Vitreous levels of placental growth factor correlate with activity of proliferative diabetic retinopathy and are not influenced by bevacizumab treatment.

PurposePlacental growth factor (PlGF) is a member of the VEGF family that plays an important role in experimental models of diabetic retinopathy and retinal neovascularization. We aimed to investigate whether vitreous levels of PlGF correlated with proliferative diabetic retinopathy (PDR) status, VEGF levels, and bevacizumab treatment. We also analysed PDR membranes to confirm the presence of the PlGF receptor, FLT1, in endothelial cells.MethodsThis was a case-control study: undiluted vitreous fluid samples were obtained from 28 active PDR patients without preoperative bevacizumab treatment, 21 active PDR patients with preoperative bevacizumab treatment, 18 inactive PDR patients, and 21 control patients. PlGF and VEGF levels in samples were determined by enzyme-linked immunosorbent assay. Immunohistochemistry for FLT1 was performed on human PDR membranes.ResultsCompared to control, vitreous PlGF levels were higher in both active PDR without bevacizumab (P<0.0001) and with bevacizumab (P<0.0001). There was no significant difference in PlGF between active PDR patients without and with bevacizumab (P=0.56). Compared to active PDR, PlGF levels were significantly reduced in inactive PDR (P=0.004). PlGF levels were highly correlated with VEGF levels in active PDR. VEGFR1 was expressed in endothelial cells in human PDR membranes.ConclusionThe strong correlation of PlGF levels with PDR disease status and expression of FLT1 in human PDR membranes suggest that PlGF has a pathogenic role in proliferative diabetic retinopathy. Therapeutic targeting of PlGF with agents like aflibercept may be beneficial.

Solid-pseudopapillary tumour of the pancreas: a report of a rare case.

The solid pseudopapillary tumour (SPT) of the pancreas is an uncommon cystic pancreatic neoplasm mostly seen in young females. We present a large SPT in a 16-year-old female who presented with acute onset upper- and mid-quadrant abdominal pain associated with nausea and vomiting for 4 days. The lesion was demonstrated by abdominal ultrasound and by computed tomography, which was successfully removed surgically.

Delayed onset of deep infection after total knee arthroplasty: comparison based on the infecting organism.

PURPOSE: To identify the organisms causing delayed deep infection following primary total knee arthroplasty (TKA) and to compare the differences in outcome based on the infecting organism. METHODS: Between the period April 1998 and March 2004 inclusive, patients presenting with delayed deep infection following primary TKA and/or those who underwent a salvage procedure (amputation or arthodesis) were retrospectively studied. RESULTS: Organisms were isolated in 27 patients; 44% were methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. When the organism was resistant, the mean number of surgical procedures per patient was significantly higher and the proportion of patients with satisfactory outcomes was significantly lower. CONCLUSION: Deep infection with methicillin-resistant S. aureus or S. epidermidis is increasing. Strict infection control measures must be in place to combat such problems.

Polyomavirus-associated nephropathy risk in kidney transplants: the influence of recipient age and donor gender.

Polyomavirus-associated nephropathy (PVAN) is a frequent cause of kidney transplant failure. We determined the risk factors for biopsy-proven PVAN among 1027 recent kidney transplant recipients by univariate and multivariate analyses. The rate of PVAN was determined over an univariate and multivariate analysis over an average of 30 months of follow-up of patients receiving predominantly living donor grafts with antibody induction and sequential surveillance biopsies to detect subclinical graft disease. Seventy-four transplant recipients were diagnosed with PVAN with the finding made on surveillance biopsy in 40 patients. These 40 cases did not differ from the 34 non-surveillance cases with respect to baseline clinical characteristics or initial histological features. Older recipient age and female donor gender were independent risks associated with PVAN. Factors not linked to PVAN risk included the use and type of induction agent, use of tacrolimus vs sirolimus, the number of human lympocyte antigen (HLA) mismatches, or the frequency of acute rejection. We conclude that PVAN preferentially affects older age patients and allografts from female donors but is unrelated to immunological risk, choice of immunosuppression, or rejection history.

Kidney transplant function and histological clearance of virus following diagnosis of polyomavirus-associated nephropathy (PVAN).

Polyomavirus-associated nephropathy (PVAN) is managed by reduced immunosuppression with or without antiviral therapy. Data from 55 patients with biopsy-proven PVAN were analyzed for adverse outcomes and influence of baseline variables and interventions. During 20+/-11 months follow-up, the frequencies of graft loss, major and any functional decline were 15%, 24% and 38%, respectively. Repeat biopsies were performed in 45 patients with persistent PVAN in 47%. Low-dose cidofovir, IVIG and cyclosporine conversion were used in 55%, 20% and 55% of patients. No single intervention was associated with improved outcome. Of the variables examined, only degree of interstitial fibrosis at diagnosis was associated with kidney function decline. In contrast, donor source, interstitial fibrosis, proportion of BKV positive tubules and plasma viral load at diagnosis were all associated with failure of histological viral clearance. This retrospective, nonrandomized analysis suggests that: (i) Graft loss within 2 years of PVAN diagnosis is now uncommon, but ongoing functional decline and persistent infection occur frequently. (ii) Low-dose cidofovir, IVIG and conversion to cyclosporine do not abrogate adverse outcomes following diagnosis. (iii) Fibrosis at the time of diagnosis predicts subsequent functional decline. Further elucidation of the natural history of PVAN and its response to individual interventions will require prospective clinical trials.

Induction of lymphomas on implantation of human oral squamous cell carcinomas in nude mice.

Cancer cells from five oral cancer patients and pleomorphic adenoma cells from one individual were inoculated as single cell suspension into subcutis of 30 Swiss nude mice and tail vein of additional 30 mice. Further, tumor tissue pieces from three oral cancer patients were xenografted s.c. in 18 nude mice, and 10 mice were kept as controls. In animals implanted with tumor pieces, 7/18 (39%) mice, developed squamous cell carcinoma at the site of inoculation within 8-15 days, while tumors were not observed in mice inoculated with single cell suspension, up to 60/90 days. In 8/68 (12%) mice, white foci were observed in several tissues, with hepatomegaly and splenomegaly noted in 27/68 (39%) mice. Histopathological examination of various tissues revealed presence of large cell lymphoma in several organs in 14/68 (21%) mice. No regional or distant metastasis of the implanted oral tumor cells was detected. Mice injected with cells from pleomorphic adenoma, also demonstrated large cell lymphoma in 2/10 (20%) mice, whereas none of the 10 control animals showed any gross abnormalities or microscopic abnormalities in several organs. 2/16 (12%) lymphomas exhibited positive reaction with mouse B cell antibodies illustrating the murine origin of the lymphomas, and these were immunophenotyed as B cell lymphomas. The lymphomas were also examined with mouse T cell antibodies and none reacted positively with the mouse T cell antibodies. The lymphomas also failed to react with human T cell, B cell and human Leucocyte common antigen (LCA) antibodies, indicating that the induced lymphomas were not of human origin. The tumor specimens from seven of eight oral cancer patients and the pleomorphic adenoma patient induced lymphomas in nude mice. Thus it appears that xenografting oral tumor cells into nude mice may cause induction of the murine lymphomas, and this needs further investigation.

Microsatellite alterations on chromosome 9 in chewing tobacco-induced oral squamous cell carcinomas from India.

Genomic instability as reflected by microsatellite alterations in specific target regions is an important characteristic of oral squamous cell carcinoma (OSCC). Microsatellite instability (MSI) and loss of heterozygosity (LOH) on chromosome 9 has been reported as an early event in oral cancers, primarily from patients in the USA and UK. Hence, we examined 77 primary oral cancer tissues and corresponding peripheral blood cell (PBC) DNA from Indian oral cancer patients for LOH and MSI, using a panel of 11 microsatellite markers spanning chromosome 9 on p and q arms. The patients were long-time (minimum 10 years) tobacco chewers. The matched DNA samples were amplified by polymerase chain reaction, resolved on a denaturing polyacrylamide gel and visualized by silver staining. An overall of 62% (48/77 cases) of the patients demonstrated microsatellite alterations including 27% MSI and 52% LOH, although at individual loci MSI was observed in 3-8% patients and LOH in the informative cases ranged from 4 to 41%. A majority of the alterations occurred on the p arm at 9p21-23, with 85% (41/48 cases) genetic alterations concentrated between markers D9S157 and D9S161. Multiple alterations were seen in 56% (27/48) of the affected cases with 17 patients showing microsatellite alterations in three to eight loci. Our data show the incidence of genetic alterations primarily in the chromosomal region 9p21-23, and may be indicative of involvement of p16 (CDKN2) tumor suppressor gene on chromosome 9p21, in a subset of chewing tobacco-induced oral cancers.

New schedule of intramuscular iron administration for pregnant women.

Pregnant women between 14 and 20 weeks were randomly recruited in 2 groups, 50 to each. One group received iron with folic acid orally, other group was given 5 injections of iron dextran spaced 4 weekly. Mean haemoglobin was same for both the groups at the beginning (p > 0.05). At 36 weeks intramuscular group has shown statistically more haemoglobin rise than oral group (p < 0.001). This new intramuscular schedule is found to be convenient, cheap and acceptable to pregnant women. It also assures at least 5 antenatal checkups to a pregnant woman.

Termination of midtrimester pregnancies with extraovular 0.1% ethacridine lactate. Accurate method for estimation of blood loss. Role of spartein sulfate.

PIP: This study evaluated the effectiveness of extraovular .1% ethacridine lactate alone and edacridine lactate plus spartein sulfate in midtrimester pregnancy termination. In the 60 cases where ethacridine lactate alone was administered, 50 cases aborted within 48 hours of instillation (83.3% success rate). Of these 50, 25 aborted within 24 hours (41.7%). Abortion was complete in 45 cases. The time of onset of uterine contractions ranged from 1 hour to 16.5 hours, with a mean 21-1/4 hours. The mean time of membrane rupture in the series was 23 hours and the induction-abortion interval averaged 27-1/4 hours. Side effects included vomiting (18.3%), shivering (16.6%), fever (3.3%), cervical injuries (6.6%), and excessive blood loss (1.7%). Blood loss until expulsion of the fetus averaged 54.1 ml, and blood loss up to 4 hours after abortion averaged 115.1 ml in cases of complete abortion and 219 ml in cases of incomplete abortion. In the 90 cases where both ethacridine lactate and spartein sulfate were used, 76 aborted within 48 hours (success rate 84.6%) and 40 aborted within 24 hours (44.4%). Abortion was complete in 75% of cases. The abortion-induction interval ranged from 4 hours to 47-3/4 hours, with a mean of 28-1/2 hours. These results, which are comparable to those obtained in other studies, indicate that extraovular ethacridine lactate alone appears to be a safe, efficient, and relatively inexpensive method of midtrimester abortion. Although there were fewer reports of side effects in the group that received spartein sulfate, use of this compound does not reduce the induction-abortion interval. The relatively low incidence of side effects such as vomiting and diarrhea, the antiseptic properties of ethacridine lactate, and the absence of serious complications such as rupture of the uterus and cervicovaginal fistula are advantages of the ethacridine lactate method that nullify the disadvantage of its slightly prolonged induction-abortion interval.^ieng