Revealing the impact of local access-site complications and upper extremity dysfunction post transradial percutaneous coronary procedures.

OBJECTIVES: Little is known about local access-site complications and upper extremity dysfunction after transradial percutaneous coronary procedures (TR-PCP). This systematic review study aimed to summarise the current knowledge on the incidences of access-site complications and upper extremity dysfunction after TR-PCP. METHODS: Two independent, trained investigators searched MEDLINE, EMBASE and CENTRAL for eligible studies published before 1 January 2015. Also, they hand-searched the conference proceedings of the annual scientific sessions of the American College of Cardiology, the American Heart Association, European Society of Cardiology, and the Trans-catheter Cardiovascular Therapeutics. Inclusion criteria were cohort studies and clinical trials discussing the incidence of access-site complications and upper extremity function after transradial percutaneous coronary intervention (TR-PCI) and/or transradial coronary angiography (TR-CAG) as endpoints. RESULTS: 176 articles described access-site complications. The incidence is up to 9.6 %. Fourteen articles described upper extremity dysfunction, with an incidence of up to 1.7 %. Upper extremity dysfunction was rarely investigated, hardly ever as primary endpoint, and if investigated not thoroughly enough. CONCLUSION: Upper extremity dysfunction in TR-PCP has never been properly investigated and is therefore underestimated. Further studies are needed to investigate the magnitude, prevention and best treatment of upper extremity dysfunction. Optimising TR-PCP might be achieved by using slender techniques, detection of upper extremity dysfunction and early referral to a hand rehabilitation centre.

Lymphoid tissue viral burden and duration of viral suppression in plasma.

OBJECTIVES: To assess virological response in lymphoid tissue and its impact on the durability of response in plasma in HIV-1-infected persons who achieved sustained suppression of plasma viraemia with different antiretroviral regimens. METHODS: Consecutive patients on first-line antiretroviral therapy were included if they had a plasma HIV-1 RNA viraemia < 20 copies/ml within the last 6 months and tonsillar tissue accessible for biopsy. First-line therapy contained two nucleoside analogues: alone (2NRTI group, n = 3); plus a HIV-1 protease inhibitor (PI group, n = 11) or plus nevirapine (NVP group; n = 16). Patients were followed until virus was detectable in plasma, they changed therapy or were lost to follow-up. RESULTS: Tonsillar HIV-1 RNA could be detected (> 100 copies/mg) in 10 patients: one in the PI group (9%), six (38%) in the NVP group and in all three patients in the 2NRTI group. Primary resistance mutations could be detected in only 2 of these 10 patients. After a median of 9 months after the biopsies, viral suppression in plasma had failed in 6 of these 10 patients whereas failure had only occurred in 1 out of 20 with initially undetectable viral load in lymphoid tissue (P = 0.01; log rank test). CONCLUSIONS: In patients with sustained viral suppression in plasma, triple therapy including a HIV-1 protease inhibitor was more potent than triple therapy containing nevirapine or dual therapy with nucleoside analogues to reduce viral burden in lymphoid tissue. A worse response in lymphoid tissue could not be explained by local selection of resistance and was associated with a less durable virological response in plasma.

Laboratory guidelines for the practical use of HIV drug resistance tests in patient follow-up.

HIV drug resistance is one of the major limitations in the successful treatment of HIV-infected patients using currently available antiretroviral combination therapies. When appropriate, drug susceptibility profiles should be taken into consideration in the choice of a specific combination therapy. Guidelines recommending resistance testing in certain circumstances have been issued. Many clinicians have access to resistance testing and will increasingly use these results in their treatment decisions. In this document, we comment on the different methods available, and the relevant issues relating to the clinical application of these tests. Specifically, the following recommendations can be made: (i) genotypic and phenotypic HIV-1 drug resistance analyses can yield complementary information for the clinician. However, insufficient information currently exists as to which approach is preferable in any particular clinical setting; (ii) when HIV-1 drug resistance testing is required, it is recommended that testing be performed on plasma samples obtained before starting, stopping or changing therapy, on samples that have a viral load above the detection limit of the resistance test; (iii) the panel recommends that genotypic and phenotypic HIV-1 drug resistance testing for clinical purposes be performed in a certified laboratory under strict quality control and quality assurance standards; and (iv) the panel recommends that resistance testing laboratories provide clinicians with resistance reports that include a list of drug-related resistance mutations (genotype) and/or a list of drug-related fold resistance values (phenotype), with interpretations of each by an experienced virologist. The interpretation of genotypic and phenotypic analysis is a complex and developing science, and in order to understand HIV-1 drug resistance reports, communication between the requesting clinician and the expert that interpreted the resistance report is recommended.

