Management of haematoma after thyroid surgery: systematic review and multidisciplinary consensus guidelines from the Difficult Airway Society, the British Association of Endocrine and Thyroid Surgeons and the British Association of Otorhinolaryngology, Head and Neck Surgery.

Haematoma after thyroid surgery can lead to airway obstruction and death. We therefore developed guidelines to improve the safety of peri-operative care of patients undergoing thyroid surgery. We conducted a systematic review to inform recommendations, with expert consensus used in the absence of high-quality evidence, and a Delphi study was used to ratify recommendations. We highlight the importance of multidisciplinary team management and make recommendations in key areas including: monitoring; recognition; post-thyroid surgery emergency box; management of suspected haematoma following thyroid surgery; cognitive aids; post-haematoma evacuation care; day-case thyroid surgery; training; consent and pre-operative communication; postoperative communication; and institutional policies. The guidelines support a multidisciplinary approach to the management of suspected haematoma following thyroid surgery through oxygenation and evaluation; haematoma evacuation; and tracheal intubation. They have been produced with materials to support implementation. While these guidelines are specific to thyroid surgery, the principles may apply to other forms of neck surgery. These guidelines and recommendations provided are the first in this area and it is hoped they will support multidisciplinary team working, improving care and outcomes for patients having thyroid surgery.

Feasibility of brachytherapy as monotherapy for high-volume, low-risk prostate cancer.

BACKGROUND: We sought to determine whether patients with high-volume, low-risk prostate cancer are suitable candidates for ultrasound-guided brachytherapy, monotherapy alone, without supplemental external beam radiation. MATERIALS AND METHODS: The study cohort comprised 200 consecutive patients who received ultrasound.guided monotherapy from November 02, 1998 to March 26, 2010. Real.time intraoperative treatment planning was performed for all patients. 145. Gy with I125 was prescribed to the prostate with no margin. The primary endpoint was time to prostate-specific antigen. (PSA) failure using the phoenix definition. Cox multivariable regression analysis was used to determine the factors significantly associated with time to PSA failure. RESULTS: Median follow-up was 59 months (range 1.2-146.8 months). The median PSA was 5.0 ng/ml. For the overall cohort, both 5- and 8-year PSA failure-free survival was 92.3% (95% confidence interval [95% CI]: 86.5-95.7%). Low-risk patients per the NCCN criteria had 5- and 8-year PSA failure-free survival of 93.6%. On cox multivariable analysis, only baseline PSA (adjusted hazard ratio: 1.29 [95% CI: 1.02-1.65], P = 0.036) was associated with outcome. Among patients with Conclusions: Our analysis indicates that patients with a high number of cores positive for cancer can be adequately treated with modern brachytherapy as monotherapy and be spared the additional morbidity and cost of supplemental external beam radiation or androgen deprivation therapy.

Cancer control and complications of salvage local therapy after failure of radiotherapy for prostate cancer: a systematic review.

The National Comprehensive Cancer Network guidelines currently endorse salvage local therapy as a reasonable alternative to observation or androgen-deprivation therapy for select men with a biopsy-proven local recurrence after definitive radiation for prostate cancer. Patients being considered for salvage therapy should have had localized disease at presentation, a prostate-specific antigen < 10 at recurrence, a life expectancy >10 years at recurrence, and a negative metastatic workup. In this systematic review, we synthesize the current literature describing the oncologic efficacy and toxicity profile of salvage brachytherapy, prostatectomy, cryotherapy, and high-intensity focused ultrasound. We found 5-year biochemical control rates to be similar across treatments, in the range of 52%-56%, although patient selection and definition of failure was variable. Toxicity profiles were also distinct between local salvage modalities.

Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation.

AIM: To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α (p38-MAPKα), Extra Cellular-Signal Regulated Kinase (ERK) and c-Jun NH2-Terminal Kinase (JNK) activity, in the pathogenesis of type 1 diabetic pre-eclampsia, and the putative modulation of these indices by maternal vitamin C and E supplementation. METHODS: Placental samples were obtained from a sub-cohort of the DAPIT trial: a randomised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy. Placenta from placebo-treated: normotensive (NT) [n=17], gestational hypertension (GH) [n=7] and pre-eclampsia (PE) [n=6] and vitamin-treated: NT (n=20), GH (n=4) and PE (n=3) was analysed. Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue. Catalytic activities of placental p38-MAPKα, ERK and JNK were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Nitrotyrosine immunostaining was present in placebo-treated NT, GH and PE placentae, with no significant difference observed between the groups. There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae. ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity. CONCLUSION: Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy, possibly due to inherent oxidative stress and peroxynitrite production. Our results suggest that p38-MAPKα, ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation.

