Morphological evidence of biofilm in chronic obstructive sialadenitis.

OBJECTIVE: Bacterial infection is a common finding in acute sialadenitis and may play a role in the chronicity of the condition. This study investigated if bacterial biofilm is present in submandibular chronic obstructive sialadenitis. METHODS: A descriptive case-control study was conducted that compared 10 histological sections of submandibular glands with chronic obstructive sialadenitis, to 10 histological sections of the healthy part of submandibular glands with pleomorphic adenoma. Fluorescence in situ hybridisation and confocal laser scanning microscopy visualised evidence of bacterial biofilm. RESULTS: In the chronic obstructive sialadenitis group, 5 out of 10 histological sections showed morphological evidence of bacterial biofilm. In the control group, there was no sign of bacterial biofilm formation. CONCLUSION: Morphological evidence of bacterial biofilm was found in the submandibular gland sections from patients with chronic sialadenitis and suggests a role in the chronicity of submandibular chronic obstructive sialadenitis.

Long-distance navigation in the wandering desert spider Leucorchestris arenicola: can the slope of the dune surface provide a compass cue?

Males of the nocturnal spider Leucorchestris arenicola (Araneae: Sparassidae) wander long distances over seemingly featureless dune surfaces in the Namib Desert searching for females. The spiders live in burrows to which they return after nearly every such excursion. While the outward path of an excursion may be a meandering search, the return path is often a nearly straight line leading towards the burrow. This navigational behaviour resembles that of path integration known from other arthropods, though on a much larger scale (over tens to hundreds of meters). Theoretically, precise navigation by path integration over long distances requires an external compass in order to adjust for inevitable accumulation of navigational errors. As a first step towards identifying any nocturnal compass cues used by the male spiders, a method for detailed 3-D recordings of the spider's paths was developed. The 3-D reconstructions of the paths revealed details about the processes involved in the spiders' nocturnal way of navigation. Analyses of the reconstructed paths suggest that gravity (slope of the dune surface) is an unlikely parameter used in path integration by the L. arenicola spiders.

Plasma disappearance of albumin and impact of capillary thickness in idiopathic dilated cardiomyopathy and after heart transplantation.

BACKGROUND-The increased plasma disappearance of albumin has previously been described in decompensated congestive heart failure (CHF); this disappearance normalized after diuretic treatment. Cardiac transplantation (HTX) and current medical treatment affect microvascular structure and function. We investigated the plasma disappearance of albumin and the impact of microvascular thickness and electrostatic properties in patients with compensated CHF and after HTX. METHODS AND RESULTS-The fraction of intravascular albumin that passes to the extravascular space per unit time, as determined from the plasma disappearance of intravenously injected (131)I-labeled albumin, was increased to 7.8+/-1.7% in 16 patients with CHF compared with 18 controls (6.5+/-1.9%, P<0.05); these levels normalized after HTX (5.8+/-2.6%, P<0.01, n=17). The change in ratio between (131)I-albumin and simultaneously injected negatively charged glycosylated (125)I-albumin (selectivity index, >1/hour in controls) was lower in patients with HTX (0.993+/-0. 022/hour) than in controls (1.008+/-0.019/hour; P<0.05), which indicated a relatively increased plasma disappearance of negatively charged albumin in HTX patients. Capillary basement membrane thickness was evaluated semiquantitatively from skin biopsies and showed no difference in the 3 groups (control, CHF, and HTX patients). However, in all 3 study groups, subjects with thicker capillary basement membranes had lower albumin escape rates (6.1+/-1. 8%, n=32, versus 7.6+/-2.6% in subjects without thickening of capillary basement membranes, n=19; P<0.05). CONCLUSIONS-The plasma disappearance of albumin increased in patients with compensated CHF and it normalized after HTX. The present normalized capillary basement thicknesses in patients with CHF and the direct association between this parameter and plasma albumin disappearance indicate that previous compensatory microvascular basement membrane growth results in restricted permeability. Microvascular electrostatic properties did not relate to plasma albumin disappearance.

Reversal of peripheral microvascular dysfunction during long-term treatment with the angiotensin-converting enzyme inhibitor fosinopril in congestive heart failure.

BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF) improves cardiac and peripheral hemodynamic function and exercise performance. However, studies on the effects of long-term treatment with an ACE inhibitor on the neurogenic and nonneurogenic regulation and structural microangiopathy of the peripheral microvasculature in CHF are lacking. METHODS AND RESULTS: We investigated the effect of 12 weeks of treatment with the ACE inhibitor fosinopril on peripheral microvascular function in a double-blind, placebo-controlled study of 12 patients treated with fosinopril and 10 patients treated with placebo. All had moderate CHF. Microvascular blood flow and resistance were calculated after application of the local isotope washout method in relaxed and nonrelaxed calf vascular beds in the supine position and during head-up tilt. Skeletal muscle vascular resistance was reduced in the fosinopril group (46 +/- 6 to 30 +/- 1 mm Hg.mL-1.100 g.min +/- standard error; P < .05) and differed compared with the effect of placebo (P < .05) where no change was seen (37 +/- 11 to 55 +/- 13 mm Hg.mL-1.100 g.min; not significant [NS]). Also, skin minimal vascular resistance was reduced during fosinopril treatment (13 +/- 0.6 to 11 +/- 0.7 mm Hg.mL-1.100 g.min; P < .05) and differed compared with the effect of placebo (P < .05) with absence of change (12 +/- 1.6 to 14 +/- 1.4 mm Hg.mL-1.100 g.min; NS). CONCLUSIONS: These results suggest that long-term ACE inhibitor treatment with fosinopril in patients with CHF improves hemodynamic status to as far as the peripheral microvascular level in both the relaxed and nonrelaxed microcirculation of the lower leg.

Skin microvascular distensibility and structural microangiopathy in idiopathic dilated cardiomyopathy and after heart transplantation.

Peripheral microvascular function plays an important role in patients with congestive heart failure (CHF). Decreased microvascular distensibility in skin and structural microangiopathy of the lower leg have been demonstrated in CHF due to idiopathic dilated cardiomyopathy. Whether microvascular skin distensibility reverses after heart transplantation and is related to the structural microangiopathy has not been elucidated before now. Distensibility (stiffness) of resistance vessels in the skin was measured using the local isotope washout method in a histamine-relaxed vascular bed at the dorsum of the foot. The structure of terminal arterioles was determined from skin biopsies. The measurements were performed in two studies. A cross-sectional study included 20 patients with clinical moderate CHF (NYHA II), 11 severe CHF patients (NYHA III and IV), and 28 patients 9 +/- 6 months (mean +/- SD) after heart transplantation (HTX). Furthermore, 12 patients were studied in a longitudinal study before (CHF) and 3 +/- 1 months (HTX-3) and 14 +/- 4 months (HTX-14) after HTX. A control group of 24 healthy subjects was included. In the cross-sectional study, distensibility in skin was reduced with increasing severity of CHF (severe CHF 22 +/- 10% and moderate CHF 38 +/- 21% vs controls 54 +/- 14%; P < 0.0001 and P < 0.01, respectively). Distensibility was reduced in patients after HTX (HTX, 41 +/- 18%) compared to controls (P < 0.01). In the longitudinal study, distensibility was decreased before transplantation (20 +/- 10%, P < 0.0001 vs controls) and increased gradually after HTX to 35 +/- 16% at 3 months (P < 0.01 vs CHF, P < 0.005 vs controls) and to 40 +/- 12% at 14 months (P < 0.05 vs controls, P < 0.01 vs HTX-3, P < 0.005 vs CHF). Structural microangiopathy was demonstrated in CHF, but not in HTX, in the cross-sectional study. However, a normalization could not be demonstrated after HTX in the longitudinal study. We conclude that the decreased microvascular skin distensibility (increased stiffness) gradually reverses after HTX. Furthermore, the structural microangiopathy seems to improve gradually.

Effects of nisoldipine and lisinopril on microvascular dysfunction in hypertensive Type I diabetes patients with nephropathy.

1. Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) compared with an angiotensin-converting enzyme inhibitor (lisinopril) on the non-neurogenic regulation of the microvascular blood flow in hypertensive Type I diabetes patients with diabetic nephropathy.2. We performed a 1-year double-blind, double-dummy randomized controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 48 hypertensive Type I diabetes patients with diabetic nephropathy. For comparison, 22 age-matched normotensive healthy control subjects were included. Measurements were performed at baseline and after 1 year of antihypertensive treatment. The minimal vascular resistance and distensibility (stiffness) of resistance vessels in skin and skeletal muscle were measured using the local isotope washout method.3. Mean arterial pressure was reduced to the same extent in both groups: nisoldipine, 113+/-2.1 to 105+/-1.6 mmHg (P<0.001); lisinopril, 110+/-2.7 to 101+/-2.1 mmHg (P<0.002) (controls, 88+/-2.2 mmHg; P<0.0001 compared with diabetic patients). Nisoldipine improved the skin vascular distensibility from 28+/-3.3 to 43+/-3.8% (P<0.005) and decreased skin minimal vascular resistance from 16.9+/-1.0 to 13.6+/-0.8 mmHg.ml-1.min.100 g (P<0. 02). Lisinopril had no significant effect on skin vascular distensibility (40+/-4.0% and 41+/-4.4%), but minimal vascular resistance tended to diminish (18.1+/-0.9 to 15.8+/-1.3 mmHg.ml-1. min.100 g (P=0.09). Nisoldipine significantly increased the skin distensibility (P=0.05) after 1 year of antihypertensive treatment compared with lisinopril.4. The control group had a skin vascular distensibility of 54+/-3.2% and a minimal vascular resistance of 10. 8+/-0.7 mmHg.ml-1.min.100 g, both significantly different from the values in the diabetic groups (P<0.0001 for all). Skeletal muscle vascular distensibility was unaltered after 1 year of treatment with both nisoldipine (22+/-3.3% and 19+/-2.7%) and lisinopril (19+/-2.1% and 24+/-2.5%), but was reduced compared with a control value of 43+/-3.7% (P<0.0001 for diabetes patients versus controls). However, neither nisoldipine nor lisinopril had any effect on the increased minimal vascular resistance or the reduced skeletal muscle distensibility.5. Enhanced thickening of the basement membranes of the terminal arteriolar wall was found in skin biopsy specimens in 91% of diabetic patients and 38% only in control subjects (P<0. 000001 both before and after treatment for diabetic patients versus controls). There was no significant effect of antihypertensive treatment on arteriolar hyalinosis.6. The reduction in systemic blood pressure was identical during 1 year of treatment with nisoldipine or lisinopril. The abnormal arteriolar stiffness was more pronounced in the group treated with nisoldipine than with lisinopril and only nisoldipine compared with lisinopril improved the abnormal arteriolar stiffness and minimal vascular resistance in the skin. This suggests that nisoldipine can reverse the peripheral skin perfusion and thereby improve the local protection against development of ischaemic skin lesions in Type I diabetes patients with clinical diabetic nephropathy.

Effects of orthotopic cardiac transplantation on structural microangiopathy and abnormal hemodynamics in idiopathic dilated cardiomyopathy.

To examine whether cardiac transplantation would reverse morphologic and hemodynamic changes in peripheral circulation in idiopathic dilated cardiomyopathy, the structure of terminal arterioles and minimal vascular resistance were measured in skin at the dorsum of the foot in the same 14 patients before and 80 +/- 21 (mean +/- SD) days and 387 +/- 46 days after transplantation. The results were compared with data from a group of 16 healthy subjects. Blood flow was measured by the local technetium-99m pertechnetate washout method in a vascular bed relaxed with histamine. Structural microangiopathy (enhanced thickening of the basement membranes) in the arterioles was disclosed in skin biopsies in 11 of 14 patients before transplant, but in none of the 16 control subjects (p < 0.002). These abnormalities were unchanged 80 days after cardiac transplantation. However, arteriolar wall thickening was significantly reduced over the 1-year period after transplantation (p < 0.05), but this was not complete. Transplantation also led to a significant delayed decrease in minimal vascular resistance: before transplantation, 10.1 +/- 3.2 mm Hg.ml-1.100 g.min (mean +/- SD); 80 days after transplantation, 9.3 +/- 3.1 mm Hg.ml-1.100 g.min (p = NS), and 1 year after transplantation 7.6 +/- 2.4 mm Hg.ml-1 100 g.min (p < 0.01). Minimal vascular resistance before and 80 days after transplantation was significantly increased compared with that in healthy control subjects (6.3 +/- 1.7 mm Hg.ml-1 100g.min [p < 0.0003 and p < 0.003, respectively]). However, 1 year after transplantation, minimal vascular resistance was reduced to comparable levels when compared with that in control subjects (p = NS). These results indicate that structural microangiopathy and minimal vascular resistance in skin are improved slowly and gradually within the first year after orthotopic cardiac transplantation in patients with idiopathic dilated cardiomyopathy, however, the remodeling of histopathology is not accompanied by complete normalization.

