Twenty-four-hour intragastric acidity and clinical trial of bedtime enprostil 70 μg compared with ranitidine 300 mg in duodenal ulcer

The effects of bedtime 70 micrograms and twice daily 35 micrograms doses of enprostil on 24-hour intragastric acidity were investigated in nine duodenal ulcer patients in remission. Median nocturnal acidity decreased significantly by 30% with 35 micrograms twice daily, and by 48% with 70 micrograms at bedtime. In a clinical trial using bedtime dosing, 102 duodenal ulcer patients randomly received either ranitidine 300 mg or enprostil 70 micrograms. More ulcers healed after 4 and 8 weeks treatment with ranitidine than with enprostil (76% ranitidine vs 52% enprostil, at 4 weeks p = 0.0065 and 94% vs 68%, respectively at 8 weeks, P = 0.0007). However, 6 months after cessation of treatment there was no material difference in overall outcome. Despite combining mucosal protection with acid inhibition enprostil treatment conferred no advantage over simple acid inhibition.     

The incidence of multifocal cerebral gliomas. A histologic study of large hemisphere sections

A series of 241 gliomas (astrocytomas, oligodendrogliomas, glioblastomas, and subependymal giant-cell astrocytomas) was studied. This represents all the gliomas examined post mortem over 25 years at one hospital. Two hundred and one cases (85%) were apparently solitary tumors; of the 40 cases with multiple tumor foci, 23 (9.5%) were true multicentric gliomas. After excluding cases in which there was concomitant disease (neurofibromatosis, tuberose sclerosis, or multiple sclerosis), 18 cases of multicentric tumor (7.5%) remained. Multicentric tumors with different histologic appearances accounted for 2.9% of the series. Celloidin-embedded whole brain sections proved invaluable for the detection of microscopic neoplastic foci and unsuspected diffuse spread. The estimated incidence of multiplicity in gliomas is higher than in most series, but the findings suggest that detection of multifocal neoplastic change in these tumors is directly related to the extent to which the brain is sampled, and that figures obtained in this study may well underestimate the true incidence.     

Improved estimates of discordance ratios in twin studies

In the study of monozygotic twins relative to disease and risk factors, particular interest focuses on the subset who are discordant for some suspected risk factor (for example, smoking), since such twins constitute a natural case-control pair. In such studies, questionnaires designed to identify the status of all twin pairs are sometimes error prone and can yield misleading estimates of the concordance-discordance ratios. Greater efforts to verify the characteristics of apparently discordant pairs than to verify those of apparently concordant pairs can result in the 'unequal ascertainment' fallacy. Using the results of a questionnaire with known error rates and the 'apparent' frequencies yielded, we present unbiased, maximum likelihood estimates of the 'true' proportions of concordant and discordant pairs. concordant and discordant pairs. We also present approximate covariances among these estimates.     

Changes in CSF neurotransmitters in infantile spasms

Cerebrospinal fluid (CSF) from 7 patients with infantile spasms (mean age: 6.7 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of neurotransmitter metabolites was analyzed using high-performance liquid chromatography and compared to the metabolite concentration in the CSF from 7 age-matched controls (mean age: 6.1 months). Pretreatment levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol (MHPG), and kynurenine were significantly lower in infantile spasm patients compared to controls. Following treatment, marked increases in 5-HIAA and decreases in kynurenine levels were observed in the CSF of the 5 infants whose seizures were eliminated or reduced by ACTH. In the 2 nonresponders 5-HIAA levels decreased. The level of MHPG was reduced slightly in 5 infants, including the 2 nonresponders, and was increased in 2 responders. CSF homovanillic acid levels increased in 4 infantile spasm infants and decreased in 3 following ACTH. These data demonstrate that the presence of seizures in infantile spasms is associated with a significant decrease in serotonergic activity and that elimination of seizures by ACTH is accompanied by increased serotonin turnover. The simultaneous increase of 5-HIAA and decrease of kynurenine, an alternate metabolite of tryptophan, suggests an underlying disturbance of tryptophan metabolism in infantile spasms. The possibility that elimination of seizures by ACTH may be related to decreased production of certain kynurenine metabolites, particularly quinolinic acid, is discussed.     

