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S Christensen

Publications and source records attributed to S Christensen.

At least 91 records · Page 5Linked to original sources

Supra-additive natriuretic synergism between bendroflumethiazide and furosemide in rats.

To examine the diuretic and natriuretic synergism between bendroflumethiazide (BFTZ) and furosemide (FUR), the acute diuretic and natriuretic response to BFTZ was compared when given alone, during acute and during chronic FUR infusion. Responses to diuretics were assessed in conscious, chronically instrumented rats and, to avoid confounding influences of diuretic-induced volume contraction, extracellular fluid volume was kept constant by a computer-driven servo-control technique. Two groups were pretreated with osmotic minipumps chronically infusing either FUR (0.25 mg/hr; group CF; n = 9) or vehicle (8% ethanolamine; group CV; n = 8) i.p. for 7 days before the experiment. During the experiment, two other groups received either acute infusion with FUR (0.25 mg/hr; group AF; n = 16) or acute infusion with vehicle (150 mM glucose; group AV; n = 11). After a 60-min control period, BFTZ (0.083 mg; 0.25 mg/hr) was administered for 90 min to all four groups. Whereas the diuretic and natriuretic response to BFTZ was similar in groups AF, AV and CV, a supra-additive response was observed in the CF group (vs. group CV: delta urine flow rate: +78%; delta urinary Na excretion: +69%). BFTZ had no effect on the fractional excretion of Li, which suggests that the supra-additive effect was due to inhibition of an enhanced distal tubular Na reabsorption induced by chronic FUR administration. Because before BFTZ administration urinary Na excretion was 3-fold higher during acute than during chronic FUR infusion, an increased delivery of NaCl to the thiazide segment cannot by itself explain the exaggerated BFTZ response during chronic FUR treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

Role of the adrenal medulla in control of blood pressure and renal function during frusemide-induced volume depletion.

OBJECTIVE: To examine the role of the adrenal medulla in reflex control of mean arterial pressure (MAP), heart rate and renal function parameters during frusemide-induced volume depletion. DESIGN: Frusemide (6 mg/kg per h) was administered intravenously to two groups of chronically instrumented rats with either sham adrenal medullectomy (n = 15) or adrenal medullectomy (n = 11). RESULTS: Adrenal medullectomy reduced adrenal adrenaline concentration by 99% and plasma adrenaline concentration by 97%. Plasma corticosterone levels were similar in the two groups, which suggests that adrenal cortical function was not affected by adrenal medullectomy. Although frusemide did not affect arterial pressure in the sham-operated rats, MAP fell by 21 +/- 3 mmHg (mean +/- SEM) during frusemide diuresis in the rats with adrenal medullectomy. Heart rate was lower in the rats with adrenal medullectomy than in the sham-operated rats throughout the study. There were no major differences in renal haemodynamics or overall renal water and sodium handling between the two groups but, at the time of maximal activation of compensatory sodium reabsorption, fractional sodium excretion in the distal nephron segment was significantly higher in the rats with adrenal medullectomy than in the sham-operated rats. CONCLUSIONS: Adrenal medullary adrenaline release is essential in the control of MAP during frusemide-induced volume depletion. Circulating adrenaline might contribute, by modifying distal tubular sodium reabsorption, to compensatory sodium reabsorption during frusemide-induced volume depletion.

Adrenal Medulla↗

Characterization of two serpins from bovine plasma and milk.

An inhibitor of pancreatic elastase (EI), which can also inhibit chymotrypsin, and an inhibitor of trypsin (TI), which can also inhibit plasmin, have been isolated from bovine plasma. EI and TI belong to the serpin family of inhibitors. The size of both inhibitors is approx. 60 kDa and they are able to form SDS-stable complexes with proteinases. Curiously, TI dimerizes in the presence of SDS, a feature which has been observed previously only in non-denaturing gels of human alpha 1-antitrypsin (alpha 1PI). EI and TI are glycosylated [16% and 19% (w/w) respectively] and their amino acid compositions are similar to those of other plasma serpins. Neither EI nor TI is the equivalent of bovine alpha 1PI, as revealed by partial sequence analysis of their N-termini and reactive sites. Rather, both inhibitors appear to be related to human alpha 1-antichymotrypsin. Inhibition of pancreatic elastase and chymotrypsin by EI occurs with a kass. approximately 10(5) M-1.s-1. TI inhibits trypsin with a kass. approximately 10(5) M-1.s-1. Plasmin is inhibited by TI with a kass. approximately 10(3) M-1.s-1. The values of the kinetic constants are similar to those determined for the well-studied human serpins. Antibodies to EI and TI reveal a set of four antigenically related proteins of similar size in plasma. In addition, they detect the same set of proteins in milk. The inhibitors isolated from milk are identical to EI and TI from plasma. EI could control the activity of chymotrypsin-like proteinases in milk. In contrast, no target proteinases of TI in milk can be suggested.

