Impact of ovarian metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancy originating from appendiceal and colorectal cancer.

AIM: Ovarian metastases from gastrointestinal tract malignancies have been considered an ominous finding with poor prognosis. The aim of this project was to determine the impact on survival, and potential cure, when cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are combined to treat peritoneal malignancy in women with Krukenberg tumours. METHOD: A retrospective analysis of prospectively collected data between January 2010 and July 2015. Female patients undergoing complete CRS (macroscopic tumour removal) and HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin, or colorectal peritoneal metastases (CPM) were included. Survival was estimated using the Kaplan-Meier method and survival rates compared using the log-rank test. RESULTS: In total, 889 patients underwent surgery for peritoneal malignancy, of whom 551 were female. Of these, 504/551 (91%) underwent complete CRS and HIPEC. Overall, 405/504 (80%) had at least one involved ovary removed either during CRS and HIPEC or at their index prereferral operation. Three hundred and fifty-two patients (87%) had an appendiceal tumour and 53 (13%) had CPM. At a median follow up of 40 months, overall survival (OS) did not differ significantly between patients with or without ovarian involvement in women with a primary low-grade appendiceal tumour or CPM. In women with high-grade primary appendiceal pathology, OS was significantly lower in patients with ovarian metastases compared with those without ovarian involvement. CONCLUSION: Women with ovarian metastases from low-grade appendiceal tumours or colorectal cancer treated with CRS and HIPEC have similar survival rates to patients without ovarian metastases. Long-term survival and cure is feasible in patients amenable to complete tumour removal.

Sacral osteomyelitis following restorative rectal cancer resection: a delayed presentation of dormant pelvic sepsis.

Sacral osteomyelitis is a rare but potentially fatal complication of pelvic surgery. It is often diagnosed late due to the presence of vague, non-specific symptoms and a low index of suspicion. Previous literature has been limited to a number of case series of patients who have undergone ileoanal pouch formation following proctocolectomy and patients who have undergone pelvic floor reconstruction with mesh sacral colpopexy. Here, we present a patient presenting with sacral osteomyelitis 12 years following anterior resection for colorectal malignancy. We then review the previous literature and discuss the salient management points that may assist in the diagnosis and management of this uncommon complication.

Outcomes of multicystic peritoneal mesothelioma treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is a rare neoplasm, generally considered a borderline malignancy, best treated by cytoreductive surgery (CRS) to remove macroscopic disease, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Owing to its rarity, little has been published on clinical presentation, clinical behaviour over time, or an optimal treatment approach. METHODS: A prospectively developed peritoneal malignancy database was interrogated for the years 2001-2018. Details on all patients with MCPM as a definitive diagnosis after CRS and HIPEC were analysed, including previous interventions, mode of presentation, surgical treatment, postoperative outcomes, and late follow-up information from abdominal CT and tumour markers. RESULTS: Some 40 patients with MCPM underwent CRS and HIPEC between 2001 and 2018. Of these, 32 presented with abdominal pain, distension or bloating, six patients presented with recurrence following previous surgery at the referring hospitals, and two had coincidental diagnoses during a surgical procedure. CRS involved peritonectomy in all 40 patients. Bowel resection was required in 18 patients, and seven had a temporary stoma. Thirty-eight patients were considered to have undergone a complete macroscopic tumour removal (completeness of cytoreduction CC0), and two had residual tumour nodules less than 2.5 mm in size, classified as CC1. Median duration of follow-up was 65 (range 48-79) months. There were no deaths during follow-up. The Kaplan-Meier-predicted recurrence-free interval was 115.4 months. CONCLUSION: MCPM is a rare peritoneal neoplasm with a heterogeneous pattern of presentation. CRS and HIPEC is an effective management option for this group of patients, with favourable long-term survival.

Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting.

BACKGROUND: Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video-conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years. METHODS: Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video-conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted. RESULTS: A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien-Dindo grade I-II complications occurred in 16 patients; there was no grade III-IV morbidity or 30-day in-hospital mortality. The median follow-up for the whole cohort was 18·7 months, and the 2-year survival rate from time of first review at the national PM MDT was 68·3 per cent. CONCLUSION: The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection.