Comparative study of 3 therapeutic methods for Pouteau Colles' fracture. Apropos of 97 cases

Results of three therapeutic modalities used for the treatment of a homogeneous series of patients with a Pouteau Colles fracture are analyzed. Orthopedic treatment provided deceiving results. Pinning was, on the contrary, very effective, intrafocal pinning with immediate mobilization of the wrist appearing perfectly effective. Few complications were reported in contrast to plastered immobilizations. Good results were obtained in 80% of cases and functional recovery was rapid, indicating that this method represents undoubted progress when compared with conventional therapies.     

Allografts of CNS tissue possess a blood-brain barrier. II. Angiogenesis in solid tissue and cell suspension grafts

Angiogenesis and patency of blood vessels were analyzed qualitatively in solid CNS and peripheral tissue syngeneic, allogeneic, and xenogeneic grafts and in individual cell suspension grafts of astrocytes, fibroblasts, PC12, and three additional tumor cell lines placed intracerebrally in adult host mice. Postgrafting survival times were 1 day through 4 weeks. The patency of graft vessels was determined in sections from immersion-fixed tissues incubated to reveal the endogenous peroxidase activity of host red cells trapped within the lumen of blood vessels. Additionally, horseradish peroxidase (HRP) was administered intravenously to live hosts; HRP labels host brain and graft vessels on the luminal surface and reveals the presence or absence of a blood-brain barrier (BBB) within the grafts. The origins of blood vessels supplying solid tissue xenografts were identified immunohistochemically with primary antibodies against host (athymic AKR mice) and donor (fetal Lewis rats) major histocompatibility complex (MHC) class I. Blood vessels supplying solid CNS grafts at 1-7 days post-transplantation were identified ultrastructurally and possessed interendothelial tight junctional complexes; however, they were not perfused with either host blood or blood-borne HRP prior to 8 days. Graft vessels at 10 days were outlined consistently by peroxidase-positive red cells in immersion-fixed material and labeled with blood-borne HRP. These vessels provided a BBB to the circulating HRP and exhibited interendothelial tight junctions. Evidence of angiogenesis within solid anterior pituitary grafts and the variety of cell suspension grafts was obtained prior to 3 days post-transplantation in immersion-fixed preparations; the vessels, with the notable exception of those supplying astrocyte cell suspensions, failed to present a BBB to blood-borne peroxidase. Endothelia in the solid pituitary allografts and the PC12 cell grafts were highly fenestrated and exhibited open interendothelial junctions; those in the tumor and fibroblast cell grafts, for the most part, appeared nonfenestrated, and many possessed open interendothelial junctional complexes. Immunostaining for host and donor MHC class I revealed that donor blood vessels predominate over host vessels in CNS xenografts and supply pituitary xenografts exclusively; in both preparations, donor vessels were not identified within the host CNS. Because cell suspension grafts were derived from endothelia-free preparations grown in culture, blood vessels supplying these grafts were necessarily of host CNS origin and manifested a morphological transformation from a BBB to a non-BBB endothelium. The data suggest that angiogenesis in solid CNS grafts placed into the adult host CNS, compared to similarly placed solid peripheral tissue/cell suspension grafts, is not rapid.(ABSTRACT TRUNCATED AT 400 WORDS)     

Gold complex research in medical science. Difficulties with experimental design

Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been established. Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium thiomalate thus can exist in several different physical states which may have different biological activity. In addition the pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action, efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist at different pH. Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow or a colourless solution. These have some similar but several different biological activities. Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to the wide variation in physical structure and biological activities exhibited by these compounds.