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Biomedical subjects

S Rose

Publications and source records attributed to S Rose.

At least 181 records · Page 10Linked to original sources
PubMed1993

Evaluation of growth hormone axis and responsiveness to growth stimulation of short children with osteogenesis imperfecta.

Growth deficiency is a cardinal manifestation of severe Osteogenesis Imperfecta (OI) and occurs frequently in moderate to mild OI. We have investigated the status of the hormones related to growth in 28 children with OI. Our goals were to determine whether there were any abnormalities of these hormones, whether the abnormalities correlated with types of OI, and whether OI bone could be safely stimulated to grow. The study group included 14 females and 14 males. Using the criteria developed by Sillence et al. [1979], 13 children had OI type III, 12 had OI type IV, and 3 had OI type I. Evaluation included 3 standard hGH provocative tests (AITT, L-Dopa), GRF stimulation, 24 hr q20 minute sampling of unstimulated growth hormone, and a somatomedin generation test. All patients except one had normal responses to standard provocative stimuli. Responses to GRF fell into 2 groups: one with a mean response similar to that of normal children, and one with a mean response resembling that of GH deficient children. The group with low response to GRF had a significantly lower area under the curve in the 24-hr test of unstimulated GH than did the normal response group. The OI children as a group showed a blunted IGF-1 response during the Somatomedin Generation Test, with 18/28 children having less than a two-fold stimulation. No test results correlated with OI type. Ten OI children were enrolled in a pilot growth stimulation study. Two children received protropin and 8 received clonidine for at least 6 months. Both children treated with protropin and 4/8 treated with clonidine experienced at least a doubling of their pre-treatment growth rates. Lack of growth hormone response did not correlate with type of OI or parameters from the hormonal evaluation. We speculate that there is a group of OI children who have a hypoactive growth hormone axis. Some OI bone appears to respond to GH and a treatment trial with protropin is planned for a larger number of children.

Body Height↗
PubMed1993

Age-related effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets.

The effect of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on juvenile (6-8 months), young adult (2-4 years) and aged (8-10 years) common marmosets were compared. Juvenile marmosets were more resistant to the actions of MPTP and required a greater cumulative dose over a longer period to induce the same degree of motor disability observed in older animals. Young adult and aged marmosets showed an equivalent motor recovery in the 4-5 weeks following cessation of MPTP treatment, but juvenile animals were less able to compensate for the motor impairments. Losses of putamen [3H]dopamine uptake and caudate nucleus dopamine content were equivalent in young adult and aged animals. However, juvenile animals showed a more marked degree of dopamine depletion and reduction in [3H]dopamine uptake. Histological analysis showed cell loss in the substantia nigra to be most prominent in juvenile animals although it was evident in all groups. No loss of cells in the locus coeruleus was apparent in any of the groups studied, and no intraneuronal eosinophilic inclusions were seen. Greater nigral cell loss and dopamine depletion were required in juvenile animals to impair motor function. The degree of behavioural recovery was less in juvenile animals than in young adult and aged marmosets. The extent of behavioural recovery appeared linked to the severity of cell loss and was not reduced in old age.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Human islet purification: a prospective comparison of Euro-Ficoll and bovine serum albumin density gradients.

Euro-Ficoll (EF) and bovine serum albumin (BSA) are the two most commonly used media for the density gradient purification of human pancreatic islets. The aim of this study was to compare these two media with respect to the efficiency of human islet isolation. Ten human pancreata were collagenase-digested, and samples of digest were separated on either a continuous linear density gradient of BSA or a discontinuous gradient of EF (1.108/1.096/1.037/Euro-Collins). Efficiency of islet purification was assessed by insulin and amylase assay of aliquots aspirated from the BSA gradients, and from the interfaces of the EF gradients. Islets were obtained from two interfaces in the EF gradients. Islet yield from the upper interface was generally poor (median 28% of total insulin; range 2-71%), but purity was better than for an equivalent yield using BSA [1% (0-3%) amylase contamination for EF versus 6% (0-37%) for BSA; P = 0.013]. Pooling both EF interfaces increased yield to 66% (17-81%) but markedly reduced purity [46% (0-50%) amylase for EF versus 31% (0-52%) for BSA]. In conclusion, the efficiency of human islet purification is similar, though disappointingly low, with BSA and with EF. Considerable scope exists, therefore, for improvement in the density gradient purification of human islets.