Ultrastructural and quantitative motoneuronal changes after ventral root avulsion favor early surgical repair.

This study assesses qualitative and quantitative morphological changes that occur in motoneurons after ventral root avulsion. The motoneuronal perikaryal changes in the ventral horn of the cat's C7 cord segment were studied after survival times of 2, 8, 14, 30, 60 and 90 days. Generally, large motoneurons showed a light type of reaction, and the small ones either light or dark. In addition, neurons with a normal ultrastructural appearance were found. These latter are considered to be in a 'steady state', which may be associated with regenerative potency. All these types of neuron reactions were present at all survival times, but the number of cells marked by a specific reaction depends on the time of survival. Qualitative and quantitative evidence is given for cell death in 36% of the motoneuronal population between 2 and 14 days after avulsion. This reduction primarily concerns large, presumably alpha motoneurons with the light type reaction. Small, presumably gamma motoneurons become seriously affected after 14 days. These findings suggest that early surgical repair may have the better chances for clinical recovery.

Genotyping of hepatitis C virus isolates using CLIP sequencing.

Determination of hepatitis C virus (HCV) genotypes and subtypes has become increasingly important for the clinical management and prognosis of HCV infections. The aim of the present study was to assess the specificity and reliability of a newly developed, commercially available HCV genotyping kit (TRUGENE HCV 5'NC genotyping kit). This technique utilizes PCR fragments previously generated by the diagnostic Roche AMPLICOR HCV test, which are subsequently subjected to simultaneous PCR amplification and direct sequencing (CLIP sequencing) of the 5' noncoding region (5'NCR). HCV isolates from 100 randomly chosen patients were genotyped by both the TRUGENE HCV 5'NC genotyping kit and DNA enzyme immunoassay (DEIA). Typing results obtained by both methods were in complete concordance in 91% of the cases. HCV RNA from the samples with discordant genotype assignment in both assays was additionally amplified with primers from the HCV core and NS5B regions. Phylogenetic analysis of the obtained sequences supported the results obtained from DEIA in six cases and CLIP sequencing in two cases. In the former six cases, the TRUGENE HCV 5'NC genotyping kit could not correctly differentiate between subtypes of genotypes 1 and 2 due to the high conservation of the 5'NCR. However, since there was not any misclassification between HCV genotypes 1 and non-1 types, the results obtained with this system are, in general, reliable and can be used in clinical practice. The TRUGENE HCV 5'NC genotyping kit in our hands proved to be a fast and convenient technique that might be an attractive option for HCV genotyping in laboratories already using the Roche AMPLICOR HCV test for diagnostic reverse transcription-PCR.

HIV-1 drug resistance genotyping. A review of clinical and economic issues.

The development of mutations associated with resistance to antiretroviral therapy (ART) has been shown to be a major cause of treatment failure in patients infected with HIV-1. These resistance mutations can be assessed by a genotyping test that probes for specific mutations within the HIV genome or sequences specific genes, at a cost $US500/test (2000 prices). The stated goal of HIV-1 genotyping is to target HIV therapy effectively. This, as shown in the preliminary research, should result in better clinical outcomes and a lower incidence of virological failure and may be associated with lower costs of treatment. Failure of ART may result in an increase in costs of at least $US250 per patient per month, as assessed in 1 study, with costs rising further as patients experience multiple virological failures. Therefore, there is an economic as well as a therapeutic premium on the prevention of ART failure. The actual economic cost of genotyping has been preliminarily explored in the context of the antiretroVIRal ADAPTation (VIRADAPT) trial, which found no significant difference in the 1-year treatment cost of patients with and without genotyping. There is some evidence of cost neutrality or savings with genotypic testing but it needs to be further explored within the context of carefully framed prospective trials.

Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS.

Ganciclovir and cidofovir, two antiviral agents used in the treatment of cytomegalovirus (CMV) retinitis, have a synergistic effect inhibiting CMV replication in vitro. In a phase I study, seven patients with AIDS-related CMV retinitis were treated with cidofovir (5 mg/kg intravenously every 2 weeks) combined with ganciclovir (1 g orally three times a day). During a median of 5.5 months (range, 1-12 months) of combined therapy, only one patient had retinitis progression, and only two of 28 blood cultures (specimens of which were obtained on a monthly basis) yielded CMV. Dose-limiting adverse ocular effects (anterior uveitis [two patients] and hypotony [two patients]) occurred in three of seven patients. The results suggest that combination therapy with intravenous cidofovir and oral ganciclovir (a regimen that does not require indwelling central venous catheter access) might enhance clinical efficacy. Less frequent administration of cidofovir in combination with oral ganciclovir should be prospectively studied to determine if the incidence of treatment-associated toxicity might be reduced.

