Von Willebrand factor: a possible biomarker for disease activity in vasculitis.

OBJECTIVE: Inflammation markers, e.g. C- reactive protein (CRP) and sedimentation rate, can be normal despite active vasculitis. Von Willebrand factor (vWF) is secreted from endothelial cells in response to vascular damage. Some reports suggest increased vWF levels in vasculitis. This study aimed to evaluate vWF serum concentration in vasculitis patients as a possible biomarker of disease activity and to review the current literature. METHOD: Adult patients with systemic vasculitis were prospectively enrolled. Disease activity was recorded using the Birmingham Vasculitis Activity Score (BVAS) version 3. Blood group-adjusted vWF antigen serum level was evaluated at diagnosis and, when available, after treatment. RESULTS: Twenty-five vasculitis patients were compared to 15 healthy controls. The mean age of patients was 56 ± 17 years and 56% were women. Forty percent had anti-neutrophil cytoplasmic autoantibody-associated vasculitis, 20% giant cell arteritis, 16% polyarteritis nodosa, 8% Takayasu arteritis, and the rest had other vasculitides. The mean disease duration was 3.4 ± 4.8 years. Mean vWF was higher in patients with active vasculitis than in healthy controls (212 ± 81% vs 106 ± 26%, p < 0.001). vWF levels directly correlated with BVAS. In 13 patients with active vasculitis who reached remission or low disease activity after treatment, vWF level at follow-up decreased significantly. In three out of five patients who were treated with interleukin-6 inhibitors, vWF was elevated despite normal CRP levels, while vasculitis was clinically active. CONCLUSION: vWF antigen serum level is increased in active vasculitis and could potentially serve as a biomarker for active disease.

Anti-IL-6 receptor antibody (tocilizumab): a B cell targeting therapy.

BACKGROUND: IL-6 mediated inflammation is induced by binding to IL-6 receptor (IL-6R) or IL-6/IL-6R complex binding gp130. Tocilizumab, a recombinant humanised monoclonal antibody that acts as IL-6R antagonist has been recently introduced for the treatment of rheumatoid arthritis (RA). OBJECTIVES: To evaluate whether tocilizumab therapy may induce B cells to undergo phenotypic changes compatible with regulatory function. METHODS: B cells from treated RA patients were isolated before and after 3 months of treatment with tocilizumab and were stained for the expression of intracellular TGF-ß, IL-10, membrane CD69, and MHCII. These markers were assessed in CD25(high) B cells considered to belong to a regulatory/suppressive subset of B cells. All markers were expressed in mean flow cytometry intensity (MFI), with results given in mean ± SEM. Data was compared before and after tocilizumab treatment. RESULTS: Clinical improvement was noted three months following the initiation of tocilizumab, namely: DAS improvement from 6.8 ± 0.3 at baseline to 3.1 ± 0.4, p<0.002, and ESR decrease from 44.4 ± 8.6 at baseline to 7.4 ± 2.3, p<0.006. This clinical benefit was found to occur in association with the expansion of a B cell subset with regulatory properties namely: the expression of intracellular TGF-ß in CD25-high B cells was significantly increased (from 5.2 ± 2.3 at baseline to 8.1 ± 2.8; p<0.02); In addition, the expression of MHC-II and of CD69 on B cells were significantly reduced (from 9.1 ± 2.2 at baseline to 4.2 ± 0.4; p<0.04), and (from 7.6 ± 2.4 at baseline to 2.7 ± 0.7; p<0.03) respectively. CONCLUSIONS: The present finding of a shift in B cell properties following tocilizumab treatment, namely the increase in TGF-ß expression and the alteration in the activation status (CD69 expression) and APC properties (MHC-II expression) in CD25(high) B cells, suggests that the induction/expansion of B regulatory cells may be one of the mechanisms by which tocilizumab may possibly produce its beneficial clinical effects.

Complement-dependent histaminase release from human granulocytes.

