Effectiveness of cisplatin, paclitaxel, and suramin against human malignant mesothelioma xenografts in athymic nude mice.

BACKGROUND AND OBJECTIVES: Malignant mesothelioma has a poor prognosis and is refractory to many agents. The antitumor effectiveness of cisplatin, paclitaxel, and suramin as single agents and in combination was evaluated in vivo against four lines of human pleural malignant mesothelioma xenografts in athymic nude mice, including one epithelial type and three fibrosarcomatous. METHODS: After growth of tumors occurred by day 54 or 55, mice were randomized in groups of four each to receive either cisplatin 4 mg/kg intraperitoneally weekly x5, or paclitaxel (Taxol) 12.5 mg/kg subcutaneously daily 5 days/week for 3 consecutive weeks, or suramin 60 mg/kg intraperitoneally daily x4,versus controls treated with normal saline. RESULTS: Cisplatin was very effective against one line and also to a lesser degree against another line. Paclitaxel showed antitumor effects similar to cisplatin, being very effective in one line, and also showed good activity in another line. Suramin was basically inactive in all four lines. Following the results obtained with these single agents, it was decided to evaluate the combination of cisplatin and paclitaxel, which resulted in more pronounced antitumor effect in all four cell lines. CONCLUSIONS: These results indicate that the combination of cisplatin and paclitaxel is superior to each agent alone in this model, and that it deserves to be evaluated in patients with malignant mesothelioma.

Different awareness of hypoglycaemia induced by human or purified pork insulin in type I diabetic patients.

Recently, there have been reports on a diminished awareness of hypoglycaemia after a switch from purified pork insulin (PPI) to human insulin (HI) in insulin-dependent diabetes mellitus (IDDM). To clarify this phenomenon we investigated nine IDDM patients without signs of autonomic neuropathy. After an overnight euglycaemic clamp, blood glucose was lowered to hypoglycaemic levels by means of an artificial pancreas (Biostator) on 2 days. Insulin was used in a double-blind, randomized, cross-over fashion, either PPI or HI. The symptomatology and the hormonal counterregulation of developing hypoglycaemia was recorded. Venous concentrations of free insulin, cortisol, glucagon, growth hormone and the prevailing blood glucose were similar under both insulins. Eight out of nine IDDM patients felt more symptoms and at a higher blood glucose concentration under PPI than under HI. The first symptom of developing hypoglycaemia appeared at a mean blood glucose concentration of 61.1 +/- 5.4 mg.dl-1 under PPI and 44.4 +/- 5.3 mg.dl-1 under HI respectively (P less than 0.05). We conclude that HI may cause symptoms of hypoglycaemia to appear later and with a lesser number in comparison to PPI.

Sexual and physical abuse in women with functional or organic gastrointestinal disorders.

STUDY OBJECTIVES: To determine the prevalence of a history of sexual and physical abuse in women seen in a referral-based gastroenterology practice, to determine whether patients with functional gastrointestinal disorders report greater frequencies of abuse than do patients with organic gastrointestinal diseases, and to determine whether a history of abuse is associated with more symptom reporting and health care utilization. DESIGN: A consecutive sample of women seen in a university-based gastroenterology practice over a 2-month period was asked to complete a brief questionnaire. MEASUREMENTS: The self-administered questionnaire requested information about demographics, symptoms, health care utilization, and history of abuse. Physicians indicated the primary diagnosis for each patient and whether she had ever discussed having been sexually or physically abused. RESULTS: Of 206 patients, 89 (44%) reported a history of sexual or physical abuse in childhood or later in life; all but 1 of the physically abused patients had been sexually abused. Almost one third of the abused patients had never discussed their experiences with anyone; only 17% had informed their doctors. Patients with functional disorders were more likely than those with organic disease diagnoses to report a history of forced intercourse (odds ratio, 2.08; 95% CI, 1.03 to 4.21) and frequent physical abuse (odds ratio, 11.39; CI, 2.22 to 58.48), chronic or recurrent abdominal pain (odds ratio, 2.06; CI, 1.03 to 4.12), and more lifetime surgeries (2.7 compared with 2.0 surgeries; P less than 0.03). Abused patients were more likely than nonabused patients to report pelvic pain (odds ratio, 4.05; CI, 1.41 to 11.69), multiple somatic symptoms (7.1 compared with 5.8 symptoms; P less than 0.001), and more lifetime surgeries (2.8 compared with 2.0 surgeries; P less than 0.01). CONCLUSIONS: We found that a history of sexual and physical abuse is a frequent, yet hidden, experience in women seen in referral-based gastroenterology practice and is particularly common in those with functional gastrointestinal disorders. A history of abuse, regardless of diagnosis, is associated with greater risk for symptom reporting and lifetime surgeries.

