Efficacy, safety and immunological actions of butanol-extracted Food Allergy Herbal Formula-2 on peanut anaphylaxis.

BACKGROUND: Therapies for peanut allergy (PNA) are urgently needed. Food Allergy Herbal Formula-2 (FAHF-2) has profound therapeutic effects in a murine PNA model and is safe for food-allergic adults in clinical trials. However, the large FAHF-2 pill-load is not conducive to clinical studies in children. Thus, refining FAHF-2 to decrease pill-load is essential for the inclusion of children in clinical trials and to facilitate studying FAHF-2 as a clinically useful botanical drug. OBJECTIVES: Testing long-term efficacy and safety of a butanol-purified extract of FAHF-2 (B-FAHF-2) in a murine model of PNA, and to explore its immunological mechanisms of action. METHODS: FAHF-2 was purified by butanol extraction. C3H/HeJ mice with established PNA received the first course of B-FAHF-2 at 6 mg, twice daily for 7 weeks (PNA/B-FAHF-2) or water (PNA/sham) and were then challenged immediately after completing the treatment and six more times every 1-2 months post-treatment up to week 50. Mice then received a second course of B-FAHF-2 treatment at week 52 and were challenged at week 65. In vivo and in vitro immunological effects on T, B and mast cells were also determined. RESULTS: Butanol purification reduced the volume of the effective dose ∼5-fold. All PNA/B-FAHF-2 mice were completely protected from PN anaphylaxis until the fifth challenge after the first course of treatment, as compared with PNA/sham mice. Partial protection persisted up to 50 weeks. A second treatment course restored complete protection. B-FAHF-2 significantly suppressed Th2 cytokine, IgE and histamine levels in vivo, and showed direct inhibition of Th2, IgE-producing B cells and mast cell activation in vitro. B-FAHF-2 had a high margin of safety. CONCLUSION AND CLINICAL RELEVANCE: B-FAHF-2 produced long-lasting protection against PN anaphylaxis for approximately half of the murine life span without side-effects. B-FAHF-2 exhibited direct effects on multiple food allergy effector cells.

Evidence of 'genuine empty follicles' in follicular aspirate: a case report.

Failure to retrieve oocytes after normal ovarian stimulation has been labeled 'empty follicle syndrome' (EFS). The existence of genuine EFS has been questioned and is still controversial. Here, we report an unusual case in which an extraordinary number of empty follicle-like structures were identified in the ovarian aspirate at the time of retrieval. A 31-year-old woman presented with a 4-year history of primary infertility and underwent ovulation induction. The patient was given hCG and oocyte retrieval was performed 36 h later. During the oocyte retrieval, more than 200 tiny structures resembling pre-antral follicles were noted in the ovarian aspirate. They exhibited two to three layers of granulosa cells and appeared to enclose an immature oocyte. They showed a great variation in size ranging between 40 and 80 microm. These structures were further characterized by electron microscopy and cultivated in vitro to assess hormone secretion. The follicles were found to be devoid of oocytes, but each had a readily identifiable zona. Hormone assays revealed that these follicles were secreting increasing levels of estradiol. A second in vitro fertilization attempt gave similar results. These data are suggestive of some failure in the oocyte maturation process. We speculate that this may be the first actual evidence to support the existence of true empty follicles, which if left to grow in vivo might lead to empty graffian follicles and genuine EFS.

Contrast-enhanced MR angiography and perfusion imaging of the hand.

OBJECTIVE: The goal of this investigation was to develop a technique for producing high-resolution gadolinium-enhanced MR images of the hand that show three-dimensional angiographic anatomy and permit measurement of distal soft-tissue perfusion. CONCLUSION: High-resolution MR angiograms of the hand, as well as qualitative perfusion information, can be produced using a rapid sequential gadolinium-enhanced three-dimensional gradient-echo technique.

Mastitis due to Mycobacterium abscessus after body piercing.

We describe a patient with granulomatous mastitis due to Mycobacterium abscessus that presented as a mass lesion and was associated with a pierced nipple. To our knowledge, this is the first reported case of mastitis due to M. abscessus and the first association of this organism with body piercing.

Mycobacterium triplex infection in a liver transplant patient.

