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Biomedical subjects

H Hedlund

Publications and source records attributed to H Hedlund.

At least 37 records · Page 2Linked to original sources
PubMed1997

Posterior sagittal resection for rectal aganglionosis: preliminary results of a new approach.

BACKGROUND: There is no general agreement about how patients who have short-segment Hirschsprung's disease should be treated. METHODS: Ten patients with Hirschsprung's disease, seven with rectal and three with rectosigmoidal aganglionosis, were operated on through a posterior sagittal incision. In nine patients, a primary rectal resection and coloanal anastomosis was performed. In one patient, a longitudinal posterior myectomy of the rectum was performed as a primary procedure, but the procedure was eventually converted to a rectal resection and coloanal anastomosis through the same incision. RESULTS: One early and one late anastomotic complication occurred. Both were successfully treated with a temporary fecal diversion (left-sided colostomy for 6 to 8 weeks). The functional results as evaluated with anorectal manometry were similar to a group of Hirschsprung's patients treated with transabdominal pull-through resection and coloanal anastomosis. CONCLUSION: This approach might prove to be a useful alternative both to the transabdominal resection and the posterior longitudinal rectal myectomy in Hirschsprung's disease with rectal aganglionosis.

Child↗
PubMed1997

Colorectal resection and anal anastomosis with an intraluminal stapler in Hirschsprung's disease.

Twenty patients aged 5 months - 4 years (mean 14 months) with Hirschsprung's disease were operated upon. In all cases a pull-through resection and stapled circular coloanal anastomosis was performed, in 11 with a single-stapling technique and in 9 with double-stapling. Isopaque rectography 4 - 10 days postoperatively showed an intact anastomosis in all 20 patients, i. e., there were no clinical or subclinical leaks. On palpation 4 - 6 weeks postoperatively, there were signs of stenosis in 4 patients. However, no. 9 - 11 Hegar dilators passed easily and there was no residual stenosis at follow-up 3 months after surgery. The technique can be recommended in children over 6 months of age.

Anal Canal↗
PubMed1996

Detubularized right colonic reservoir with intussuscepted ileal nipple valve or stapled ileal ("Lundiana") outlet. Clinical and urodynamic results in a prospective randomized study.

In a prospective randomized study, patients undergoing cystectomy and continent urinary diversion by means of a detubularized right colonic reservoir were randomized to one of two types of outlet: either an intussuscepted ileal nipple valve (n = 15) or a stapled ileal ("Lundiana") outlet (n = 15). There were no early complications from the reconstruction. Subsequently, one ileal nipple outlet required revision because of progressive catheterization difficulties. In the Lundiana group, perforation of the reservoir occurred in one case and a narrow stomal opening was revised in local anesthesia in two cases. Urodynamic assessment revealed similar pressures at rest for the two outlets. At stress (concomitant with reservoir contraction), there was a distinct increase in outlet pressure in the nipple valves, but this was rarely encountered in the Lundiana group. Questionnaires showed episodes of urinary leakage to be more common in the Lundiana group, whereas the reverse applied to catheterization difficulties. In both groups, however, the great majority of patients were satisfied or very satisfied with the function of the urinary tract.

Adult↗
PubMed1996

Ultrastructural changes in primary guinea pig osteoarthritis with special reference to collagen.

Collagen fibril distribution and surface and volume densities in proximal tibial articular cartilage were measured in 6- and 12-month-old Dunkin-Hartley guinea pigs developing primary osteoarthritis. At 12 months, gross fibrillation and ulceration of the articular cartilage were observed on the medial but not on the lateral condyle. Collagen volume density decreased with age in the interterritorial compartments in the superficial zone, medially by 16% and laterally by 8%. In the upper radial zone, collagen volume density decreased interterritorially by 10% on the medial condyle only. Despite gross osteoarthritic changes, only moderate and predominantly focal ultrastructural collagen changes were observed. Thus neither gross network disruption nor fibril thickening seems to be a general feature in early guinea pig osteoarthritis.

Animals↗
PubMed1996

Pharmacotherapy in erectile dysfunction agents for self-injection programs and alternative application models.