The role of particle-bound complement proteins in the induction of noncytotoxic enzyme release from human granulocytes was investigated with the use of sera genetically deficient in complement and highly purified complement components. Release of histaminase, one of two important histamine catabolizing enzymes, and beta-glucuronidase from polymorphonuclear leukocytes was solely dependent on particle-bound C3b (the larger cleavage product of the third component of complement) when fluid-phase complement was excluded. The extent of enzyme release was a function of particle-bound C3b input, was reduced by exposing the particles to C3b inactivator, and was blocked by fluid-phase C3b. Phagocytosis of the C3b-coated particles was not required for enzyme release from neutrophils. In contrast, phagocytosis of "opsonized" particles was required for noncytotoxic release of histaminase and arylsulfatase from eosinophils; other proteins, as well as C3b, were able to opsonize particles for induction of enzyme release from eosinophils. These studies suggest a dual role for complement (particularly C3) in modulating vascular permeability phenomena, i.e., release of vasoactive mediators by the action of C3a and C5a, and release of the corresponding enzymes that inactivate the mediators by C3b.

Whole-eye transplantation: a look into the past and vision for the future.

Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye transplantation (WET) provides the opportunity to replace diseased retinal ganglion cells, as well as the entire optical system and surrounding facial tissue, if necessary. Recent success in face transplantation demonstrates that this may be a promising treatment for what has been to this time an incurable condition. An animal model for WET must be established to further enhance our knowledge of nerve regeneration, immunosuppression, and technical aspects of surgery. A systematic review of the literature was performed to evaluate studies describing animal models for WET. Only articles in which the eye was completely enucleated and reimplanted were included. Study methods and results were compared. In the majority of published literature, WET can result in recovery of vision in cold-blooded vertebrates. There are a few instances in which mammalian WET models demonstrate survival of the transplanted tissue following neurovascular anastomosis and the ability to maintain brief electroretinogram activity in the new host. In this study we review in cold-blooded vertebrates and mammalian animal models for WET and discuss prospects for future research for translation to human eye transplantation.

Nonspecific dizziness: frequency of supine hypertension associated with hypotensive reactions on head-up tilt.

The clinical syndrome of supine hypertension associated with orthostatic hypotension (OH) in given individuals is recognized by specialists, but is underdiagnosed in the community. The objective of this study was to assess supine hypertension associated with hypotensive reactions on head-up tilt (SH-HRT) among patients evaluated for nonspecific dizziness. Consecutive patients with nonspecific dizziness were studied with a 10-min supine 30-min head-up tilt test. Supine hypertension (SH) was diagnosed when supine systolic blood pressure (SBP) was > or = 140 mmHg and/or supine diastolic blood pressure (DBP) was > or = 90 mmHg. Hypotensive reactions on tilt (HRT) were diagnosed when SBP decreased by > or = 30 mmHg on tilt and/or DBP decreased by > or = 15 mmHg. Of 430 patients tested, 42 (9.8%) had SH-HRT. The median age was 67 years; 37 had a pretest diagnosis of hypertension, with treatment. The median supine BP was 162/90 mmHg; the median nadir BP on tilt was 118/78 mmHg. Four SH-HRT patterns were recognized: (I) SH with typical neurogenic OH (n = 6), (II) SH with vasovagal reaction on tilt (n = 4), (III) SH with sustained HRT (n = 28), and (IV) SH with mixed orthostatic-vasovagal reaction on tilt (n = 4). Dizziness on tilt occurred in 25% of patients category III (SH with sustained HRT), while appearing universally in other SH-HRT patterns. In conclusion, nonspecific dizziness may be the chief complaint in patients with SH-HRT, a disorder often unrecognized by clinicians. Different patterns of SH-HRT on HUTT may reflect different aberrations in cardiovascular homeostasis and may require differentiated management strategies.

Aortic involvement in rheumatic diseases.

OBJECTIVE: To review the prevalence, mechanisms, presentations and clinical significance of aortic involvement in rheumatic inflammatory diseases. METHODS: The medical literature, available through a PUBMED search was reviewed and the relevant information was summarized. In addition, selected articles related to aortic involvement in rheumatic diseases were included in this review. RESULTS: Rheumatic disorders may be categorized by their propensity to involve the aorta: conditions with a prevalence of 10% and more (Takayasu's arteritis, temporal arteritis, long-standing ankylosing spondylitis, Cogan's syndrome and relapsing polychondritis), disorders with uncommon but well documented aortic involvement and rheumatic conditions with rare case reports of such involvement. Clinical presentation of aortic disease is dependent on the part of aorta involved and may manifest by aortic pain and/or other symptoms caused by aortic dilatation, narrowing or aneurysm. The histopathology of inflammatory aortitis is characterized by lymphoplasmacytic infiltration with or without giant cells or granulomas. On the other hand, non-inflammatory aortic damage in rheumatic diseases may include Marfan-like cystic disintegration of the aortic media as well as accelerated atherosclerosis. Awareness of rheumatic conditions with a high potential for clinically significant aortic involvement may promote referral of such patients for aortic imaging and sometimes surgery before fatal complications intervene. CONCLUSION: Early diagnosis of aortic involvement can be advanced by informed consideration of such a complication in a rheumatic patient.

