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Biomedical subjects

M Loeb

Publications and source records attributed to M Loeb.

At least 19 recordsLinked to original sources
PubMed1995

Treatment with letrazuril of refractory cryptosporidial diarrhea complicating AIDS.

Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic cryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial. Treatment was continued for > or = 10 days and for as long as there was a response. The majority of subjects (91%), had previously failed paromomycin treatment. At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (> 10 bowel movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation. Twenty-two patients had a partial response (> 50% reduction in bowel movements per day for > or = 1 week), one patient had a complete response (two or fewer bowel movements per day). Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 months following initiation of letrazuril. The other eight (35%) had had symptom control for an average of 2.9 months from initiation of letrazuril to the latest follow-up. Microbiologic eradication was demonstrated in 10 (40%) of 25 patients with follow-up stool examinations. Seven patients (20%) experienced a rash, all within 1 week of starting the drug, and resolved in all patients when the drug was discontinued. In conclusion, severely immunocompromised AIDS patients with refractory cryptosporidiosis may show a modest, short-lived response to letrazuril. Microbiologic response is variable and relapse high. Rash is a major limiting side effect of the drug.

Acetonitriles↗
PubMed1995

5-HT4 receptor mediated stimulation of gastric emptying in rats.

It is well documented that certain substituted benzamides, such as cisapride, and benzimidazolones, such as BIMU 8, enhance gastric emptying in rats. As these compounds possess 5-HT3 antagonistic and 5-HT4 agonistic properties, the precise mechanisms (5-HT3 or 5-HT4) underlying their gastroprokinetic effects is still unclear. In the present study, we used SC 49518 (a benzamide and selective 5-HT4 receptor agonist) and two selective 5-HT4 receptor antagonists (RS 23597-190 and SB 204070) to elucidate the role of 5-HT4 receptors in gastroprokinesis. SC 49518 (1-316 micrograms/kg; ip) produced significant and dose-dependent stimulation of gastric emptying in rats (ED50 = 2.3 micrograms/kg; ip). SC 49518 also produced dose-dependent inhibition of bradycardia induced by 2-methyl 5-HT (von Bezold-Jarisch reflex) but with a 156 fold lower potency (ID50 = 0.36 mg/kg; ip). The gastroprokinetic effects of SC 49518 (3-316 micrograms/kg; ip) were significantly antagonized by the selective 5-HT4 receptor antagonist RS 23597-190 (0.1 mg/kg/min; iv). SB 204070 (0.003-1 mg/kg; ip), another selective 5-HT4 receptor antagonist, produced dose-dependent inhibition of the gastroprokinetic effects of SC 49518 (10 micrograms/kg; ip), the inhibition attaining statistical significance at the dose of 0.1 mg/kg; ip. RS 23597-190 had no effects on gastric emptying per se whereas SB 204070 significantly increased gastric emptying by itself at 1 mg/kg; ip but not at 0.1 mg/kg; ip. These findings show, for the first time, that SC 49518, a selective 5-HT4 receptor agonist, produces potent stimulation of gastric emptying in rats via a mechanism involving activation of 5-HT4 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Can psychological traits predict the outcome of lumbar disc surgery when anamnestic and physiological risk factors are controlled for? Results of a prospective cohort study.

In a prospective study 122 patients with herniated lumbar disc pre-operatively completed psychological questionnaires. Surgical outcome was evaluated 12 months post-operatively mainly by a composite clinical overall score (COS), and by its separate elements. Anxiety (HAD-A scale) and psychosomatic symptoms (MSPQ) had predictive value: fewer symptoms favoured a satisfactory overall outcome, and vice versa. The HAD-A Scale had a predictive power of poor (ppp) and satisfactory (pps) outcome of 28 and 81%, respectively. Correspondingly, for the MSPQ, the ppp and pps were 42 and 85%. Anamnestic and biological variables (including fibrinolytic variables: ECLT and PAI-1) predicted 20% of the outcome. By adding all psychological variables the prediction increased only to 24%, but the HAD-A Scale and the MSPQ were still significant. The results suggest that in order to further improve prediction of outcome, future studies should combine biological variables sensitive to the mental state of the patient, with psychometric assessments.

