Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 893

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 1918

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 1990

Deprecated: mysql_connect(): The mysql extension is deprecated and will be removed in the future: use mysqli or PDO instead in /www/htdocs/w00a10d9/html/includes/classes/adodb/drivers/adodb-mysql.inc.php on line 360

Deprecated: Function split() is deprecated in /www/htdocs/w00a10d9/html/includes/pnLang.php on line 62

Strict Standards: Declaration of pnRender::clear_cache() should be compatible with Smarty::clear_cache($tpl_file = NULL, $cache_id = NULL, $compile_id = NULL, $exp_time = NULL) in /www/htdocs/w00a10d9/html/includes/pnRender.class.php on line 45

Strict Standards: Declaration of pnRender::is_cached() should be compatible with Smarty::is_cached($tpl_file, $cache_id = NULL, $compile_id = NULL) in /www/htdocs/w00a10d9/html/includes/pnRender.class.php on line 45

Strict Standards: Declaration of pnRender::fetch() should be compatible with Smarty::fetch($resource_name, $cache_id = NULL, $compile_id = NULL, $display = false) in /www/htdocs/w00a10d9/html/includes/pnRender.class.php on line 45

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 41

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 42

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 43

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 44

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 45

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 46

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 47

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 48

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 49

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 50

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 51

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 52

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 53

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 54

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 41

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 42

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 43

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 44

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 45

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 46

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 47

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 48

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 49

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 50

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 51

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 52

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 53

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 54

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 41

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 42

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 43

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 44

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 45

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 46

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 47

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 48

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 49

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 50

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 51

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 52

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 53

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 54

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 41

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 42

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 43

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 44

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 45

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 46

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 47

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 48

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 49

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 50

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 51

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 52

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 53

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 54

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 41

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 42

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 43

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 44

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 45

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 46

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 47

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 48

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 49

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 50

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 51

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 52

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 53

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/pnAntiCracker.php on line 54

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/safehtml.php on line 607

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 161

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 163

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 164

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 165

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 167

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 168

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 169

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 244

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 251

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 260

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 267

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 274

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 281

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 289

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 486

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 488

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/includes/classes/safehtml/HTMLSax3.php on line 490

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 51

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 51

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 51

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 51

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 51

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 53

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 54

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 55

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 56

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 57

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 58

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 63

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 64

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 64

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 65

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 66

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 67

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 68

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 69

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 70

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/includes/legacy/counter.php on line 71

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/modules/Xanthia/pnuserapi.php on line 70

Deprecated: Assigning the return value of new by reference is deprecated in /www/htdocs/w00a10d9/html/modules/Xanthia/pnuserapi.php on line 119

Strict Standards: Declaration of pnCEHTML::URL() should be compatible with pnHTML::URL($url = '', $text = '') in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 238

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 16

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 18

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 20

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 22

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 45

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 47

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 48

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 50

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 52

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 54

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 56

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 58

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 60

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 62

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 16

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 18

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 20

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 22

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 45

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 47

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 48

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 50

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 52

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 54

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 56

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 58

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 60

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 62

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/header.php on line 30
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Strict Standards: Non-static method ADOConnection::UnixTimeStamp() should not be called statically, assuming $this from incompatible context in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 3007

Strict Standards: Non-static method ADOConnection::UnixTimeStamp() should not be called statically, assuming $this from incompatible context in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 3007

Strict Standards: Non-static method ADOConnection::UnixTimeStamp() should not be called statically, assuming $this from incompatible context in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 3007

Strict Standards: Non-static method ADOConnection::UnixTimeStamp() should not be called statically, assuming $this from incompatible context in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 3007

Strict Standards: Non-static method ADOConnection::UnixTimeStamp() should not be called statically, assuming $this from incompatible context in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 3007

Strict Standards: Non-static method ADOConnection::UnixTimeStamp() should not be called statically, assuming $this from incompatible context in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 3007

Strict Standards: Non-static method ADOConnection::UnixTimeStamp() should not be called statically, assuming $this from incompatible context in /www/htdocs/w00a10d9/html/includes/classes/adodb/adodb.inc.php on line 3007

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 16

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 18

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 20

Deprecated: Function eregi() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 22

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 45

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 47

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 48

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 50

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 52

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 54

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 56

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 58

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 60

Deprecated: Function ereg() is deprecated in /www/htdocs/w00a10d9/html/modules/ContentExpress/pneditor/pnCEHTML.php on line 62

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

Deprecated: preg_replace(): The /e modifier is deprecated, use preg_replace_callback instead in /www/htdocs/w00a10d9/html/includes/pnAPI.php on line 589

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Special Lecture

on the occasion of the award of Honorary Membership
to

Fred S. ROSEN, M.D.