Mycobacterium triplex was first named in 1996 as an acid-fast bacillus with features that most resemble Mycobacterium simiae and Mycobacterium avium-intracellulare complex but which possesses a distinct mycolic acid pattern as well as a distinctive 16S rRNA hypervariable region. It has been isolated from lymph node, sputum, and cerebrospinal fluid specimens, but to date only rare clinical cases of this organism have been reported in the literature. The following is a case report of M. triplex that was isolated from the pericardial and peritoneal fluid of a 13-year-old female liver transplant patient.

Human immunodeficiency virus-related mortality in infants and children: data from the pediatric pulmonary and cardiovascular complications of vertically transmitted HIV (P(2)C(2)) Study.

OBJECTIVES: To identify the causes of mortality in children with vertically transmitted human immunodeficiency virus (HIV) infection and to study age-related mortality trends. METHODS: In the multicenter P(2)C(2) HIV Study, 816 children born to HIV-infected mothers were followed for a median of 3.6 years. Two hundred five study participants with HIV infection were enrolled at a median age of 23 months; 611 were enrolled either prenatally or in the neonatal period before their HIV infection status was known. There were 121 deaths in study patients. The cause of death for all patients, its relationship to HIV infection, and pulmonary or cardiac involvement were determined. Age trends in disease-specific mortality were summarized for the HIV-related deaths. RESULTS: Ninety-three children died of HIV-related conditions. Infection was the most prevalent cause of death for children under 6 years of age with 32.3% caused by pulmonary infection and another 16.9% caused by nonpulmonary infection. The frequency of pulmonary disease as the underlying cause of death decreased significantly with increasing age: 5/9 (55.6%) by age 1, 1/12 (8.3%) after age 10 years. The frequency of chronic cardiac disease as the underlying cause increased with age-0% by age 1 year, 3/12 (25.0%) after age 10 years, as did the frequency of wasting syndrome with disseminated Mycobacterium avium complex-0% by age 1 year, 6/12 (50.0%) after age 10 years. CONCLUSIONS: Children with HIV who survive longer are less likely to die of pulmonary disease or infection and more likely to die of cardiac causes or with wasting syndrome.pediatric acquired immunodeficiency syndrome, mortality, human immunodeficiency virus.

Single breath-hold multi-slab and cine cardiac-synchronized gadolinium-enhanced three-dimensional angiography.

The rest period of the coronary arteries has been shown to be on the order of 120-160 msec. Restriction of the acquisition window in breath-hold cardiac-synchronized gadolinium-enhanced imaging to this duration limits the amount of sampled k-space data and hence the information when compared with conventional gadolinium-enhanced imaging. Two techniques for gadolinium-enhanced cardiac-synchronized angiography were implemented that acquire additional data during the unused portions of the cardiac cycle. Data acquisition is synchronized with the heart cycle and is restricted to a short period of each heart cycle. In a single breath-hold, a multi-slab acquisition (n = 5) allowed ECG-synchronized imaging of the entire heart or a CINE acquisition (n = 5) provided multiple stacks of images at different phases in the cardiac cycle over a smaller area. Preliminary results acquired in healthy volunteers and patients with aortic disease indicate that additional information can be acquired without an increase in breath-hold duration or a reduction in image quality.

Captopril MR renography in a swine model: toward a comprehensive evaluation of renal arterial stenosis.

PURPOSE: To test the feasibility of captopril magnetic resonance (MR) renography and to validate the technique in an animal model of renal arterial stenosis. MATERIALS AND METHODS: Seven pigs with induced renal arterial stenosis were studied. MR renography was performed with a T1-weighted approach by using three-dimensional fast imaging with steady-state precession, or FISP, sequences after administration of a bolus of 0.1 mmol of gadopentetate dimeglumine per kilogram of body weight. Captopril was administered to improve the specificity. RESULTS: The results demonstrate that differences in renographic curves and indices are observed only if an anatomically substantial stenosis, typically a diameter reduction of more than 70%, is present and captopril is administered. CONCLUSION: In this preliminary experience in an animal model, captopril MR renography provided data consistent with expectations based on conventional renographic results.

Partially parallel imaging with localized sensitivities (PILS).

