Replacement of aprotinin by ε-aminocaproic acid in infants undergoing cardiac surgery: consequences for blood loss and outcome.

BACKGROUND: Once aprotinin was no longer available for clinical use, ε-aminocaproic acid (EACA) and tranexamic acid became the only two options for antifibrinolytic therapy. We compared aprotinin and EACA with respect to their blood-sparing efficacy and other major clinical outcome criteria in infants undergoing cardiac surgery. METHODS: We retrospectively analysed data from a large consecutive cohort of infants (n=227) aged 31-365 days undergoing primary cardiac surgery requiring cardiopulmonary bypass encompassing the transition from aprotinin to EACA (aprotinin n=88, EACA n=139); all other aspects including the medical team and departmental protocols remained unchanged. The primary outcome was postoperative blood loss measured as chest tube output (CTO). Secondary outcome parameters were transfusion requirements, reoperation due to bleeding, renal, vascular, and neurological complications, and in-hospital mortality. RESULTS: CTO was significantly higher in the EACA patients {aprotinin 18 (13-27) ml kg(-1) 24 h(-1), EACA 23 (15-37) ml kg(-1) 24 h(-1) [mean (inter-quartile range)], P=0.001}, but transfusion requirements and donor exposures were not significantly different. A sensitivity analysis strengthened our finding that the increased blood loss in the EACA group was attributable to lower efficacy of EACA. There were no significant differences in the other clinical outcome measures. CONCLUSIONS: CTO was lower in aprotinin-treated patients. Nonetheless, EACA remains a suitable substitute without measurable differences in other clinical outcome criteria.

Switch from aprotinin to ε-aminocaproic acid: impact on blood loss, transfusion, and clinical outcome in neonates undergoing cardiac surgery.

BACKGROUND: With the withdrawal of aprotinin from worldwide marketing in November 2007, many institutions treating patients at high risk for hyperfibrinolysis had to update their therapeutic protocols. At our institution, the standard was switched from aprotinin to ε-aminocaproic acid (EACA) in all patients undergoing cardiac surgery with extracorporeal circulation including neonates. Although both antifibrinolytic medications have been used widely for many years, there are few data directly comparing their blood-sparing effect and their side-effects especially in neonates. METHODS: Perioperative data from 235 neonates aged up to 30 days undergoing primary cardiac surgery were analysed. Between July 1, 2006 and November 5, 2007, all patients (n=95) received aprotinin. Starting November 6, 2007 until December 31, 2009, all patients (n=140) were treated with EACA. The primary outcome criterion was blood loss; secondary outcome criteria were transfusion requirements, renal, vascular, and neurological complications and also in-hospital mortality. RESULTS: All descriptive and intraoperative data variable were similar. Blood loss was significantly higher in the EACA group (P=0.001), but there was no difference in the rate of re-operation for bleeding (P=0.218) nor the number of transfusions. There were no differences in the incidences of postoperative renal, neurological, and vascular events or in-hospital mortality. CONCLUSIONS: In neonatal patients undergoing cardiac surgery, the switch to EACA treatment led to a higher postoperative blood loss. However, there were no differences in transfusion requirements or major clinical outcomes.

Comparison of blood-sparing efficacy of ε-aminocaproic acid and tranexamic acid in newborns undergoing cardiac surgery.

BACKGROUND: ε-Aminocaproic acid (EACA) and tranexamic acid (TXA) are used for antifibrinolytic therapy in neonates undergoing cardiac surgery, although data directly comparing their blood-sparing efficacy are not yet available. We compared two consecutive cohorts of neonates for the effect of these two medications on perioperative blood loss and allogeneic transfusions. MATERIAL AND METHODS: Data from the EACA group (n = 77) were collected over a 12-month period; data from the tranexamic acid group (n = 28) were collected over a 5-month period. Blood loss, rate of reoperation due to bleeding, and transfusion requirements were measured. RESULTS: There was no significant difference in blood loss at 6 hours (EACA 24 [17-30] mL/kg [median (interquartile range)] vs. TXA 20 [11-34] mL/kg, P = 0.491), at 12 hours (EACA 31 [22-38] mL/kg vs. TXA 27 [19-43] ml/kg, P = 0.496) or at 24 hours postoperatively (EACA 41 [31-47] mL/kg vs. TXA 39 [27-60] mL/kg; P = 0.625) or transfusion of blood products. CONCLUSIONS: ε-Aminocaproic acid and tranexamic acid are equally effective with respect to perioperative blood loss and transfusion requirements in newborns undergoing cardiac surgery.

