Delayed muscular rigidity and respiratory depression following fentanyl anesthesia

A delayed effect of fentanyl used for anesthesia may be respiratory distress several hours after surgery. The findings are muscular rigidity, fall in chest wall compliance, hypoventilation, respiratory acidosis, and hypotension. In the past, to our knowledge, this complication was exclusively reported in patients undergoing cardiac surgery, when large fentanyl dosages are employed. This article describes three general surgical patients in whom respiratory distress developed three to five hours following colon surgery when a moderate dose of fentanyl citrate, 55 to 75 micrograms/kg, was used. Initially, all patients had a normal recovery from anesthesia. Later, respiratory distress was successfully treated with a fentanyl antagonist and ventilatory assistance. This delayed toxic phenomenon is thought to be due to the reentry of fentanyl into plasma from deposits in adipose tissue, muscle, and the gastrointestinal tract, leading to a secondary rise in the plasma concentration. It is more likely to be encountered when hypothermia, rewarming, and acidosis are present in the postoperative period. This life-threatening complication is treacherous, since it may occur when the patient has been transferred to the surgical ward and is less closely monitored.     

Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.

The exact opioid-sensitive receptors participating in EtOH-seeking behaviors remains unclear. Previous studies have reported higher densities of micro-opioid receptor binding in the nucleus accumbens (NACC) of P relative to NP rats; however, no differences were seen in delta-receptor binding. In contrast to the NACC, substantially lower levels of micro-receptor binding have been observed in the ventral tegmental area (VTA) of both P and NP rats, albeit no line differences have been observed. In the present study, opioid receptors in the NACC, VTA, and hippocampus were evaluated for their capacity to regulate both EtOH- and saccharin-motivated behaviors in the genetically selected alcohol-preferring (P) rat. To accomplish this, nalmefene, an opiate antagonist with preferential binding affinity for the micro-opioid receptor was unilaterally or bilaterally infused during concurrent availability of 1 h daily EtOH (10% v/v) and saccharin (0.025 or 0.050% w/v) solutions. Rats performed under a two-lever fixed ratio (FR) schedule in which four responses on one lever produced the EtOH solution, and four on a second lever produced the saccharin solution. The results demonstrated that when responding maintained by both EtOH and saccharin are matched at basal levels, unilateral (1-60 microg) or bilateral (0.5-10 microg) microinjections of nalmefene into the NACC produced selective dose-dependent reductions on responding maintained by EtOH. Unilateral (40, 60 microg) and bilateral (10 microg) VTA infusions were also observed to selectively reduced EtOH responding; however, greater nalmefene doses were required and the magnitude of suppression on EtOH responding was markedly less compared with the NACC. The greater sensitivity of nalmefene to suppress EtOH responding in the NACC is likely due to the greater number of opioid receptors in the NACC relative to the VTA. Only bilateral infusion of the 40 microg dose in the NACC and VTA suppressed responding maintained by both EtOH and saccharin. In contrast, intrahippocampal infusions dose dependently suppressed EtOH- and saccharin-maintained responding over a range of doses (1-20 microg). The present study provides evidence that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.     

Nuclear morphometry and DNA flow cytometry as prognostic factors in female breast cancer.

OBJECTIVE--To evaluate the predictive value of traditional prognostic factors, nuclear morphometry, and flow cytometric data in invasive breast cancer. DESIGN--Open study. SETTING--One university hospital in Finland. SUBJECTS--248 women with invasive breast cancer followed up for more than 11 years. MAIN OUTCOME MEASURES--Univariate and multivariate analysis of factors thought to indicate prognosis. RESULTS--Diameter of the tumour, lymph node status, S phase fraction. DNA index, the age of the patient, and the SD of nuclear perimeter were significant independent predictors in the whole series in a multivariate analysis. In node negative patients the SED of the nuclear perimeter and diameter of the tumour had independent prognostic value, whereas in node positive patients diameter of the tumour and the S phase fraction were independently related to survival. CONCLUSIONS--Diameter of the tumour is an important prognostic factor in breast carcinomas. Histoquantitative methods are superior to conventional histological techniques for the prediction of outcome in women with breast cancer.     

