Search PubMed⌕ Search

Biomedical subjects

A Bohle

Publications and source records attributed to A Bohle.

At least 19 recordsLinked to original sources
PubMed2002

Optimal treatment of systemic bacillus Calmette-Guérin infection: investigations in an animal model.

PURPOSE: Hematogenous spread of bacillus Calmette-Guerin (BCG) after intravesical instillation for bladder cancer is rare but it may result in systemic infection and hypersensitivity reaction. We investigated fluoroquinolones and steroids in an animal model to improve the therapeutic options in local and systemic BCG infection. Furthermore, the antitumor effectiveness of intravesical BCG with simultaneous application of fluoroquinolones and/or steroids was tested. MATERIALS AND METHODS: Oral antimicrobial therapy with and without steroids was started immediately after intraperitoneal injection using fluoroquinolones or trimethoprim-sulfamethoxazole. To evaluate the therapeutic options against a hyperergic reaction after repeat systemic BCG infection re-challenge was performed with intraperitoneal BCG 7 days after primary infection and oral therapy was given with fluoroquinolones or trimethoprim-sulfamethoxazole with and without steroids. The influence of continuous oral fluoroquinolone therapy on the antitumor effect of BCG was also tested in the MB 49 orthotopic murine bladder tumor model. RESULTS: After primary systemic infection fluoroquinolone therapy alone led to significantly prolonged survival in mice (log rank test p = 0.041), whereas trimethoprim-sulfamethoxazole was ineffective. There was no additional effect of steroid administration. Steroids alone led to premature death (log rank test p = 0.022). After secondary BCG infection only steroid treated animals had prolonged survival (log rank test p = 0.032), whereas antimicrobials alone had no effect. The therapeutic efficacy of BCG in the orthotopic bladder tumor model was not affected by continuous oral fluoroquinolones in terms of survival (log rank test p = 0.001) or bladder weight (Wilcoxon test p = 0.001) compared with untreated controls. CONCLUSIONS: In a mouse model fluoroquinolones had a beneficial effect for primary systemic BCG infections, whereas the hyperergic reaction after repeat BCG infection was susceptible only to steroids. Administering fluoroquinolones during an intravesical treatment course does not affect the antitumor efficacy of BCG.

Animals↗
PubMed1999

Abnormal growth and clonal proliferation of fibroblasts in an animal model of unilateral ureteral obstruction.

The time course for the development of renal interstitial fibrosis (RIF) in rats between days 5 and 25 after unilateral ureteral obstruction (UUO) was studied. In kidneys with UUO under histological examination, an interstitial fibrosis was observed after more than 10 days with progression up to day 25. On day 5, collagen peptidase activity in homogenates of UUO kidneys was about 50% higher than in controls but gradually declined afterwards until reaching the level obtained from contralateral kidneys (CL) on day 25. 10 days after UUO, renal hydroxyproline content was elevated about twofold as compared to CL and sham-operated rats, and increased considerably by day 25 of UUO. In primary cultures of cells obtained from UUO kidneys, fibroblast proliferation increased regardless of the extent of fibrosis. This could be a result of an early inflammatory process. Renal fibroblasts from rats are heterogenous when studied in vitro. When fibroblasts of passage 1 obtained from kidneys 25 days after UUO were plated at low density, the number of mitotic type I clones was elevated 5.5-fold as compared with cultures from CL kidneys. The majority of type I clones in UUO cultures from fibrotic kidneys developed in an unusual fashion with formation of three-dimensional structures. The changes detectable under the unfavorable conditions of clonal culture suggest phenotypical differentiation of a small fraction of fibroblasts from kidneys with RIF. These cells are able to overgrow cell monolayers forming circular growing colonies. Obviously, one needs to distinguish between intensive proliferation as a consequence of acute inflammation, and the changes in phenotype of a small fraction of renal fibroblasts which are resistant to normal physiologic regulative mechanisms in cell culture. The latter may contribute to matrix disorders and RIF.

