Estrogen dependence of primary breast cancer--correlation with histologic type and grade. The purpose of this study was to investigate whether histologic type and grade of primary breast cancer are related to the estrogen and progesterone receptors. Our results showed that histologic type influenced the estrogen dependence through histologic grade. There was no difference in the estrogen and progesterone receptor content, when corresponding grades of different histologic types and estrogen dependence were confirmed by quantitative non-parametric analysis. It showed a direct relationship between estrogen and progesterone receptor content in all the three histologic grades and further that histologic grade defines three different groups in regard to progesterone receptor content.


The diagnosis of breast cancer--experiences from the community of Kungsbacka, Sweden. In Kungsbacka, Sweden, with about 48,000 inhabitants, the records of all subjects who had been diagnosed to have breast cancer during a 3-year period were studied. The incidence was 41 per 100,000 inhabitants per year. A palpable mass in the breasts was the most common initial sign (77%). Most patients first visited a physician working within the primary health care system. In 94% of the patients a palpable mass in their breasts had been found by the physician. In 16% of the cases a better or a more regular breast self-examination could have reduced the patients' delay. Mean doctor's delay was approximately five weeks. Subjects with no spread to the axillary lymph nodes had a favorable prognosis with a 5-year mortality rate of 12% during the follow-up study period as compared with patients who had distant metastases and/or axillary node involvement, in whom a mortality rate of 67% was observed during the same study period.


Survival rates for childhood malignancies in Slovakia. Survival rates (SR) for population-based series of 1564 cases of cancer in children aged 0-14, diagnosed during the decade 1978-1987 in Slovakia and derived from the National Cancer Registry, were examined. The overall 5-year SR (all types of childhood malignancies combined) was 49.8%. Different SR were ascertained for leukemias -43.8%, lymphomas -59.1%, CNS tumors -42.7% and for other remaining diagnostic groups and subgroups of childhood malignancies. Generally, the SR were slightly better for girls than for boys. Cancer patients being diagnosed during the first two years of age showed worse prognosis with a 5-year survival rate of 36.8% as compared to 52.6% for children aged 2-14 at diagnosis. Differences in 5-year survival were also found between urban and rural areas: 56.8% and 48.8%, respectively. The 5-year SR increased during the study period from 48.5% for 1978-1982 to 50.0% for 1983-1987. Comparison of SR from Slovakia with the corresponding rates observed recently in some developed countries indicated possibilities to improve prognosis of childhood malignancies in this country.


Influence of tobacco on laryngeal carcinoma in Spain. Spain is one of the countries with the highest incidence of laryngeal cancer in the world. Many risk factors have been linked to this neoplasm, such as tobacco, alcohol and occupation. In order to evaluate the effect of tobacco, a case-control study was performed. Cases included 85 patients with cancer of the larynx diagnosed in La Paz, Madrid, between 1983 and 1988, whereas a sample of 170 patients from the same hospital was used as control. Our study revealed that tobacco was significantly associated with laryngeal cancer. Filter-tipped cigarette was shown to be a risk factor as well as consumption of non-filtered cigarettes at first followed by consumption of filter-tipped cigarettes. An association was found between laryngeal cancer and smoking more than 15 cigarettes a day, as well as between cancer of the larynx and being in the habit of smoking for more than 15 years.


[Atypical facial pain--quality of IHS (International Headache Society) criteria and psychometric data]. Atypical facial pain is generally an unclearly defined pain syndrome. We tested in 35 patients (31 women, 4 men) with a mean age of 53.2 +/- 14.9 years and a chronic facial pain syndrome the quality of the new diagnostic criteria of the International Headache Society (IHS), at the same time using the SCL-90-R (Self-Report Symptom Inventory), to identify any associated psychopathology. In accordance with the literature there is a marked female preponderance, an altogether vague description of symptoms and a long history of incorrect diagnoses. Of note is the high number of invasive procedures (3.5 +/- 3.0). In agreement with the IHS commentary, an operation or injury to the face was a suspected cause in 43%. In contrast to the IHS criteria, we found in our patient sample dysaesthesia (63%), bilateral occurrence (37%), remission periods (57%), pain attacks (23%) and presence of superficial as well as deep pain. Depression is by no means the only psychopathological abnormality in atypical facial pain; a broad spectrum of complaints is seen. The IHS classification appears insufficient to separate atypical facial pain from other primary headache and facial pain syndromes. We therefore suggest a modified version of the IHS criteria for atypical facial pain.


[Diagnosis of dysarthria with the "Munich Intelligibility Profile"--construction of the procedure and its use]. No German-based methods for reliable assessment of the intelligibility of dysarthric speech have yet been described. The techniques usually applied in clinical diagnostics take no account of the various factors influencing the understanding of spoken language. They also fail to differentiate between individual patterns of impaired intelligibility. The intelligibility profile presented here controls for the most relevant influencing factors and allows us to discern therapeutically relevant patterns of disturbed intelligibility. The principles of its construction and some applications are presented.


[Brain mapping for discriminating age related changes from dementia]. BM-EEG (Brain Mapping) and BM-P300 was studied for age related changes in 63 healthy controls (17.1-87.9 years). Additionally the discriminative power of both functional measures was tested in 21 patients with the clinical diagnosis (NINCDS-ADRDA) of probable dementia of Alzheimer type (DAT) of mild to moderate degree (Global Deterioration Scale, 4.2 +/- 2.6). For global and regional absolute and relative power values in the 4 frequency bands alpha, beta, theta and delta, the alpha-peak, P300 latency and amplitudes, quantitative and topographical aspects were analysed. Despite a broad variation of normal values both tests revealed age related changes. For separation between DAT and normal controls BM-EEG was superior to BM-P300. Relative global and regional theta power was the most sensitive parameter to discriminate both groups. BM data are compared with reported findings of traditional EEG and cognitive evoked potentials.


[Correlation between neurologic disease and Borrelia burgdorferi antibodies in 800 paired serum/cerebrospinal fluid samples]. Paired serum and cerebrospinal fluid (CSF) samples from 800 patients of a neurological clinic were tested for antibodies to Borrelia burgdorferi. A flagellum enzyme-linked immunosorbent assay was used for antibody screening. All serum/CSF pairs with any elevated antibody response were also tested by a Western blot, a method for confirmation. 65 patients (8.1%) had serum IgG antibodies on ELISA screening and 22 of these (2.8%) were confirmed by Western blot. 20 patients (2.5%) had elevated antibody titers in CSF by ELISA and 12 of these (1.5%) reacted to the Western blot. Clinical features of Bannwarth's syndrome (BS) were present in 12 patients (1.5%) and four patients (0.5%) showed other manifestations of Lyme borreliosis. All patients with Bannwarth's syndrome were positive in serum by both methods and 10 had elevated antibody activity in the CSF proven by the two methods. The combination of a sensitive ELISA for screening and a sensitive and specific Western blot for confirmation reduces the number of positive results but is sensitive in detecting active disease.


[Coma polyneuropathy after cardiopulmonary resuscitation]. A 60 year old female patient developed an acute polyneuropathy a few days after a successful cardiopulmonary reanimation followed by coma for several days. Recovery was good as demonstrated at one year follow-up. Residual damage consisted in very mild myoclonic jerks (abortive Lance-Adams syndrome).


[Damage to the lateral cutaneous femoral nerve after transfemoral angiography]. We report on two patients with lesions of the lateral cutaneous nerve of the thigh after transfemoral angiography. Symptoms were hypesthesia, dysesthesia and hypalgesia of the right lateral thigh. One patient had no hematoma, the other a hematoma of the medial thigh which did not enlarge thigh circumference. Both patients had had a tight pressure bandage applied for 24 hours. There were no signs of a femoral nerve lesion. Both patients were severely distressed by paresthesia. The numbness subsided after three weeks in one patient, but pain persisted. The other patient had symptoms for over six months. The lateral cutaneous nerve of the thigh is located distinctly lateral to the puncture site in transfemoral angiography. Hence we suggest that the nerve lesion was caused neither by the puncture itself nor by a hemorrhage, but by the tight bandage.


[Supranuclear, bilateral and distal-symmetric arm paralysis in central cervical spinal cord trauma]. A case of central spinal cord trauma following hyperextension of the cervical spine and with the finding on MRT of lesions at the level of C 2/3 to C 4/5 disks is reported. A supranuclear paralysis of the lower segments with complete paralysis of the hands and a transient atrophy of the intrinsic hand muscles could be demonstrated. In this connection we refer to the original clinical descriptions of O. Foerster, which have almost been forgotten in the mean time.


[Extensive brain injury caused by attempted suicide with an airgun and ultrasound controlled removal of the deep intracranial projectile]. A 65-year-old man attempted suicide by shooting himself in the right temple with an air-gun. There was no loss of consciousness. He remained neurologically asymptomatic. On plain x-rays, the pellet was found in the left frontal lobe and CT-scans revealed a vast cerebral injury with a large hematoma in the right frontotemporal region and along the bullet track. The entry wound was opened and the hematoma was evacuated after removal of small bone fragments and limited osteoclastic enlargement of the bullet hole under the view of the microscope. No attempt was made to remove the pellet through the bullet track in order to avoid additional injury to delicate frontal midline structures. A left frontal burr hole was made and a thin silastic tube, as used for ventricular drainage, was placed with its tip at the projectile under ultrasonic guidance. Along the tube, the pellet was removed through a 5 mm cortical incision with the use of the microscope. The postoperative course was uneventful, the patient had no neurological deficit and early postoperative CT-scans showed complete removal of the hematoma and the bullet without additional brain injury.


Effects of ACE inhibition on the course of nephropathy in type I diabetes mellitus. Nephropathy is a severe complication of type I diabetes mellitus. About 25% of all new candidates for renal replacement therapy consist of diabetic patients. Glomerular hyperfiltration is an important causative factor in the development of this nephropathy. Microalbuminuria is the clinical first symptom of glomerular hypertension. New information stresses the importance of angiotensin II. Systemic as well as local reduction of angiotensin II formation can reduce glomerular hyperfiltration. Angiotensin-converting enzyme inhibitors should therefore be considered as first anti-hypertensive agents in type I diabetics with microalbuminuria.