James L. Gamble Professor of Pediatrics

The Center for Blood Research, Harvard Medical School, Boston, USA

November 22, 1996, Vienna

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Fred S. ROSEN: 'Immunology comes to Austria'

Two hundred years ago, on July 1, 1796, Edward Jenner inserted live smallpox virus into the arm of a child, James Phipps. As Jenner anticipated, the child did not develop small- pox. On the preceding May 14, Jenner had removed pustular matter from a cowpox lesion on the hand of the milkmaid, Sarah Nelmes, and had made two scratches in the skin of the arm of James Phipps and applied the cowpox containing pustular exudate to the abrasions on the child's arm. Sarah Nelmes had acquired cowpox from milking a cow whose name was Blossom. Jenner reasoned that the child would be rendered immune to smallpox so he proceeded with this brazen experiment without benefit of the gratuitous advice of anyone preoccupied with medical ethics. I hasten to add that the word 'immune' was first used by Louis Pasteur in this context almost a century later. And in deference to Jenner, Pasteur applied the word 'vaccinate' to any procedure where an attenuated or killed microorganism would render a subject immune. The value of vaccination was rapidly appreciated in the whole civilized world but nowhere more so than in Vienna where the first laws were passed by the Austrian government to make vaccination compulsory in 1802. Later I will tell you how it came to pass that immunology came to Austria.

One hundred years ago the centenary of vaccination was celebrated worldwide. This year the bicentennial of this amazing discovery has gone practically unnoticed. Probably because smallpox has been eradicated and we have become blase and demanding of ever increasing numbers of medical wonders. The story of Jenner's discovery is worth recounting. Edward Jenner was the youngest of six children born to the Reverend Stephen Jenner and his wife in the village of Berkeley in Gloucestershire, which is in the western part of England. He was orphaned at an early age and his oldest brother sent him off to school at Wotton-Under-Edge and then to Cirencester, after which he was apprenticed at age 14, to a surgeon, a Mr. Ludlow, who practiced medicine such as it was, in the market town of Chipping Sodbury, close to Bristol. During these years Jenner learned that the milkmaids of the region never came down with smallpox and was specifically told this by one dairymaid who appeared in his consulting room with a pustular rash; she stated that smallpox could be ruled out because she had had the cowpox. This was in the 1760's, fully thirty years before Jenner performed his historic experiment. What took him so long? It is estimated that 60 million people died of the smallpox in the course of the 18th century. There were 35,000 deaths per annum in London alone and many thousands more were grossly disfigured after surviving the disease. Why did he delay despite the fact that he was obsessed with the notion that smallpox could be eradicated by protection afforded by cowpox inoculation? The answer can only be surmised but takes us back some 40 years.

When, in 1715, the Elector of Hannover was invited to sit on the English throne, the ascendancy of the Whig party became a fact of political life in England. Amongst them was a boring gentleman by the name of John Wortley-Monatgue, who was dispatched by George the First to the Sublime Porte of the Ottoman Turks to mediate peace between the Hapsburgs and the Sultan, the Turkish siege of Vienna having only been lifted some 22 years before this. So John Wortley-Montague plunged into Balkan politics to start a vexatious train of events that is alas still with us.

Fortunately he took along his astute and clever wife, albeit that she was grossly disfigured from having had the smallpox. They stopped in Vienna en route to Istanbul and Lady Mary Wortley-Montague made a number of astute observations on the Austrian court, but I shall not go into that today because it is not relevant to our tale. She was an avid letter writer and 52 of her letters from Istanbul have survived the ravages of time and come down to us. In several of these letters to her friend Sarah Chiswell of Nottingham she describes the practice among the Turks of variolation when old women went about and scraped smallpox lesions and inoculated the pustular material into susceptible subjects in the hope of producing a controlled mild smallpox infection that would protect against the real thing. The content of these letters found their way into the Transactions of the Royal Society.
Now amongst the subscribers to the Transactions was none other than the Calvinist leader of the Massachusetts Bay Colony, Cotton Mather, who decided that a massive variolation experiment should be carried out in the most populous of the English colonial cities, namely Boston, then comprised of some 50,000 Calvinist saints -and strangers, who plied more ancient professions. He enlisted the help of Dr. Zabdiel Boylston, whose house still stands where the Worcester Pike (or route 9) rises from Brookline Village, to speed travelers to the Wild West. In any event Boylston variolated over 2000 people in the winter of 1720-1721. There were two deaths, to be sure among Indian serving girls, certainly not due to the variolation, but panic spread, a bomb was thrown into Cotton Mather's house (civil violence had already been much manifest among these colonials) and the experiment was stopped. Mather's black slave told him he knew much about variolation as it had long been practiced in West Africa whence he came. In any event, Boylston was invited by the Princess of Wales to come to London to variolate the royal children. But first he had to prove his skill by experimenting on the prisoners at Newgate. Slowly the practice of variolation became widespread in the western world. Curiously, the best morbidity statistics were gathered by Benjamin Franklin in Boston in 1753-1754. He noted that one in a hundred subjects who were variolated died of the smallpox. This was to be compared with a mortality of approximately 15 to 20 % among those who acquired the infection naturally, a vast improvement.