Animals↗
PubMed1998

The long-term prognosis of benign nephrosclerosis accompanied by focal glomerulosclerosis and renal cortical interstitial fibrosis, designated so-called decompensated benign nephrosclerosis by Fahr, Bohle and Ratscheck.

The long-term prognosis of decompensated benign nephrosclerosis (DBN) was investigated by a retrospective analysis of the fate of 170 patients with this disease, which yielded the following results: 1) DBN carries a particularly poor prognosis. The renal survival rate (RSR) was 35.9% at 5 years and 23.6% at 10 years. The prognosis is therefore worse than that of any other primary glomerulopathy, with the exception of rapidly progressive glomerulonephritis. 2) DBN mainly affects males (sex ratio 5:1) and differs in this respect, among others, from focal sclerosing glomerulonephritis, in which the male:female ratio is 1.2:1. 3) The prognosis for females is no better than for males. 4) The severity of proteinuria at the time of biopsy has no influence on the prognosis. 5) The prognosis is particularly poor in cases in which the serum creatinine concentration is already elevated to more than 2.0 mg% at the time of biopsy. We conclude from these findings that not only the blood pressure, but also the serum creatinine concentration, should be assessed at regular intervals in all hypertensive individuals, so that DBN can be treated at an early stage, when it is still amenable to treatment.

Adult↗
PubMed1998

Osteopontin expression, tubulointerstitial disease, and essential hypertension.

A role has recently been proposed for the tubulointerstitium in the pathogenesis of salt-dependent essential hypertension. In this study, biopsies from patients with essential hypertension with either minimal ("benign") or severe ("decompensated") tubulointertitial injury were analyzed for the expression of osteopontin, a protein known to modulate tubulointerstitial damage and nitric oxide production. In biopsies from patients with decompensated arteriolosclerosis, osteopontin mRNA and protein were increased in tubules in association with expression of alpha-smooth muscle actin by interstitial fibroblasts and increased type IV collagen deposition. The relevance of these findings to the pathogenesis of essential hypertension is discussed.

Actins↗
PubMed1998

Human glomerular structure under normal conditions and in isolated glomerular disease.

Investigation of the human glomerulus in health and disease shows that the human glomerulus comprises seven lobule-like structures with numerous anastomoses. The total length of the capillaries in a single glomerulus is 0.95 cm, making a total of 19 km for all 2-million glomeruli. The total surface area of all glomerular capillaries is 6,000 cm2. The total filtration surface area is 516.1 cm2. Severe isolated disease of the glomerulus, as seen in acute endocapillary glomerulonephritis, membranoproliferative glomerulonephritis types I and II, membranoproliferative glomerulonephritis plus chronic membranous glomerulonephritis, diabetic glomerulosclerosis, and glomerular amyloidosis, does not lead to elevation of serum creatinine concentration, even if the filtration area is reduced to about 20% (as in diabetes) of the normal value. It is concluded that isolated glomerular disease does not lead to elevation of the serum creatinine concentration. Glomerulopathies in which there is acute or chronic elevation of the serum creatinine concentration are accompanied by acute renal failure or involvement of the renal cortical interstitium, respectively.

Acute Kidney Injury↗
PubMed1998

Renal morphology in essential hypertension: analysis of 1177 unselected cases.

Morphological and clinical analysis of 1177 renal biopsies from nonselected patients with essential hypertension revealed compensated benign nephrosclerosis in 775 cases. Decompensated benign nephrosclerosis was found in 251 cases, and secondary malignant nephrosclerosis was found in 151 cases. This article describes the morphological and clinical features of decompensated benign nephrosclerosis, which has received little recognition until now. The morphological and clinical features of secondary malignant nephrosclerosis, which is induced by hypertension, are also considered. There is also a discussion of the differentiation of the latter from primary malignant nephrosclerosis, in which stenosis of the preglomerular vessels develops in the presence of normal blood pressure and leads secondarily to renal hypertension.