Adaptation, Psychological↗
PubMed1995

Effects of an acidic beverage (Coca-Cola) on absorption of ketoconazole.

Absorption of ketoconazole is impaired in patients with achlorhydria. The purpose of this study was to determine the effectiveness of a palatable acidic beverage (Coca-Cola Classic, pH 2.5) in improving the absorption of ketoconazole in the presence of drug-induced achlorhydria. A prospective, randomized, three-way crossover design with a 1-week wash-out period between each treatment was employed. Nine healthy nonsmoking, nonobese volunteers between 22 and 41 years old were studied. Each subject was randomized to receive three treatments: (A) ketoconazole 200-mg tablet with water (control), (B) omeprazole (60 mg) followed by ketoconazole (200 mg) taken with water, and (C) omeprazole (60 mg) followed by ketoconazole (200 mg) taken with 240 ml of Coca-Cola Classic. The pH values of gastric aspirates were checked after omeprazole was administered to confirm attainment of a pH of > 6. Multiple serum samples were obtained for measurements of ketoconazole concentrations by high-pressure liquid chromatography. The mean area under the ketoconazole concentration-time curve from zero to infinity for the control treatment (17.9 +/- 13.1 mg.h/liter) was significantly greater than that for treatment B (3.5 +/- 5.1 mg.h/liter; 16.6% +/- 15.0% of control). The mean peak concentration was highest for the control treatment (4.1 +/- 1.9 micrograms/ml), for which the mean peak concentration showed a significant increase over that for treatment B. The absorption of ketoconazole was reduced in the presence of omeprazole-induced achlorhydria. However, drug absorption was significantly increased, to approximately 65% of the mean for the control treatment, when the drug was taken with an acidic beverage, such as Coca-Cola.

Achlorhydria↗
PubMed1995

Bacillus species pseudobacteremia following hospital construction.

A 13-fold increase (0.08 to 1.05%) in the isolation rate of Bacillus species from in-patient blood cultures led to the investigation of pseudobacteremia over a four-month period. Data on blood isolates (BACTEC NR 660, bottle types 6A and PEDS) of Bacillus species were compiled between July and October 1993. BACTEC bottles, as well as their plastic lids and rubber septa (representing 20% of stored bottles), and alcohol swabs, iodine preparation pads and butterfly collection systems were cultured. Air plates inside the BACTEC 660 instrument were cultured, as well as swabs of both the BACTEC needles and the interior of the BACTEC handling area. To investigate carry-over contamination, sterile BACTEC bottles were tested immediately following bottles containing Bacillus species. Growth of Bacillus species was obtained from 16% of the plastic lids and 1.3% of the rubber septa. No growth was obtained from other cultures. The outbreak coincide with construction on a driveway of the hospital over the area where BACTEC bottles were stored. Upon completion of construction in November 1993, the isolation of Bacillus species returned to baseline. No pseudobacteremia isolates occurred in areas where the trained intravenous team was assigned. In conclusion, hospital construction leading to airborne spread of Bacillus species may cause Bacillus species pseudobacteremia, and failure to disinfect blood culture bottles adequately may predispose to such an outcome.

Bacillaceae Infections↗
PubMed1995

Pharmacological evaluation of 1229U91, a novel high-affinity and selective neuropeptide Y-Y1 receptor antagonist.

