The face of postural tachycardia syndrome - insights from a large cross-sectional online community-based survey.

BACKGROUND: Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community-based survey highlights patients' experience with POTS. It consists of the largest sample of POTS patients reported to date. OBJECTIVES: To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. METHODS: Postural tachycardia syndrome patients completed an online, community-based, cross-sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. RESULTS: The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). CONCLUSIONS: These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.

The SW(HEL) system for high-resolution analysis of in vivo antigen-specific T-dependent B cell responses.

T cell-dependent B cell responses generate optimal antibodies to combat foreign antigens. Naïve B cells responding to antigen undergo a complex series of differentiation events and cell fate decisions to provide long-lived memory B cells and plasma cells. Historically, B cell biologists have been challenged by the task of investigating rare antigen-specific B cells in an in vivo setting such that their interactions with antigen, regulation and migration may be accurately tracked. We have developed the SW(HEL) experimental system capable of accurately monitoring B cells that interact with a protein antigen and then subsequently undergo isotype switching, somatic hypermutation, and affinity maturation within germinal centers (GC) to generate high-affinity antibodies. Here we provide a comprehensive description of the procedures involved in establishing and using the SW(HEL) system to assess B cell responses to a foreign antigen. This system can provide a valuable measure of the functional capabilities of T follicular helper cells, whose role is ultimately to support and shape long-term humoral immunity.

Cushing's syndrome due to medullary thyroid carcinoma: diagnosis by proopiomelanocortin messenger ribonucleic acid in situ hybridization.

Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 micro g/d), epinephrine (66 micro g/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 micro g/dl and decreased to 12.9 and 4.5 micro g/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was -4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 micro g/d), epinephrine (0 micro g/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing's syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.

Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2.

There is considerable interest in developing topical microbicides; products to be used intravaginally by women for protection against sexually transmitted diseases. Many compounds derived from plants have been shown to have antimicrobial properties. We examined 19 such compounds in vitro by plaque reduction assay to determine their activity against a common sexually transmitted pathogen, herpes simplex virus type 2. Compounds with an ED50 < or = 7.0 mg/ml were tested for efficacy in vivo. Four compounds, carrageenan lambda type IV, cineole, curcumin, and eugenol, provided significant protection (P < 0.05) in a mouse model of intravaginal HSV-2 challenge. Eugenol, which provided the greatest protection in mice was also evaluated using the guinea pig model of genital HSV-2 infection where it also demonstrated significant protection. Based on these results, several plant-derived compounds appear to warrant further evaluation as potential microbicides.

Assessment of vision in infants and children.

An understanding of vision development is important in the assessment of visual problems. The authors look at this factor and outline testing procedures useful in the assessment of vision in the paediatric patient.

Visual acuity development: a study of preterm and full-term infants.

Visual acuity was measured in both preterm and full-term infants by means of forced-choice preferential looking. The ages of infants tested ranged from one month to 12 months. The results of both groups were considered and compared in terms of natal and conceptional age. The data suggested that preterm infants show visual responses equivalent to their full-term counterparts by nine months of age. Trends indicate that visual acuity development in healthy preterm infants appears to be accelerated when compared with full-term infants of the same post-conceptional age.

Inhibition of murine sarcoma virus induced transformation in an adenovirus -- NRK system.

Cell transformation induced by murine sarcoma virus (MSV-M) is significantly inhibited (80--90%) in a clonal line of normal rat kidney (NRK) cells when they are infected with rat cell passaged adenovirus 12 (R-Ad12). No inhibition is seen when R-Ad12 is added simultaneously with, or 1 1/2 or 24 hr after, MSV-M infection, suggesting that inhibition occurs most probably intracellularly. There is also a direct correlation between the extent of focus formation and the concentration of R-Ad12 used. Concentrations of R-Ad12 used to inhibit cell transformation do not affect cell growth. Significant inhibition in foci (90--100%) is also evident in the first two subcultures of R-Ad12 infected NRK cells. The mechanism of the inhibition is not yet known.

Bacteremia due to Bifidobacterium, Eubacterium or Lactobacillus; twenty-one cases and review of the literature.

Twenty-one cases of bacteremia due to Bifidobacterium, Eubacterium and Lactobacillus are described. Transient bacteremic episodes with these organisms may follow trauma to the mouth, intestine, or vagina. The majority of the patients were female and most had an underlying condition that may have predisposed to bacteremia. Ten of the patients died despite antibiotic treatment.

A variant of adenovirus 12 producing cytoplasmic accumulation of capsid proteins.

A variant of adenovirus type 12 (R-Ad12) has been isolated by infecting a clonal line of normal rat kidney cells (NRK) with wild-type adenovirus 12. Although R-Ad12 failed to produce infectious progeny virions when cycled a second time through NRK cells, it nevertheless retained the ability to code for virus structural proteins that accumulated in the cytoplasm.

Effect of dilution on recovery of bacteria from blood.

The multiplication rate of bacteria in undiluted blood containing sodium polyanethol sulfonate was compared with growth rates obtained in dilutions of blood ranging from 1:2 to 1:8. Although all organisms tested grew in the undiluted blood, increased growth rates were seen in the 1:2 dilution. Further dilution resulted in growth rates equivalent to that obtained with the 1:2 dilution. In view of these results, we question the present recommendations that blood be diluted 1:10 or 1:20.