We left Edward Jenner in Chipping Sodbury. Now in 1770 he responded to an ad of Sir John Hunter. 'On Monday evening the 4th of October, at seven o'clock, Mr. John Hunter will begin, at No. 28 in the Haymarket, London, a course of Lectures on the Principles and Practice of Surgery in which will be introduced so much of the Animal Economy as may illustrate the Principles of those Diseases which are the Object of Surgery. This course will be continued on Mondays, Wednesdays and Fridays, through the whole Winter, at the Hour above mentioned. Proposals may be seen, and Tickets will be delivered, in Jermyn Street. No Person will be admitted to the first Lecture without a Ticket for the course. Jenner went to 42 Jermyn Street to study with John Hunter, who took his students into his residence by St. James' in Picadilly, the westernmost of the Wren churches, still standing. Mrs. Hunter was an accomplished musician who befriended Franz Josef Haydn on his visits to London and she wrote the words for Haydn's Creation. Jenner was a competent flutist and must have spent many a musical soiree in this abode. But he came to hate London and longed to return to his native village. He hated the filth and the frenzied mobs attending the public hangings at Tyburn, within earshot of St. George's Hospital, where he worked. And the fashionable pastime of gawking at the inmates and whores at Newgate Prison was not his idea of amusement. Five million gallons of gin were consumed a year in London at a ha'penny a glass, untaxed, it replaced mother's milk. Hogarth's 'Gin Lane' was not a vision but a reality.


Fig. 1

Hunter was impressed with his young student. He asked him to stay on in London. He sent him to Sir Joseph Banks to classify all the botanical specimens that had been brought back to London from Cook's first voyage to the South Pacific ocean. It was a rigorous assignment. He was asked to join Cook's next voyage to collect specimens but declined the offer and returned to Berkeley. By this time he was a polymath with broad scientific interests and Hunter had become the parent that he really never knew. He remained demanding of Jenner who kept sending him specimens of hedgehogs and fish from the Bristol channel and all manner of biological curiosities. Jenner set about to solve the problem of the nesting habits of English cuckoos. His startling findings were eventually published by the Royal Society and he was elected to membership in the Royal Society on the basis of this landmark study. He also was the first to examine a heart from a patient with angina pectoris, which had just been described as a clinical entity by Heberden. He established that it was due to calcification of the coronary arteries; his first thought was that plaster had dropped from the ceiling of his dissecting room onto the specimen, he was so amazed by his findings. He reported his findings to local medical clubs that he organized but refused to publish his report on the causes of angina pectoris because he knew that Hunter had developed symptoms of the disease and was afraid of dismaying his mentor. In an age when theory triumphed over experiment, Hunter wrote him 'Just do the experiment!' while Jenner procrastinated. But this comment was not evoked by the musings about cowpox but about the cuckoos. Hunter died three years before Jenner undertook to vaccinate James Phipps.

This is the only portrait we have of Jenner, done by Northcote in 1803 (Fig. 1). He has an intelligent and kindly face, a combination of characteristics rarely encountered among the English. Fig. 2 shows the chantry house where he lived and practiced medicine and where he vaccinated James Phipps. Grape vines that he planted are still on the south side of the house and are not visible in this picture. Off to the right of the figure is the parish church where Jenner and his wife are buried and in the back can be seen the wall of Berkeley Castle, whose owner, the Earl of Berkeley, was a staunch supporter of Jenner. Fig. 3 shows the so-called Temple of Vaccinia, in the garden of the house. Here Jenner attended to hundreds of eager patients who came to be vaccinated. His wife, Katharine Jenner preferred not to have the local peasants tramping through her house. Fig. 4 is an artist's rendition of Jenner while vaccinating James Phipps. Fig. 5 shows immortal Blossom. Nothing has changed in two centuries in the village of Berkeley and I warmly recommend that you pay a visit to this place if you are in the neighborhood. Oxford is an hour and a quarter away.