ANTECEDENTES: El mesotelioma peritoneal (peritoneal mesothelioma, PM) es una neoplasia primaria del peritoneo muy poco frecuente, con una incidencia creciente en todo el mundo. La cirugía citorreductora (cytoreductive surgery, CRS) con quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) se ha mostrado prometedora como estrategia de tratamiento. En marzo de 2016, se organizó una reunión por videoconferencia del equipo multidisciplinar nacional de PM (national PM multi-Disciplinary Team, MDT) en el Reino Unido e Irlanda, con el objetivo de planificar un tratamiento óptimo, registrar los resultados y proporcionar evidencia de los beneficios de la centralización. Este manuscrito presenta las actividades y los resultados de los primeros 2,5 años. MÉTODOS: Entre marzo de 2016 y diciembre de 2018, 155 pacientes con PM, remitidos a centros de cirugía oncológica peritoneal en Basingstoke, Good Hope Hospital en Birmingham, Christie Hospital en Manchester y Mater Misericordiae en Dublín, fueron discutidos en el National PM MDT a través de una videoconferencia. El MDT estaba compuesto por cirujanos, radiólogos, enfermeras especializadas y patólogos. Los pacientes fueron considerados para CRS e HIPEC si se determinaba que eran aptos para la cirugía y si las imágenes radiológicas sugerían que se podía lograr una citorreducción quirúrgica completa. Se analizó la morbilidad y mortalidad después de la cirugía. Se realizó un análisis de supervivencia tras la discusión en el MDT. RESULTADOS: En total, se discutieron 155 pacientes (tasa varón/mujer 0,96) con una edad media de 57 ± 17 años. Hasta el momento, 22 (14,2%) habían sido sometidos a CRS y HIPEC y la mediana de PCI en el grupo quirúrgico fue de 17,0. La citorreducción completa se logró en 19 (86,4%), las complicaciones de Clavien-Dindo grado I/II ocurrieron en 16/22, sin morbilidad de grado III/IV, ni mortalidad a los 30 días. La mediana de seguimiento fue de 15,0 meses y la supervivencia a los 2 años desde el momento de la revisión en el National PM MDT fue del 66,7%. CONCLUSIÓN: El National PM MDT centralizado fue eficaz en la selección de pacientes adecuados para CRS e HIPEC, presentando un buen resultado a partir de dicha selección.

Biological mesh is a safe and effective method of abdominal wall reconstruction in cytoreductive surgery for peritoneal malignancy.

BACKGROUND: Patients with peritoneal malignancy often have multiple laparotomies before referral for cytoreductive surgery (CRS). Some have substantial abdominal wall herniation and tumour infiltration of abdominal incisions. CRS involves complete macroscopic tumour removal and hyperthermic intraperitoneal chemotherapy (HIPEC). Abdominal wall reconstruction is problematic in these patients. The aim of this study was to establish immediate and long-term outcomes of abdominal wall reconstruction with biological mesh in a single centre. METHODS: A dedicated peritoneal malignancy database was searched for all patients who had biological mesh abdominal wall reconstruction between 2004 and 2015. Short- and long-term outcomes were reviewed. All patients had annual abdominal CT as routine peritoneal malignancy follow-up. RESULTS: Some 33 patients (22 women) with a mean age of 53·4 (range 19-82) years underwent abdominal wall reconstruction with biological mesh. The majority (23) had CRS for pseudomyxoma (19 low grade), six for colorectal peritoneal metastasis and four for appendiceal adenocarcinoma; 18 had undergone CRS and HIPEC previously. Twenty-five of the 33 patients had abdominal wall tumour involvement and eight had concurrent hernias. The mean duration of surgery was 486 (range 120-795) min and the mean mesh size used was 345 (50-654) cm2. Ten patients developed wound infections and four had a seroma. Two developed early enterocutaneous fistulas. Mean follow-up was 48 months. Five patients developed an incisional hernia. Four died from progressive malignancy. A further 15 patients had disease recurrence, but only one had isolated abdominal wall recurrence. CONCLUSION: Biological mesh was safe and effective for abdominal wall reconstruction in peritoneal malignancy. Postoperative wound infections were frequent but nevertheless incisional hernia rates were low with no instances of mesh-related bowel erosion or fistulation.

Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways.

Hepatic steatosis is common in patients having severe hyperhomocysteinemia due to deficiency for cystathionine beta-synthase. However, the mechanism by which homocysteine promotes the development and progression of hepatic steatosis is unknown. We report here that homocysteine-induced endoplasmic reticulum (ER) stress activates both the unfolded protein response and the sterol regulatory element-binding proteins (SREBPs) in cultured human hepatocytes as well as vascular endothelial and aortic smooth muscle cells. Activation of the SREBPs is associated with increased expression of genes responsible for cholesterol/triglyceride biosynthesis and uptake and with intracellular accumulation of cholesterol. Homocysteine-induced gene expression was inhibited by overexpression of the ER chaperone, GRP78/BiP, thus demonstrating a direct role of ER stress in the activation of cholesterol/triglyceride biosynthesis. Consistent with these in vitro findings, cholesterol and triglycerides were significantly elevated in the livers, but not plasmas, of mice having diet-induced hyperhomocysteinemia. This effect was not due to impaired hepatic export of lipids because secretion of VLDL-triglyceride was increased in hyperhomocysteinemic mice. These findings suggest a mechanism by which homocysteine-induced ER stress causes dysregulation of the endogenous sterol response pathway, leading to increased hepatic biosynthesis and uptake of cholesterol and triglycerides. Furthermore, this mechanism likely explains the development and progression of hepatic steatosis and possibly atherosclerotic lesions observed in hyperhomocysteinemia.

The modified Glasgow prognosis score predicts for overall and disease-free survival following cytoreductive surgery and HIPEC in patients with pseudomyxoma peritonei of appendiceal origin.

BACKGROUND: The modified Glasgow prognostic score (incorporating C-reactive protein and albumin) predicts survival in patients with gastro-intestinal tract cancer but has not been evaluated in patients with peritoneal malignancy. The aim was to evaluate the modified Glasgow score preoperatively in patients undergoing complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin. METHODS: Prospectively collected data from patients with PMP of appendiceal origin following CCRS and HIPEC between January 2007 and December 2011 were analysed. The mGPS was calculated from preoperative C-reactive protein and albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each mGPS score were calculated using the Kaplan-Meier model. In a separate analysis, a comparison was made between mGPS and Tumour Markers (TM). RESULTS: 260 patients were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and 19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9, and 54.4 months respectively. As mGPS increases, there is a reduction in long-term survival. There was no difference between mGPS and TM. CONCLUSION: Preoperative mGPS may be a cost effective prognostic tool for predicting OS and DFS in patients following complete CRS-HIPEC, and performs well compared to TM for predicting patients at high risk of recurrence.

Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice.

Hyperhomocysteinemia is associated with increased risk for cardiovascular events, but it is not certain whether it is a mediator of vascular dysfunction or a marker for another risk factor. Homocysteine levels are regulated by folate bioavailability and also by the methyl donor S-adenosylmethionine (SAM) and its metabolite S-adenosylhomocysteine (SAH). We tested the hypotheses that endothelial dysfunction occurs in hyperhomocysteinemic mice in the absence of folate deficiency and that levels of SAM and SAH are altered in mice with dysfunction. Heterozygous cystathionine beta-synthase-deficient (CBS(+/-)) and wild-type (CBS(+/+)) mice were fed a folate-replete, methionine-enriched diet. Plasma levels of total homocysteine were elevated in CBS(+/-) mice compared with CBS(+/+) mice after 7 weeks (27.1+/-5.2 versus 8.8+/-1.1 micromol/L; P<0.001) and 15 weeks (23.9+/-3.0 versus 13.0+/-2.3 micromol/L; P<0.01). After 15 weeks, but not 7 weeks, relaxation of aortic rings to acetylcholine was selectively impaired by 35% (P<0.05) and thrombomodulin anticoagulant activity was decreased by 20% (P<0.05) in CBS(+/-) mice. Plasma levels of folate did not differ between groups. Levels of SAH were elevated approximately 2-fold in liver and brain of CBS(+/-) mice, and correlations were observed between plasma total homocysteine and SAH in liver (r=0.54; P<0.001) and brain (r=0.67; P<0.001). These results indicate that endothelial dysfunction occurs in hyperhomocysteinemic mice even in the absence of folate deficiency. Endothelial dysfunction in CBS(+/-) mice was associated with increased tissue levels of SAH, which suggests that altered SAM-dependent methylation may contribute to vascular dysfunction in hyperhomocysteinemia.