Biopsy↗
PubMed1996

Significance of postglomerular capillaries in the pathogenesis of chronic renal failure.

Correlations between the relative volume of the intertubular capillaries in the renal cortex and the serum creatinine concentration in primary glomerulopathies, renal vasculopathies, and chronic interstitial nephritides are reported. In the mesangioproliferative glomerulonephritides, there are significant negative correlations between the number and area of the intertubular capillaries in the cortex and the serum creatinine concentration. In diabetic glomerulosclerosis, renal glomerular amyloidosis, decompensated benign nephrosclerosis, secondary malignant nephrosclerosis, and chronic interstitial nephritis, there is a significant negative correlation between the relative area of the intertubular capillaries and the serum creatinine concentration. Thus, in these diseases, there is progressive narrowing/ obliteration of the postglomerular capillaries which leads to a progressive decrease in glomerular filtration rate and thus to a rise in serum creatinine concentration.

Capillaries↗
PubMed1996

The quality of life during intravesical bacillus Calmette-Guerin therapy.

PURPOSE: In the treatment of cancer the subjective evaluation of therapy induced side effects and quality of life must be considered. Adjuvant intravesical bacillus Calmette-Guerin (BCG) immunotherapy is regarded as highly effective but associated with significant side effects. To clarify whether these side effects significantly impact on patient satisfaction with life, a prospective survey of the health related quality of life and side effects was performed during an intravesical BCG treatment course. MATERIALS AND METHODS: Symptoms and side effects were recorded daily during the 6-week instillation period in 30 patients. The quality of life was determined before, during and after intravesical therapy with the assistance of a self-reported questionnaire. RESULTS: Due to a detailed subjective assessment of side effects, the course of local symptoms could be characterized with great reliability. Although side effects occurred, satisfaction with life in the patients studied was high and was not impaired during the treatment. The incidence of side effects correlated well with patient subjective evaluation of quality of life. CONCLUSIONS: Assessment of side effects and quality of life, as presented in this pilot study, can assist in the quantification of localized symptoms in intravesical therapy could contribute to the comparability of clinical studies. With regard to intravesical BCG immunotherapy, our results suggest that the specific side effects do not seriously impair satisfaction with life in these patients.

Adjuvants, Immunologic↗
PubMed1994

Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application.

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1994

The pathogenesis of chronic renal insufficiency in renal vasculopathies.

Comparative clinical and morphological investigations on the pathogenesis of chronic renal insufficiency in various types of renal vasculopathy revealed the following: 1) Compensated benign nephrosclerosis, with hyalinosis of the walls of the afferent vessels, does not lead to renal insufficiency, since relatively few glomeruli, mostly subcapsular, become obliterated in this disease. 2) In decompensated benign nephrosclerosis, in which not only the afferent vessels but also the glomeruli and the cortical interstitium are involved, there is a significant positive correlation between the relative width of the renal cortical interstitium and the serum creatinine concentration and a significant negative correlation between the relative volume of the postglomerular capillaries and the serum creatinine concentration, as in the primary glomerulopathies. 3) In primary malignant nephrosclerosis, which is always accompanied by haemolytic-uraemic syndrome, the relative width of the cortical interstitium is not related to the serum creatinine concentration. Chronic renal insufficiency develops in this disease as a result of a fall in glomerular filtration rate to inadequate levels due to impairment of renal perfusion by stenotic changes in the preglomerular vessels. 4) In secondary malignant nephrosclerosis, which is never accompanied by haemolytic-uraemic syndrome, there is, as in the primary glomerulopathies, a significant positive correlation between the relative width of the renal cortical interstitium and the serum creatinine concentration and a significant negative correlation between the relative capillary volume and the serum creatinine concentration. 5) In decompensated benign nephrosclerosis the severity of the renal insufficiency depends largely on the degree of obliteration of the postglomerular capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterioles↗
PubMed1994

[Acute noninflammatory renal failure. New pathogenetic aspects in light of findings obtained in autopsy and biopsy of kidneys].