Microvascular distensibility in two different vascular beds in idiopathic dilated cardiomyopathy.

The local isotope-washout technique allows discrimination between blood flow in skin and muscle. Arteriolar constriction, mediated by the sympathetic nervous system, is abolished in a papaverine-histamine-relaxed vascular bed. Microvascular distensibility of relaxed resistance vessels was measured in skeletal muscle and skin of the lower limb in patients with congestive heart failure (CHF) secondary to idiopathic dilated cardiomyopathy and in healthy subjects. Vascular transmural pressure was elevated 40 mmHg by head-up tilt and caused muscle blood flow to increase by 11 +/- 9% in 20 CHF patients compared with 44 +/- 20% in 11 control subjects (P < 0.0003). Also the increase in skin blood flow was significantly reduced: 31 +/- 18% in 42 CHF patients compared with 62 +/- 29% in 25 control subjects (P < 0.001). Regression analysis demonstrated a significant association between microvascular distensibility in skin and skeletal muscle tissue (P = 0.003, r = 0.51, n = 31). Structure of terminal arterioles was determined in skin biopsies, and structural microangiopathy was found in 32 of 42 CHF patients. Multiple regression analysis demonstrated the degree of microangiopathy to be the only parameter significantly associated with microvascular distensibility (P = 0.005, r = 0.42). (There was no association to NY Heart Association functional class, left ventricular ejection fraction, duration of CHF, age of subject, or mean arterial blood pressure.) We conclude that patients with idiopathic dilated cardiomyopathy have similar decreased microvascular distensibility in skeletal muscle and skin. Furthermore, structural alterations in terminal arterioles seem to be associated with decreased distensibility and increased stiffness of the cutaneous microvascular bed.

DNA aneuploidy in gastric carcinoma. Flow cytometric data related to survival, location, and histopathologic findings.

BACKGROUND: The aim of the study was to evaluate the prognostic significance of DNA ploidy of gastric carcinomas. METHODS: The DNA content was analyzed by flow cytometry on archival paraffin-embedded material from tumors of 97 consecutive patients. RESULTS: A multivariate analysis showed that the DNA ploidy pattern and lymph node metastasis were the only independent prognostic markers for survival (p = 0.01 and p = 0.02, respectively). The relative risk of death due to gastric cancer was three times greater for patients with DNA hypertetraploid tumors than for patients with DNA diploid tumors and twice as high for patients with lymph node metastasis as for patients without. Well and moderately differentiated carcinomas were more frequently aneuploid than tumors with poor differentiation (p = 0.047). There was no correlation between tumor ploidy pattern and location. In univariate analysis tumor growth through the serosal wall was predictive of poor survival (p = 0.003). CONCLUSIONS: DNA ploidy is an independent prognostic indicator for cancer-specific survival in gastric cancer.

Oral hairy leukoplakia in an HIV-negative woman with Behçet's syndrome.

The first case of oral hairy leukoplakia in an HIV-negative patient with Behçet's syndrome is reported. The patient was a 47-year-old woman with bilateral lesions on the tongue. The clinic and histologic appearances were typical of hairy leukoplakia, and Epstein-Barr virus was demonstrated in the epithelial cells by DNA in situ hybridization. The patient had been on systemic steroid therapy for 15 years to control lesions of Behçet's syndrome. The literature now records 30 HIV-negative patients with hairy leukoplakia.

Evidence of increased microvascular resistance and arteriolar hyalinosis in skin in congestive heart failure secondary to idiopathic dilated cardiomyopathy.

