Vascular endothelial growth factor and diabetic nephropathy

The field of vascular endothelial growth factor (VEGF) has recently witnessed a surge of research into its role in diabetic kidney disease. Based on its credentials as a potent inducer of vasopermeability and angiogenesis, podocyte-derived VEGF is believed to participate in the glomerular capillary hyperpermeability of macromolecules that potentially underlies the pathogenesis of diabetic albuminuria. The evidence for VEGF’s role is relatively straightforward in animal models of diabetes, establishing that VEGF is upregulated in the diabetic kidney, that VEGF alone reproduces some aspects of diabetic glomerulopathy, and that antagonism of VEGF attenuates diabetic albuminuria and other associated features of the podocytopathy. However, the promise shown in the animal studies has not carried over as convincingly into the realm of human studies, as some investigators find a negative or no relationship between VEGF and diabetic nephropathy, whereas others find a positive correlation between the two. If VEGF does play a role in diabetic renal disease, its observed effects and known mechanisms seem to point squarely at the podocyte as a central target of the maladaptive VEGF overactivity.     

Human Cyclic Neutropenia: Urinary Colony-stimulating Factor and Erythropoietin Levels

Daily levels of urinary colony-stimulatingfactor (CSF) were measured in two patients with cyclic neutropenia. The CSFlevels increased during the neutropenicperiod concomitant with the maximumperipheral monocytosis. Simultaneouserythropoietin (ESF) levels were measuredin one of these patients. ESF also increasedin the neutropenic period antecedent tothe periodic reticulocytosis. These studiesare compatible with a negative feedbacksystem regulating both granulocytopoiesisand erythropoiesis. Whether the cyclic fluctuations of these substances are causallyrelated to the cyclic marrow proliferationis uncertain.

Submitted on September 5, 1973 Revised on February 10, 1974 Accepted on February 11, 1974     

Steroid pulse therapy for rheumatoid arthritis: effect on lymphocyte subsets and mononuclear cell adhesion

Eighteen patients with clinically active rheumatoid arthritis, satisfying the ARA criteria, were admitted to hospital for i.v. methylprednisolone pulse therapy. Studies of circulating lymphocyte subsets 1 h before and 24 h after pulsing were carried out together with studies on their adhesion to endothelium-containing lamina propria of porcine gut at various time points. Additionally, circulating VCAM-1 was estimated pre- and post-pulse by ELISA. We observed a marked fall (59%) in mononuclear cell adhesion 24 h post-pulse therapy (P < 0.001). Accompanying this was a significant, though slight, fall in circulating mononuclear cells (P < 0.01), mainly involving T cells. However, the degree of reduction in cell adhesion did not appear to reflect change in any particular circulating subset, but was more likely due to changes in adhesion molecule expression of several subsets. No significant change in circulating VCAM-1 was observed. It would appear, therefore, that the early beneficial effect of steroid pulsing in rheumatoid arthritis coincides with a demonstrable reduction in cell adhesion to gut. This may have implications for the pathogenesis of this disease.      

A Personal Experience in Comparing Three Nonoperative Techniques for Treating Internal Hemorrhoids

Infrared photocoagulation therapy was used on a total of 302 patients. Approximately 20% of the patients experienced minor bleeding; however, two required surgery, and 30% of the patients experienced discomfort during a 14-day period following the procedure. Good results were obtained in patients with first- and second-degree hemorrhoids. Heater probe coagulation therapy was conducted in a total of 264 patients. Good results were achieved in 90% of patients with first- and second-degree hemorrhoids, minor pain and bleeding occurred in approximately 10% of these patients, and one patient with third-degree hemorrhoids who was treated with this technique failed to respond and required surgery. Ultroid d.c. current therapy was utilized in 192 patients, and follow-up results were good in 95% of these cases. Minor bleeding occurred in four patients. It is concluded that all three techniques, performed on an outpatient basis with little or no sedation, are effective modalities for first- and second-degree hemorrhoids, but that Ultroid d.c. current therapy is associated with less discomfort and fewer complications and that Ultroid therapy may yield good results in some patients with third- or even fourth-degree hemorrhoids.     

Relation of Childhood Sexual Abuse,Intimate Partner Violence,and Depression to Risk Factors for HIV Among Black Men Who Have Sex With Men in 6 US Cities

Objectives. We assessed the relation of childhood sexual abuse (CSA), intimate partner violence (IPV), and depression to HIV sexual risk behaviors among Black men who have sex with men (MSM).Methods. Participants were 1522 Black MSM recruited from 6 US cities between July 2009 and December 2011. Univariate and multivariable logistic regression models were used.Results. Participants reported sex before age 12 years with someone at least 5 years older (31.1%), unwanted sex when aged 12 to 16 years (30%), IPV (51.8%), and depression (43.8%). Experiencing CSA when aged 12 to 16 years was inversely associated with any receptive condomless anal sex with a male partner (adjusted odds ratio [AOR] = 0.50; 95% confidence interval [CI] = 0.29, 0.86). Pressured or forced sex was positively associated with any receptive anal sex (AOR = 2.24; 95% CI = 1.57, 3.20). Experiencing CSA when younger than 12 years, physical abuse, emotional abuse, having been stalked, and pressured or forced sex were positively associated with having more than 3 male partners in the past 6 months. Among HIV-positive MSM (n = 337), CSA between ages 12 and 16 years was positively associated with having more than 3 male partners in the past 6 months.Conclusions. Rates of CSA, IPV, and depression were high, but associations with HIV sexual risk outcomes were modest.Despite significant medical advances, the HIV epidemic remains a health crisis in Black communities. The Black population represents only 14% of the total US population but accounted for 44% of all new HIV infection (68.9 of 100 000) in 2010.1 Black men who have sex with men (MSM) are disproportionately impacted by HIV compared with other racial/ethnic groups of MSM.1,2 Male-to-male sexual contact accounted for 72% of new infections among all Black men.1 Young Black MSM (aged 13–24 years) have a greater number of new infections than any other age or racial group among MSM.1 Researchers have been challenged with developing HIV prevention strategies for Black MSM.3–7 Higher frequencies of sexual risk behaviors, substance use, and nondisclosure of sexual identities do not adequately explain this disparity.8,9 High rates of sexually transmitted infections (STIs), which facilitate HIV transmission, and undetected or late diagnosis of HIV infection only partially explain disproportionate HIV rates.8Researchers have begun to examine a constellation of health factors that may contribute to HIV among MSM. For example, syndemic theory or the interaction of epidemics synergistically, such as intimate partner violence (IPV) and depression, may help explain HIV-related sexual risk behaviors among Black MSM.9 Childhood sexual abuse (CSA), IPV, and mental health disorders including depression may comprise such a constellation and warrant further exploration.Experiences of CSA have been identified as being associated with negative sexual health outcomes, with MSM reporting higher CSA rates than the general male population.10–12 Men with CSA experiences are more likely than men without CSA experiences to engage in high-risk sexual behaviors,13–21 have more lifetime sexual partners,13–16 use condoms less frequently,13,14,16 and have higher rates of STIs,13,14,17 exchanging sex for drugs or money,13,14,17 HIV,13,14 alcohol and substance use,13–21 and depression.13–15,18,21 Such findings suggest that sexual risk reduction counseling may need to be tailored for MSM with CSA experiences.15Childhood sexual abuse histories have also been correlated with sexual revictimization, including IPV.22–24 One study with population-based estimates of CSA found that gay and bisexually identified men had higher odds of reporting CSA (9.5 and 12.8, respectively) compared with heterosexual men.25 For sexual minority men, CSA histories were associated with higher HIV and STI incidence.25 However, research examining CSA, revictimization, and sexual risk behaviors is lacking among Black MSM.In one existing study, Black and Latino MSM with CSA histories identified their trauma experiences as influencing their adult sexual decision-making.26 Among Black MSM in 2 additional studies, emotional distress and substance use were attributed to having CSA experiences (Leo Wilton, PhD, written communication, October 2, 2013).27 In an ethnically diverse sample of 456 HIV-positive MSM, CSA was associated with insertive and receptive condomless anal sex.19Similar to CSA, IPV has not been extensively examined among MSM or Black MSM,28 but may be associated with sexual risk behaviors. Intimate partner violence is defined as a pattern of controlling, abusive behavior within an intimate relationship that may include physical, psychological or emotional, verbal, or sexual abuse.29 Little research exists on IPV among same-sex couples despite incidence rates being comparable to or greater than that of heterosexual women.28,30–34 Important IPV information comes from the National Intimate Partner and Sexual Violence Survey, a nationally representative survey for experiences of sexual violence, stalking, and IPV among men and women in the United States.28 Among men who experienced rape, physical violence, or stalking by an intimate partner, perpetrator differences by gender were found among gay, bisexual, and heterosexual men; 78% of bisexual and 99.5% of heterosexual men reported having only female perpetrators, and 90.7% of gay men reported having only male perpetrators.28 Being slapped, pushed, or shoved by an intimate partner during their lifetime was reported by gay (24%), bisexual (27%), and heterosexual (26.3%) men.28Intimate partner violence has been linked to condomless anal sex, HIV infection, substance use, CSA, and depression.35–37 Being an HIV-positive MSM has been linked with becoming a victim of IPV.38,39 Welles et al. found that being an African American MSM who initially disclosed having male partners and early life sexual abuse experiences was associated with IPV victimization.39 Wilton found that a high percentage of Black MSM reported IPV histories: emotional abuse (48.3%), physical abuse (28.3%), sexual abuse (21.7%), and stalking abuse (29.2%; Leo Wilton, PhD, written communication, October 2, 2013). Such findings lend to the importance of exploring, both independently and together, the association of CSA and IPV with sexual risk behaviors.Some studies have reported the influence of mental health (e.g., depression) on sexual risk behaviors among MSM,9,40,41 whereas others have not corroborated such findings.42 Greater rates of depression among MSM than among non-MSM samples43–45 and elevated rates of depression and anxiety among Black MSM have been reported.46 The Urban Men’s Health Study, a cross-sectional sample of MSM in 4 US cities, did not find a significant relationship between high depressive symptoms and condomless anal sex.42 However, the EXPLORE study, a randomized behavioral intervention for MSM in 6 US cities, supported the association between moderate depressive symptoms and an increased risk for HIV infection.47 Moderate levels of depression and higher rates of sexual risk were also reported for HIV-infected MSM over time.48 Another study conducted with 197 Black MSM found that moderate depressive symptoms were associated with having condomless anal sex with a serodiscordant casual partner.49 These mixed findings support the need to better understand the relationship between the severity of depression (i.e., moderate vs severe) and HIV risk behaviors.The HIV Prevention Trials Network 061 study, also known as the BROTHERS (Broadening the Reach of Testing, Health Education, Resources, and Services) Project, was a multisite study to determine the feasibility and acceptability of a multicomponent intervention for Black MSM. The current analysis aims to assess the prevalence of CSA, IPV, and depressive symptomology, and examine the relationships between these factors and insertive and receptive condomless anal sex and number of sexual partners in a large cohort of Black MSM.     

Clinical comparison of two stylet angles for orotracheal intubation with the GlideScope video laryngoscope

Study ObjectiveTo compare the success of orotracheal intubation in 62 seconds or less using the GlideScope video laryngoscope (GVL) and a 60° or 90° angled stylet with reverse loading of the endotracheal tube (ETT).DesignProspective, randomized study.SettingOperating room of a university hospital.Patients120 ASA physical status I, II, and III adult patients undergoing elective surgery requiring general anesthesia with orotracheal intubation.InterventionsPatients were randomly allocated to two groups (n = 60 each); both groups received general anesthesia and neuromuscular relaxation. A conventional ETT was styleted and then bent from its straight configuration just above the cuff, either at 60° or 90° against its concave natural curve (reverse loading). Four attending anesthesiologists, who were blinded as to stylet assignment (the 60° or 90° group), intubated the tracheas of all patients with the GVL using either the primary or secondary stylet.MeasurementsThe primary outcome was success of orotracheal intubation in 62 seconds or less. The secondary outcome was actual time to intubation (TTI).Main ResultsThe odds ratio (OR) for intubation success was higher in the 90° group than the 60° group (OR = 10.41; P < 0.03), as evidenced by 59 of 60 patients whose tracheas were intubated successfully within 62 seconds, compared with 51 of 60 patients in the 60° group. Seven of the 9 failures were due to inability of the 60° stylet to reach the glottic opening. The three remaining failures were associated with TTI of more than 62 seconds.ConclusionsThe 90° angled malleable stylet with reverse loading of the ETT provided more reliable ETT delivery to the glottic opening and had a higher success rate than the 60° stylet.     

t(9;22)(q34;q11.2) is a recurrent constitutional non-Robertsonian translocation and a rare cytogenetic mimic of chronic myeloid leukemia

The diagnosis of hematologic malignancy can be greatly aided by the detection of a cytogenetic abnormality. However, care must be taken to ensure that constitutional chromosomal abnormalities are not misattributed to a putative population of malignant cells. Here we present an unusual case in which a constitutional balanced t(9;22)(q34;q11.2) cytogenetically mimicked the acquired, t(9;22)(q34;q11.2), that is characteristic of chronic myeloid leukemia. Of special note, fluorescence in situ hybridization (FISH) analysis for this constitutional translocation (9;22)(q34;q11.2) using standard probes for BCR and ABL1 resulted in an abnormal pattern that was potentially misinterpretable as a BCR-ABL1 fusion. This is the first reported FISH analysis of a constitutional t(9;22)(q34;q11.2), and overall only the second report of such an abnormality. In light of the isolated prior report, our case also suggests that the constitutional t(9;22)(q34;q11.2) is one of the very few?recurrent constitutional non-Robertsonian translocations described in humans. Our case underscores the necessity of complete clinical and laboratory correlation to avoid misdiagnosis of myeloid malignancy in the setting of rare constitutional cytogenetic abnormalities.