Changes in discharge rate of fusimotor neurones provoked by fatiguing contractions of cat triceps surae muscles.

1. Changes in discharge rate of thirty-one fusimotor neurones to triceps surae muscles during long-lasting, fatiguing contractions of these muscles were studied in decerebrate cats. Discharges of fusimotor neurones were recorded from the nerve filaments. Muscle contractions were elicited by electrical stimulation of either the muscle nerves (twenty-one neurones) or the corresponding ventral roots (ten neurones), until the muscle tension fell to about 30% of its initial value. 2. Early and late changes could be recognized in fusimotor discharge rate during long-lasting muscle contraction. The early changes obviously not related to muscle fatigue, consisted of an initial increase at the onset of muscle contraction and a subsequent decrease to or below the resting discharge level. The late change in discharge rate, supposedly related to muscle fatigue, was an increase developing gradually towards the end of muscle contraction, ranging at its peak from 2 to 15 impulses/s (mean value 5.5 impulses/s, n = 31) and outlasting the contraction for 20-320 s. 3. When the contracting muscle was made ischaemic the late increase in fusimotor discharge rate started earlier and was maintained until the arterial clamp was removed. After severing the muscle nerves distal to the site of stimulation no changes, a slight sustained increase, or else a decrease in fusimotor discharge rate occurred during electrical stimulation of either muscle nerves or ventral roots. At its cessation the spontaneous firing rate was reassumed immediately. Stimulation of the distal stumps of the severed nerves elicited no changes in fusimotor discharge rate. 4. It is proposed that the late increase in fusimotor discharge rate may appear due to autogenetic excitation of fusimotor neurones by discharge from group III and IV muscle afferent fibres provoked and/or enhanced by metabolic products liberated in muscle tissue during the fatiguing contraction. The fusimotor firing was estimated to remain elevated to a level twice that of the spontaneous activity on average for approximately 120 s after the muscle contraction. Its functional role in muscle fatigue is discussed.


Muscle history dependence of responses to stretch of primary and secondary endings of cat soleus muscle spindles.

1. Responses were recorded from both primary and secondary endings of soleus muscle spindles in the anaesthetized cat during slow stretches of the muscle after conditioning contractions at different lengths. 2. After a 5 mm length step and a fusimotor-strength contraction given at the longer length, on return to the initial length the response to a slow test stretch (0.5 mm s-1) showed a change in slope midway through the stretch which was attributed to taking up of slack in intrafusal fibres. 3. The onset of the change in slope during the test stretch depended on the size of the conditioning step. With no conditioning length change, just a fusimotor-strength contraction, there was no slope change and the response consisted of an initial burst followed by a maintained high rate of discharge. 4. Following a conditioning length step, the point of onset of the slope change during the test stretch could be altered by stimulating single identified fusimotor fibres to the spindle. Stimulating some static axons produced large changes in the stretch response while other static axons and dynamic axons had only small effects. 5. Many secondary endings showed a delay in onset of their response to a test stretch, dependent on the size of the preceding conditioning step, signalling the presence of slack in much the same way as the primary endings. Other secondary endings, however, appeared to have stretch responses that were largely independent of muscle conditioning. 6. Muscle history-independent responses of secondary endings were associated with low axonal conduction velocities. It is proposed that secondary endings which remain unaffected by muscle conditioning lie on more distal regions of nuclear chain fibres in the S2-S5 position. Here they are stimulated during both the take-up of slack and the subsequent direct stretch of the intrafusal fibres.


Occlusal discrepancies after sealant therapy.

To date there has been no evidence concerning the need for adjusting the occlusion after sealant placement. Thus, this study investigated the occlusal effects of filled and unfilled sealants. For each of 18 subjects a sealant was applied and the occlusion monitored for 1 week. Each participant received a filled and an unfilled sealant for the specified period. With the filled sealant, nearly all subjects experienced a perceptable occlusal change and most were unable to abrade the interferences to a comfort level. These results indicate that the occlusion should be routinely verified and, if necessary, adjusted immediately after placement of a filled sealant.


The radiologic features of cardiac rotation: a pictorial essay.

Rotation of the heart results from enlargement of individual cardiac chambers and influences significantly the configuration of the cardiomediastinal silhouette. Left ventricular enlargement leads to dextrorotation. Conversely, right ventricular enlargement leads to levorotation. The axis of rotation is nearly vertical and extends from the top of the aortic arch through the anterior wall of the left atrium and the proximal interventricular septum. Pericardial defect, deformity of the thoracic skeleton, and lower lobe atelectasis can also lead to cardiac rotation. An understanding of this concept facilitates the interpretation of chest radiographs in patients with heart disease. The terms clockwise and counterclockwise rotation of the heart should be abandoned.


Toxicity of chemically generated nitric oxide towards pancreatic islet cells can be prevented by nicotinamide.

Previous studies have indicated that nitric oxide is involved in the lysis of pancreatic islet cells by inflammatory macrophages. Here we show that the incubation of islet cells with chemical NO-donors leads to cell lysis in a concentration and time dependent way. Islet cell death could be prevented by nicotinamide and 3-aminobenzamide, which are known to inhibit ADP-ribosylation, while several scavengers of oxygen radicals, N-acetylcysteine, dihydrolipoic acid, dimethylthiourea and citiolone, provided no protection.


Percutaneous transluminal angioplasty of an occluded distal splenorenal shunt.

A distal splenorenal (Warren) shunt was performed on a 39-year-old female with bleeding esophageal varices secondary to portal hypertension and cirrhosis. On the twelfth postoperative day, however, she rebled, and angiography revealed that the shunt was occluded. Using a percutaneous approach, successful balloon angioplasty and recanalization was performed. The patient did well and was discharged without further bleeding. Percutaneous transluminal angioplasty (PTA) appears to be effective in dilating occluded splenorenal shunts, obviating a second surgical procedure in high-risk patients.


Anatomy of a transcription factor important for the start of the cell cycle in Saccharomyces cerevisiae.

Entry of yeast cells into the mitotic cell cycle (Start) involves a form of the CDC28 kinase that associates with G1-specific cyclins encoded by CLN1 and CLN2 (ref. 1). The onset of Start may be triggered by the activation of CLN1 and CLN2 transcription in late G1 (ref. 2). SWI4 and SWI6 are components of a factor (SBF) that binds the CACGAAAA (SCB) promoter elements responsible for activation in late G1 of the HO endonuclease, CLN1 and CLN2 genes. A related factor (MBF) containing SWI6 and a 120K protein binds to the ACGCGTNA (MCB) promoter elements responsible for late G1-specific transcription of DNA replication genes. Nothing is known about how these heteromeric proteins bind DNA. We show here that SWI4 contains a novel DNA-binding domain at its N terminus that alone binds specifically to SCBs and a C-terminal domain that binds to SWI6. SWI4's DNA-binding domain is similar to an N-terminal domain of the cdc10 protein that is a component of an MBF-like factor from Schizosaccharomyces pombe and is required for Start. An involvement of this kind of DNA-binding domain in transcriptional controls at Start may therefore be a conserved feature of eukaryotic cells.


Effect of malnutrition on aerobic and anaerobic performance of fast- and slow-twitch muscles of rats.

The effect of malnutrition on the functional properties of fast- and slow-twitch muscles from rats was studied using aerobic and anaerobic preparations. A 2-day fast and hypocaloric feeding to a weight loss of 25% were used as models of malnutrition. Soleus (slow-twitch) and extensor digitorum longus (EDL) (fast-twitch) muscles were studied using an in situ preparation with the blood supply intact and an in vitro preparation to which cyanide had been added to render the muscles anaerobic. We found that a 2-day fast had little effect on the function of muscles stimulated in situ, whereas anaerobic stimulation produced a decrease in force per gram of muscle weight in the soleus, but not in the EDL, compared with control values. Hypocaloric feeding resulted in a slowed relaxation rate, an increased Fs/Fmax ratio, and an upward shift of the force-frequency curve relative to controls when studied in situ. Under anaerobic conditions, soleus muscles from hypocaloric rats continued to show a slow relaxation rate and demonstrated a loss of force per gram of muscle weight compared with controls, particularly at low stimulation frequencies. EDL muscles from hypocaloric rats had an increased relaxation rate and were able to maintain force with anaerobic stimulation. Soleus and EDL muscles from the fasted and hypocaloric groups had lower activities of phosphofructokinase. We conclude that slow-twitch muscles from malnourished rats are at a disadvantage when required to function under anaerobic conditions. These findings suggest that muscle performance may be impaired in malnourished patients subjected to hypoxia.


Hepatitis B vaccination in dialysis patients and nutritional status.

35 dialysis patients underwent anti-HBV vaccination. We classified patients in responders or non-responders using an anti-HBs titer of 50 UI/l as the discriminating serum level and tried to assess whether the antibody response bears any relationship with the nutritional status. 26 patients (74%) reached the target atb titer, which was maintained during follow-up (average 360 UI/l). The weak response in the other 9, with values never exceeding 20 UI/l, was short-lived. Anthropometric and impedenziometric parameters were higher in responders than in nonresponders, but the difference did not reach statistical significance. We conclude that the atb titer which discriminates uremics in responders or not must be greater than 50 UI/l and that the nutritional status may interfere with the seroconversion rate, but this conclusion needs to be validated in a wider population.


HBV infection in hemodialysis patients: monitoring and prevention.

From 1986 to 91, 174 dialysis patients were studied. The prevalence of previous HBV infection and of chronic carriers was 33.3 and 4.6%, respectively. Immunization rate after vaccination (3 doses) was 63%. In 1991, we proposed a vaccination with 4 doses and recommend a 6-monthly anti-HBs evaluation to assess the timing of any booster dose needed.


Epidemiology of viral hepatitis in dialysis centers: a national survey.