Amino Acid Sequence↗

[Treatment of episiotomy wound infections. Incision and drainage versus incision, curettage and sutures under antibiotic cover--a randomized trial].

Conventional, "open" treatment of episiotomy wound infections was compared to incision, curettage and primary suture under antibiotic cover in a prospective, randomized study. During the period 1.5.1986-31.12.1988 there were 4154 vaginal deliveries with episiotomy, of which 20 (0.48%) became infected. Seventeen of these patients consented to enter the study. Median time for healing was 12 days following suture and 19 days after "open" treatment (not significant). Hospitalization time was the same in the two groups. No re-infections were seen. A need for vaginal plastic repair was found in three of nine of the conventionally treated patients and in none of the patients in the suture group (not significant). It is concluded that treatment of episiotomy wound infections with incision, curettage and primary suture under antibiotic cover is an attractive, safe ad convenient alternative treatment.

Adult↗

Aberrant 3H labelling of ATP during in vivo labelling of Ehrlich mouse ascites tumour cells with [2-3H]inositol is significant in the study of isomers of InsP3 and InsP4.

Neutralized perchloric acid extracts of intra-abdominally proliferating Ehrlich mouse ascites-tumour cells harvested after 24 h exposure to [2-3H]inositol were analysed by Mono Q HR5/5 anion-exchange h.p.l.c. using an ammonium formate/phosphoric acid gradient or by ambient-pressure small-column anion-exchange chromatography (Bio-Rad AG 1-X8, 200-400 mesh). The results showed that cellular ATP contained aberrant 3H label in excess of 3H in the isomers of InsP3 and InsP4. The putative ATP 3H radioactivity showed: (i) h.p.l.c. run time as the material causing the largest A254 peak traced, (ii) precise spiking with ATP and [14C]ATP and (iii) specific absorption to charcoal. Moreover, enzymic conversion of ATP into ADP changed putative ATP 3H into putative ADP 3H. In addition, aberrant 3H labelling of cellular ADP and GTP was detected, although at a lower level.

Adenosine Diphosphate↗

Primary structure of bovine alpha 2-antiplasmin.

The primary structure of bovine alpha 2-antiplasmin (alpha 2AP) has been determined from cDNA and partial peptide sequencing. Mature bovine alpha 2AP contains 470 residues and is 6 residues longer than human alpha 2AP. Alignment of the two protein sequences show that 81% of their amino acid residues are identically located. Bovine alpha 2AP has 5 N-linked carbohydrate groups, of which four are found in human alpha 2AP (Asn105, 274, 288 and 295). Asn227 is the fifth carbohydrate attachement site in bovine alpha 2AP. The 3 Cys residues of bovine alpha 2AP are present as an unpaired residue (Cys131) and as a pair in a disulfide bridge (Cys49-Cys122). The assignment of the bridge in bovine alpha 2AP is at variance with the previous assignment of the two disulfide bridges in human alpha 2AP [Lijnen, H.R. et al. (1987) Eur. J. Biochem. 166, 565-574].

Amino Acid Sequence↗

Disease activity of hepatitis C correlates with single-stage polymerase chain reaction detection of hepatitis C virus.

Hepatitis C virus (HCV) RNA was amplified and detected in the serum of 17 anti-HCV antibody positive patients using a single-stage (30 cycles) polymerase chain reaction (PCR). Specific amplification, targeted to the C-100 protein (anti-HCV) region, was confirmed by direct sequencing of the PCR product. Single-stage PCR detected the virus in 11 patients. Polymerase chain reaction-positive patients demonstrated a significantly higher histologic activity index (10.3 + 1.2 standard error of mean [SEM] than those testing negative (5.8 + 1.5 SEM, P < .05). Nine of 11 PCR-positive patients exhibited a rise in alanine transaminase (ALT) values within 1 month of assay, compared with only 1 of 6 PCR-negative patients. The correlation between rising ALT levels and PCR positivity was significant (P < .01). Direct sequencing revealed mutability in all cases, some of which resulted in amino acid substitutions. The authors concluded that HCV detection using single-stage PCR correlates with biochemical and histologic features of disease activity. Mutability is likely an important feature of HCV pathobiology and may significantly affect detection methods.

Adult↗

The number and size of glomeruli in long-term lithium-induced nephropathy in rats.

