Tuesday, 1 November 2011

Spam: Opportunity





When I was a kid, this neighborhood was really different.  People were trusting and respectful. They left their doors open. If anyone had news, good or bad, it was shared, and everyone offered congratulations or sympathy. Nobody shouted or mouthed off; nobody pretended to be a friend just to sell you something. And every night, as the electron wind whispered through the silicon leaves, we slept contented… well, the leaves are an invention. And I wasn’t a kid: because the neighborhood I’m describing is the internet. On this day in 1994, it lost its innocence.



The serpent in this electronic garden was the firm of Canter & Siegel, husband-and-wife practitioners of immigration law in Phoenix, Arizona. Their plan was to get clients to pay for something – Green Card lottery entries – that the government actually provides free of charge; not, you rightly assume, a new dodge in the legal profession. The difference is that instead of a small ad in 
La Voz or Prensa Hispanica, they put their spiel up on Usenet, the internet’s first forum system – in six thousand places:
55,000 Green Cards will be 
given to those who register correctly.  NO JOB IS REQUIRED.
THERE IS A STRICT JUNE DEADLINE. THE TIME TO START IS 
NOW!!
They received, they said, around twenty thousand favorable replies, which translated into a thousand paying clients and $100,000 in income: an amazing result when compared with conventional print advertising or direct mail. They also received some 25,000 outraged messages from other Usenet members – so many that their ISP’s servers crashed. Programmers rushed to create methods to intercept and bulk-erase Canter & Siegel’s postings (called, in a nerdly tip of the hat to Monty Python, “spam”). The two were expelled from the American Immigration Lawyer’s Association; Canter was disbarred in Tennessee for “illegal advertising.” Martha Siegel and Laurence Canter remained, though, unrepentant: “Freedom of speech has become a cause for us.” “The Internet is a very powerful communications vehicle, and it should be available for everyone.” They switched from law to internet-advertising consultancy and wrote How to Make a Fortune on the Information Superhighway, a guide to marketing on the InternetHow to Make a Fortune did not itself make a fortune. The consultancy, Cybersell, was dissolved in 1998; but Canter & Siegel’s influence remains pervasive. Your owe to them your constitutional right to be offered Viagra and viagra cialis online pharmacy pharmacy two hundred times a day.



“Somebody would have done it, if we hadn’t done it,” explained Laurence Canter in 2002, during an interview in which he also complained about the volume of e-mail spam he received. He’s right: the discrepancy between cost and return is too large for a thick-skinned marketeer to ignore.  When you have essentially free access to people’s electronic doorsteps, it doesn’t matter if 99.999% slam their doors in your face and threaten to let out the dogs. One sale in a hundred thousand attempts is still profitable – indeed, the estimated conversion rate for pharmaceutical e-mail spam is one in 12,000,000. No wonder the vast bulk of message capacity, energy, and money invested in the internet is wasted.



Computer 
simulations of trusting and suspicious communities, using game theory’s well-known “prisoner’s dilemma” as a generic transaction, reveal that the unscrupulous go through an open society like a buzzsaw through balsa – but that simple social conventions soon repair the damage. Merely preferring to transact with a known person or a neighbor in preference to the traveling stranger allows the law to return to Dodge City. We have neighborhoods because neighborliness is the prerequisite for all the benefits we seek from society. The internet, though, is a metropolis of conflicting desires: we want to be visible – yet, at other times, anonymous; we want trustworthy information, but don’t want to be held to account; we want to make money (I wouldn’t object, for instance, if you bought a copy of one of my books); but we don’t want to be asked for it. We live here as in a medieval market-town, where honest citizens feel themselves surrounded by beggars, cutpurses, voyeurs – all sins are catered for, and only a mug lets himself be taken. We can never go home to the old neighborhood.





Saturday, 29 October 2011

Straight to the Central Nervous System - Intraspinal Analgesia & Anaesthesia

Spinal Analgesia





 Intrathecal: online pharmacy injected directly into the "dura matter" of the subarachnoid space containing the cerebrospinal fluid coating the spinal cord. This procedure uses a much smaller needle than is used in epidurals, in order to avoid leakage of cerebrospinal fluid. Fluid leakage can result in "spinal headaches". This is an occasional occurrence in epidural procedures when the dura matter is accidentally punctured with the larger 'epi' needle.


Epidural: Medication injected into the epidural space, between the bony walls of the spinal canal and the dura matter surrounding the spinal cord.


Sometimes, a catheter is inserted into the epidural space, or less often the intrathecal sac itself, to allow continuous infusions of medications; such as opioids, general anaesthetics or local anaesthetics; for those undergoing a long surgery or requiring round-the-clock analgesia.




Spinal Catheter (with depth-markings) infusing drugs into the epidural space


Dura Matter: A tube of tissue which coats the arachnoid matter/spinal fluid surrounding the spinal cord. The dura is the layer which separates the epidural space from the inner-most arachnoid membrane and spinal cord.