Because of the great problem of viral hepatitis in hemodialysis patients, the Italian Society of Nephrology decided to perform a national epidemiologic survey. We contacted 467 nephrological centers by a questionnaire which let us have information on 25,746 uremic patients: 18,338 on HD, 2,250 on PD and 5,176 with kidney transplant, respectively 78.5% of the total Italian dialysed patients and 91.4% of the total transplanted patients. Statistical analyses were performed. HBV infections occur in 7.8% of the patients (2,008 cases) but considering that 485 cases became spontaneously negative, the true overall incidence of chronic carriers falls to 4.9%. The main causes of the infection are reported as transfusions (64.3%) and dialysis environment (12%). The vaccination program performed by 93.2% of the centers, obtained an efficacious seroconversion in 4,626 of 7,790 cases vaccinated: the vaccine currently most utilized is the recombinant type administered by means of 3 versus 4 boosters. In the 2nd part of the survey, we report information concerning the presence of nephropaties associated with HBV infections in nonuremic patients (208 cases). We present and discuss the clinical picture of the nephropaties, the hystologic bioptic pattern and the prognosis of the kidney pathology.


Hepatitis B vaccination in dialysis centres: advantages and limits.

A review is presented on the results achieved in HBV immunization of hemodialysis patients with aluminum-adsorbed, subunit plasma-derived and yeast-derived vaccines. The main host-related and immunization-related causes of low response are discussed. Various possibility to improve the vaccine performance through appropriate dosage and schedule, as well as immunopotentiating procedures are reported.


Expectation of impaired response to recombinant hepatitis B vaccination.

A controlled trial of hepatitis B vaccination with recombinant antigen was undertaken in 18 hemodialysed end-stage renal failure (ESRD) patients (P) and 16 members of our staff (controls, C). In order to identify expected nonresponders (NR), we monitored T lymphocyte (Tc) subsets, peripheral blood mononuclear cells (PBMC), total leukocytes (WBC) and IgG. After 3 vaccine doses of 40 and 20 IU, respectively, for P and C, at 0, 1 and 6 months, 11 P(61.1%) and all C (100%) responded, as in previous reports [1-3]. The 7 NR presented lower CD4+ Tc fraction, compared to responders (R) and C (p less than 0.05), and higher monocyte (p less than 0.00001) and WBC (p less than 0.002) counts, with lower lymphocyte fraction (p less than 0.001), compared to R. We suggest that NR could represent a selected group of ESRD patients, screenable by these easily detectable features, probably markers of a specific immune dysfunction.


Immunization and vaccination protocol in hemodialysis patients with naturally acquired hepatitis B antibody.

Long-term behavior of naturally acquired anti-HBs antibody was tested every 6 months for 3 years in 22 dialysis patients. Fifteen of them maintained protective levels throughout follow-up (102 and 85.5 mUI/ml at the beginning and the end, respectively). Seven of them became anti-HBs and were submitted to a 40-micrograms booster injection of hepatitis B vaccine. Seroconversion was observed in 6 of 7 patients (85.7%) with a mean anti-HBs titer of 90.4 and 47.3 mUI/ml after 3 and 6 months, respectively. Protective anti-HBs level may be maintained longer in patients with natural immunity than in HBsAg-negative vaccinated subjects. Effectiveness of a reduced vaccination protocol in patients who have lost their natural immunization should be confirmed with further studies.


Immunogenicity and efficacy of anti-hepatitis B vaccines in hemodialysis patients.

The 7-year follow-up with plasma-derived and 2-year follow-up with r-DNA vaccines have indicated the safety, immunogenicity and persistence of a vaccine-induced antibody response in hemodialysis patients. The results of our study indicate that these subjects have a lower and often inadequate immunogenic response to the HB vaccine and that the r-DNA vaccine gives a better seroconversion rate than the plasma-derived vaccines.


Hepatitis B vaccination in uremic patients: comparison between recombinant and plasma-derived vaccine.

The immune response to recombinant and plasma-derived vaccines was evaluated in 53 and 43 uremic patients, respectively. The total rate of seroconversion was around 80% with both vaccines, although a significantly higher response was obtained with the protocol using recombinant vaccine.


Control of hepatitis B virus infection in dialysis units in Latium, Italy.

The prevalence of hepatitis B virus (HBV) markers was assessed in 1,841/2,178 (84.5%) dialysis patients (DP) cared for in 38/47 dialysis units (80.9%) in Latium. Among DP, 205 (11.1%) were HBsAg positive: 13.8% of males and 7.1% of females (p less than 0.001); the prevalence increased with the length of time on dialysis (p for trend less than 0.001). No differences in HBV (HBsAg and/or anti-HBc) distribution were seen related to age and sex. Of 664/1,539 vaccinated DP, 150 (22.6%) were anti-HBc positive and 239 (36.0%) positive for anti-HBs alone. Of 875/1,539 nonvaccinated patients, 146 (16.7%) had no HBV marker. Vaccination against HBV did not influence the diffusion of HBV in our dialysis units and must be coupled with the implementation of long-standing infection control strategies.


A successful two-step integrated protocol of anti-HBV vaccination in chronic uremia.

A prospective study was performed in 40 chronic uremics which included: (1) the intramuscular administration to all patients of 40 micrograms of a DNA-recombinant vaccine (Engerix-B) at 0, 1, 2, 6 months; (2) an intramuscular booster dose of 40 micrograms at 18 months in patients having an anti-HBs titer greater than 100 mIU/ml at the 7th month (group A); (3) a further intramuscular supplementary dose of 40 micrograms at 12 months (besides that at 18 months) in patients developing an antibody titer less than 100 mIU/ml at the 7th months (group B); (4) an intradermal course of 5 micrograms of vaccine every 2 weeks until the protective titer (greater than or equal to 10 mIU/ml) was achieved, and then every month for a total of 6 months in patients who did not develop a protective titer even after 19 months (group C). At the end of the study, all patients had developed a protective titer: 77.5% after the 4th intramuscular dose, 12.5% after the 5th and 10% after 3.5 +/- 0.5 (mean +/- SEM) intradermal inoculations. The mean antibody titers were 1,461 +/- 98 mIU/ml in group A, 594 +/- 684 in group B and 131 +/- 133 in group C. In conclusion, our two-step integrated protocol gives an anti-HBs protective titer in all our patients.


Immune response after vaccination with recombinant hepatitis surface antigen in maintenance hemodialysis patients and healthy controls.

We evaluated anti-HBs titers 2 months after vaccination with recombinant hepatitis surface antigen (rDNA-HBsAg) in 43 maintenance hemodialysis patients (MHP). Of these, 34 had not undergone hepatitis B virus vaccination previously (NV-MHP) and 9 had shown negative response to vaccination with plasma-derived HBsAg (HEVAC Pasteur; V-MHP). 120 healthy workers from the same hospital undergoing rDNA-HBsAg immunization were used as controls. All low responders (LR) (anti-HBs less than 100 mIU/ml) and nonresponders (NR; anti-HBs less than 10 mIU/ml) were given a booster dose 3 months after the last dose of vaccine. Seroconversion rates were lower in NV-MHP (52.9%) than in controls (98.4%). V-MHP showed higher seroconversion rates (88.9%) than NV-MHP. In each group, the number of responders (R; anti-HBs greater than or equal to 100 mIU/ml), LR and NR was as follows: controls 101, 17, 2; NV-MHP 6, 12, 16; V-MHP 8, 0, 1. After booster dose, 17/17 controls LR and no NV-MHP LR showed a rise in anti-HBs titers over 100 mIU/ml. Six months after the last dose of vaccine or the booster dose, anti-HBs titer fell under 10 mIU/ml in 4/12 MHP LR and under 100 mIU/ml in 6/14 MHP R. To achieve high seroconversion rates and to avoid the decline of anti-HBs to nonprotective titers in MHP, a booster injection should be made at different dates after the first vaccination.


Immunogenicity of a recombinant hepatitis B vaccine in hemodialysis patients: a two-year follow-up.

The immunogenicity of a recombinant hepatitis B vaccine was evaluated in 35 hemodialysis patients who received a standard dose (20 micrograms) of the vaccine at 0, 1, 2 and 6 months. After the full vaccination course (month 7), 60% (21/35) of the patients had seroconverted (anti-HBs titer greater than or equal to 10 mIU/ml). The duration of protection lasted up to 18 months after the start of vaccination in 85.7% (18/21) of the responders. At that time, an additional dose was given to all the patients: 1-2 months later, the overall immunization rate had increased to 65.7% (23/35); lastly, in month 24 (i.e., 6 months after the booster dose), 62.5% (15/24) of the patients available for evaluation were still maintaining protective levels of anti-HBs antibodies. Comparable results had previously been obtained in 21 well-matched patients on our dialysis program who were vaccinated with a plasma-derived vaccine according to the recommended schedule.


Use of immunomodulators (thymopentine) in hepatitis B vaccine in elderly patients undergoing chronic hemodialysis.

Thymopentine is a synthetic immunomodulator that positively affects T-lymphocyte maturation, reproduction and differentiation. In elderly uremic patients nonresponders to hepatitis B vaccine, the administration of this drug has been shown to improve the response to the new vaccination.


Primary prevention: HBV vaccination in hemodialysis unit.

The authors evaluated the response rate to HBV vaccination in 27 dialyzed patients. In the 1st stage, the response was 70.37%; nonresponder patients (n = 8) were treated with thymostimulin and revaccinated. The total percentage increased to 85.18%. In order to restore a normal response, the authors suggest to treat nonresponder patients with thymostimulin before revaccination.


Evaluation of treatments for the vaccination against hepatitis B + thymopentine.

We have studied a series of 43 patients--who were suffering from uremia, subject to hemodialysis treatment, resulting seronegative to the test for HBV and who had never been vaccinated before--considering the HBS antibody as seroconversion index. We subdivided our patients into three groups, according to the treatment employed. First group: French vaccine; 2nd group: French vaccine+thymopenthine; 3rd group: recombining DNA vaccine+thymopentine. From a statistical point of view, in the 3rd group we obtained a significant seroconversion in terms of patients, if compared with the other groups.


Effect of dietary sodium on atrial natriuretic factor released in rats with chronic renal failure.