Thorough studies of kidney specimens obtained at autopsy or by renal biopsy revealed, that in noninflammatory acute renal failure oliguria/anuria is caused by increased activation o the renal renin-angiotensin system and increased generation of adenosine. At the polyuric phase moderately increased adenosine in kidney tissue seems to be the main factor responsible for decreased glomerular filtration.

Acute Kidney Injury↗
PubMed1994

Pathogenesis of chronic renal failure in primary glomerulopathies.

Comparative analysis of renal biopsy findings and clinical status in patients with different types of glomerulopathy (primary glomerulonephritis, 1747; diabetic glomerulosclerosis, 488; renal AA and AL amyloidosis, 225) was undertaken to investigate the pathogenesis of chronic renal failure in these diseases. Morphometric, cytological and electron-microscopic investigations were undertaken and yielded the following results: 1. Disease of the renal corpuscles alone, even if it is very severe, does not lead to renal insufficiency or even elevation of the serum creatinine concentration. 2. Chronic renal insufficiency develops only in those cases of glomerulopathy in which the postglomerular capillaries in the renal cortex exhibit chronic inflammation that causes such severe narrowing of these vessels as to impair glomerular perfusion. 3. The passage of basement membrane material from the glomerular capillaries into the primary urine may play a critical role in the pathogenesis of some forms of chronic renal failure, since this material can be reabsorbed by the tubules and is probably presented as an autoantigen to intraepithelial T lymphocytes by proximal tubular epithelial cells that express distinct HLA class II antigens and ICAM-1. 4. The presentation of these autoantigens to intraepithelial T lymphocytes leads in genetically predisposed individuals to an autoimmune response with a consequent marked increase in numbers of T lymphocytes and an increase in macrophages/monocytes, fibroblasts/fibrocytes and plasma cells, and increased production of extracellular matrix by fibroblasts/fibrocytes. 5. The increase in extracellular matrix leads to obliteration of the postglomerular capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillaries↗
PubMed1993

The long-term prognosis of AA and AL renal amyloidosis and the pathogenesis of chronic renal failure in renal amyloidosis.

Investigation of the long-term prognosis and pathogenesis of chronic renal failure in 225 cases of AA and AL renal amyloidosis (perireticular and perireticular + pericollagenous amyloidosis) yielded the following results: 1) The prognosis of both AA and AL amyloidosis is poor, and is worse than all other types of glomerulopathy with the exception of rapidly progressive glomerulonephritis. 2) The probability of maintaining renal function in AL amyloidosis is no lower than that in AA amyloidosis. 3) The prognosis of both AA and AL amyloidosis is significantly worse in cases in which the renal cortical interstitium exhibits fibrosis at the time of the biopsy than in those in which it is normal. 4) In AA and AL amyloidosis, as in various types of inflammatory glomerulopathy, the relative area of the renal cortical interstitium shows a significant positive correlation with the serum creatinine concentration and a significant negative correlation with the creatinine clearance. However, the extent of interstitial amyloid deposition does not correlate with the serum creatinine concentration. Deposition of amyloid in the renal cortical interstitium has no effect on renal excretory function. 5) The long-term prognosis of renal amyloidosis is related to the severity of the glomerular amyloidosis in as much as it is generally worse in Grades III to V than in Grades I and II. However, it must be borne in mind that the incidence of interstitial fibrosis, which is decisive for the long-term prognosis, increases with the severity of glomerular changes. 6) The long-term prognosis of renal amyloidosis is worse if acute renal failure or interstitial fibrosis is present at the time of the biopsy. Patients with both acute renal failure and interstitial fibrosis have the worst prognosis. 7) Isolated glomerular amyloidosis, even if there is severe vascular amyloidosis (vas afferns), does not lead to renal insufficiency or even to a rise in serum creatinine concentration. 8) The number of T lymphocytes in the tubular epithelium in AA and AL amyloidosis is significantly greater than normal, and the number of T lymphocytes, macrophages/monocytes, and fibroblasts/fibrocytes per unit area of interstitium is also significantly increased. 9) As far as the pathogenesis of renal cortical interstitial fibrosis in renal amyloidosis is concerned, it is proposed that, in some cases, this develops from the interstitial edema that is seen in biopsy specimens of patients with renal amyloidosis and acute renal failure.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

