Liver operations in Sweden in 1987-99.

BACKGROUND AND AIMS: Liver surgery is developing with new techniques and treatment modalities. The aim of this study is to describe liver surgery over a long period of time in a country with a public health care system. PATIENTS AND METHOD: A register study including adult patients admitted for liver resection in Sweden (population 8.8 million) selected from the Inpatient Register 1987-99. Additional data were collected from the Swedish Cancer Register and the Cause of Death Register. Analyses of the patients, indications, mortality and causes of death are presented. RESULTS: 2,405 operations were performed (21 per million per year). The most frequent indication was colorectal metastases (27%). The 5-year survival after an operation for primary liver cancer and colorectal liver metastases was 27% and 26%, respectively. CONCLUSIONS: Few patients were admitted for liver operations compared to expected figures. The survival rates are in conformity with those previously published. With an increasing awareness of the relatively favourable prognosis and the introduction of new methods, the volume of liver operations will probably increase in Sweden.     

Effects of PEEP on extra vascular lung water and central blood volume in the dog

Twenty-four mongrel dogs were anaesthetized and ventilated mechanically in the supine position. Extravascular lung water (EVLW) and central blood volume (CBV) were measured with a double indicator (dye/cold) dilution technique. Both indicators were detected intravascularly in the aortic root with a fibreoptic thermistor catheter. Seven dogs ventilated with a positive end-expiratory pressure (PEEP) of 1.0 kPa (10 cmH2O) for a short period of time (less than 20 min) displayed no significant change in EVLW as measured with the indicator dilution technique (= EVLWi), while reductions were seen in both CBV (15%, P less than 0.01) and cardiac output (CO-thermodilution technique) (10%, P less than 0.05). Another seven dogs ventilated with a PEEP of 1.0 kPa for 8 h showed a gradual increase in EVLWi. After 8 h, a mean increase of 34% (P less than 0.01) was recorded, and the increase was also verified by post-mortem gravimetric determination of EVLW (= EVLWg), displaying an increase of 61% (P less than 0.01). In five dogs ventilated with zero end-expiratory pressure (ZEEP) for 8 h, no changes in EVLWi, CO, and CBV were observed, and EVLWg was mean 4.39 g/kg body weight (BW). Five additional dogs were sacrificed after 15 min of anaesthesia without catheterization and EVLWg was found to be 4.24 g/kg BW. It is concluded that EVLWi does not change measurably during ZEEP or short periods of PEEP. However, long periods (8 h) of PEEP result in elevated EVLWi values. Gravimetry supports these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)     

The combination of radiotherapy, adjuvant chemotherapy (cyclophosphamide-doxorubicin-ftorafur) and tamoxifen in stage II breast cancer. Long-term follow-up results of a randomised trial.

Two hundred patients with node positive stage II breast cancer were randomised to four groups after radical mastectomy and axillary evacuation: (1) Postoperative radiotherapy, (2) Adjuvant chemotherapy with eight courses of CAFt (cyclophosphamide 500 mg m-2 + doxorubicin 40 mg/m-2 + ftorafur 20 mg kg-1 orally day 1-14) every fourth week, (3) Postoperative radiotherapy and adjuvant chemotherapy and (4) postoperative radiation, adjuvant chemotherapy and tamoxifen 40 mg daily for 2 years. Thirty-two per cent of the patients discontinued treatment due to GI-toxicity, while 26% required dose reductions due to leukopenia. Radiation pneumonitis was more frequent after the combination of postoperative radiotherapy with chemotherapy. There was a better relapse-free survival in the groups receiving chemotherapy compared to radiotherapy alone (P = 0.05), which was highly significant in a multivariate Cox analysis (P = 0.004). No significant survival differences were seen. Tamoxifen had no clear overall effect but there were better relapse-free (P = 0.04) and overall (P = 0.004) survival with tamoxifen in estrogen receptor positive patients, while estrogen receptor negative patients had a somewhat poorer survival (P = 0.07) after tamoxifen. Local control was better (NS) after the combination (93%) radiotherapy and chemotherapy compared to either treatment alone (76% with radiotherapy and 74% with chemotherapy at 5 years).     

