Analgesics: high dose aspirin reduces ● May cause neurological side eﬀects in excretion (risk of toxicity) buy generic sildenafil 75mg on-line cialis causes erectile dysfunction. Some editors every 8 hours report no experience of interaction locally; ● Herpes simplex encephalitis: normal or possibly increased risk of nephrotoxicity purchase discount sildenafil line erectile dysfunction protocol secret. Antibiotic dosing in critically ill ● Monitor aciclovir levels in critically ill adult patients receiving continuous renal patients cheap sildenafil 50 mg without prescription elite custom erectile dysfunction pump. Assume dose as ● Start with the lowest dose possible and in normal renal function. Molecular weight (daltons) 148 000 ● Manufacturer is unable to provide a dose % Protein binding No data in renal impairment due to lack of studies. Te half-life in ● Neither the kidney nor the liver are vitro is estimated to be less than 10 seconds, involved in the degradation of exogenous and may be even shorter in vivo. Albendazole sulfoxide is eliminated in the bile; only a small amount appears to be excreted in the urine. Clearance decreases antihistamine and paracetamol 30 minutes with repeated administration due to before treatment. Combination therapy tissues but is then rapidly redistributed to with alendronate and intravenous bone or excreted in the urine. Tere is no calcitriol for the treatment of secondary evidence that alendronate is metabolised hyperparathyroidism in hemodialysis in animals or humans. Calcitriol is inactivated in both the kidney and the intestine, ● Adjust dose according to response. Vitamin an oral solution (2 micrograms/mL) are D compounds and their metabolites are also available. Alternatively, give considered to have a negligible contribution 5 micrograms immediately prior to to vitamin D status. Potentially hazardous interactions with other Discontinue infusion 30 minutes before drugs anticipated end of surgery. Alfentanil is metabolised in the liver; ● Sodium oxybate: enhanced eﬀect of oxidative N - and O-dealkylation by the sodium oxybate – avoid concomitant use. Fluid Restricted Critically Ill Patients, 3rd ● Analgesic potency = 1/4 that of fentanyl edition, 2006). Te relationship of the excretion products in ● Signiﬁcant amounts of alimemazine urine and faeces is 75:25%. Volume of distribution 135 litres ● Grapefruit juice: concentration of (L/kg) aliskiren reduced – avoid concomitant Half-life – normal/ 34–41/Unchanged administration. Terefore eﬀective ● Take as a single daily dose, preferably after inhibition of xanthine oxidase is maintained food. After 4 to 5 days, ● Peripheral oedema may occur in some 90% of the dose appears unchanged in patients; should be considered when urine. Te rate is considerably inﬂuenced by the drug is prescribed for those with urinary pH: a rise in pH brings about a fall in congestive heart failure. Ambrisentan is excreted mainly by the liver, although the contribution of Reference: hepatic metabolism and biliary excretion is 1. Dose as in normal renal cisplatin of less than 100 mg/m2 are used: ﬂ u x function. It is excreted over 30 minutes in the urine unchanged, primarily by ● (Diluents: sodium chloride 0. Fluid Restricted Critically Ill Patients, 3rd 10–20 3–4 mg/kg every 24 hours or as per edition, 2006). Tere is ventricular arrhythmias with chloroquine, very little urinary excretion of amiodarone hydroxychloroquine, meﬂoquine and or its metabolites, the major route of quinine and possibly with piperaquine excretion being in faeces via the bile; some with artenimol – avoid concomitant use; enterohepatic recycling may occur. Care Group, Minimum Infusion Volumes ● Fingolimod: possible increased risk of for Fluid Restricted Critically Ill Patients, bradycardia. Half-life – normal/ 12/Unchanged ● Antidepressants: increased level of tricyclics. Amisulpride is eliminated ● Antipsychotics: increased risk of unchanged in the urine. Fifty per cent of an ventricular arrhythmias with droperidol, intravenous dose is excreted via the urine, of sertindole – avoid concomitant use. Te area under the curve of amisulpride in mild renal failure is increased 2-fold, and almost 10-fold in moderate renal failure. Amitriptyline is excreted in the urine, mainly ● Antimalarials: avoid concomitant use with in the form of its metabolites, either free or artemether/lumefantrine and piperaquine in conjugated form. Calcium- channel blocker: ● Antibacterials: metabolism possibly ● Hypertension inhibited by clarithromycin, erythromycin ● Angina prophylaxis & telithromycin. Volume of distribution 20 ● Lipid lowering agents: possibly increased (L/kg) risk of myopathy – do not exceed 20 mg of Half-life – normal/ simvastatin. Te metabolic fate of amphotericin B in ● Increased risk of nephrotoxicity with humans has not been fully elucidated. Over a 7-day hypokalaemia (avoid concomitant use period, the cumulative urinary excretion of unless corticosteroids are required to a single dose of conventional amphotericin