Studies were done in partially nephrectomized rats to examine the effect of dietary sodium intake on atrial natriuretic factor (ANF) released by the atria. Experiments were done in four groups of male Wistar rats. Group 1 (n = 10) and 3 (m = 10) rats were sham-operated. Group 2 and 4 were 5/6 nephrectomized. Group 1 and 2 were fed a sodium-supplemented diet. Group 3 and 4 received a sodium-deficient diet. Renal functions were similar between group 2 and 4. Plasma ANF level was raised in group 2 (182 +/- 17 pg/ml). Circulating ANF levels in group 1,3 and 4 were 95 +/- 5, 90 +/- 5 and 95 +/- 4 pg/ml, respectively. Atrial ANF contents were higher in partially nephrectomized rats after receiving a sodium-supplemented diet. A reduction in atrial ANF contents occurred when fed a sodium-deficient diet. In vitro studies were done to assess the rate of ANF released. ANF secretory rates were highest in group 2 (11 +/- 1.5 pg/min/mg). There was no difference between group 1,3 and 4. A positive correlation was found between plasma ANF and ANF released in all groups examined. Thus, plasma ANF levels were a good reflection of ANF secretory rates. A significant correlation existed between plasma ANF and sodium excretion in chronic renal failure rats (r = 0.78; p less than 0.01). A dissociation between plasma ANF and water excretion was seen. These results suggest that in chronic renal failure rats, ANF played a role in sodium adaptation.


Involvement of 5-HT1, 5-HT2, and 5-HT3 receptors in the mediation of the prolactin response to serotonin and 5-hydroxytryptophan.

Serotonin (5-HT) is involved in the neuroendocrine regulation of prolactin (PRL) secretion as a stimulator. Within the last decade several 5-HT receptor types have been identified, but their individual role in the mediation of the PRL response to 5-HT is only partly understood. We investigated in conscious male rats the effect of different 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytrytophan (5-HTP) which was administered in combination with the 5-HT reuptake inhibitor fluoxetine. 5-HT (0.5-5.0 mg/kg BW i.v.) or 5-HTP (25-100 mg/kg i.p.) in combination with saline or fluoxetine (10 mg/kg i.p.) increased the plasma PRL concentration dose-dependently. Pretreatment with the 5-HT1+2 receptor antagonist methysergide (2.5 mg/kg i.p.) prevented the stimulatory effect of 5-HT or 5-HTP + fluoxetine. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (2.5 mg/kg i.p.) inhibited the PRL response to 5-HT by approximately 80% and to 5-HTP + fluoxetine approximately 100%. A higher dose (10 mg/kg) of the 5-HT2 receptor antagonists possessed only 50% inhibitory effect. Pretreatment with the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the PRL response induced by 5-HT or by 5-HTP + fluoxetine. The maximal inhibitory effect (approximately 80%) was obtained by a dose of 0.1 mg/kg of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)


Loss of the acoustic startle response following neurotoxic lesions of the caudal pontine reticular formation: possible role of giant neurons.

The effect of the excitotoxic N-methyl-D-aspartate agonist quinolinic acid in the caudal pontine reticular formation on the acoustic startle response was investigated in rats. Bilateral injections of 90 nmol of quinolinic acid led to large lesions in the reticular formation characterized by the loss of all neurons and a marked reduction or even abolition of the acoustic startle response; 18 nmol of quinolinic acid led to smaller lesions characterized by a selective loss of giant neurons within the caudal pontine reticular formation and a reduction of the startle amplitude. The partial correlation analysis revealed that the reduction of the amplitude of the acoustic startle response can be correlated with the loss of the giant neurons (r = 0.575; d.f. = 29; P less than 0.001) but not with the reduction of the number of all neurons (r = 0.207; d.f. = 29; P greater than 0.2) in the caudal pontine reticular formation. These findings were reconciled with electrophysiological and anatomical data indicating that the giant neurons in the caudal pontine reticular formation receive acoustic input and project to motoneurons of the spinal cord. It is concluded that the caudal pontine reticular formation is an important element of the startle pathway and that the giant reticulospinal neurons constitute an important part of the sensorimotor interface mediating this response.


Nerve growth factor selectively prevents excitotoxin induced degeneration of striatal cholinergic neurones.

Selective neuronal death is a prominent feature of human neurodegenerative disease both of genetic and idiopathic origin. Huntington's disease is characterised by the selective degeneration of striatal projection neurones, with the relative preservation of a variety of interneurones. The ability of the endogenous excitotoxin, quinolinic acid, to produce a pattern of selective neuronal cell death was investigated using immunocytochemical and histochemical techniques. We find that the large striatal, cholinergic interneurones are relatively spared, and that this sparing can be enhanced by the co-administration of the neurotrophin, nerve growth factor (NGF). Further, a single co-injection of NGF will selectively prevent both the cell death and morphological changes that occur within cholinergic cells when assessed 2 weeks later. These results suggest that an interaction between growth factors and excitotoxins can dramatically modify patterns of selective neuronal death.


Intracerebroventricularly administered pertussis toxin blocks the central vasopressor action of neuropeptide Y(13-36) in the awake unrestrained male rat.

The effects of intracerebroventricular (i.v.t.) injections of pertussis toxin (PTX) (10 micrograms/30 microliters, 48 h) were studied on the cardiovascular actions of i.v.t. administered neuropeptide Y(13-36) (NPY(13-36)) as evaluated in the awake unrestrained male rat. The vasopressor action of NPY(13-36) in the peak dose of 3000 pmol per rat was significantly inhibited by pretreatment by PTX. Pertussis toxin treatment alone significantly reduced the baroreceptor reflex elicited by L-phenylephrine. The results are compatible with the view that G-proteins mediate the central vasopressor actions of NPY(13-36) and thus probably are involved in NPY Y2-receptor transduction in cardiovascular areas of the brainstem.


[Treatment of ectopic pregnancy by laparoscopy].

12 ectopic pregnancy were operated by laparoscope. Earlier 2 patients had tubal pregnancy on the same side, and 3 had contralateral ectopic pregnancy. There were used aspiration method in 3 cases and salpingotomy + aspiration in 9 cases. The aspirated blood volume was 103.3 ml in average, the mean hospitalization time period were 3.1 days. The urinary HCG was negative after 1.9 days in average. There was neither early nor late operative complications. The authors suggest, that the introduction of the method has more advantages, when there are subjective and objective circumstances.


Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol.

A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate-induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf PSK stimulation by nerve growth factor (NGF) in PC12 pheochromocytoma cells. Mitogen stimulation of Raf kinase was measured by determination of Raf hyperphosphorylation and activity towards exogenous substrates and both of these events were inhibited in cells expressing M17 Ras. In contrast, tyrosine phosphorylation of a direct substrate of activated tyrosine kinase receptors, phospholipase C-gamma 1 (PLC-gamma 1), was unaffected. These data indicate that tyrosine phosphorylation of PLC-gamma 1 is not sufficient for growth induction in NIH3T3 cells and that Ras mediates signal transfer from activated membrane receptors to Raf kinases in the cytosol. As activated Raf induced differentiation in PC12 cells expressing M17 Ras we conclude that Raf kinase activation may be sufficient to account for this aspect of NGF function.


Rorschach movement responses and the TAT Transcendence Index in physically handicapped children.

It has been supposed that those who give many Rorschach movement responses and score high on the TAT Transcendence Index are more inhibited in their motor activity. In previous studies motor inhibition was investigated by experimentally preventing motor activity. In the present study the effects of long-term motor inhibition on movement perception and fantasy level were explored in 19 physically handicapped children, ages 11 to 15 years. Analysis showed that the physically handicapped children produced more (both human and animal) movement responses than the 19 normal children. Fantasy in the TAT was also higher in the former group. The theoretical basis of projective movement responses and fantasy in physical handicap needs more clarification. A more detailed approach in qualitative analysis of the movement responses is also important.


The experiences of women pediatric dental residents: a survey.

A survey of 430 female pediatric dentists in the United States determined concerns and experiences they had during their advanced training programs. The return rate was 54%. Up to 83% (24) of the women who were pregnant during their residencies asked not to be exposed to certain environmental hazards during pregnancy and the postpartum period. They requested that program directors establish policies on known environmental hazards. Eighty-eight women (41%) commented that programs should offer flexible, preestablished and preannounced maternity leave policies. Survey respondents also expressed concerns about personal safety (5%), the lack of female role models (9%), and the need for more information on business management (30%). When the women were analyzed according to age, the following were significant (P less than .05): professional acceptance was of greatest concern to women ages 41-48; pregnancy and maternity leave, and balancing career with parenthood, significantly concerned women 25-32; and women ages 33-40 said business management was the issue causing the greatest frustration as a practicing pediatric dentist. While most respondents felt that they have the same professional opportunities as men, their greatest frustrations are a lack of acceptance by the professional and lay communities and trying to balance a career and motherhood.


Attitudes of program directors toward women in pediatric dentistry training programs.

The number of women entering pediatric dentistry graduate programs is increasing. A formal survey was conducted in the fall of 1990 to determine what impact, if any, this increase is having on the programs. The survey sample consisted of the 57 pediatric dentistry graduate program directors from the United States and Canada. The survey form included program data about gender distribution in the current and previous classes, and female faculty distribution within the programs. The survey requested information about the attitudes of various groups of individuals who interacted with the residents relative to the gender of the resident and again, relative to whether the resident was pregnant. Inquiry was made concerning maternity leave policies and selected treatment scenarios involving pregnant residents. Finally, questions were asked about motivational factors, personal priorities, and policy change for female vs. male residents. Fifty forms were returned for a return rate of 88%. The 48 forms analyzed revealed that 52% of current classes are female and 51% of applicants for 1991 were female. Women comprise 23% of full-time and 26% of part-time faculty. There was no single issue perceived by program directors as a group to be a significant concern or problem relating to gender. Program directors would consider removing pregnant females from contact with combative patients (83%) and environmental hazards (85%), but fewer would consider removing them from contact with for HIV+ or Hb+ patients.


A carboxyl-terminal-domain kinase associated with RNA polymerase II transcription factor delta from rat liver.

We previously purified RNA polymerase II transcription factor delta from rat liver and found that it has an associated DNA-dependent ATPase (dATPase) activity. In this report, we show that delta is also closely associated with a protein kinase activity that catalyzes phosphorylation of the largest subunit of RNA polymerase II. Kinase activity copurifies with transcription and DNA-dependent ATPase (dATPase) activities when delta is analyzed by anion- and cation-exchange HPLC as well as by sucrose gradient sedimentation, arguing that delta possesses all three activities. Phosphorylation of the largest subunits of both rat and yeast RNA polymerase II is stimulated by DNA, whereas phosphorylation of a synthetic peptide containing multiple copies of the carboxyl-terminal heptapeptide repeat is not. Although both ATP and GTP appear to function as phosphate donors, GTP is utilized less than 10% as well as ATP. These findings suggest that delta may exert its action in transcription at least in part through a mechanism involving phosphorylation of the largest subunit of RNA polymerase II.


