Pain syndromes in the setting of haematopoietic stem cell transplantation for haematological malignancies.

Severe pain syndromes may be recorded during all phases of haematopoietic stem cell transplantation (HSCT) for haematological malignancies: from stem cell mobilization to the long-term post transplant period. Although the major cause of pain in the setting of HSCT is injury to mucosal tissues induced by the conditioning regimen, pain from several other causes has been reported. In this paper, we review pain and its management in the setting of HSCT.

Detection of alpha 1-antitrypsin from recombinant Escherichia coli lysates utilizing the particle concentration fluorescence immunoassay.

A particle concentration fluorescence immunoassay for the quantitative determination of human alpha 1-antitrypsin in Escherichia coli is described. The principle advantages of this system are speed, automation and a high level of sensitivity compared with enzyme assays and Western blot analysis. Two monoclonal antibodies recognizing different epitopes on the protein are used for the detection and quantitation of alpha 1-antitrypsin. This method has a measured range of 30-2500 ng/ml with a mean accuracy of 5.5% and a precision of 5.1%.

Mu3 opiate receptor expression in lung and lung carcinoma: ligand binding and coupling to nitric oxide release.

The mu3 opiate receptor subtype is expressed in human surgical specimens of both normal lung and non-small-cell lung carcinoma. Nitric oxide (NO) release is mediated through the mu3 receptor, and in lung carcinoma, morphine-stimulated NO release is significantly higher and prolonged than in normal lung. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis we show that specific mu opioid receptor transcripts are present in lung carcinoma and other cells with the mu3 profile. Our findings identify a unique role for the mu3 opiate receptor in opiate-mediated NO release and suggest that endogenous opiates, through their release of NO, may play a role in cancer progression.

Effect of local anesthetic ropivacaine on isolated rat liver mitochondria.

Ropivacaine is a new long-acting aminoamide local anesthetic with a reduced systemic and cardiac toxicity. Since the latter seems to be related, at least partially, to an interference with mitochondrial energy transduction, the effect of ropivacaine on the metabolism of rat liver mitochondria was studied. Ropivacaine alone exhibited little effect on mitochondrial metabolism, whereas effects were strongly enhanced by tetraphenylboron (TPB-) anion. At low drug concentrations, state 4 respiration was stimulated and mitochondrial membrane potential collapsed. At higher concentrations, state 4 and uncoupled respiration were inhibited by impairment of electron transfer from NAD- and flavine adenine dinucleotide-linked substrates to the respiratory chain. The fact that TPB- increased drug effects indicated that stimulation of respiration was due to dissipation of the electrochemical proton gradient caused by its electrophoretic uptake, although a classical uncoupling mechanism cannot be excluded. The mechanism for the lower toxicity of ropivacaine in vivo was ascribed to low liposolubility leading to reduced access to the mitochondrial membrane, resulting in a minimal perturbation of mitochondrial metabolism.

Toxic shock syndrome due to group C streptococci. A case report.

BACKGROUND: Streptococcal toxic shock-like syndrome is a life-threatening illness which is on the increase. In early reports, only group A beta-hemolytic streptococcus was associated with the disease, but recent evidence indicates non-A streptococci groups are also involved. OBSERVATIONS: We describe the first reported case of streptococcal toxic shock-like syndrome caused by a group C strain in Italy. Prior to the disease, the patient, a 46-year-old man, had been in good health and had only a 3-day history of sore throat, low grade fever, vomiting, diarrhea, and myalgia before admission. Initially, diagnosis was based only on clinical evidence: shock, multiorgan failure, profound hypothermia, and no apparent signs of infection. Toxic cardiomyopathy was also present. RESULTS: Positive throat swab and blood culture confirmed a "definite case" following established criteria. Anamnesis showed a diagnosis of monoclonal gammopathy. Antibiotic treatment was begun immediately on admission of the patient, who was discharged 20 days later in good health. CONCLUSIONS: This case illustrates how an early diagnosis and prompt antibiotic therapy can determine a more favorable outcome.

Effect of the local anesthetic bupivacaine on the energy metabolism of Ehrlich ascites tumor cells.

The effect of the local anesthetic bupivacaine on the energy metabolism of Ehrlich ascites tumor cells has been investigated. Even at low concentrations, bupivacaine decreased the oxygen uptake rate, but its effect was remarkably higher on the uncoupled respiration. Experiments on specific segments of the respiratory chain have shown that bupivacaine did not inhibit electron transport from Q to oxygen. Spectroscopic evidences demonstrated a NAD(P)H oxidation in bupivacaine-treated cells respiring on endogenous substrates, indicating that the inhibition of oxygen depended on a reduced electron transport from site 1-entering substrates to respiratory chain. The aerobic glycolysis was stimulated by low and inhibited by high bupivacaine concentrations. The increased lactate production rate was due to an activation of mitochondrial ATPase, whereas its decrease was related to an inhibition of the hexokinase activity.

