Clinical evaluation of clarithromycin in pediatric patients

A clinical evaluation of clarithromycin (TE-031, A-56268), a newly synthesized macrolide antibiotic, was made for its efficacy and safety in 30 patients with ages ranging from 8 month-old to 12 year- 2 month-old with mycoplasmal and bacterial infections. The obtained results are summarized below. 1. A pharmacokinetic study following oral administration of TE-031 at 10 mg/kg (granule) or 5.5 mg/kg (tablet) resulted in blood concentrations and urinary recovery rates higher than with other macrolides. 2. TE-031 was administered orally to 5 patients with Mycoplasma pneumonia, 21 patients with pneumonia or bronchopneumonia, 2 patients with pertussis and 2 patients with enterocolitis at daily dosages ranging 11.1-31.6 mg/kg divided into 3. Clinical evaluations of these 30 patients were as follows; excellent: 19 patients, good: 11 patients. The efficacy rate was 100%. 3. Neither clinical adverse reaction nor abnormal laboratory data was found in any of these 30 patients. 4. MICs of TE-031 against 10 strains of bacteria isolated from 10 patients with pneumonia or bronchopneumonia were as follows. MICs against 3, 2 and 2 out of 7 strains of Streptococcus pneumoniae were less than 0.025 microgram/ml, 0.05 microgram/ml and 0.10 microgram/ml, respectively. MIC against a strain of Haemophilus influenzae was 3.13 micrograms/ml. MICs of 2 strains of Branhamella catarrhalis were 0.20 microgram/ml. 5. TE-031 is considered to be a new useful and safe antibiotic in pediatric patient with an excellent bactericidal capacity.     

O2 uptake and CO2 elimination during mechanical ventilation with high frequency oscillation.

This study was intended to elucidate gas exchange in a quasi-steady state during high frequency oscillatory ventilation (HFO) in terms of arterial blood gases, tidal volume(VT) and frequency of oscillation (f). Firstly, experiments were performed on anesthetized, paralyzed and tracheostomized dogs using a piston-type oscillator with a fresh air bias flow. The f values employed in the animal experiments were 10 to 30 Hz, and VT values were 1 to 3 ml/kg of body weight. Changes in PaO2 observed during HFO could be expressed by the equation PaO2 = 125.2-60.3/(VT X f), which closely coincided with the alveolar ventilation equation for O2, i.e., PaO2 = 125-78/, VA, Where P(A-a) O2 and O2 consumption were assumed to be 25 Torr and 90 ml/min, respectively. PaCO2 during HFO deviated from the curve of the alveolar ventilation equation, PaCO2 = constant/, VA at a higher VT x f, and was distributed along the hyperbolic curve of PaCO2 = 1/, VA + 14.7. This suggested that HFO shows a certain limitation in CO2 elimination. Secondly, indicator gas transport through straight tube models for two directions, i.e., wash-in and wash-out, were observed. Wash-in of indicator gases (He, N2 and SF6) in terms of indicator appearance time at the other end of the tube changed as a function of VT x f. The effect of increasing f at a fixed VT on the wash-in was much less than that of increasing VT at a fixed f. The heavier gas (SF6) was washed in faster than the lighter gas (He) although wash-in of each indicator gas was closely related to the function VT x f. Washout in terms of the appearance time of indicators in the opposite direction was, however, strongly dependent on VT, and the effect of increasing f at a fixed VT on wash-out reached a limit beyond a certain f. It was concluded from the present study, that both convective dispersion and augmented diffusion play important roles, although they are not clearly distinguished, as gas transport mechanisms during HFO. The difference between inspiratory and expiratory gas transport modes could be explained by differences in flow profiles, relative important of convective dispersion, and/or time required for gas mixing in the airways.     