In this study a novel partially parallel acquisition method is presented, which can be used to accelerate image acquisition using an RF coil array for spatial encoding. In this technique, Parallel Imaging with Localized Sensitivities (PILS), it is assumed that the individual coils in the array have localized sensitivity patterns, in that their sensitivity is restricted to a finite region of space. Within the PILS model, a detailed, highly accurate RF field map is not needed prior to reconstruction. In PILS, each coil in the array is fully characterized by only two parameters: the center of coil's sensitive region in the FOV and the width of the sensitive region around this center. In this study, it is demonstrated that the incorporation of these coil parameters into a localized Fourier transform allows reconstruction of full FOV images in each of the component coils from data sets acquired with a reduced number of phase encoding steps compared to conventional imaging techniques. After the introduction of the PILS technique, primary focus is given to issues related to the practical implementation of PILS, including coil parameter determination and the SNR and artifact power in the resulting images. Finally, in vivo PILS images are shown which demonstrate the utility of the technique.

Morphological evaluation of human embryos and derivation of an embryo quality scoring system specific for day 3 embryos: a preliminary study.

A scoring system specific for day 3 embryos has not been extensively explored. Most IVF laboratories continue to grade embryos solely on the basis of cell number and percentage fragmentation as was traditionally done for day 2 embryos. Additional morphological features, some unique to day 3 embryos, may be useful in selecting embryos most likely to blastulate and implant. The objective of this study was to derive an embryo scoring system for day 3 transfers which is predictive of positive pregnancy outcomes. A total of 316 transferred embryos from 93 patients was recorded on videotape and evaluated. The following parameters were used to grade the embryos: cell number, fragmentation pattern (FP), cytoplasmic pitting, compaction, equal sized blastomeres, blastomere expansion and absence of vacuoles. The clinical pregnancy rate was 41.9%, with an implantation rate of 18% per embryo transferred. The mean number of embryos transferred per patient was 3.4. Three formulae were derived to score embryo quality in each transfer based on the average score of individual embryos transferred. In the first scoring system, cell number alone was used to predict pregnancy outcome. The second scoring system was based on blastomere number and the observed FP. The third scoring system utilized both blastomere number and FP but also combined this with five morphological criteria to yield a final day 3 embryo quality (D3EQ) score. We found the D3EQ score to be prognostic of pregnancy outcome. This study suggests that although cell number and FP are certainly predictors of positive pregnancy outcomes, additional parameters specific to day 3 embryos should be used to stratify a cohort of embryos further.

Prospective 5-year study of peripheral blood CD4, CD8, and CD19/CD20 lymphocytes and serum Igs in children born to HIV-1 women. The P(2)C(2) HIV Study Group.

BACKGROUND: Peripheral blood CD4(+) and CD8(+) T cells, CD19(+)/20(+) B cells, and serum Igs are known to be altered by the progression of pediatric HIV-1 infection, but their evaluation as predictors of survival needs further definition. OBJECTIVE: To determine the natural history of these immune factors and their importance in predicting survival, we studied 298 HIV-1 vertically infected (HIV-1(+)) children over a 5-year period. METHODS: These immune factors and serum HIV-1 RNA levels were measured in two groups: (1) a birth cohort of children enrolled up to age 28 days postnatally, including 93 HIV-1(+) and 463 HIV-1 uninfected infants (HIV-1(-)), and (2) an older cohort of 205 HIV-1(+) children enrolled after the age of 28 days, who were classified as survivors or nonsurvivors. RESULTS: In the birth cohort HIV-1(+) children had significantly lower CD4(+) T-cell counts, higher CD8(+) T-cell counts, and lower CD19(+)/20(+) B-cell counts and higher IgG, IgA, and IgM levels than HIV-1(-) children. In the older cohort survivors had significantly higher CD4(+) and CD8(+) T-cell and CD19(+)/CD20(+) B-cell counts and higher IgG, lower IgA, and lower IgM levels than did nonsurvivors. In univariable analysis factors affecting survival in the older cohort were baseline CD4(+) and CD8(+) T-cell and CD19(+)/20(+) B-cell counts and IgG and HIV-1 RNA levels (all P <.05). In multivariable analysis high baseline CD4(+) T-cell count and low baseline HIV-1 RNA load remained important. CONCLUSION: The longitudinal mean profiles of CD4 and CD8 T-cell and CD19/20 B-cell counts and serum IgG levels helped to describe the natural progression of HIV-1 disease in children. However, only baseline CD4 T-cell count independently predicted survival.