PIP: This study aims to determine the prevalence of sexual and physical abuse among women seen in a gastroenterology clinic. A total of 206 patients, who completed a self-administered questionnaire, were included in the analysis. Results indicated that 89 patients (44%) reported a history of sexual abuse or physical abuse in childhood or later in life; and all except one of the physically abused were also sexually abused. Among them, only 17% had informed their doctors about the abuse. Moreover, the 75 patients (36%) with functional gastrointestinal disorders were more likely than those with organic disease diagnosis to report a history of forced intercourse, frequent physical abuse, chronic or recurrent abdominal pain, and more lifetime surgeries. They were also more likely to be receiving psychological counseling for emotional concerns. Furthermore, abused patients were more likely than nonabused patients to report pelvic pain, multiple somatic symptoms, and more lifetime surgeries. In conclusion, this study discovered that there is a high prevalence of a history of sexual and physical abuse among women seen in a referral-based gastroenterology clinic, particularly those with functional gastrointestinal disorders.

Symptoms of hypoglycemia--a comparison between porcine and human insulin.

For more than 2 years now it has been controversially debated whether awareness of hypoglycemia is reduced when type I diabetic patients are switched from porcine to human insulin. In order to address this question, we studied nine C-peptide negative diabetics (age 27.6 years, Broca index 106%, duration of diabetes 5.7 years, HbA1, 8.8%) in comparison with eight healthy volunteers (age 22.4 years, Broca index 104%). Following euglycemic monitoring overnight, a controlled hypoglycemia was induced by altering the algorithms of the Biostator. This was done in a double-blind, cross-over fashion using porcine or human insulin on 2 nonconsecutive days. There were no differences between the results obtained with respect to the time course of the study, blood glucose, amount of insulin infused, and concentration of venous free insulin achieved. Of the nine diabetics, eight were aware of hypoglycemia at a higher blood glucose level under porcine insulin. The first symptom of hypoglycemia was perceived at a mean blood glucose level of 61.1 +/- 5.4 mg/dl under porcine insulin and of 44.4 +/- 5.3 mg/dl under human insulin (P less than or equal to 0.05). Thirty symptoms were noted under porcine insulin exclusively or preferentially as opposed to only eight which were observed exclusively or preferentially under human insulin. The healthy volunteers evidenced fewer symptoms at lower blood glucose concentrations than the diabetics. The clear difference between human and porcine insulin could not unequivocally be reproduced in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive and psychomotor function during hypoglycemia: a comparison between porcine and human insulin.

After an overnight euglycemic clamp, blood glucose levels were precisely lowered on two nonconsecutive mornings via a glucose-controlled insulin infusion system (GCIIS, Biostator) using either purified porcine insulin (PPI) or human insulin (HI). Two cognitive and psychomotor tests were significantly different in 8 type-I diabetic subjects and 8 healthy volunteers at four timepoints, when mean blood glucose concentrations (BGCs) were 100, 65, 50, and 40 mg/dl. Also, a significant difference (p = 0.005) could be found between the mean of all reaction time testing (RTT) values under HI as compared with the mean of all RTT values under PPI. Lowering the BGC resulted in a significant increase in the reaction time (p = 0.012). These effects were not dependent on the type of insulin being used nor were they typical of a particular study group.

The risk of AIDS: psychologic impact on the hemophilic population.