The patient with supine hypertension and orthostatic hypotension: a clinical dilemma.

Coexistent supine hypertension and orthostatic hypotension (SH-OH) pose a particular therapeutic dilemma, as treatment of one aspect of the condition may worsen the other. Studies of SH-OH are to be found by and large on patients with autonomic nervous disorders as well as patients with chronic arterial hypertension. In medical practice, however, the aetiologies and clinical presentation of the syndrome seem to be more varied. In the most typical cases the diagnosis is straightforward and the responsible mechanism evident. In those patients with mild or non-specific symptoms, the diagnosis is more demanding and the investigation may benefit from results of the tilt test, bedside autonomic tests as well as haemodynamic assessment. Discrete patterns of SH-OH may be recognisable. This review focuses on the management of the patient with coexistent SH-OH.

The emergency room in systemic rheumatic diseases.

Complications of systemic rheumatic diseases frequently have protean manifestations and may present a diagnostic problem. Patients with connective tissue diseases and vasculitides may have dangerous or life threatening conditions, which must be recognised and treated promptly to prevent rapidly evolving morbidity and mortality. Knowledge of possible emergencies in the context of a defined rheumatic disease may aid in promoting a high index of suspicion and contribute significantly to the timely diagnosis of many potentially dangerous conditions. This review is written for the emergency room physician and discusses the early recognition of selected emergencies in the context of a defined rheumatic disease.

A prospective, randomized, placebo-controlled trial of on-Demand vs. nightly sildenafil citrate as assessed by Rigiscan and the international index of erectile function.

Multiple studies have evaluated the use of PDE5 inhibitors in penile rehabilitation following nerve-sparing prostatectomy. These studies have evaluated the use of various pharmacologic agents as well as various approaches to treatment (on-demand vs. rehabilitative). Most of these studies relied on self-reported outcomes to determine efficacy of the therapy which could allow response bias to affect their results. The aim of this study was to evaluate the effects of nightly sildenafil citrate therapy during penile rehabilitation, using nocturnal penile rigidity (RigiScan(™), Gotop Medical, Inc., St. Paul, MN, USA) in addition to the IIEF-EF. Patients with localized prostate cancer and normal erectile function prior to nsRP were randomized to take either nightly 50 mg sildenafil citrate or placebo starting the night following surgery. Both groups were allowed on-demand sildenafil citrate. Erectile function was evaluated at 2 weeks, 3, 6, 9 and 12 months post-operatively, with a final assessment made at 13 months, following a 1 month drug washout. At all time points, self-reported (IIEF-EF) and objective (RigiScan(™)) measures were obtained and evaluated. About 74 of 97 randomized patients completed the study. On completion, 40% of patients in each group had normal erectile function based on RigiScan(™) (p = 1.0). Additionally, no statistical differences were seen using the IIEF-EF domain (32.4% of placebo, 29% of treatment; p = 0.79). Multivariable analysis showed no significant differences in erectile function based on treatment intervention. Results did show that African-American men in this cohort were at higher risk for lower RigiScan(™) scores over time (OR: 0.48, p = 0.0399). This study demonstrates that nightly sildenafil citrate does not provide a therapeutic benefit for recovery of erectile function post-prostatectomy when compared to on-demand dosing using both self-reported as well as objective measures. Differences in objective recovery parameters based on patients' race/ethnicity warrant further investigation.

Increased spontaneous apoptosis of CD4+CD25+ T cells in patients with active rheumatoid arthritis is reduced by infliximab.