Opinions of pediatric dentists regarding their board certification process.

Despite frequently heard criticisms of the board certification process in pediatric dentistry, pediatric dentists have never been surveyed on this issue. To achieve a representative opinion, a formal survey was conducted during the summer and fall of 1990. The survey sample consisted of 300 practitioners selected randomly from the list of 4300 United States pediatric dentists. The survey form included demographic data, board status, general opinions about the process, and specific estimates of the reliability, validity, and utility of each of the five examination components. Comments were encouraged. A follow-up reminder was sent several weeks after the initial mailing. Ten forms were returned as undeliverable, reducing the sample to 290. In all, 150 forms were returned, for a return rate of 52%. One hundred and thirty-eight forms were completed and analyzed. This number included 54 pediatric Diplomates and 84 nonboarded pediatric dentists. The Written and Oral sections generally were rated more favorably than the Case History, Site Visit, and Simulation sections. Nonboarded respondents were significantly more critical of the process on every item, without exception. All differences exceeded the 0.01 level.


Developmental changes in the fatty acids of rat uterus and the influence of dietary essential fatty acids.

The effect of age on uterine fatty acid composition was studied in rats fed diets of differing fatty acid composition. Uteri of newly weaned 23-day rats had a higher fatty acid content and a higher proportion of short-chain (less than or equal to C18) fatty acids. Higher incorporation of C less than or equal to 18 fatty acids into neutral lipid (NL) and phospholipid (PL) of young 42-day rats compared with adult 240-day rats was detected. Uterine NL incorporated predominantly C less than or equal to 18 fatty acids which may be an important metabolic energy store in developing uterine tissue. Incorporation of C less than or equal to 18 fatty acids by uterine PL and NL was relatively unselective. In contrast, there was selective retention of arachidonic acid (AA) and docosahexanoic acid (DHA) throughout uterine development. An effect of dietary EFA on uterine n-3 and n-6 EFA was detected in each age group. There was marked retention of uterine AA when dietary supplies of n-6 EFA were low, but the total AA, eicosapentaenoic acid (EPA) and DHA in uterine PL remained constant in the three diet groups, and a constant content of AA, EPA and DHA was maintained throughout uterine development, regardless of diet. The degree of n-3 substitution achieved in this study inhibited uterine release of PG and parturition in adult rats.


Mechanisms of cell killing in photodynamic therapy using a novel in vivo drug/in vitro light culture system.

Photodynamic therapy of certain neoplasms has emerged as a promising form of cancer treatment. This type of therapy involves the exogenous administration of a photosensitizer with subsequent exposure to light. The ensuing photochemical reaction results in destruction of the tumor. Whether tumor cells are destroyed directly by the photodynamic treatment or indirectly as a result of destruction of the tumor microvascular bed is unknown. To address this question, methods were adapted to test whether combinations of a photosensitizer and light resulted in direct cell killing of precision cut tissue slices placed in culture. The major advantages of this culture system are that photosensitizers are administered in vivo, tissue slices produced in minutes, placed in culture medium, and irradiated in vitro. Any resulting cellular destruction occurs in the absence of a functioning vascular system and indicates that photodynamic therapy acts through a direct cell killing mechanism. Tissue slice viability was monitored by two standard methods: assay for intracellular potassium and morphological examination at the electron microscopic level. The effects of hematoporphyrin derivative and light were examined on tissue slices produced from a prostate adenocarcinoma transplanted into male Copenhagen rats. The data indicate that direct killing of tumor slices occurs and is dependent on the irradiation protocol used.


Tumoricidal capacities of macrophages photodynamically activated with hematoporphyrin derivative.

Four days after administration to mice of small amounts (30-600 ng/mouse) of hematoporphyrin derivative (HPD), peritoneal macrophages exhibited a greatly enhanced Fc-receptor mediated phagocytic capacity as assayed by ingestion activity of IgG-coated sheep erythrocytes. Much higher doses (greater than 3000 ng/mouse) did not have this effect. The peritoneal macrophages activated by administration of HPD have tumoricidal capacity for IgG-coated retinoblastoma cells. We then studied in vitro photodynamic activation of macrophages by white and red fluorescent light irradiation of mouse peritoneal cells (mixture of macrophages and B and T lymphocytes) in media containing very low concentrations of HPD. A short (5 s) white fluorescent light exposure (1Wm-2) of peritoneal cells in a medium containing 0.03 ng HPD/mL produced the maximal level of ingestion activity of macrophages. A 15 s red fluorescent light exposure (1Wm-2) of peritoneal cells in a medium containing 0.1 ng HPD/mL produced the maximal level of ingestion activity of macrophages. Thus, photodynamic activation of macrophages with white fluorescent light is more efficient than that with red fluorescent light. This can be explained by the fact that HPD has a large absorption peak at about 364 nm which extends into the visible range, and decreasingly smaller absorption bands at 500, 535, 570 and 630 nm. In vitro photodynamically activated macrophages showed efficient tumoricidal activity regardless of the type (white or red) of light used. These results suggest that a low level of HPD promotes therapeutic immunopotentiation.


Effect of warm air on the shear bond strength of composite resins.

This investigation evaluated the operating characteristics of a recently introduced tooth dryer and its effect on the bond strength of three composite resins to etched enamel. The effect of varying air pressure, distance from the tip of the tooth dryer, and distance laterally from mid-air stream on temperature were measured using a rapid-response thermocouple. Specimens were subjected to shear forces either immediately after bonding or after 5 days of water storage. The air stream required from 32 to 41 seconds to reach maximal temperature; however, more than 90% of the maximal temperature was obtained in 20 seconds. There was an increase in temperature with increased air pressure and a decrease in temperature with increasing distance from the tip. The temperature dropped rapidly laterally from the center of the air stream. The shear bond strength measurements were significantly higher for the specimens prepared using the tooth dryer for one composite resin tested immediately after bonding; there was no statistically significant difference for the other resins. The effect of warm air on the shear bond strength of composite resins to etched enamel may be dependent on the resin used and the time between bonding and testing.


[Role of percutaneous angioplasty in keeping vascular access for hemodialysis].

The stenoses of anastomosed vessels or of implantation grafts are among the most frequent causes of insufficiency of vascular hemodialysis accesses. Percutaneous angioplasty allows the interventional radiologist too to participate in the salvage of shunts. From 1985 to 1991, 46 patients underwent the procedure. Angioplasty could be performed in 43 of them, and had to be repeated in some cases because of either relapse or malfunctioning new vascular access. On the whole, 59 maneuvers were performed, and 96 stenoses treated, 71 in Brescia-Cimino fistulas and 25 in Gore-Tex prostheses. The optimized standard technique employs access through the efferent vein and a diagnostic evaluation after blocking the flow with an inflatable cuff; 2-3 distensions lasting 2-3 minutes are performed with a 3.5-4 mm x 20 mm balloon catheter for the anastomosis. One or more 15-20-minute distensions follow, with a 6-8 mm x 20-40 mm Zijlstra balloon catheter (Schneider) for the lesions in the efferent vein. Our initial success rate was 88.7% (55 of 62 procedures). Follow-up results at 3, 6, 12, 24 months proved that for this type of lesion, which is usually supported by fibrosis and endarterial hyperplasia, estimated relapse rates exceed 50% in the first year and are lower than 10% a year in the following years. Complications are quite rare and can be partly prevented if the correct indications are followed, overdistension is avoided and the proper material is used. On account of the good results it yields, of its relative simplicity and of the very low incidence of complications, angioplasty should be considered as the treatment of choice for stenoses and their relapses in vascular hemodialysis accesses. As for treatment protocol, angioplasty is not a procedure to occasionally replace surgery, but a therapeutic approach which can be repeated at regular time intervals and can prolong the life of hemodialysis fistulas, thus delaying surgical reconstruction.


[Focal infections caused by non-typhi Salmonella: a review of our case series and comparison with other series].

Nine cases of local infection due to non typhi Salmonella enterica, some of them of unusual localization, in 8 patients (mean age 64.9 +/- 12.4 years) attended in Zamora's Virgen de la Concha Hospital over a period of five years, are described. Focal salmonellosis represented 1.5% of non-typhi salmonellosis cases in that period (9 out of 606 detected cases). 6 of the 8 patients (75%) showed a predisposing disease. In two patients the previous existence of gastroenteritis due to Salmonella was assessed and only in one of them concomitant bacteremia was detected. Soft-tissue infections were the more frequent clinical feature: plantar abscess, two abdominal wall abscesses--one of them after cholecystectomy--post-pericardiotomy thoracic wall abscess and perianal abscess. Three soft-tissue infections were due to group B serotypes. 4 out of five soft-tissue infections evolved favorably with surgical treatment. The rest of the series is formed by two cases with acute cholecystitis in patients with previous cholelithiasis (one of whom relapsed originating an abdominal wall abscess), a recurrent pleural empyema and a purulent pericarditis. The pericarditis was produced by S. enteritidis. Patient showed signs of cardiac tamponade, his condition improving after pericardial drainage and parenteral and intrapericardial administration of ciprofloxacin. Epidemiologic and clinic characteristic of our series are compared with other series of focal salmonellosis.


Co-expression of T-cell receptor beta and delta mRNA detected at high frequency in hybridomas derived from adult thymus.

Two different hybridoma collections from adult C3H/HeJ thymus were generated in order to analyse T-cell receptor (TcR) rearrangements, surface expression of T-cell receptors and differentiation markers as well as lymphokine production. Large, low density thymocytes were either directly fused to the thymoma BW 5147 alpha-beta- variant, or fused after stimulation with Concanavalin A in the presence of interleukin-2 for 48 h. The hybrids obtained from Concanavalin A-stimulated cells represented rather mature thymocytes, with regard to TcR rearrangements and surface T-cell receptor expression. The collection of hybrids derived from freshly isolated large thymocytes contained cells in various stages of T-cell development. An unexpectedly large number of hybrids (46 out of 84) from this group expressed full-length C beta together with full-length, or shorter, C delta mRNA. This finding suggests that a considerable proportion of alpha beta T cells proceeds through a stage in development where delta genes are being rearranged and transcribed.


Cytoplasmic calcium fluxes induced in cytotoxic effector cells by engagement of Fc gamma receptors I, II, and III.

Changes in the intracellular calcium ion concentration ([Ca2+]i) of monocytes, granulocytes, and NK cells have been studied following either (1) independent cross-linking of Fc gamma receptors (Fc gamma R) I, II, or III, with F(ab gamma')2 fragments of monoclonal antibodies; or (2) linking of a selected Fc gamma R to a tumour cell target with bispecific F(ab' gamma)2 antibodies. Upon cross-linking each Fc gamma R with antibody an increase in the [Ca2+]i was observed, although all receptors apart from Fc gamma RIII on NK cells required additional cross-linking with an anti-mouse Fab' gamma. These results indicate that each type of receptor can transduce signals to the cell independently. Bispecific antibodies (anti-Fc gamma R x anti-target) linking cytotoxic Fc gamma R-bearing effector cells to tumour target cells also mediated increases in [Ca2+]i for all Fc gamma R tested except for Fc gamma RIII on granulocytes. The failure to transduce a signal via this receptor may be related to the GPI link, which is in contrast to the transmembrane link of Fc gamma RIII on NK cells. Significant lysis of tumour cell targets occurred when bispecific antibodies recruited NK cells or monocytes, but not granulocytes, via Fc gamma R. Chelation of intracellular Ca2+ in the effector cells reduced the observed lysis, suggesting a role for Ca2+ in the pathways leading to cytotoxicity.


Identification of human T cells that require zinc for growth.

Zinc is an essential trace element required for normal function of the immune system. Deficiency of zinc results in marked thymic atrophy in experimental animals, and in man immunodeficiency is a recognized complication of zinc deprivation. Although numerous proteins require zinc as a cofactor, its precise functions in the immune system remain unknown. The mechanism by which metals stimulate lymphocytes, whether all T cells are responsive, and the relationship to zinc requirements have not been determined. We unexpectedly isolated a number of human T-cell lines that have a highly specific requirement for zinc. The ability to respond to zinc resides in only a subset of T cells since antigen-specific clones are not stimulated by zinc. Although proliferation requires the presence of antigen-presenting cells and is restricted by class II MHC antigens, antigen-presenting cells could not be pulsed with zinc to induce T-cell activation. Our results suggest that zinc-dependent T cells are a subset of CD4+ cells present in all normal individuals and that zinc stimulates their growth by novel mechanisms.


Coding region polymorphisms of human T-cell receptor V beta 6.9 and V beta 21.4.

Two new TCRV beta coding region polymorphisms were identified: V beta 6.9a/b and V beta 21.4a/b. In both cases, a single nucleotide difference gives rise to an amino acid exchange. Genomic typing by the PCR/sequence-specific oligonucleotide probing technique was performed to study a possible contribution of these two new polymorphisms in susceptibility to autoimmune diseases. However, there was no association with insulin-dependent diabetes mellitus, rheumatoid arthritis, juvenile rheumatoid arthritis, multiple sclerosis, myasthenia gravis or coeliac disease. On the other hand, significant differences were found between Caucasoid and Oriental populations in frequencies of the V beta 6.9 and V beta 21.4 alleles.


Computerized tomography in persons with Down syndrome and atlantoaxial instability.

Atlantoaxial instability has been reported to occur in 9-31% of persons with Down syndrome. The authors studied a subsample of patients with this chromosomal disorder who had both routine roentgenograms and computerized tomographic examinations. Computerized tomography revealed numerous skeletal anomalies of the C1-C2 region as well as spinal cord compression that were not visualized on plain roentgenograms. In addition, an apparent discrepancy of the atlanto-dens interval measurements between the two procedures was noted. The measurements of the plain roentgenograms were significantly greater than those obtained by computerized tomography, which is due to the magnification factor in plain roentgenograms.


Use of the International Classification of Diseases (ICD-9-CM) to identify hospitalizations for mechanical low back problems in administrative databases.

Large administrative databases are increasingly valuable tools for health care research. Although increased access to these databases provides valuable opportunities to study health care utilization, costs and outcomes and valid and comparable results require explicit and consistent analytic methods. Algorithms for identifying surgical and nonsurgical hospitalizations for "mechanical" low back problems in automated databases are described. Sixty-six ICD-9-CM diagnosis and 15 procedure codes that could be applied to patients with mechanical low back problems were identified. Twenty-seven diagnosis and two procedure codes identify hospitalizations for problems definitely in the lumbar or lumbosacral region. Exclusion criteria were developed to eliminate nonmechanical causes of low back pain, such as malignancies, infections, and major trauma. The use of the algorithms is illustrated using national hospital discharge data.


Calphobindin I (annexin V) inhibits protein kinase C.

We investigated the inhibitory effect of calphobindin I (CPB I) on protein kinase C activity. CPB I inhibited protein kinase C activity in a concentration-dependent manner with an IC50 value of 70 nM. The inhibition of protein kinase C by CPB I was Ca(2+)-dependent, and was partially overcome by increasing the concentration of phosphatidylserine. Since CPB I is widely distributed in various organs and cells, it is presumed that CPB I is an endogenous inhibitor of protein kinase C.


Laparoscopic cholecystectomy during pregnancy.

There is a strong association between pregnancy and gallstones. When acute cholecystitis or recurring bouts of biliary colic occur during pregnancy, medical therapy is usually initiated but occasionally fails. Laparoscopic cholecystectomy has recently been described for the treatment of symptomatic cholelithiasis, but many authors consider pregnancy to be an absolute contraindication to this operation. We herein describe the management of markedly symptomatic cholelithiasis during the second trimester of pregnancy using laparoscopic techniques in five patients. Tocolytic medications were administered perioperatively in two patients, and open laparoscopy or the use of an alternative site for insertion of the initial port was used in all patients. Laparoscopic cholecystectomy without cholangiograms was successful in all five patients and postoperative hospitalization ranged from 24 to 48 h. Uncomplicated term delivery has occurred in three of the five patients; in the other two patients, normal pregnancies are continuing. Laparoscopic cholecystectomy can be performed safely during pregnancy, as long as the patient is monitored carefully and specific precautions are observed.


Techniques for laparoscopic cholangiography and removal of common duct stones.

As laparoscopic cholecystectomy becomes more prevalent, the unexpected finding of common duct stones by operative cholangiography presents a therapeutic dilemma for the surgeon. We present our current techniques for laparoscopic cholangiography and management of choledocholithiasis, including the use of angioplasty balloons for ampullary dilation.


Laparoscopic occlusion of testicular veins for clinical varicocele.

Surgery via the laparoscope is now a reliable and cost-effective alternative to some open surgical procedures. Advances in videoendoscopy, incorporating optical magnification combined with the development of instruments with which to dissect, ligate, and transect blood vessels provide the urologist the opportunity to surgically correct a varicocele. In the outpatient setting, 4 patients (14-26 years of age) underwent laparoscopic ligation of the left internal spermatic veins for painful left varicocele. Carbon dioxide pneumoperitoneum was obtained using a Veress needle. A 10-mm laparoscope was placed intraperitoneally through a cannula inserted in the infraumbilical border. Utilizing two additional endosurgical ports (5 mm and 10 mm) through which 5-mm dissecting instruments and vaso-occlusive endoclips were placed, three veins were individually isolated and ligated in each of the 4 patients. In all 4 patients, the left testicular artery was visualized and preserved. There was no blood loss or other intraoperative complication. In each patient the varicocele was successfully corrected. Analgesic medication was not required postoperatively. We conclude that laparoscopic ligation of the internal spermatic veins is a safe and effective way of treating a varicocele without immediate postoperative sequelae. Long-term follow-up is necessary to determine the place of the endoscopic approach.


The efficacy of moxidectin against Dictyocaulus viviparus in cattle.

The efficacy of an injectable and a pour-on formulation of moxidectin against Dictyocaulus viviparus in cattle was examined. The results show that both formulations have an efficacy of 100% against adult worms and developing and inhibited larval stages of D. viviparus.


A newly designed single dissector useful for laparoscopic cholecystectomy.

We developed a modified dissector capable of carrying out a one-hand operation involving three fundamental functions: grasping, sharp or blunt dissection, and dividing the tissues. With this single dissector, laparoscopic cholecystectomy can be rapidly and safely performed without changing the forceps or instruments through the trocar.


The absorbance spectrum and photosensitivity of a new synthetic "visual pigment" based on 4-hydroxyretinal.

The firefly squid, Watasenia scintillans, is the only animal known to possess a visual pigment in which the chromophore is 4-hydroxyretinal. This paper describes the absorbance spectrum and some properties of a synthetic "A4" visual pigment generated from bovine opsin and 4-hydroxyretinal. The absorbance spectrum of this pigment is compared with (a) bovine rhodopsin and (b) a rhodopsin template with the same lambda max as the synthetic visual pigment. The A4 pigment is shown to have an absorbance spectrum that is almost identical to that of a rhodopsin template. It is also shown that the photosensitivity and thermal stability of the A4 pigment, dispersed in detergent micelles, is essentially similar to that of rhodopsin.


Cellular response and anti-HBs synthesis in vitro after vaccination with yeast-derived recombinant hepatitis vaccine.

Two groups of subjects receiving two different doses of yeast-derived recombinant hepatitis B surface antigen (rHBsAg) (10 micrograms Gen-HB-Vax, Merck Sharp and Dohme and 20 micrograms Engerix-B, Smith Kline and French) were investigated for in vitro specific humoral and cellular response to the native protein. In vitro proliferative response was dependent on the following critical variables: (1) antigen-specific precursor lymphocytes were present in the peripheral blood for a very short time; (2) the number of circulating specific precursors was dependent on the dose of HBsAg used for vaccination; (3) the presence of antigen-presenting cells was necessary to obtain a blastogenic response in vitro. In vitro proliferation was enhanced by the addition of recombinant interleukin 2 (rIL-2). Spontaneous and stimulated (anti-CD3, pokeweed mitogen) anti-HBs antibody production in vitro was obtained in only eight out of 20 subjects after the fourth boost. Although a different immunogenicity of the two vaccines cannot be excluded, these data strongly suggest that T and B cells responsive to HBsAg present different kinetics of recirculation in the peripheral blood, depending on the antigen dose used for immunization.