Adolescent↗
PubMed1993

Storage of porcine pancreatic digest prior to islet purification. The benefits of UW solution and the roles of its individual components.

The aim of this study was to establish the beneficial effect of storage of pancreatic digest in University of Wisconsin solution on porcine islet purification, the mechanism of this effect, and the components of UW responsible. Ten porcine pancreata were collagenase-digested, and samples of digest were washed and stored for 1 hr in either UW or minimum essential medium at 4 degrees C, prior to separation on continuous linear density gradients of bovine serum albumin. Samples of digest from a further ten pancreata were similarly treated, comparing storage in MEM, UW, and five solutions varying in lactobionate:chloride ratio and raffinose content. The purity of the islet preparations and the densities of islets and exocrine tissue were determined from insulin and amylase assay of aliquots aspirated from these gradients. Washing and storage of digest in UW markedly improved islet purity, compared with MEM, due to an increase in the density of exocrine tissue. Exocrine tissue density following storage was dependent upon the control of acinar cell volume, rather than exocrine enzyme discharge, and was determined primarily by the chloride:lactobionate ratio of the storage solution. Raffinose was of little additional benefit, while the beneficial effect of UW was greater than that due to its lactobionate and raffinose content alone. In conclusion, inadequate purification of islets results from exocrine tissue swelling. This swelling is reduced by storage of the pancreatic digest in UW solution, due primarily to the replacement of chloride by lactobionate in UW.

Adenosine↗
PubMed1993

Chronic administration does not alter the pharmacokinetic profile of L-dopa in the rat.

Chronic administration of L-dopa (200 mg kg-1 day-1 for 12 months) plus carbidopa (25 mg kg-1 day-1) or carbidopa (25 mg kg-1 day-1) alone did not alter the t1/2, AUC0-infinity k10, k12, k21, CLp or Vdss of L-dopa following intra-aortic (i.a.) administration (50 mg kg-1) alone or after carbidopa (25 mg kg-1, i.p.) pretreatment, or the t1/2, AUC0-infinity, tmax or the bioavailability (F) of L-dopa (50 mg kg-1) administered orally, alone or after acute pretreatment with carbidopa (25 mg kg-1 i.p.). The peripheral metabolism of L-dopa was unaltered by chronic administration of L-dopa plus carbidopa or carbidopa alone as measured by unaltered AUC0-360 min for 3-O-methyldopa, dopamine, DOPAC or homovanillic acid in the plasma of rats following acute administration of L-dopa (50 mg kg-1, p.o. or i.a.) alone or following pretreatment with carbidopa, and unaltered hepatic dopa decarboxylase activity.

Administration, Oral↗
PubMed1993

The growth hormone and somatomedin axis in short children with osteogenesis imperfecta.