Increased secretion of tumor necrosis factor-alpha (TNF-alpha), along with interleukin-1 (IL-1) and interleukin-6 (IL-6), is important in the pathogenesis of rheumatoid arthritis (RA). T regulatory CD4(+)CD25(+) cells play a role in maintaining self-tolerance by downregulating Th1-induced proinflammation. This function has been found to be altered in active RA, whereas anti-TNF-alpha therapy has been found to improve the suppressive abilities of these cells. Our objectives were to investigate whether T regulatory cells in patients with active RA display a higher sensitivity to spontaneous apoptosis than in normals, and to look into the potential of infliximab (anti-TNF-alpha therapy) to reduce the sensitivity of these cells to spontaneous apoptosis. Seventeen patients suffering from active RA, having failed multiple disease-modifying antirheumatic drug (DMARD) therapies, were treated with infliximab. Spontaneous apoptosis (as detected by annexin V binding) was determined in all patients and compared with a group of normal individuals at baseline and after three months on infliximab treatment. Peripheral blood mononuclear cells were incubated in 24-well plates at 1 x 10(6) cells/mL for 48 hours. Annexin V binding on CD4(+)CD25(+) was assessed using three-color assay by flow cytometry. Prior to infliximab initiation, spontaneous apoptosis of T regulatory cells from active RA patients was found to be increased in comparison with controls (26 +/- 4.2% vs. 19.8 +/- 4.8%, respectively; P = 0.01). Three months later (while still on infliximab) spontaneous apoptosis was comparable in the two groups (20.7 +/- 5.2% vs. 20.9 +/- 3.4%; P 5 0.8). The absolute number of CD4(+)CD25(+) cells/mL in the peripheral blood at baseline was reduced in 11 out of 17 active RA patients when compared with that of the control group (24 +/- 7 vs. 32 +/- 11, respectively; P = 0.02). Following anti-TNF-alpha therapy, CD4(+)CD25(+) cell counts of patients were equivalent to those of normals. The alteration and reversal in both spontaneous apoptosis and cell count of T regulatory cells was found to correlate with RA disease activity. CD4(+)CD25(+) T regulatory cells display increased proclivity to undergo spontaneous apoptosis in active RA. Alterations in CD4(+)CD25(+) cell apoptosis and cell count were found to correlate with RA disease activity. Reversal of these deviations from normal was documented in association with the beneficial outcome of infliximab therapy.

Hyperventilation and amplified blood pressure response: is there a link?

Based on prior studies, the hypothesis that hyperventilation (HV) may have a pressor effect and play a causal role in hypertension has been suggested. The objective of this study was to correlate HV with blood pressure (BP)-change during a postural challenge. Consecutive subjects referred for evaluation of syncope, dizziness, chronic fatigue syndrome (CFS), fibromyalgia, or non-CFS fatigue were assessed with a 10-min supine 30-min head-up tilt test combined with capnography. We selected for analysis the records of patients aged 17-70 years, not taking vasoactive medications, having sitting systolic BP (SBP) < 140 mmHg, sitting diastolic BP (DBP) < 90 mmHg, and who completed 30 min of tilt. HV was diagnosed when end-tidal pressure of CO2 < 30 mmHg was recorded consecutively for > or = 10 min. Postural hypertension (PHT) was diagnosed when DBP on tilt > or = 90 mmHg was recorded consecutively for > or = 10 min. DBP-change was computed as (median DBP on tilt) -(median DBP supine). PHT and DBP-change were correlated with HV. A total of 320 patient charts were reviewed. PHT was present in 30 cases. The mean DBP-change in patients with PHT was +9.9 mmHg (s.d. 5.8), with three patients manifesting HV. Of the remaining 290 patients, 56 had HV, their mean DBP-change was -0.3 mmHg (s.d. 7.2). The other 234 patients without HV had a mean DBP-change +0.95 mmHg (s.d. 5.7), comparable to the DBP-change in patients with HV. In, conclusion, posturally induced HV was not associated with an increase in BP, nor was PHT associated with HV, except in a small minority of cases.

Pseudopodagra: A presenting manifestation of infective endocarditis.

Podagra is a term used to describe acute monoarthritis of the first metatarsophalangeal (1st MTP) joint. The most common diagnoses of arthritis in this joint are: crystal-induced synovitis, septic arthritis, traumatic conditions and reactive arthritis. When etiologies other than gout are involved this is frequently referred to as pseudopodagra. We report the case of a patient who presented with pain and swelling of the 1st MTP The absence of intraarticular crystals and hyperuricemia encouraged further evaluation of the patient. A cardiac murmur was investigated by echocardiography, which revealed valvular vegetations and the diagnosis of infective endocarditis (IE) was established. This is the first reported case of a podagra-like presentation of IE. As in this case, the diagnosis of gout should rest on findings beyond the presence at 1st MTP arthritis, with evaluation of all extraarticular signs in order to rule out other possible diagnoses.