The long-term prognosis of the primary glomerulonephritides. A morphological and clinical analysis of 1747 cases.

Long-term studies of all types of primary glomerulonephritis (GN) taking into consideration the major morphological and clinical findings revealed the following: 1) Endocapillary GN, post-streptococcal type has a very good prognosis when only glomerulitis is present. The prognosis is significantly worse if either interstitial inflammation with fibrosis or nephrotic syndrome (NS) is present at the time of the biopsy. 2) The prognosis of the various types of mesangioproliferative GN (IgA nephritis, non-IgA nephritis, and immunohistologically negative GN) is very good if there is only glomerulitis. The prognosis is worse for all three types when the renal cortical interstitium exhibits inflammation with fibrosis at the time of the biopsy, and is worst of all when both interstitial fibrosis (IF) and the signs of acute renal failure (ARF) are present. Of this group, the type in which there are negative immunohistological findings exhibits the best prognosis. No difference in prognosis is found between IgA nephritis and non-IgA nephritis. 3) Minimal changes GN with NS has a very good prognosis when the interstitium is not involved. The presence of interstitial inflammation and fibrosis worsens the prognosis significantly. 4) Focal sclerosing GN has a much poorer prognosis than minimal changes GN with NS, even when there is glomerulitis only (5- and 10-year renal survival rates (RSRs) of 90% and 67%, respectively). If interstitial inflammation and fibrosis are present, the prognosis is significantly worse (5- and 10-year RSRs of 84% and 55%, respectively). The prognosis is worst when both ARF and IF are present at the time of the biopsy (5- and 10-year RSRs of 56% and 46%, respectively). From the clinical side, the prognosis is significantly worse if, at the time of the biopsy, NS is present or the serum creatinine concentration is elevated to more than 1.3 mg%. 5) Chronic membranous GN has a better prognosis than focal sclerosing GN if glomerulitis only is present (5-year RSR, 88%; 10-year RSR, 77%). If the renal cortical interstitium is also involved (in the form of IF), the prognosis is significantly worse (5-year RSR, 65%; 10-year RSR, 38%). The prognosis in this disease, too, is worst when both ARF and IF are present at the time of the biopsy (5-year RSR, 38%; 10-year RSR, 25%). 6) Membranoproliferative GN has a worse prognosis than any of the types of GN so far mentioned (5-year RSR, 51%; 10-year RSR, 32%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Human cytomegalovirus in immunoglobulin A nephropathy: detection by polymerase chain reaction.

Human cytomegalovirus (HCMV) has been suspected to participate in the pathogenesis of IgA nephropathy (IgAN). However, with regard to the presence of HCMV in the renal tissue of IgAN, conflicting results have been reported using a variety of different techniques. Renal biopsies of 29 patients with IgAN, of 7 with focal segmental glomerulosclerosis (FSGS) and of 11 normal kidneys were analyzed for the presence of HCMV-DNA using the polymerase chain reaction. HCMV-DNA was detected by hybridization with digoxigenin-labelled probes in 14 of 19 analyzed frozen renal biopsies from patients with IgAN. However, only 1 of 17 renal biopsies of IgAN embedded in paraffin was positive for HCMV-DNA. Furthermore, HCMV-DNA was detected in 4 of 18 frozen normal kidneys but in none of the tissues from patients with FSGS. The present results provide further evidence of an association between the presence of HCMV in renal tissue and IgAN.

Adult↗