Betaxolol in obese hypertensive patients. Long-term effects on blood pressure and serum lipids. The antihypertensive and metabolic effects of betaxolol (20 mg/day) were monitored in 40 patients (17 male), aged 54 +/- 2 yr (mean +/- SEM), with moderate essential hypertension. In a subgroup, consisting of 35 obese patients with a Quetelet index greater than 25.0, blood pressure, heart rate, side effects and biochemical variables were registered bi-monthly for a period of 6 months and after a placebo run-in and run-out period of 2 weeks. Betaxolol decreased blood pressure from 165 +/- 3/107 +/- 1 to 151 +/- 3/95 +/- 2 mmHg after 2 weeks and further to 151 +/- 3/93 +/- 2 mmHg after 6 months (p less than 0.001). Ninety percent of the patients responded to therapy with betaxolol. Heart rate fell from 77 +/- 2 to 64 +/- 1 bpm (p less than 0.001). No significant changes were observed in levels of total cholesterol, LDL-cholesterol or HDL-cholesterol. Triglycerides tended to increase from 2.2 +/- 0.3 to 2.8 +/- 0.4 mmol/l after 4 months of treatment (NS). Renal function was not influenced by betaxolol. Side effects, recorded on a standard questionnaire, did not differ between betaxolol and placebo. In conclusion, betaxolol in a fixed dose of 20 mg/day is an effective antihypertensive drug in the long-term treatment of obese, hypertensive patients, without adverse effects on lipoproteins.


Lupus peritonitis presented as vague abdominal complaints in a SLE patient. A 40-yr-old Caucasian woman who had been suffering from systemic lupus erythematosus (SLE) since five years developed vague abdominal complaints whilst under treatment with a low dose of steroids. She had been admitted because of vomiting and abdominal tenderness. The ESR and CRP levels were rising and the C4 level had been persistently low in the preceding months. Normal non-invasive procedures did not allow a diagnosis to be made. Therefore exploratory laparotomy was performed and revealed a non-bacterial peritonitis and an oedematous jejunum. She responded well to a high dose of prednisone. Serositis of the peritoneum as well as bowel vasculitis may be a rare manifestation of SLE despite apparent control of other lupus manifestations. In this patient serositis flares were associated with a rise in CRP level.


Familial nonparasitic splenic cysts.

Familial nonparasitic splenic cysts. Only three times the occurrence of splenic cysts in siblings has been reported. This is the first report of a nonparasitic splenic cyst in mother and daughter. This improbable coincidence may perhaps give a better insight in the histogenesis of splenic cysts. A practical classification of nonparasitic splenic cysts is presented.


Octreotide for medullary thyroid carcinoma associated diarrhoea. Medullary thyroid carcinoma associated diarrhoea can be disabling. A 75-yr-old man with metastatic medullary thyroid carcinoma and refractory diarrhoea is described. Subcutaneous administration of the somatostatin analogue, octreotide, 100 micrograms thrice daily, resulted in a sustained improvement in diarrhoea and disappearance of faecal incontinence without reducing calcitonin levels. Octreotide therapy should be considered as symptomatic treatment for otherwise refractory diarrhoea associated with medullary thyroid carcinoma.


Glucagon-stimulated insulin secretion in patients with type 2 diabetes mellitus: support for the concept of glucose toxicity. Parameters of blood glucose control and insulin secretion were evaluated in 114 patients with type 2 diabetes mellitus, who were no longer controlled satisfactorily by maximal doses of oral hypoglycaemic agents, and compared with those obtained in 11 healthy control subjects, 32 patients with recently-diagnosed type 2 diabetes, and 16 tablet-treated and 36 insulin-treated patients. Newly-diagnosed patients were slightly younger (60 +/- 13 yr) and had a slightly higher body mass index (29.4 +/- 6.5 kg/m2). Known duration of diabetes was 9 yr (range 1-37) in secondary failure, and 11 yr (range 1-31) in insulin-treated patients. Fasting blood glucose was the highest (13.8 +/- 2.8 mmol/l) in secondary failure and newly-diagnosed patients (12.6 +/- 3.8 mmol/l) compared to tablet-treated (8.7 +/- 3.3 mmol/l) and insulin-treated patients (9.6 +/- 3.2 mmol/l, p less than 0.05). HbA1c levels were comparably elevated. In insulin-treated patients, fasting plasma C-peptide levels were lower relative to the mutually comparable levels in the other 3 diabetic groups. Fasting plasma insulin levels did not differ between the 4 diabetic groups. C-peptide release after glucagon (C-peptide AUC) was comparable in all 4 diabetic groups, although in tablet-treated patients the ratio C-peptide AUC/fasting blood glucose was higher (p less than 0.05). We conclude that the clinical usefulness of determining residual insulin secretion in type 2 diabetic patients is limited, and that the similar reduction of insulin secretion in severely hyperglycaemic newly-diagnosed and secondary failure type 2 diabetic patients supports the concept of "glucose toxicity".


Hand bone growth during puberty and in Turner's syndrome. Measurements were made on hand radiographs of normal girls and patients with Turner's syndrome. Normal girls going through puberty display increases in hand bone dimensions which are highly correlated with height and bone age. We report such changes in length and total bone width of metacarpal II (MCII) and proximal phalanx II (PPII), and in combined cortical thickness and cortical area of MCII. For the relative cortical area, the correlations are less pronounced. In comparison with controls of similar height, MCII of patients with Turner's syndrome has greater length and total bone width and combined cortical thickness. Turner patients treated with sex steroids undergo skeletal maturation as well as a rise in MCII relative cortical area (a measure of bone density), but fail to show a commensurate increase in MCII length and in MCII cortical area (a measure of bone mass). It is concluded that in untreated Turner patients, bone density as well as bone mass are normal for the (retarded) bone age, and that sex steroids which promote skeletal maturity likewise raise bone density but not bone mass. The (relative) insensitivity of bone mass and the lack of accelerated statural growth in response to administered sex steroids may be inborn characteristics of the Turner skeleton.


Paget's disease with osteolytic lesions: combining medical and surgical treatments. A patient with extensive Paget's disease of bone presented with severe bone pain, hypercalcaemia and a large osteolytic lesion of the femur which developed during long-term therapy with etidronate. Treatment with pamidronate normalized serum calcium concentration and induced a complete biochemical remission. The osteolytic lesion was grafted with bone chips. A recurrence of the Paget's disease was associated with clear autonomous hypercalcaemic hyperparathyroidism. Five years after removal of 3 1/2 hyperplastic parathyroid glands, the patient remains in complete clinical and biochemical remission. These findings illustrate the pitfalls encountered in the management of Paget's disease and the value of combining medical and surgical interventions.


Pneumatosis intestinalis in mixed connective tissue disease. Two young female patients with established mixed connective tissue disease (MCTD) are described, in whom the disease course was complicated by intestinal pseudo-obstruction and pneumoperitoneum due to pneumatosis intestinalis. Conservative management of this rare complication in MCTD, which included the use of high-flow normobaric oxygen by mask, led to a complete resolution of the abdominal symptoms in both patients.


Glyburide-induced cholestatic hepatitis and liver failure. Case-report and review of the literature. As sulphonylurea derivatives are used ubiquitously, the possibility that they may cause liver disease deserves attention. In contrast to the known pattern of reversible parenchymal liver disease due to sulphonylurea derivatives, we describe a fatal case of glyburide-induced cholestatic hepatitis with liver failure.


Successful ultrasonically guided percutaneous ethanol injection for secondary hyperparathyroidism. Ultrasonically guided percutaneous ethanol injection to all of four enlarged parathyroid glands, which were confirmed by fine-needle aspiration biopsy, was successfully performed in a hemodialysis patient with secondary hyperparathyroidism. In addition to marked reduction of serum parathyroid hormone, the size of parathyroid glands was significantly decreased after the procedure. As an adverse effect, the patient experienced a transient self-limiting dysphonia due to right recurrent nerve palsy after the first injection. This procedure may be an effective alternative to surgical treatment or administration of high-dose 1,25(OH)2 vitamin D3 in uremic patients with sonographically verified multiple enlarged parathyroid glands.


Fully enzymatic inulin determination in small volume samples without deproteinization. A fully enzymatic method for the determination of inulin in serum or plasma without deproteinization is described. The assay is carried out by means of a fructose determination after hydrolysis of inulin via inulinase and simultaneous oxidation of the native glucose using glucose oxidase and H2O2. This time-saving procedure of high specificity, sensitivity and accuracy requires only small sample volumes. The usefulness of the method is shown by analysis of blood levels in humans and rabbits after an intravenous administration of Inutest.


Amino-aciduria and enzymuria in patients with artificial heart valves. Fifteen patients with artificial heart valves and evidence of chronic intravascular haemolysis were studied for proximal tubular dysfunction. Three patients had haemosiderinuria and haemoglobinuria; 2 had haemoglobinuria alone. Increased urinary amino acid nitrogen occurred in 8, raised fractional beta 2-microglobulin excretion in 2, hypophosphataemia in 4, renal glycosuria in 1 and enhanced fractional urate excretion in 1. Urinary N-acetyl-beta-glucosaminidase (NAG) excretion increased in 7; the mean urinary NAG/creatinine ratio was raised to twice the upper limit of the normal range. Renal haemosiderosis due to chronic intravascular haemolysis could cause tubular injury.


Plasma levels of the anaphylatoxins C3a and C4a in patients with IgA nephropathy/Henoch-Schönlein nephritis. Measurements of plasma anaphylatoxins C3a and C4a were carried out as an indicator of in vivo complement activation in 46 patients suffering from IgA nephropathy/Henoch-Schönlein nephritis. There was a significant correlation between plasma levels of C4a and plasma creatinine and urea. We also found a significant correlation of plasma levels of C3a with plasma creatinine. We propose that the measurement of anaphylatoxin levels provides a sensitive indicator of in vivo complement activation and may serve as an additional method for monitoring the progress of disease in these patients.


Inhibition of vascular permeability factor production by ciclosporin in minimal change nephrotic syndrome. In order to ascertain whether ciclosporin (Cs) has an inhibitory effect on the vascular permeability factor (VPF) production, various quantities of Cs were added to T lymphocyte cultures from 8 children with minimal change nephrotic syndrome (MCNS) and the VPF activity of culture supernatants was assayed. As a result of the addition of Cs, a dose-dependent inhibition of VPF production was seen. VPF production was inhibited by a level of between 100 and 250 ng/ml of Cs in vitro. The reduction of proteinuria by Cs in MCNS might be due to the inhibition of VPF production.


Lipids in the progression of chronic renal failure. Lipid disturbances have been linked to the progression of chronic renal disease. We examined 52 patients with a creatinine clearance (CCr) of 38.5 +/- 7.9 ml/min due to various nephropathies, on free diet. Bimonthly, over a 12-month period, we assessed: serum creatinine (Cr); CCr; daily urinary urea excretion; urinary protein excretion per unit of residual renal function (UProt/CCr); total, HDL, VLDL and LDL cholesterol; triglycerides; Apo A, Apo B. Chronic renal failure was progressive in 22 patients with a slope of 1/Cr-0.00358 +/- 0.00247, stable in 30 with a slope of 0.00420 +/- 0.00285. Lipid parameters did not differ significantly between the two groups but for the lower Apo A and Apo A/Apo B ratio values in the progressive group. Overall slope inversely correlated with basal CCr; in the progressive patients the slope correlated with the percentage variation of UProt/CCr and only partially with the altered Apo profile.


