Extensive nodular secondary syphilis

An indigent male patient presented with a widespread nodular eruption involving the torso and limbs. The differential diagnosis included nodular secondary syphilis, Kaposi's sarcoma, sarcoidosis, and lymphoma. Investigation confirmed secondary syphilis with positive cerebrospinal fluid serologic findings. Penicillin therapy produced a Jarisch-Herxheimer reaction despite pretreatment to diminish this. Discussion on the clinical features and treatment of syphilis is presented.     

Reliability of CD4 quantitation in human immunodeficiency virus-positive children: implications for definition of immunologic response to highly active antiretroviral therapy

Our objective was to develop data-based algorithms for definition of immunologic response to AIDS therapies in pediatric patients, taking account of T-cell subset measurement errors. The study design involved cross-protocol analysis of 2,148 enrollees in six completed Pediatric AIDS Clinical Trials Group trials. We used standard quantitation of T-cell subsets; linear modeling with mean-dependent measurement error variance was used to develop 95% tolerance limits for change in CD4%. For individuals with a CD4% of approximately 25%, the measurement error-based 95% tolerance interval ranges from 15% to 35%, whereas for individuals with a CD4% of approximately 5%, the tolerance interval ranges from 3% to 7%. When pairs of CD4% measures taken within a time interval of less than 30 days are averaged to estimate steady-state CD4%, tolerance interval width decreases by approximately 30%. A simple graphical tool that provides a data-based criterion for immunologic response over and above variation ascribable to T-cell measurement error is provided. Variability in CD4% due to measurement error is substantial, increases with level of CD4%, and complicates assessment of immunologic response to therapy. Replicates of CD4% measures could be used to improve precision of interpretation of CD4% measures.     

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

Improved therapeutic responses in a xenograft model of human B lymphoma (Namalwa) for liposomal vincristine versus liposomal doxorubicin targeted via anti-CD19 IgG2a or Fab' fragments.

PURPOSE: Monoclonal antibody-mediated targeting of liposomal anticancer drugs to surface antigens expressed on malignant B cells can be an effective strategy for treating B-cell malignancies. In a murine model of human B-cell lymphoma, we have made in vitro and in vivo comparisons of long-circulating sterically stabilized (Stealth) immunoliposome (SIL) formulations of two anticancer drugs, vincristine (VCR) and doxorubicin (DXR), with different mechanisms of action and drug release rates. EXPERIMENTAL DESIGN: SIL formulations of VCR or DXR were conjugated to the monoclonal antibody anti-CD19 (SIL[alphaCD19]) or its Fab' fragments (SIL[Fab']). Specific binding of SILs to Namalwa cells was studied using radiolabeled liposomes, and cytotoxicities of DXR- or VCR-loaded SILs were quantitated by a tetrazolium assay. Pharmacokinetic and drug leakage experiments were performed in mice using dual-labeled liposomes, and the therapeutic responses of SILs were evaluated in a Namalwa (human B lymphoma) cell xenograft model. RESULTS: SIL[alphaCD19] or SIL[Fab'] had higher association with and cytotoxicity against Namalwa cells than nontargeted liposomes. SIL[Fab'] had longer circulation times than SIL[alphaCD19], and VCR had faster release rates from the liposomes than DXR. SIL formulations of either VCR or DXR had significantly better therapeutic outcomes than nontargeted liposomes or free drugs. SILs loaded with VCR were superior to those loaded with DXR. SIL[Fab'] had better therapeutic outcomes than SIL[alphaCD19] for the drug DXR but were equally efficacious for the drug VCR. CONCLUSIONS: Treatment of a B lymphoma model with single injections of anti-CD19-targeted liposomal formulations of VCR resulted in high levels of response and long-term survivors. Responses to anti-CD19-targeted liposomal DXR were more modest, although the longer circulation times of SIL[Fab'] versus SIL[alphaCD19] led to superior therapeutics for DXR-loaded immunoliposomes.     

Psychosocial Correlates of Monocyte Activation and HIV Persistence in Methamphetamine Users

This cross-sectional study investigated the associations of psychosocial factors relevant to recovery from substance use disorders with monocyte activation and HIV persistence in a sample of 84 HIV-positive, methamphetamine-using sexual minority men with undetectable HIV viral load (<40 copies/mL). We examined if psychosocial factors were associated with decreased soluble CD14 (sCD14) and lower proviral HIV DNA. Multiple linear regression models adjusted for age, anti-retroviral therapy regimen, and CD4+ T-cell count. Time on ART was also included in models examining proviral HIV DNA. Greater self-efficacy for managing methamphetamine triggers and higher social support for abstinence were independently associated with lower sCD14. Greater social support for abstinence was also independently associated with lower proviral HIV DNA. Psychosocial factors relevant to recovery from substance use disorders are associated with lower monocyte activation and decreased proviral HIV DNA. Findings underscore the need for longitudinal research to identify plausible mechanisms linking psychosocial factors and substance use with biological processes relevant to HIV pathogenesis.

