MedStar Good Samaritan Hospital

Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Good Samaritan Hospital, Baltimore, Maryland 21239.

OBJECTIVE: To conduct a systematic review and metaanalysis of the prevalence, risk factors, and prevention/treatment strategies for posttraumatic stress disorder symptoms in critical illness survivors. DATA SOURCES: PubMed, Embase, CINAHL, PsycINFO, and Cochrane Library from inception through March 5, 2014. STUDY SELECTION: Eligible studies met the following criteria: 1) adult general/nonspecialty ICU, 2) validated posttraumatic stress disorder instrument greater than or equal to 1 month post-ICU, and 3) sample size greater than or equal to 10 patients. DATA EXTRACTION: Duplicate independent review and data abstraction from all eligible titles/abstracts/full-text articles. DATA SYNTHESIS: The search identified 2,817 titles/abstracts, with 40 eligible articles on 36 unique cohorts (n = 4,260 patients). The Impact of Event Scale was the most common posttraumatic stress disorder instrument. Between 1 and 6 months post-ICU (six studies; n = 456), the pooled mean (95% CI) Impact of Event Scale score was 20 (17-24), and the pooled prevalences of clinically important posttraumatic stress disorder symptoms (95% CI) were 25% (18-34%) and 44% (36-52%) using Impact of Event Scale thresholds greater than or equal to 35 and greater than or equal to 20, respectively. Between 7 and 12 months post-ICU (five studies; n = 698), the pooled mean Impact of Event Scale score was 17 (9-24), and pooled prevalences of posttraumatic stress disorder symptoms were 17% (10-26%) and 34% (22-50%), respectively. ICU risk factors for posttraumatic stress disorder symptoms included benzodiazepine administration and post-ICU memories of frightening ICU experiences. Posttraumatic stress disorder symptoms were associated with worse quality of life. In European-based studies: 1) an ICU diary was associated with a significant reduction in posttraumatic stress disorder symptoms, 2) a self-help rehabilitation manual was associated with significant posttraumatic stress disorder symptom reduction at 2 months, but not 6 months; and 3) a nurse-led ICU follow-up clinic did not reduce posttraumatic stress disorder symptoms. CONCLUSIONS: Clinically important posttraumatic stress disorder symptoms occurred in one fifth of critical illness survivors at 1-year follow-up, with higher prevalence in those who had comorbid psychopathology, received benzodiazepines, and had early memories of frightening ICU experiences. In European studies, ICU diaries reduced posttraumatic stress disorder symptoms.

BACKGROUND: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS: or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS: A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.).

An in vivo model of human allergic disease has been developed in which nasal challenge with antigen leads to physiologic changes, together with a release of increased amounts of inflammatory mediators into nasal secretions obtained by washing the nose with saline. In 105 experiments involving 35 subjects, only allergic subjects consistently demonstrated an increase in the concentrations of the mast cell mediator, histamine, and the putative mast cell mediators, TAME-esterase and PGD2. The release of each mediator was significantly (p less than 0.001) related to the physiologic change (sneezing). The release of each mediator also correlated significantly with the release of the other 2 mediators (p less than 0.001). This system, for the first time, clearly relates an in vivo symptom and mediator release and thus should provide an excellent tool for the further study of the allergic response and nasal pathophysiology.

BACKGROUND AND PURPOSE: Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. METHODS: Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3x/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), o2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. RESULTS: Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, delta% T-AEX versus R-CONTROL, P<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%, P<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%, P<0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P<0.05), but not fitness gains. CONCLUSIONS: T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.

One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.

