Consensus on the Management of Posterior Urethral Valves from Antenatal Period to Puberty.

The need for successful management of posterior urethral valves always captivates the minds of pediatric surgeons. Its success, however, depends on several factors ranging from prenatal preservation of upper tracts to postoperative pharmacological compliance. Regardless of measures available, some cases do not respond and progress to end stage. The management depends on several issues ranging from age and severity at presentation to long-term follow-up and prevention of secondary renal damage and managing valve bladder syndrome. This article is based on a consensus to the set of questionnaires, prepared by research section of Indian Association of Paediatric Surgeons and discussed by experienced pediatric surgeons based in different institutions in the country. Standard operating procedures for conducting a voiding cystourethrogram and cystoscopy were formulated. Age-wise contrast dosage was calculated for ready reference. Current evidence from literature was also reviewed and included to complete the topic.

Multicomponent gas analysis using broadband quantum cascade laser spectroscopy.

We present a broadband quantum cascade laser-based spectroscopic system covering the region between 850 and 1250 cm(-1). Its robust multipass cavity ensures a constant interaction length over the entire spectral region. The device enables the detection and identification of numerous molecules present in a complex gas mixture without any pre-treatment in two minutes. We demonstrate that we can detect sub-ppmv concentration of acetone in presence of 2% of water at the same wavenumber region.

Laser-speckle-based detection of fluid pulsation in the presence of motion artifacts: in vitro and in vivo study.

We have performed an in vitro and in vivo study, based on laser speckle contrast analysis, to detect fluid pulsation in the presence of artifacts caused by the relative motion between the sample and the illumination source. We observe that the pulsation signal is clearly detectable for a range of motion amplitudes and oscillation frequencies; however, for higher amplitudes and oscillation frequencies of motion, the signal, due to pulsation, becomes increasingly difficult to detect.

Many-wavelength interferometry with thousands of lasers for absolute distance measurement.

We demonstrate a new technique for absolute distance measurement with a femtosecond frequency comb laser, based on unraveling the output of an interferometer to distinct comb modes with 1 GHz spacing. From the fringe patterns that are captured with a camera, a distance is derived by combining spectral and homodyne interferometry, exploiting about 9000 continuous wave lasers. This results in a measurement accuracy far within an optical fringe (λ/30), combined with a large range of nonambiguity (15 cm). Our technique merges multiwavelength interferometry and spectral interferometry, within a single scheme.

Long distance measurement with femtosecond pulses using a dispersive interferometer.

We experimentally demonstrate long distance measurements with a femtosecond frequency comb laser using dispersive interferometry. The distance is derived from the unwrapped spectral phase of the dispersed interferometer output and the repetition frequency of the laser. For an interferometer length of 50 m this approach has been compared to an independent phase counting laser interferometer. The obtained mutual agreement is better than 1.5 µm (3×10(-8)), with a statistical averaging of less than 200 nm. Our experiments demonstrate that dispersive interferometry with a frequency comb laser is a powerful method for accurate and non-incremental measurement of long distances.

Time-frequency distribution of interferograms from a frequency comb in dispersive media.

We investigate general properties of the interferograms from a frequency comb laser in a non-linear dispersive medium. The focus is on interferograms at large delay distances and in particular on their broadening, the fringe formation and shape. It is observed that at large delay distances the interferograms spread linearly and that its shape is determined by the source spectral profile. It is also shown that each intensity point of the interferogram is formed by the contribution of one dominant stationary frequency. This stationary frequency is seen to vary as a function of the path length difference even within the interferogram. We also show that the contributing stationary frequency remains constant if the evolution of a particular fringe is followed in the successive interferograms found periodically at different path length differences. This can be used to measure very large distances in dispersive media.

Impact of the cyclin-dependent kinase inhibitor p27Kip1 on resistance of tumor cells to anticancer agents.