Chronic renal failure was induced in 10 Wistar rats using a lithium-containing (40 mmol/kg) diet from time of birth until an age of 55-65 weeks. Nine Wistar rats served as controls. The plasma lithium, the plasma urea, and the inulin clearance were measured, and one kidney was fixed by vascular perfusion with glutaraldehyde. The number of glomeruli was estimated stereologically by the fractionator method. The total number of glomeruli per kidney was 23.9 x 10(3) +/- 3.65 x 10(3) (+/- SD) in controls and 22.0 x 10(3) +/- 1.48 x 10(3) in the lithium-treated group, showing no statistically significant difference. The mean glomerular volume was also estimated using stereological methods. The number-weighted mean volume was reduced by 42% in the lithium-treated group, whereas the volume-weighted mean volume was unchanged. This can be attributed to the occurrence of many small glomeruli and a few very large glomeruli in the lithium-treated group. The many small glomeruli have in a previous study been shown to be atubular. The present study showed that the glomerular population is quite resistant to the deleterious effect of lithium; thus glomerular atrophy was seen, but no loss of glomeruli occurred.

Animals↗

Histological characteristics and expression of acidic and basic fibroblast growth factor genes in intracerebral xenogeneic transplants of human glioma cells.

Eleven athymic nude rats had stereotactic intracerebral inoculation of cells from one of three established human glioma cell lines (A172, A1207, and A1235). The implants grew progressively in 9 of 11 instances, which led to spontaneous death of the host in 14 to 37 days. For comparison, two Sprague-Dawley normal albino rats were implanted with the rat C6 glioma cell line. One rat died at 14 days, and the other was killed at Day 16. The human glioma cells developed into partially (A172, A1235) or totally (A1207) circumscribed tumor masses. Invasion, when present, was manifested as infiltrating prongs of cells rather than as individual cell infiltration. The growth of the human glioma cells was accompanied by a small zone of surrounding edema and marked central necrosis. These features were not encountered in the C6 implants. Inflammatory changes were minimal to nonexistent in all cases. All tumor lines produced internal cerebral herniation and neuraxis spread with implants seeded throughout the ventricular system, often associated with ventricular dilation. In situ hybridization, by the use of isotopic and nonisotopic detection methods, was used to study the cellular expression of the acidic fibroblast growth factor and basic fibroblast growth factor genes in A172 glioma xenografts. The expression of these genes was not seen in normal rat brain, but the genes were selectively overexpressed by the glioma cell implants, with especially high signal in the tumor periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Initial management of recurrent vulvovaginal candidiasis with oral ketoconazole and topical clotrimazole.

In a randomized study, 151 women with a history of recurrent vulvovaginal candidiasis and suffering from an acute episode of candidal vaginitis were assigned to receive either oral ketoconazole, 400 mg daily for 14 days, or clotrimazole vaginal suppositories, 100 mg daily for 7 days. One week after completion of therapy, evaluation revealed a clinical cure or improvement in 86.4% of ketoconazole- and 81.7% of clotrimazole-treated patients (P > .5), with a mycologic response in 80.3% and 81.7%, respectively. In the absence of maintenance suppressive antimycotic therapy, further follow-up for two months revealed an extremely high rate of clinical and mycologic failure in both groups, reaching 52.5% after ketoconazole and 62.6% after clotrimazole (NS). Adverse effects were significantly more common with systemic ketoconazole than accompanying topical clotrimazole therapy. Although both forms of antifungal therapy were highly successful in inducing clinical and mycologic remission in patients with recurrent vulvovaginal candidiasis, this study emphasized the need for immediate initiation of maintenance therapy following an initial clinical improvement.

Acute Disease↗

Compensatory growth of glomeruli is accomplished by an increased number of glomerular capillaries.

BACKGROUND: The number of glomerular capillaries were unbiasedly estimated in the very heterogeneous population of glomeruli found in rats with lithium-induced nephropathy. The glomeruli are atubular, connected to atrophic tubules, or connected to normal proximal tubules. In rats with lithium nephropathy, hypertrophy is found in glomeruli with normal tubular connection. This hypertrophy may take place by an increase in the number, length, or diameter of the capillaries. EXPERIMENTAL DESIGN: In serial sections, the glomeruli were sampled at random and followed to detect whether they were connected to an atrophic tubule, a normal proximal tubule, or no tubule at all. On 1-micron-thick serial sections, the number of capillaries was estimated using a method based on a topologic definition of the capillary. The number was estimated for three categories of glomeruli: normal glomeruli from control animals, hypertrophic glomeruli connected to normal proximal tubules from lithium-treated animals, and atrophic glomeruli being either atubular or connected to atrophic tubules from lithium-treated animals. On the same sections, stereologic methods were used to estimate the cross-sectional area and the length density of the glomerular capillaries. RESULTS: The mean number of capillaries in normal, hypertrophic, and atrophic glomeruli was 188 +/- 26 (+/- SD), 271 +/- 32 (+44%), and 65 +/- 12 (-65%), respectively. Whereas the total length of the capillaries per glomerulus was increased in hypertrophic glomeruli and decreased in atrophic glomeruli compared to normal glomeruli, the mean capillary length of 48.3 +/- 3.7 microns, and 53.0 +/- 11.3 microns in the hypertrophic and atrophic glomeruli, respectively, was significantly higher than the 41.0 +/- 4.6 microns in the controls. CONCLUSIONS: We conclude that in lithium-induced nephropathy, glomerular hypertrophy is mainly due to the increased numbers of capillaries, whereas the increase in the individual capillary length is of lesser importance.