OBJECTIVES: To quantify the prevalence of frailty in adults of all ages undergoing chronic hemodialysis, its relationship to comorbidity and disability, and its association with adverse outcomes of mortality and hospitalization. DESIGN: Prospective cohort study. SETTING: Single hemodialysis center in Baltimore, Maryland. PARTICIPANTS: One hundred forty-six individuals undergoing hemodialysis enrolled between January 2009 and March 2010 and followed through August 2012. MEASUREMENTS: Frailty, comorbidity, and disability on enrollment in the study and subsequent mortality and hospitalizations. RESULTS: At enrollment, 50.0% of older (≥ 65) and 35.4% of younger (<65) individuals undergoing hemodialysis were frail; 35.9% and 29.3%, respectively, were intermediately frail. Three-year mortality was 16.2% for nonfrail, 34.4% for intermediately frail, and 40.2% for frail participants. Intermediate frailty and frailty were associated with a 2.7 times (95% confidence interval (CI) = 1.02-7.07, P = .046) and 2.6 times (95% CI = 1.04-6.49, P = .04) greater risk of death independent of age, sex, comorbidity, and disability. In the year after enrollment, median number of hospitalizations was 1 (interquartile range 0-3). The proportion with two or more hospitalizations was 28.2% for nonfrail, 25.5% for intermediately frail, and 42.6% for frail participants. Although intermediate frailty was not associated with number of hospitalizations (relative risk = 0.76, 95% CI = 0.49-1.16, P = .21), frailty was associated with 1.4 times (95% CI = 1.00-2.03, P = .049) more hospitalizations independent of age, sex, comorbidity, and disability. The association between frailty and mortality (interaction P = .64) and hospitalizations (P = .14) did not differ between older and younger participants. CONCLUSIONS: Adults of all ages undergoing hemodialysis have a high prevalence of frailty, more than five times as high as community-dwelling older adults. In this population, regardless of age, frailty is a strong, independent predictor of mortality and number of hospitalizations.

The search for biocompatible materials that can support the growth and phenotypic expression of osteoblasts and chondrocytes is a major challenge in the application of tissue engineering techniques for the repair of bone and cartilage defects. Chitosan, a copolymer of glucosamine and N-acetylglucosamine, may provide an answer to this search. Chitosan is the deacetylated product of chitin, a ubiquitous biopolymer found in the exoskeleton of insects and marine invertebrates. Little is known about the utility of chitosan in propagating human osteoblasts and chondrocytes. In this study, we test the hypothesis that chitosan promotes the survival and function of osteoblasts and chondrocytes. Chitosan (4%, w/v in 2% HAc) was coated onto plastic coverslips that had been fitted into 24-well plates. Human osteoblasts and articular chondrocytes were seeded on either uncoated or chitosan-coated coverslips at 1 x 10(5)/cells per well. Cultures were incubated at 37 degrees C, 5% CO(2) for a period of 7 days. Cell viability was assessed at that time using a fluorescent molecular probe. The phenotypic expression of osteoblasts and chondrocytes was analyzed by reverse transcriptase-polymerase chain reaction and immunocytochemistry. Osteoblasts and chondrocytes appeared spherical and refractile on chitosan-coated coverslips. In contrast, greater than 90% of cells on plastic coverslips were elongated and spindle shaped after 7 days of culture. Similar to cells propagated on uncoated control wells, greater than 90% of human osteoblasts and chondrocytes propagated on chitosan remained viable. Human osteoblasts propagated on chitosan films continued to express collagen type I whereas chondrocytes expressed collagen type II and aggrecan, as shown by reverse transcriptase-polymerase chain reaction analysis and immunostaining. The present in vitro work demonstrates the biocompatibility of chitosan as a substrate for the growth and continued function of human osteoblasts and chondrocytes. Chitosan may have potential use as a tissue engineering tool for the repair of osseous and chondral defects.

