat Malaysia mencapai masyarakat sifar-dadah. Setelah bertahun menimbang pelbagai faktor akhirnya kerajaan akur dengan kesan positif yang diharapkan dari program rawatan dan rehabilitasi ini. Antara faktor penarik adalah:
1. Kebayakan kes penyalah-gunaan dadah melibatkan heroine
2. 75% peratus dari kes HIV di Malaysia berkait dengan perkongsia jarum suntikan dadah
3. Pendekatan mengurangkan permintaan dadah di Malaysia jelas tidak begitu berjaya.

Kejayaan awal yang dicapai menyebabakan kerajaan semakin serius dengan kaedah perawatan ini dan menyasarkan sehingga 5000 subjek untuk rawatan. Seperkara lagi jelas didapati bahawa penghidap HIV akibat suntikan lebih tetap dalam mendapatkan rawatan antiretroviral berbanding pesakit HIV bukan akibat suntikan.

Sebanyak 58 lokaliti terlibat sebagai pusat perawatan termasuk hospital, klinik kerajaan dan swasta. Bagi merancak lagi kesan positif perawatan ini beberapa agensi turut terlibat sebagai pusat rawatan seperti penjara dan Pusat Anti-Dadah kebangsaan. Kerajaan juga berjaya mengurangkan kos perawatan dari RM5 kepada RM1.80

How to PASS the first years in Medicine

Salam everyone..at present many university students are facing mid term or block exams. Some are ever ready to enter the exam hall. But the majoriity of them I think are not very comfortable thinking about it. Especially so for medical students. Thus I would like to share few tips.

There are few reasons that make you feel uncomforatble:
1. You are not prepared
2. You are not prepared
3. You are not prepared...

ha ha..funny eh..But I think that is the main cause of 'failure' for student. Thus the only way to feel comfortable is to BE PREPARED. So HOW?

1. Plan your study - ahhh some said..easy said than done. But believe me because I ve been through it and succeed. So what you should do is have a good plan since day 0..ie before you start your term. This was what I did when I was a medical student way back in the 90's. This is especially true for those in the basic medical science years.
- Know the subjects that you are going to study for the whole term/ block/ semester
- scrutinise your time table. See how many free hours in between lectures/ practicals
- Ensure all the gadgets needed to study are there - books, text books, stationaries, dictionary - I love DOrlands, papers, now adays..lap top? not that crucial at this stage.
- Ensure your brain/mind free from 'unnecessary' matters - Lu pikir lah sendiri
- Attend lectures, attend lectures, attend lectures - you are big enough by now to think and set your alarm.
- Browse through quickly topics that will be covered by lecturers the next day
-In the lecture hall - listen, take note, understand, ask questions.
- make sure you read , revise , understand the topics ON the same DAY. Ask friends, compare notes.
- Read text books, read text books, read text books. Tuch up notes.
- Make diagrams, paste on wall
- Raed and study at any time..Bring paper or fuulscap when watching TV or see friend plays games. Sketch, draw, anatomical diagrams- blood vessels, nerves, drug pathways, drugs mechanism..Check later when you are at your room
- Discuss with friends - while playing, while eating
- Divide time appropriately according to topics.
- Extra time on weak subjects.
- Make friend with lecturers , not because you want tips, but enable to discuss topics more comfortable..Dont let your Uni days pass without your lecturer noticing you..They may help you later during work or post grad study
- Eat well
- Rest as necessary
- Game - mmm kurangkan or reward yourself after exam..
- Always contact parents...
- Pray (Try to be a better Muslim everyday
- Doa................
- Finally ...Tawakkal......

If despite all this you still did nt MAKE it...Only Allah knows the BEST for YOU

Say No to clots!

Anticoagulation Drugs

Ubatan yang digunakan dalam permasalahan trombosis

Beberapa permasalahan dicetuskan oleh sifat darah yang mudah berketul. Ketulan kecil yang terbentuk boleh mengancam nyawa. Pesakit mungkin datang ke jabatan kecemasan dengan serangan jantung, sesak nafas atau angin ahmar. Dalam keadaan ini, ubatan antikoagulan dapat membantu 'mencairkan' atau melancarkan semula peredran darah atau mengurangkan pembentukan ketulan..Tetapi ingat segalanya atas izin Allah....