Glycosaminoglycans in urolithiasis.

Glycosaminoglycans in urolithiasis. To determine if there are differences in urinary glycosaminoglycan (GAG) concentrations, 43 stone-forming patients and 37 healthy control subjects of both sexes were studied. Urinary concentrations of calcium, magnesium, creatinine, uric acid and GAGs were determined. GAGs were measured by the Di Ferrante precipitation procedure followed by the Bitter and Muir reaction. Urinary GAG concentration and daily output were significantly lower in stone-forming patients. The present study clearly demonstrates the decreased urinary GAG concentration and excretion in stone-forming patients and suggests an interaction between GAGs and urate that could modify the inhibitory potency of GAGs.


Effect of simvastatin on qualitative and quantitative changes of lipoprotein metabolism in CAPD patients. The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia. After a 4-week placebo period, simvastatin was administered in increasing doses over a period of 3 months (1st month 10 mg; 2nd month 20 mg and 3rd month 40 mg day-1). Simvastatin reduced total serum cholesterol (300.0 +/- 15.5 vs. 193.0 +/- 8.0; -35%), LDL cholesterol (203.8 +/- 13.0 vs. 104.7 +/- 6.0; -48.0%) as well as apolipoprotein B (132.3 +/- 6.6 vs. 77.8 +/- 2.7 mg/dl; -40%). Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.55 +/- 0.016 vs. 0.64 +/- 0.027). Another remarkable effect was the reduction of cholesterol concentration in VLDL (47.8 +/- 5.6 vs. 30.4 +/- 5.2; -35%). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.57 +/- 0.3 vs. 4.28 +/- 0.29), indicating VLDL formation poor in cholesterol and rich in triglycerides. However, HDL cholesterol increased significantly from 48.6 +/- 4.4 to 57.9 +/- 5.3 mg/dl (23%). Lipoprotein(a) levels were increased as compared to controls (420 +/- 73 vs. 145 +/- 26 U/l), but were not influenced significantly by simvastatin treatment (539 +/- 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of simvastatin plasma levels 12 h after drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that CAPD patients with high serum cholesterol are good candidates for the treatment with HMG-CoA reductase inhibitors.


A case of POEMS syndrome showing elevated serum interleukin 6 and abnormal expression of interleukin 6 in the kidney. A 46-year-old female presented with POEMS syndrome. Hemodialysis was initiated to control severe anasarca and declining renal function. Corticosteroids were effective in treating renal insufficiency and other symptoms. Serum interleukin 6 (IL-6) was elevated before the corticosteroid therapy but returned to the normal level under the therapy. Immunostaining for the kidney tissue obtained by a renal biopsy showed a diffuse distribution of IL-6 in the glomeruli; thus, in contrast to normal, IL-6 was detected not only in mesangial cells but also in endothelial cells. IL-6 was also distributed in capillaries in the interstitium. While these results suggest a pathogenic role of IL-6 in POEMS syndrome, other factors may be necessary for the full expression of symptoms. Furthermore, it is suggested that chronically stimulated glomerular endothelial cells are capable of producing IL-6.


Shape of the relationship between hypertension and the rate of progression of renal failure in autosomal dominant polycystic kidney disease. The effect of hypertension on the rate of progression of renal failure was analyzed in 26 patients with autosomal dominant polycystic kidney disease relating the slopes of progression (linear regression of the reciprocal serum creatinine on time) with the average mean arterial pressure, systolic and diastolic pressure, derived over the entire follow-up period for each patient. Hypertension was found in 19 of the 26 patients. Using simple linear regression, there was no significant correlation between the two variables in any case. Using polynomial regression (quadratic and cubic), this relationship fits a sigmoid (for diastolic pressure) or a negative parabolic curve (for mean arterial pressure and systolic pressure); i.e. the lowest and the highest values of mean arterial pressure and systolic pressure were associated with faster rates of progression. Thus, an appropriate model to study this relationship is not the linear but the polynomial regression.


Induction of interleukin 6 synthesis in mouse glomeruli and cultured mesangial cells. Interleukin 6 (IL-6) is an autocrine growth factor of cultured mesangial cells (MC) and intraglomerular IL-6 production is suggested to be closely associated with the pathogenesis of human mesangial proliferative glomerulonephritis (mesPGN). In this study, to elucidate the mechanisms regulating the intraglomerular production of IL-6, we examined what kinds of stimuli are significant in the induction of IL-6 synthesis in vitro and in vivo. Incubation of cultured mesangial cells with interleukin 1 (IL-1) or bacterial lipopolysaccharide (LPS) induced significant IL-6 production, and intravenous injection of IL-1 or LPS into normal BALB/c mice induced significant intraglomerular IL-6 mRNA expression. Furthermore, we indicated in this study that IL-6 mRNA expression was augmented in the glomeruli of mice with immune complex-mediated glomerulonephritis.


Cystic radiolucencies of carpal bones, distal radius and ulna as a marker for dialysis-associated amyloid osteoarthropathy. Patients on long-term hemodialysis (HD) are known to develop amyloid osteoarthropathy, evidenced as cystic radiolucencies on X-rays of the affected joints. To study the relationship between cystic radiolucencies and amyloid osteoarthropathy in 394 patients, we classified the severity of the cystic radiolucencies seen in the wrist joint on a 4-point scale and evaluated the association between lesion severity (grade) and several parameters. Biopsy was performed in 8 patients with 11 bone cysts of the wrist joint who had been operated for carpal tunnel syndrome. HD for 10 years or longer, age 50 or older and the presence of carpal tunnel syndrome were associated with severe cyst rating. There was no association between lesion grade and serum level of PTH-C, aluminum or beta 2-microglobulin (B2M). Ten of the 11 biopsied bone cysts in 8 patients with carpal tunnel syndrome demonstrated amyloid deposits which reacted with B2M. We conclude that a cystic radiolucency observed in the wrist joint of a patient undergoing HD indicates the deposition of amyloid. The cyst grade provides a useful marker for the severity of amyloid osteoarthropathy in HD patients.


Verapamil increases the nephrotoxic potential of gentamicin in rats. The effect of verapamil on the nephrotoxic potential of gentamicin was examined in rats. Rats were injected with one of the two or both drugs for 6 days and sacrificed 48 h after the last injection. In verapamil-treated rats (5 mg/kg/day), no histological or biochemical evidence of renal injury was detected. In all gentamicin-treated rats (100 mg/kg/day), a significant increase in kidney weight was observed (p less than 0.001). The renal histopathologic lesions were more extensive in rats treated simultaneously with both gentamicin and verapamil. These rats exhibited a decline in body weight earlier (from day 4) than rats injected with gentamicin alone (from day 6). Serum urea nitrogen and creatinine in the latter group of rats were 24.9 +/- 3.7 and 1.1 +/- 0.1 versus 47.4 +/- 8.6 and 1.6 +/- 0.2 mg/dl, respectively, in rats treated with the combined therapy (p less than 0.05). These results indicate that verapamil increases the severity of gentamicin nephrotoxicity. This interaction should be considered as a factor that can potentially increase the nephrotoxic risk associated with gentamicin administration.


Effects of acyclovir on renal function.

Effects of acyclovir on renal function. The renal effects of acyclovir (100 mg/kg body weight i.p. for 7 days) were studied in rats. All animals became polyuric and presented an increase in blood urea nitrogen and fractional excretion of sodium and potassium. During hypotonic saline infusion, the acyclovir-treated rats showed higher distal fractional delivery compared to normal rats (27.8 +/- 4.7 vs. 11.3 +/- 0.9%, p less than 0.01) and a lower ratio of free-water clearance to distal sodium delivery (33.5 +/- 7.8 vs. 57.2 +/- 3.9%, p less than 0.02). Following hypertonic saline infusion, the ratio of osmolar to inulin clearance was higher in acyclovir rats (47.8 +/- 7.4%) than in normal rats (27.0 +/- 4.8%), whereas the ratio of free-water reabsorption to osmolar clearance was lower in the acyclovir rats (13.6 +/- 4.6 vs. 38.2 +/- 3.2%, p less than 0.01). These findings suggest an effect of acyclovir on the proximal tubule, thick ascending limb and/or inner medullary collecting duct (IMCD). In vitro measurements of 3H2O permeability of perfused IMCD of normal rats showed that vasopressin (50 microU/ml) added to the bath increased the diffusional water permeability (43.4 +/- 4.8 vs. 105.6 +/- 9.1 x 10(-5) cm/s), while in acyclovir rats, the control value (58.8 +/- 9.1 x 10(-5) cm/s) did not increase significantly in the presence of vasopressin (71.3 +/- 13.6 x 10(-5) cm/s). These results suggest that high doses of acyclovir produce azotemia and an abnormal function of the proximal tubule and thick ascending limb associated with resistance to vasopressin of the IMCD.


L-arginine reduces glomerular basement membrane collagen N epsilon-carboxymethyllysine in the diabetic db/db mouse. The present study was carried out to examine the effect of L-arginine on advanced stage nonenzymatic glycosylation end products in glomerular basement membrane (GBM) as represented by carboxymethyllysine (CML). Twelve db/db mice were given a solution containing a daily dosage of L-arginine of 50 mg/kg body weight orally. Twelve db/db mice served as controls. At the end of the 4-months study period treated animals had significantly lower concentrations of CML (0.084 +/- 0.008, 0.071-0.098 nmol/mumol OH-proline; mean +/- SD, range, p less than 0.01) compared to untreated controls (0.11 +/- 0.018, 0.095-0.152 nmol/mumol OH-proline). In addition, there was a significant positive correlation between GBM thickness and concentrations of CML (r = 0.86, p less than 0.001). We conclude that reduction of CML concentrations in treated db/db mice possibly reflects a beneficial effect of L-arginine on advanced stage nonenzymatic glycosylation end-products in GBM. In addition, measuring CML concentrations might have future clinical implications as a noninvasive parameter for basement membrane thickening.