The determination of nicotinic acid in plasma by mixed-mode liquid chromatography-tandem mass spectrometry following ion exchange solid phase extraction.

An assay for nicotinic acid in plasma samples has been developed using ion exchange solid phase extraction in 96-well format followed by mixed-mode ion exchange/reversed-phase liquid chromatography with positive ion tandem mass spectrometry detection. The assay avoids the need for time-consuming derivatisation procedures or involatile ion-pair chromatography reagents. The assay is linear over the wide range 0.05-20 microg/mL, based on a 100 microL sample (correlation coefficient>0.99). The assay is accurate and precise (bias and coefficient of variation<18%) over this calibration range.

Attitudes towards breast conservation in patients aged over 70 with breast cancer.

BACKGROUND: The majority of breast conserving surgery (BCS) is performed in younger women. There is little published information about the views of women aged over 70 regarding BCS. The aim of this study was to investigate the attitudes of this age group towards BCS, and factors which may influence their treatment decision-making. METHODS: A questionnaire was sent to all patients who were aged 70 or over at the time they had breast cancer surgery in NHS Lanarkshire between 1999 and 2013. This detailed surgical options and recommendations, timing of decision making, treatment expectations, psychological and cosmetic concerns and other factors which may have influenced any decision made e.g. travel for radiotherapy and potential side effects. RESULTS: Responses were received from 339 patients, 192 of whom had a mastectomy with the remaining undergoing BCS. In the mastectomy group 18 % (35) would have preferred to have BCS had it been an option, with 40 % (76) of group being happy to take neoadjuvant endocrine therapy to try and facilitate this. However, only 14 % (26) of patients would have considered neoadjuvant chemotherapy with the same aim. Almost half (82) of the mastectomy patients said that the risk of local recurrence following BCS was a factor which influenced their decision. CONCLUSION: BCS is something that patients aged over 70 are interested in considering in the same way as younger patients. More than a third of patients requiring mastectomy would be willing to take neoadjuvant endocrine therapy to attempt to downstage their tumour to facilitate BCS.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1000 patients with perforated appendiceal epithelial tumours.

PURPOSE: To report early and long term outcomes following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in 1000 patients with perforated appendiceal epithelial tumours, predominantly with pseudomyxoma peritonei (PMP). METHODS: Retrospective analysis of a prospective database of 1000 consecutive patients undergoing CRS and HIPEC for perforated appendiceal tumours between 1994 and 2014 in a UK National Peritoneal Malignancy unit. RESULTS: Overall 1000/1444 (69.2%) patients treated for peritoneal malignancy had appendiceal primary tumours. Of these 738/1000 (73.8%) underwent complete cytoreductive surgery (CCRS), 242 (24.2%) had maximal tumour debulking (MTD) and 20 (2%) had laparotomy and biopsies only. Treatment related 30-day mortality was 0.8% in CCRS and 1.7% in MTD group with major postoperative morbidity rates of 15.2% (CCRS) and 14.5% (MTD). Five- and 10-year overall survival was 87.4% and 70.3% in the 738 patients who had CCRS compared with 39.2% and 8.1% respectively in the MTD group. On multivariate analysis, significant predictors of reduced overall survival were male gender (p = 0.022), elevated CEA (p = 0.001), elevated CA125 (p = 0.001) and high tumour grade or adenocarcinoma (p = 0.001). CONCLUSIONS: Perforated epithelial appendiceal tumours are rare, though may be increasing in incidence and can present unexpectedly at elective or emergency abdominal surgery, often with PMP. CRS and HIPEC results in good long term outcomes in most patients.

Genetic polymorphism of alpha-lactalbumin gene in riverine buffalo.

Alpha-lactalbumin (alpha-LA) is a major whey protein found in milk. Polymorphs of alpha-LA gene are reported to be significantly associated with milk production and constituent traits. Therefore, the present study was undertaken to detect polymorphism in alpha-LA at the genic level and to explore allelic variability at this locus. A total of 196 animals, belonging to four breeds of riverine buffalo viz. Bhadwari, Mehsana, Surti and Murrah were included under the present investigation. Two fragments i.e. 133 bp (Exon 1) and 159 bp (Exon 2) of alpha-LA gene were amplified by polymerase chain reaction and subsequently, single strand confirmation polymorphism (SSCP) study was carried out to identify different allelic pattern and genotypes of the animal included in the study. Both fragment of alpha-LA gene was found to be polymorphic in all the four breeds of riverine buffalo. Number of genotypes and allele varied breed to breed for both the fragments. In case of 133 bp fragment, four alleles A, B, C and D were found among different breeds of buffalo whereas in 159 bp fragment, five alleles namely A, B, C, D and E was found in different breeds. Nucleotide sequence data of different alleles showed the presence of both silent as well as functional mutation leading to variability in polypeptide chain.

Risk of definitive stoma after surgery for peritoneal malignancy in 958 patients: comparative study between complete cytoreductive surgery and maximal tumor debulking.

INTRODUCTION: Complete cytoreductive surgery (CRS) can achieve cure or long-term survival in selected patients with peritoneal malignancy. In selected patients, due to extensive disease, complete tumour removal is impossible and optimal strategy may be maximal tumour debulking (MTD). We analysed the stoma related outcome in a series of patients undergoing surgery in a National Peritoneal Malignancy Referral Centre. METHODS: All patients who underwent CRS, with or without, intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) between 1994 and 2012 were included. Data was collected prospectively in an institutional database and analysed retrospectively. RESULTS: CRS was performed in 958 patients (female: 595, male: 363) of whom 781 (81.5%) had a primary appendix tumour, 63 (6.6%) had a colorectal primary, 47 (4.9%) peritoneal mesothelioma, 38 (4%) an ovarian tumour and 29 patients (3%) other tumours. Complete CRS was achieved in 72% (693/958). Overall 352/958 (37%) had a stoma, which was permanent in 165/958 (17.2%). The median time interval from CRS to reversal of stoma was 4.4 months (range: 1.4-13.8). Stomas were created in 113/265 (42.6%) at MTD (permanent: n = 105 (93%), temporary: n = 8 (7%)), and 239/693 (34.5%) at complete CRS (permanent: n = 60 (25%), temporary: n = 179 (75%)) (p = 0.020). All temporary stomas in the 168/693 (24.4%) of patients who had complete CRS were subsequently reversed. CONCLUSION: To achieve complete CRS for peritoneal malignancy a stoma is often required and in a proportion this will be permanent. Overall over one third had a stoma at surgery with almost half subsequently reversed.

Masked polycythaemia vera in a patient with extrahepatic portal venous obstruction.

Myeloproliferative disorder (MPD) is an important cause of thrombosis of the hepatic and portal venous system. The diagnosis in many of these patients is missed as they have an atypical clinical presentation and may have a normal haematological profile at presentation. We report a 30-year-old patient with features of portal hypertension due to extrahepatic portal venous obstruction. She had a normal haemoglobin level and haematocrit at presentation, but the red cell mass was found to be elevated even in the presence of low serum iron levels. A diagnosis of polycythaemia vera as the underlying disease was made.

The female gender protects against pulmonary injury after trauma hemorrhagic shock.

BACKGROUND: Previously, we have documented that lung injury after trauma-hemorrhagic shock (T/HS) is related to gut injury and that females are more resistant to T/HS-induced lung injury than males. However, it is not known if the estrus cycle stage at the time of injury influences the female rat's resistance to T/HS-induced lung injury. Therefore, the goal of this study was to determine if the protective effect of the female gender on lung injury after T/HS is estrus cycle stage-specific. To test this hypothesis, female rats were subjected to trauma (laparotomy) and hemorrhagic shock (T/HS) during different stages of the estrus cycle. Female animals subjected to trauma with sham hemorrhagic shock served as the control. METHODS: Female Sprague-Dawley rats during the proestrus, estrus, metestrus, or diestrus stages of the menstrual cycle were subjected to a midline laparotomy (trauma) and either hemorrhagic shock (MAP = 30 mm Hg x 90 min) or sham shock. The total volume of blood necessary to induce and maintain the shock state was recorded. At the end of the shock period, the animals were resuscitated with their shed blood. At 6 h postresuscitation, the animals were sacrificed and lung permeability was measured using the Evans blue dye technique and by determining the bronchoalveolar (BALF) to plasma protein ratio. Additionally, pulmonary leukosequestration was quantitated by measuring pulmonary myeloperoxidase levels. RESULTS: T/HS-induced lung injury and increased pulmonary leukosequestration were not observed in female rats in the proestrus or estrus stages of the menstrual cycle. In contrast, pulmonary permeability was increased significantly in the diestrus stage animals after T/HS. That is, the diestrus females subjected to T/HS had increased pulmonary permeability to Evans blue dye than sham or T/HS proestrus, estrus, and metestrus rats (6.49 +/- 1.33% versus 1.7 +/- 0.87%, 1.57 +/- 0.54%, 1.78 +/- 0.82%, 3.33 +/- 0.68%, p < 0.01, respectively). Similar results were obtained with the BALF protein/plasma protein ratio (0.15 +/- 0.017 versus 0.09 +/- 0.009, 0.09 +/- 0.03, 0.08 +/- 0.022, 0.11 +/- 0.029 p < 0.05, respectively). Although the T/HS metestrus rats had mildly increased lung permeability, this increase in T/HS-lung permeability did not reach statistical significance. Pulmonary myeloperoxidase levels after T/HS displayed a similar trend, with diestrus rats subjected to T/HS having the highest level of MPO (p < 0.05 versus sham or T/HS proestrus and estrus but not metestrus groups). Linear regression analysis of MPO versus Evans blue dye leak revealed a significant correlation between pulmonary neutrophil sequestration and lung leak (r = 0.9549; p < 0.0001). CONCLUSION: Protection against T/HS-induced lung injury was greatest during the estrus and proestrus stages of the menstrual cycle and decreased with progression to diestrus. During the diestrus stage of the menstrual cycle when gonadal hormone levels are lowest, the rats are more sensitive to T/HS-induced lung injury, indicating that gonadal hormones modulate T/HS-induced lung injury.

Resistance to activated protein C (APC) in Indian patients of thrombophilia.

In a pilot study, 28 consecutive patients with thrombosis and 23 age and sex matched healthy normal controls were investigated with normalised APC sensitivity ratio (n-APC-SR) to know the defect exists and if so its prevalence in India. Six of the 28 (21.4%) thrombotic patients had n-APC-SR of < 0.76 (range 0.55 to 0.74) as compared to the normal control value (0.97 +/- 0.105). Our study shows APC resistance defect in a significant proportion (21.4%) of Indian patients with thrombotic disorders.

Variability of milk fat globule membrane protein gene between cattle and riverine buffalo.

A study on butyrophilin (BTN) gene was conducted to detect variability at nucleotide level between cattle and buffalo. Hae III PCR-RFLP was carried out in crossbred cattle and it revealed polymorphism at this locus. Three genotypes namely, AA, BB and AB and two alleles were observed with frequencies 0.78, 0.17, 0.04 and 0.87, 0.13, respectively. The sequences of different cattle, buffalo and sheep breeds have been reported in the EMBL gene bank with accession numbers: AY491468 to AY491475. The nucleotides, which have been substituted from allele A to B, were found to be C to G (71st nucleotide), C to T (86th nucleotide), A to T (217th nucleotide), G to A (258th nucleotide), A to C (371st nucleotide) and C to T (377th nucleotide). The nucleotide substitution at 71st, 86th and 377th position of the fragment were expected to be a silent mutation where as nucleotide changes at 217th, 258th and 371st positions were expected to be substituted by lysine with arginine, valine with isoleucine and leucine with proline in allele B. The differences of nucleotides and amino acids between cattle, buffalo and sheep breeds have been revealed and on the basis of nucleotide as well as protein variability the phylogenetic diagram have been developed indicating closeness between cattle and buffalo.