Reliability of quantitative reverse-transcriptase-PCR-based detection of tumour cells in the blood between different laboratories using a standardised protocol.

Differences in methods of reverse-transcriptase (RT)-polymerase chain reaction (PCR)-based detection of tumour cells in the blood gives rise to conflicting results, and standardisation is urgently needed. This pilot study aimed to assess the variation of RT-PCR-based detection of tumour cells in blood between four different laboratories using a commercially available kit with a standardised protocol. This kit allows comparison of results from different laboratories and facilitates the investigation of the influence of pre-analytical parameters. All laboratories analysed identical sets of blood samples spiked with tumour cells in a concentration range of 1-100 tumour cells/ml. To study at which level variation was introduced, three kinds of sample sets were generated in which (i) tumour cell RNA was spiked in the RNA of mononuclear cells (MNC), (ii) tumour cells were spiked in isolated MNC, and (iii) tumour cells were spiked in blood. Real-time quantitative RT-PCR was used to detect and quantify cytokeratin 20 (CK20) expression, which is indicative for the presence of epithelial tumour cells. All laboratories were able to detect CK20 expression in all spiked-RNA samples with limited variation in expression levels between laboratories. There was a positive correlation between the amount of spiked tumour cell RNA and CK20 expression level. RT-PCR analysis of spiked-MNC samples resulted in more variation in the CK20 expression levels between laboratories, however again all spiked samples were reported to be positive by all of the laboratories. The evaluation of spiked-blood samples gave rise to considerable quantitative and qualitative variation between the laboratories. Our results underline the importance and need for standardisation and extended quality control studies in the field of pre-analytics.

Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood.

BACKGROUND: The detection of disseminated tumor cells in peripheral blood is limited by the presence of very few tumor cells within a large number of blood cells. Therefore, tumor cell detection calls for enrichment systems with effective depletion of blood cells and high tumor cell recovery. METHODS: We compared the new density gradient centrifugation method OncoQuick with the standard method of Ficoll. The enriched cell fractions were quantified. Tumor cell spiking experiments examined the recovery of tumor cells as detected by immunocytochemistry and cytokeratin-20 reverse transcriptase-polymerase chain reaction (RT-PCR). Clinical application of OncoQuick was evaluated in 37 peripheral blood samples of patients with gastrointestinal carcinomas. RESULTS: The depletion of mononuclear cells (MNCs) in the enriched cell fraction after OncoQuick centrifugation was 632-fold, with an average cell number of 9.5 x 10(4), compared with Ficoll, with a depletion factor of 3.8 and a mean number of 1.6 x 10(7) MNCs. The mean tumor cell recovery rates were 87% for OncoQuick and 84% for Ficoll. The increased depletion of MNCs with OncoQuick centrifugation further simplified immunocytochemical evaluation by reducing the number of cytospins and increasing the tumor cell density. Due to the reduced number of co-enriched MNCs by OncoQuick, the blood volume, which could be analyzed in one RT-PCR reaction, was increased up to 30 ml. Examination of peripheral blood samples from 37 patients with gastrointestinal tumors showed a cytokeratin-20 detection rate of 30% and a significant correlation with the presence of distant metastases (P < 0.02). CONCLUSIONS: OncoQuick significantly reduced the co-enriched number of MNCs, with a high tumor cell recovery rate. Processing blood from tumor patients with OncoQuick increased the chance of detecting circulating tumor cells.

Dexmedetomidine: a novel sedative-analgesic agent.