Ability of ketanserin to block different receptors in human placental vessels

5-Hydroxytryptamine (5-HT), noradrenaline (NA) and histamine induced concentration-dependent contractions in segments of human chorionic arteries and veins, whereas clonidine, an alpha 2-adrenoceptor agonist, had no effect. 5-HT and histamine induced strong contractions, while NA elicited weak contractions in some segments. The maximal response was similar for 5-HT and histamine. The order of potency (EC50 values) was: 5-HT greater than or equal to NA greater than or equal to histamine. These agonists induced tachyphylaxis, and single concentrations caused transient contractions. Contractions elicited by 5-HT were antagonized by ketanserin, a 5-HT2-receptor antagonist, which also antagonized the responses to NA and histamine, but at greater concentrations than those needed for 5-HT responses. Contractions elicited by histamine were reduced by diphenydramine. Low concentrations of 5-HT amplified contractions caused by NA and histamine. The results indicate that: (i) 5-HT is the most potent constrictor agent tested in these vessels; (ii) its effects are mediated by 5-HT2-receptors; and (iii) ketanserin at therapeutic plasma concentrations (10(-7) M) seems to block mainly 5-HT2-receptors, and alpha 1-adrenergic- and H1-receptors to a small extent only.     

Early changes in hemoglobin and hematocrit levels after packed red cell transfusion in patients with acute anemia

BACKGROUND: Equilibration of hemoglobin concentration after transfusion has been estimated to take about 24 hours, but some studies have shown that earlier measurements reflect steady-state values in persons who have not bled recently. This study was aimed at assessing the changes over time in hemoglobin concentration after transfusion in acutely anemic patients because of recent bleeding. STUDY DESIGN AND METHODS: Thirty-two normovolemic patients recovering from an acute bleeding episode who were no longer thought to be bleeding and who received a 2- unit red cell transfusion were studied. At baseline and 15, 30, 60, and 120 minutes and 24 hours after transfusion, hemoglobin concentration and hematocrit values were measured. RESULTS: The administration of 2 units of packed red cells elicited a 24-hour increase of 22.4 +/− 6.8 g per L in hemoglobin concentration. Hemoglobin values were not different at any of the defined posttransfusion times. Hematocrit levels experienced similar changes over time. Agreement between 15-minute and 24-hour values was excellent, as only 6 percent of patients exhibited a clinically significant difference (> 6 g/L) between the hemoglobin measurements. CONCLUSION: Hemoglobin and hematocrit values rapidly equilibrate after transfusion in normovolemic patients who are recovering from an acute bleeding episode. This fact would allow a rapid assessment of the effects of transfusion and of the recurrence of bleeding in patients remaining at risk.     

HBV-DNA sequences are rarely detected in the liver of patients with HBsAg-negative chronic active liver disease and with hepatocellular carcinoma in Italy

Hepatitis B virus sequences were studied by molecular hybridization in liver biopsies from patients with HBsAg-negative chronic liver disease or hepatocellular carcinoma, collected in Italy. Among the 42 patients with chronic liver disease who had no history of drug addiction, alcohol abuse nor evidence of metabolic and autoimmune disorders, only two (5%) had HBV-DNA sequences in the liver, although 23 of them (57%) were positive for antibodies to HBV in serum. HBV-DNA was also demonstrated in integrated form in the tumorous tissue of one out of eight cases with HBsAg-negative hepatocellular carcinoma. These incidences of HBV-DNA positivity in the liver are lower than those reported from other Mediterranean areas and similar to those of North Europe, United States and Japan, suggesting that etiologic factors other than HBV are responsible for the majority of HBsAg-negative chronic liver diseases in our region.     

Clinical and molecular study in congenital muscular dystrophy with partial laminin alpha 2 (LAMA2) deficiency

Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients.