PR05POST‐OPERATIVE HAEMATOMAS IN MICROVASCULAR FREE FLAP RECONSTRUCTION OF THE HEAD AND NECK: THE INCIDENCE,AETIOLOGY AND OUTCOME MODIFICATIONS

Background Free tissue transfer using microvascular surgery has become a safe a reliable means to repair soft tissue and/or bony defects of the head and neck. Operative success reaches 98%, however the incidence of significant post‐operative complication is also relatively high (32%). One common and often severe complication is haematoma formation at either donor or recipient sites. The incidence of recipient site haematoma is reported at 6%, however the causes and outcomes of haematomas have not been well investigated. A retrospective historical analysis of both donor and recipient site wound haematoma was performed to identify causative factors and the effect on patient outcome. Methodology A five year review was conducted for microvascular free tissue transfer to defects in the head and neck at The Royal Melbourne Hospital, for the period from February 2001 until February 2006. The medical records of these 150 patients were reviewed for donor and recipient site wound haematoma and outcomes. Results Significant factors for the development of post‐operative haematomas included lood pressure control during the first post‐operative, correlating with the likelihood of developing either a donor or recipient site haematoma (p value < 0.001), drain‐tube outputs (both high and low), smoking and the use of pre‐operative NSAIDs. Conclusion There are significant reversible factors that contribute to the development of post‐operative haematomas in head and neck surgery. Close monitoring of patient blood pressure by theatre and recovery nursing staff, close monitoring of drain outputs, and pre‐operative counselling on the use of NSAIDs and smoking may all be useful in the prevention of haematoma formation.     

Colorectal tumor screening in women with a past history of breast, uterine, or ovarian malignancies

Epidemiologic studies have shown that women who have successfully recovered from breast, uterine, or ovarian cancer have about twice the expected risk of developing colorectal cancer. These high-risk women were entered, therefore, into a large bowel screening program based on fecal occult blood detection, flexible sigmoidoscopy, and colonoscopy, when appropriate. The study group consisted of 183 women and the results were compared with 252 comparison subjects of similar age and ethnic origin. Neoplastic lesions, adenomatous polyps, or cancer were 2.5 times more frequent in the study group. However, for the largest group, women with a past history of breast cancer, the relative risk, adjusted for a family history of gastrointestinal cancer, was 3.0 (P = 0.03). This pilot study confirms the value of continuing to screen these patients, especially those with a positive family history of gastrointestinal malignancies. However, for psychological and administrative reasons, it may be better that their colon screening be integrated into a combined colon, breast, and gynecologic tumor follow-up, and not be part of a separate service.     

Prolonged red blood cell glycerol hemolysis in mice inhaling benzene

Inhalation of benzene produces a prolongation of mouse red blood cell glycerol hemolysis time. This was not observed in red blood cells directly incubated in benzene. Increased resistance to the hemolytic action of glycerol should be explored as a potentially useful biological monitoring procedure in the red blood cells of benzene-exposed humans.     

Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content and their significance for the realization of an estrogen effect on angiotensinogen blood level in rats.

The use of a modified, adequate method of quantification of estrogen receptors has permitted us to prove the existence of sex-specific peculiarities in rat liver estrogen reception and their significance for the realization of sex-dependent changes in angiotensinogen plasma level after estrogenization. Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content in rats were investigated in detail. The investigation shows that androgens have negative regulatory influence on the hepatic estrogen receptor level in rats. Estrogens and adrenal and thyroid hormones do not take part in the regulation of hepatic estrogen receptor content in rats. It has been proven that the decisive role in keeping up a certain estrogen receptor concentration in hepatocytes belongs to pituitary growth hormone. It was shown for the first time that androgens are able to inhibit the stimulatory effect of growth hormone on hepatic estrogen receptors.     

Features of the formation, expression and transmission of basic genetic and androgen programs of the level of unusual estrogen-binding protein in sexually mature female rat hepatocytes under experimental conditions]

Some features of the formation, expression and inheritance of basic genetic and androgen programs of the level of unusual estrogen-binding protein (UEBP) in mature female rat hepatocytes under experimental conditions were investigated. Liver regeneration after partial (2/3) hepatectomy of mature rats was used for generation of a new population of differentiated hepatocytes. The UEBP content was determined by radioligand technique in control liver and at 2, 4, 14 days of liver regeneration and related to the total DNA content as an indicator of cell proliferative activity. It was revealed that the basic genetic program of low UEBP level of hepatocytes of ovariectomized females was fully transferred to daughter cell during cell proliferation and characterized by a temporary elevation of its expression during initial steps of liver regeneration. It was shown that the androgen program of a high UEBP level was completely and stably formed after androgen action in hepatocytes of ovariectomized females and was fully transferred to daughter cells during hepatocyte proliferation. However experimentally formed androgen program of a high UEBP level in female hepatocytes was completely revealed only during early steps of liver regeneration (the 4th day), its expression was essentially declined after regeneration process was over.     

