Requirement of MyD88 for macrophage-mediated islet xenograft rejection after adoptive transfer

BACKGROUND: Porcine antigen primed and CD4+ T-cell activated macrophages are able to migrate to and destroy porcine xenografts. However, the specific signaling mechanisms involved remain to be identified. METHODS: In this study macrophages which lack the universal toll-like receptor (TLR) adaptor MyD88 were used to investigate the role of TLR in the recognition and activation of macrophages in islet xenograft rejection. Macrophages were isolated from rejecting MyD88(-/-) and wild-type C57BL/6 mice that were recipients of neonatal porcine pancreatic cell cluster (NPCC) xenografts, and were transferred to NPCC recipient NOD-SCID mice. RESULTS: Both wild-type C57BL/6 and MyD88(-/-) mice rejected NPCC xenografts 8 and 10 days, respectively after transplantation, and the grafts were heavily infiltrated with CD4+ T cells and macrophages. However, graft infiltrating macrophages from rejecting MyD88(-/-) recipients demonstrated impaired up-regulation of TLR expression and impaired activation phenotype, when compared to those from rejecting C57BL/6 recipients. Transfer of NOD-SCID recipients with macrophages from rejecting C57BL/6 mice resulted in NPCC xenograft rejection along with massively infiltrated macrophages 8 days after transfer, whereas NPCC xenografts in NOD-SCID mice transferred with macrophages from rejecting MyD88(-/-) mice remained intact until the end of this study, 90 days after transfer, with insulin-positive islets and no infiltration by macrophages. CONCLUSION: This study demonstrates that deletion of MyD88 causes impaired macrophage activation after pig islet xenotransplantation. However, graft survival is not prolonged and xenografts are rejected rapidly by alternate mechanisms.     

Metachronous Multiple Primary Malignant Neoplasms of the Stomach and the Breast: Report of Two Cases With Review of Literature

Multiple primary malignant neoplasm is the occurrence of a second primary malignancy in the same patient within 6 months of the detection of first primary (synchronous), or 6 months or more after primary detection (metachronous). Multiple primary malignant neoplasms are not very frequently encountered in clinical practice. The relative risk for a second primary malignancy increases by 1.111-fold every month from the detection of the first primary malignancy in any individual. We present 2 patients treated for carcinoma of the breast who developed a metachronous primary malignancy in the stomach to highlight the rare occurrence of multiple primary malignant neoplasms. These tumors were histologically dissimilar, with distinct immunohistochemical parameters. The importance lies in carefully identifying the second primary malignancies, not dismissing them as metastases, and treating them accordingly.Key words: Breast neoplasms, Stomach neoplasms, Neoplasms, Second primaryBreast cancer is the most common malignancy among women worldwide. With proper screening, earlier detection, and improved treatment, survival has greatly increased, with the result that there is now a large population of women with a present or past history of breast cancer. This has led to an increased detection of second primary malignancies among these women. The relative risk for a second primary malignancy increases by 1.111-fold every month from the detection of the first primary malignancy in any individual.¹ Several authors have reported on a lesion in the stomach being labeled as a second primary malignancy and subsequently found to be metastasis. When the primary breast tumor is positive for estrogen and progesterone receptors (ER/PRs) and the stomach tumor is ER/PR negative, the diagnosis is established easily.² However, studies have shown that some primary gastric cancers can have ER/PR positivity. Further, if the primary breast lesion is ER/PR negative, the same cannot be used as a marker. Here, we present 2 breast cancer patients who developed second primary malignancies in the stomach and the final diagnosis was established based on histopathology and immunohistochemistry.     

Results of triple muscle (sartorius,tensor fascia latae and part of gluteus medius) pedicle bone grafting in neglected femoral neck fracture in physiologically active patients

Background:

Femoral neck fractures are notorious for complications like avascular necrosis and nonunion. In developing countries, various factors such as illiteracy, low socioeconomic status, ignorance are responsible for the delay in surgery. Neglected fracture neck femur always poses a formidable challenge. The purpose of this study was to evaluate the results of triple muscle pedicle bone grafting using sartorius, tensor fasciae latae and part of gluteus medius in neglected femoral neck fracture.