A low proliferating fraction in solid tumors limits the effectiveness of cell cycle-dependent chemotherapeutic agents. To understand the molecular basis of such "kinetic" resistance we cultured tumor cells as multicellular spheroids and examined levels of p27Kip1, a cyclin-dependent kinase inhibitor known to be upregulated by intercellular contact in normal cells. When transferred from monolayer to three-dimensional culture, a consistent upregulation (up to 15-fold) of p27 protein was observed in a panel of mouse and human carcinoma cell lines. Antisense-oligonucleotide-mediated downregulation of p27 in EMT-6 mammary tumor cell spheroids reduced intercellular adhesion, increased cell proliferation, sensitized tumor cells to 4-hydroperoxycyclophosphamide, and restored drug- or radiation-induced cell-cycle perturbations repressed in spheroid culture. Our results implicate p27 as a regulator of drug resistance in solid tumors and suggest that tumor-targeted p27 antagonists may be useful chemosensitizers in conjunction with conventional anticancer therapy.

Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27Kip1, a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27Kip1 protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-beta (TGF-beta) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27Kip1, a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27Kip1 mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27Kip1 protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27Kip1 is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

MYC gene amplification reveals clinical association with head and neck squamous cell carcinoma in Indian patients.

BACKGROUND: Amplification of the MYC gene is reported to be associated with the development of head and neck squamous cell carcinoma (HNSCC). This study is focused to analyze the correlation between MYC gene amplification and various clinicopathological features and outcome in a cohort of 49 dysplastic and 187 primary head and neck lesions. METHODS: MYC gene amplification was assessed by differential polymerase chain reaction using primer sets from the MYC gene as target locus and DRD2 gene as the control locus. RESULT: The MYC gene amplification was detected in a total of 23.7% (56/236) head and neck lesions comprising 14.2% (7/49) dysplastic lesions and 26% (49/187) HNSCC samples. The clinicopathological association study between MYC gene amplification with the different clinical parameters like sex, tumor stage, tumor differentiation, lymph node status, tobacco habit and HPV 16/18 status determined significant association of MYC amplification with tumor progression (P = 0.009). Kaplan Meier analysis revealed MYC gene has no prognostic significance on survival in HNSCC. CONCLUSION: In conclusion, our results suggest that MYC gene amplification is associated with tumor progression in HNSCC.

High fat diet induces obesity in British Angora rabbit: a model for experimental obesity.

A reliable and cost-effective animal model for human obesity with its manifested disorders is yet to be established in the context of increased morbidity and mortality due to obesity and its related problems. Therefore, an attempt was made to produce obesity in locally available British Angora Rabbits (BAR) and examine the effect on metabolic and cardiovascular parameters. Adult male BARs weighing nearly 2 kg were randomly divided into two groups, one of the groups was fed with high fat diet (HFD) ad libitum for 10 weeks and the control group received standard normal rabbit chow for same period. Body weight, skinfold thickness, serum cholesterol, serum glucose and resting heart rate were measured before and after the dietary regimens. After 10 weeks, HFD group of rabbits demonstrated significant (P < 0.05) increase in body weight (+24%) and skinfold thickness (+37%). The gain in body weight was positively correlated to skinfold thickness (r = 0.61). Serum cholesterol, serum glucose and resting heart rate were also increased by 46%, 52% and 15%, respectively. Whereas no such increases in any of these parameters were observed in control group of rabbits. Our results suggest that obesity can be produced in BARs by feeding HFD. The obesity manifests with cardiovascular and metabolic changes. It is proposed that this may serve as a valid and reliable model of experimental obesity.

Obesity attenuates formalin-induced tonic pain in British Angora rabbits.

Obesity is known to alter various physiological parameters including the pain sensitivity. There are conflicting reports on the pain sensitivity in obesity. In this context, the present study was aimed to investigate the tonic pain response in obese rabbit model. To achieve this aim, two groups of adult male British Angora rabbits were used. One of the groups was fed with standard rabbit chow and served as control. The other group was fed high fat diet (HFD) for 10 weeks to produce obesity. The standard formalin test was performed at the start and after 10 weeks of dietary regimen in both the groups. Timed behavioral responses (limping, elevation of paw, licking, biting, grooming etc.) were categorized and quantified with the help of standard pain rating scale. The total average pain rating score decreased significantly from 2.01 +/- 0.02 to 1.47 +/- 0.08 (P < 0.05) in HFD group after 10 weeks of dietary regimen, whereas there was no change in the control group. A significant negative correlation was observed between body weight and pain rating score in HFD group of rabbits (P < 0.05, r = -0.62). Results suggest that obesity attenuates the tonic pain responses induced by formalin in British Angora rabbits.

Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells.

The effects of transforming growth factor beta (TGF-beta) were studied in closely related human mammary epithelial cells (HMEC), both finite-life-span 184 cells and immortal derivatives, 184A1S, and 184A1L5R, which differ in their cell cycle responses to TGF-beta but express type I and type II TGF-beta receptors and retain TGF-beta induction of extracellular matrix. The arrest-resistant phenotype was not due to loss of cyclin-dependent kinase (cdk) inhibitors. TGF-beta was shown to regulate p15INK4B expression at at least two levels: mRNA accumulation and protein stability. In TGF-beta-arrested HMEC, there was not only an increase in p15 mRNA but also a major increase in p5INK4B protein stability. As cdk4- and cdk6-associated p15INK4B increased during TGF-beta arrest of sensitive cells, there was a loss of cyclin D1, p21Cip1, and p27Kip1 from these kinase complexes, and cyclin E-cdk2-associated p27Kip1 increased. In HMEC, p15INK4B complexes did not contain detectable cyclin. p15INK4B from both sensitive and resistant cells could displace in vitro cyclin D1, p21Cip1, and p27Kip1 from cdk4 isolated from sensitive cells. Cyclin D1 could not be displaced from cdk4 in the resistant 184A1L5R cell lysates. Thus, in TGF-beta arrest, p15INK4B may displace already associated cyclin D1 from cdks and prevent new cyclin D1-cdk complexes from forming. Furthermore, p27Kip1 binding shifts from cdk4 to cyclin E-cdk2 during TGF-beta-mediated arrest. The importance of posttranslational regulation of p15INK4B by TGF-beta is underlined by the observation that in TGF-beta-resistant 184A1L5R, although the p15 transcript increased, p15INK4B protein was not stabilized and did not accumulate, and cyclin D1-cdk association and kinase activation were not inhibited.

Temperature measurement using frequency comb absorption spectroscopy of CO2.

Absorption spectroscopy on CO2 for the determination of gas temperature is reported. Direct absorption of a frequency comb laser through a gas cell at atmospheric conditions is analysed with a virtually imaged phased array spectrometer. Several measurement and analysis techniques are investigated to find the parameters most sensitive to changes in the temperature. Some of these show qualitative agreement with theoretical predictions where the trend is similar to the calculated values.

A study of placental umbilical cord whole blood transfusion in 72 patients with anemia and emaciation in the background of cancer.

In the under-resourced world, transfusion to advanced oncological patients involves two major problems, i.e., (a) transfusion transmitted disease, and (b) infrastructural deficiency. Many hospitals cannot cope with the specialized requirements of immunocompromised cancer victims, for instance, leucoreduction, selective apheresis, irradiation of the blood, viral inactivation of the blood by solvent and/or detergent treatment or photochemical inactivation using psoralen or long wavelength ultraviolet light and cytomegalovirus safe blood. The exorbitant cost of red blood cell (RBC) substitutes like hemoglobin-based oxygen carriers or perflurocarbon emulsions, liposome encapsulated hemoglobin, is simply unacceptable for an average oncological patient in the developing world. Moreover, it should be underscored that none of the total blood functions are replaced by any available so-called blood substitute, the primary function of which is oxygen delivery and volume expansion only. A more accurate term should be red cell substitute. Cord blood, because of its rich mix of fetal and adult hemoglobin, platelet and white blood cell (WBC) count, and plasma filled with cytokine and growth factors--as well as its hypoantigenic nature and altered metabolic profile--has all the potential of a real and safe alternative to adult blood during emergencies or any etiology of blood loss. In the present series, the collection of cord blood varied from 54 ml-128 ml, mean 82 ml +/- 7.6 ml SD; mean packed cell volume 48 +/- 4.1% SD; mean percent hemoglobin concentration 16.4 g/dl +/- 1.6 g/dl SD. Not a single case of immunological or non immunological reaction has been encountered so far after transfusion of cord blood to cancer patients with percent of hemoglobin 8 g/dl or less. It appears that the medical fraternity can safely use this precious gift of nature-- which is free from infection, hypoantigenic with altered metabolic profile, filled with growth factors and cytokine-filled plasma, and has the potential of a higher oxygen carrying capacity than adult blood--as an emergency source of blood for the management of advanced cancer cases with anemia.