control reactions). It ● Cytotoxics: increased risk of ventricular has been estimated that only about 2–5% of arrhythmias with arsenic trioxide. Prepare to phospholipids; the pharmacokinetic intermittent infusion in glucose 5% properties of Abelcet and conventional (incompatible with sodium chloride 0. Pharmacokinetic studies showed that, after ● Dilute to a concentration of 1–2 mg/mL. Over a 7-day ● Corticosteroids: increased risk of period, the cumulative urinary excretion of hypokalaemia (avoid concomitant use a single dose of conventional amphotericin unless corticosteroids are required to B is about 40% of the administered drug. Prepare intermittent infusion reported in the literature for conventional in glucose 5% (incompatible with sodium presentations of amphotericin B, with higher chloride 0. Volume of distribution ● Corticosteroids: increased risk of 4 (L/kg) hypokalaemia – avoid concomitant use unless corticosteroids are required to Half-life – normal/ 24–48 (up to 15 days control reactions. Prepare intermittent infusion kidneys; slow release of the drug from the in glucose 5% (incompatible with sodium peripheral compartment may account for chloride 0. Over a 7-day Reconstitute vial contents with water for period, the cumulative urinary excretion of injection. Fluid Restricted Critically Ill Patients, 3rd <10 Dose as in normal renal function. Can also synergistically when co-administered give antihistamines and corticosteroids to enabling lower doses to be used eﬀectively. High concentrations are reached ● Ampicillin may be used in peritoneal in bile; it undergoes enterohepatic recycling dialysis ﬂuids for treatment of peritonitis. Te principal metabolites, produced ● Increased risk of side eﬀects in renal via microsomal oxidation, are much more impairment.
Whenever ablation is performed in the region of the sinus node discount sildenafil 50 mg online erectile dysfunction hypothyroidism, the patient should be apprised of the chance of needing a pacemaker after the procedure purchase sildenafil 50 mg amex impotence 16 year old. Results Although a good technical result may be obtained at the time of the procedure for inappropriate sinus tachycardia 100mg sildenafil with visa erectile dysfunction ka desi ilaj, symptoms often persist because of recurrence of rapid sinus rates (at or near preablation rates) or for nonarrhythmic reasons. In some, after the atrial rate decreases, an inappropriately rapid junctional rhythm (80 to 90/min) is present; this may indicate an overall increased sensitivity of cells with pacemaker capacity to catecholamines in these patients. Multiple ablation sessions are needed in some patients, and approximately 20% eventually undergo pacemaker implantation; however, not all these patients have relief of symptoms, including palpitations, despite a normal heart rate. Radiofrequency Catheter Ablation of Atrial Tachycardia Atrial tachycardias are a heterogeneous group of disorders; causative factors include rapid discharge of a focus (focal tachycardia) and reentry. Sites tend to cluster near the pulmonary veins in the left atrium and the mouths of the atrial appendages and along the right atrial crista terminalis (Figs. Ablation should not be performed at a site at which this is seen, if at all possible. In both panels the interval from the end of one P wave to the beginning of the next (atrial diastole) is in gray. Two tachycardia complexes are shown; the earliest site found (Abldist, at which ablation eliminated the tachycardia) is shown as a multicomponent recording that starts only approximately 40 milliseconds before onset of the P wave. The unipolar recording (AblUni-d) has a deep negative deflection (indicating propagation away from the electrode). The ablation catheter is in the posterior right atrium, where a fragmented signal (between arrows) is recorded that almost fills atrial diastole. The atria are viewed from the front with the right atrial free wall retracted to show the interior. Structures are labeled as shown; right atrial foci appear in shades of blue, left atrial foci in shades of red. Arrows depict a double loop of reentry around presumed scars with a common diastolic pathway between scars. The tachycardia cycle length (240 msec) is entirely represented in the range of colors. The region of slow conduction is typically related to an end of an atriotomy or previous ablation scar, the location of which varies from patient to patient. Therefore, preprocedural review of operative and ablation procedure reports and careful electrophysiologic mapping are essential. Because reentry within a complete circuit is occurring, activation can be recorded throughout the entire cardiac cycle. The ablation strategy is to identify regions with mid-diastolic atrial activation during tachycardia (Fig. Focal ablation of these sites can then be performed, but often tachycardia can still be initiated (usually at a slower rate) or recurs after the procedure. Because these sites are typically located at a relatively