Behçet's disease, myelodysplastic syndrome, trisomy 8, gastroenterological involvement--an association.

Only a limited number of cases of Behçet's disease and hematological malignancies have been reported in the literature. We report the case of a 45 year old female patient with Behçet's disease who developed myelodysplastic syndrome, refractory anemia with excess blasts in transformation subtype, with complex chromosomal abnormalities, including excess of chromosome 8, following several years of treatment with chlorambucil for Behçet's disease. As has been described in most such cases, gastrointestinal involvement was most prominent. This case is described and the occurrence of myelodysplastic syndrome in Behçet's disease reviewed.

Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test.

Adrenal response to iv administration of 1-24 ACTH (250 micrograms) was examined in normal volunteers under various conditions. The effect of basal cortisol levels was examined by performing the tests at 0800 h with and without pretreatment with dexamethasone. The effect of time of day was evaluated by performing the tests at 0800 h and at 1600 h, eliminating possible basal cortisol influence by pretreatment with dexamethasone. In the first set of tests, despite significantly different baseline levels, 30-min cortisol levels were not different (618 +/- 50 vs. 590 +/- 52 nmol/L). Afternoon cortisol levels in response to ACTH were found to be significantly higher than morning levels at 5 min (254 +/- 50 vs. 144 +/- 36 nmol/L, p less than 0.01) and at 15 min (541 +/- 61 vs. 433 +/- 52 nmol/L, p less than 0.02). This difference in response was no longer notable at 30 min (629 +/- 52 and 591 +/- 52 nmol/L). We tried also to determine the lowest ACTH dose which will elicit a maximal cortisol response. No difference was found in cortisol levels at 30 and 60 min in response to 250 and 5 micrograms 1-24 ACTH. Using 1 micrograms ACTH, the 30-min response did not differ from that to 250 micrograms (704 +/- 72 vs. 718 +/- 55 nmol/L, respectively). However, the 60-min response to 1 microgram was significantly lower (549 +/- 61 vs. 842 +/- 110 nmol/L, p less than 0.01). Using this low dose ACTH test (1 microgram, measuring 30-min cortisol level), we were able to develop a much more sensitive ACTH test, which enabled us to differentiate a subgroup of patients on long-term steroid treatment who responded normally to the regular 250 micrograms test, but had a reduced response to 1 microgram. The stability of 1-24 ACTH in saline solution, kept at 4 C, was checked. ACTH was found to be fully stable after 2 hs in a concentration of 5 micrograms/ml in glass tube and 0.5 micrograms/ml in plastic tube. It was also found to be fully stable, both immunologically and biologically, for 4 months, under these conditions. We conclude that the 30-min cortisol response to ACTH is constant, unrelated to basal cortisol level or time of day. It is therefore the best criterion for measuring adrenal response in the short ACTH test. The higher afternoon responses at 5 and 15 min suggest greater adrenal sensitivity in the afternoon, but further studies are needed to clarify this issue.(ABSTRACT TRUNCATED AT 400 WORDS)

Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF).

Familial Mediterranean Fever is one of the most frequent recessive disease in non-Ashkenazi Jews. The gene responsible for the disease (MEFV) has very recently been identified. The M694V ('MED') mutation was found in about 80% of the FMF Jewish (Iraqi and North African) chromosomes. To see if the presence of this mutation could be correlated with particular traits of the disease, we examined a number of clinical features in a panel of 109 Jewish FMF patients with 0, 1 or 2 MED mutations. We showed that homozygosity for this mutation was significantly associated with a more severe form of the disease. In homozygous patients, the disease started earlier (mean age 6.4 +/- 5 vs 13.6 +/- 8.9) and both arthritis and pleuritis were twice as frequent as in patients with one or no M694V mutation. Moreover, 3/3 patients with amyloidosis displayed two MED mutations. No association was found with fever, peritonitis, response to colchicine and erysipeloid eruption. The present result strongly suggests the potential prognostic value of the presence of this mutation.

The fasciitis-panniculitis syndromes. Clinical and pathologic features.