Glomerular epithelial cell endocytosis in puromycin-induced glomerulopathy. Glomerulopathy and nephrotic syndrome were induced in rats by intravenous puromycin aminonucleoside. Ten days after the injection of puromycin, the animals have developed heavy proteinuria. During this phase, glomerular epithelial cell endocytosis was studied by injecting a conjugate of horseradish peroxidase and poly-L-lysine. This conjugate has been shown to be endocytosed by glomerular epithelial cells. The rats were serially sacrificed from 1 min to 24 h after this injection. Peroxidase was localised cytochemically and observed at light and electron microscopy. The early events of endocytosis in glomerulopathy (namely the binding to the plasma membrane, the membrane invagination and the formation of the early vesicles) were qualitatively similar to those in the normal. The later events (the fusion of the vesicles and their movement within the cells) were inhibited. The results show that puromycin aminonucleoside damages epithelial cell endocytotic activity and affects the later processing of the conjugate within the cells.


Decreased aortic valve prosthesis-associated haemolysis after changing from haemodialysis to peritoneal dialysis. We report here a chronic haemodialysis patient who had severe anaemia following replacement of his aortic valve. The investigations confirmed a traumatic valve effect. The surgeons were reluctant to replace the valve because of the high cardiothoracic risk and absence of significant leak or stenosis. Furthermore, the patient refused to consider additional surgery. We changed his modality of dialysis to continuous ambulatory peritoneal dialysis; subsequently, there was a dramatic decrease in his transfusion requirement, and the patient was symptomatically and functionally better. A literature search indicates that this therapeutic response has not been reported before.


Severe tubulopathy and kidney graft rupture after coadministration of mannitol and ciclosporin. Spontaneous allograft rupture after kidney transplantation is a rare complication usually due to an acute rejection of the interstitial type. In a 32-year-old man kidney transplantation was performed under immunosuppression with prednisolone and ciclosporin (CS). The dose of CS was 5 mg/kg body weight intravenously for the first 24 h, on the 2nd day 10 mg/kg/day orally, with gradually decreasing doses thereafter. The patient remained oliguric in the postoperative period and received additionally 600 ml mannitol solution intravenously for osmodiuresis within a period of 6 days. On the 8th postoperative day, 48 h after the last intravenous infusion of mannitol, spontaneous renal rupture occurred. The CS concentrations in the blood during the days before the rupture were within the upper normal range for effective immunosuppression (300-600 ng/ml). Intraoperatively the kidney appeared enlarged due to edematous swelling of the graft, but it showed no signs of rejection. The histological finding was a toxic tubulopathy with extensive isometric vacuolization and peritubular congestion, a known side effect of both of CS and of mannitol. The rupture was successfully repaired. Thirty-four days after the transplantation diuresis increased and hemodialysis therapy could be discontinued. In a second biopsy of the kidney the signs of toxic tubulopathy with isometric vacuolization were reduced. On the following days the serum creatinine dropped below 160 mumol/l. It can be assumed that the combination of CS therapy and administration of massive and continued doses of mannitol in an oliguric patient with allograft kidney may potentiate severe tubulopathy with concomitant edematous swelling of the graft. This can result in an increasing danger of spontaneous renal rupture.


Marked eosinophilia induced by nafamostat mesilate, an anticoagulant in a hemodialysis patient. A 61-year-old Japanese female on hemodialysis developed marked eosinophilia induced by nafamostat mesilate as an anticoagulant for hemodialysis. This is the first case of hypereosinophilic syndrome induced by nafamostat mesilate in a hemodialysis patient. The elevated eosinophil counts (51,900/mm3) are the highest for hemodialysis-associated eosinophilia. This eosinophilia was eliminated after cessation of nafamostat mesilate. We confirmed that the cause of this eosinophilia was nafamostat mesilate by using the challenge test.


Intraglomerular foam cells and human focal glomerulosclerosis. Experimental evidence suggests a pathogenetic role for lipids in focal glomerulosclerosis (FGS) analogous to atherosclerosis. As foam cells (FC) are an important factor in atherosclerosis, a retrospective comparative study was done to evaluate the significance of intraglomerular FC in human FGS. Glomerular FC infiltration was evaluated in 115 biopsies of FGS, 120 biopsies of membranous glomerulonephritis (MGN) and 50 biopsies of minimal-change disease (MCD). Selected clinical and laboratory data collected at about the time of biopsy were reviewed. The proportion of biopsies showing glomerular FC was much higher in FGS (70%) than in either MGN (12%) or MCD (0%) p less than 0.001. The mean percent (+/- SD) of glomeruli with FC per biopsy was significantly greater in FGS (7.9 +/- 9.9) than in MGN (2.0 +/- 7.8; p less than 0.0001). Of the 14 MGN biopsies with FC, 13 showed superimposed FGS. Mean serum total cholesterol and triglyceride were not significantly higher in FGS than in either MGN or MCD. The results demonstrate a close association of glomerular FC infiltration with FGS.


Decreased renal phosphate threshold in patients with gout. Serum and 24-hour urinary phosphate levels in primary gout patients and control subjects were measured. About 45% of gouty patients showed mild hypophosphatemia. However, mean 24-hour urinary excretion of phosphate was significantly elevated as compared with that of controls. Gouty patients showed a significantly decreased tubular reabsorption of phosphate and renal phosphate threshold. It seems that tubular phosphate transport in gouty patients is impaired, and this is the major cause of hypophosphatemia.


Evolution of serum prealbumin following hemodialysis: effect of different dialysis membranes. The effects of hemodialysis on the levels of serum prealbumin (pA) were studied on a crossover basis in 17 uncomplicated patients. Bicarbonate dialysate was used exclusively, and two different membranes, cuprophane and polysulfone, were compared. We aimed to prove the induction of an acute-phase response during the procedure. Serum pA, corrected for hemoconcentration, decreased significantly 24 h after the start of cuprophane hemodialysis and returned to the initial value within 48 h. No such change was observed using polysulfone membranes. These results were seemingly correlated with the effects of the membranes on complement activation. It is concluded that cuprophane hemodialysis is indeed associated with an acute-phase response, probably due to interleukin-1 release during the treatment, and that the membrane composition has some role in inducing it. Thus, serum pA analysis may prove useful as an indicator of the biocompatibility of the dialysis procedure.


Circulating burst-forming-unit erythroid and the responsiveness to recombinant human erythropoietin in patients on regular hemodialytic treatment. The dose of recombinant human erythropoietin (r-HuEpo) required to correct anemia of end-stage renal disease varies among patients. The possible factors that interfere with the responsiveness to r-HuEpo were not completely known. In 32 patients on regular hemodialytic treatment with marked anemia (Hb 5.6 +/- 0.7 g/dl), we evaluated circulating erythroid progenitor cells [burst-forming-unit erythroid (BFU-E)], erythropoietin, ferritin, folate and 1-84-parathormone levels before r-HuEpo therapy. In 12 patients, the aluminum levels after deferoxamine were also evaluated. The possible correlation between these factors and the response to r-HuEpo therapy was then evaluated. The number of circulating (c) BFU-E was highly variable (521 +/- 447 colonies/ml of blood; normal level 742 +/- 192) and does not correlate with erythropoietin, ferritin, folate, 1-84-parathormone or aluminum levels. A direct correlation between basal cBFU-E and the responsiveness to r-HuEpo therapy was recorded while no correlation was found with the other analyzed parameters. We hypothesized that low basal cBFU-E (interleukin-3 deficiency?) could reduce the response to r-HUEpo because of failure of this hematopoietic stem cell compartment to replenish the pool of more mature erythropoietic progenitor cells during the phase of accelerated maturation induced by r-HuEpo.


Phosphate dialytic removal: enhancement of phosphate cellular clearance by biofiltration (with acetate-free buffer dialysate). Phosphate dialytic removal (PDR) depends in part on the type (acetate or bicarbonate) and the concentration of the buffer dialysate. Plasma phosphate reduction or PDR during a dialysis treatment is the algebraic sum, of phosphate cellular flux (removal or captation) and of phosphate tissular precipitation. High bicarbonate levels induce an intracellular shift of phosphate, thus not available for dialytic removal. On the contrary, acidosis prevents P shifting into the intracellular space, thus more P is available for dialytic removal. In order to evaluate cellular phosphate sequestration (CPS) we tested PDR in a crossover study. Three children were dialyzed (18 sessions) successively using either biofiltration with free buffer dialysate and a constant bicarbonate fluid infusion rate (BF) or using sequential biofiltration (SBF) with an initial controlled acidosis period realized by bicarbonate reinjection fluid rate modelling. PDR was higher in SBF (32 +/- 4 mmol/session) than in BF (24 +/- 6 mmol/session). SBF seemed to be efficient against CPS; it clearly demonstrates that bicarbonate modelling is a promising dialytic approach to enhance PDR. The real clinical relevance of these biological results needs clinical long-term evaluation.


Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease. From a total of 81 patients on maintenance hemodialysis who underwent coronary angiography, 8 patients fulfilled the criteria: significant coronary artery disease, hematocrit less than 27%, reproducible (ECG) positive treadmill test, no disturbance of repolarization in ECG at rest. Exercise stress testing was performed at a hematocrit of 25 +/- 2% and following erythropoietin therapy at a hematocrit of 34 +/- 0.5%. Symptom-limited exercise performance increased in all patients (1.10 +/- 0.3 W/kg b.w. vs. 1.44 +/- 0.31 W/kg b.w., p less than 0.01) as well as exercise duration (489 vs. 362 s, p +/- 0.01). ST segment depression during maximal exercise was reduced from a mean of 2.1 to 0.4 mm (p less than 0.01). It is concluded that amelioration of renal anemia by erythropoietin in dialysis patients with significant coronary artery disease reduces exercise-induced myocardial ischemia.