Growth deficiency is a cardinal feature of severe osteogenesis imperfecta (OI) and a frequent feature of mild to moderate forms of this disease. We have investigated the status of hormones related to growth in 22 short prepubertal children, 13 males and 9 females, with various types of OI. Ten children had Sillence type III OI, 10 had type IV, and 2 had type I. Evaluation included GRH stimulation, three standard GH provocative tests (arginine-insulin tolerance test, L-dopa), 24-h sampling for measurement of unstimulated GH secretion and a somatomedin-C generation test. None of these children had GH deficiency by standard criteria. We found that 9 OI children had decreased responsiveness to GRH, similar to the GRH response of GH-deficient children. Overall, however, mean 24-h GH values and mean peak GH response to provocative agents of OI children were within the normal range. In the somatomedin generation test, the OI children as a group showed a blunted response, with 13 of 22 having less than a 2-fold stimulation of somatomedin-C by GH. This suggested resistance of the liver and other somatomedin-C secreting tissues to GH. The group with blunted insulin-like growth factor-I response did not correlate significantly with the group with decreased GRH response. To investigate the responsiveness of OI bone to growth stimulation, six OI children with less than average integrated GH secretion were enrolled in a pilot study in which one child received exogenous GH and six received clonidine for at least 6 months. The child treated with exogenous GH and three of six treated with clonidine experienced at least a 4.7 cm/yr increase over their pretreatment growth rates. Growth response could not be predicted from baseline studies. We conclude that abnormalities of the GH-somatomedin axis exist in some children with OI. Administration of GH or clonidine may augment growth rates in OI children; however, the effect of these agents on final stature is unknown.

Adolescent↗
PubMed1993

Color Doppler imaging findings in patients with Budd-Chiari syndrome: correlation with venographic findings.

OBJECTIVE: This study was undertaken to evaluate color Doppler imaging findings in patients with Budd-Chiari syndrome and to compare these findings with results of venography. SUBJECTS AND METHODS: In a prospective study, 21 patients with proved Budd-Chiari syndrome had color Doppler imaging. Sonographic evaluations ware performed to detect appropriately directed flow in the hepatic veins, portal vein, and inferior vena cava. Intrahepatic collaterals were characterized when present. Results of color Doppler imaging were compared with those of angiography in 20 patients. Color Doppler images of the hepatic veins were also obtained in a reference group (20 control subjects, 20 patients with hepatomegaly, and 20 patients with cirrhosis). RESULTS: Color Doppler imaging showed abnormalities of anatomy or flow in one or more of the main hepatic veins in all 21 patients with Budd-Chiari syndrome. Commonly observed abnormalities were visualization of a hepatic vein on real-time sonograms that had no flow or retrograde flow on color Doppler sonograms (11 cases) and no visualization of part or all of a hepatic vein on either real-time or color Doppler sonograms (10 cases). When compared with venographic findings (16 patients), findings on color Doppler sonograms could be used to distinguish patent from occluded hepatic veins in all cases. In our reference group, real-time and color Doppler sonograms showed normal hepatic veins in all control subjects. Real-time sonograms clearly showed hepatic veins in 12 of 20 patients with hepatomegaly; color Doppler sonograms showed flow in the hepatic veins in all 20 of these patients. Among 20 patients with cirrhosis, real-time sonograms showed hepatic veins in only seven; color Doppler imaging confirmed patent veins in 17. Intrahepatic collaterals typical of Budd-Chiari syndrome were observed in 10 of 21 patients with the syndrome. The portal vein was assessed by using color Doppler imaging in all 21 patients with Budd-Chiari syndrome; portograms were available for comparison in 10 patients. Findings were consistent in eight; in two cases, the direction of flow was reversed on color Doppler sonograms compared with portograms. For the inferior vena cava, venographic and sonographic findings correlated in 16 of 20 cases. Color Doppler sonograms did not show a caval web in one patient. CONCLUSION: Abnormalities of the hepatic veins, portal veins, and inferior vena cava detected on color Doppler sonograms in patients with Budd-Chiari syndrome correlate well with findings on venograms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

[Value of cytometric parameters the planning of therapy of urothelial carcinoma].

The prognostic value of cytometric DNA parameters and their possible influence on the planning of treatment were investigated in 44 patients with transitional carcinoma of the urinary bladder (17 G1 tumours, 15 G2 tumours, 12 G3 tumours) as compared with normal urothelium of 7 patients. The nuclear DNA content was measured by scanning cytophotometry in Feulgen stained cytological smears. A statistically significant correlation was found to exist between the combination of the DNA parameters stem line quotient, 5c exceeding rate and DNA malignancy grade and the appearance of recurrences. A discrimination of a low grade and a high grade tumour group was based on this result within the G1 and the G2 transitional carcinomas as well. All patients with a carcinoma classified as low grade were recurrence-free within an observation period of more than 10 years. Further studies should clarify if this group can be treated without a topic chemotherapy after transurethral electroresection in contrast to the high grade group in which a topic chemotherapy is necessary.