Arachnoid Matter: Membrane which is contained within the dura matter which encomasses the spinal cord and fluid.




This shows an injection into the empty epidural space; the blue liquid is the injection solution. When the intrathecal route is selected, the dura matter itself is punctured (shown as dark area surrounding the spinal cord) which contains cerebrospinal fluid
Opioids (Spinally)

Opioids are effective and may be given by the spinal route; by both intrathecal and epidural injection, or infusion using a catheter. Opioids which are administered into the CNS by either of these routes will provide analgesia with much fewer side effects such as sedation and pruritis. Differing opioids have differing efficacy by this route depending on their individual properties.


Lipophilic opioids are rapidly absorbed by spinal lipid tissues, usually most targeted near the area of the injection site/puncture. Fentanyl and its analogues all share this property of high solubility, and should generally be administered as close as possible to area of the spine mediating pain signals.


Less absorbed opioids such as morpine generally spread throughout more area of the spinal canal, often making their way up to higher regions of the CNS via cerebrospinal fluid. In both cases, the opioid given intraspinally will make it's way to the subarachnoid space containing cerebrospinal fluid, and be absorbed by neural tissue.


Spinal Anaesthesia



The intraspinal route is commonly used in anaesthesia; for procedures which general anaesthesia cannot be used or puts the patient at risk, etc. This is typically done with a local anaesthetic such as bupivacaine, and is called regional anaesthesia. A spinally administered anaesthetic depending on dose and concentration, will effectively block pain or all sensation in the lower area of the body (below the navel cavity is the general rule of thumb). With a sufficient level of anaesthesia, patients may remain conscious during the procedure if this is desired; however in the US, Anaesthetists usually administer sedatives for the procedure.


Regional anaesthesia is often done by the epidural route to women during labor, and for C-Section procedures. Most commonly in Western medicine, potent opioids are administered (spinally) along with the anaesthetic - this provides a 'smoother' and more effective anaesthesia and also serves to provide post operative analgesia for up to 12 hours after the procedure. Spinal anaesthesia is extremely prevalent in India, where it is common to administer an infusion of buprenorphine along with bupivacaine.


Side Note: A vasoconstrictor such as phenylephrine can be used in the spinal to prolong the effect of anaesthetic.


Midazolam (Versed) can be used in conjunction with other good stuff, for sedation during regional spinal anaesthesia.









Fentanyl: Perfect combo with midazolam; or given spinally by itself or along with anaesthesia


Tuesday, 3 May 2011

Conatus Pharmaceuticals - Phase II data on Hepatitis C MMP inhibitor CTS-1027 to be presented at EASL

Privately-held Conatus Pharmaceuticals will have two posters on the Phase II trial of it's purchase cialis of matrix metalloprotease (MMP) activity, CTS-1027 - the only MMP cheap cialis currently in development for HCV at this time.



Conatus Pharmaceuticals Inc. today announced the acceptance of two poster presentations of Phase 2 clinical trial data of CTS-1027 for the treatment of hepatitis C virus-infected patients at the 46th annual meeting of the European Association for the Study of the Liver (EASL) to be held in Berlin, Germany, on March 30 to April 3, 2011.



Specifically, abstract 562 entitled: 24-WEEK TREATMENT WITH CTS-1027 IN COMBINATION WITH RIBAVIRIN REDUCES HCV-RNA IN TREATMENT NAIVE GENOTYPE-1 PATIENTS will be presented.



In addition, abstract 549 entitled: UNIQUE PATTERN OF VIROLOGIC RESPONSE IN PATIENTS WITH GENOTYPE-1 HCV: A PHASE II STUDY OF CTS-1027 IN COMBINATION WITH PEGINTEFERON/RIBAVIRIN (SOC) IN NULL RESPONDERS will also be presented.



"This will be the first public disclosure of these exciting clinical results and represents a significant step forward to raise awareness of CTS-1027 for the treatment of HCV," said Alfred P. Spada, Ph.D., Senior Vice President, Research and Development at Conatus.



"CTS-1027 is a first-in-class oral, small molecule inhibitor of host matrix metalloprotease (MMP) activity. There are no other drugs under development for HCV that operate by the same mechanism of action. Most other approaches to treat HCV infection are direct-acting anti-viral drugs whose activity is directed against virus proteins or enzymes with the objective of reducing the production of virus in infected cells. CTS-1027 by comparison is distinctly different in that its activity is hypothesized to facilitate the immune clearance of virus-infected cells and decrease the frequency of new infections, both of which are of key importance in curing HCV infections," said Steven J. Mento, Ph.D, President and CEO of Conatus.



Conatus Pharmaceuticals Inc. is a privately-held biopharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease and oncology. Conatus' lead drug candidate, CTS-1027 is in multiple Phase 2 clinical trials for the treatment of hepatitis C virus (HCV). Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the sale of Idun to Pfizer.



SOURCE Conatus Pharmaceuticals Inc.