Does nervous microvascular stress from backward cardiac failure and abnormal baroreceptor-mediated vasodilation in the upright position alter the microvascular resistance and structure of the resistance vessels with time? The minimal vascular resistance and structure of the terminal arterioles were measured in skin at the dorsum of the foot in 14 healthy subjects, in 12 patients with short-term congestive heart failure (CHF) (New York Heart Association functional class greater than or equal to II for less than 1 year), and in 14 with long-term CHF (New York Heart Association functional class greater than or equal to II for greater than 1 year). Blood flow was measured by the local technetium-99m-pertechnetate washout method in a vascular bed paralyzed by histamine before, during and after 3 to 5 stepwise increases of external counter pressure. Minimal vascular resistance was calculated from the relation between blood flow and applied pressure. Minimal vascular resistance was significantly increased in both short-term (9.0 +/- 1.9 mm Hg.ml-1.100 g.min; p = 0.0003) and long-term (9.1 +/- 3.6 mm Hg.ml-1.100 g.min; p = 0.008) CHF patients compared with that in healthy control subjects (6.0 +/- 1.7 mm Hg.ml-1.100 g.min). Structural microangiopathy (increased hyalinosis of the basement membranes in the terminal arterioles) was found in skin biopsies in 21 of 24 patients with CHF in whom biopsies were obtained, but in none of the 14 control subjects (p less than 0.002). Multiple regression analysis demonstrated a weak but significant direct association between minimal vascular resistance and the degree of structural microangiopathy (p less than 0.03; r = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

[Idiopathic interstitial pulmonary fibrosis. Clinical picture, diagnosis, treatment and prognosis]. / Idiopatisk interstitiel lungefibrose. Klinisk billede, diagnostik, behandling og prognose.

Idiopathic pulmonary fibrosis (IPF) was found to have a higher incidence than previously assumed and the population involved was younger. These findings were made in a retrospective investigation during the period 1986-1990. The condition should be suspected on the basis of the radiographic characteristics, reduced lung volume (TLC), decreased DLco during testing of pulmonary function, hypoxemia at rest and also the symptoms revealed in the medical history. It is of importance for planning of treatment that the diagnosis of IPF is confirmed early by excision biopsy of pulmonary tissue. Patients with IPF were treated successfully by intravenous administration of a solution of 500 mg methylprednisolone in 500 ml isotonic glucose. This regime is administered for three consecutive days and supplemented by azathioprine as required. In order to prevent further progression of this chronic disease, patients with IPF should be followed-up at frequent intervals.

Nocturnal subcutaneous hyperaemia in the lower leg and foot of type 1 diabetic patients.

Nocturnal fluctuations in subcutaneous blood flow in the lower leg and foot were measured during sleep in Type 1 diabetic patients without autonomic neuropathy. Subcutaneous blood flow was measured, simultaneously, 100 mm above the malleolus on the medial aspect of the right lower leg and at the dorsum of the left foot in 10 diabetic patients, and on the right lower leg only in 10 normal human subjects over 12-20 h. The 133Xe wash-out technique, portable CdTe (Cl) detectors and a portable data storage unit were used. The tracer depots were applied by means of the epicutaneous, atraumatic labelling technique. In diabetic patients, subcutaneous blood flow increased 102 +/- 68% in the lower leg and 111 +/- 98% in the foot at 113 +/- 32 min and 107 +/- 37 min, after going to sleep. The hyperaemic phase lasted 128 +/- 43 min and 150 +/- 42 min, respectively. The hyperaemic response was not different from that in the control subjects (89 +/- 61%). There was no significant correlation between the absolute hyperaemia in the leg and that in the foot. In conclusion, Type 1 diabetic patients without autonomic neuropathy have normal nocturnal hyperaemia during sleep.

Histological grade and steroid receptor content of primary breast cancer--impact on prognosis and possible modes of action.

The clinical course of breast cancer was related to degree of anaplasia (DA) and steroid receptor (SR) content of primary tumours in 743 patients (pts) with clinical recurrence, initially enrolled in the DBCG-77 protocols. The oestrogen receptor (ER) and the progesterone receptor (PgR) content was known in 110 and 67 pts. The recurrence-free interval, survival after recurrence, and the overall survival were all prolonged in patients with well differentiated tumours or with high SR content. The tumour growth rates were estimated as clinical rates of progression (i.e., the time elapsed from a single distant metastasis until dissemination). The progression rate was prolonged in relatively well differentiated as well as in receptor rich tumours. The extent of dissemination, as indicated by the number of metastatic sites, was not associated with either DA or SR content. However, the anatomical distribution of metastases varied with both DA and SR content: signs of poor prognosis (high DA or low SR content) were associated with occurrence of visceral metastases. In contrast, SR rich tumours had a propensity for recurrence in bone. The results suggest that the impact on prognosis of the features examined here includes both variations in growth rate and metastatic pattern.