narrow zone between the ends of previous scars, surgical incisions, or ablation lines and another nonconducting barrier (e. Understanding of the reentrant pathway in all forms of atrial flutter is essential for development of an ablation strategy (see Chapter 37). Reentry in the right atrium, with the left atrium passively activated, constitutes the mechanism of the typical electrocardiographic variety of atrial flutter, with caudocranial activation along the right atrial septum and craniocaudal activation of the right atrial free wall (Fig. Ablating tissue in a line between any two anatomic barriers that transects a portion of the circuit necessary for perpetuation of reentry can be curative. Typically, this is across the isthmus of atrial tissue between the inferior vena caval orifice and the tricuspid annulus (the cavotricuspid isthmus), a relatively narrow point in the circuit. Less frequently, the direction of wavefront propagation in this large right atrial circuit is reversed (“clockwise” flutter proceeding cephalad up the right atrial free wall and caudad down the septum, with upright flutter waves in the inferior leads; Fig. Ablation can be more difficult in these cases, which often occur in the setting of advanced lung disease or previous cardiac surgery or ablation. A common theme in these complex reentrant arrhythmias is the presence of an anatomically determined zone of inexcitability around which an electrical wavefront can circulate. Specialized mapping tools and skills are necessary to achieve successful ablation in these cases. On the left, the wavefront of atrial activation proceeds in a clockwise fashion (arrows) along the annulus, whereas on the right, the direction of propagation is the reverse. B, Ablation of the isthmus of atrial tissue between the tricuspid annulus and the inferior vena caval orifice for cure of atrial flutter. Recordings are displayed from the multipolar catheter around much of the circumference of the tricuspid annulus (see the left anterior oblique fluoroscopic images). In the two beats on the left, atrial conduction proceeds in two directions around the tricuspid annulus, as indicated by arrows and recorded along the halo catheter. In the two beats on the right, ablation has interrupted conduction in the floor of the right atrium, thereby eliminating one path for transmission along the tricuspid annulus. The halo catheter now records conduction, proceeding all the way around the annulus. This finding demonstrates a unidirectional block in the isthmus; block in the other direction may be demonstrated by pacing from one of the halo electrodes and observing a similar lack of isthmus conduction. However, with use of these criteria, up to 30% of patients had recurrent flutter because of lack of complete and permanent conduction block in the cavotricuspid isthmus. Thus the current endpoint of ablation has changed to ensuring a line of bidirectional block is present in this region, usually by pacing from opposite sides of the isthmus (Fig. Results Regardless of circuit location, atrial flutter can be ablated successfully in more than 90% of cases, although patients with complex right or left atrial flutter require more extensive and complex procedures. Recurrence rates are less than 5% except in patients with extensive atrial disease, in whom new circuits can develop over time as new areas of conduction delay and block form. Complications are rare and include inadvertent heart block and phrenic nerve paralysis. To achieve this, a catheter is placed across the tricuspid valve and positioned to record a small His bundle electrogram associated with a large atrial electrogram. These patients can undergo an attempt from the left ventricle with a catheter positioned along the posterior interventricular septum, just beneath the aortic valve, to record a large His bundle electrogram. Since then, backup pacing rates are set to 80 to 90/min for the first 1 to 3 months after ablation in most cases, which has almost entirely eliminated this problem. Improvements in quality-of-life indices, as well as in cost-effectiveness, have been demonstrated for this procedure. Also, the target for ablation must be fairly circumscribed and preferably endocardially situated, although catheter mapping and ablation from the epicardial surface after percutaneous pericardial access is performed in many centers. In patients with bundle branch reentry, ablation of the right bundle branch eliminates the tachycardia. In the recordings from the unsuccessful ablation site, the unipolar signal (arrowhead) has a small r wave, which indicates that a portion of the wavefront from the focus of tachycardia is approaching the site from elsewhere. As a result of the extensive derangement in electrophysiology caused by the previous damage (e.