The training & support programme for parents of children with ataxia: a pilot study.

The aim of the study was to evaluate the impact of the Training and Support Programme among parents of children with ataxia. A total of 39 parents expressed an interest in the TSP, 27 (mean age 41; range 25-58) returned baseline questionnaires and completed the study. Twenty-four children (mean age 12.5 years, SD=12.4) received the TSP. Data were collected by self-administered questionnaires mailed to parents immediately before attending the TSP and at 4-month follow-up. Interviews were conducted with 10 parents immediately following TSP completion. Comparisons over time revealed significant decreases in parental anxious mood (p=.011), depressed mood (p=.046) and perceived stress (p=.020) and significant improvements in generalized self-efficacy (p=.010), satisfaction with life (p=.045) and parental health status (p=.020). Parents reported improvements in children's mobility, "jumping legs", sleep patterns, energy and activity levels, relaxation, and happiness (e.g., more smiles). Parents felt closer to their children and one parent had become "more accepting" of their child's ataxia. Results indicate that the TSP may enhance the psychosocial well-being of parents of children with ataxia although a randomized controlled trial would be necessary to determine whether the changes reported here are in fact due to attending the TSP.

Seminal plasma trace metal levels in industrial workers.

This study compares the seminal plasma trace metal levels of hospital workers with groups of industrial workers in a petroleum refinery, smelter, and chemical plant. The metals measured were the essential metals (copper, zinc, nickel, cobalt, and manganese) and the toxic metals (lead, cadmium, and aluminum). The group mean +/- SE metal level for each group (50 subjects per group) was calculated, and the statistical significance of the group mean differences of the industrial groups with the hospital group (control) was determined by the Student's t-test. The differences observed in the smelter group were increased copper and zinc (p < or = 0.001) and decreased nickel, cobalt, and manganese (p < or = 0.001, < or = 0.01). The refinery group differences were increased copper, zinc, and nickel (p < or = 0.001) but decreased cobalt and manganese (p < or = 0.001). The chemical group differences were increased zinc (p < or = 0.001) and decreased cobalt (p < or = 0.001). The seminal plasma levels of the toxic metals lead and aluminum were increased in each of the industrial groups (p < or = 0.001). Concurrent differences were (1) decreased accumulation of nickel, cobalt, and manganese in the smelter group, (2) decreased cobalt and manganese in the refinery group, and (3) only decreased cobalt in the chemical group.

Management of hemochromatosis. Hemochromatosis Management Working Group.

The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management. Therapeutic phlebotomy is used to remove excess iron and maintain low normal body iron stores, and it should be initiated in men with serum ferritin levels of 300 microg/L or more and in women with serum ferritin levels of 200 microg/L or more, regardless of the presence or absence of symptoms. Typically, therapeutic phlebotomy consists of 1) removal of 1 unit (450 to 500 mL) of blood weekly until the serum ferritin level is 10 to 20 microg/L and 2) maintenance of the serum ferritin level at 50 microg/L or less thereafter by periodic removal of blood. Hyperferritinemia attributable to iron overload is resolved by therapeutic phlebotomy. When applied before iron overload becomes severe, this treatment also prevents complications of iron overload, including hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy. In patients with established iron overload disease, weakness, fatigue, increased hepatic enzyme concentrations, right upper quadrant pain, and hyperpigmentation are often substantially alleviated by therapeutic phlebotomy. Patients with liver disease, joint disease, diabetes mellitus and other endocrinopathic abnormalities, and cardiac abnormalities often require additional, specific management. Dietary management of hemochromatosis includes avoidance of medicinal iron, mineral supplements, excess vitamin C, and uncooked seafoods. This can reduce the rate of iron reaccumulation; reduce retention of nonferrous metals; and help reduce complications of liver disease, diabetes mellitus, and Vibrio infection. This comprehensive approach to the management of hemochromatosis can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity.