Aged↗
PubMed1993

Interaction between patient and test administrator may influence the results of edrophonium provocative testing in patients with noncardiac chest pain.

Edrophonium is a widely used provocative agent in the evaluation of noncardiac chest pain, with reported positivity rates of 30-55%. The influence of a subjective response and psychological factors on test results have not been examined previously. A retrospective analysis was performed to compare positivity rates for three physicians in the same laboratory. This was followed by a prospective study of 62 patients with noncardiac chest pain randomized to two groups. Group 1 patients were told that intravenous medication was given to observe changes in the tracing. Group 2 patients were told that the injection was to elicit their usual pain. During the 2-yr retrospective review, 260 patients were tested. The positivity rate varied from 31.1% with physician A to 20.2% with physician B and 7.5% for physician C (p = 0.001 for A vs. C, and p = 0.04 for B vs. C). In the prospective study, chest pain was elicited in nine of 62 patients (14.5%). Two of the 29 patients in group 1 (6.9%) and seven of 33 patients in group 2 (21.2%) contributed to this result. Contraction amplitude and duration increased similarly in all groups. These data suggest that edrophonium testing may be influenced by coaching, that manometric changes are similar in positive and negative tests, and that the prevalence of positive tests is lower than previously reported.

Adult↗
PubMed1993

Modified method for determining carcinoembryonic antigen in the presence of human anti-murine antibodies.

The increasing use of monoclonal antibodies (MAbs) for disease diagnosis and therapy has created a class of patients at risk for systematic error in clinical testing due to interference by human anti-murine antibodies (HAMA). HAMA interference is often difficult to detect and can cause either an increase or a decrease in apparent concentrations of antigen present. We undertook a clinical study to test a HAMA-resistant enzyme immunoassay (EIA) format for carcinoembryonic antigen (CEA) determination. Using the Food and Drug Administration-approved CEA-EIA Monoclonal One-Step Assay (Abbott) with the addition of an acid/heat extraction of patients' specimens, we found that the resulting CEA values accurately reflected the patients' status. We demonstrated that the acid/heat-extracted specimens yield linear dilution curves and show analytical recoveries of added CEA in the range of 76-123% in HAMA-positive specimens and 86-103% in HAMA-negative specimens. The correlation of CEA values in extracted vs unextracted specimens from 184 patients and control subjects was 0.9963. The CEA detection limit of the assay was 1.6 micrograms/L for the extracted samples.

Animals↗
PubMed1992

Effects of a unilateral 6-hydroxydopamine lesion and prolonged L-3,4-dihydroxyphenylalanine treatment on peptidergic systems in rat basal ganglia.

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle or of a sham lesion on the neuropeptide content of the striatum and substantia nigra was investigated with or without 6 months L-3,4-dihydroxyphenylalanine (L-DOPA; 200 mg/kg per day) plus carbidopa (25 mg/kg per day) treatment. [Met5]- and [Leu5]enkephalin, substance P (SP), neurotensin (NT) and cholecystokinin (CCK) were measured by a combined HPLC/RIA method. Neurotensin levels were increased in the striatum, and [Leu5]enkephalin, and SP levels were reduced in the substantia nigra as a consequence of the lesion, while the levels of other peptides were unaltered. Administration of L-DOPA to sham-operated rats bilaterally increased SP levels in striatum and substantia nigra, and [Met5]enkephalin and CCK content in substantia nigra. L-DOPA treatment of 6-OHDA-lesioned rats increased [Met5]- and [Leu5]enkephalin and CCK levels in the striatum ipsilateral to the lesion but not on the intact side. In the substantia nigra, the lesion-induced decrease in [Leu5]enkephalin and SP was reversed by L-DOPA treatment, [Met5]enkephalin and CCK levels ipsilateral to the lesion were further enhanced, and there was an increase in NT ipsilateral to the lesion. Cryptic [Met5]- and [Leu5]enkephalin increased in the ipsilateral striatum following an 6-OHDA lesion. L-DOPA treatment did not alter cryptic enkephalin levels or the lesion-induced increase in cryptic [Met5]enkephalin, while cryptic [Leu5]enkephalin was further increased in lesioned animals given L-DOPA. These results suggest that the pattern of change in basal ganglia peptides in Parkinson's disease is not due solely to the destruction of the nigrostriatal pathway, the drug treatment of the disease or a combination of these factors.