     

Clinically significant differences between point-of-care analysers and a standard analyser for monitoring the International Normalized Ratio in oral anticoagulant therapy: a multi-instrument evaluation in a hospital outpatient setting.

The increasing number of patients requiring oral anticoagulant therapy has lead to an expansion in the use of point-of-care test (POCT) analysers for measuring the International Normalized Ratio (INR) for monitoring purposes. Availability of new technology inevitably leads to comparisons with standard methodologies, and studies to date have reached varying conclusions about the comparability of POCT INRs with conventional testing. We compared the performance of five POCT instruments (Hemochron Junior Signature, ProTime, CoaguChek S, INRatio and TAS) against Innovin thromboplastin on a Sysmex CA1500 automated analyser. The Hemochron Junior Signature, ProTime and CoaguChek S demonstrated strong correlation with the laboratory method (R2 > 0.94). These three analysers demonstrated higher percentages of paired results within 0.5 INR units (81.5, 92.0 and 74.0%, respectively); the INRatio and TAS demonstrated 54.2 and 62.2%, respectively. Within INR ranges of up to 2.0, 2.1-3.0, 3.1-4.0 and above 4.0, none of the POCT analysers demonstrated significant agreement with the standard method in every range. All POCT instruments showed a degree of bias and greater variation from the standard method at INR values above 3.0. These data indicate the potential for POCT analysers to generate INR values sufficiently different from conventional methods that they may impact on clinical decision-making.     

Endoscopic management of pancreatic pseudocysts and walled-off pancreatic necrosis: A two-decade experience

Aim

To determine long-term outcome of endoscopic management of pancreatic pseudocyst/walled-off pancreatic necrosis (WOPN) without necrosectomy.

Methods

One-hundred and sixty-five pancreatic pseudocysts/WOPN managed endoscopically over a period of 22 years were analyzed retrospectively for technical success, complications, and recurrence.

Results

Symptomatic 118 males and 47 females with mean age of 35.8 years were included. Alcohol was the most common etiology (41.2 %). Transmural endoscopic drainage was done in 144 patients, while 21 patients underwent transpapillary drainage. All the patients were subjected to contrast computed tomography (CT) abdomen or routine/Doppler ultrasound. Endoscopic ultrasound was done in last 11 patients. One or two double pigtail 7 Fr stents were placed when clear watery fluid came out from cyst (130 patients, 78.8 %), and nasocystic drainage (NCD) tubes were placed in addition to two 7 Fr stents when there were frank pus, thick dark fluid, or solid components inside the cyst (35 patients). All these patients settled on this treatment. Thirty-three of 35 patients of WOPN could be managed endoscopically without necrosectomy. Complications occurred in 9.2 % of pseudocysts and 40 % of WOPN. Thirty-five patients were followed up for more than 5 years (3 patients more than 10 years), and 130 patients were followed up for up to 5 years. Recurrence occurred in 8.1 % of pseudocysts and 5.7 % of WOPN.

Conclusion

Majority of pancreatic pseudocysts/WOPN can be managed with endoscopic drainage without necrosectomy with high success, low complication, and recurrence rates.

     

Platelet glycoprotein IIb/IIIa inhibition using eptifibatide with primary coronary stenting for acute myocardial infarction: a 30-day follow-up study.

The results of primary coronary stenting for acute myocardial infarction (AMI) have been reported to improve significantly with the concomitant administration of platelet glycoprotein IIb/IIIa inhibitor abciximab. There are, however, no data available with the use of eptifibatide, a more cost-effective, small-molecule GP IIb/IIIa blocker with a shorter half-life. In a prospective multicenter feasibility and efficacy study, we assigned 55 consecutive patients with AMI being taken up for primary stenting to receive eptifibatide just before the procedure (two boluses of 180 microg/kg 10 min apart and a 24-hr infusion of 2 microg/kg/min). Clinical outcomes were evaluated at 30 days after the procedure. The angiographic patency of the vessel with TIMI flow rates, TIMI myocardial perfusion (TMP) grade, and corrected TIMI frame counts were assessed at the end of procedure and before hospital discharge. At 30 days, the primary endpoint, a composite of death, myocardial infarction, and urgent target vessel revascularization (TVR) was seen in 12.7% of patients. The TIMI 3 and TMP grade 3 flow, which was seen in 93% and 86% of patient, respectively, at the end of the procedure, declined to 86% and 78%, respectively (P < 0.05) before hospital discharge. Corrected TIMI frame counts also decreased from 25.7 +/- 7.2 to 22.9 +/- 6.8 (P < 0.05). There were five (9.1%) instances of subacute thrombosis (SAT) presenting as AMI, needing urgent TVR in all, within 3-5 days of the primary procedure. No excessive bleeding complication, directly attributable to the use of eptifibatide, was observed. The study was terminated prematurely because of an unacceptable SAT rate. Administration of eptifibatide along with primary stenting for AMI is associated with a high TIMI 3 and TMP grade 3 flow acutely. However, these flows decline significantly before hospital discharge and lead to a high rate of SAT. The dosage and duration of infusion of eptifibatide in this setting needs further evaluation.