Clinical and laboratory features as well as immunogenetic markers were analyzed in 150 patients with SLE to determine if demographic factors--age at diagnosis, sex and race--influenced the expression of disease. The overall series included 103 white females, 35 black females, 10 white males and 2 black males; the mean age at diagnosis was 32.5 years. Males had a significantly older mean age at diagnosis than females (40.4 versus 31.8 years) and a significantly higher frequency of peripheral neuropathy (50% versus 18.8%). No other differences in clinical or laboratory features or HLA-DR or DQ phenotype frequencies were noted. Blacks had a significant younger mean age at diagnosis than whites (26.9 versus 33.4 years) as well as significantly higher frequencies of nephritis, hypertension, acute lupus pneumonitis, discoid rash, hyperglobulinemia and hypocomplementemia. There were no differences in autoantibody frequencies between race-specific subgroups. HLA-DR2, DRw52 and DQ1 were significantly associated with SLE in whites compared to controls; no HLA-DR or DQ associations were found with SLE in blacks. In whites, HLA-DR2 was associated with the presence of anti-Ro(SS-A) antibody while HLA-DR3 was associated with the presence of both anti-Ro(SS-A) and anti-La(SS-B) antibody. In blacks, HLA-DR2 was associated with the presence of anti-nDNA antibody. In whites, patients with late-onset SLE (age at diagnosis greater than or equal to 50 years) had significantly lower frequencies of nephritis and mesenteric vasculitis but, on the other hand, a higher frequency of secondary Sjögren syndrome than patients with age at diagnosis less than or equal to 22 years. Similar findings were noted when blacks aged 35 and above were compared to those aged 17 and below at diagnosis. In whites, the frequency of both anti-Ro(SS-A) and La(SS-B) antibodies increased with increasing age as did that of HLA-DR3; HLA-DR2, however, was more frequent in those with younger age at diagnosis. These data suggest the existence of two serologic-genetic subsets of SLE with different age at diagnosis.

The position of the tongue relative to the upper and lower jaws is regulated in part by the position of the hyoid bone, which, with the anterior and posterior suprahyoid muscles, controls the angulation and length of the floor of the mouth on which the tongue body 'rides'. The instantaneous shape of the tongue is controlled by the 'extrinsic muscles' acting in concert with the 'intrinsic' muscles. Recent anatomical research in non-human mammals has shown that the intrinsic muscles can best be regarded as a 'laminated segmental system' with tightly packed layers of the 'transverse', 'longitudinal', and 'vertical' muscle fibers. Each segment receives separate innervation from branches of the hypoglosssal nerve. These new anatomical findings are contributing to the development of functional models of the tongue, many based on increasingly refined finite element modeling techniques. They also begin to explain the observed behavior of the jaw-hyoid-tongue complex, or the hyomandibular 'kinetic chain', in feeding and consecutive speech. Similarly, major efforts, involving many imaging techniques (cinefluorography, ultrasound, electro-palatography, NMRI, and others), have examined the spatial and temporal relationships of the tongue surface in sound production. The feeding literature shows localized tongue-surface change as the process progresses. The speech literature shows extensive change in tongue shape between classes of vowels and consonants. Although there is a fundamental dichotomy between the referential framework and the methodological approach to studies of the orofacial complex in feeding and speech, it is clear that many of the shapes adopted by the tongue in speaking are seen in feeding. It is suggested that the range of shapes used in feeding is the matrix for both behaviors.

In the course of a controlled study to evaluate different forms of immunotherapy for subjects with insect-sting hypersensitivity, we observed 11 subjects who had systemic cutaneous urticarial reactions and 3 subjects who experienced systemic anaphylaxis. With the exception of tachycardia, there were no cardiopulmonary changes in the subjects with urticaria, whereas the major manifestation of anaphylactic shock in the other three subjects was severe hypotension that was probably secondary to peripheral vasodilation. Significant abnormalities in gas exchange developed in two subjects. In one, bronchospasm precipitated a respiratory arrest followed by endotracheal intubation with mechanical ventilation. Although plasma histamine levels were not related to the development of cutaneous reactions, the plasma histamine levels correlated with the severity and duration of the cardiopulmonary changes observed during anaphylactic shock. The two subjects with the most severe shock showed evidence of intravascular coagulation characterized by a diminution of Factor V, Factor VIII, fibrinogen, and high molecular weight kininogen, as well as changes in components of the complement system. Standard therapy with epinephrine and fluids, usually recommended for the treatment of systemic anaphylaxis, did not immediately reverse either the hemodynamic or the respiratory abnormalities in the two subjects with the most severe anaphylactic shock. Hemodynamic recovery was gradual and did not seem directly related to any specific therapeutic intervention.