The psychologic impact of the risk of the acquired immune deficiency syndrome (AIDS) was evaluated by questionnaire survey of 116 hemophiliacs, age 16 or older, and 40 mates and 94 parents of hemophiliacs. Although the mean group distress ratings indicate a lessening of emotional discomfort over time, ongoing distress as well as interference with life activities are reported. Parents indicate more distress than either hemophiliacs or mates. Health preoccupation, the fear of being contagious, interference with parent-child intimacy and sexual intimacy between hemophiliac and mate are noted. A significant decrease in the use of clotting factor concentrates for the treatment of bleeding episodes is reported because these products have been linked to the transmission of AIDS. Although the overall hemophilic population is coping effectively with the AIDS risk, some hemophiliacs are at increased risk for psychiatric morbidity, social isolation, hypochondriasis, and medical noncompliance. Increased parental anxiety is likely to lead to over-protective child-rearing practices. Although it examines only the hemophilic population, this study describes stress responses likely to be present in other at risk groups and suggests that specific psychosocial interventions are urgently needed.

Slow and multiple unit potentials in trace and temporal conditioning controlled by electrical reward in the rat.

Rats trained to expect medial forebrain bundle electrical reward every 17 sec acquire, in their visual cortex, a linear gradient of increasing negative potential over the prereinforcement half of the interval. The postreinforcement half of the interval is occupied by a less linear reversal of the negative shift. Integrated multiple unit activity from the same electrodes shows for the same half intervals, respectively, acquisition of progressive increase and sudden decrease. Behaviorally, naive subjects are most active following the reinforcement, becoming progressively less active in the second half of the interreinforcement interval. After training, the above pattern is reversed with sudden cessation of activity following reinforcement and progressive increase beginning about 5 sec later and continuing to the time of reinforcement. Slopes for the negative anticipatory potential gradient (APG) ranged from 8 to 28 microV/sec in different subjects on the 17 sec interreinforcement interval. Doubling the interval halved the slope, the maximum prereinforcement negative voltage remaining constant. The phenomenon thus appears as a relative or pacing dynamic rather than as an absolute or fixed microvolts/second function. Making the interreinforcement interval variable caused loss of both the anticipatory gradient and the integrated multiple unit increment. Trace conditioning with variable intertrial interval restored an anticipatory gradient and multiple unit increment. The specific dissociation of unit firing activity during the APG previously reported in the quietly expectant cat is not seen in this study owing to the excited expectancy in the rat anticipating MFB reward. Although the longer periods of negative potential gradient and unit action potential activity appear associated rather than dissociated, transient dissociations in patterns were observed during shorter duration shifts in the slow potential. Resolution of these variations must await more definitive study of unit activity and sustained potential genesis.

EEG activity in the 13-15 Hz band correlates with intelligence in healthy elderly women.

Thirty-five elderly women in excellent health received a neuropsychological battery and resting electroencephalograms (EEGs) from bilateral parietal scalp electrodes. Spectral density analysis of the EEGs was designed to evaluate two levels each of slow activity (delta, 0.2-3.8 Hz and theta, 4.0-7.8 Hz), alpha activity (slow alpha, 7.0-9.8 Hz and fast alpha, 10.0-12.8 Hz) and fast activity (sigma, 13.2-14.8 Hz and beta, 15.0-20.0 Hz). There was no relationship between alpha slowing and cognitive impairment. However, significant correlations emerged between sigma activity and Wechsler Adult Intelligence Scale Scores. This association was strongest between right parietal sigma activity and WAIS Performance Scale weighted scores.

[Rubella immunization with HPV77DE5 and RA 27/3 vaccines of 11 to 16-year-old girls: studies of antibody formation and antibody resistance after 4 and 8 years]. / Die Rötelnschutzimpfung mit HPV77DE5- und RA 27/3-Impfstoffen von 11-16 Jahre alten Mädchen: Untersuchungen zur Antikörperentwicklung und Antikörperpersistenz nach 4 und 8 Jahren.