Animals↗
PubMed1992

Dissociation of the striatal D-2 dopamine receptor from adenylyl cyclase following 6-hydroxydopamine-induced denervation.

Intracellular cyclic AMP accumulation following exposure to dopamine (DA) agonists and and antagonists was measured in striatal slices from rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway and which showed contralateral circling to apomorphine. Both DA (10-320 microM) and the D-1 agonist SKF 38393 (0.1-32 microM) increased cyclic AMP accumulation in striatal slices from the lesioned and intact hemispheres. The EC50 for DA to increase cyclic AMP accumulation in slices was greater in the 6-OHDA-lesioned striata compared to the intact striatum, but the EC50 for SKF 38393 was not affected. The D-1 antagonist SCH 23390 (10 microM) completely inhibited the ability of DA and SKF 38393 to increase cyclic AMP accumulation in striatal slices from both denervated and intact sides of the brain. In slices from the intact hemisphere the increase in DA-induced cyclic AMP accumulation was enhanced by the D-2 antagonist (+/-)-sulpiride (50 microM) but (+/-)-sulpiride had no effect on the DA response in slices from the lesioned side. Similarly, the ability of SKF 38393 to enhance cyclic AMP accumulation was blocked by the D-2 agonist quinpirole (10 microM) in striatal slices from the intact hemisphere but not in tissue from the lesioned side. The density of striatal D-1 and D-2 receptors assessed by [3H]SCH 23390 and [3H]spiperone binding did not differ between the hemispheres although there was an increase in the affinity of D-1 receptors for [3H]SCH 23390 in the lesioned striatum. After striatal deafferentiation there appears to be an uncoupling of the "inhibitory" D-2 receptor from the D-1 receptor-associated adenylyl cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Acute reserpine treatment induces down regulation of D-1 dopamine receptor associated adenylyl cyclase activity in rat striatum.

Behavioural studies suggest a functional interaction between D-1 and D-2 systems in normal rat striatum to alter motor behaviour and which is disrupted by dopamine depletion induced by acute reserpine treatment. Consequently, we have investigated the effect of acute reserpine treatment on the biochemical interaction between D-1 and D-2 receptors present in rat striatal slices. Twenty-four hours following the administration of reserpine (5 mg/kg i.p.), striatal dopamine content was depleted by more than 73%; the density (B(max)) of D-1 receptor sites measured by the in vitro binding of [3H]SCH 23390 to striatal membranes was increased while the binding of [3H]spiperone to D-2 receptor sites was unaltered. Reserpine treatment had no effect on the affinity (Kd) of [3H]SCH 23390 or [3H]spiperone for D-1 and D-2 sites. Basal levels of cyclic AMP accumulation in striatal slices prepared from reserpine-treated rats were lower than those observed in control slices. In striatal slices prepared from normal rats, dopamine (10-320 microM) and the D-1 agonist SKF 38393 (0.1-3.2 microM) induced concentration-dependent increases in cyclic AMP accumulation. The D-1 antagonist SCH 23390 (10 microM) abolished the accumulation of cyclic AMP produced by dopamine or SKF 38393. The D-2 antagonist (+/-)-sulpiride (50 microM) enhanced the response to dopamine (10-320 microM) while the D-2 agonist quinpirole (10 microM) abolished the response to SKF 38393 (0.1-3.2 microM). However, 24 hr after reserpine treatment the ability of dopamine (10-320 microM) and SKF 38393 (0.1-3.2 microM) to elicit an increase in cyclic AMP accumulation was markedly reduced in striatal slices. SCH 23390 (10 microM) did not enhance the trend for an increase in cyclic AMP accumulation produced by dopamine. Also, quinpirole (10 microM) did not affect the response to SKF 38393 (0.1-3.2 microM) in striatal slices from reserpine pretreated rats. The data confirm the positive linkage between D-1 receptors and adenylyl cyclase and the inhibitory coupling to D-2 sites in striatal slices from normal, rats. Acute reserpine treatment appears to cause an uncoupling of D-1 receptors associated with adenylyl cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Peptide-containing nerves in labial salivary glands in Sjögren's syndrome.