Subclavian deep vein thrombosis associated with the use of recombinant follicle-stimulating hormone (Gonal-F) complicating mild ovarian hyperstimulation syndrome.

OBJECTIVE: To describe two cases of subclavian deep vein thrombosis (DVT) associated with the use of recombinant gonadotropins and mild ovarian hyperstimulation syndrome (OHSS) and review the literature associated with this condition. DESIGN: Retrospective study (case report). SETTING: Tertiary academic IVF program. PATIENT(S): Two women undergoing IVF with intracytoplasmic sperm injection due to male factor infertility. INTERVENTION(S): Ovaluation induction with recombinant FSH, IVF, and therapeutic heparinization. MAIN OUTCOME MEASURE(S): Coagulation studies, resolution of DVT, delivery at term. RESULT(S): Mild OHSS with left subclavian thrombosis occurred in two patients. Laboratory evaluation revealed normal protein C, protein S, antinuclear antibodies (ANA), and absence of antiphospholipid (APA) and anticardiolipin antibodies (ACA). Antithrombin III levels and coagulation studies were also within normal limits. Both patients tested negative for a factor V Leiden mutation and delivered healthy infants at term. CONCLUSION(S): Arm swelling associated with the use of gonadotropins during controlled ovarian hyperstimulation should be promptly evaluated and treated. Subclavian vein thrombosis is a rare complication of ovulation induction, and the possibility that recombinant gonadotropins increase the risk for this complication should be further studied.

Local GABAergic modulation of acetylcholine release from the cortex of freely moving rats.

Cortical perfusion with GABA agonists and antagonists modulates the spontaneous release of cortical acetylcholine and GABA in freely moving rats. Twenty-four hours after implantation of a dialysis fibre, cerebral cortex spontaneously released acetylcholine (3.8 +/- 0.2 pmol/10 min) and GABA (6.6 +/- 0.4 pmol/10 min) at a stable rate. Local administration of GABA (1 or 5 mM) or the GABAA agonist muscimol (25 or 50 microM) had no effect on the spontaneous release of acetylcholine. However, bicuculline (1-25 microM), a GABAA antagonist, added to the dialysis perfusate, elicited a concentration-dependent increase of acetylcholine release to approximately double that of control. This effect of bicuculline (25 microM) was completely prevented by coperfusion with muscimol (50 microM). Local administration of the GABAB receptor agonist baclofen (10 or 50 microM) elicited a concentration-dependent increase in spontaneous acetylcholine release with a maximal increase of about 60%. Intracortical administration of baclofen also decreased the spontaneous release of GABA. The GABAB receptor antagonist CGP 35348 (1 mM), administered alone for 20 min through the dialysis fibre, was without effect on spontaneous acetylcholine release; however, it completely blocked both the baclofen-induced increase in acetylcholine release and the decrease in GABA release. These results suggest that cortically released GABA exerts a tonic influence on cholinergic activity.

The youthful forehead: placement of skin incisions in hidden furrows.

BACKGROUND: Attaining good aesthetic results remains a primary goal in removal of benign cutaneous facial lesions. OBJECTIVE: Strategic planning of the incision is perhaps the most critical step in excision of such a lesion. METHODS: A study of one case of epidermoid cyst excision from a youthful forehead was undertaken. RESULTS: Poor surgical planning of a simple cyst excision from the forehead resulted in placement of the incision inferior to a natural furrow and within the basin defect, producing a noticeable scar. Facial animation accentuates the aesthetically poor placement of the surgical incision. CONCLUSION: The detection of hidden furrows through facial animation during preoperative planning, especially in the youthful forehead, is imperative for achievement of an optimal aesthetic result. When possible, incisions should be concealed within natural furrows.

Fifteen years experience with an in-vitro fertilization surrogate gestational pregnancy programme.