Cerebro-oculo-hepato-renal syndrome (Arima's syndrome) with slowly progressive renal insufficiency and epilepsy]

We reported an additional case of Arima's syndrome with slowly progressive renal insufficiency and epilepsy. The patient is a 20-year-old man whose parents are consanguineous. He had a history of mild asphyxia at birth, and unexplained tachypnea developed during the neonatal period. But it disappeared later, and he have had no respiratory problem since then. Physical examination on admission at the age of 19 years revealed bilateral blephaloptosis, narrow palate, searching nystagmoid movement, absence of light reflex, muscle hypotonia and wasting of extremities. Funduscopic study showed optic hypoplasia, choroid coloboma and narrowing of vessels. Head CT scan showed agenesis of cerebellar vermis and hypoplasia of brainstem. CT scan and echography of the kidney disclosed the bilateral multiple cysts. Liver was hyperechoic in echographic study; this finding is consistent with fatty change. EEG showed dysrhythmic slow wave activity with sporadic spike and wave complex. Compared with previously reported cases, the present case has the following features: (1) slowly progressive renal insufficiency, (2) generalized tonic clonic convulsion developing from the age of 11 months, (3) ABR abnormalities including the right-sided shortening of wave I-II interpeak latency and bilateral ill-defined wave V. Slow progress of renal failure in our case may reflect the mild pathological process of the kidney with sparing functional nephrons. It shows the diversity of the kidney pathology in Arima's syndrome. Epilepsy is a less common association in the syndrome, whereas EEG abnormalities were reported. ABR abnormalities may reflect the morphological alteration of the brainstem structure including auditory pathway. In our case it is uncertain whether the neonatal tachypnea was due to birth asphyxia or brainstem malformation responsible for abnormal respiration as suggested in Joubert's syndrome.     

AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not alpha-sarcoglycan deficiency

Myostatin is a negative regulator of muscle mass whose inhibition has been proposed as a therapeutic strategy for muscle-wasting conditions. Indeed, blocking myostatin action through different strategies has proved beneficial for the pathophysiology of the dystrophin-deficient mdx mouse. In this report, we tested the inhibition of myostatin by AAV-mediated expression of a mutated propeptide in animal models of two limb-girdle muscular dystrophies: LGMD2A caused by mutations in the calpain 3 (CAPN3) gene and LGMD2D caused by mutations in the alpha-sarcoglycan gene (SGCA). In the highly regenerative Sgca-null mice, survival of the alpha-sarcoglycan-deficient muscle fibers did not improve after transfer of the myostatin propeptide. In calpain 3-deficient mice, a boost in muscle mass and an increase in absolute force were obtained, suggesting that myostatin inhibition could constitute a therapeutic strategy in this predominantly atrophic disorder.     

Detection of varicella-zoster virus DNA in cultured cells and tissue specimens by in situ hybridization using biotin-labeled probes

A method of in situ hybridization with biotinylated probes is described for specific detection of varicella-zoster virus (VZV) DNA in infected cell cultures and in human biopsied or autopsied materials. From molecularly cloned EcoRI-fragments of VZV DNA, we selected as probes for in situ hybridization three fragments (B, H, and K) which had any detectable homology neither with human cell DNA nor with DNAs of VZV-related viruses (herpes simplex virus type 1, type 2 and human cytomegalovirus). The procedure of in situ hybridization was based on that of Brigati et al. (Virology 126, 32-50, 1983), but following modifications were made. 1) The concentration of probe DNA was lowered to 100 ng per ml. 2) Streptavidin-biotin system was used for detection of hybridization. 3) Acid phosphatase was used to generate color development discernible from melanin present in skin. 4) Before hybridization, deparaffinized sections were treated with trypsin by the procedure routinely employed for detection of viral antigens in paraffin-embedded sections.     

Management of pain in elderly patients receiving infusion of zoledronic acid for bone metastasis: a single-institution report

Goals of work Bone metastases are a common cause of morbidity in elderly patients with solid tumors and myeloma. We studied the safety and the effect of a new bisphosphonate, zoledronic acid (ZA), on pain and on quality of life (QoL) in elderly patients with bone metastases. Materials and methods From January 2004 to December 2005, we have enrolled elderly patients with bone metastasis for receiving ZA administration. Visual analog scale (VAS) and Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire were used to assess potential benefits of ZA therapy. Results Eighty-six patients were included; the median age was 75.5 years. Before starting treatment, the mean VAS was 6.8 (±0.24), after three infusions 5.4 (±0.3), and after six courses 4.5 (±0.3) with a significant improvement of bone pain. Moreover, we found a statistically significant improvement of QoL measured by FACT-G questionnaire after six courses (p = 0.010). Median baseline and final value of serum creatinine were 0.73 and 0.72 mg/dl, respectively (p = 0.11); creatinine clearance was also normal for most patients. Osteonecrosis of the jaw was diagnosed in one patient who received a prolonged ZA treatment. Conclusions These data confirm the benefits of ZA on pain and QoL also in elderly patients with bone metastasis from solid tumors.     

GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells

Committed T helper type 1 (Th1) and Th2 effector cells, resulting from chronic antigenic stimulation in interleukin (IL)-12 and IL-4, are implicated in the pathology of autoimmune and allergic diseases. Committed Th1 cells cannot be induced to change their cytokine profiles in response to antigenic stimulation and Th2 cytokine-inducing conditions. Here, we report that ectopic expression of GATA-3 induced Th2-specific cytokine expression not only in developing Th1 cells but also in otherwise irreversibly committed Th1 cells and a Th1 clone, HDK1. Moreover, cAMP, an inhibitor of cytokine production by Th1 cells, markedly augmented Th2 cytokine production in GATA-3-expressing Th1 cells. Ectopic expression of GATA-3 in developing Th1 cells, but not in Th1 clone HDK1, induced endogenous GATA-3, suggesting an autoregulatory mechanism for maintenance of GATA-3 expression in Th2 cells. Structure-function analyses of GATA-3 revealed that the NH(2)-terminal transactivation domain and the COOH-terminal zinc finger domain of GATA-3 were critical, whereas the NH(2)-terminal zinc finger domain was dispensable for the induction of IL-4. Both zinc fingers, however, were required for IL-5 induction. A Th2-specific DNaseI-hypersensitive site of the IL-4 locus was detected in GATA-3-expressing Th1 cells. Thus, GATA-3 can change the phenotype of committed Th1 cells, previously considered to be irreversible.     

Development and validation of 3D printed virtual models for robot-assisted radical prostatectomy and partial nephrectomy: urologists’ and patients’ perception

Purpose

To test the face and content validity of 3D virtual-rendered printed models used before robot-assisted prostate cancer and nephron-sparing surgery.

Methods

Patients who underwent live surgery during an international urological meeting organized in January 2017 were enrolled. Those with organ-confined prostate cancer underwent robot-assisted radical prostatectomy. Patients with a single renal tumor underwent minimally invasive nephron-sparing surgery. High-resolution (HR) imaging was obtained for all patients. Those with kidney tumors received contrast-enhanced CT scan with angiography; those with prostate cancer underwent mp-MRI. Images in DICOM format were processed by dedicated software. The first step was the rendering of a 3D virtual model. The models were then printed. They were presented during the live surgery of the urological meeting. All the participants and the operated patients were asked to fill a questionnaire about their opinion expressed in Likert scale (1–10) about the use and application of the 3D printed models.

Results

18 patients were enrolled, including 8 undergoing robot-assisted radical prostatectomy and 10 undergoing minimally invasive partial nephrectomy. For each patient, a virtual 3D printed model was created. The attendants rated the utility of printed models in surgical planning, anatomical representation and the role of technology in surgical training as 8/10, 10/10 and 9/10, respectively. All patients reported favorable feedbacks (from 9 to 10/10) about the use of the technology during the case discussion with the surgeon.

Conclusions

In our experience, 3D printing technology has been perceived as a useful tool for the purpose of surgical planning, physician education/training and patient counseling. Further researches are expected to increase the level of evidence.

     

Selective absence of immunoglobulin A1 or A2 among blood donors and hospital patients

A hemagglutination inhibition assay was developed for the determination of immunoglobulin A1 and A2 (IgA1 and IgA2) with subclass-specific rabbit antiserums. Among 93,020 apparently healthy blood donors, selective absence of IgA1 was found in six and that of IgA2 in 15, at a prevalence much higher than the absence of total IgA that was revealed by only one donor. Among 6800 hospital patients with various disorders, the absence of IgA1 was found in one with breast cancer and that of IgA2 in two with rheumatoid arthritis.