CD1 assembly and the formation of CD1-antigen complexes

The CD1 antigen presentation system presents lipid antigens to effector T cells, which have diverse roles in antimicrobial responses, antitumor immunity and in regulating the balance between tolerance and autoimmunity. The trafficking of CD1 molecules and lipid antigens facilitates their intersection and binding in specific intracellular compartments. Recent studies have now identified unexpected accessory molecules that are critical to CD1 assembly and lipid loading. The atomic structures of CD1-antigen complexes have defined both the orientation of polar headgroups between the alpha1 and alpha2 helices of CD1 and the manner in which distinct CD1 isoforms bind a range of lipids that have different lengths and numbers of hydrocarbon chains.     

In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locus.

Mutations at the phenylalanine hydroxylase (PAH) locus are the major cause of hyperphenylalaninemia. We have previously described four mutations (M1V, IVS12nt1, R408W, and S349P) at the PAH locus in French Canadians with ancestry in eastern Quebec. Here we report (1) identification of another mutation, on a haplotype 9 chromosome, which converts codon 65 from isoleucine (ATT) to threonine (ACT), (2) expression analysis of the I65T mutation in COS cells demonstrating 75% loss of both immunoreactive protein and enzyme activity, and (3) expression analysis of the most prevalent PKU allele (M1V) in eastern Quebec, showing nondetectable levels of PAH protein and activity, a finding compatible with a mutation in the translation initiation codon. Homozygosity for M1V and codominant inheritance of I65T/R408W were both associated with classical phenylketonuria.     

Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts

Purpose

Uncertainties remain regarding the clinical efficacy of ovarian tissue cryopreservation and grafting. We report a retrospective analysis of reproductive outcomes and lessons learnt following 55 ovarian tissue transplant procedures at our center from 2006 to 2019.

Methods

We analyzed variables related to graft success such as tissue volume, follicular density, total follicular volume, and age on the duration of graft function.

Results

Follicular density and total follicular volume correlate positively with duration of graft function. All clinical pregnancies in our cohort occurred in women who were aged 35 or less at the time of ovarian tissue cryopreservation.

Conclusion

Graft success, as determined by eventual pregnancy and the longevity of graft function, may be impacted by factors including age at cryopreservation, follicular density, and total follicular volume.

     

Comparison of action of the anti-neoplastic drug lonidamine on drug-sensitive and drug-resistant human breast cancer cells:31 P and 13C nuclear magnetic resonance studies

Lonidamine (LND) is a relatively new anti-cancer drug,and several clinical trials have indicated that it may be effectivein combinations with other therapeutic modalities. LND isclassified within the metabolic inhibitor agents. Multidrugresistance (MDR) phenomenon is often associated with increasedenergy requirements, and enhanced glycolysis rate. These studieswere performed to delineate the mechanism of action of LNDon MDR human breast cancer cells, and to investigate whetherLND as a single agent, or in combination with anotheranti-metabolism drug, 2-deoxyglucose (2-DG), may be usefulagainst MDR tumors. The effects of LND on intact perfuseddrug-sensitive (WT) and 33-fold resistant to Adriamycin(Adr) MCF-7 cells, embedded in alginate micro capsules, were continuouslymonitored by ³¹P and ¹³C nuclearmagnetic resonance (NMR) spectroscopy. ³¹PNMR studies showed that LND induced intracellular acidificationand depletion of NTP in both WT and Adr cells. However, pH and NTPlevels decreased less in the Adr cells than in the WT cells(p < 0.05 for both parameters). ¹³CNMR demonstrated that LND inhibited lactate transport,and lactate signals were elevated in both cell lines. However, theintracellular lactate levels increased to a greater extentin the WT than in the Adr cells (p < 0.05).There were major differences in the effects of LND onmetabolism between sensitive and resistant cells.While LND enhanced glucose uptake in the WT cells, and itsadministration was followed by continuous increase oflactate signal, both processes were not affected by LNDin the Adr cells. 2-DG is a glucose analogue that inhibitsboth cellular uptake and utilization of glucose, leading to cell starvation. Combined treatment with LND and2-DG yielded at best additive, but not synergistic,cellular toxicity, and the metabolic effects of LNDwere attenuated by 2-DG. These results showed that the principalmechanism of action of LND is inhibition of lactate transportleading to intracellular lactate accumulation and acidificationin both WT and Adr cells. The Adr cells were only 2-fold resistantto LND (compared to the WT cells), and since cellular uptakeof alkaloid chemotherapy is improved in acidic environment,LND may have a role in the treatment protocols of MDR tumors,especially when given as the initial means for inductionof intracellular acidification.