Materials and Methods:

This is a retrospective study with medical record of 50 patients, who were operated by open reduction, internal fixation along with muscle pedicle bone grafting by the anterior approach. After open reduction, two to three cancellous screws (6.5 mm) were used for internal fixation in all cases. A bony chunk of the whole anterior superior iliac spine of 1 cm thickness, 1 cm width and 4.5 cm length, taken from the iliac crest comprised of muscle pedicle of sartorius, tensor fascia latae and part of gluteus medius. Then the graft with all three muscles mobilized and put in the trough made over the anterior or anterosuperior aspect of the femoral head. The graft was fixed with one or two 4.5 mm self-tapping cortical screw in anterior to posterior direction.

Results:

14 patients were lost to followup. The results were based on 36 patients. We observed that in our series, there was union in 34, out of 36 (94.4%) patients. All patients were within the age group of 15-51 years (average 38 years) with displaced neglected femoral neck fracture of ≥30 days. Mean time taken for full clinicoradiological union was 14 weeks (range-10-24 weeks).

Conclusion:

Triple muscle pedicle bone grafting gives satisfactory results for neglected femoral neck fracture in physiologically active patients.     

Influence of the Leaf Extract of Mentha arvensis Linn. (Mint) on the Survival of Mice Exposed to Different Doses of Gamma Radiation

BACKGROUND: The aim of the present study was to evaluate the radioprotective effect of Mentha arvensis (mint) on the survival of mice exposed to various doses of whole-body gamma radiation. MATERIAL AND METHODS: The radioprotective effect of various doses (0, 2.5, 5, 10, 20, 40 and 80 mg/kg body weight) of chloroform extract of mint (Mentha arvensis Linn.) was studied in mice exposed to 10 Gy gamma radiation. RESULTS: The 10 mg/kg of mint extract was found to afford best protection as evidenced by the highest number of survivors in this group at 30 days post-irradiation, and further experiments were carried out using this dose of mint extract. The mice treated with 10 mg/kg body weight mint extract or oil were exposed to 6, 7, 8, 9 and 10 Gy of gamma radiation and observed for the induction of radiation-sickness and mortality up to 30 days post-irradiation. The mint extract pretreatment was found to reduce the severity of symptoms of radiation sickness and mortality at all exposure doses and a significant increase in the animal survival was observed when compared with the oil + irradiation group. All of the animals that were treated with 10 mg/kg mint extract and then exposed to 7 Gy irradiation were protected against the radiation-induced mortality when compared with the concurrent oil + irradiation group, in which 20% animals died by 30 days post-irradiation. The mint extract treatment protected the mice against the gastrointestinal death as well as bone marrow deaths. The DRF was found to be 1.2. The drug was non-toxic up to a dose of 1,000 mg/kg body weight, the highest drug dose that could be tested for acute toxicity. CONCLUSION: From our study it is clear that mint extract provides protection against the radiation-induced sickness and mortality and the optimum protective dose of 10 mg/kg is safe from the point of drug-induced toxicity.     

Regional wall motion improvement after coronary thrombolysis with recombinant tissue plasminogen activator: importance of coronary angioplasty

To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.     

Perioperative risk factors in patients with liver disease undergoing non-hepatic surgery

The patients with liver disease present for various surgical interventions. Surgery may lead to complications in a significant proportion of these patients. These complications may result in considerable morbidity and mortality. Preoperative assessment can predict survival to some extent in patients with liver disease undergoing surgical procedures. A review of literature suggests nature and the type of surgery in these patients determines the peri-operative morbidity and mortality. Optimization of premorbid factors may help to reduce perioperative mortality and morbidity. The purpose of this review is to discuss the effect of liver disease on perioperative outcome; to understand various risk scoring systems and their prognostic significance; to delineate different preoperative variables implicated in postoperative complications and morbidity; to establish the effect of nature and type of surgery on postoperative outcome in patients with liver disease and to discuss optimal anaesthesia strategy in patients with liver disease.     

The impact of subtrochanteric fracture criteria on hip fracture classification

Summary  

Hospital diagnosis codes are useful for assessing hip fracture rates in large populations. However, these codes do not reliably differentiate hip fractures that occur in the subtrochanteric region. Identification of subtrochanteric fractures requires review of radiographic images to distinguish these fractures from the more commonly occurring trochanteric fractures.     

Long-term outcomes of patients with chronic kidney disease

This Practice Point commentary discusses a recent paper by Menon et al. that described the natural history of a cohort of nondiabetic patients with stage 2-4 chronic kidney disease (CKD) who had been recruited from nephrology practices and screened for entry into the Modification of Diet in Renal Disease (MDRD) trial. Kidney failure was the most common outcome during long-term follow-up among these patients and there was a low competing risk of death, findings in contrast to observations in other cohorts of patients with CKD. Patients with lower glomerular filtration rate and greater proteinuria at baseline were at increased risk for both kidney failure and death, but kidney failure remained more likely than death in all glomerular filtration rate subgroups. These results emphasize the heterogeneity of the CKD population. Nephrologists should not rely on CKD staging alone to direct management of or risk-stratify patients with CKD, but should also consider the etiology and rate of progression of kidney disease, patient age and cardiovascular disease risk factors.     

Limb conservation in extremity soft tissue sarcomas with vascular involvement

Background:

The major neurovascular involvement and large primary tumors are indication of amputation. The present study is an attempt to explore the feasibility of a limb salvage surgery in extremity sarcoma cases with major vessel involvement. Oncological outcomes and surgery-related morbidities are compared with those reported in literature.

Materials and Methods:

A retrospective review of all limb salvage surgeries done in our department between 2005 and 2008 was done and four cases of extremity sarcoma of lower limb involving femoral vessels analyzed. Interpretation of data from these cases, along with review of literature, is done.

Results:

In all these cases a wide monobloc excision was done adhering to oncological principles. This required resection of superficial femoral artery alone in two cases, resection of superficial femoral artery along with common femoral vein and femoral nerve in another, and of common femoral vein alone in yet another. Reconstruction was done in all these cases with reversed long saphenous vein graft. Histopathology of resected margins was free of tumor in all the four patients. One patient developed local recurrence and one developed distant metastsis. Two were disease free for one year with good functional limb, one has been disease-free for three years and another was disease-free at two years, after which he defaulted further follow-up. One patient developed arterial blowout which required ligation of common femoral artery which resulted in gangrene of the limb. He underwent amputation.

Conclusion:

Major neurovascular involvement in extremity sarcoma is not considered a contraindication for limb salvage surgery. Review of literature also supports our view. Post-operative wound related complications are more in this group of patients. However, long term functional outcome is good. Literature suggests a good long term local control after vascular resection and reconstruction.     

Combined trans-sphenoidal and simultaneous trans-ventricular-endoscopic decompression of a giant pituitary adenoma: case report

Objective  This is the first report of the simultaneous combined use of trans-sphenoidal and trans-ventricular-endoscopic route for decompression of a giant pituitary adenoma. Method  A 38 year old man presented to us with symptoms of raised intracranial pressure along with visual and hypothalamic disturbances. The CT scan revealed destruction of the sella by a large (5 × 3.5 × 2.5 cm) well defined enhancing mass in the sella and suprasellar region extending laterally up to the cavernous sinuses and both carotid arteries and superiorly into the lumen of the 3rd ventricle producing obstructive hydrocephalus. On T2WI of the non-contrast MRI scan the mass was iso-intense to grey matter suggesting the possibility of a firm nature of the adenoma. The tumour was first approached by the standard trans-sphenoidal route and as predicted from the pre-operative MRI, the tumour was found to be firm and not amenable to suction. After decompression of the intra-sellar part of the tumour, the intracranial pressure was raised in an attempt to make the remainder of the tumour descend into the sella but without success. The suprasellar part of the tumour was then simultaneously addressed via a trans-ventricular-endoscopic route but the firm tumour did not yield to endoscopic instruments viz. biopsy forceps, angiographic catheter and electrosurgical probes. It was then gently pushed down towards the sella and decompressed piecemeal by using trans-sphenoidal instruments. The sellar cavity was reconstructed using fat, fascia lata graft and a piece of septal bone. Results  Post-operatively, the patient showed a remarkable improvement of his symptoms of raised intracranial pressure, hypothalamic dysfunction and visual disturbances. Follow-up imaging at 2 months and 1 year, did not show any residual or recurrent tumour. Conclusions  This novel technique of the combined trans-sphenoidal and simultaneous trans-ventricular-endoscopic approach is a viable option for patients with giant fibrous pituitary adenoma when the tumour is not yielding to the trans-sphenoidal route alone.