Auscultate the Cranium Assess occupational exposure to other toxins through Intracranial arteriovenous malformations may mimic an occupational history buy sildenafil with a mastercard erectile dysfunction medication patents. Auscultate the orbit and skull to evaluate for heater may cause headaches that occur during winter cranial bruits buy sildenafil once a day erectile dysfunction pills cvs. Observe the Patient Ipsilateral lacrimation generic sildenafil 25 mg mastercard erectile dysfunction treatment emedicine, ptosis, and pupillary con- Assess level of alertness and orientation to person, striction are seen with cluster headache. A half-feld defect is seen with Rhinorrhea and congestion are seen with sinus head- parietal lobe tumor. Observe teeth and oral mucosa because upper cause an enlargement of the pupil from compres- molar disease and poor dentition can cause headache. The di- Tapping on the teeth or biting down on a tongue blade lated pupil is always on the side of the expanding can elicit pain from sinusitis. See eyes in a lateral direction) may be found with acute Chapter 15 for a discussion of examination techniques. Nystagmus sug- Enlarged pupils seen during a headache indicate gests a brainstem or cerebellar lesion and is usually migraine; however, if they outlast a headache, then ipsilateral. Vertical and Upper motor neuron facial weakness may be pre- rotatory nystagmus suggests central posterior fossa sent in hemiplegic migraine. Trigeminal neuralgia pain can be On ophthalmoscopic examination, note contour of the triggered by stimulation of the affected nerve. Test taste on the anterior two Papilledema is often caused by an expanding intra- thirds of the tongue for sweet and salt discrimination. Retinal deafness should be investigated to rule out acoustic hemorrhage in children may indicate abuse. The sense of smell resis that can be assessed by observing the protruded may be lost when the olfactory nerve is damaged by tongue drift laterally or by the inability to hold position head injury or by a tumor in the vicinity of the olfac- against resistance. Herpes simplex encephalitis can lead to a destruction of the olfactory cortex or olfactory Examine the Neck nerve. Rarely does of the neck to observe for stiffness or diffculty with poor vision contribute to a headache. Poor vision movement, which may indicate muscle tension or men- may contribute to eye pain, but children equate this ingismus. Headaches as a result of pituitary tumors are usually Test for Meningismus associated with defects in the peripheral vision. Uni- Normally the chin can be fexed passively to touch the lateral or homonymous hemianopsia (a loss of the chest. If neck stiffness (nuchal rigidity) is present, this same half of the visual feld of both eyes) can occur maneuver is not possible. With the patient supine, with migraines or brain tumor headaches when the attempts to fex the neck cause involuntary hip fexion, tumor is in the occipital lobes or adjacent to the and the hips rise (Brudzinski sign). Assess Motor Strength and Coordination Blood Cultures of Extremities Blood cultures should be drawn in a patient who has a Asymmetrical increase in muscle tone on the affected fever, headache, nuchal rigidity, and altered mental side, contralateral to the hemisphere lesion, suggests a status. The gait is also wide-based and Magnetic Resonance Imaging halting, and the patient turns with jerky movements. It is the frst imaging choice for hops on either foot or stands tandem (one foot behind a brain abscess. Increase in, or asymmetry of, refexes is seen mal values of components that are altered by disease with cerebral lesions. The plantar or Babinski response such as lymphocytes, glucose, protein, and presence is often present with cerebral lesions. The need Skull Radiograph to lie down is also associated with migraine head- A radiograph of the skull is useful in posttraumatic ache. Even very observe intracranial structures such as the pituitary young children (age 4) are able to draw stick fgures gland or paranasal sinuses. In bacterial nism of tension headache is uncertain but is related to 230 Chapter 19 • Headache sustained muscle contraction. Tension headache pro- cycles of days or weeks with remission lasting months duces a bilateral pain, general or localized, often de- to years. Associated symptoms include ipsilateral rhinor- scribed as a frontotemporal band-like distribution. The rhea, conjunctival injections, facial sweating, ptosis, and discomfort is described as a mild to moderate, non- eyelid edema. Alcohol ingestion, stress, or vasodilation throbbing pain, tightness, or pressure with a gradual secondary to wind or heat exposure may precipitate onset. Benign Exertional Headache These headaches occur suddenly and are related Migraine Without Aura (Common) to coughing, sneezing, straining, running, or orgasm. About 20% of adults experience migraines, and epi- Headache is the result of stretching the pain-sensitive sodes are not uncommon in children as young as structures in the posterior fossa. The onset is sudden and “splitting,” and and most often accompanied by nausea, photophobia, pain may last from seconds up to 30 minutes. Migraine headaches are Secondary Headaches most commonly found in adults 25 to 34 years of age Infectious Origin and are rare during pregnancy. Sinusitis is frequently associated with a sore present when attacks occur more than 15 days in throat irritated by postnasal discharge, facial or tooth a month. Migraine With Aura (Classic) There frequently is a cough that worsens in a lying Neurological signs that indicate cortical and/or brainstem position, morning periorbital swelling, fever, malaise, involvement precede classic migraine headaches. Ethmoid sinusitis pro- pain may be associated with photophobia, phonophobia duces medial orbit pain. Patients with dental abscess, precedes but may accompany a headache or occur with- nerve root dysfunction, or infection may have head- out headache. Tenderness elicited by tapping on the maxillary teeth Mixed Headache with a tongue blade may indicate dental root infection Mixed headaches are a combination of muscular con- or maxillary sinusitis. The headache is reveal ulceration or infection of pain-sensitive struc- experienced as a throbbing, constant pain during wak- tures in the oral mucosa and gingiva. Family history of migraine is not sensitive structures in the oropharynx, leading to uncommon. Recurrent otitis media with sequelae Cluster Headache of mastoiditis or chronic infection may result in head- Cluster headaches are of vascular origin and are less ache. Bacterial meningitis begins as bacteria The pain is unilateral, ocular, or periocular, and de- colonize in the nasopharynx and enter the central ner- scribed as burning, piercing, or neuralgic. Cluster vous system through the dural venous sinuses or cho- headaches occur more often in men and last 15 minutes roid plexus into the subarachnoid space. The episodic recurrences are “clustered” in organisms in adults are Staphylococcus pneumoniae Chapter 19 • Headache 231 and meningitidis. In children, common organisms are ciliary branches of the internal carotid artery. Other symptoms include fever, malaise, anorexia, systemic toxicity and mental status changes (encephali- weight loss, and/or polymyalgia rheumatica. In contrast, aseptic meningitis caused by enterovi- jaw pain and face pain are rare but highly suggestive.
Throughout the virus life cycle generic 75mg sildenafil with visa food erectile dysfunction causes, the relative levels of different viral proteins are controlled by promoter usage and by differen- tial splice site selection purchase generic sildenafil line erectile dysfunction pills walgreens, with an increase in the level of E1 and E2 allowing an increase in viral copy number in the upper epithelial layers (Ozbun and Meyers 1998a) generic 25mg sildenafil otc erectile dysfunction pills cheap. To compensate the role of E7 in reducing unlimited replication potential, high- risk E6 proteins have evolved to target the tumor suppressor p53 for degradation, preventing cell growth inhibition in both undifferentiated and differentiated cells. These results indicate that the role of E6 is not to overcome p53 induced apoptosis as previously proposed from studies in cell lines. As highlighted by this recent study, the exact role of E6 in the viral life cycle remains to be understood. As a result, virus copy-number ampliﬁes from 50 to 200 copies to several thousands of copies per cell (Bodily and Laimins 2010; Bedell et al. Genetic analyses have shown that both E1^E4 and E5 are necessary and contribute to the activation of late viral functions upon differentiation (Fehrmann et al. Viruses adapt to this constraint by causing G2 arrest, thus creating a window of opportunity for their own ampliﬁcation (Chow et al. The ability to induce G2/M arrest is a feature of viruses from a range of different families. It has also been reported that low level caspase activation by E6 and E7 upon differentiation, induces cleavage of the E1 protein, which results in enhanced binding of E1 to the origin and the ability to replicate in an E2- independent manner (Moody et al. The primary role of miR-203 is to suppress the proliferative capacity of epithelial cells upon differentiation (Sonkoly et al. One signiﬁcant target of miR-203 is the transcription factor p63, a p53 family member which is known to be critical in the development of stratifying epithelia in human (Rinne et al. Since p63 promotes cellular proliferation, reduced levels of p63 are important for normal epithelial differentiation in which cells exit the cell cycle. The molecular mechanisms that lead to activation of the late promoter and up- regulation of E1/E2 expression are not yet well understood, and it remains possible that this promoter is constitutively active at all stages during the productive cycle (Doorbar 2005). The newly replicated genomes would serve as templates for the further expression of E1 and E2, which would facilitate additional ampliﬁcation of viral genomes and in turn, further expression of the E1 and E2 replication proteins (Middleton et al. In two dimensional gels, this pattern has been demonstrated