Intraglomerular expression of MHC class II and Ki-67 antigens and serum gamma-interferon levels in IgA nephropathy. In order to clarify intraglomerular cellular activation and cytokine involvement in IgA nephropathy, the glomerular expression of MHC class II antigens (HLA-DR and DQ) and cellular proliferative nuclear antigen (Ki-67), and serum gamma-interferon (gamma-IFN) levels were evaluated in 49 patients with IgA nephropathy. HLA-DR was detected in all but 4 patients in whom glomerular sclerosis was present. HLA-DQ and Ki-67 were observed in 51 and 38% of the patients, respectively. Proteinuria, recent macroscopic hematuria, mesangial proliferation, and extracapillary and endocapillary lesions were more frequent and more severe in HLA-DQ-positive than in HLA-DQ-negative patients. In 10 patients with acute exacerbation, endocapillary lesions and HLA-DQ and Ki-67 expression were present in 70, 80 and 88%, respectively. Serum gamma-IFN levels were high in the patients (2.0 +/- 0.3 U/ml, n = 40), especially during acute exacerbation (3.4 +/- 1.1 U/ml, n = 9). Glomerular HLA-DO and Ki-67 expression correlated with serum gamma-IFN levels (r = 0.73, p less than 0.01 for HLA-DQ; r = 0.75, p less than 0.01 for Ki-67). Renal biopsy specimens taken before and after prednisolone and/or urokinase therapy were available from 4 patients. There was strong reactivity to HLA-DQ in the glomerular tufts of all 4 pretreatment samples. However, HLA-DQ reactivity disappeared after treatment in 3 samples, concomitant with normalization of serum gamma-IFN levels. We conclude that serum gamma-IFN levels are related to glomerular HLA-DQ and Ki-67 expression and acute exacerbation in patients with IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)


A new kindred with hereditary hypophosphatemic rickets with hypercalciuria: implications for correct diagnosis and treatment. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a new autosomal form of hypophosphatemic rickets, recently described. This disease is characterized, and differs from other forms of hereditary hypophosphatemic rickets and/or osteomalacia by increased serum levels of 1,25-dihydroxyvitamin D, hypercalciuria and complete remission of the disease on phosphate therapy alone. However, only another probable Israeli kindred, and seemingly a few sporadic cases from Europe, North America and Japan have been reported in the literature. We describe here a new kindred of Jewish Yemenite origin (unrelated to other Israeli families) with typical HHRH. Two additional members of this family suffer from a milder asymptomatic form of the disease, which presents as absorptive hypercalciuria without signs or symptoms of bone disease. It seems to us that HHRH is underdiagnosed, due to its similarity to other hypophosphatemic syndromes in clinical, radiological and most biochemical parameters. Therefore, it is recommended that urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations be measured in every patient with hypophosphatemic rickets/and or osteomalacia before the initiation of any therapy. The correct diagnosis of HHRN is of immense therapeutic implications. Phosphate therapy alone could cause a complete remission in HHRH, while the addition of active vitamin D metabolites, as is recommended in hypophosphatemic vitamin D resistant rickets, could cause deterioration in the patient's condition.


Biosynthesis of methylguanidine in the hepatic microsomal fraction. We have investigated various synthetic mechanisms for the production of methylguanidine, a potent uremic toxin, and reported a role for active oxygen in its biosynthesis from creatinine in studies using isolated hepatocytes. In this study, we turn our attention to the hepatic microsomes. Liver homogenates were made from rats, and various organelles were obtained by centrifugation and incubated with creatinine. The results show that methylguanidine synthesis occurs only in the microsomal fraction in the presence of nicotinamide adenine dinucleotide phosphate, reduced form. The microsomal activity is inhibited by the addition of methimazole, metyrapone, superoxide dismutase, catalase or dimethylsulfoxide. These results suggest that methylguanidine is synthesized from creatinine by microsomes, and at least 2 enzymes are involved, an FAD-containing monooxygenase and a P-450-dependent oxidase based on the inhibitory effect of methimazole and metyrapone, respectively. Moreover, the inhibition by various scavengers of active oxygen suggests that active oxygen plays a role in the intermediate steps of the enzymatic reaction.


Quantitative relationships between body weight, kidney weight and nephron size in mongrel dogs. Mammalian species of large stature have larger kidneys with larger nephrons than smaller animals, although this relationship is not linear. In order to investigate whether in animals of different sizes within the same species similar differences exist, a study in mongrel dogs was undertaken. In animals weighing between 9 and 42 kg with kidney weights from 25 to 79 g the area and perimeter of the glomeruli and the cortical width were measured. The number of glomeruli per unit area was counted and corrected for the size of the glomeruli. The results show that larger dogs have larger kidneys and that this enlargement is due to the increase in size of the nephrons and not in their number.


Role of glutathione metabolism in the reduction of proteinuria by dimethylthiourea in adriamycin nephrosis. Glutathione (GSH) metabolism, a tissue detoxification pathway, was evaluated in rats with adriamycin nephrosis (AN) treated with dimethylthiourea (DMTU), a free radical scavenger. After 7 days of DMTU, a significant reduction in proteinuria occurred as compared to AN controls (62.4 +/- 13.3 vs. 155.0 +/- 24.0 mg/24 h). A significant increase in renal cortical GSH content as well as glutathione peroxidase (GP) and transferase (GT) activities occurred in DMTU-treated rats as compared to controls. Glutathione monoethyl ester (GME) administration alone reduced proteinuria by 21% in AN, which was not significant despite a large increase in the renal GSH content, however, GP and GT activities were not increased by GME. We conclude that DMTU ameliorates glomerular injury in AN by stimulating GSH metabolism.


Correlation between tubulointerstitial nephropathy and glomerular lesions induced by adriamycin. This paper describes a morphometric study of the evolution of tubulointerstitial nephropathy in adriamycin-induced focal and segmental glomerulosclerosis in Wistar rats over 32 weeks old. The earliest changes were located in the glomeruli. In the 10 week of the study, tubulointerstitial nephropathy appeared and, although the interstitial space increased after the 2nd week, this increase only became statistically significant after the 10 week. Proteinuria showed the highest correlation with the interstitial space, however, the interstitial space showed the highest correlation indices with the total number of glomeruli affected and to a lesser extent with adhesions to and thickening of Bowman's capsule.


Immune deposits in the glomerular extracellular matrix detected by the quick-freezing and deep-etching method. Chronic serum sickness nephritis was induced in rats by sensitization with egg albumin. The glomeruli were then examined by the quick-freezing and deep-etching method with immunohistochemical identification of immune complex deposits on replica membranes. In control rats, the glomerular basement membrane showed a three-layered structure. The middle layer was composed of a compact meshwork of fine fibrils that was connected to adjacent endothelial and epithelial cells by perpendicular fibrils in the inner and outer layers. The mesangial matrix contained a similar but looser meshwork structure. In the nephritic rats, small granular deposits were observed within the meshwork, distorting its fine structure. Larger nodular aggregates extended continuously from the middle layer to the epithelial side. Disruption of the connecting fibrils overlying these larger aggregates was noted. The deposits were stained by antiegg albumin or antirat IgG antibodies. Gold particles immunostaining for the sensitizing antigen were also localized within the deposits. These findings suggest that the deposition of immune complexes occurs in the fibrillary meshworks of the mesangium and lamina densa in this experimental model, with the resultant distortion of their meshwork structures and the formation of nodular aggregates.


Role of plasminogen activator inhibitor on nephrotoxic nephritis and its modulation by tumor necrosis factor. To evaluate the suggested imbalance between coagulation and fibrinolysis in the development of glomerulonephritis, plasminogen activator inhibitor (PAI) activity was studied in the plasma of rats with nephrotoxic nephritis. PAI activity rose within 1 h of the injection of nephrotoxic globulin (NTG), peaked at 2 h and returned to the normal range within 24 h. PAI activity was dependent on the dose of NTG and increased significantly during passage through the kidney. PAI activity was also detected in the culture supernatant from isolated glomeruli with nephrotoxic nephritis. Intracapillary fibrin deposits were formed within 2 h; their numbers increased gradually over 24 h. Tumor necrosis factor (TNF) also induced a progressive increase in PAI activity in normal rats. The injection of TNF to rats with NTG synergistically accelerated both the increase in PAI activity and the prevalence of fibrin deposits. These results suggest that PAI may be released from the glomeruli affected by nephrotoxic nephritis and imply that PAI may play a role in the local coagulation in the capillaries of the nephritic kidneys, although this is probably not the only mechanism which explains the continued formation of the glomerular fibrin deposits.


Glomerulonephritis associated with Robertsonian translocation t(13;14). We report the first case of glomerulonephritis associated with Robertsonian translocation t(13;14) in a 18-year-old female. The renal biopsy revealed mesangial proliferative glomerulonephritis with mesangial IgG and C3 deposits. The patient also has congenital absence of ovaries and an underdeveloped uterus. Our report suggests that renal abnormalities may be found in patients with Robertsonian translocation.


Measurement of vascular access recirculation without contralateral venous puncture. The rate of recirculation is an important variable in calculating the correct dose of dialysis delivered to a patient. Traditionally it is calculated using blood results obtained from the arterial and venous lines and from venous puncture of the opposite arm. To avoid this venipuncture, cessation of the blood pump for 1 or 2 min was attempted to mimic the systemic circulation. This technique underestimated recirculation but was statistically correlated with the result obtained by the classical method, thus it is possible to derive a formula to obtain the recirculation value without contralateral venipuncture.


Autosomal dominant polycystic kidney disease complicated by glomerulonephritis. Two patients with autosomal dominant polycystic kidney disease (ADPKD) and concurrent glomerulonephritis are described. Both developed nephrotic-range proteinuria and one showed a concomitant acceleration in the rate of decline of renal function. Subsequent open renal biopsy revealed membrano-proliferative type-1 and mesangio-proliferative glomerulonephritis, respectively. Nephrotic-range proteinuria in the presence of ADPKD, with or without an accompanying decline in renal function, should prompt further investigation to exclude coexisting glomerular disease.


Dialysis efficacy and itching in renal failure. Itching in nondialyzed uremic subjects and patients on dialysis remains incompletely explained and poorly treated. We evaluated our chronic hemo- and peritoneal dialysis patients for this symptom and synthetically reviewed previous reports on itching and renal failure. We found no biochemical correlates of itching but did find that itching was less with better dialysis as defined by urea kinetic modelling. We conclude that improved dialysis techniques will continue to reduce the prevalence of itching in end-stage renal disease patients.


Evaluation of flowcytometric crossmatching in renal allograft recipients. Forty-four cadaver renal allograft recipients who had flowcytometric cross-match (FCXM) testing and sequential quadruple immunosuppression were studied with respect to the number of rejection episodes and the functional viability of the graft in the first year after transplantation. Fourteen of these patients had antibodies to donor T cells by FCXM. All were negative by conventional crossmatch. Multiple-regression analysis with HLA mismatches, panel-reactive antibody (PRA) percentage, flowcytometric channel shifts and transplant number as independent variables revealed that transplant number and high PRA (> 50%) impacted (p < 0.05) on serum creatinine at 1 month and 1 year, and graft survival at 1 year. In first transplants, a positive FCXM had no impact on 1-year graft survival rates; however, in retransplants, a positive FCXM and/or high PRA had a significant negative impact on 1-year graft survival. This study indicates that the FCXM should be utilized for retransplant patients, and in patients with a high PRA, in an attempt to improve graft survival for these high-risk recipients.