A placebo controlled trial of remoxipride in the prevention of relapse in chronic schizophrenia

Sixty-two DSM III chronic schizophrenic inpatients were selected for a double-blind, placebo controlled, multi-centre, relapse prevention study of remoxipride, a selective dopamine (D₂)-receptor antagonist. After a 1 month placebo washout, 23 patients had relapsed and were withdrawn. Of the remaining patients 19 were randomised to remoxipride (150–300 mg daily) and 20 to placebo. Their median age was 58 years, 26 were male, and the median duration of illness was 33 years. After 24 weeks a further total of 8 remoxipride and 17 placebo patients had been withdrawn. Excluding three patients withdrawn for reasons other than relapse, the comparative relapse rates were 37% and 75%, respectively (P=0.015). Efficacy analyses using clinical global impression (P=0.04) and change in BPRS scores (P=0.016) were in favour of remoxipride. Extrapyramidal symptoms were minimal in both groups. Treatment emergent adverse events were similar in the two groups. Remoxipride is therefore of potential value as a safe drug which is both effective and well tolerated in the long term management of chronic schizophrenic patients.     

Cutaneous lymphocyte antigen expression on human effector B cells depends on the site and on the nature of antigen encounter

In contrast to T cells, information on skin-homing B cells expressing the cutaneous lymphocyte antigen (CLA) is sparse. CLA expression on human B cells was investigated among circulating immunoglobulin-secreting cells (ISC) and among antigen-specific antibody-secreting cells (ASC) elicited by parenteral, oral or rectal primary immunization, or by parenteral or oral secondary immunization with Salmonella typhi Ty21a. CLA expression was examined by combining cell sorting with an enzyme-linked immunospot assay. Among all ISC, the proportion of CLA(+) cells was 13-21%. Parenteral immunization induced antigen-specific ASC of which 13% were CLA(+), while oral and rectal immunizations were followed by only 1% of CLA(+) ASC (p<0.001). Oral re-immunization was followed by an up-regulation of CLA (34-48%) regardless of the route of priming. Parenteral re-immunization elicited ASC of which 9-14% were CLA(+). In conclusion, the expression of CLA on human effector B cells depends on the site of antigen encounter: intestinal stimulation elicits cells with no CLA, while parenteral encounter elicits significant numbers of CLA(+) cells. Even though primary antigen encounter in the intestine failed to stimulate CLA expression, up-regulation of CLA was found upon intestinal antigen re-encounter. These findings may be of relevance in the pathogenesis of some cutaneous disorders.     

The central projection of muscle afferent fibres to the lower medulla and upper spinal cord: an anatomical study in the cat with the transganglionic transport method

The projection of muscle afferent fibres to the medulla oblongata and upper spinal cord was studied in the cat by using transganglionic transport of wheat germ agglutinin-horseradish peroxidase conjugate. The results demonstrate a precise, musculotopic termination pattern in the external cuneate nucleus; thus, fibres from the intrinsic muscles of the paw terminate medially; those from forearm, arm, and shoulder muscles terminate progressively more laterally; and those from neck and thoracic muscles terminate in the ventrolateral and dorsolateral parts, respectively. Muscle afferent fibres to the main cuneate nucleus terminate in the ventral "reticular" region of the nucleus, with a sparse projection also to the ventral part of the rostral and caudal regions, including the base of the dorsal horn. Fibres from the neck muscles terminate slightly more laterally in the ventral region than do those from the limb muscles, but otherwise, and thus contrary to the case in the external cuneate nucleus, no topographic organization was detected. In the spinal cord, projection was found to laminae I and V, and from the musculature of the back of the neck to the central cervical nucleus.     

