Absence of human T-cell lymphotropic virus type I coinfection in human immunodeficiency virus-infected hemophilic men

Concern for transmission of human T-cell lymphotropic virus, type 1 (HTLV-1) infection to recipients of infected cellular blood products has prompted development of tests to eliminate blood units with HTLV-I antibodies. Most hemophilic men from the United States became infected with human immunodeficiency virus (HIV) before HIV donor screening and before blood products were processed to inactivate the virus. To assess whether these men might also be infected with HTLV-I, we examined the HTLV-I antibody status of 127 factor VIII (hemophilia A) recipients and 71 factor IX (hemophilia B) recipients. One HIV-seronegative and four HIV-seropositive persons were HTLV-I reactive by enzyme-linked immunosorbent assay (ELISA). Four of five ELISA-reactive serum samples were negative by HTLV-I immunoblot assay (IB); 1 reactive and 1 borderline reactive serum were indeterminate on IB (p19 reactivity), but negative by radioimmunoprecipitation assay (RIPA). Peripheral blood mononuclear cells from one patient with indeterminate HTLV-I IB were negative for HTLV-I genomic sequences by polymerase chain reaction. The other indeterminate patient's serum antibody pattern was stable over a 2-year period, suggesting this was not an instance of early HTLV-I seroconversion. These results reaffirm the safety of factor components in the United States with regard to HTLV-I but emphasize the importance and need for further testing of reactive HTLV-I ELISA results with a second more specific technique.     

Transformed T lymphocytes infected by a novel isolate of human T cell leukemia virus type II

Human T cell leukemia virus type II (HTLV-II) has been isolated from a patient (Mo) with features of leukemic reticuloendotheliosis (LRE) and from a patient with acquired immunodeficiency syndrome (AIDS). We have obtained another isolate of HTLV-II from a patient (CM) with severe hemophilia A, pancytopenia, and a 14-year history of staphylococcal and candidal infections but no evidence of T cell leukemia/lymphoma, AIDS, or LRE. Fresh mononuclear cells and cultured lymphocytes from CM express retroviral antigens indistinguishable by molecular criteria from HTLV-IIMo. Leukocyte cultures from CM yield hyperdiploid (48,XY, +2, +19) continuous lymphoid lines; human fetal cord blood lymphocytes (CBL) are transformed by cocultivation with these CM cell cultures but retain normal cytogenetic constitution. Electron microscopic examination of the CM cultures and transformed CBL reveals budding of extracellular viral particles, intracellular tubuloreticular structures, and viral particles contained within intracellular vesicles. CM cell cultures and the transformed CBL do not require exogenous interleukin 2, have T cell cytochemical features and mature T helper phenotypes, and exhibit minimal T helper and profound T suppressor activity on pokeweed mitogen-stimulated differentiation of normal B cells. These characteristics, which are similar to those observed with the first HTLV-II isolate, may represent properties of all HTLV-II-infected T cells.     

Tumor necrosis factor-alpha downregulates protein S secretion in human microvascular and umbilical vein endothelial cells but not in the HepG- 2 hepatoma cell line

Protein S deficiency, which is associated with thrombosis, can either be inherited or acquired. Recently, we reported that a decrease in free protein S was observed in 19 of 25 persons with HIV/AIDS. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been reported to be elevated in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and has been shown to induce a procoagulant state on the surface of endothelial cells. We report here that recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the SV-40T transfected human microvascular endothelial cell line (HMEC-1) model system by approximately 70% and in primary human umbilical vein and dermal microvascular endothelial cell cultures by approximately 50%. Using the HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at 24 hours that was corroborated by Western blot analysis and enzyme- linked immunosorbent assay (ELISA) quantification. Evidence supporting the specificity of the TNF-alpha effect included the following: (1) TNF- alpha down-regulation of protein S was completely blocked by TNF neutralizing antibody; (2) the effect was transient, and protein S was restored to near normal levels after TNF was removed from cell cultures; (3) an antibody directed to the TNF RI (55-kD receptor) was shown to mimic the action of TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines, interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S secretion. However, TNF-alpha showed no regulatory control over protein S synthesis in the human hepatocellular carcinoma cell line HepG-2. We suggest that TNF-alpha downregulation of protein S may be a mechanism for localized procoagulant activity and thrombosis recently reported in some AIDS patients with associated protein S deficiency.     

Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction

A murine model of bone marrow (BM) transplantation in which donor (B10.D2) and recipient (BALB/c) mice were major histocompatibility complex (MHC) (H-2d) and Mls-1 identical, but incompatible at multiple non-MHC minor histocompatibility (H) antigens, and at Mls-2,3 was used to examine regeneration of B-cell development during the minor H antigen graft-versus-host reaction (GVHR). Mice that received T-cell- depleted allogeneic BM regained significant pre-B cells (sIg- 14.8+) in their BM. Mice undergoing GVHR after transplantation with allogeneic BM + T cells had less than 2% pre-B cells in their BM at day 7 and only 12% to 14% pre-B cells at days 21 and 28 compared with greater than 20% pre-B cells in the allogeneic controls. After partial recovery, the pre- B cells in the BM of GVH mice again decreased to less than 3% by day 42. This abnormal pattern of pre-B cell development in mice undergoing GVHR was associated with a reduced response to interleukin-7 (IL-7) in vitro. The delay in B-lineage cell reconstitution in mice with GVHR correlated with the expansion of donor V beta 3+ T cells in both the spleen and BM. BM T cells from mice with GVHR as well as isolated V beta 3+ T cells inhibited IL-7 colony-forming units from normal BM in co-culture assays. This inhibition could be reversed with anti- interferon gamma (IFN gamma) antibody. These data suggest that the delay in appearance and the reduction in proportion and number of pre-B cells observed early during the GVH reaction in this model is caused, in part, by the inhibitory actions of IFN gamma derived from donor V beta 3+ T cells on B-lineage cell development.     

Childhood-onset pathologic skin picking: clinical characteristics and psychiatric comorbidity

There has been little research examining clinical correlates of childhood-onset pathologic skin picking in a sample of individuals with a primary diagnosis of pathologic skin picking. Using a sample of 40 consecutive subjects with current pathologic skin picking, we compared subjects with childhood-onset (before 10 years of age) pathologic skin picking to those with later onset on a variety of clinical measures. Symptom severity was examined by assessing time spent picking per day, intensity and frequency of thoughts and urges to pick, and social and occupational functioning. Of the 40 subjects, 19 (47.5%) reported onset of skin picking before 10 years of age. Subjects with childhood-onset had significantly longer durations of illness before receiving treatment and were more likely to pick unconsciously. Symptom severity, comorbidity, and social functioning did not differ between groups. These preliminary results suggest that although onset before 10 years of age is fairly common among people with pathologic skin picking, individuals developing this behavior earlier in life have similar clinical characteristics as those with later onset but may be less likely to seek treatment.     

A clinical comparison of pathologic skin picking and obsessive-compulsive disorder

Background

It has been hypothesized that pathologic skin picking (PSP) shares many of the same biological and phenomenological characteristics as obsessive-compulsive disorder (OCD). This study sought to examine the clinical similarities between PSP and OCD.

Method

Demographic and clinical characteristic data were examined in a treatment-seeking sample of 53 PSP (mean age, 34.2 ± 13.1 years; 86.8% female) and 51 OCD (mean age, 36.5 ± 11.7 years; 35.3% female) subjects. Psychiatric comorbidity and family history data were also obtained.

Results

The PSP subjects were more likely to be female (P < .001), report higher rates of co-occurring compulsive nail biting (P < .001), and have a first-degree relative with a grooming disorder (P < .001). The OCD subjects spent significantly more time on their thoughts and behaviors (P < .001) and were more likely to have co-occurring body dysmorphic disorder (P = .001).

Conclusion

Although PSP and OCD share some clinical similarities, important differences exist and cast doubt on the conceptualization of PSP as simply a variant of OCD.     

Pathologic gambling and bankruptcy

Background

Although prior studies have examined rates of bankruptcy in pathologic gambling (PG), there are only limited data regarding the clinical correlates of those with PG who declare bankruptcy because of gambling.

Method

Five hundred seventeen consecutive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PG (54.7% females; mean age 47.6 years) were grouped into 2 categories: those who had (n = 93; 18.0%) and had not (n = 424; 82.0%) declared bankruptcy secondary to gambling. Groups were compared on clinical characteristics, gambling severity (using the Yale-Brown Obsessive-Compulsive Scale Modified for Pathological Gambling, Gambling Symptom Assessment Scale; Clinical Global Impression—severity scale, and time and money spent gambling), and psychiatric comorbidity.

Results

Gamblers who had declared bankruptcy were more likely to be single (P = .004); have an earlier age of problem gambling onset (P = .032); and have more financial (P < .001), work-related (P = .006), marital (P < .001), and legal (P < .001) problems secondary to their gambling. They also reported higher rates of depressive disorders (P < .001), substance use disorders (P = .005) and were more likely to be daily users of nicotine (P = .022). Money spent gambling did not differ significantly between groups.

Conclusion

These preliminary results suggest that bankruptcy in PG may be associated with specific clinical differences. Treatment strategies may want to assess bankruptcy status to develop more effective treatments that take account of these clinical differences.     

Nalmefene in the treatment of pathological gambling: multicentre, double-blind, placebo-controlled study

Pathological gambling is a disabling disorder experienced by about 1% of adults. We randomised 233 participants (41.6% women) 1:1:1 to nalmefene (20 or 40 mg) or placebo. In analyses performed using an intention-to-treat (ITT) population, nalmefene failed to show statistically significant differences from placebo on primary and secondary outcomes. Post hoc analyses of only participants who received a full titration of the medication for at least 1 week demonstrated that nalmefene 40 mg/day resulted in significantly greater reductions on the primary outcome measure. These findings suggest that medication dosing may be an important consideration in achieving symptom control.