Since the first report of clonidine, an alpha2-adrenoceptor agonist, the indications for this class of drugs have continued to expand. In December 1999, dexmedetomidine was approved as the most recent agent in this group and was introduced into clinical practice as a short-term sedative (<24 hours). Alpha2-adrenoceptor agonists have several beneficial actions during the perioperative period. They decrease sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; reduce anesthetic and opioid requirements; and cause sedation and analgesia. They allow psychomotoric function to be preserved while letting the patient rest comfortably. With this combination of effects, alpha2-adrenoceptor agonists may offer benefits in the prophylaxis and adjuvant treatment of perioperative myocardial ischemia. Furthermore, their role in pain management and regional anesthesia is expanding. Side effects consist of mild to moderate cardiovascular depression, with slight decreases in blood pressure and heart rate. The development of new, more selective alpha2-adrenoceptor agonists with improved side effect profiles may provide a new concept for the administration of perioperative anesthesia and analgesia. This review aims to give background information to improve understanding of the properties and applications of the novel alpha2-adrenoceptor agonist, dexmedetomidine.

Different radiosensitivity of smooth muscle cells and endothelial cells in vitro as demonstrated by irradiation from a Re-188 filled balloon catheter.

There is an increasing interest in irradiation to control restenosis after balloon angioplasty by an internal radioactive source. Differences in radiosensitivity of the predominant cells of the human coronary artery (i.e. endothelial cells (HCAEC), smooth muscle cells from the media (HCMSMC) and from plaque material (HCPSMC), are issues of controversal discussion. Therefore, we investigated the graded inhibition of cells by irradiation from a balloon catheter filled with a high-energy beta-emitter (Rhenium-188) in vitro. HCPSMC, HCMSMC and HCAEC were cultured and irradiated with increasing dose from 7.5 to 37.5 Gy at a dose rate of 1.5+/-0.3 Gy/min. After irradiation, bromodeoxyuridine (BrdU) was added and cells were fixed 18 h later. In a limited field opposite to the balloon, the number of BrdU-positive cells were analysed in comparison to non-irradiated controls. Significant inhibition was demonstrated in HCPSMC and HCMSMC at 7.5 Gy while HCAEC needed 22.5 Gy for similar effects. The antiproliferative effect was dose dependent in all cell strains. The effect of irradiation with 22.5 Gy on smooth muscle alpha-actin, vimentin, and alpha-tubulin of HCPSMC and HCMSMC and on von Willebrand factor (vWF), vimentin, and alpha-tubulin of HCAEC was investigated by means of indirect immunofluorescence. Within 18 h after irradiation no effect on cytoskeletal components and vWF was documented. This in vitro study demonstrates that irradiation inhibits HCMSMC and HCPSMC at lower dose rates compared to HCAEC.

Acute mastoiditis: a 10-year review.

PURPOSE: To study how antibiotic treatment and an early decision to aspirate subperiosteal abscesses can reduce hospitalization periods and costs in patients with acute mastoiditis. PATIENTS AND METHODS: During a 10-year period, 134 patients were diagnosed with acute mastoiditis at the Department of Ear, Nose, and Throat and Head and Neck Surgery (Kaplan Medical Center, Rehovot, Israel). The diagnoses was based on physical findings of retroauricular swelling and erythema and tenderness, with protrusion of the auricle forward and downward. The majority of patients (77) reached medical treatment during the first 3 days of their disease. Wide myringotomy and intravenous antibiotic treatment, aspiration, and complete cortical mastoidectomy were the treatment options. RESULTS: With the administration of wide myringotomy and intravenous antibiotic treatment, 115 patients recovered; nine received aspiration and did not need surgery; and only 15 patients who received the antibiotic treatment needed a complete cortical mastoidectomy. CONCLUSION: With the wise use of antibiotics and early decision to aspirate subperiosteal abscesses, the hospitalization period, the cost, and the need for surgery can be reduced.

A comparison of purging and nonpurging eating-disordered outpatients: mediating effects of weight and general psychopathology.

OBJECTIVES: The present study compared purging and nonpurging eating-disordered outpatients on key behavioral and psychological features of their disorder. It also investigated the possible mediating effects of current level of depression, anxiety or general psychopathology, and current weight on differences between purgers and nonpurgers. METHOD: Seventy-seven patients from an outpatient eating disorder clinic who purged were compared to 48 clinic patients who did not purge on measures of eating behavior disturbances and specific psychopathology while controlling for weight, level of depression, anxiety, and general distress. RESULTS: Purgers reported significantly more eating behavior disturbance and higher scores on measures of specific psychopathology than the nonpurgers. These differences were unrelated to current weight, level of anxiety, or general distress. However, severity of depression did moderate some of the difference between the groups. CONCLUSION: These data provide further support for the proposition that purging is a distinctive clinical marker in all types of eating-disordered patients.