In the first prepubertal study 292 girls aged 11-15 years from 5 secondary schools were immunized with HPV77DE5 with the normal dose and 1/10 of it. The seronegative rate was 30.4%. HAI-antibody conversion occurred in 98.2 to 100%. The mean antibody titer in the two groups with 1:80 and 1:84 were 2 titer steps below the mean HAI-titer of the prevaccinal seropositive girls. The booster effect on the pre-existing titers was minimal. In the second prepubertal study with 625 girls aged 11-16 years from 3 gymnasiums 50.4% were seronegative. Of 312 seronegative girls, 56 had been immunized with HPV77DE5 s.c., 151 with RA 27/3 s.c. and 105 with RA 27/3 i.n. HAI-antibody conversion was observed in 98.2%, 100% and 100% respectively. The mean HAI-antibody titer following HPV77DE5 was +/- 2 titer steps, following RA 27/3 s.c. and RA 27/3 i.n. only 0.6 titer steps lower than the mean titer of the prevaccinal seropositive group. The individuals with a low prevaccinal antibody titer showed a significant but transient antibody booster response. Antibody titer controls 4 years post vaccination in 213 of the girls (160 prevaccinal seronegative, 53 prevaccinal seropositive) showed that all prevaccinal seronegatives had remained antibody-positive. The mean HAI-titer following HPV77DE5 was only slightly lower (1: 97) than 8-12 weeks post vaccination (1: 104) wereas the mean titers following RA 27/3 s.c. and i.n. showed a decline from 1: 158 to 1: 119 and from 1: 181 to 1: 111. The comparison of negative, low and higher HAI-antibody titers with neutralisation antibody titers in sera taken before, 8-12 weeks and 4 years after vaccination gave a perfect correlation between negative and positive results in both tests. Also 8 years post vaccination all vaccinees had remained seropositive. In comparison to the 4-year value, the geometric mean HAI antibody titer had dropped to somewhat lower levels of 1: 64, 1: 74 and 1: 64 respectively in the prevaccinal seronegative vaccinees so that no titer differences existed 8 years following vaccination in the different vaccine groups. Low positive HAI titers of 1: 16 were found in 3 of 23 (13%) in the HPV77DE5 group and in 2 of 76 (2.6%) in the RA 27/3 s.c. group but in none of 54 in the RA 27/3 i.n. group. The low positive HAI titer of 1: 16 could be confirmed in the HiG and ELISA IgG tests.(ABSTRACT TRUNCATED AT 400 WORDS)

Amplitude/standard deviation functions of somatosensory evoked potential recovery in healthy elderly and young adults.

Adjusted recovery ratios of somatosensory evoked potentials were computed using Callaway's amplitude/standard deviation measure of electrocortical activity in post-stimulus epochs of 15-30, 31-50, 51-90, and 90-240 msec. Significant differences in amount of recovery and shape of the recovery functions between young and elderly adults were observed only in early (15-90 msec) phases of the responses; subjects aged 60-70 did not differ from those aged 71-80. The results demonstrate a complex interaction between age and recovery, with stability of recovery functions after age 60.

The influence of high doses of oral medroxyprogesterone acetate on glucose tolerance, serum insulin levels and adrenal response to ACTH. A study of 17 patients under treatment for endometrial cancer.

Seventeen women aged 55 to 76 years who had been treated for endometrial cancer by surgery or radiotherapy or a combination of both were given 300 mg of medroxyprogesterone acetate (MPA) daily by mouth. Before treatment and again during the 3rd week of treatment an oral glucose tolerance test (with measurement of serum insulin levels) and an ACTH-stimulation test were done. All blood glucose levels tended to be higher with MOA therapy and serum insulin levels were significantly increased 3 h after a glucose load. The rise of serum cortisol 30 min after ACTH-stimulation was significantly less with MPA therapy. Oral MPA thus appeared to have a glucocorticoid-like action.

[Immunity against poliomyelitis in the German Federal Republic (author's transl)]. / Untersuchungen zur Immunitätslage gegen Poliomyelitis in Deutschland.

The immunity of the populations of several countries of the GFR against poliovirus 1, 2 and 3 was investigated in 11 laboratories. Sera of 4707 persons aged 0 to 30 years were assessed for neutralising antibodies (serum dilution 1:4) against the 3 types of poliovirus. 34.5% of the 4707 investigated sera had no neutralising antibodies at least against one type of the poliovirus, 4.7% showed no antibodies against all 3 types of the virus. Especially children aged 0 to 4 years were protected incompletely against the 3 types of poliovirus. In comparison with similar investigations of 1969 and 1972 no decisive change of immunity of the population of the GFR against poliomyelitis has occurred.