by the well- characterized T4 in vitro replication system (Belanger et al. The loss of E7 function initiates a switch from the early viral replicative phase to the late phase, during which the capsid proteins are expressed for virion morphogenesis (Wang et al. After translation in the cytoplasm, L1 proteins pentamerize into capsomeres, and are then imported into the nucleus using the cellular alpha and beta karyopherins (Bird et al. In natural lesions, expression and nuclear translocation of L2 precedes expression of L1 (Florin et al. Nuclear translocation of L2 also requires Hsc70 that transiently associates with viral capsids during the integration of L2, possibly via the L2 C terminus. Comple- tion of virus assembly results in displacement of Hsc70 from virions (Florin et al. Virus like particles, however can be assembled by expression of L1 alone, the L2 protein is thought to enhance packaging and infectivity (Stauffer et al. L2 interacts with L1 pentamers through the hydrophobic region in its C-terminus (Finnen et al. The interaction between capsomeres is mediated by the C-terminus of the L1 protein (Modis et al. Papillomavirus virions undergo a very long assembly process within tissue which is dependent on disulﬁde bond formation (Conway and Meyers 2009). Ultimately, virus release requires efﬁcient escape from the corniﬁed envelope at the cell surface. Thus, it represents a by-product of viral infection that may confer a selective advantage to the host cell without any apparent advantage to the virus (Pett and Coleman 2007; Jeon et al. Disruption of the viral genome also dissociates viral early (E) gene transcription from the viral early polyadenylation signal. Using host poly(A) signals, increases the stability of virus–host fusion transcripts with a longer half life (Jeon and Lambert 1995). In general, integration leads to increased expression and stability of transcripts encoding the E6 and E7 proteins, along with the disruption of E2 protein. The overall differentiation-dependent papillomaviral gene expression observed in vivo and in vitro involves promoter repression in the lower strata and activation in the upper, differentiated strata. In contrast, malignant cervical cancer cells retained the ability to express viral oncogenes following grafting (including basal layers), suggesting that mechanisms of viral transcriptional silencing were no longer functional in these cells. These new insights indicate earlier assumption that cervical neoplastic progression occurs through integrant-only cells outgrowing episome-only cells is likely to be oversimpliﬁed. Progression of precursor lesions to cervical malignancy is characterized by a complex interplay between viral and host events. Progression of low-grade disease represents a breakdown of host controls that normally inhibit expression of episomal E6/E7 in the proliferating basal cells of the cervical squamous epithelium. Late events are host genomic changes that are associated with acquisition of the invasive phenotype. Progression of high-grade disease is characterized by clonal expansion of cells expressing E6 and E7 at an elevated level, with consequent high- level genomic instability and acquisition of mutations (Pett et al. Other factors, such as secondary infection with other pathogens, may cause integrant selection by activating innate immune mechanisms that lead to episome clearance (See Chap. Increased acetylation, especially of the late promoter region suggests that altered chromatin structure may have been responsible, at least in part, for the transcriptional deregulation in episome- associated neoplastic progression. The L1 major capsid protein of human papillomavirus type 11 recombinant virus- like particles interacts with heparin and cell-surface glycosaminoglycans on human keratinocytes. Biology of the syndecans: a family of transmembrane heparan sulfate proteoglycans. Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses. Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. Inhibition of transfer to secondary receptors by heparan sulfate-binding drug or antibody induces noninfectious uptake of human papillomavirus. Mechanisms of human papillomavirus type 16 neutralization by l2 cross-neutralizing and l1 type-speciﬁc antibodies. Viral entry mechanisms: human papillomavirus and a long journey from extracellular matrix to the nucleus. Keratinocyte- secreted laminin 5 can function as a transient receptor for human papillomaviruses by binding virions and transferring them to adjacent cells. Human papillomaviruses bind a basal extracellular matrix component secreted by keratinocytes which is distinct from a membrane-associated receptor. Human papillomavirus type 31 uses a caveolin 1- and dynamin 2-mediated entry pathway for infection of human keratinocytes. Human papillomavirus type 16 infection of human keratinocytes requires clathrin and caveolin-1 and is brefeldin a sensitive. Analysis of the infectious entry pathway of human papillomavirus type 33 pseudovirions.