Statistical analysis of gastrointestinal transit time of pharmaceutical formulations: comments on the letter by Devereux & Newton.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K Schmidt.
Explore the source record for details and available documents.
A description of development in the utilization pattern of cimetidine (Tagamet) in Denmark is given on the basis of 19 154 granted applications for individual drug reimbursement submitted to the National Board of Health from the initial registration of cimetidine in September 1977 until general reimbursement was introduced in July 1981. The application rate per 100 000 inhabitants increased steeply from 49 in 1978 to 148 in 1980 and decreased to 127 in 1981. Despite this rapid introduction, however, hospital utilization for ulcer disease was constant during this period. Half of the applications treated diagnosed duodenal ulcers and a third gastric ulcers. Only 50% of those gastric ulcers were diagnosed by endoscopy. The age-specific application rate reached a peak in the age group of 50-69 years. There was a considerable geographical variation in the rate of application. The reason for this is unknown, since the variations in the ages of patients and years of application were different in different counties, and no correlation between application rate and proxy variables for standard of health and special interest in ulcer disease between the different counties could be shown.
A study lasting 1 year assessed the effectiveness and tolerance of depot neuroleptic treatment with pipothiazine palmitate in 52 patients suffering from schizophrenia or related conditions (17 acute and 35 chronic). A 100 mg dose was given to 31 patients and 50 mg to 21 patients: 40 patients received injections 4-weekly, 8 patients 3-weekly and 4 patients 2-weekly. Duration of treatment ranged from 3 to 12 months, involving a total of 347 patient-months. The significant improvement produced by pipothiazine palmitate as shown by patient assessment, based on the Parkside Behaviour Rating Scale (p less than 0.05), a Hamilton-based affect scale (p less than 0.05) and a global rating scale of affect and psychomotor activity (p less than 0.01). Most target symptoms were relieved. A particularly favourable affective response was noted. The incidence of adverse reactions was low and did not present major problems; 6 cases of dystonic reaction were seen, but dealt with promptly and effectively.
The effect of in vivo diethylstilbestrol (DES) treatment on the MtT/W15 transplantable pituitary tumor was examined in dissociated pituitary cells by measuring the rate of incorporation of [3H]thymidine into DNA and the synthesis of prolactin (PRL) and growth hormone (GH) as assessed by the rate of incorporation of [3H]leucine. MtT/W15 transplantable pituitary tumors from rats treated for 3 weeks with DES showed significant reduction in the extent of [3H]thymidine incorporation compared with tumor cells from untreated rats (2231 +/- 182 vs 172 +/- 17 dpm/10(5) cells; n = 3). In addition, tumor cells from DES-treated rats showed a significant increase in GH synthesis compared with tumor cells from untreated rats. In contrast to these findings, dissociated pituitary cells from non-tumor-bearing rats given 10 mg DES in Silastic tubing for 3 weeks showed a three-fold increase in PRL synthesis compared to cells from untreated control rats (29.3 +/- 1.5 vs 10.0 +/- 0.9% of total radioactivity in gel; n = 3. There was also a four-fold increase in the rate of [3H]thymidine incorporation after DES-treatment in non-tumor-bearing rats (695 +/- 114 vs 178 +/- 13.9 dpm/10(5) cells; n = 3). These results indicate that DES inhibits MtT/W15 pituitary tumor cell proliferation, while stimulating synthesis of GH.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A rapid immunostaining method utilizing a preformed antibody-avidin-biotin-peroxidase complex that produces staining in paraffin sections and in frozen sections of tissues in 15 minutes is described. Although the complex did not produce staining with the common leukocyte monoclonal antibody, consistent staining was seen with most antibodies used. The complex gave consistent and reproducible staining for at least three months when maintained in storage at 4 degrees C. The results show that many available antibodies can be adapted to a rapid one-step staining procedure employing the avidin-biotin-peroxidase complex system.
Branched chain alpha-ketoacid dehydrogenase (BCKAD) deficiency, or maple syrup urine disease (MSUD), can be categorized as classical, intermediate, intermittent or thiamine responsive, based on generally concordant in vitro BCKAD activity and severity of phenotype. We present clinical and enzymatic data on a boy with intermediate maple syrup urine disease, and suggest that he represents a novel category of mutation. He presented at age 10 months in ketoacidotic coma, with a history of irritability, poor feeding and growth and developmental delay. Branched chain amino acid restriction effected normal growth and developmental parameters by age 42 months. In contrast to previous patients with intermediate MSUD, his fibroblasts and fibroblast extracts failed to decarboxylate [1-14C]-alpha-ketoisovalerate (KIV). The defect is not in mitochondrial transport of substrate, but rather in the catalytic activity of the E1 component of the BCKAD. Disrupted cells of the proband exhibited negligible BCKAD activity over a wide range of keto acid substrate concentrations, irrespective of the presence of added thiamine pyrophosphate (TPP). These results differ from the sigmoidal kinetics observed using classical MSUD extracts, and the hyperbolic kinetics with control preparations under the same assay conditions. We propose that the structurally altered enzyme possesses reduced but not negligible activity in vivo, and exists as an unstable complex in vitro under assay conditions used, even in the presence of added TPP.