Evolution and evaluation of a medical psychiatric unit.

In 1991, the first Medical Psychiatric Unit (MPU) in Australia was established at the Royal Prince Alfred Hospital, Sydney. The processes involved in introducing it to the hospital staff and administration, as well as its structure and criteria for admission, are described. Its development was compared to the experiences of others in North America over the past 15 years. The functioning of the MPU over the subsequent 2 years was evaluated by assessing demographic and clinical criteria of patients admitted. Data were obtained from patient medical records and compared with similar data on patients admitted to a General Psychiatric Unit (GPU). It was found that patients of the MPU tended to be older, more often male, and suffering from organic brain syndromes and/or alcohol or drug abuse. Despite the multiplicity of diagnoses and the complexity of treatment procedures, the MPU patients' duration of stay was similar to the GPU patients'. The MPU was found to have achieved goals of clinical and cost-effectiveness. It has become an established subunit within the Department of Psychiatry.

Psychosocial Outcome and Long-term Weight Loss after Gastric Restrictive Surgery for Morbid Obesity.

Forty-five of 60 consecutive morbidly obese patients who had a vertical banded gastroplasty carried out by the one surgeon between 1982 and 1988 were assessed by questionnaire at long-term follow-up in 1993. Eighteen patients (40%) had maintained their BMI at close to the lowest achieved levels. Twenty-seven patients (60%) had had a significant rise in BMI, and 14 of these (31%) had gained weight to return close to or above their pre-surgery BMI levels. No reliable predictors of successful long-term weight loss were detected in the pre-operative data. Forty-eight patients (84%) were satisfied with their surgical treatment. Twenty patients (44%) reported improved social life after surgery. Twenty-one patients (46%) reported a similar social life and only four patients (9%) a worse social life. At follow up five patients (12%) reported emotional problems related to their weight loss surgery and two of this group had had psychiatric counseling for depression. Pre-operative psychiatric assessment appeared to have facilitated intervention by the psychiatrist with these patients. Gastric restrictive surgery, however, remains unpredictable in its long-term weight loss effect.

Ionic signalling in mast cells; antigen and ionophore induced changes in cytosolic pH.

Stimulation of cells of the rat basophilic leukemia line RBL-2H3, which are used as a model in biochemical studies of mast cells, by antigen or by the calcium ionophore ionomycin, are known to cause secretion of mediators of inflammation. These stimuli have now been found to cause a decrease in the cells' cytosolic pH. This acidification process was monitored by the fluorescent indicator 2',7'-bis (carboxyethyl)-5(6)-carboxyfluorescein (BCECF) introduced into these cells. The antigen induced acidification was the result of specific aggregation of membrane residing IgE, reached values up to 0.03 pH units and required the presence of sodium and calcium ions in the incubation medium. It was amiloride resistant but was blocked by the metabolic inhibitor deoxyglucose. Ionomycin caused a dose dependent decrease in cytosolic pH which was also sensitive to the pH of the extracellular medium. The acidification reached more than 0.1 pH units at optimal, non-cytotoxic, doses of ionomycin (1 microM) and decreased markedly as the medium pH increased from 7.0 to 8.0. The antigen and ionophore induced cytosolic acidification processes are interpreted as being the result of the increased concns of free cytosolic calcium ions rather than the effect of direct activation of a sodium-proton exchanger. Further investigation of this process is in progress.

Anorexia nervosa in a woman totally blind since birth.

A 19-year-old woman, blind since birth, lost 26 kg over a 7-month period. This was achieved by restriction of food intake, excessive exercise, laxative abuse, and self-induced vomiting. Although the visual experience is often believed to be an integral component of body-shape perception and the overvaluation of thinness in contemporary society, it does not preclude the development of anorexia nervosa.

Comparison of the effects of pancuronium and tubocurarine on different muscles of young and old mice.