The authors propose to encompass under the designation of "fasciitis-panniculitis syndromes" (FPS) a group of disorders characterized by induration of the skin due to chronic inflammation and fibrosis of the subcutaneous septa and muscular fascia. The prototype of the FPS is eosinophilic fasciitis. Thirty-two consecutive patients with FPS were cared for at the author's hospital during a 10-year period. The association of the FPS with other diseases, clinical presentations, histologic features, and response to treatment were analyzed. Idiopathic FPS, that is, eosinophilic fasciitis, was diagnosed in 14 patients. In the remaining 18 cases, the FPS were ascribed to vascular disorders (n = 6), infections (n = 6), and neoplastic disorders (n = 3), while trauma, insect bites, and Sweet syndrome antedated the FPS in 1 patient each. The lesions had a sleeve-like distribution in 20 patients, plaque-like distribution in 7, and a combined pattern in 5. Skin biopsies revealed lesions in the deep subcutaneous layers with the pathologic triad of septal and fascial fibrosis, chronic inflammatory infiltration, and small-vessel vasculopathy. Spontaneous improvement occurred in 4 cases. Following cimetidine monotherapy, complete remission was achieved in an additional 3 of 5 patients. The concept of the FPS serves to advance our understanding on several fronts: emphasizing the clinical and etiologic diversity; recognizing a stereotypic tissue reaction pattern; highlighting the panniculitis in addition to the fasciitic component; and describing a similar response to drug therapy in different clinical settings. Based on the results of the present series, cimetidine may be recommended as first-line treatment.

Arthropathy, hypouricemia and normal serum iron studies in hereditary hemochromatosis.

A patient manifesting the arthropathy of hemochromatosis without abnormal serum iron studies is described. Hemochromatosis was confirmed by liver biopsy. This case serves to emphasize the diagnostic value of the characteristic arthropathy of hemochromatosis. Our observations in this patient support the hypothesis that the pathogenesis of hereditary hemochromatosis differs from that of acquired iron overload states. The concurrent presence of hypouricemia is explored in this patient and in 18 other patients with hereditary hemochromatosis. Men with hereditary hemochromatosis were found to have lower serum uric acid levels than expected. In our patient, a renal defect in tubular reabsorption of uric acid appears responsible for hypouricemia. The apparent association of hemochromatosis and hypouricemia deserves further investigation.

Arthritis of hemochromatosis. Clinical spectrum, relation to histocompatibility antigens, and effectiveness of early phlebotomy.

Five patients who presented with arthritis as the sole manifestation of hereditary hemochromatosis and 51 family members were studied. Studies included clinical evaluation for the presence of arthritis and hemochromatosis, roentgenography of hands, knees, and pelvis, serum iron and serum ferritin measurements, complete HLA typing for 50 of the A and B loci, and, when indicated, liver biopsy. Arthritis occurred in 45 percent of persons with hemochromatosis. Although typical involvement of second and third metacarpophalangeal joints was observed in all five patients and some family members, two with typical arthritis did not have characteristic radiographic changes, two had constitutional symptoms without arthropathy, and one had unilateral hand changes. A specific HLA haplotype (A2/B17 in Family 1 and A29/B15 in Family 2) correlated with hereditary hemochromatosis but not with the arthropathy. Phlebotomy alleviated the early constitutional symptoms but did not help advanced arthritis. Anti-inflammatory drugs, intraarticular injections of glucocorticoids, and resection osteotomies of metacarpal heads were other treatment modalities.

Microbiology of the vagina in children: normal and potentially pathogenic organisms.

Vaginal cultures from 100 healthy girls, 2 months to 15 years of age, were examined for the presence of normal and potentially pathogenic microorganisms. Corynebacterium vaginale, yeast species, and genital mycoplasmas were isolated from vaginal cultures from 13.5 %, 28%, and 28% of the girls examined, respectively. Colonization with these organisms was not associated with signs or symptoms of vaginitis. Neisseria gonorrhoeae was isolated from a 4-year-old with purulent vaginitis. Trichomonas vaginalis was recovered from two 13-year-olds, both of whom had an abnormal vaginal discharge. Vaginal antibody to Chlamydia trachomatis was found in two girls 4 and 13 years of age. In neither girl was the organism recovered from the vaginal culture. Chlamydia trachomatis was recovered from the vaginal culture of another 4-year-old who had no abnormal findings on examination. Cultures from 59 of the girls were examined for aerobic and facultatively anaerobic bacteria. Diphtheroids and Staphylococcus epidermidis were the most frequently isolated organisms. Lactobacilli were isolated most frequently from the older girls, whereas enteric organisms were isolated most frequently from the younger girls.