The use of combination antiretroviral therapy in HIV-infected patients.

OBJECTIVE: To review the published clinical trials of combination antiretroviral therapy, current guidelines about the use of combination antiretroviral therapy, information regarding the impact of adherence on treatment effect, and the effects of combination antiretroviral therapy on morbidity and mortality. METHODS: A MEDLINE search (January 1986-March 1998) was performed to identify all relevant articles. Selected articles and abstracts from this time period and references from these selections were included for review. DISCUSSION: Nucleoside analog monotherapy treatment of HIV infection is inferior to treatment with multiple antiretroviral agents. With the availability of new classes of medications (protease inhibitors, nonnucleoside reverse transcriptase inhibitors [NNRTIs], and new nucleoside analogs, combination antiretroviral therapy is now more potent and more complex than ever. The use and effects of protease inhibitors in combination with nucleoside analogs has been well documented. The use of NNRTIs and combination protease inhibitor regimens are not as well documented but may prove to be at least as efficacious as single protease inhibitor-containing regimens. Increases in CD4+ cell counts of >100 cells/mm3 and decreases in HIV RNA (viral load) of >2 log are common with these medications, with antiretroviral naive patients being more likely to have substantial responses to therapy than experienced patients. CONCLUSIONS: Combination antiretroviral therapy in HIV-infected patients is now the standard of care. Combination antiretroviral regimens have been shown to reduce, at least temporarily, the morbidity and mortality associated with HIV infection and AIDS. However, these regimens are quite complex for patients to adhere to successfully. While the true long-term effects of combination antiretroviral therapy are unknown, their current effects on the HIV epidemic are unquestionable.

Three dimensional registration of mechanical bladder activity using polystyrene fluorescent spheres: A technical note.

Optical marker tracing methods have been applied successfully in recent years to quantify local material deformation of heart tissue, skin and striated muscles. In this study, polystyrene fluorescent spheres (d = 0.6 mm) are glued to the ventral serosal bladder wall in the rabbit. Three dimensional video registration of the polystyrene spheres is used to calculate two directions of principal strain (epsilon (1), epsilon (2) ) on the bladder surface in vivo. The aim is to investigate the feasibility of the technique for this new application in two experimental circumstances: during spontaneous bladder wall activity and after electrical stimulation of bladder innervating nerve fibers. During spontaneous activity, random contraction and relaxation occurred simultaneously and separately across the bladder wall for the two principal strains epsilon (1) and epsilon (2). After extradural electrical stimulation of sacral nerve root S2, the principal strains epsilon ( 1) and epsilon (2) synchronized in time in such a way that epsilon ( 1) and epsilon (2) both represented contraction or both represented relaxation. One and the same bladder wall area passed through phases of contraction followed by relaxation and vice versa. After multiple stimulation periods, the coordination between the two principal strains during stimulation was reduced. This technique allows to identify local areas of contraction and relaxation in the intact bladder wall in vivo. Three dimensional video registration of polystyrene fluorescent spheres to study bladder wall contraction and its relaxation proved to be a feasible technique, with which electrical stimulation effects and spontaneous activity could be measured.

Cross-reactivity in HIV-infected patients switched from trimethoprim-sulfamethoxazole to dapsone.

STUDY OBJECTIVE: To evaluate the cross-reactivity of dapsone after a documented hypersensitivity reaction to trimethoprim-sulfamethoxazole (TMP-SMX) during prophylaxis for Pneumocystis carinii pneumonia. DESIGN: Retrospective, chart review, cohort study. SETTING: Two university-affiliated teaching hospitals. PATIENTS: Sixty patients infected with the human immunodeficiency virus. MEASUREMENTS AND MAIN RESULTS: Thirteen patients (21.7%) had cross-reactivity to dapsone after the reaction to TMP-SMX. No significant risk factors for this response were identified. Most reactions were of mild or moderate severity and rated as possibly or probably caused by one of the agents. Of the 13 patients, 4 (30.8%) continued therapy. CONCLUSIONS: Although cross-reactivity can occur, dapsone may be considered in patients with mild hypersensitivity reactions to TMP-SMX.

The process of decompaction and myelin removal after C7 ventral root avulsion in the cat.

An electron microscopical study was carried out on the ventral horn in order to investigate the microvascular changes after C7 ventral root avulsion in cats. Endothelial cells: At 2 days after avulsion the endothelial cells contained vacuoles filled with fibrous-like substances. After 14 days the endothelial phagosomes also contained myelin sheath-like and "soap-bubble" structures. Tight junctions between the endothelial cells remained present without exception. From 14 up to 90 days, intraluminal debris was observed. Edema and glia: From 2 up to 30 days after avulsion perivascular edema was noted around blood vessels and polymorphonuclear granulocytes were found mainly in the peri-endothelial space. Eight days after avulsion, the number of astrocytic processes around the blood vessels and the phagocytic activity of perivascular cells increased. Myelin sheath-like structures were encountered in phagosomes of the pericytes. After 14 days the distribution of astrocytic processes around the blood vessels had stabilized and remained so until day 90 after avulsion. In the same period the phagocytic activity decreased, and the myelin sheath-like material in the perivascular cell phagosomes gradually disappeared. The amount of microglial cells around the blood vessels showed an increase after 30 days survival and then stabilized. These results indicate transport of debris from the neuropil across the endothelial cells into the blood vessel lumen after ventral root avulsion.

Phenytoin-induced thrombocytopenia.

OBJECTIVE: To describe a patient with severe thrombocytopenia induced by the administration of phenytoin for prevention of seizures. A review of the literature supplements this case description to alert clinicians to this potentially serious hematologic reaction. CASE SUMMARY: A woman who had experienced two seizures was prescribed phenytoin to prevent seizure recurrence. Further evaluation revealed a tumor, which was resected, and phenytoin was continued. Thrombocytopenia was noted 15 days after initiation of phenytoin, which was replaced with phenobarbital. Platelet transfusion and administration of intravenous immune globulin were used to treat her thrombocytopenia. Platelets were within the normal range by day 8 after the operation. DISCUSSION: Phenytoin has been reported to induce various hematologic reactions, including thrombocytopenia. An intermediate epoxide metabolite of phenytoin is suspected as the cause of platelet destruction, which may occur via a complement-antibody reaction. Our patient experienced some confusion as a possible consequence of her thrombocytopenia, but no long-term sequelae followed. CONCLUSIONS: Due to widespread use of phenytoin, clinicians must recognize the potential for the rare but serious adverse effect of thrombocytopenia, particularly in the neurosurgical population. Confusion, as observed in our patient, makes postoperative evaluation of central nervous system and cognitive function difficult, and can obscure the clinical presentation. At its worst extreme, disruption of platelet function may produce cerebral hemorrhage, which results in long-term functional deficits.

Nerve grafting from spinal cord to spinal nerve: a microsurgical technique in cats.

A ventral surgical approach is described for the grafting of autologous saphenous nerves between the spinal cord and the avulsed C7 ventral root in the cat. To overcome serious blood loss from the epidural venous plexus, the cats were hyperventilated (end tidal PCO2 to about 23 mmHg) and controlled hypotension was induced (mean arterial pressure to about 60 mmHg). After selective avulsion of the ventral rootlets C7 the saphenous grafts were implanted into the spinal cord and coaptated to the avulsed spinal nerve. The combination of advanced anesthetic methods and microsurgical techniques appeared to be mandatory to achieve a low surgical mortality. Regenerated axons were retrogradely traced using retrograde horseradish peroxidase (HRP), and their functional recovery was evaluated by means of electrophysiological methods.

Recycling of glutathione during oxidative stress in erythrocytes of the newborn.

The ability of erythrocytes from newborn babies and adults to maintain reduced glutathione levels during oxidative stress was studied. In vitro incubation of erythrocytes with H2O2, with or without inactivation of catalase, caused a rapid depletion of reduced glutathione (GSH) and concomitant accumulation of oxidized glutathione followed by recovery of GSH and fall of oxidized glutathione to initial values in all subjects. Inactivation of catalase resulted in a 50% loss of intracellular glutathione (p less than 0.005), a larger maximum GSH depletion (p less than 0.05), and a longer GSH recovery time (p less than 0.005). Erythrocytes from newborn babies showed a smaller maximum GSH depletion (p less than 0.05) and a shorter GSH recovery time (p less than 0.005) compared with those from adults. These differences between the newborn and adult groups persisted after inactivation of catalase. An increase in maximum GSH depletion and GSH recovery time (p less than 0.005) was observed when a lower hematocrit was used for these GSH recovery studies. Effective glutathione recycling in erythrocytes may protect immature tissues of the newborn baby from peroxidative damage.