Spontaneous transient rise of CD34 cells in peripheral blood after 72 hours in patients suffering from advanced malignancy with anemia: effect and prognostic implications of treatment with placental umbilical cord whole blood transfusion.

UNLABELLED: Cord blood, because of its rich mix of fetal and adult hemoglobin, platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood during emergencies or any etiology of blood loss. STUDY DESIGN: In the present study transfusion-related CD34 levels of the peripheral blood from six randomly selected patients suffering from advanced clinical Stage IV malignancy were analyzed between 16 August 1999 and 16 May 2001. This study attempts to ascertain the fate of hematopoietic stem cells (CD34) after placental umbilical cord whole blood transfusion, as assessed from the peripheral blood CD34 level 72 hours after cord blood transfusion in sex- and HLA-randomized patients. RESULTS AND ANALYSIS: Among the six cases, Case 2 (breast sarcoma) received the lowest amount of card blood (6 units), while Case 6 (breast cancer) received the largest amount (32 units). The youngest patient, suffering from non-Hodgkin's lymphoma (Case 3), was a 16-year-old boy who received eight units of cord blood to combat anemia. Other patients received amounts varying from 7-15 units: Case 4 received 15 units (metachronous lymph node metastatsis), Case 1 received 14 units (breast cancer), and Case 5 received seven units (lung cancer). There was no transfusion-related clinical immunological or nonimmunological reaction. Studies of CD34 levels showed an initial rise followed by a fall in two cases, two cases registered very little effect on the CD34 level, i.e., no change from the baseline, and one case demonstrated a very slow rise from the baseline. However, one case showed a frequent steep rise up to 99% and a sustained high CD34 level. This patient is alive with clinical remission of the disease. CONCLUSION: It appears from this preliminary study that freshly collected cord blood transfusion may cause a transient transplant impact of transfused cord blood CD34 stem cells on the host without provoking clinical graft vs host disease due to a of background immune suppression in advanced malignancy. The growth factor cytokine system of freshly collected cord blood may have a potentiating role on the immune system of the host.

Transient spontaneous engraftment of CD34 hematopoietic cord blood stem cells as seen in peripheral blood: treatment of leprosy patients with anemia by placental umbilical cord whole blood transfusion.

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our experience of 74 units (50 ml-146 ml mean, 86 ml +/- 7.6 ml SD, median 80 ml, mean packed cell volume 48 +/- 4.1 SD, mean percent hemoglobin concentration 16.2 g/dl +/- 1.8 g/dl of placental umbilical cord whole blood collection (from 1 April 1999) after lower uterine cesarean section (LUCS) from consenting mothers and transfusion of the same to 16 informed, consenting patients with percent plasma hemoglobin 8 g/dl or less, is presented here. After collection the blood was immediately preserved in the refrigerator and transfused within 72 hours of collection. Fifteen males and one female, aged 12-72 yrs (mean 48.4 yrs) participated: five cases were pausibacillary type (PB) and 11 cases were multibacillary type (MB). The clinical spectrum of the cases varied widely from the tuberculoid to the lepromatous type and one patient presented with gangrene of the leg preceding an auto amputation which was infested with maggots. Each case was approved by the institutional ethical committee and received two to eight units of freshly collected placental umbilical cord blood in one transfusion without encountering any clinical, immunological or non-immunological reaction. Seven days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 3.6% to 16.2%, in 75% of the cases, without provoking any clinical graft vs host reaction in any of the leprosy victims. This value returned to normal within three months in most cases.

Placental umbilical cord blood transfusion: a new method of treatment of patients with diabetes and microalbuminuria in the background of anemia.

Diabetes mellitus is the commonest endocrine disease in all populations and all age groups. It is a syndrome of disturbed intermediary metabolism caused by inadequate insulin secretion or impaired insulin action, or both. Anemia is a common accompaniment of diabetes, particularly in those with albuminuria justifying tubulointestitial injury or reduced renal function. There are other additional factors present in diabetes, which may contribute to the development of an increased risk of anemia. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, hypo-antigenic nature, altered metabolic profile and high affinity for oxygen, may be an ideal choice for cases of diabetes with severe anemia necessitating blood transfusion. This article presents my team's experience with 78 units of placental umbilical cord whole blood (from 1 April 1999 to April 2005), collected after lower uterine cesarean section (LUCS) from consenting mothers (56 ml-138, ml mean 82 ml +/- 5.6 ml SD, median 84 ml, mean packed cell volume 49.7 +/- 4.2 SD, mean percent hemoglobin concentration 16.6 g/dl +/- 1.5 g/dl SD) and transfused to diabetes patients with microalbuminuria and severe anemia necessitating transfusion. After collection, the blood was transfused, in most cases immediately after completion of the essential norms of transfusion. In rare cases, it was kept in the refrigerator and transfused within 72 hours of collection to a suitable recipient. For inclusion in this study, the patient's percent plasma hemoglobin had to be 8 g/dl or less (the pretransfusion hemoglobin in this series varied from 5.2 g/dl to 7.8 g/dl) in the background of type two diabetes (fasting sugar 200 mg or more), along with features of microalbuminuria (albumin excretion 30-299 mg/g creatinine). This study included 39 informed consenting patients (22 males + 17 females, aged 48-74 yrs, mean 59.6 yrs). The patients were randomized into two groups: Group A (control cases N = 15, males = 8 and females = 7) and Group B (study group N = 24, males = 14 and females = 10). In Group A the rise of hemoglobin (Hgb) after two units of adult blood transfusion was 1.5 to 1.8 g/dl, as seen after a 72-hour blood sample assessment. The rise of Hgb as noted after 72 hours of two units of freshly collected cord blood transfusion was .6 g/dl to 1.5 g/dl. Each patient received two of four units of freshly collected cord blood transfusion (two units at a time), depending on availability and compatibility. Microalbuminuria was assessed in both groups after one month of treatment with transfusion and other identical support. The mean result was 152 +/- 18 m SD of albumin per gram of creatinine excreted through 24-hour urine (pre-transfusion mean excretion was 189 +/- 16 mg) in Group A and 103 +/- 16 mg SD of albumin excretion per gram of creatinine in 24-hour excretion of urine in Group B (pretransfusion mean excretion was 193 +/- 21 mg). Univariate analysis using Fisher's exact test was performed for the results of Groups A and B. The difference between Group A and B values and its comparison with the pre-transfusion microalbuminuria appeared to be statistically significant (p < less than .003). We have not encountered any clinical, immunological or non-immunological reaction so far in either group. Fetomaternal cell traffic has been implicated as the cause of scleroderma in mothers delivering male babies. In the present series, we did not see any such rare and unusual complication due to neonatal blood transfusion in the adult system in Group B patients in the six years from the initiation of the study.

Placental umbilical cord whole blood transfusion to combat anemia in the background of tuberculosis and emaciation and its potential role as an immuno-adjuvant therapy for the under-resourced people of the world.

Tuberculosis causes approximately 1.5 billion latent infections, 8 million new clinical cases, and 3 million deaths annually, making it the most prevalent infectious disease in the world. Anemia and malnutrition are essential comorbidities with tuberculosis. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypo-antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. We transfused 106 units (48 ml-148 ml mean 81 ml +/- 6.6 ml SD, median 82 ml, mean packed cell volume 49.4 +/- 3.1 SD, mean percent hemoglobin concentration 16.3 g/dl +/- 1.7 g/dl SD) of placental umbilical cord whole blood (from 1 April 1999 to 1st 2005) after lower uterine cesarean section from consenting mothers to 21 informed consenting patients with tuberculosis who had percent plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received 2-21 units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.99% to 33%, which returned to base level in 66.66% at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients.