Risk Factors for Severe Retinopathy of Prematurity in Preterm Low Birth Weight Neonates

Objective  

To evaluate the risk factors predisposing to severe retinopathy of prematurity (ROP) in a level III neonatal unit. This retrospective study was conducted in a tertiary care neonatal and ophthalmic center.     

Is serum gentamicin level a good predictor of graft injury in intestinal transplantation?

INTRODUCTION: Following intestinal transplant (SBT), the early diagnosis and treatment of rejection is a major management aim. The diagnosis of rejection is based on histology of stomal biopsies. Oral gentamycin (2.5 mg/kg) was used for selective decontamination of the digestive system. Our hypothesis was that gentamycin might be absorbed in the presence of graft dysfunction. AIM: Our goal was to assess the correlation between serum gentamycin level and the health of the intestinal graft. SUBJECTS AND METHODS: Among 33 SBT performed from 1993 to 2005, serum gentamycin levels were performed once weekly or more often when there was a suspicion of rejection. All data were analyzed retrospectively. RESULTS: Adequate trough levels were achieved for only 23 patients, six of whom had histologically proven rejection and only one did not have a raised gentamycin content. Five patients with raised levels but no rejection included two with severe intestinal ischemia and three with bowel obstruction/ileus. Four of the five patients required laparotomies. CONCLUSION: We concluded that in our study raised serum gentamycin levels were a good predictor of rejection or significant injury to the graft.     

In vitro combination treatment with perifosine and UCN-01 demonstrates synergism against prostate (PC-3) and lung (A549) epithelial adenocarcinoma cell lines.

PURPOSE: Antineoplastic agents often achieve antitumor activity at the expense of close to unacceptable toxicity. One potential avenue to improve therapeutic index might combine agents targeting distinct components of the same growth regulatory pathway. This might lead to more complete modulation of the target pathway at concentrations lower than those associated with limiting adventitious toxicities from either agent alone. The protein kinase antagonist UCN-01 is currently used in Phase I/II trials and has recently been demonstrated to inhibit potently PDK1. We have recently documented that the alkylphospholipid perifosine potently also inhibits Akt kinase (PKB) activation by interfering with membrane localization of Akt. This leads to the hypothesis that these two agents might act synergistically through distinct mechanisms in the PI3K/Akt proliferation and survival-related signaling pathway. EXPERIMENTAL DESIGN: The synergistic effects of UCN-01 and perifosine, on two cell lines (A-549 and PC-3), were examined using various long-term in vitro assays for cell growth, cell cycle distribution, clonogenicity, survival morphology, and apoptosis. Along with Western blotting experiments were performed to determine whether this synergistic combination of two drugs has significant effect on their downstream targets and on biochemical markers of apoptosis. RESULTS: After 72 h, perifosine at concentrations of 1.5 and 10 microM UCN-01 at 40 and 250 nM did not significantly affect the growth of PC-3 and A459 cells, respectively. However, in combination at the same respective individual concentrations (1.5 microM and 40 nM of perifosine and UCN-01, respectively, in PC-3 cells and 10 microM perifosine and 0.25 microM UCN-01 in the somewhat more resistant A549 cells), virtually complete growth inhibition of both the cell lines resulted. Supra-additive inhibition of growth was also demonstrated in independent clonogenic assays. Mechanistic studies in cell culture models suggest enhanced depletion of the S-phase population in cells treated by the combination. This correlated with enhanced inactivation of Akt along with activation of caspases 3 and 9 and poly(ADP-ribose) polymerase cleavage. Evidence of synergy was formally demonstrated and occurred across a wide range of drug concentrations and was largely independent of the order or sequence of drug addition. CONCLUSIONS: As the concentrations of UCN-01 and perifosine causing synergistic inhibition of cell growth are clinically achievable without prominent toxicity, these data support the development of clinical studies with this combination.     

Quantitation of antibody uptake on a group erythrocytes using immunoautoradiography and monoclonal IgM anti-A

Summary The number of antibody molecules on individual erythrocytes was counted in A₁, A₂, A₃ B and A group individuals using immunoautoradiography (IAR) and monoclonal IgM anti-A₁. Quantitation was also done for A group pregnant women. The number of antibody molecules on different red cells of an individual varied widely. Gross variations were also noted in cells of different individuals from one and the same group. The mean values of the uptake of the number of antibody molecules showed the following range A₁>A₂>A_x>A₃B. When compared to the average for total A₁ adults, red cells of pregnant women and newborn infants showed a 10.7% and 19.7% reduction respectively, in antibody uptake. The mean number of antibody molecules per A₁ adult red cells was 5.6±3×10⁴, while A₂ had 0.85±0.35×10⁴ molecules, thus showing a significant quantitative variation.     