Previously, men with erectile dysfunction (ED) were frequently treated with penile prosthesis implants or considered to have psychogenic impotence. Since the reports by Virag and Brindley in 1932 and 1983, pharmacotherapy, by self-injection programs has become a new therapeutic concept for impotent men. In clinical practice, this application model has been generally accepted as the "golden standard" in the treatment of ED. Papaverine was first used as monotherapy, but because of side-effects such as prolonged erection, priapism, and fibrosis of the corpus cavernosum, single use of the drug was abandoned. Instead, papaverine was introduced in mixtures, e.g. together with alpha adrenoceptor-blockers as phentolamine, and/or prostaglandin E1 (PGE1) in these "cocktails", the dose of papaverine is reduced to 10-15 mg compared to the high doses (80-120 mg) that were used initially. By having two or more drugs in the mixture, a facilitating cascade effect as probably obtained. PGE1 is the only drug that has been approved by the FDA and is today registered in more than 50 countries. Other combination therapies such as vasoactive intestinal polypeptide+ phentolamine, or calcitonin gene-related peptide+ PGE1, have been suggested as suitable alternatives for intracavernosal injection. Transdermal and intraurethral application models may be considered in selected patients. Recently, oral administration of a phosphodiesterase inhibitor (UK-92.480) was reported to improve penile erection in patients with psychogenic impotence. Further clinical results from controlled trials will probably explain if this new oral drug will compete with PGE1 or other agents in self-injection programs.

Erectile Dysfunction↗
PubMed1995

Pituitary adenylate cyclase-activating polypeptide, helospectin, and vasoactive intestinal polypeptide in human corpus cavernosum.

1. The distribution and effects of pituitary adenylate cyclase-activating polypeptide (PACAP-27 and -38), helospectin (Hel-1 and Hel-2), and vasoactive intestinal polypeptide (VIP), were investigated in isolated preparations of human corpus cavernosum (CC). 2. Immunohistochemistry revealed coinciding profiles of nerve structures that showed immunoreactivities for VIP and PACAP, and VIP and Hel. Confocal microscopy showed the co-existence of VIP- and PACAP-immunoreactivities, and VIP- and Hel-immunoreactivities in most (90%) varicose nerve structures. 3. As determined by radioimmunoassay, the amounts of VIP, PACAP-27, and PACAP-38 in the preparations were 61.7 +/- 11.6, 0.1 +/- 0.05, and 3.7 +/- 0.5 pmol g-1 wet weight of tissue (pmol g-1 wet wt.), respectively. In tissue from patients with diabetes, the content of VIP was lower (13.7 +/- 0.5 pmol g-1 wet wt.), whereas that of PACAP (-27 and -38) was unchanged. 4. Cyclic nucleotide levels were determined in preparations exposed to PACAP-27, PACAP-38, Hel-1, Hel-2, and VIP. All the peptides, but Hel-2, significantly increased the concentrations of cyclic AMP, whereas the levels of cyclic GMP were unchanged. 5. The peptides concentration-dependently relaxed noradrenaline-contracted preparations. The order of potency was VIP > PACAP 27 > Hel-1 > Hel-2 > PACAP-38. 6. Hel-1, VIP and PACAP-27 effectively counteracted electrically induced contractions. At 10(-6) M, the highest peptide concentration used, the inhibitory effects obtained reached 96 +/- 3%, 87 +/- 6%, and 80 +/- 3%, respectively. 7. The results suggest that PACAP and Hel-1 are co-localized with VIP in nerve structures within the human cavernous tissue, and that the peptides are effective relaxants of CC preparations in vitro. The role of the investigated peptides for penile erection remains to be established.

Adult↗
PubMed1995

Estrogen receptors in the human male bladder, prostatic urethra, and prostate. An immunohistochemical and biochemical study.

The distribution and quantity of estrogen receptors (ERs) in the human male bladder, prostatic urethra and the prostate were studied in eight males with recurrent papillomas of the bladder or monosymptomatic hematuria (median age 61 years), 14 men undergoing transurethral resection due to benign prostatic hyperplasia (median age 70 years), and nine men undergoing cystectomy due to malignant tumour of the bladder (median age 70 years). In the first group of patients, biopsies for immunohistochemical examination were obtained from the bladder vault, bottom, both side-walls, the trigone area, and the mid-portion of the prostatic urethra, and in the second group from three locations of the prostatic urethra (bladder neck, mid-portion and veramontanum). In the third group, tissue specimens were taken from the vault of the bladder, prostatic urethra, and the prostate, for immunohistochemical as well as biochemical analysis. In the first group, ERs were found in three out of eight specimens of the prostatic urethra, and in one of these, ERs were confined to periurethral glands. ERs could not be demonstrated in any of the bladder-biopsies. In the second group, ERs were not found in the bladder neck, but were seen in four preparations from the veramontanum and in two from the midportion of the urethra. ERs were located in the urothelium and periurethral glands. In the third group, ERs were seen immunohistochemically in the prostatic urethra (two cases) and the prostatic stromal tissue (two cases). ERs could be demonstrated in the bladder neither by immunohistochemistry nor biochemically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Fibromodulin distribution and association with collagen.