Pharmacokinetics and antipsychotic effect of remoxipride in chronic schizophrenic patients

Single dose pharmacokinetics and the antipsychotic effect of 4 weeks treatment with three fixed dose levels of remoxipride (a selective D(2) receptor antagonist) were studied in chronic, stable schizophrenic inpatients. After a placebo washout of 1 month, 15 patients entered the study. Of these, 11 patients received a single 50 mg oral dose of remoxipride for pharmacokinetic evaluations. All 15 patients were randomly assigned to treatment with oral remoxipride either 25 mg t.i.d., 50 mg t.i.d. or 100 mg t.i.d. for 4 weeks. Blood samples for remoxipride and prolactin assays were taken at 0, 0.33, 0.5, 0.66, 1.0, 1.5, 2, 3, 4, 8, 12, 24, 28, 32 and 48 h after drug intake. The pharmacokinetic characteristics were similar to those previously found in normal healthy volunteers: the mean peak plasma concentration of remoxipride after 50 mg was 3.3 μmol/l, the mean time to reach this was 2.1 h; the mean area under the plasma concentration/time curve was 27.8 μmol/1.h.1( -1) and the mean elimination half-life of remoxipride was 5.5 h. A significant increase in prolactin levels was detected 2 h after administration of remoxipride but they had reverted to normal 8 h after drug intake in all but one patient. Antipsychotic effects were estimated using the brief psychiatric rating scale (BPRS) and the Krawiecka rating scale (KRS) at admission, baseline (end of the 4 week placebo washout period) and after 7, 14 and 28 days treatment. Following an increase in mean psychosis ratings for both positive and negative symptoms during the placebo washout period, these decreased during active treatment and at the end of the study were similar to the scores on admission. Thus the possible efficacy of remoxipride in chronic patients with negative symptoms should be further explored in placebo controlled studies. Remoxipride was well tolerated. Sleep disorders occurred in three patients, extrapyramidal symptoms were not aggravated and no clinically significant effects were observed on the cardiovascular system, in clinical chemistry or haematology.     

The yohimbine-induced anticonflict effect in the rat,part I. Involvement of noradrenergic,serotonergic and endozepinergic(?) mechanisms

Summary The ₂-adrenoceptor antagonist yohimbine has in several previous studies been found to produce anticonflict effects comparable to those produced by the benzodiazepines (BDZ) in rat punished conflict models. In this and a following paper we have tried to elucidate the neurochemical mechanisms underlying these effects in a modified Vogel's drinking conflict test. Since yohimbine previously has been demonstrated to interfere both with noradrenaline (NA) and serotonin (5-HT) neurochemistry, and, in addition, shows affinity for the BDZ binding site, we have focused on the putative involvement of these neuronal systems in the yohimbine-induced anticonflict effect. The ₂-adrenoceptor agonist clonidine (10 g/kg, i.p.) completely antagonized the anticonflict effect of yohimbine (4.0 mg/kg, i.p.), whereas the ₁-adrenoceptor agonist ST 587 (1.0 mg/kg, i.p.) had no effect. The anticonflict effect of yohimbine was totally abolished also following lesioning of NA neurons with 6-hydroxy-dopamine. A high dose of the mixed ₁ and ₂ adrenoceptor antagonist propranolol (8.0 mg/kg, i.p.) caused a partial blockade of the yohimbine-induced effect in intact animals, whereas the selective ₁-adrenoceptor antagonist metoprolol (4.0 mg/kg, i.p.) had no significant effect and the ₁-adrenoceptor antagonist prazosin instead potentiated the anticonflict action. The anticonflict effect of yohimbine was dose-dependently antagonized also by the 5-HT precursor L-5-hydroxytryptophan (25–100 mg/ kg, i.p.). The BDZ receptor antagonist flumazenil (10 mg/kg, p.O.), as well as Ro 15-4513 (1.0 mg/kg, p.o.), a partial inverse agonist at BDZ receptors, partly, but significantly, counteracted the yohimbine-induced anticonflict effect, whereas low doses of both the chloride channel blocker picrotoxin and the GABA_A antagonist bicuculline only tended to counteract the yohimbine effect. Taken together, the results in the present behavioral paper indicate that the anticonflict effect of yohimbine involves both increased NA and decreased 5-HT activity, and that direct or indirect activation of BDZ receptors may also be involved. Neurochemical findings related to these behavioral results are presented in a following paper.