The physiological role of neuropeptide Y (NPY), peptide YY (PYY) and their receptors (Y1 and Y2) has been difficult to elucidate mainly due to the lack of selective and high-affinity antagonists. Recently, Burroughs Wellcome disclosed a series of cyclic peptides, including the compound 1229U91, which were reported to be selective NPY receptor antagonists (PCT Publication No. WO 94/00486). The objective of this study was to evaluate the pharmacological properties of 1229U91. In radioligand binding studies, 1229U91 displaced specifically bound [125I]PYY from SK-N-MC cells (Y1 receptors) and SK-N-BE(2) cells (Y2 receptors) yielding pKi +/- S.E.M. estimates of 10.9 +/- 0.2 and 7.9 +/- 0.2, respectively. In the isolated perfused kidney of rat (Y1 receptor assay), NPY (10-1000 ng, bolus injection) evoked concentration-dependent increases in perfusion pressure (EC50 = 54.5 ng). In this assay, 1229U91 (1, 10 and 100 nM) produced concentration-dependent dextral displacement of the concentration-effect curve to NPY. The antagonism was surmountable at 1 nM 1229U91 (apparent pA2 estimate +/- S.E.M. = 9.3 +/- 0.4). At concentrations of 10 and 100 nM, 1229U91 produced significant depression of the maximum response to NPY (36 and 67%, respectively). In the vas deferens of rat (Y2 receptor assay), 1229U91 (3 microM) had no effect on NPY-induced inhibition of electrically evoked twitch response. In pithed rats, 1229U91 (0.3, 1 and 3 micrograms/kg/min i.v.) produced dose-dependent dextral displacement of the pressor dose-response curve to NPY yielding dose-ratio estimates of 2.4, 25.4 and 57.5, respectively. 1229U91 (3 micrograms/kg/min i.v.) had no effect on the pressor responses to norepinephrine or angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

[Vegetarians and vitamin B12. A controlled trial of vitamin B12 status in 63 lactovegetarians].

In this study vitamin B12 status was assessed in 63 adult long-term lactovegetarians and 63 controls. No significant difference in mean plasma levels of vitamin B12 was found between the two groups. In contrast to what might have been expected, the vegetarians showed a slight increase in the vitamin B12 levels with increasing number of years as vegetarians. There was a significant (r = 0.34, p = 0.01) correlation between oral intake of vitamin B12 in the lactovegetarians and the plasma levels of the vitamin. Folate in plasma and whole blood were significantly higher (p < 0.001) in the vegetarian group than in the control group. The findings do not indicate that lactovegetarians risk developing dietary-induced vitamin B12 deficiency.

Adult↗
PubMed1994

Evidence for the involvement of 5-hydroxytryptamine 4 receptors in 5-hydroxytryptophan-induced diarrhea in mice.

The objective of this study was to characterize the receptor(s) to 5-HT mediating 5-HTP-induced diarrhea in mice. The severity of diarrhea in mice was assessed using an arbitary scoring scale ranging from 0 (normal stools) to 3 (watery diarrhea). Administration of 5-HTP (1-30 mg/kg i.p.) produced a dose-dependent increase in diarrhea score (ED50, 1.47 mg/kg i.p.). 5-HTP (10 mg/kg i.p.)-induced diarrhea was unaffected by atropine (3 mg/kg i.p.) but was completely abolished by the aromatic L-amino acid decarboxylase inhibitor benserazide (10 mg/kg i.p.). Pretreatment (5 min before 5-HTP) with DAU 6285, a marginally selective 5-HT4 receptor antagonist, significantly inhibited 5-HTP-induced diarrhea (ID50, 0.58 mg/kg i.p.). Pretreatment (5 min before 5-HTP) with GR 113808 or SB 204070, two highly selective 5-HT4 antagonists, significantly inhibited 5-HTP-induced diarrhea with ID50 estimates of 0.31 and 0.003 mg/kg i.p., respectively. The maximal inhibition produced by DAU 6285, GR 113808 and SB 204070 was 63%, 68% and 36%, respectively. Neither GR 113808 (1 and 3 mg/kg i.p.) nor SB 204070 (0.1 and 1 mg/kg i.p.) had any effect on 16,16-dimethyl prostaglandin E2 (30 micrograms/kg i.p.)-induced diarrhea in mice. DAU 6285 significantly inhibited 16,16-dimethyl prostaglandin E2-induced diarrhea at the highest dose (3 mg/kg i.p.). Pretreatment (30 min before 5-HTP) with methysergide (0.1-3 mg/kg i.p.), metergoline (0.01-0.1 mg/kg i.p.), ketanserin (0.01-1 mg/kg i.p.), YM 060 (0.01-0.1 mg/kg i.p.) or ondansetron (0.01-3 mg/kg i.p.) had no significant effects on 5-HTP-induced diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1993

Rheumatoid arthritis and vertebral artery occlusion: a case report with angiographic and magnetic resonance demonstration.