Effect of local anesthetic ropivacaine on the energy metabolism of Ehrlich ascites tumor cells.

The effect of local anesthetic ropivacaine on the energy metabolism of Ehrlich ascites tumor cells has been investigated. Ropivacaine impaired energy metabolism of Ehrlich ascites tumor cells by affecting primarily mitochondrial metabolism. Even at low concentrations ropivacaine decreased the rate of oxygen uptake, but its effect was remarkably higher on the uncoupled respiration and, in both cases, it was strongly enhanced by hydrophobic anion tetraphenylboron (TPB-). The decrease of oxygen uptake was ascribed to an impairment of electron transport from site 1- and 2-entering substrates to respiratory chain. The inhibition of respiration, coupled to a true uncoupling mechanism by an electrophoretic mechanism, impaired ADP phosphorylation, decreased ATP content, and collapsed mitochondrial membrane potential. Ropivacaine, at all concentrations tested, stimulated aerobic lactate production, and this increase, in addition to the inhibition of respiration, was also due to an activation of mitochondrial ATPase.

Changes in membrane potential induced by local anesthetic bupivacaine on mitochondria within Ehrlich ascites tumor cells.

The effect of the local anesthetic bupivacaine on transmembrane potential of mitochondria within Ehrlich ascites tumor cells has been investigated by the safranine method. The following summarizes the results. 1) When Ehrlich ascites tumor cells were added into a medium containing safranine, a differential spectrum with a decrease at 520 nm appeared. The addition of bupivacaine did not reverse the response but resulted in a spectrum similar to that observed with deenergized mitochondria, with a maximum at 550 nm and a minimum at 495 nm. 2) The addition of glucose to bupivacaine- or rotenone-treated cells also produced a shift in safranine spectrum similar to that observed upon energization of mitochondrial membranes by ATP, thus suggesting that glycolytically generated ATP was responsible for this spectral change. 3) The ability of bupivacaine to decrease the membrane potential in mitochondria within Ehrlich ascites tumor cells was due to two different effects: inhibition of the energy-conserving site 1 of the respiratory chain and uncoupling by a true protonophoretic mechanisma.

Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.

Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation ("empty head") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.

Peritonectomy and hyperthermic antiblastic perfusion in the treatment of peritoneal carcinomatosis.

AIMS: Some low-grade malignant tumours arising in the abdomen tend to remain loco-regionally confined to peritoneal surfaces, without systemic dissemination. In these cases complete surgical tumour cytoreduction followed by intra- or post-operative regional chemotherapy has curative potential. The aim of this study was to evaluate the outcome for patients treated in this way. METHODS: Peritonectomy was performed, involving the complete removal of all the visceral and parietal peritoneum involved by disease. After peritonectomy, hyperthermic antiblastic perfusion was carried out throughout the abdominopelvic cavity for 90 min, at a temperature of 41.5-42.5 degrees C, with mitomycin C (3.3 mg/m2/l) and cisplatin (25 mg/m2/l) (for appendicular or colorectal primaries), or cisplatin alone (for ovarian primaries). Alternatively, the immediate post-operative regional chemotherapy was performed with 5-fluorouracil (13.5 mg/kg) and Lederfolin (125 mg/m2) (for colonic or appendicular tumours) or cisplatin (25 mg/m2) (for ovarian tumours), each day for 5 days. RESULTS: Thirty-five patients affected by extensive peritoneal carcinomatosis were submitted to peritonectomy, with no residual macroscopic disease in all cases except three. Twenty-six patients were able to undergo the combined treatment involving loco-regional chemotherapy. Complications were observed in 54% of the patients and led to death in four of them. At a mean follow-up of 17 months overall 2-year survival was 55.2%, with a median survival of 26 months. CONCLUSIONS: After a learning curve of 18 months the feasibility of the integrated treatment increased to more than 90%, while mortality decreased dramatically. The curative potential of the combined therapeutic approach seems high in selected patients with peritoneal carcinomatosis not responding to systemic chemotherapy. Careful selection of patients can minimize the surgical risk, but the treatment should currently be reserved for clinical trials.

Systemic and haemodynamic toxicity after isolated limb perfusion (ILP) with TNF-alpha.