Fibromodulin, an acidic 59-kDa proteoglycan, binds to collagen and inhibits collagen fibril formation in vitro. To determine whether fibromodulin is also bound to collagen in vivo, we used immunocytochemical methods to study the spatial relation of the proteoglycan to collagen fibrils in cartilage and tendon. We also studied the quantitative distribution of fibromodulin among compartments in articular cartilage at the ultrastructural level. Fibromodulin was identified with polyclonal antibodies raised in rabbits, and immunoreactivity was detected with protein-A gold. As the major proportion of fibromodulin immunoreactivity was localized along the periphery of the collagen fibrils, the relationship to the banding pattern of the collagen fibrils was mapped. The proteoglycan showed a non-random distribution, with preference to the gap region, axially within the D-period. Reactivity differed among the tissue compartments, with the lowest degree of labelling pericellularly, increasing with distance from the cell, the highest levels being observed in the interterritorial matrix. Labelling density was highest at the articular surface, gradually decreasing towards the cartilage-bone junction. The correlation between collagen fibril diameter and fibromodulin concentration also varied among compartments. Thus, the ratio of fibromodulin to collagen surface density was highest at the surface of the joint cartilage, exhibiting a gradient with higher values in the territorial matrix, decreasing towards the cell in all layers. These findings indicate that fibromodulin represents a factor used by chondrocytes to regulate assembly and function of collagen fibrils.

Animals↗
PubMed1994

Effects of nicorandil on human isolated corpus cavernosum and cavernous artery.

Nitric oxide (NO) released from nonadrenergic-noncholinergic (NANC) nerves seems to be a principal mediator of the relaxation of penile erectile tissue necessary for erection, and drugs acting by release of NO have been shown to produce erection when injected intracorporeally into impotent patients. By producing hyperpolarization, K+ channel openers are effective in relaxing isolated penile erectile tissue from rabbit and man, and can produce tumescence and erection when injected intracorporeally into animals. Nicorandil is classified as a K+ channel opener, but it also acts as a donor of NO. In the present study, the effects of nicorandil on isolated preparations from human corpus cavernosum (CC) and deep cavernous artery (Acc) were compared with those of cromakalim (K+ channel opener) and SIN-1 (NO donor). Nicorandil produced a concentration-dependent relaxation of CC and Acc preparations. The relaxations obtained at the highest nicorandil concentration used (10(-4) M.) were 75 +/- 3% and 66 +/- 4% in CC preparations contracted by noradrenaline and endothelin-1, respectively. The corresponding effects in Acc preparations were 70 +/- 14% and 73 +/- 5%. Glibenclamide (blocking ATP-dependent K+ channels) significantly reduced the nicorandil-induced relaxation in CC, but not in Acc. Methylene blue (believed to block soluble guanylate cyclase) reduced nicorandil's relaxant effect in CC, although statistical significance was not obtained. NG-nitro-L-arginine 10(-4) M. (NO synthase inhibitor) did not significantly influence the effect of nicorandil on precontracted preparations in either tissue. In CC preparations contracted by electrical field stimulation, nicorandil and cromakalim concentration dependently inhibited the responses. This effect was significantly counteracted by glibenclamide. It is concluded that nicorandil is effective in relaxing human CC chiefly by its K+ channel opening action, and to some extent by its ability to release NO. For nicorandil's relaxing effect on Acc, ATP dependent K+ channels seem to be of limited importance. If effective in impotent patients, the drug may represent a new, interesting approach to the treatment of erectile dysfunction.

Adult↗
PubMed1994

Angiotensin I is converted to angiotensin II by a serine protease in human detrusor smooth muscle.

The aim of the present study was to investigate whether a pathway for conversion of angiotensin I (ANG I) to angiotensin II (ANG II) other than that via angiotensin-converting enzyme (ACE) is present in the smooth muscle of the human detrusor. Isolated detrusor strips from 11 patients were contracted by ANG I (1 microM) in the absence or presence of enalaprilat (10 microM), soybean trypsin inhibitor (STI, 200 micrograms/ml), or both. The metabolic activity in detrusor membranes from four patients was studied separately using Hip-Gly-Gly or ANG I as a substrate, with or without various protease inhibitors. The contractile response to ANG I (1 microM) was depressed by enalaprilat from 66 +/- 22 (mean +/- SD) to 39 +/- 13% of the K+ (124 mM)-induced response (P < 0.01, n = 11), and the combination of enalaprilat and STI resulted in a further reduction in contractile amplitude to 25 +/- 14% (P < 0.01 vs. K+, and P < 0.05 vs. enalaprilat alone) and a significantly slower developing contraction with a time to peak of 3.7 +/- 1.7 vs. 1.1 +/- 0.3 min for ANG I alone (P < 0.01). In detrusor membranes, a low ACE activity, inhibitable by captopril, was demonstrated by the formation of hippuric acid (0.70 nmol.min-1.mg protein-1) from the synthetic ACE substrate, Hip-Gly-Gly. However, the conversion of ANG I (166 nmol.min-1.mg protein-1) to ANG II was not affected by ACE inhibition, while serine protease inhibitors, e.g., STI and chymostatin, completely prevented ANG II formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Actions of 3-morpholinosydnonimin (SIN-1) on rabbit isolated penile erectile tissue.