In order to evaluate the sensitivity of different muscle types to neuromuscular blocking drugs, a system using mouse muscles in vitro was developed and applied to detect changes in drug sensitivity in relation to age. The effect of pancuronium and tubocurarine on initial twitch and on the ratio of fourth twitch to first twitch (T4/T1) of a train-of-four at 2 Hz were compared in fast-twitch, slow-twitch and respiratory muscles in the mouse. The muscles used were: extensor digitorum longus (EDL), soleus (SOL) and diaphragm (DIA). For both drugs the order of decreasing sensitivity was EDL greater than SOL greater than DIA. This result was the same whether first twitch or T4/T1 was used, although the latter was a more sensitive indicator. The sensitivity of neuromuscular block was less in muscles from old (30-33 month) animals than in the equivalent muscles from young (8-12 month) animals.

Pre-operative psychiatric assessment of patients presenting for gastric bariatric surgery (surgical control of morbid obesity).

One hundred and fifty-three consecutive patients referred to the Royal Prince Alfred Hospital for consideration of gastric bariatric surgery (surgery for obesity) were assessed pre-operatively by the one psychiatrist, with regard to social, psychological and psychiatric factors. Fifty-one patients (33%) were considered to be uncomplicated from a psychiatric point of view. Eighty-eight patients (58%) had identifiable psychopathology and 14 patients (9%) were of doubtful motivation. Thirty patients (20%) were rejected from the treatment programme after the initial assessment because of overt psychiatric illness, severe situational stress, insufficient motivation or lack of significant support. Six of these patients after further assessment or after responding to psychiatric treatment were reviewed and found suitable for a bariatric operation. Of the 113 patients who had a bariatric procedure performed, 17 patients (15%) required postoperative psychiatric management. while the need for psychiatric assessment of patients presenting for bariatric surgery is disputed by some, our experience would indicate that careful pre-operative screening by a liaison psychiatrist, familiar with morbid obesity and its surgical management, is useful in any bariatric surgical programme. Such screening should identify and enable exclusion of the small number of patients who for psychiatric reasons, are poor risk candidates. A number of other patients in whom identifiable psychopathology will be discerned, will require pre-operative psychiatric management. While such a programme will decrease postoperative psychiatric problems, these will not be eliminated in the morbidly obese, and the assessing liaison psychiatrist will have a valuable role to play in the collaborative postoperative management of such patients.

Aural tuberculosis: a series of 25 patients.

Twenty-five patients with thirty ears affected by tuberculosis of the middle ear cleft were diagnosed and treated at Groote Schuur Hospital, Cape Town, during the years 1972 to 1983. This series is a sequel to the series of 1967 to 1971 and reported by Sellars and Seid (1973). The classical disease presentation will be reviewed and compared to that found in our patients. The modern trends in diagnosis and management will be discussed. The emphasis is on early diagnosis and treatment in an eminently curable disease.

Tuberculous laryngitis--a one year harvest.

We present nine patients with tuberculous laryngitis seen in our otolaryngology out-patient department during the year of 1983. Four patients were previously diagnosed as having pulmonary tuberculosis and were receiving or had received treatment for the complaint prior to our consultation. Of the nine patients, eight had positive chest X-rays for pulmonary tuberculosis. Three patients were known to have positive sputum results; in three patients the result was not known, whilst in the remaining three patients the result was recorded as negative. Biopsies done on four patients were compatible with the diagnosis of tuberculous laryngitis. Two of these four were undisputedly confirmed by the presence of Acid-fast Bacilli on histological sections. Two patients demonstrated permanent structural derangement of the larynx as end-result manifestations. The incidence, site and appearance of the lesions, diagnosis and treatment are discussed.

Paragangliomas of the petrous temporal bone.

The natural behaviour, clinical diagnosis and treatment of paragangliomas of the petrous temporal bone are reviewed. Nine patients with this tumour treated at Groote Schuur Hospital are presented; 2 patients had tympanic paragangliomas and 7 jugular paragangliomas. Surgical excision is recommended as the primary treatment. However, in poor-risk patients or when tumour growth is extensive, irradiation may be of benefit. Although rare, this eventually life-threatening lesion can be successfully removed if diagnosed early enough.