Aging↗

[Stomach rupture after nasal oxygen therapy].

A 69-year-old male developed a spontaneous rupture of the normal stomach during oxygen administration via a nasopharyngeal catheter. The clinical picture and treatment is discussed.

Aged↗

Genotypic classification of colorectal adenocarcinoma. Biologic behavior correlates with K-ras-2 mutation type.

BACKGROUND: New measures enabling better prediction of biologic behavior of large bowel cancer are highly desirable. One hundred ninety-four consecutive primary, recurrent, and metastatic colorectal adenocarcinomas, accessioned during 1991 at Rhode Island Hospital, were classified according to the presence and specific type of K-ras-2 point mutation. METHODS: An integrated histopathologic-genetic approach was used to detect mutations starting with minute, topographically selected, tissue samples from formaldehyde-fixed, paraffin-embedded specimens. RESULTS: Each colorectal adenocarcinoma exhibited either no or only one of seven specific types of K-ras-2 mutation. The mutation type of each primary tumor was present consistently in its metastatic deposits. Thirty-five percent of primary colorectal adenocarcinomas were found to be mutated (42 of 119). A significantly higher mutation rate (65%) was seen in lymphogenous-hematogenous metastases as a group (35 of 54; P < 0.005). By contrast, 22% of anastomotic recurrences and transcoelomic metastasis were mutated (4 of 18). Twenty-eight percent of adenocarcinomas with invasion limited to muscularis propria (Tis, T1, T2) were mutated (16 of 57), compared to 41% for more deeply invasive tumors (T3, T4; 26 of 63). When colorectal adenocarcinomas were analyzed by specific K-ras-2 mutation type, it was found that codon 13 mutated tumors did not progress to local or distant metastasis (P < 0.01). Tumors having a codon 12 valine substitution did not metastasize beyond pericolonic-perirectal lymph nodes. In contrast, colorectal cancers with codon 12 aspartic acid substitutions accounted for most of the distant hematogenous deposits (P < 0.01). Tumors with normal K-ras-2 accounted for most intraperitoneal deposits. CONCLUSIONS: Genotyping of colorectal adenocarcinoma by K-ras-2 status can identify subsets of patients likely to pursue indolent and aggressive forms of disease. The integrated histopathologic-genetic approach outlined is feasible for use in diagnostic pathology, providing information that together with clinicopathologic staging may individualize and optimize treatment.

Adenine↗

Effect of water deprivation, desmopressin (DDAVP) infusion, and oral loads of water, Na+ and NH4+ on urinary excretion of epidermal growth factor in the rat.

UNLABELLED: Epidermal growth factor (EGF) is synthesized in the kidneys and excreted in urine. Administration of exogenous EGF modulates the reabsorption of Na+ and the vasopressin stimulated reabsorption of water in the collecting tubules. In order to clarify whether this reflects a physiological role for urinary EGF we examined the effects of changes in the oral loads of water, Na+ and NH4+ as well as the effect of infusion of the vasopressin analogue, desmopressin (DDAVP) on the endogenous urinary EGF excretion in the rat. Water deprivation for 48 h reduced the urinary excretion of EGF by 25% and the urinary EGF/creatinine ratio by 8%. Also, urinary volume, Na+ excretion, and urinary pH were reduced by water deprivation. Infusion of DDAVP, low plasma vasopressin induced by polydipsia, and changes in the renal excretion of Na+ and H+ did not affect the urinary excretion of EGF. IN CONCLUSION: it seems unlikely that nephrogenous EGF excreted in the urine plays a physiological role in the regulation of the renal excretion of Na+ and H+ and in the vasopressin stimulated reabsorption of water in the rat. However, since water deprivation reduced the urinary excretion of EGF it remains possible that urinary EGF plays a role in the complex physiological response to dehydration.

Administration, Oral↗

[A broken hip].

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Aged↗