Intracellular actions of gonadotropic and peptide hormones and the therapeutic value of GnRH-agonists in ovarian cancer.

During the last two decades, considerable experimental evidence has been collected indicating that epithelial ovarian cancer might be gonadotropin dependent. LH and FSH receptors have been described in some of these tumors. The proliferation of ovarian cancer cells could be stimulated in vitro by gonadotropins. Suppression of endogenous LH and FSH secretion by GnRH-agonist treatment inhibited the growth of experimental or heterotransplanted ovarian cancers in various animal models. A number of recent phase II clinical trials have shown that the application of GnRH-agonists can lead to remission or stable disease in patients with relapsed advanced ovarian cancer. At present, prospective controlled clinical studies are being performed to assess the efficacy of GnRH-agonist treatment in addition to conventional surgical and cytostatic therapy in ovarian cancer in FIGO stages III and IV. Also, direct effects of GnRH analogues on ovarian cancer seem possible: a GnRH-like protein has been found in the human ovary. Our group discovered and partially characterized a specific GnRH-binding site (mol. wt 63.2 kDa) in ovarian cancer which is very similar to other human extrapituitary GnRH-binding sites of the low affinity, high capacity type, e.g. in breast cancer or the placenta. Recently, other groups have described also high affinity GnRH-agonist binding sites in ovarian cancer as well as in other extrapituitary tissues. First results from our laboratory indicate that the proliferation of certain ovarian cancer cell lines in vitro is reduced by both agonistic and antagonistic analogues of GnRH. Other authors were able to inhibit gonadotropin-induced in vitro proliferation of ovarian cancer cell lines by co-incubation with a GnRH-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)


Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process.

In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased.


Is 3 alpha, 17 beta-androstanediol-glucuronide a diagnostic marker in women with androgenic manifestations?

3 alpha, 17 beta-androstanediol-glucuronide (Adiol-G) has been described as a marker of local androgen excess due to the increased activity of 5 alpha-reductase in the cells of the hair follicles. In order to test the diagnostic value of Adiol-G, the serum level was compared to that of testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione and to the body mass index in 44 women with androgenic symptoms (Group I), 27 women with menstrual disturbances but no androgenic symptoms (Group II), and 48 healthy women (Group III) who served as controls. Adiol-G was significantly higher (7.8 +/- 5.1 nmol/l) in women with androgenic symptoms than in the other groups, but there was a considerable overlap. Serum testosterone was also found to be higher in Group I than in Groups II and III, respectively. There was a significant correlation between Adiol-G and testosterone, and Adiol-G and DHEA-S. No significant correlation could be shown to exist between androstenedione and Adiol-G. When Adiol-G and testosterone were simply classified as 'normal' or 'increased' (Adiol-G 9.4 nmol/l; testosterone greater than 2.4 nmol/l), higher than normal values of the former were found in the presence of normal testosterone in only 4% of the cases. It is concluded that the level of Adiol-G generally parallels that of testosterone. Consequently, it does not seem to be an effective marker of peripheral androgen excess.


[Renal artery angioplasty].

In the 59 hypertensive patients submitted to percutaneous transluminal angioplasty (PTA) of the renal artery, there was an immediate success in the blood pressure in 91.5% and a later one of 79.6%. In these patients we obtained better results: 81.4% in the unilateral lesions, more than in the bilateral ones--72.7%; 82.5% in the renal artery trunk lesions, more than in the ostium ones--71.4%; 88.9% in the lesions of fibromuscular origin, more than in the aterosclerotic ones--75%; 84.4% in up to 55 years old patients, more than in older ones--71.4%. These differences were not significant. The results of renal angioplasty in renovascular hypertension suggest this type of intervention as an alternative treatment.


[Functional and anatomic involvement of the right ventricle in arterial hypertension].

The early cardiac involvement is well known in arterial hypertension, particulary the diastolic and left ventricular hypertrophy. The right ventricle and pulmonary circulation may likewise be affected early in the course of disease. Scarce though it is, studies on the right repercussion of hypertension have shown an increase in pulmonary resistance and right-sided pressures in hypertensive patients. In spite of the limitations arising from the complex geometry of the right ventricule, echocardiography may be the most important non-invasive technique in the evaluation of the structural and functional repercussion of hypertension on the right ventricle. Our studies have revealed an increase in the diastolic thickness of the right ventricular free wall in hypertensive patients, as well as a good correlation between the diastolic thickness of the free walls of both ventricles. Most studies suggest a functional relationship between both ventricles. Structural alterations may occur in the right ventricle, along with hemodynamic alterations, thus suggesting structural and functional similarity of both ventricles, regarding cardiac response to arterial hypertension.


[Precocity of diastolic dysfunction in hypertensive cardiopathy].

Left ventricular hypertrophy (LVH) is a well defined cardiovascular risk factor and is frequently detected by echocardiography in hypertensive patients. Systolic cardiac function at rest is usually preserved in hypertension, however, diastolic function may be frequently altered. Evidence for these changes has been demonstrated by Echo-Doppler even without concomitant existence of LVH. Quantitative and qualitative changes in contractile proteins and interstitial tissue as well as reduction of coronary reserve may be related to the mentioned dysfunction. Recent studies have confirmed the precocity of diastolic dysfunction both in laboratory animals as well as man. Further significant differences have been shown between normotensives with and without a family history of systemic hypertension. The relative importance of diastolic disfunction is also related to its possible role in the genesis of cardiac failure and its probable role in the modulation of cardiopulmonary reflexes in addition to the hemodynamics of arterial hypertension. It is not yet known if the presence of diastolic dysfunction is a mechanism or a risk marker like LVH.


The development of functionally responsive T cells.

The work reviewed in this article separates T cell development into four phases. First is an expansion phase prior to TCR rearrangement, which appears to be correlated with programming of at least some response genes for inducibility. This phase can occur to some extent outside of the thymus. However, the profound T cell deficit of nude mice indicates that the thymus is by far the most potent site for inducing the expansion per se, even if other sites can induce some response acquisition. Second is a controlled phase of TCR gene rearrangement. The details of the regulatory mechanism that selects particular loci for rearrangement are still not known. It seems that the rearrangement of the TCR gamma loci in the gamma delta lineage may not always take place at a developmental stage strictly equivalent to the rearrangement of TCR beta in the alpha beta lineage, and it is not clear just how early the two lineages diverge. In the TCR alpha beta lineage, however, the final gene rearrangement events are accompanied by rapid proliferation and an interruption in cellular response gene inducibility. The loss of conventional responsiveness is probably caused by alterations at the level of signaling, and may be a manifestation of the physiological state that is a precondition for selection. Third is the complex process of selection. Whereas peripheral T cells can undergo forms of positive selection (by antigen-driven clonal expansion) and negative selection (by abortive stimulation leading to anergy or death), neither is exactly the same phenomenon that occurs in the thymic cortex. Negative selection in the cortex appears to be a suicidal inversion of antigen responsiveness: instead of turning on IL-2 expression, the activated cell destroys its own chromatin. The genes that need to be induced for this response are not yet identified, but it is unquestionably a form of activation. It is interesting that in humans and rats, cortical thymocytes undergoing negative selection can still induce IL-2R alpha expression and even be rescued in vitro, if exogenous IL-2 is provided. Perhaps murine thymocytes are denied this form of rescue because they shut off IL-2R beta chain expression at an earlier stage or because they may be uncommonly Bcl-2 deficient (cf. Sentman et al., 1991; Strasser et al., 1991). Even so, medullary thymocytes remain at least partially susceptible to negative selection even as they continue to mature.(ABSTRACT TRUNCATED AT 400 WORDS)


[Delayed treatment with dextromethorphan can reduce ischemic retinal damage in rabbit].

Previous studies have suggested that prophylactic treatment by dextromethorphan (DEX), N-methyl-D-aspartate (NMDA) receptor antagonist can protect the retina against ischemia. To investigate the effect of DEX on the proceeding ischemic retina, 0.1% DEX hydrobromide was intravenously administered in rabbits immediately (group A), 1 hour (group B) or 2 hours (group C) after the release from ischemia induced by increasing intraocular pressure to 130 mmHg for 90 min. Normal saline was infused immediately after the release from ischemia as control rabbits. Retinal function was monitored by recording electroretinogram (ERG). Twenty four hours after the release of ischemia, the recovery rates of ERG.b-wave amplitudes in groups A, B and C were 61.3 +/- 3.3, 52.2 +/- 9.0 and 43.6 +/- 8.4% of the preischemic amplitude, respectively. The recovery rate of the group A was higher than that of the control (41.9 +/- 10.6%), while no significant differences were seen between groups B or C and the control. The results suggest that DEX can protect the retina if it is administered immediately after the release of ischemia.


Revising axis V for DSM-IV: a review of measures of social functioning.

Axis V, which uses the Global Assessment of Functioning Scale in the multiaxial system of DSM-III-R, is under review for DSM-IV. This article examines what is known about axis V and selectively reviews the literature on measures of social functioning to identify potential alternatives to the Global Assessment of Functioning Scale. About 25 studies on the use, reliability, and validity of axis V in DSM-III and DSM-III-R are reviewed. In addition, nearly 30 measures of social functioning are reviewed and analyzed as potential substitutes for the Global Assessment of Functioning Scale. The analysis focuses on the strengths and weaknesses of each measure for assessing functioning on axis V. Axis V measures are modestly reliable and valid but not widely used. The authors identify and discuss two particular limitations of the Global Assessment of Functioning Scale: 1) the combination of measures of symptoms and measures of social functioning on a single axis and 2) the exclusion of physical impairments from the rating of functioning. None of the measures of social functioning reviewed is clearly superior to the Global Assessment of Functioning Scale for use on axis V. A modified version of the Global Assessment of Functioning Scale, separating the measures of social and occupational functioning from the measures of symptoms and psychological functioning, is proposed for field testing, along with a new set of instructions permitting the rating of limitations due to both physical and mental impairments.


The effect of mutation on linkage disequilibrium.