The effects of the NO-donor 3-morpholinosydnonimin (SIN-1) on isometric tension, cyclic guanosine 3',5'-monophosphate (cyclic GMP) accumulation and neuronal release of 3H-noradrenaline were investigated in rabbit isolated corpus cavernosum (CC), and compared to the actions of sodium nitroprusside (SNP) and the cyclic GMP-specific phosphodiesterase inhibitor zaprinast. SIN-1, zaprinast and SNP concentration dependently relaxed rabbit CC preparations contracted by 1 microM. phenylephrine. All the drugs were highly effective, and the order of potency was SNP > zaprinast > SIN-1. SIN-1 had a biphasic effect on contractions evoked by electrical field stimulation of nerves: at low concentrations (1 and 10 microM.), SIN-1 inhibited the contractions, while at concentrations > or = 100 microM., the contractions were again increased. There were no changes in baseline tension. Electrically evoked contractions were inhibited by zaprinast in a concentration-dependent manner. Compared with controls, 1 mM. SIN-1 caused a significant (p < 0.05) increase in both the basal efflux and in the electrically induced release of 3H from CC preparations incubated with 3H-noradrenaline. SIN-1, zaprinast and SNP increased tissue levels of cyclic GMP. There was no positive correlation between cyclic GMP accumulation and the relaxant effects of the drugs. The effects of SIN-1 and SNP on the tissue content of cyclic GMP were not significantly affected by methylene blue, an inhibitor of soluble guanylate cyclase. It may be concluded that SIN-1, zaprinast and SNP are effective in relaxing isolated penile erectile tissue, and this effect is associated with an increase in the tissue content of cyclic GMP via pathways not sensitive to methylene blue. However, additional mechanisms beside stimulation of adrenergic neurotransmission and activation of guanylate cyclase in the smooth muscle cell seem to participate in the action of SIN-1 on rabbit penile erectile tissue.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1993

Stereologic studies on collagen in bovine articular cartilage.

In an ultrastructural stereologic study on bovine articular cartilage we found that collagen volume density increased with increasing distance from the joint surface and from the chondrocyte. These results not only corroborate previous biomechanical data of a vertical stiffness gradient, but they also suggest that the mechanical forces are unevenly distributed horizontally. On the other hand, although mean collagen fibril diameter showed large differences between the interterritorial compartments of the three zones, there was a population of slender fibrils in all zones and compartments. Since the coarser fibrils provide the high tensile strength (Nimni 1988), the role of the slender fibrils may be to enhance the deformability of the tissue. Moreover, in spite of substantial differences in mean fibril diameter, collagen surface densities were in the same order of magnitude in the territorial and interterritorial compartments, and only slightly lower in the pericellular compartments. The surface parameter may be important for specific molecular interactions. The collagen fibrils have different polarity, i.e. the direction of the fibrils appears to be parallel and antiparallel, about 50% running in each direction. This, together with the very high length/diameter ratio (Clark 1985), may indicate that each fibril is assembled by the concerted action of many cells. The characteristic properties of articular cartilage depend on interactions between its macromolecular components, and the present quantitative data form a basis for discussions on the specificity and regulation of such interactions.

Animals↗
PubMed1992

Long-term anorectal function in imperforate anus treated by a posterior sagittal anorectoplasty: manometric investigation.

Thirty imperforate anus patients were investigated by anorectal manometry 5 to 10 years after a posterior sagittal anorectoplasty. Anal resting tone (ART) and anal squeezing pressure (ASP) were subnormal in most patients. Rectal volume (RV) and sensation to balloon distension were within the normal range. Rectoanal reflex inhibition was demonstrated in 9 of 30 patients. Soiling was more common in patients with a very low ART (less than 40 cm H2O) and a low ASP (less than 100 cm H2O). Constipation was more common in patients with a large RV (greater than 150 mL). Still, the correlation to clinical results was incomplete. As regards to the correlation to type of malformation the rectal atresia patients showed near normal results. The vestibular fistula patients were next in results showing rectoanal reflex inhibition in 5/6 patients. There was no difference in the results between bulbar and prostatic fistula patients.

Adolescent↗