The purpose of our study was to review and evaluate retrospectively the experience of an in-vitro fertilization (IVF) surrogate gestational programme in a tertiary care and academic centre. In a 15 year period from 1984 to 1999, a total of 180 cycles of IVF surrogate gestational pregnancy was started in 112 couples. On average, the women were 34.4 +/- 4.4 years of age, had 11.1 +/- 0.72 oocytes obtained per retrieval, 7.1 +/- 0.5 oocytes fertilized and 5. 8 +/- 0.4 embryos subsequently cleaved. Sixteen cycles (8.9%) were cancelled due to poor stimulation. Except for six cycles (3.3%) where there were no embryos available, an average of 3.2 +/- 0.1 embryos was transferred to each individual recipient. The overall pregnancy rate per cycle after IVF surrogacy was 24% (38 of 158), with a clinical pregnancy rate of 19% (30 of 158), and a live birth rate of 15.8% (25 of 158). When compared to patients who underwent a hysterectomy, individuals with congenital absence of the uterus had significantly more oocytes retrieved (P < 0.006), fertilized, cleaved and more embryos available for transfer despite being of comparable age. IVF surrogate gestation is an established, yet still controversial, approach to the care of infertile couples. Take-home baby rates are comparable to conventional IVF over the same 15 year span in our programme. Patients with congenital absence of the uterus responded to ovulation induction better than patients who underwent a hysterectomy, perhaps due in part to ovarian compromise from previous surgical procedures.

Preoperative MRA assessment of the coronary arteries in an ascending aortic aneurysm.

We present a patient with an aneurysm that included both the aortic root and the ascending aorta. Visualization of the coronary arteries by x-ray angiography was not technically feasible. Magnetic resonance angiography (MRA) was thus performed and allowed an accurate evaluation of the involvement of the coronary arteries in the aneurysm and the patency of the proximal coronaries, as well as visualization of the aneurysm itself.

Dynamic three-dimensional magnetic resonance abdominal angiography and perfusion: implementation and preliminary experience.

Implementation of and preliminary experience with an ultra-fast partial-Fourier radiofrequency (RF) spoiled gradient-echo sequence for gadolinium-enhanced imaging are presented. Three-dimensional angiograms can be acquired in less than 6 seconds. Repetition of the acquisition allows the three-dimensional visualization of several distinct vascular phases. Feasibility is demonstrated in three healthy volunteers. The trade-offs among spatial resolution, temporal resolution, and spatial coverage as well as the technical aspects of gadolinium-enhanced pulse sequences are discussed.

Assessment of growth factor effects on post-thaw development of cryopreserved mouse morulae to the blastocyst stage.

The objective of this study was to assess the influence of specific factors on post-thaw development of mouse cryopreserved morulae. Thawed morulae (n = 206) were randomly distributed between 10 treatment groups: medium alone control (CT), Vero (VR) cells, leukaemia inhibitory factor (1 ng/ml), interleukin-6 (1 ng/ml), transforming growth factor (TGF) alpha (2 ng/ml), epidermal growth factor (EGF) (4 ng/ml), platelet-derived growth factor (1 ng/ml), insulin-like growth factor (IGF)-I (30 ng/ml), IGF-II (1 ng/ml) and TGFbeta (2 ng/ml). At 4, 8, 20, 30 and 48 h, a digitized image of each thawed embryo was captured and stored for later analysis. The following parameters were examined: blastocoel formation, blastocyst expansion, zona thickness and hatching. At termination of the experiment, cell number per embryo was determined by bisbenzimide staining. When contrasted to the medium alone control, co-culture consistently accelerated the development of frozen-thawed morulae to the hatched blastocyst stage, allowing embryos to recover rapidly from any damage sustained during the cryopreservation process. While no single growth factor/cytokine was able to completely mimic the results achieved with co-culture, all of the growth factors impacted positively on at least one of the morphological parameters studied. Cell proliferation was significantly stimulated by just 48 h exposure to growth factors, either through co-culture or by direct media supplementation. Co-culture again yielded the best results with a mean cell count of 217 +/- 76 cells per blastocyst as compared with 131 +/- 36 in control medium alone. Amongst the factors tested, IGF-I, IGF-II and EGF had the greatest impact, with mean cell counts of 172 +/- 50, 168 +/- 50 and 179 +/- 55 respectively. Whereas only 5% of CT embryos developed to blastocysts with > 200 cells, 51% of thawed embryos placed on co-culture monolayers and 25-32% of embryos cultured with IGF-I, IGF-II or EGF had > 200 cells. This study for the first time systematically describes the effect of culture regimen and growth factor additives on the post-thaw development of cryopreserved embryos.