Hemodialysis intravascular hemolysis and kinked blood lines. Between May 29 and September 13, 1991, 4 patients developed acute intravascular hemolysis during hemodialysis with Monitral-S delivery systems and Hospal BSM A77 blood lines. All had malaise, nausea and headache; 3 had severe abdominal pain and 2 became very ill. Plasma hemoglobins were 3-21 g/l and LDH 542-3,300 IU in the 4 patients. Hepatoglobin became unmeasurable in 3 and was 0.09 g/l in the 4th patient. Soon afterwards, we found the arterial blood line tightly kinked at the dialyzer inlet port in the 4th patient and released it; he developed abdominal pain, hemolysis was present. We then found these lines had an extra long pump segment, and the rest was short and fitted poorly. When put in the first tubing organizer, severe kinking could occur just after the pump segment, causing back pressure but no alarm. We produced early visible hemolysis in a 1-liter circulating closed loop blood system with the blood line kinked either at the dialyzer inlet or just below the first arterial line tubing organizer with 40 g/l free plasma hemoglobin by 30 min. We excluded reported causes of intravascular hemolysis during hemodialysis. No hemolysis occurred before or during the 9 months after we discarded BSM A77 lines. The evidence indicates that kinked blood lines caused the hemolysis.


Causes of late renal allograft failure in the ciclosporin era. A single center experience of 514 ciclosporin-treated renal allografts which survived longer than 1 year was reviewed in order to analyze the causes of renal allograft loss beyond the 1st year post-transplantation and the contribution of selected parameters to long-term survival. 83 grafts were lost between 1 and 5 years with the most common causes of graft loss being chronic rejection (54%), death (14%), noncompliance (13%) and sepsis (11%). Actuarial 5-year graft survival rates, decaying from 100% at 1 year, of living related and cadaveric grafts were 88.6 and 79.5%, respectively. Parameters with a substantial influence on long-term survival included the quality of early graft function and incidence of acute rejection in the 1st year post-transplantation. A marker for long-term survival (> 5 years) was a significantly lower serum creatinine (177 mumol/l; < or = 2 mg/dl) at 1 year. We conclude that chronic rejection is responsible for the majority of late graft losses in the ciclosporin era as in the earlier azathioprine period.


Neurotoxicity associated with oral acyclovir in patients undergoing dialysis. Neurotoxicity associated with intravenous acyclovir therapy is well documented. We report 4 cases of acyclovir-induced neurotoxicity in dialysis patients receiving oral therapy at a reduced dose.


Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin. A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.


Nodular diabetic glomerulosclerosis without diabetes mellitus. A 66-year-old white man presented with severe chronic renal failure. He had no past or present symptomatic glucose intolerance nor a family history of diabetes mellitus. Several fasting plasma glucose determinations, hemoglobin Alc and an oral glucose tolerance test were normal. Funduscopic ophthalmoscopy and retinal fluorescein angiography did not demonstrate diabetic retinopathy. The kidney biopsy showed nodular diabetic nephropathy, with increased mesangial matrix, thickened glomerular basement membrane, and afferent and efferent glomerular arteriolar hyalinization. The diagnosis of nodular diabetic nephropathy was made in this patient in the absence of past or present or familial evidence of diabetes mellitus.


Peritoneal hemosiderosis in pediatric patients with nephrogenic ascites. Nephrogenic ascites associated with maintenance hemodialysis is a complex problem with poorly understood pathophysiology. We report 4 pediatric patients investigated between 1986 and 1990. All the patients treated with maintenance hemodialysis required multiple blood transfusions. Each patient was carefully evaluated for factors potentially relevant to ascites, and serum ferritin levels were found to be extremely high. Peritoneoscopy which was utilized in all patients led to a specific diagnosis of hemosiderosis in the peritoneum and liver biopsies. In 1 patient, lymph node biopsy also showed iron deposition. We believe that iron deposition played a role in changing the permeability of the peritoneum and is presumed to be a pathogenetic factor in nephrogenic ascites.


Hypocomplementemia and leukocytosis in diarrhea-associated hemolytic uremic syndrome. Sixty-eight children with diarrhea-associated hemolytic uremic syndrome (D+HUS) were retrospectively examined to assess clinical variables associated with the combination of leukocytosis and hypocomplementemia. There was a statistically significant association between the white blood cell count (WBC) and the level of the third component of the complement system (C3). Children with both a low C3 and a high WBC were significantly younger and required hospitalization for a significantly longer period of time. Although there were also trends to increases in the presence of anuria and central nervous system complications and in the duration of anuria, elevated WBC, thrombocytopenia, dialysis, and hemorrhagic colitis in children with both an elevated WBC and a low C3, these changes did not achieve statistical significance. The presence of a low C3 and an elevated WBC may indicate a subset of children with D+HUS with a more severe episode.


Hemodynamic changes in the dog connected to a dialysis circuit: influence of the body temperature. Eighteen sessions in 9 mongrel dogs were carried out to know the hemodynamic effects produced by body temperature variation, when blood passes through a dialysis circuit with a Cuprophan dialyzer, without dialysate contact. The decrease of 2 degrees C in body temperature caused a decrease in heart rate and cardiac index (-8.6 and -17.6%, respectively) without significant changes in blood pressure. The increase of 2 degrees C in body temperature increased the heart rate, the cardiac index and the first derivative of ventricular pressure (+14.8, +17.3 and +27.8%, respectively) with a decrease of 13.6% in the systemic vascular resistance. Blood pressure did not change significantly. We conclude that the dog maintains the hemodynamic stability by two different mechanisms: when body temperature rises, by increasing the cardiac index; when body temperature decreases, by increasing the systemic vascular resistance.


Effects of oral adsorbent in the rat model of chronic renal failure. The effects of oral adsorbent, AST-120 (Kureha Chemical Ind. Co., Tokyo), were studied in the rat model of subtotal nephrectomy. In 34 female Sprague-Dawley rats, three quarters of the renal mass were removed from the left kidney by ligation of 3 branches of the left renal artery. One week later, the right kidney was removed. Two days after right nephrectomy, control rats were fed standard rat chow ad libitum, while AST-120-treated rats were fed standard rat chow containing AST-120 ad libitum. The animals were observed for 9 weeks. Of the control rats, some became severely ill and appeared to be almost dying before 9 weeks, while paired AST-120-treated rats appeared well. Body weight was maintained better in AST-120-treated rats than in control rats. At completion of the study, levels of BUN and serum creatinine were lower and glomerular filtration rate and renal plasma flow rate were higher in AST-120-treated than in control rats (p < 0.05), although there was no statistically significant difference in proteinuria. Serum uremic peak 2a measured by high-performance liquid chromatography, which is considered to correspond to uremic toxins, was statistically lower in AST-120-treated rats (p < 0.05). Finally, a marked reduction in the degree of glomerular sclerosis was noted in AST-120-treated versus control rats (p < 0.05). The results indicate that AST-120 is effective in the treatment of chronic renal failure in terms of reducing uremic symptoms as well as preserving renal function and glomerular architecture. The data also indicate that a reduction in uremic toxins could delay the progressive damage of renal function and glomerular architecture in chronic renal failure.


Angiotensin-converting enzyme inhibition attenuates hypercholesterolemia and glomerular injury in hyperlipidemic Imai rats. Hyperlipidemic Imai rats spontaneously develop hypercholesterolemia, proteinuria and glomerulosclerosis. We investigated the effect of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on spontaneous hypercholesterolemia and the progressive renal injury in this rat strain. Male Imai rats (n = 7) were treated with enalapril at a dose of 50 mg/l in drinking water starting at 6 weeks of age. Body weight, blood pressure, urinary protein excretion and serum constituents were checked and compared with untreated controls (n = 5) up to 38 weeks of age. Enalapril treatment significantly reduced hypercholesterolemia (247 +/- 41 vs. 102 +/- 13 mg/dl, p < 0.01, at 38 weeks) and proteinuria (766 +/- 290 vs. 206 +/- 119 mg/kg/day, p < 0.01, at 38 weeks). The glomerulosclerosis index (SI) was significantly higher in untreated control rats than in the enalapril-treated group (227 +/- 57 vs. 27 +/- 9, p < 0.01). Although we could not clarify whether hypercholesterolemia is a primary event or secondary to the nephrotic syndrome, these results indicate that the ACE inhibitor has the property to protect remnant glomeruli from glomerulosclerosis in male Imai rats as well as in other animal models in which focal and segmental glomerulosclerosis is believed to represent a common pathologic pattern. This rat strain represents a unique model of a spontaneous proteinuria which can provide an important information on the pathogenesis of human focal and segmental glomerulosclerosis.


Relationship between renin, angiotensinogen and histone H2b messenger ribonucleic acid in the maturing rat kidney. Postnatal nephrogenesis and growth of the rat kidney is greatest during the first 10 days of life. The renin-angiotensin system has important growth-promoting effects. To explore the relationship between postnatal renal development and the renin-angiotensin system, we examined the steady-state levels of messenger ribonucleic acid (mRNA) for renin, angiotensinogen, histone H2b (a marker of DNA synthesis) and the structural protein actin. The pattern of expression for renin and histone H2b were similar, with maximal levels of both mRNAs occurring during the first 10 days of life, the time of most marked postnatal nephrogenesis and kidney growth. A different pattern was seen for angiotensinogen mRNA, with low to undetectable levels during the first 15 days of life, and for actin mRNA, with fairly stable expression at the time points examined, providing evidence that the increase in renin and histone H2b mRNA was not due to a nonspecific increase in mRNA in the newborn kidney. In conclusion, the increase in renal histone H2b mRNA during the early postnatal period is consistent with this being a time of increased DNA synthesis. The similar time course for renin mRNA, histone H2b mRNA and previously defined changes in postnatal nephrogenesis suggests a role for the renin-angiotensin system in postnatal nephron formation.


Retroviral envelope glycoprotein (gp 70) is not a prerequisite for pathogenesis of primary immunoglobulin A nephropathy in ddY mice. Deposition of a major retroviral envelope glycoprotein, gp 70, in renal glomeruli of ddY mice, an animal model for primary IgA nephropathy, was examined by immunofluorescence. The positive staining of gp 70 was not observed in glomeruli of our substrain of ddY mice at any ages examined using two different anti-gp 70 antisera and three different staining conditions, whereas deposition of IgA, IgG and IgM was manifest in mice aged over 40 weeks. As a control, NZB x NZW F1 mice from 4 months of age onwards showed severe glomerular deposition of gp 70, in keeping with previous reports. Thus, it appears that gp 70 deposition may not be sine qua non for the pathogenesis of IgA nephropathy of all substrains of ddY mice.