Di bawah ini adalah kumpulan ubatab yang digunakan dalam menghalang koagulasi:
A. Drugs used in disorders of coagulation
1. Anti coagulants
2. Fibrinolytic agents
3. Antiplatelet agents


ANTI KOAGULASI

Indirect thrombin inhibitors

1. Unfractionated Heparin (UFH = HMWH)
2. Low molecular weight heparin (LMWH)
3. Fondaparinux

Heparin
• Sulfated polysaccharides. Source of commercial heparin:
– porcine intestine
– bovine lung

• Mechanism:
– Binds to and accelerates 1000x the action of ATIII (an endogenous anticoagulant). ATIII inhibit proteases: thrombin, IXa, Xa  retard thrombus formation. Heparin (co-factor) is released intact for renewed binding.

Unfractionated Heparin (UFH)

• inhibit thrombin, IXa, Xa. Route: continuos IV infusion or SC intermittent injection (rarely used except for prophylaxis), binds to heparin-binding-proteins in blood stream. Only free UFH is active. Clearance through kidney, t ½ 30-60 minutes. Heparin has pharmacokinetic limitations not shared by LMWHs  Heparin therapy is usually restricted to the hospital setting (can be monitored and its dosage adjusted frequently)

Low-molecular weight heparin (LMWH)

• inhibit thrombin (less effect on IXa and Xa. Better bioavailability, less frequent dosing requirement. Clearance: less rapidly through kidney than UFH, accumulation occurs overtime. can be administered: in-hospital or out-of-hospital setting because can be administered SC (No need for laboratory monitoring).

Fondaparinux (synthetic)

• selective inhibitor of activated factor X (factor Xa). An entirely synthetic pentasaccharide that is structurally related to the antithrombin-binding site of heparin. Compare to heparin, pentasaccharide selectively binds to antithrombin, causing it to rapidly inhibit factor Xa

Kegunaan di peringkat klinikal: Heparin clinical application
1. Langkah awal dalam merawat trombosis: Initial phase of long-term anticoagulant therapy: start with heparin or LMWH. Followed by: oral anticoagulants. (except: in pregnancy and in patients who develop recurrent venous thromboembolism while on oral anticoagulants)
2. Prevention of venous thromboembolism - venous thrombosis and pulmonary embolism (PE)
3. Early treatment of patients with unstable angina and acute myocardial infarction.
4. Patients who undergo cardiac surgery using cardiac bypass, vascular surgery, and coronary angioplasty;
5. Patients with coronary stents
6. Selected patients with disseminated intravascular coagulation.


LMWHs. Tidak begitu berbeza dari HMWH
1. Prevention of venous thromboembolism - venous thrombosis.
2. Treatment of acute PE.
3. The early treatment of patients with unstable angina

Perlu berhati hati kerana bukan semua pesakit boleh diberi heparin. Heparin contraindications
• Patient with HIT, Drug hypersensitivity, Active bleeding, Significant thrombocytopenia, Purpura, Severe hypertension, Intracranial hemorrhage, Infective endocarditis, Active tuberculosis, GIT ulcerative lesions, Threatened abortion, Visceral carcinoma, Advanced hepatic/ renal disease, Post brain, spinal cord, eye surgery. Lumbar puncture, regional anaesthesia block


Dan ingat perlu diawasi penggunaan nya: Monitoring of heparin effects
• Activated Partial Thromboplastin Time (APTT). Monitor time for a specific clotting process to occur (in the laboratory test) then compare to a “control” sample of normal blood. Unit (seconds

Kesan sampingan nya: Adverse effects
• Bleeding – careful in patient selection, control dosage, close monitoring (elderly, renal failure)
• Allergy (animal origin)
• Osteoporosis/ spontaneous fracture
• Mineralocorticoid deficiency
• Alopecia
• Heparin-induced thrombocytopenia (HIT) (systemic hypercoagulable state) – especially surgical patient on UFH bovine origin.
• Monitor platelet.

Treatment of bleeding with heparin treatment:
1. Rx: stop heparin ! Use Protamine sulfate - Use to reverse the effects of heparin (UFH). Route: Intravenous. Source: basic protein from fish sperm.1 mg will neutralise 100 IU of UFH

Direct thrombin inhibitors - bertindak secara langsung dalam penghasilan faktor koagulan

• Warfarin – dulunya racun tikus! initially used as rodenticide. 1950s – used as antithrombotic agent in human

Mechanisms of action

• Block γ-carboxylation of glutamate residues in prothrombin, factors VII, IX, X, protein C and S  formation of incomplete coagulation factor molecules  biologically inactive.
• How? - Coupled to Vitamin K oxidation
• Warfarin action is delayed: 8-12 hours delay of action (compare to Heparin – immediate effect). Why? Time taken to achieve Balanced between partially inhibited synthesis and unaltered degradation of the 4 vitamin-K-dependent clotting factors = VII, IX. X, II (t ½ = 6, 24, 40, 60 hours)

Clinical

• Administration & dosage:
– 5-10 mg loading dose. Adjust in 1/52. Maintenace dose 5-7 mg/day
– Monitor Prothrombin time (PT), therapeutic range = INR.
– Recommended INR for prophylaxis/ treatment of thrombotic disease 2-3.
– artificial heart valve/ other medical condition with thrombotic risk 2.5-3.5.
– Be aware of patient with resistant to warfarin treatment  raise target INR.