Effect of the microtubular inhibitor vinblastine on ferritin clearance and release in the rat.

We have previously demonstrated that colchicine inhibits ferritin clearance from the circulation of normal and iron-loaded rats and stimulates endogenous ferritin release into both the serum and bile of iron-loaded rats. The aim of the present study was to determine the effect of vinblastine on ferritin clearance and release in normal and iron-loaded rats. Vinblastine was administered at either 1 or 10 mg/kg to both normal and iron-loaded rats, infused over a 5 h period with either a rat liver ferritin or saline solution. Serum and biliary ferritin levels were determined every 30 min. After 5 h, 90% of the infused ferritin was cleared from the circulation in the absence of vinblastine. Low-dose vinblastine decreased ferritin uptake 10-20% in iron-loaded rats. High-dose vinblastine inhibited ferritin clearance by 25% in normal rats and 20-40% in iron-loaded rats. Vinblastine administration caused a 2-3-fold increase in the serum ferritin concentration and a 3-5-fold peak in biliary ferritin levels. Thus, vinblastine caused the release of endogenous ferritin into both the serum and bile of iron-loaded rats in the presence of a ferritin load. We therefore conclude that disturbed microtubule function accounts for the observed inhibition of ferritin uptake and intracellular transport; however, the mechanism of increased ferritin release remains unclear.

Molecular cloning of a partial cDNA of a novel gene in iron metabolism.

In order to elucidate the possible role played by human hepatic ferritin-associated protein in normal cellular iron metabolism and in iron overload diseases, malignancies and hepatic fibrosis, we attempted to isolate genes for ferritin associated proteins. Here we describe the cloning of a novel cDNA fragment of a 10 kb mRNA transcript from human liver and human T lymphoid (MOLT-4) cells using a short degenerate 5'-primer derived from six amino acid residues of an affinity purified ferritin associated protein from human liver. Northern analysis of this clone has revealed the presence of a 10 kb mRNA species in both human liver and MOLT-4 cell RNA.

Molecular cloning of a novel mRNA highly expressed in haemochromatotic human liver and proliferating cells.

Pathological changes arising in altered cell biology and diseases such as cancer are driven by changes in gene expression. In the inherited disease haemochromatotis (HC) progressive iron loading of the parenchymal cells (hepatocytes) of the liver leads to cellular toxicity. If left untreated, fibrosis, cirrhosis and ultimately liver cancer occur. By using differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) techniques, we have identified and isolated several differentially displayed mRNAs that are excessively expressed or repressed in HC liver compared to normal human liver. One of these mRNAs was found to be strongly expressed in the liver of a patient with HC and in tumour tissue from a subject with hepatocellular carcinoma complicating HC (HC/HCC). The message of this gene was detected at a very low level in normal human liver. Northern analysis showed that this gene is also expressed in lymphocytes of HC patients and in MOLT-4 human T-lymphoid cells irrespective of iron status. The partial 1.0 kb cDNA sequence of the 9.5 kb transcript of this gene is unique and we propose that this gene may be related to cell proliferation and HC/HCC human liver.

Tyrosine 27 of the specificity polypeptide of EcoKI can be UV crosslinked to a bromodeoxyuridine-substituted DNA target sequence.

The specificity (S) subunit of the restriction enzyme EcoKI imparts specificity for the sequence AAC(N6)GTGC. Substitution of thymine with bromodeoxyuridine in a 25 bp DNA duplex containing this sequence stimulated UV light-induced covalent crosslinking to the S subunit. Crosslinking occurred only at the residue complementary to the first adenine in the AAC sequence, demonstrating a close contact between the major groove at this sequence and the S subunit. Peptide sequencing of a proteolytically-digested, crosslinked complex identified tyrosine 27 in the S subunit as the site of crosslinking. This is consistent with the role of the N-terminal domain of the S subunit in recognizing the AAC sequence. Tyrosine 27 is conserved in the S subunits of the three type I enzymes that share the sequence AA in the trinucleotide component of their target sequence. This suggests that tyrosine 27 may make a similar DNA contact in these other enzymes.