Cultured human vascular endothelial cells obtained from umbilical cord veins were observed to acquire adhesive properties for purified neutrophils after exposure to IL 1, endotoxin, and tumor-promoting phorbol diesters. Adhesiveness induced by IL1 and endotoxin had similar kinetics of onset, producing no change after 30 min incubation and reaching optimal change by 4 hr of incubation. The phorbol diester TPA induced changes in adhesiveness more rapidly, with half maximal increase induced by a 15- to 30-min exposure. TPA, but not IL 1 or LPS, induced significant morphologic changes in the endothelial cell monolayer. None of the stimuli decreased endothelial cell viability. All stimuli induced increased adhesiveness at relevant concentrations, i.e., endotoxin, 0.01 to 1 microgram/ml; IL 1, 0.5 to 2 U/ml; and TPA, 1 to 30 ng/ml. Structure activity relationships among phorbol diesters indicate that the response occurs through a typical phorbol diester "receptor." A protein synthesis inhibitor (cycloheximide) and an RNA synthesis inhibitor (actinomycin D) prevented the acquisition of adhesiveness stimulated by IL 1 and endotoxin but not by TPA. In addition, TPA showed a differential temperature sensitivity in inducing adhesiveness in endothelial cells. IL 1 and endotoxin did not produce the effect with a 4-hr incubation at 22 degrees or 4 degrees C, whereas TPA was effective at these lower temperatures. Purified human IL 2 and recombinant-derived interferon-gamma failed to induce adhesiveness in vascular endothelial cells, indicating that this is not a general property of lymphokines. We conclude that endothelium may, under some circumstances, play an active role in producing a leukocyte infiltrate at a local tissue site by acquiring adhesive properties. The production of IL 1 by tissue macrophages, etc., may serve as an important initiator of an inflammatory cell infiltrate. Finally, an action of tumor-promoting phorbol diesters in increasing endothelial cell adhesiveness, combined with their known effects in activating leukocytes, may help explain the extraordinary inflammatory potency of these compounds.

Abstract The hemolysis of sheep red blood cells (SRBC) occurs via the classical complement pathway and is blocked by ethylene glycol bis-amino tetraacetate (EGTA). By contrast, fresh normal human serum in EGTA buffer was found to cause &amp;gt;90% hemolysis of unsensitized rabbit red blood cells (RaRBC) at a final dilution of 1:15. Absorbing human serum with RaRBC at 0°C will remove only 45% of this hemolytic activity and the same activity is present in human hypogammaglobulinemic serum. When rabbit lymphocytes were incubated with human serum in EGTA buffer, complement fixation occurred on their surface which was demonstrated with radiolabeled antibodies to human C3 or as “blocking” of the complement receptor. With purified complement components it was shown that the EGTA buffer completely blocked C1 but not C4, C2, or the late complement components. These findings show that a rabbit cell surface component can activate the alternate pathway of complement in human serum and suggest that this activation does not involve antibody.

Abstract The in vitro destruction (51Cr release) of DBA/2 mastocytoma cells by lymphocytes from immune C57BL mice has been used as a system to study the relationship between lymphocyte cyclic 3′,5′-adenosine monophosphate (cAMP) levels and cytolytic activity. It was established that there is a direct correlation between increased intracellular levels of cAMP and the inhibition of cytolytic activity of a lymphocyte population. Treatment of lymphocytes with adenyl cyclase stimulating agents (histamine, isoproterenol and prostaglandins E1 and E2) caused increases in cAMP levels and inhibited cytolytic activity. The time course of the increase in cAMP content following exposure to drug paralleled closely the time course of inhibition of cytolytic activity. The effect of isoproterenol on both cAMP content and cytolytic activity was short lived; the prostaglandins produced longer lasting effects on both systems. Theophylline, which inhibits the enzymatic degradation of cAMP also inhibited cytolysis. This inhibitory effect was at least additive to that produced by isoproterenol. The specificity of the relationship between intracellular cAMP levels and cytolytic activity was shown by the following observations. 1) Cyclic AMP and dibutyryl cyclic AMP inhibited lymphocyte activity. 5′-AMP at comparable concentrations did not. 2) The prostaglandins PGE1 and PGE2 both increased cyclic AMP content and consistantly inhibited lymphocyte-mediated cytolysis. Prostaglandin PGF 1α was inactive in both systems. 3) Propanolol, a β-adrenergic blocking agent, specifically prevented the effect of isoproterenol, a β-adrenergic agonist, on both cyclic AMP and cytolytic activity, but did not prevent the effect of the prostaglandins or histamine in either system. These results suggest that cAMP occupies a central modulatory role in the expression of cytolytic activity by lymphocytes.