OBJECTIVE: The presence and spatial distribution of peptide-containing nerves in labial salivary glands from 10 Sjögren's syndrome patients were compared with those in salivary glands from 7 healthy controls. METHODS: Immunoperoxidase staining was used to demonstrate vasoactive intestinal peptide (VIP)-immunoreactive (IR) fibers, postganglionic sympathetic fibers containing the C-flanking peptide of neuropeptide Y (CPON), and sensory fibers containing calcitonin gene-related peptide (CGRP) and substance P. RESULTS: Acini, intralobular ducts, small arteries, and postcapillary veins were richly innervated by VIP-IR fibers, whereas CPON-, CGRP-, and substance P-IR fibers were restricted to blood vessels. Peptide-containing nerves were found surrounding, but not in the middle of, the highly inflamed mononuclear cell areas. CONCLUSION: This topologic distribution suggests involvement of VIP-IR fibers in vascular, motor, and secretory components of the reflex salivary secretion, whereas the distribution and the vasoactive actions of CPON, CGRP, and substance P suggest a role in the regulation of the salivary gland circulation, and thus of transcapillary flow. Excessive release may contribute to a neurogenic inflammation. Local depletion and absence of trophic neuropeptide stimuli may contribute to acinar atrophy.

C-Peptide↗
PubMed1992

Storage of human pancreatic digest in University of Wisconsin solution significantly improves subsequent islet purification.

Density-gradient purification of human pancreatic islets from the collagenase-digested pancreas relies on the exocrine tissue being denser than the islets. Cold storage of the pancreas before and after digestion causes cell swelling, which can decrease the density of pancreatic exocrine tissue and adversely affect subsequent purification. Using 14 human pancreata (seven perfused in situ with hyperosmolar citrate (HOC) and seven with University of Wisconsin solution (UW)), it is shown that storage of the pancreatic digest in UW significantly increases the density of pancreatic exocrine tissue compared with storage in minimal essential medium (MEM) (P = 0.009). This results in an improvement in islet purity (P = 0.036) for HOC- but not UW-perfused pancreata. Storage in UW for 1 h not only prevented the deterioration that occurred in MEM, but resulted in an improvement in islet purity for five of the seven HOC-perfused pancreata. Most pancreata in the UK are perfused with HOC, but storage of the digest in UW results in significantly better islet purity and, when islets cannot be purified immediately, a period of storage will often improve separation and allow islets to be purified.

Adenosine↗
PubMed1992

Adventurous outdoor activities: a review and a description of a new service delivery package for clients with learning difficulties who have behaviours which challenge services or society.

The purpose of this paper is to describe the need for and the creation of a new service delivery package for the client with learning difficulties whose behaviour challenges services or society, or who is a 'victim of the system', and not responding to available resources. Adventure-based courses are delivered in a context of supportive therapy which effects measurable change. There is continuing research-based evaluation of this new approach which will be reported in due course.

Camping↗