Early intervention for alcohol use: family physicians' motivations and perceived barriers.

OBJECTIVE: To elucidate family physicians' motivations concerning early intervention for alcohol use and their perceived barriers to such intervention. DESIGN: Qualitative study with the use of focus groups and semistructured interviews. SETTING: Community-based, fee-for-service family-medicine practices in London, Ont. PARTICIPANTS: Twelve focus-group participants recruited through telephone contact by two family physicians on the project team. Participants were required to be physicians in family practice in London. Twelve interview participants recruited through a grand-rounds presentation at two local hospitals. Participants were required to be physicians in a community-based family practice in which primary care was not delivered by residents and to have agreed to participate in all phases (e.g., needs assessment, training and evaluation) of a training program on interventions to help patients reduce alcohol consumption or quit smoking. MAIN OUTCOME MEASURES: Motivations concerning early intervention for alcohol use and perceived barriers to such intervention, as identified by physicians. RESULTS: Physicians in the focus groups and those interviewed endorsed their role in helping patients to reduce alcohol consumption and cited several reasons for the importance of that role. There was strong support for viewing alcohol use as a lifestyle issue to be dealt with in the context of a holistic approach to patient care. Participants cited many barriers to fulfilling their role and were particularly concerned about the appropriateness of asking all adolescent and adult patients about alcohol use, even at visits intended to discuss other issues and concerns. Physicians gave several motivations for improving their work in reduction of alcohol consumption, including their current frustration with the lack of a systematic strategy or tangible materials to help them identify and manage patients. CONCLUSIONS: Interventions with patients who use alcohol should be framed in the context of a holistic approach to family medicine. Qualitative knowledge of the motivations and barriers affecting physicians can inform future research and educational strategies in this area.

Establishment of a cell line from a hepatocellular carcinoma from a patient with hemochromatosis.

We describe the establishment and characterization of a novel hepatoma cell line. This cell line, designated RBHF-1, was established from a hepatocellular carcinoma of a 67-yr-old man with a history of genetic hemochromatosis. At this writing, the cells have been maintained in RPMI-1640 tissue-culture medium and fetal calf serum without any additional supplements for 30 mo. The cells form colonies on soft agar and are not tumorigenic in nude mice. The cell line is polymorphic and displays characteristics of mature hepatocytes by synthesizing albumin, alpha 2-macroglobulin, fibronectin and alpha-fetoprotein. Cytogenetic analysis shows multiple chromosomal aberrations, with a consistent deletion in the long arm and deletions or rearrangements in the short arm of chromosome 1. There is no evidence for hepatitis B or hepatitis C virus infection of the cell line. The cells contain no detectable intracellular iron after staining with Perls' stain. Unlike other hepatoma cell lines, there is no detectable binding of epidermal growth factor to RBHF-1 cells. This is the first cell line to be established from a patient with hemochromatosis, and it provides a potentially important model for the study of hepatocyte transformation in association with iron overload.

Effect of ascorbic acid supplementation on the sperm quality of smokers.

OBJECTIVE: To determine the effect of ascorbic acid supplementation on the sperm quality of heavy smokers. DESIGN: Microscopic examination of semen for 1 month during supplementation with placebo or ascorbic acid at dose levels of 200 or 1,000 mg/d. SETTING: Department of Obstetrics and Gynecology, The University of Texas Medical Branch. PARTICIPANTS: Seventy-five men (20 to 35 years old) randomly divided into one of three supplementation groups: placebo, 200 mg and 1,000 mg of ascorbic acid. MAIN OUTCOME: Improvement in sperm quality as compared with presupplementation levels and between the three treatment groups. RESULTS: The placebo group showed no improvement in sperm quality. The groups receiving ascorbic acid showed improvement in sperm quality with most improvement in the 1,000-mg group. Pearson's correlation showed statistically significant relationships between the weekly group means of serum and seminal plasma ascorbic acid levels and sperm qualities. CONCLUSIONS: Ascorbic acid supplementation of heavy smokers in excess of 200 mg/d results in improved sperm quality.

The clinical manifestations of chronic iron overload.