Drug interaction
• Pharmacokinetics - enzyme induction, enzyme inhibition, reduced plasma protein binding.
• Drugs that increase warfarin effect: Phenyl butazone, sulfinpyrazone
• Pharmacodynamics – synergism, competitive antagonism.
• Drugs that increase warfarin effect: aspirin, heparin

Warfarin adverse effects
• Birth defects and hemorrhagic disorder in fetus. Never administer in pregnancy
• Cutaneous necrosis
• Reduced protein C activity
•  frank infarction of breast, fatty tissues, intestine, extremities.

Reversal of warfarin action
• Stop the drug
• Administer vitamin K, fresh frozen plasma (FFP), prothrombin complex concentrates, recombinant factor VIIa
• Consider repeat administration of (2) because of warfarin long t ½


Fibrinolytic drugs - Ubatan ini menghalan penghasilan fibrin

• Mechanism:
– lyse thrombi by catalyzing the formation of serine protease PLASMIN from PLASMINOGEN. Cause generalised lytic state.

The drugs
1. Streptokinase
2. Urokinase
3. Anistreplase
4. Tissue plasminogen activators (t-Pas)
5. Reteplase
6. Tenecteplase

Clinical Indications:
• Acute myocardial infarction
• Pulmonary embolism
• Severe DVT
• Ascending thrombophlebitis

The antiplatelet- Bahan ini pula mencegah aktiviti platlet
1. Aspirin
2. Clopidogrel & ticlopidine
3. Blockade of platelet glycoprotein IIB/IIIA receptors
4. Others


Aspirin (acetylsalicylic acid)
• Prototype of NSAIDs. Mechanism: Irreversibly acetylate and inactivate cycloxygenase (COX) Inhibit synthesis of thromboxane A2,(An arachidonate product that causes platelets to change shape, release granules and aggregates). Side effects: bleeding, gastric side effects

Clopidogrel & ticlopidine
Mechanism: Block ADP receptor irreversibly. No effect on prostaglandin metabolism. Indication: TIA, completed stroke, unstable angina pectoris, patient set for coronary stent

Adverse effects
• Ticlopidine(250 mg daily):
– Leukopenia (monitor WBC count first 3 month Rx) ,
– Nausea, dyspepsia, diarrhoe,
– hemorrhage.

• Clopidogrel (75 mg daily) – fewer side effects

IIB/IIA receptor blocker
• Receptor for fibrinogen, vitronectin, vWF
• Mechanism: inhibit final common pathway for platelet aggregation
• Drugs:
1. Abciximab
2. Eptifibatide
3. Tirofiban

Anda berpenyakit lelah?

Are you asthmatic?

Do you know your medicine?

Drugs (Kumpulan ubat yang diguna dalam rawatan lelah)

1. Symptomimetic agents
2. Methylxanthine drugs
3. Antimuscarinic agents
4. Corticosteroids
5. Cromolyn & Nedocromil
6. Leukotriene pathway inhibitors


Asthma

Bagaimana lelah terjadi:
• Chronic inflammatory disorder of the airways (Radang)
– Clinical - Bouts of coughing, SOB, Chest tightness, wheezing
– Physiological - Widespread narrowing bronchial airways, increased bronchial responsiveness to inhaled stimuli (Alahan)
– Pathological - Remodelling of bronchial mucosa, deposition of collagen beneath basement membrane, hyperplasia of the cells of all structural elements.

Histopathological changes (Perubahan patologi yang berlaku)
• Cells infiltration: eosinophils, T-lymphocytes, mast cells; Plasma exudation; Oedema; Smooth muscle hypertrophy; Mucus plugging; Epithelial changes;
•
Patogenesis
• Genetic – Atopy - Masalah keturunan
• Airway hyperesponsiveness - Kerengsaan
• Common allergens - Terdapat beberapa bahan penyebab alergi seperti debunga, habuk
• Non specific precipitants - Bersenam juga boleh menyebabkan lelah
• Occupational

Ubatan mengikut kumpulan:

1. Sympathomimetic agents

1. Adrenaline
2. Ephedrine
3. Isoproterenol
4. Albuterol (Salbutamol)
5. Terbutaline
6. Salmeterol
7. Metaproterenol
8. Isoetharine

Mechanisms - Bagaimanakah ia bertindak:
• Relax airway smooth muscle.
• Inhibit release of some bronchoconstricting mediators from mast cells.
• Inhibit microvascular leakage
• Increase mucociliary transport by increase in ciliary activity.
• Stimulates adenyl cyclase and catalyze the formation of cAMP in air way tissue

β2 Agonists – most widely used anti asthmatic today. Less side effects from of β1 stimulation.