The aim of this study was to evaluate the systemic and haemodynamic postoperative effects of ILP with medium-low dose of TNF alpha in patients diagnosed with primary or recurrent limb melanoma or sarcoma, and to compare the resulting toxicity with Systemic Inflammatory Response Syndrome (SIRS). A prospective study on 17 consecutive patients with primary or recurrent limb tumor (melanoma or sarcoma) subjected to ILP with escalating doses of TNF alpha (0.5-2.0mg) was carried out. Seventeen patients with primary or recurrent limb melanoma or sarcoma were subjected to ILP with escalating doses of TNF alpha. ILP was carried out with the standard techniques, blood being warmed at 42 degrees C for an hour. Serial serum TNF alpha determinations were performed before, during and after limb perfusion in nine patients. Systemic and pulmonary haemodynamics, by a radial and pulmonary artery catheter inserted before the induction of anesthesia, were monitored at 5 different times: before the induction of anesthesia (T0), and 6, 12, 24 and 48 hours after treatment (T1-4). Complete isolation of the limb was not always achieved, therefore leakage of TNF alpha occurred frequently during the perfusion in all patients with maximum systemic TNF alpha concentrations ranging from 431 to 111000 pg/ml. After perfusion only two patients showed detectable TNF alpha levels in peripheral blood which returned to baseline values within nine hours. These two patients had serious systemic toxicity: shock and respiratory failure secondary to pulmonary edema. Acute pulmonary edema was also observed in another patient. All three cases required supportive therapy provided by means of mechanical ventilation. In the remaining 14 patients a sepsis-like syndrome was observed. The most significant haemodynamic changes were due to the CO, which rose by 35%, and the SVR, which remained consistently low throughout. A reduction in Hb was observed in all patients (with an average decrease of 4 g/dl), while DO2 and VO2 levels rose, though not to statistically significant levels. Hypoxia occurred in all 14 patients. In three of the remaining 14 cases bilateral pulmonary leaks were noted, however the use of mechanical ventilation was not required. No perioperative death occurred and the aforementioned side effects were all reversible resulting in a patient's mean postoperative ICU permanence of 4 days (range 3 to 7 days). In conclusion, ILP with TNF alpha induces cardiovascular, respiratory and hematological toxicity with haemodynamic parameters being similar to those noted in SIRS probably due to leakage of TNF alpha in the systemic circulation during the perfusion. Nevertheless, this systemic toxicity was short-lived resulting in an acute reaction following a single application.

The integrated treatment of peritoneal carcinomatosis. A preliminary experience.

Some low-grade malignant tumors arising in the abdomen, lack of infiltrative attitude and "redistribute" on the peritoneum with no extraregional spreading. In this cases the complete tumor cytoreduction followed by intra- or postoperative regional chemotherapy has curative intent. Peritonectomy is the complete removal of all the parietal peritoneum and the visceral peritoneum involved by disease. After peritonectomy hyperthermic antiblastic perfusion is carried out throughout the abdomino-pelvic cavity for 60 minutes, at a temperature of 41.5 degrees C, with mitomycin C (3.3 mg/m2/Lt of perfusate) and cisplatin (25 mg/m2/Lt) (appendicular or colorectal primary), or cisplatin alone is (ovarian primary). Alternatively the immediate postoperative regional chemotherapy is performed with 5-fluorouracil (13.5 mg/Kg) and Lederfolin (125 mg/m2) (colic or appendicular tumor) or cisplatin (25 ng/m2) (ovarian tumor), each day for 5 days. Twenty patients affected by extensive peritoneal carcinomatosis (12 ovarian, 5 colonic, 1 appendicular, 1 mesothelial and 1 gastric primary) were submitted to peritonectomy with no residual macroscopic disease in all cases except three. Six patients were treated with intraoperative intra-abdominal hyperthermic antiblastic perfusion, while immediate postoperative intra-abdominal chemotherapy was given in 4 patients and systemic chemotherapy in other 5. Hospital mortality was 20%. At a mean follow-up of 11 months 14 patients are alive, 11 without disease and the median overall survival is 10.2 months. The curative potential of the combined therapeutic approach seems high in patients with peritoneal carcinomatosis from ovarian or colorectal primary not responding to systemic chemotherapy. Selection criteria of patients can strictly affect the surgical risk and the treatment has to be reserved for controlled clinical trials.

Pulse pressure as a function of cuff width.

Pulse pressure was investigated by indirect sphygmomanometry using two different cuff widths, standard (12 cm) versus correct (20% wider than arm diameter). Following the American Heart Association's recommendation for arterial pressure measurements, 7 cuffs of various widths (8 to 14 cm) were used as correct cuffs on 900 subjects; in only 50 was the standard cuff appropriate. Pulse pressure as a function of cuff width was significantly lower (P less than 0.001) with the standard cuff on subjects with diastolic pressure less than 90 mmHg (36.4 +/- 0.3 mmHg vs 41.8 +/- 0.3 mmHg) and above 90 mmHg (39.6 +/- 1.2 mmHg vs 43.8 +/- 1.3 mmHg). Mean systolic and diastolic arterial pressures were underestimated by 12.7 mmHg and 7.7 mmHg, respectively. These results suggest that cuff width influences data obtained by indirect sphygmomanometry, producing over- or underestimates when the ratio of arm circumference to cuff width differs from 0.38.