Renal involvement in leptospirosis: a pathophysiologic study. The kidney involvement in leptospirosis appears to be a special form of acute renal failure due to a higher frequency of polyuric forms and the presence of hypokalemia with an elevated urinary fractional excretion of potassium. Using a clearance technique, we detected higher fractional urinary potassium excretion in leptospirotic guinea pigs (26.5 +/- 4.7%) than in normal animals (14.1 +/- 2.8%, p < 0.05). After blocking distal NaCl reabsorption with furosemide, it was observed that in leptospirotic animals both fractional sodium excretion (40.0 +/- 7.4%) and fractional potassium excretion (136.3 +/- 32.7%) were higher than in normal animals (20.4 +/- 3.8%, p < 0.05, and 43.6 +/- 9.0%, p < 0.05, respectively). Microperfusion studies showed that the normal and leptospirotic medullary thick ascending limb had both identical transepithelial potential difference (+3.7 +/- 0.4 vs. 3.9 +/- 0.2 mV) and relative sodium-to-chloride permeability. The same technique showed that the osmotic water permeability (Posm; 0.9 +/- 0.4 x 10(-5) cm/s.atm) and diffusional permeability (34.7 +/- 6.6 x 10(-5) cm/s) observed in the leptospirotic inner medullary collecting duct (IMCD) in the presence of vasopressin were unchanged, as was also the case for urea permeability (3.74 +/- 0.7 x 10(-5) cm/s). These data show that acute renal failure in leptospirosis is characterized by tubular changes leading to potassium secretion probably due to a decrease in proximal sodium reabsorption. Furthermore, the inability to concentrate urine evidenced by the low P(o)sm present in leptospirotic animals is due, at least in part, to IMCD resistance to vasopressin.


Familial hypokalemia-hypomagnesemia or Gitelman's syndrome: a further case. A woman aged 33 years presented hypokalemia and hypomagnesemia associated with renal potassium and magnesium wasting. Her mean 24-hour urinary calcium excretion was strikingly low despite normocalcemia, normal creatinine clearance, normal serum PTH and calcitriol. Normal distal fractional chloride reabsorption [CH2O/(CH2O + CCl)] was noted during water load but was reduced during hypotonic saline infusion. In response to intravenous furosemide (1 mg/kg), the patient showed significant increments in sodium, chloride and magnesium excretion as well as abolition of hypocalciuria. The association of renal calcium transport from magnesium transport together with exaggerated natriuresis after furosemide suggests the presence of a defect in the distal tubule rather than in the loop of Henle. We propose that our patient is affected by the syndrome of primary renotubular hypomagnesemia-hypokalemia with hypocalciuria, known as Gitelman's syndrome.


Hyperreninemia and secondary hyperaldosteronism in a patient with pheochromocytoma and von Hippel-Lindau disease. In a 21-year-old Caucasian women with von Hippel-Lindau disease, norepinephrine-producing adrenal pheochromocytoma was identified as the underlying cause of severe hypertension. She was found to have extremely elevated levels of circulating renin and aldosterone, and she was markedly hypokalemic. Administration of captopril further enhanced renin secretion, while her blood pressure improved. The patient became normokalemic following tumor removal, and her blood pressure decreased to normal levels with reestablishment of normal circadian blood pressure rhythm. This case demonstrates that, in the absence of renovascular or malignant hypertension, pheochromocytoma can be the underlying cause for the clinical syndrome of hypertension associated with severe hypokalemia and hyperreninemic hyperaldosteronism.


Abuse of germanium associated with fatal lactic acidosis. Germanium compounds are marketed as nonprescription drugs in Europe and are recommended by the suppliers for AIDS and metastatic cancer disease. We observed a patient with nonmetastatic breast cancer who died because of severe lactic acidosis (plasma lactate concentration = 27 mmol/l) after ingestion of 25 g of elemental germanium over a 2-months period. Renal failure and hepatotoxicity had newly developed during germanium intake. Postmortem examination revealed severe hydropic vacuolation of tubule cells and the presence of inclusion bodies predominantly in straight proximal tubule cells with normal appearance of renal interstitium and glomeruli. The liver showed panlobular steatosis. Urine, blood and tissue (kidney, liver, muscle, pancreas) levels of germanium were high. Lactic acidosis may have been caused by the combined, germanium-induced renal and hepatic failure (underutilization), but it remains to be seen whether germanium can affect lactate production and/or metabolism directly.


Assessment of quality of survival in patients with surgically treated meningioma. A prospective study carried out between 1982 and 1991 encompassed 179 patients who had been operated upon for meningiomas (Neurosurgical University Clinic Heidelberg and Mannheim). History, neurological status, neuroradiological findings, surgical procedure and histology were documented. Within the framework of regular postoperative reexaminations, indices were recorded regarding life quality as standardized by Karnofsky and Spitzer. Following HRDP (Hamburg Rating Scale for Emotional Disturbances), a depression score was evaluated with 32 patients pre and postoperatively. Psychosocial disturbances, which can develop a permanent character, were observed, particularly within the first 12 months after the operation. Depressive moods were noticed quite frequently. The age of the patients proved to be a decisive prognostic factor.


[Legal evaluation of intervertebral disk surgery including post-discotomy syndrome]. Although lumbar disc surgery (discectomy) definitely improves the overall situation of the patient in most cases, it does create problems of a hitherto absent kund in about 6% of the patients. Expertising of uncomplicated cases should not be too difficult. However, modulated by individual disposition, a syndrome may develop known as "failed back surgery syndrome" caused by intersegmental loosening, crumbling or fusing and scarification. The pain it causes is decisive for its assessment, not so much any motor or other neurological deficits. In mild cases the loss in capacity for gainful employment may be assessed at between 20% to at the most 30%, but the severely handicapped are unable to cope with their daily life without assistance, their incapacitation amounting to as much as 100%. If the patient concerned is on a job that places stress on this spine, he may be unfit for work even if the affliction is relatively mild.


Clinical features of intradural neurinomas in the cauda equina and around the conus medullaris. In this contribution the clinical features of eleven patients suffering from a neurinoma in the cauda equina and around the conus medullaris are analysed. Because of the relative mobility of the roots and the wide space in the spinal canal, tumours arising in the cauda equina or around the conus medullaris can become larger than any other spinal tumours. Lumbago was the predominant symptom as the initial complaint. Nocturnal pain relieved by walking was noticed in one patient. Two cases showed spontaneous remission and relapse. Multiple tumours were found in 6 cases (55%). Macroscopic cyst formation was found in 5 cases (45%). Among the eleven patients, total removal of the tumour, including the involved root, was performed in ten. The numbers of the resected nerve roots were one root in 6 cases, two roots in 2, and three roots in 2. Only one patient showed postoperative slight weakness of the leg.


Management of missile wounds of the cerebral dura mater: experience with 69 cases. Over the period of seven months: from July 1991 to January 1992 sixty-nine patients with penetrating head war-injuries, were admitted in our hospital. Missile wounds of the dura mater require in most cases urgent operative management: watertight closure of the dura defects. However, a dilemma still exists as to the best material to be used to restore the missile dural defects. There are several possibilities: an autologous substitute as periosteum (pericranium) from surrounding, fascia of the temporalis muscle, fascia lata, or allograft transplant as lyophilised cerebral dura mater (lyodura). In the group of 69 patients, 7 were treated conservatively, 13 were treated surgically, but without closing the dural wounds because of their critical condition, and in 45 surgically treated patients the dural defects were covered with 53 transplants: with periosteum in 22 patients but 24 coverings, with fascia of temporalis muscle in 2 patients, with lyodura in 6 patients, with fascia lata in 15 patients but 21 coverings. In 4 patients the dura wounds were sutured by interrupted sutures. The best results were obtained in the fascia lata group.


Unique complications of cerebrospinal fluid shunts in children--a report of two cases. The authors report on two cases with unusual CSF shunt complications. The first case had a peritoneal catheter which migrated down a patent processus vaginalis into a hydrocoele. The second case had an atrial catheter which perforated the atrial wall and came to lie in the pericardium causing an effusion. Clinicians should be aware of the frequent and occasionally bizarre complications of CSF shunting.


[Intracerebral metastasis of a bronchial carcinoid tumor]. The authors report on a female patient of 45 years of age suffering from multiple intracerebral metastases of a bronchial carcinoid. Neurologically, intermittent short-term disturbances of word finding were noticeable. Multiple cerebral foci surrounded by pronounced concomitant oedemas were seen in MR and CT with inhomogeneous contrasts. The diagnosis was confirmed histologically by treatment concepts besides radiotherapy (1, 15, 17) are: intravenous administration of cisplatinum (14), interferon (16) and cyproheptadine (9). The treatment course adopted by the authors is based on an aetiopathogenetic approach, using somatostatin analogues. In the case under report, the somatostatin analogue SMS-201-995 (Sandostatin Sandoz) was applied in doses of 3 x 100 micrograms for a period of eight weeks, in short-term combination with daily doses of methyl prednisolone 40 mg (Urbason Höchst). With this treatment course the patient became free from complaints. No increased growth of the cerebral foci of infection could be observed neuroradiologically during the follow-up period of up to now six months.


Cervical intramedullary sarcoidosis.

Cervical intramedullary sarcoidosis. Spinal cord involvement by sarcoid is quite rare. Only fourteen cases of histologically proven sarcoid without meningeal infiltration have been reported. We present the first CT scan description and the second description of the findings on MR imaging of intramedullary sarcoidosis. We also report successful surgical intervention in this case. In a review of surgical reports, we could find only 2 cases of improvement in symptoms after surgical intervention. Additionally, we stress the importance of early diagnosis using the various neuroradiological methods described. We feel that if surgery is performed at an early stage, it may be possible to obtain successful resection of the mass and a good clinical outcome.


Recurrence of brain abscess associated with asymptomatic arteriovenous malformation of the lung. On the basis of the data provided by literature the majority of patients with an arteriovenous malformation of the lung who develop a brain abscess suffer from hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease. Only nine cases of brain abscesses in which the arteriovenous malformation of the lung was isolated have been described and in all of these, clinical signs and/or alterations in the laboratory data were detected which can be attributed to the arteriovenous malformation itself. The case taken in this article would seem to be the first case of a recurrent brain abscess in a patient not suffering from Rendu-Osler-Weber with a completely asymptomatic arteriovenous malformation of the lung, both from the clinical point of view and from laboratory data. The authors stress the appropriacy of an angiographic pulmonary study in cases of recurrent brain abscesses, even where the chest X-ray has been negative.


A giant hyperostosing meningioma in a child. A case of 15-year-old boy with a giant hyperostotic meningioma is presented. The patient had a huge prominence at the posterior parietal region. The CT scan showed a giant intracranial tumor in the left parieto-occipital region under the hyperostotic bone. The tumor and hyperostotic bone were totally resected with the involved portion of the sagittal sinus. Histological study revealed a meningioma. The presence of such a huge hyperostosis and some peculiarities of childhood meningiomas are discussed.