The standard formula for the approach to linkage equilibrium between two diallelic loci, initially at disequilibrium, is expressed in terms of their probability of recombination (Li, 1955). By a simple extension, we show how to incorporate the effects of mutation at one or both loci. It can thereby be inferred that in general these effects are unlikely to be of major importance, contrary to some recent suggestions.


4-week treatment of streptococcal native valve endocarditis with high-dose teicoplanin.

The efficacy and safety of a 4-week course of intravenous teicoplanin (500 mg every 12 h for the first 2 days and 10 mg/kg of body weight every 24 h thereafter) in the treatment of streptococcal native valve endocarditis in 20 patients were evaluated. All blood isolates were inhibited by a concentration of 0.12 micrograms of teicoplanin per ml. Serum bactericidal activity levels were measured 1/2 and 24 h after antibiotic infusion on days 5 to 7 of therapy in 19 patients, and titers of greater than or equal to 1:32 and greater than or equal to 1:8, respectively, were obtained with 17 patients (89%). On the other hand, for two patients who were infected with teicoplanin-tolerant Streptococcus bovis, serum bactericidal activity levels of less than 1:2 were found. Of 20 patients, 4 were excluded from further analysis because of protocol violation or prosthetic valve infection. Of the remaining 16 patients, 6 did not complete teicoplanin therapy because of early death (1 patient) or drug fever (5 patients). Among patients who developed drug fever, three who discontinued teicoplanin by day 15 were switched to penicillin therapy, whereas the remaining two, who discontinued teicoplanin on day 22 and 25, respectively, did not receive any further therapy and have shown no relapse during the follow-up. Of 10 patients who completed trial therapy, 9 were cured and 1 relapsed. It is concluded that a 4-week course of high-dose teicoplanin may be a useful regimen for home treatment of selected cases of streptococcal native valve endocarditis. However, drug fever and infection with teicoplanin-tolerant S. bovis may be factors of concern with this therapeutic approach.


In vitro activity of decaplanin (M86-1410), a new glycopeptide antibiotic.

The in vitro activity of decaplanin (formerly M86-1410), a novel glycopeptide antimicrobial agent, was tested against 169 gram-positive bloodstream isolates from patients at the University of Iowa Hospitals and Clinics and 12 selected vancomycin-resistant strains. Enterococcus faecalis, E. faecium, Staphylococcus aureus, streptococci, bacilli, corynebacteria, and listeria were inhibited by decaplanin (MICs for 90% of the strains tested [MIC90s], 0.12 to 4 micrograms/ml). However, some rarely isolated and selected Enterococcus sp. populations had a MIC90 of 16 micrograms/ml, and S. haemolyticus strains had a MIC90 of 8 micrograms/ml. These in vitro results suggest that decaplanin may be useful against most gram-positive strains, even though some Enterococcus species and coagulase-negative staphylococci were potentially resistant (MICs, greater than or equal to 8 micrograms/ml).


Disulfide-linked and non-disulfide-linked gamma/delta T-cell antigen receptors: differential expression on T-cell lines and clones derived from normal donors and patients with primary immunodeficiency disorders.

We studied the expression of gamma delta T cell receptors (TCR) on T-cell lines and clones derived from peripheral blood lymphocytes (PBL) from certain patients with primary immunodeficiency disorders and normal donors. Immunoprecipitation with the anti-Leu 4, anti-gamma-chain and/or anti-delta-chain monoclonal antibodies followed by SDS-PAGE analysis revealed that 7 of 13 (54%) T-cell lines and clones developed from PBL of patients with primary immunodeficiency disorders expressed non-disulfide-linked gamma delta TCR, utilizing either the C gamma 2abc or the C gamma 2bc gamma-chain constant region gene segment. 5 of 13 (38%) T-cell lines/clones expressed disulfide-linked gamma delta TCR, whereas an additional T-cell line was comprised of T cells expressing either disulfide-linked (C gamma 1) or non-disulfide-linked (C gamma 2bc) gamma delta TCR. T-cell lines and clones developed from four of light patients with primary immunodeficiency disorders exhibited exclusively non-disulfide-linked gamma delta TCR utilizing either the C gamma 2abc or the C gamma 2bc gamma-chain segment. T-cell lines derived from a fifth patient exhibited primarily non-disulfide-linked gamma delta TCR, bringing to five of eight the numbers of patients that expressed exclusively or primarily non-disulfide-linked gamma delta TCR. T-cell lines/clones derived from the remaining three patients exhibited exclusively disulfide-linked gamma delta TCR. The age of these patients varied over a wide range and there was not an association between their age and the type of gamma delta TCR expressed on T-cell lines derived from their PBL. In contrast, to these findings 14 of 16 (87.5%) T-cell clones derived from PBL of normal donors expressed disulfide-linked gamma delta TCR, whereas only 2 of 16 (12.5% expressed non-disulfide linked gamma delta TCR. Among the T-cell clones from normal donors which express disulfide-linked gamma delta TCR two different types were identified. Those exhibiting under reducing conditions on SDS-PAGE two completely resolved polypeptide chains in the range of 37 kD to 44 kD, and those exhibiting under the same conditions indistinguishable overlapping gamma- and delta- chains in the range of 40-42 kD. Several T-cell lines and clones from normal donors or patients with primary immunodeficiency that expressed either disulfide- or non-disulfide-linked gamma delta TCR were delta TCS1+, demonstrating that the delta TCS1 determinant is expressed on both types of gamma delta TCR.(ABSTRACT TRUNCATED AT 400 WORDS)


[Combination therapy of doxifluridine (5'-DFUR) + cyclophosphamide (CPA) + tamoxifen (TAM) for advanced or recurrent breast cancer. Joint Research Group in the Osaka Area for Combination Therapy of 5'-DFUR with Other Drugs].

Outpatients with advanced and recurrent breast cancer were treated by a combination therapy of the following drugs: doxifluridine (5'-DFUR) orally administered at a dose of 1200 mg/day; cyclophosphamide (CPA) orally given at dose of 100 mg/day; and tamoxifen (TAM) orally given at dose of 20 mg daily. 5'-DFUR and CPA were administered on consecutive days 1-14, then discontinued for 14 days. The response rate was 44.8% including five CR and eight PR out of 29 complete cases. As for response cases in terms of the subject lesions, corresponding cases were chiefly found in soft tissue and the lung. As for the response rate with or without pretreatment, cases previously treated showed a higher response rate such as 42.9% indicating that the present therapy was effective in pretreatment cases. The main side effect was leukopenia, but not so severe. Few cases with diarrhea were found. Based on the above findings, the present treatment is conceivably a highly useful therapy, on an outpatient basis, for advanced and recurrent breast cancer, especially metastatic lesions of soft tissue and the lung.


Antitumor activity of 5'-deoxy-5-fluorouridine in human digestive organ cancer xenografts and pyrimidine nucleoside phosphorylase activity in normal and neoplastic tissues from human digestive organs.

5'-Deoxy-5-fluorouridine (5'-DFUR) is believed to be metabolized to 5-fluorouracil (5-FU) by pyrimidine nucleoside phosphorylase (PyNPase). PyNPase activity is reported to be higher in neoplastic tissues than in normal tissues, and this has been proposed as an explanation for the selective cytotoxicity of 5'-DFUR against tumors. In the present study, PyNPase activity was measured in 95 neoplastic and normal specimens from human digestive organ tissues. In specimens from the esophagus, stomach, intestine and pancreas, PyNPase activity was higher in neoplastic tissues than in normal tissues. However, PyNPase activity in non-malignant liver tissues, especially cirrhotic liver tissues, was much higher than in the normal tissues of the other digestive organs. PyNPase activity in non-malignant liver tissues was a high as in primary liver tumors, and PyNPase activity in metastatic liver tumors was lower than in primary tumors and non-malignant cirrhotic tissues. The in vivo antitumor activities of oral 5'-DFUR and intravenous 5-FU were also assessed in 6 human digestive organ cancer xenograft lines transplanted subcutaneously in nude mice, and the relationship between the in vivo antitumor effects of 5'-DFUR and PyNPase activity in the tumors was assessed. However, there was no statistically significant correlation between them. Although the in vivo antitumor effect of intravenous 5-FU correlated significantly with the in vitro sensitivity of the tumors to 5-FU (assessed by DNA synthesis inhibition assay), the in vivo effects of 5'-DFUR did not correlate with the in vitro sensitivity to 5-FU. It is suggested that: (a) the liver may be the major site for metabolizing 5'-DFUR to 5-FU, and (b) measuring PyNPase activity in the tumor may not be a useful indicator for chemotherapy with 5'-DFUR.


[Clinical evaluation of ondansetron (injection of a single intravenous dose) against nausea and emesis associated with anti-cancer drugs--dose-finding study in patients receiving cisplatin].

We examined anti-emetic effects, safety and the optimal dose of Ondansetron Injection given in a single intravenous dose in patients receiving a single high dose of cisplatin in randomized controlled comparative study using telephone registration. Ondansetron was injected intravenously in a single dose of 4 mg, 8 mg or 12 mg, at 15 minutes before administration of cisplatin. Nausea and emesis were observed for 24 hours after administration of cisplatin. Efficacy rate of inhibitory effects on nausea and emesis were 76% (19/25 cases) in the 4 mg dose group, 57% (12/21 cases) in the 8 mg dose group and 83% (20/24 cases) in the 12 mg dose group, without a statistically significant difference among 3 dose groups. Hence, it was estimated that the low dose of 4 mg was adequate to exert satisfactory anti-emetic effects. No clear relationship between onset time of the initial emetic episode and plasma concentrations of Ondansetron was found in 16 cases of the 4 mg dose group, 11 cases in the 8 mg dose group and 15 cases in the 12 mg dose group. Side effects observed during this study period were headache and diarrhea in 1 case in the 12 mg dose group. Both symptoms were mild and resolved without treatment. No abnormal findings attributable to Ondansetron were observed in clinical laboratory test. From the above, it was considered that Ondansetron given by a single intravenous injection was highly effective to inhibit nausea and emesis induced by cisplatin, and was highly safe. As to the dose, 4 mg once daily was considered to be adequate for prophylaxis of cisplatin-induced nausea and emesis.


Chemoprevention of MNU-induced mammary tumors in the mature rat by 4-HPR and tamoxifen.

The chemopreventive efficacies of the retinoid all-trans-N-(4-hydroxyphenyl)-retinamide (4-HPR) and the anti-estrogen tamoxifen citrate were evaluated against N-methyl-N'-nitrosourea (MNU) induced mammary cancer in 120-day old female Sprague-Dawley rats. The agents were tested alone and in combination. They were administered in a modified AIN-76A diet, beginning 60 days prior to a single i.v. dose of 50 mg MNU/kg-bw and continuing until the end of the study, 180 days post-carcinogen treatment. At 782 mg/kg diet, 4-HPR alone significantly inhibited the induction of mammary adenocarcinomas compared with carcinogen controls. At 0.250 mg/kg diet, tamoxifen alone reduced tumor incidence compared with carcinogen controls. At 0.125 mg/kg diet, tamoxifen was ineffective. Combinations of 782 mg 4-HPR/kg diet with either 0.250 or 0.125 mg tamoxifen/kg diet were effective in inhibiting MNU-induced adenocarcinomas. The reductions in tumor incidence were greater for these combinations than for either agent alone. 4-HPR and 0.250 mg tamoxifen/kg diet decreased tumor incidence 81% (p less than 0.005), whereas 4-HPR and 0.125 mg tamoxifen/kg diet decreased tumor incidence 72% (p less than 0.005) compared with carcinogen controls. The combination of 391 mg 4-HPR/kg diet and 0.500 mg tamoxifen/kg diet was also tested and was effective in reducing tumor incidence.


[Examination of anti-emetic effect, safety and usefulness of single oral dose of ondansetron tablet in nausea and emesis induced by anti-cancer drugs--dose-finding study of ondansetron tablet in patients receiving non-platinum anti-cancer drugs].

Inhibitory effects on acute nausea and emesis, safety and usefulness of a single oral dose of Ondansetron tablet were evaluated in 3 different dose levels for comparison by telephone registration system, in patients receiving non-platinum anti-cancer drugs. A single dose of ondansetron at 4 mg, 8 mg or 12 mg was given orally at 2 hrs before the initial administration of anti-cancer drugs. The patients were observed for 24 hours after administration of anti-cancer drugs, for occurrence of nausea and emesis. Efficacy rates of inhibitory effects on nausea and emesis were 83.3% (10/12 cases) in 4 mg dose group, 78.6% (11/14 cases) in 8 mg dose group and 84.6% (11/13 cases) in 12 mg dose group, without statistically significant difference. Side effects were observed in 3 cases (headache, cold feeling and trembling in limbs, sleepiness) in 12 mg dose group, but these symptoms were not severe and disappeared after several hours or several days. No abnormality in clinical laboratory findings attributable to Ondansetron was observed. From the above, it was considered that Ondansetron was a clinically useful anti-emetic for nausea and emesis induced by non-platinum anti-cancer drugs and that 4 mg once daily was the optimal dose.


Suppressive effect of sesamin against 7,12-dimethylbenz[a]-anthracene induced rat mammary carcinogenesis.

The effects of dietary supplementation of sesamin on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats were studied. Experimental diets containing 0.2% sesamin (an equiweight mixture of sesamin and episesamin) or 0.2% alpha-tocopheryl acetate were given to rats starting 1 week before intragastric administration of DMBA (10 mg/rat). Sesamin significantly (p less than 0.05) reduced the cumulative number of palpable mammary cancers by 36% at 12 weeks post-DMBA administration compared with animals on a control diet. Alpha-tocopheryl acetate inhibited both the incidence and the cumulative number of mammary tumors by 20% and 45%, respectively. Concentrations of lipid peroxides in plasma, liver and tumors were all decreased in both sesamin and alpha-tocopheryl acetate groups. The activity of peripheral blood mononuclear cells (PBMC) increased in rats fed sesamin (140 to 150% of the control and alpha-tocopheryl acetate groups). Fatty acid compositions of plasma, liver and tumor phosphatidylcholine showed a decreased tendency of the metabolism of linoleic acid to arachidonic acid and hence of the plasma concentration of prostaglandin E2 in the sesamin group. The inhibitory effect of sesamin on DMBA-induced mammary carcinogenesis may be ascribed, at least in part, to immunopotentiation and increased antioxidative activity.


[Anti-emetic effect and safety of consecutive use of ondansetron injection in cisplatin-induced nausea and emesis].

Anti-emetic effect, safety and clinical usefulness of Ondansetron injection given in the dose of 4 mg once daily by intravenous administration for 3-5 consecutive days were examined in patients receiving a high single dose (not less than 50 mg/m2 or over 75 mg/body) and lower multiple doses (over 15-20 mg/m2 once daily, for 3-5 consecutive days) of cisplatin. Efficacy rates of inhibitory effects on nausea and emesis in patients receiving the high single dose of cisplatin were 76% on the 1st day, 67% on the 2nd day and 78% on the 3rd day, the average being 71% (86/121 cases) for the 3 days. Those in patients receiving lower multiple doses of cisplatin were 83% on the 1st day, 78% on the 2nd day, 61% on the 3rd day, 65% on the 4th day and 57% on the 5th day, the average being 72% (13/18 cases) for the 3-5 days. Side effects were observed in 15 cases out of 207 (1st course, 182 cases; 2nd course, 21 cases; 3rd course, 4 cases), and major symptoms were headache and fever. Also, abnormalities in clinical laboratory findings attributable to Ondansetron were observed in 13 cases, mainly consisting of elevation of the hepatic function values. From the above, Ondansetron injection which showed sufficient anti-emetic effects on acute emesis and delayed emesis induced by a high single dose or lower multiple doses of cisplatin with its once daily intravenous dose given for 3-5 consecutive days, were considered a safe and clinically useful anti-emetic.


[Examination of anti-emetic effect and safety of multiple intravenous doses of ondansetron in patients receiving nonplatinum anti-cancer drugs].

Anti-emetic effects, safety and usefulness of Ondansetron given intravenously at 4 mg once daily for consecutive 3-5 days were investigated against nausea and emesis induced by non-platinum anticancer drugs. Efficacy rates in control of nausea and emesis were 59% (20/34 cases) and 68% (23/34 cases), respectively. The efficacy rate for inhibition of nausea and emesis, calculated based on the control of nausea and emesis, was 68% (23/34 cases). Adverse events (headache and constipation) were observed in 1 case and abnormal change in clinical laboratory findings (increase in eosinophil count) in another case. Out of 42 cases in which safety was evaluated, 41 (98%) cases were assessed as "no problem in safety." However, one case with side effect was assessed as a "Minor problem in safety." From the above, it was confirmed that Ondansetron injection exerted excellent inhibitory effects against nausea and emesis induced by non-platinum anti-cancer drugs, and this drug was a highly safe and useful anti-emetic.


[A case of gastric cancer with recurrent bone metastases successfully treated with induced hypertension chemotherapy using cisplatin].

A sixty-eight-year-old female with bone metastases from gastric cancer successfully treated with induced hypertension chemotherapy using cisplatin is reported. She had undergone R2 curative subtotal gastrectomy in June 1985, and had orally taken tegafur 600 mg/day and then changed to doxifluridine 800 mg/day as postoperative adjuvant chemotherapy. Five months after the operation she had back pains and both 99mTc-MDP and 67Ga-citrate scintigram showed L1 vertebra and rib bone metastasis. Induced hypertension chemotherapy using cisplatin was then intermittently performed from January 1986 to September 1990, a single course of which was 25 mg/body div x 2/week for serial 4 weeks; a total of seven courses were carried out and consequently the total volume of the administered cisplatin reached 1,100 mg. Neither medullar nor renal toxicities were observed, but mild gastrointestinal symptoms were noted. The patient no longer has back pains, and no signs of bone metastases were seen on both scintigrams for two years and eight months from December 1988 to August 1991. This case is very rare because her bone metastases were successfully treated with induced hypertension chemotherapy using cisplatin. However, metastatic bone tumors from gastric cancer usually resist any treatments. It is expected that the successfully treated patients even with bone metastasis will be increasingly reported from now as various new approaches including induced hypertension chemotherapy are introduced.


Sensitivity of hysterosalpingography after tubal surgery.

Hysterosalpingography (HSG) to assess tubal patency in the postoperative evaluation of the infertile patient has been well described. However, the sensitivity and specificity of HSG after tubal surgery has not been reported. We correlated HSG and laparoscopic findings in 25 patients who had tubal surgery (microsurgical tubal reanastomoses [11] and distal salpingostomies [14]). HSG provided a more reliable means of assessing tubal patency (sensitivity and specificity of 96% and 61% respectively) than in detecting pelvic adhesive disease (PAD) (sensitivity and specificity of 12% and 75% respectively) regardless of tubal surgical procedure. HSG was associated with a high false negative rate (60%) due primarily to the inability to detect PAD. Complete agreement between HSG and laparoscopy was noted in only 15% of cases. These data suggest that HSG is a sensitive means to determine tubal patency, but was not sufficiently sensitive or specific to detect PAD after tubal surgery. These limitations should be noted in the interpretation of HSG in any infertile patient with a history of tubal surgery, and severely limits the application of HSG to the management of the post-operative infertile patient.


Laparoscopic cholecystectomy in the obese patient.

The authors' experience with laparoscopic cholecystectomy (LC) in obese (O, n = 96) and morbidly obese (MO, n = 27) patient groups was compared with that in the normal weight (NW, n = 174) group of patients as well as the whole group (WG). There were no operative deaths. There were no significant differences between groups for any of the following: successful intraoperative cholangiography (WG, 52.2%; NW, 52.9%; O, 51.1%; MO, 55.6%), conversion to open cholecystectomy (WG, 9.6%; NW, 9.2%; O, 10.4%; MO, 11.1%), incidence of major complications (WG, 4.1%; NW, 3.4%, O, 5.2%; MO, 0%), incidence of minor complications (WG, 7.4%, NW, 7.5%; O, 6.3%; MO, 3.7%), and length of hospitalization after successful LC (WG, 1.25 days; NW, 1.31 days; O, 1.16 days; MO, 1.13 days). Duration of operation did not differ except LC in the MO group (136.4 +/- 6.9 minutes) was longer when compared with NW patients (123.0 +/- 2.9 minutes, p less than 0.05). The authors conclude LC is a safe and effective treatment for obese patients with symptomatic cholelithiasis.


Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis.

This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.