A 40-year-old woman with rheumatoid arthritis (RA) who presented with vertigo and nausea, was found to have left vertebral artery occlusion on angiography. There was minimal atlantoaxial subluxation and no odontoid herniation. Magnetic resonance imaging (MRI) was suggestive of a left vertebral artery dissection. This is the first report of MRI of vertebral artery occlusion in RA. It will be important to accumulate MR images of this complication in future cases.

Adult↗
PubMed1992

Hemolymph concentrations of host ecdysteroids are strongly suppressed in precocious prepupae of Trichoplusia ni parasitized and pseudoparasitized by Chelonus near curvimaculatus.

Regulation of ecdysteroid production in lepidopteran prepupae was studied using a parasitic wasp (C. near curvimaculatus) which specifically suppresses host prepupal ecdysteroid production after the induction of precocious host metamorphosis. At the developmental stage at which the hemolymph of the unparasitized metamorphosing host has its maximum titer of prepupal ecdysteroids, the hemolymph of 4th instar "truly parasitized" hosts (hosts with a surviving endoparasite) had a strongly reduced ecdysteroid titer. However, during the photophase about 12 h later, just prior to emergence of the parasite larva, an ecdysteroid peak was observed in the host hemolymph. Fourth instar pseudoparasitized prepupal hosts (in which the endoparasite was not present or died early in development) exhibited a sustained suppression in the hemolymph ecdysteroid titer. Small 5th instar pseudoparasitized hosts, which normally would molt to a 6th instar prior to metamorphosis, but which precociously attained the prepupal stage, also had a strongly reduced ecdysteroid titer. The late increase observed in truly parasitized hosts could be completely prevented by surgical removal of the parasite 24 h earlier, resulting in a titer similar to that in pseudoparasitized hosts. HPLC analysis of ecdysteroids in normal, truly parasitized, and 4th or 5th instar pseudoparasitized prepupae showed that both ecdysone and 20-OH ecdysone* were suppressed in truly and pseudoparasitized prepupae, with ecdysteroid levels being lowest in pseudoparasitized hosts. These data, and those of Brown and Reed-Larsen (Biol Contr 1, 136 [1992]), showing endoparasite secretion of ecdysteroids just prior to its emergence from the host, strongly indicate that: (1) the prepupal peak in truly parasitized hosts originates from the endoparasite, and (2) the low level of ecdysteroids in pseudoparasitized hosts results from the host's intrinsic inability to express a normal level of prepupal ecdysteroid titer. While precocious 4th or 5th instar prepupae of similar size had similarly suppressed ecdysteroid titers, smaller 4th instar prepupae had a lower ecdysteroid titer than larger, precocious 5th instar prepupae. Rare 5th instar pseudoparasitized prepupae that were of nearly normal size showed a prepupal ecdysteroid titer distinctly greater than those of the usual smaller, precocious 5th instar prepupae. The data suggest that the competence of the host to express a normal hemolymph titer of prepupal ecdysteroids is more closely correlated with the size of the prepupae than with the instar attained.

Animals↗
PubMed1992

Fibrinolytic activity as a predictor of the outcome of prolapsed intervertebral lumbar disc surgery with reference to background variables: results of a prospective cohort study.

In a prospective study 122 patients with a slipped lumbar disc and no previous surgery were preoperatively examined for fibrinolytic activity. Surgical results for these patients were evaluated 12 months postoperatively by clinical overall assessment. In a multiple linear regression analysis fibrinolytic variables, euglobulin clot lysis time and plasminogen activator inhibitor 1, were shown to have predictive value regarding outcome of surgery; that is, normal fibrinolytic activity favors a satisfactory outcome and vice versa. Background variables and lipid profile were also recorded preoperatively. Body mass index, gamma-glutamyl transpeptidase, triglycerides and smoking were of statistical significance in relation to euglobulin clot lysis time and plasminogen activator inhibitor 1. Postoperative fibrinolytic re-examination of 20 patients seem to confirm that patients at risk of surgical failure have a prolonged depression of fibrinolytic activity.

Cohort Studies↗
PubMed1986

Postoperative radiotherapy in breast cancer--long-term results from the Oslo study.

The long-term results of a randomized clinical trial evaluating the effect of postoperative radiotherapy as an adjuvant to radical mastectomy are presented. There were 1115 patients including 27 protocol deviants. The follow-up time is 11-20 years. In the first part a conventional roentgen unit was used, and in the second part a 60Co unit, with considerably increased dosage and altered treatment plan. Both types of radiation techniques lowered the incidence of loco-regional recurrences significantly, but had no significant influence on the overall survival. The relapse-free survival was significantly improved by 60Co radiation in Stage II patients, but was unaffected by radiation in the other subgroups. Regarding survival, Stage II patients with medially located tumors seemed to benefit more from 60Co radiation than those with lateral tumors. A significant increase in the number of deaths caused by myocardial infarction was observed in Stage I patients having 60Co radiation, indicating that the radiation dose to the heart is of significance.

Aged↗
PubMed1985

Doxifluridine (5'-dFUrd) in patients with advanced colorectal carcinoma. A phase II study.

Infusion of 5'-dFUrd (2.0-3.0 g/m2 over 1 h on days 1-5 every 3rd week) resulted in one partial response in 21 patients with advanced and progressing colorectal cancer. No patient had received chemotherapy before the 5'-dFUrd trial. Hematological and gastrointestinal toxicity were generally mild. In 4 patients peripheral neurotoxicity was diagnosed during treatment, whereas transient cerebellopathy was observed in one. Cardiac side effects (repeated angina pectoris following 5'-dFUrd infusion) led to discontinuation of treatment after two courses in one patient. It is concluded that 5'-dFUrd at the above doses is not superior to conventional 5-FU treatment in colorectal cancer. Neurological and cardiac side effects are rare but may be a problem in individual patients.

Angina Pectoris↗
PubMed1985

Post-treatment fertility in patients with testicular cancer. I. Influence of retroperitoneal lymph node dissection on ejaculatory potency.

"Dry ejaculation" occurred in none of 15 patients with testicular cancer treated by right-sided retroperitoneal lymph node dissection (RLND). After left-sided and bilateral RLND, "dry ejaculation" was observed in 7/21 and 51/61 men respectively. Twelve of 21 patients with "dry ejaculation" or small volumes of seminal fluid had true retrograde ejaculation. In 7 of 10 men the ejaculatory volume increased significantly after treatment with imipramine chloride. Four men impregnated their wives during treatment with the drug. Without impairing the results of therapy it is possible to spare fibres from the sympathetic chains and pre-sacral plexus during RLND due to testicular cancer, thus preserving fertility in at least 40% of patients.

Adolescent↗
PubMed1985

Post-treatment fertility in patients with testicular cancer. II. Influence of cis-platin-based combination chemotherapy and of retroperitoneal surgery on hormone and sperm cell production.

Active sperm production was observed in 20 of 35 patients with testicular cancer 1 year after discontinuation of all treatment (retroperitoneal surgery only: 13; cis-platin-based chemotherapy (CVB) +/- other treatment: 22). The percentage of patients who regained spermatogenesis increased slightly after a further 1 to 2 years. Fourteen patients (of 121 under observation) impregnated their wives (after retroperitoneal surgery: 9; after CVB +/- other therapy: 5). The individual serum FSH values correlated significantly with the results of sperm analysis: an FSH value greater than or equal to 20 iu/l indicated azoospermia in 8 of 12 patients, whereas only 5 of 30 patients with FSH levels less than or equal to 12 iu/l were azoospermic. Serum testosterone and pituitary serum LH were virtually unaffected by the treatment. In conclusion, 1 to 3 years after cis-platin-based multi-modality treatment for testicular cancer, 50 to 60% of patients have active spermatogenesis and fatherhood can be achieved by a significant number of them.

Antineoplastic Combined Chemotherapy Protocols↗