Vasectomy modulates the local effect of intratesticular opioids on the gonad of immature rats. Previous studies indicate that 7 days after testicular administration of naloxone, serum testosterone (T) concentration and basal T secretion in vitro decrease significantly. In neonatal rats, short-term (2 h) intratesticular treatment with 0.3 micrograms (D-Met2-Pro5)-enkephalinamide suppresses steroidogenesis. In the present study, testicular treatment with naloxone or enkephalinamide was combined with hemivasectomy (which also includes transection of the inferior spermatic nerve). When local treatment with naloxone was combined with vasectomy in 15-day-old rats, the opioid antagonist-induced increase in testicular weight, the decrease in basal T secretion of the treated gonad and the drop in serum T level could not be observed 7 days postsurgery, despite the fact that in immature rats, hemivasectomy, by itself, also reduces steroid secretion. Similarly, in 5-day-old animals, the short-term (2 h) effect of testicular enkephalinamide on T secretion was prevented by vasectomy. These data suggest that local testicular actions exerted by endogenous opioid peptides might be modulated by the inferior spermatic nerve.


Development of pituitary pro-opiomelanocortin gene and peptide expression: characterization and effect of repeated intermittent maternal isolation. The dynamics of pro-opiomelanocortin (POMC) biosynthesis in the adult rat are altered by demands imposed on the system, such that acute stress increases in the efficiency of anterior pituitary (AP) posttranslational events, while repeated stress increases pretranslational events. In contrast, the developing animal has a limited adrenocortical response to acute stress during the first 2 weeks of life (stress nonresponsive period). In this study, we investigated how the maturing AP and intermediate lobe (IL) POMC cells respond to repeated demand. Measurements of AP and IL POMC mRNA and POMC peptides were performed using Northern gels and radioimmunoassay, respectively. Plasma ACTH and corticosterone measurements were also performed. Maternal isolation, for 1 h on 3 consecutive days, was used as a repeated stress stimulus. The developing AP and IL exhibit an age-related increase in POMC mRNA and peptide levels. On the other hand, AP and IL do not respond to repeated intermittent maternal isolation during the first 2 weeks of life. However, a significant corticosterone release is seen in the 14 and 21-day-old animals. A change in POMC mRNA level is only detected in the 21-day-old AP where levels decrease. Therefore, an adrenocortical response to repeated intermittent maternal isolation predates the appearance of glucocorticoid inhibition of POMC expression in the 21-day-old animal. We propose that an immature neuronal inhibitory circuit during the 3rd week of life causes a sustained corticosteroid response which may in turn trigger AP-delayed feedback.


Effect of growth retardation on pituitary luteinizing hormone and hypothalamic neuropeptide Y in ovariectomized sheep. The possible role of neuropeptide Y (NPY) in mediating the relationship between pituitary LH secretion and growth retardation due to restricted feeding was examined in ovariectomized (OVX) prepubertal ewe lambs. One specific objective examined whether there was an inverse relationship between concentrations of NPY in four diencephalic brain regions and pituitary LH secretion in ewe lambs 29-30 weeks old which had been growth retarded since 8 weeks and OVX at 24 weeks. Through dietary restriction, body weight was held constant at 20.7 +/- 0.5 kg in 13 growth-retarded ewes as compared with 48.0 +/- 0.6 kg for 5 age-matched control ewes at 29-30 weeks of age. Episodic LH was quantified at 10-min intervals for 190 min/day on 3 of the 8 days immediately before euthanasia. Serum LH averaged 6.5 +/- 0.6 ng/ml in control ewes with a mean pulse frequency of 1.0 +/- 0.1 pulses/h. Serum LH in growth-retarded ewes was much less episodic (0.2 +/- 0.05 pulses/h) and averaged only 1.2 +/- 0.2 ng/ml. All ewes were euthanized during week 30, and the following brain regions were dissected: basal forebrain, preoptic area, median eminence and remainder of hypothalamus. Following extraction, NPY concentrations (pg/mg of original tissue) were quantified by radioimmunoassay. In each brain region, NPY concentrations were greater (p < 0.05) in 6 growth-retarded ewes than in 5 control ewes (median eminence: 5.2 vs. 0.6; remainder of hypothalamus: 3.3 vs. 0.8; preoptic area: 3.1 vs. 0.8, and basal forebrain: 2.2 vs. 1.2). A secondary objective examined whether the LH and NPY parameters were rapidly altered by transient changes in feed consumption.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of starvation and subsequent refeeding on thyroid function and release of hypothalamic thyrotropin-releasing hormone. Effects of starvation on thyroid function were studied in 5- to 6-week-old (R x U) F1 rats. Starvation lowered plasma TSH in female, but not in male rats. Plasma T4 and T3 levels decreased, whereas the dialysable T4 fraction increased during starvation. Free T4 (FT4) levels decreased rapidly in females, but only after prolonged fasting in male rats. Glucose decreased, and free fatty acid levels increased during starvation. Peripheral TRH levels did not change during food deprivation. Since effects of starvation were most apparent in young female rats, such rats were used to study hypothalamic TRH release during starvation and subsequent refeeding. Basal in vitro hypothalamic TRH secretion was less in starved rats than in control or refed animals. In vitro hypothalamic TRH release in medium with 56 mM KCl increased 3-fold compared to basal release, and in these depolarization conditions TRH release was similar between hypothalami from control, starved and refed rats. In rats starved for 2 days, TRH level in hypophysial portal blood was lower than that of controls. Thus, diminished thyroid function during starvation may at least in part be caused by a reduced hypothalamic TRH release.


Melatonin treatment delays reproductive aging of female rat via the opiatergic system. In female rat age-related reproductive decline is accompanied by progressive impairment of the neuroendocrine mechanisms that regulate LH secretion. The biosynthetic activity of the pineal gland is markedly depressed and the nocturnal secretion of melatonin decreases significantly. The aim of the present study was to evaluate whether the nocturnal administration of melatonin via the drinking water (0.4 micrograms/ml) throughout the course of aging from 14 to 24 months of age could (1) influence the age-related changes that occur in basal serum levels of LH and in the LH response to GnRH or to naloxone stimulation at 16, 18 and 20 months of age, and (2) delay the onset of the postreproductive constant estrous-anovulatory state as evaluated by the daily recording of vaginal smears and by occurrence of polyfollicular ovaries at 24 months of age. Our results demonstrate that melatonin replacement delays the increase in LH serum levels and the decrease in LH response to GnRH that occur in 18-month-old control animals. Furthermore, they show that melatonin treatment prevents the loss of LH response to naloxone manifested in control rats between 16 and 20 months of age. Melatonin also appears to prevent the progressive increase in the monthly occurrence of estrus phases as well as to decrease the number of rats with polyfollicular ovaries at 24 months of age in comparison to control animals. These results suggest that the age-related decrease in circulating melatonin during the night may contribute to the reproductive decline of aging, and that this effect may involve the central opioid system.


Effect of serotonin 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the prolactin response to restraint and ether stress. Serotonin (5-HT) appears to be involved in the central control of the prolactin (PRL) response to suckling and estrogen. Furthermore, 5-HT may participate in the mediation of stress-induced PRL release. In order further to elucidate the role of 5-HT and the type of 5-HT receptor(s) involved in the PRL response to stress, we investigated the effect of blockade of 5-HT1, 5-HT2 or 5-HT3 receptors on the restraint or ether stress-induced release of PRL in male rats. Pretreatment with the 5-HT1 + 2 receptor antagonist methysergide (0.5 or 2.5 mg/kg i.p.) inhibited or prevented the PRL response to restraint or ether stress. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (0.5 or 2.5 mg/kg i.p.) inhibited the response to restraint or ether stress approximately 30 or 60%, respectively. Higher doses of both 5-HT2 receptor antagonists (10 mg/kg i.p.) had a minor inhibitory effect (5-30% for ketanserin and 50% for LY 53857). Prior intraperitoneal administration of the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the restraint stress-induced PRL release dose-dependently. Both compounds inhibited the PRL response to ether stress, but only the effect of GR was dose-related. The maximal inhibitory effect (70% inhibition of the PRL response to restraint or ether stress) was obtained for both compounds at a dose of 0.1 mg/kg. We conclude that serotonergic neurons are involved in the mediation of the stress-induced PRL release by activation of 5-HT1, 5-HT2 as well as 5-HT3 receptors.


Activation of central D-1 dopamine receptors stimulates oxytocin release in the lactating rat: evidence for involvement of the hypothalamic paraventricular and supraoptic nuclei. The stimulatory effect of dopamine (DA) on the release of oxytocin (OT) in lactating rats is exerted at the D-1 DA receptor subtype. Because the neural loci mediating this effect have not been identified, the objective of the present studies was to test whether OT release in the lactating rat would be elevated after central administration of a D-1 DA receptor agonist into the third ventricle (3V) or directly into either the rostral paraventricular/anterior commissural nucleus area (PVN/ACN), the central paraventricular nucleus area, or the supraoptic nucleus (SON), all of which contain OT neurosecretory cells. Lactating rats were implanted with a stainless steel cannula directed into one of the above areas or into the arcuate-ventromedial region of the medial basal hypothalamus (MBH), or sites dorsal to the PVN/ACN or SON, which served as anatomical controls. After 6-7 days of recovery, each animal received an intra-atrial cannula for sequential blood sampling, and was used in experiments 24 h later. Animals were separated from their litters, and following a period of basal blood sampling, received central microinjections of either vehicle, the D-1 DA receptor agonist SKF-38393, or the D-2 DA receptor agonist quinpirole, and blood samples were removed periodically for 60 min. An injection of angiotensin II (Ang II, 100 ng) was made into each site as a positive control for OT release.(ABSTRACT TRUNCATED AT 250 WORDS)


Reflexive ovulation in the rat, induced by caesarean section, is blocked by pelvic and/or hypogastric nerve transection. Reflexive ovulation in the rat, induced by caesarean section performed on day 22 of pregnancy, was blocked by prior bilateral transection of the pelvic and/or hypogastric nerves, which convey afferent activity from the reproductive tract. Tubal ova and hemorrhagic ovarian follicles were counted 24 h after bilateral nerve transections or sham neurectomy. Whereas the median numbers of ova and hemorrhagic follicles in the sham neurectomy group were 4.5 and 3.5, respectively, these values in each of the neurectomy groups were 0. The present findings indicate that caesarean section activates the pelvic and hypogastric nerves to trigger ovulation. This suggests that normally the rat is a spontaneous ovulator during the estrous cycle (nonpregnancy) phase of its reproductive cycle, and may become a reflexive ovulator at the parturient phase of its reproductive cycle.