Frequency of partial D in Western India

summary .  Partial D is of clinical importance as the partial D-positive individuals who lack some epitopes of D antigen can develop anti-D if exposed to normal D antigen. The frequency of partial D varies in different populations. The majority of molecular studies on D variants have been reported in European, African and some East Asian populations, but no study has been reported in the Indian population so far. The aim of the study was to screen Indian population for detection of partial D by serology and classify them by multiplex polymerase chain reaction (M-PCR). The study population, consisting of 10 000 RhD-positive individuals from West India, was screened for detection of partial D using the partial D kit. In addition to these, blood samples referred because of serological RhD discrepant results from blood banks of West India were also investigated. The samples identified as partial D from these two groups were further characterized by M-PCR. Fifteen partial D cases were identified by population screening and 45 were identified from referred samples. Population screening revealed that one third of partial D was DFR when tested by partial D kit. We were able to classify 63·4 and 76·6% of partial D by partial D kit and M-PCR, respectively. The incidence of partial D in West India was found to be at least 0·15% when tested with partial D kit. DFR partial D was found to be predominant in the present study.     

Hindfoot plantarflexion: a radiographic aid to the diagnosis of achilles tendon rupture

Although tendo Achilles (TA) rupture is a clinical diagnosis, radiographs are sometimes taken to exclude bony injury. In equivocal clinical examination findings, an ultrasound examination is often performed. We investigated whether any radiographic signs of TA rupture existed that could help diagnose TA rupture in equivocal cases. We examined the case notes of 25 consecutive patients who had undergone repair for complete TA rupture. Their lateral radiographs were reviewed and the following angles were measured: calcaneal pitch, lateral talocalcaneal, and tibiocalcaneal. These were compared with a control group of patients who had undergone radiographic examination for ankle injuries resulting in a diagnosis of ankle sprain. The results were compared using an unpaired Student's t test. The mean tibiocalcaneal angle of the patients with complete TA rupture was 87.0 compared with 69.4 for the control group (p < .05). No significant difference was found with the other angles measured. The tibiocalcaneal angle can be a useful adjunct to the clinical examination in the diagnosis of TA rupture. It might also have a role in the evaluation of serial cast application after TA repair.     

Monitoring and management of antituberculosis drug induced hepatotoxicity

BACKGROUND: Hepatotoxicity to antituberculosis therapy (ATT) poses a major challenge. This often results in inadequate therapy. The risk of fulminant hepatic failure and mortality is high once icteric hepatitis develops. There is no consensus on monitoring protocols and for the reintroduction of ATT. METHODS: All patients (from the Department of Internal Medicine and Gastroenterology, Jagjivanram Hospital and the Department of Gastroenterology, Bombay Hospital, Mumbai, India) with a diagnosis of tuberculosis, who were to receive ATT during the study period, were included in the present study for prospective periodic laboratory monitoring for the development of hepatotoxicity. Those patients who developed hepatotoxicity formed Group A (n = 21), whereas those who did not develop hepatotoxicity were included in Group C (n = 179). For the purpose of comparison with Group A, all the patients who presented directly with ATT induced hepatotoxicity during the study period were categorized as Group B (n = 24). Group A and B were further studied after normalization of liver functions for sequential reintroduction with therapeutic doses at a weekly interval. RESULTS: In Group A, 66.6% (14 patients) of the patients were diagnosed in the asymptomatic period. Seven patients had symptomatic hepatitis, but none had icteric illness. There were no mortalities in Group A. In contrast, all the patients in Group B had symptomatic hepatitis (75% icteric hepatitis). There was a mortality rate of 16.6% (four patients). Of the 41 patients from Groups A and B who survived, reintroduction was successful in 38/39 (97.4%). In the remaining two patients who were in Group B, reintroduction was not attempted because of decompensated liver disease. CONCLUSIONS: Periodic laboratory monitoring is important in detecting hepatotoxicity at an early stage, thereby preventing mortality. Sequential reintroduction is often successful.