Primary or genetic haemochromatosis is an inherited disease characterized by an inappropriate degree of iron absorption with accumulation of excessive amounts of tissue iron. Parenchymal iron accumulation results in the typical clinical features of the disease including hepatic cirrhosis, diabetes, testicular atrophy and skin pigmentation. The disease is inherited in an autosomal recessive manner. The gene for the disease has not been identified but is tightly linked to the A locus of the histocompatibility complex on chromosome 6. The approximate homozygote frequency in Caucasians is 0.3% with an equal sex ratio. Excessive body iron stores have been described in a number of other conditions, particularly alcoholic liver disease. There is increasing evidence that many of these individuals are in fact also suffering from genetic haemochromatosis. Diagnostic tests including serum iron, transferrin saturation, serum ferritin and liver iron concentration make it possible to detect sufferers of the disease. Screening relatives of affected individuals with these tests allows a diagnosis to be made before permanent tissue damage has occurred. Removal of excess iron stores by repeated phlebotomy is the primary treatment. If iron is removed before significant tissue damage has occurred, the complications and natural course of the disease will be prevented provided reaccumulation of iron does not occur. Excessive iron accumulation with resultant organ damage also occurs in anaemias associated with ineffective erythropoiesis and after excessive parenteral iron administration or repeated blood transfusions. Similar clinical features may be seen. Chelation therapy is the mainstay of treatment in these cases where long-term venesection is not possible.

Influence of alcohol and caffeine consumption on caffeine elimination.

Ten healthy male volunteers were each studied on four separate occasions to assess the role of regular caffeine and alcohol intake on caffeine elimination. Antipyrine disappearance was also studied as an established quantitative test of hepatic microsomal function. Regular caffeine intake in high doses for 1 week failed to alter either antipyrine or caffeine pharmacokinetics. In contrast, alcohol intake of 50 g/day significantly prolonged caffeine half-life by 72% (P less than 0.005) and diminished caffeine clearance by 36% (P less than 0.0005). However, antipyrine kinetics were unaltered. These results demonstrate that alcohol, in amounts commonly consumed, is a strong inhibitor of caffeine metabolism.

Decreased response of human milk leukocytes to chemoattractant peptides.

To test the hypothesis that neutrophils and macrophages in human milk may not defend by classical inflammatory mechanisms, experiments were conducted to ascertain whether adherence, orientation, and directed motility of these leukocytes would be enhanced by exposure to chemoattractant peptides including N-formyl-L-methionyl-L-phenylalanine and N-formyl-L-methionyl-L-leucyl-L-phenylalanine and C5a generated from zymosan activated human serum. Adherence and spatial orientation were tested on coverglasses and in Zigmond chambers, and chemotaxis was examined by Boyden chambers and a subagarose technique. Whereas, the adherence, orientation, and directed movement of adult peripheral blood neutrophils and monocytes were significantly enhanced by those chemotactic agents, human milk leukocytes failed to respond. The failure of the response of human milk leukocytes was not due to alterations in maternal peripheral blood leukocytes but appeared to be due partially to inhibitors in human milk. The experiments suggest that human milk leukocytes may be modified in the mammary gland to protect by noninflammatory mechanisms.

Drug metabolism in liver disease. Identification of patients with impaired hepatic drug metabolism.

Antipyrine half-life (AP t1/2) was measured in 62 patients with, and 10 control patients without, liver disease to ascertain possible factors which may be useful in identifying patients with abnormal drug metabolism. Antipyrine metabolism was normal or marginally impaired in patients with compensated cirrhosis or acute hepatitis, whereas it was frequently abnormal in those with chronic active hepatitis or advanced alcoholic liver disease. A high degree of correlation was found among AP t1/2 and prothrombin time, hepatic encephalopathy, and ascites. Of patients with severely impaired drug metabolism, 80% had one or more of these features. The severity of histological changes in liver biopsies was of additional help in predicting impaired drug metabolism. Concurrent drug ingestion enhanced antipyrine metabolism in most patients with liver disease as well as in control patients. Inadequate diet was associated with prolongation of AP t1/2, but other environmental factors such as alcohol ingestion, cigarette smoking, and coffee consumption did not affect rates of drug metabolism in patients with liver disease. Consideration of all of the above factors allows qualitative predictions of the rate of hepatic drug metabolism in patients with liver disease, as assessed by the AP t1/2.