Electrodermal activity of 11 children with conduct disorder (CD) and 11 normal children were compared during periods of rest, moderate tone and loud bell stimulation. The CD group was best differentiated from controls by lower reactivity to the first bell, while on tonic measures they showed normal values. The electrodermal profile of the CD children thus resembled that of adult sociopaths on phasic measures only. The possibility of using electrodermal measures for predicting outcome and for differential diagnosis is raised.
The authors report a prospective, randomized 18-month study on the effect of prophylactic antibiotic treatment in 152 hydrocephalic patients in whom clean shunt operations or revisions were done. The treated group received methicillin (totally 200 mg/kg) divided into six i.v. doses during 24 hours starting at the induction of anesthesia. Patients allergic to penicillin received erythromycin instead. Seventy-nine patients received antibiotics, and 73 (the control group) received none. All patients were followed at least 6 months after operation or to their death. Eleven patients developed signs of infection, giving an overall infection rate of 7.2%; however, the infection occurred less than 1 month after the operation in only half of these. Six of the patients had septicemia, 4 had peritonitis, and 1 had meningitis. In the treated group, the infection rate was 8.9%; in the control group, the rate was 5.5%. There was no statistically significant difference. The prophylactic antibiotic regimen in this investigation did not reduce the infection rate connected with cerebrospinal fluid shunting procedures.
Since there is evidence suggesting that nicorandil (SG-75) relaxes coronary arterial smooth muscle by increasing cGMP levels, the effects of this vasodilator on soluble guanylate cyclase from bovine coronary arteries were studied more closely. It was found that nicorandil stimulated guanylate cyclase dose-dependently (3-30 mM) up to 100-fold the control value. Similar to nitroglycerin but in contrast to sodium nitroprusside, cysteine (0.5-20 mM) was required to obtain this stimulation. All other investigated thiols, except thiosalicylic acid which was partially able to mimic the cysteine effect, were ineffective. As evident from time course studies, nicorandil induced stimulation of guanylate cyclase was characterized by a lag-phase which could be avoided by preincubating the enzyme with nicorandil. The stimulatory effect of nicorandil was diminished in the presence of methylene blue, ferricyanide or hydroquinone. These results give further evidence that a) nicorandil exerts its vasodilating effect via stimulation of guanylate cyclase and b) nitrate esters, such as nitroglycerin or nicorandil, stimulate the enzyme, at least in vitro, only in the presence of cysteine or, to a lesser extent, thiosalicylic acid.
Explore the source record for details and available documents.
The cellular localization and regional distribution of peptides of the gastrin/cholecystokinin family was investigated in human fetal, neonatal and adult brains by use of immunohistochemical techniques. It could be revealed that a cholecystokinin-like immunoreactivity is already present in human brain at the 11/12th gestational weeks. With the 19th week a strong increase in number of CCK reactive cells and the reaction intensity is obvious. The data are compared with the distribution pattern of the adult brain. Our data permit to conclude that gastrin/CCK-related material might play roles independent of neurotransmitter functions during early human brain development.
Explore the source record for details and available documents.
Forskolin binding sites have been identified in a preparation of rat myocardium using [3H]forskolin and [3H]14,15-dihydroforskolin ([3H]DHF) as radioligands. It could be shown that both ligands bind to the same site with only a slight difference in their affinities. Using the filtration method the binding sites were characterized by an affinity of about 250 nM for forskolin and about 650 nM for dihydroforskolin (DHF). The binding capacity was about 5 pmol/mg protein with both compounds. When using the centrifugation technique similar binding affinities were obtained; the binding capacity, however, was around 3 fold higher than with the filtration method. Under all conditions only one single group of independent binding sites was found. In contrast, stimulation of adenylate cyclase by forskolin was found to be negatively cooperative. These results indicate that stimulation of adenylate cyclase by forskolin is a very complicated mechanism and the binding procedure of forskolin to its binding sites can represent only a small part of this process.
Hyperplastic anterior pituitary glands were produced in female rats by treatment with 10 mg of diethylstilbestrol in Silastic tubing. This led to increased numbers of immunoreactive prolactin cells and increased serum prolactin levels. After 6 weeks of diethylstilbestrol treatment, one group of rats was treated with daily injections of pergolide for 3 weeks. Pergolide produced a significant decrease in pituitary gland weight and in serum prolactin levels but did not change the percentage of prolactin cells significantly, compared with that of control rats. Ultrastructural studies showed a significant increase in the numbers of prolactin secretory granules and numerous large intracellular bodies with associated secretory granules in pituitaries from rats treated with pergolide. In one group of rats in which the diethylstilbestrol was discontinued for 3 weeks after 6 weeks of treatment there was a significant decrease in pituitary gland weight and serum prolactin and a significant decrease in the percentage of prolactin cells, compared with values in the rats treated with diethylstilbestrol for 9 weeks. These results indicate that pergolide causes decreased release of prolactin from secretory granules in anterior pituitary prolactin cells and an increase in the numbers of PRL secretory granules per cell but does not change the percentage of prolactin-producing pituitary cells after 3 weeks of treatment.
Explore the source record for details and available documents.