Serological studies were performed on sera from 66 patients with the clinical picture of systemic lupus erythematosus (SLE). These sera failed to give a positive antinuclear antibody test when tested on cryostat sections of mouse liver and thus these patients' sera appear to be ANA negative. Precipitating antibodies to the cytoplasmic antigen Ro were found in 41 cases and of the remaining 25 sera, 18 were found to have antibodies to single stranded DNA detectable by radioimmunoassay. Thus, 50 of the 66 patients exhibited serological findings which are commonly found in ANA positive SLE patients. Studies with KB cells as immunofluorescent substrate revealed that 66% of these sera were positive for nuclear staining demonstrating that at least part of the failure of these sera to stain mouse liver is due to antigenic deficiency of this substrate. The clinical picture of these patients was dominated by a severe photosensitive dermatitis but more than half of the patients had widespread multisystem disease. As a group these patients had a low frequency of nephritis and neuropsychiatric disease. Detection of these antibodies relates these patients serologically to other SLE patients and suggests that they are best perceived as part of the clinical spectrum of SLE.

Using a recently developed model of nasal challenge, we have obtained data that clearly demonstrate, for the first time, kinin generation during a local allergic reaction in vivo. Allergic individuals (n = 8) and matched nonallergic controls (n = 8) were challenged intranasally with the appropriate antigen and nasal washes were taken before and after challenge. Washes were assayed for kinin, histamine, and [3H]-N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity. Increased kinin generation was found by radioimmunoassay (RIA) in the nasal washes of all the allergics (5,560 +/- 1,670 pg/ml) but in none of the controls (38 +/- 16 pg/ml). The presence of kinin was highly correlated with that of histamine and TAME-esterase activity and with the onset of clinical symptoms (P less than 0.001). Serial dilutions of nasal washes produced RIA displacement curves that paralleled the standard curve, and recovery of standard kinins that were added to nasal washes was 100 +/- 4% (n = 14). Kinin recovery was identical in both allergics and controls and did not vary significantly with antigen challenge. The immunoreactive kinin in nasal washes was stable to boiling and not precipitated by ethanol, but completely destroyed by carboxypeptidase B. It was evenly distributed between the sol and gel phases of nasal washes. High performance liquid chromatography analysis of the immunoreactive kinin in nasal washes showed it to be a mixture of lysylbradykinin and bradykinin. We conclude that kinins are produced during local allergic reactions in the nose and may contribute to the symptomatology of the allergic response.

BACKGROUND: Evidence linking increased body weight to osteoarthritis of the knee and the high prevalence of obesity underscore the importance of defining the outcome of total knee arthroplasty in obese patients. The purpose of this study was to compare the clinical and radiographic results of total knee arthroplasties performed in obese patients with those of total knee arthroplasties performed in nonobese patients. METHODS: Clinical and radiographic data on seventy-eight total knee arthroplasties in sixty-eight obese patients were compared with data on a matched group of nonobese patients. The analysis was also performed after stratification of the obese group for the degree of obesity. All patients had the same prosthesis. The clinical data that were analyzed included the Knee Society objective and functional scores, patellofemoral symptoms, activity level, and complications. RESULTS: The percentage of knees with a Knee Society score of > or =80 points at an average of eighty months was 88% in the obese group, which was significantly lower than the 99% rate in the nonobese group at the same time. The morbidly obese subgroup had a significantly higher revision rate than did the nonobese group (p = 0.02). CONCLUSIONS: The results of the present study suggest that any degree of obesity, defined as a body mass index of > or =30, has a negative effect on the outcome of total knee replacement.