Complications with fully implantable venous access systems in oncologic patients.

AIMS: To evaluate the complications caused by long-term central venous catheterization in patients with malignant hemopathies or solid tumors. METHODS: Retrospective study from June 1988 to June 1993 in 211 consecutive patients who required 223 venous access devices for long-term use. A consistent analysis was possible only in 161 of these patients. RESULTS: Fourteen catheter systems were removed for complications. Infections were the most common complications, with an overall incidence rate of 9.6%, i.e. 0.033/100 catheter days/patient. A significant difference was noted between the two groups of patients: 10 cases (24%) in malignant hemopathies, 6 cases (4.8%) in solid tumors (P = 0.0002). The main mechanical complication was thrombosis, with an incidence rate of 3%. CONCLUSIONS: Given the cost-benefit ratio, our study indicates that fully implantable venous access systems in oncologic patients are extremely useful.

Neuroadenolysis of the pituitary.

The authors describe the neuroadenolysis of the pituitary (NALP), an original antalgic technique consisting in the injection of small amounts of alcohol into the sella turcica. Used for diffuse pain from advanced cancer, NALP determines, in addition to the antalgic effect, a temporary regression in the evolution of the neoplastic disease in approximately 30% of the cases of hormonedependent tumors. The consequences and complications are generally not very serious, allowing the use of this technique in poor-risk patients. The authors also discuss the results, the mechanism of the antalgic effect and the studies carried out with a view to defining such mechanism. To this end, the authors stress the importance of the electrophysiological approach and described the first experiments involving the technique of cortical evoked potentials in patients who have undergone NALP. (Acta anaesth. belg., 1981, 32, 87-99).

[Transdermal route as an alternative to oral administration of opioids in cancer pain]. / La via transdermica come alternativa agli oppioidi per os nel dolore oncologico.

Fentanyl TTS, the only transdermal opioid, represents a real tool for a better quality of life in patients with cancer pain. In this paper we report a short description of the pharmacologic properties and administration procedures of this drug that is a useful alternative when other opioids recommended on the third step of the WHO analgesic ladder, are ineffective or present unbearable side effects (nausea and/or vomiting-severe mucosites and dysphagia). In particular we indicated some changes and adjustments switching from morphine per os to fentanyl TTS. In addition we report the results of a study carried out in our Pain Therapy Center on 49 patients with severe oncologic pain, previously treated with opioids and other drugs associations. Our results indicated a good control of continuous nociceptive cancer pain, with a better quality of life and lesser side effects to respect the previous regime of orally opioids.

[Blood pressure measurement in pregnancy]. / Medida da pressão arterial em gestante.

This study deals with the review of the literature regarding the indirect blood pressure measurement in normal pregnant women. It shows the changes that happened with the blood pressure due to pregnancy. Polemical aspects in the procedure of blood pressure measurement are discussed; for example, which one of the Korotkoff phases (4 or 5) that better represent the diastolic blood pressure and the use of Ambulatory Blood Pressure Monitoring in pregnancy. The recommendations from different societies are emphasized (American Heart Association, British Hypertension Society, Australasian Society, National High Blood Pressure Education Program and World Health Organization).

[Effect of anatomical and physiological factors on the indirect blood pressure measurement: identification of nurses' knowledge]. / Influência de fatores anátomo-fisiológicos na medida indireta da pressão arterial: identificação do conhecimento dos enfermeiros.

The study was developed by clinical nurses specialized in cardiology and had the purpose to characterize the knowledge about the conceptual aspects and the anatomical and physiological factors that interfere in the marks of blood pressure.

Is early diagnosis of hypertension a function of cuff width?

This study followed blood pressure in 11 subjects 5 years after slight or established hypertension had been revealed using a cuff of the correct width (appropriate to arm circumference); at that time, the use of a standard-width cuff (12 cm) had shown a blood pressure within the normal range. For the present study, blood pressure was determined indirectly under very strict conditions so that a faithful comparison between the readings with both cuffs could be achieved. An important underestimate of blood pressure was detected in thin arms when the standard width cuff was used. The present measurements showed a consistent increase in blood pressure with standard-width cuff readings, confirming the hypertension that had been identified using the correct cuff width 5 years previously. These results support our previous hypothesis that early diagnosis of hypertension can be masked by the standard-width cuff, particularly in lean persons.

[The indirect measurement of arterial pressure: a review]. / Medida indireta da pressão arterial: revisão.

This study deals with the indirect arterial blood pressure measurement, particularly the American Heart Association recommendations for sphygmomanometry References are made regarding the ratio arm circumference/cuff width and the errors caused by inadequate cuff size. Several variables involved in the procedure of arterial blood pressure measurement are discussed.