Jenner's experiment received instant notoriety and within a very short time cowpox virus was disseminated around the world. His Quaker friend John Lettsom, sent cowpox in a quill to Benjamin Waterhouse, Hersey Professor of the Theory of Physics at the Harvard Medical School and physician-in-chief at the Massachusetts General Hospital. Vaccination became the rage. President Thomas Jefferson got hold of some of the material from Waterhouse and vaccinated a few thousand people.
He also invented a special flask for the safe transport of vaccination material. Expeditions were sent out by the Royal Navy and the King of Spain to vaccinate hundreds of thousands of people. Jenner's fame was such that when an aide read Napoleon a letter from an Englishman asking for the release of prisoners and then informed him that the Englishman with such audacity was Jenner, 'Ah Jenner' replied Bonaparte, 'Nous ne pouvons refuser rien a cet homme!'. Yet the Royal Society refused to publish his manuscript. It was all too novel and the editor, Sir Joseph Banks, thought it might ruin Jenner's reputation.


Fig. 2

Rather than battle the editors, Jenner published at his own expense 'An Inquiry into Cause and Effects of the Variolae Vaccinate, a Disease discovered in some of the Western Counties of England, particularly Gloucestershire, and known by the name of Cow Pox'. It sold for 7 shillings six pence. When I last inquired at Mott's in Berkeley Square for a copy it was quoted at seven thousand five hundred pounds sterling, if a copy were available.

Within a few months the Inquiry had been translated into German by one Dr. Ballhorn of Hanover. This undoubtedly came into the hands of Dr. Jean De Carro, who was resident in Vienna. He had been born and reared in Geneva but had left that city during the political upheavals that led to this canton joining the Swiss confederation. He went to Edinburgh to receive a medical education and then came to Vienna where he remained to practice medicine. In May, 1799 he carried out the first vaccinations in this City. He had written to Jenner for cowpox matter as he could find none in the local cows. Lord Grenville, the foreign secretary despatched cotton threads soaked with cowpox, to Mr. Stratton, Secretary of the British Legation in Vienna for De Carro's use. I might add that the correspondence between Jenner and Jean De Carro lasted for the rest of Jenner's life, for some 25 years.


Fig. 3

In 1801 De Carro vaccinated an English couple visiting Vienna, the parents of Lady Elgin whose husband, Lord Elgin was the British ambassador in Istanbul. Material was sent to Lord Elgin by De Carro to vaccinate his son and from this child's arm vaccinia was spread from Istanbul to Corinth and Athens and eventually to India, all from this Viennese source. Since cowpox vaccination was not standardized and frequently confused with variolation, which served as a source of smallpox itself, several accidents occurred and the compulsory vaccination laws were temporarily suspended throughout Austria in 1803 but re-instituted in 1806. Vienna was, with Copenhagen, the first city in the world to rid itself of smallpox, because of the industry and zeal of Jean De Carro. As I mentioned De Carro continued a vigorous correspondence with Jenner, who, among other things, urged De Carro to give cowpox to dogs to prevent distemper. De Carro wrote to Jenner, who thought otherwise, that the experiment did not work. In the 18th century scientists conducted research at their own expense.


Fig. 4

If they were successful they were recompensed by the sovereign authority. Indeed a Committee of Enquiry set up by the Commons and the House of Lords voted Jenner 10,000 pounds, after deciding that his work was original and for the public good. And a few years later another 20,000 pounds were granted him because he had become impoverished by his exertions to prove the value of vaccination. Now two centuries later we have come to a different modus operandi when scientists expect to be kept in the proper style from the public coffers. The gainfully unemployed no longer do science. The last person I knew who so qualified was John Enders, who cultivated poliovirus and measles virus for the ultimate benefit of mankind, largely at his own expense. When he was finally rewarded with the Nobel Prize, he insisted on sharing it with two young colleagues. Then he called his father, chairman of the Federal Reserve Bank for the District of New York, and his news was greeted with 'Who ever heard of getting a prize for doing your work?' Maybe we could take a lesson from the way things were. After all it took almost a century before Harrison succeeded in collecting the prize awarded by the English Parliament for determining the longitude of Kingston, Jamaica.


Fig. 5

I have now told you something of Edward Jenner and I could go on with much more about this fascinating man - clearly no country doctor as is much advertised. And perhaps I have told you enough about him for you to surmise why it took him 30 years to undertake what is arguably the most important experiment ever performed in medicine. His correspondence with De Carro, which vividly depict the origins of immunology in Austria, are on file at the Royal Society of Medicine in Wimpole Street, London.



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