Previous studies have demonstrated symptoms and mediator release occurring as long as 11 h after nasal challenge with antigen in selected allergic subjects. Pretreatment with systemic steroids reduced symptoms and mediators including histamine, TAME-esterase activity, and kinins. The aims of the present study were to characterize the cell influx during the late-phase response to antigen challenge and to determine the effect of pretreatment with systemic steroids on this response. We examined cytospin slides of nasal washings obtained before and hourly for 11 h after nasal antigen challenge in 10 asymptomatic allergic subjects with a history of seasonal rhinitis and 5 normal, nonallergic subjects. Allergic subjects received oral prednisone (20 mg 3 times a day) or placebo in a random, double-blind crossover manner for 2 days before each of 2 challenges 1 month apart. On placebo days, a mixed cell influx occurred in allergic subjects during the late response that was 50-fold greater than the cell influx in the nonallergic control subjects (p less than 0.005). During the first 3 h after antigen challenge, eosinophils (p less than 0.005), but not neutrophils or mononuclear cells, were observed. During the late phase (4 to 11 h), neutrophils, eosinophils, and mononuclear cells were all increased. Oral steroid pretreatment blocked the influx of eosinophils (p less than 0.005), but not that of other cells. These data demonstrate an inflammatory cell influx associated with the nasal late-phase response and suggest an important pathogenetic role for the eosinophil.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE: to assess temporal changes in the incidence of human immunodeficiency virus-1-associated nephropathy (HIVAN), and the association with use of highly active antiretroviral therapy (HAART). METHODS: HIVAN incidence and risk factors were assessed in 3976 HIV-1-infected individuals followed in clinical cohort in Baltimore, Maryland, USA from 1989 to 2001. The incidence of HIVAN, defined by biopsy or a conservative uniformly applied clinical coding protocol, was expressed in terms of person-years, and Poisson regression was used for multivariate analysis. RESULTS: Ninety-four patients developed HIVAN over the course of the study for an incidence of 8.0 per 1000 person-years [95% confidence interval (CI), 6.5 to 9.8]. African American race and advanced immunosuppression were strongly associated with HIVAN risk. HIVAN incidence declined significantly in 1998-2001 compared with 1995-1997. Among patients with a prior diagnosis of AIDS, HIVAN incidence was 26.4, 14.4, and 6.8 per 1000 person-years in patients not receiving antiretroviral therapy, treated with nucleoside analogue therapy only, or treated with HAART, respectively (P < 0.001 for trend). In multivariate analysis, HIVAN risk was reduced 60% (95% CI, -30 to -80%) by use of HAART, and no patient developed HIVAN when HAART had been initiated prior to the development of AIDS. CONCLUSION: HAART was associated with a substantial reduction in HIVAN incidence. Additional follow-up will be needed to determine if renal damage in susceptible individuals is halted or merely slowed by HAART, particularly when control of viremia is incomplete or intermittent.

The prevalence of insect sting reaction and of venom sensitization in adults is unknown. We report the results of intake evaluation of a stratified random sample of a large adult population previously studied for the determinants of atopic disease. In 269 subjects, the prevalence of systemic allergic sting reactions was 3.3% and 26.5% had IgE antibodies to venom demonstrated by skin test or radioallergosorbent test. Asymptomatic sensitization (positive venom skin test) was observed in 15% of subjects with no history of an allergic sting reaction. Positive venom skin tests were more frequent in men, in those with positive skin tests to inhalant allergens, and in subjects aged 20 through 29 years. A positive venom skin test or radioallergosorbent test was more frequent in subjects who had been stung within the previous 3 years (35%) than in those stung more than 3 years before (20%). We conclude that both systemic allergic reactions to insect stings and asymptomatic sensitivity to venom are common and that most affected persons never seek medical advice. The significance of asymptomatic venom sensitization is unknown.