• Short-acting β2 Agonists. Albuterol (=salbutamol), Terbutaline, Metaproterenol. Route: MDI, nebuliser, oral: bronchodilation achieved within 15-30 minutes. Last 3-4 hours. SC injection: terbutaline:for severe asthma for emergency treatment. Caution: cumulative effect from longer t ½

• Long-acting β2 Agonists. Salmeterol, Formoterol. Long acting (≥ 12 hours) because of high lipid solubility

2. Methylxanthine drugs

Mechanism of action

 Inhibit PDE enzymes. PDE hydrolyzes the cAMP. cAMP. PDE4 inhibition  reduce release of cytokine/chemokine
 Inhibit receptors for adenosine that modulate adenyl cylase activity. Adenosine causes contraction of isolated airway smooth muscle and enhance histamine release

Kesan Sampingan:

1. Theophylline – requires TDMbecause therapeutic and toxic effects - related to plasma concentration
2. Narrow Therapeutic index (TI), requires monitoring. Active plasma conc = 5-20 mg/ L
3. At 15mg/L - anorexia, nausea, vomiting, abdominal discomfort, headaches, anxiety
4. At > 40 mg/L –seizures, arrhythmia.
5. IV injection: do it slowly (over 30 minutes) - because rapid injection cause transient toxic plasma levels with the risk of seizure or cardiac arrhythmia
6. Metabolism in the liver – liver disease  decreased clearance. Enzyme induction eg. Smoking  increased clearance
7. Clearance vary with age
8. Overdose: Death
9. Lost its importance in asthma treatment due to narrow TI.

3. Antimuscarinic agents

1. Atropin
2. Ipratropium bromide

Mechanism of action
• Competitive inhibitor of acetylcholine at muscarinic receptors
• Block the contraction of airway smooth muscle and the increase in the secretion of mucus that occurs in response to vagal activity
• Response to treatment varies: Involvement of parasympathetic on bronchospasm vary between individuals

4. Corticosteroids

Mechanism of action
– Broad anti-inflammatory effect of airways. Inhibit lymphocytes, eosinophils.
– reduce bronchial reactivity/asthma exacerbation.
– Contraction of engorged vessel.

Clinical use
– Reduce severity of symptoms, increase airway calibre, reduce bronchial reactivity, reduce exacerbations, improve quality of life.
– Indications: those need urgent treatment (oral or IV ), or worsening symptoms.usually discontinued after a week or ten days.
– Route: Oral/ IV/aerosol = inhalation
– Reduce dose as symptoms improve, discontinue 7-10 days treatment. Adrenal suppression may occur based on the dose.
– Aerosol treatment – decrease systemic adverse effects

• Chronic use – effective reduce symptoms
• Improve pulmonary function
• Eliminate need for oral steroid in severe disease
• Reduce bronchial activityNow routinely prescribed for patients who require more than occasional sympathomimetic agent. Continue to 12 week. Evaluate. ? Prolong treatment needed.

Adverse effects (Kesan sampingan)

• oropharyngeal candidiasis,
• hoarseness of voice,
• ? Osteoporosis and cataract
• Reduce growth in children ? transient
• Catarract, Muscle weakness, Glaucoma, Glucose intolerance, Depression, hypertension

5. Cromolyn and Nedocromil (Ubatan profilaksis)
– Prophylactic drugs. Not effective in reversing asthmatic bronchospasm and no effects on smooth muscle
– Inhibit antigen and exercise induced asthma
– Route: aerosol (extremely insoluble salt)

Mechanism of actions
• Alter function of delayed chloride channels in the cell membrane.Thus inhibit cell activation.
• Nerve cell Inhibits cough
• Mast cellinhibit response to antigen challenge
• Eosinophilsinhibit late response. Effective even after mast cell degranulation

Cromolyn indication
• Asthma – use before eg exercise, occupational related cause (aerosol inhalation)
• Allergic rhinoconjunctivitis. (Spray)

6.Leukotriene pathway inhibitor

Mechanism of drug actions
Interrupt leukotriene pathway
– inhibit 5-lipoxygenase prevent the synthesis of leukotriene (Zileuton).
– inhibit binding of leukotriene D4 to its receptor (Zafirlukast, Montelukast).Role in aspirin induced asthma