Nuclear DNA content in prostatic carcinoma measured by flow cytometry: a retrospective study on paraffin-embedded tissue.

The nuclear DNA content in 67 prostatic carcinomas was measured by flow cytometry of nuclear suspensions prepared from paraffin-embedded tissue blocks. A method was developed that provided nuclear suspensions of good quality whether tissue blocks from transurethral resections or transvesical prostatectomies were used. Thirty (43.7%) of the tumors were found to be aneuploid. No significant correlation between clinical stage or histological grade and aneuploidy was demonstrated.

Immunohistochemical steroid receptor detection in frozen breast cancer tissue. A multicenter investigation.

Now that monoclonal antibodies against the estrogen receptor (ER) have become available, it is possible to detect the presence of ER immunohistochemically. In order to evaluate the validity of the immunohistochemical (ERICA) method in a routine detection of ER, we have tested the method in a multicenter investigation. As reference is used a conventional biochemical assay, dextran-coated-charcoal assay (DCC). The investigation analyzes the validity of the ERICA-assay, including a semiquantitative estimation of the ER-content, when the method is used in several independent departments of pathology, and the interobserver variation of the analysis. The results show that the qualitative detection of ER, obtained by the ERICA-assay and the DCC-assay has a concordance of about 90% for all the participating departments. The concordance is around 60-70%, when a semiquantitative estimation of the ER-content is used. The interobserver variation is also very low, with full agreement in 58 of 59 cases. The ERICA-assay may, therefore, be a relevant alternative to the DCC-assay. However, its clinical importance still has to be fully elucidated.

Increased minimal vascular resistance and arteriolar hyalinosis in skin on the leg in insulin-dependent diabetic patients.

Minimal vascular resistance (MVR) was determined in a paralysed cutaneous vascular bed at the dorsum of the foot in diabetic patients. Twelve long-term insulin-dependent diabetic (IDDM) patients with and nine short-term IDDM patients without nephropathy and retinopathy and eight control subjects were investigated. The vascular bed was paralysed by local injection of histamine. Skin perfusion pressure was varied by applying graded external counter pressure over the investigated area. Skin blood flow was measured by the local 99mTc wash-out technique before, during and after three to five step-wise increases of external counter pressure. The MVR was calculated from the reciprocal of the slope of the relationship between blood flow and applied pressure. The MVR was significantly increased in diabetic patients with (mean: 9.3 mmHg ml-1.100 g.min) and without nephropathy and retinopathy (8.5 mmHg ml-1.100 g.min) compared with non-diabetic subjects (5.2 mmHg ml-1.100 g.min) (p less than 0.001 and p less than 0.005, respectively). Diabetic microangiopathy (increased hyalinosis of the basement membranes in the terminal arterioles) was found in skin biopsies in nine of the 12 long-term IDDM patients and in four of the nine short-term IDDM patients, but not in the control subjects. Multiple regression analysis demonstrated a highly significant direct association between MVR and degree of diabetic microangiopathy in the same skin area (p less than 0.0002). A less significant direct association between MVR and arm diastolic blood pressure (p less than 0.05) and blood glucose concentration (p less than 0.05) was also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriolar hyalinosis does not interfere with the local veno-arteriolar reflex regulation of subcutaneous blood flow in insulin-dependent diabetic patients.

The function of the local nervous veno-arteriolar reflex regulation of blood flow in subcutaneous tissue of the lower leg was studied in diabetic patients. The material comprised 11 long-term insulin-dependent diabetic (IDDM) patients with retinopathy and nephropathy and eight short-term IDDM patients without retinopathy or nephropathy and 11 non-diabetic subjects. The diabetic patients had no or a slight to moderate degree of peripheral autonomic and sensoric neuropathy. Blood flow was measured by the local 133Xe wash-out technique. Blood flow was determined before, during and after an approximately 40 mmHg increase in venous transmural pressure, induced by lowering the lower leg 50 cm below heart level. During lowering of the leg, the subcutaneous blood flow decreased to the same level in long-term IDDM patients (mean: 46%), short-term IDDM patients (53%) and control subjects (53%). There was no association between the relative local blood flow during lowering and the degree of terminal arteriolar hyalinosis studied in skin biopsies from the same tissue area. Our results suggest that terminal arteriolar hyalinosis does not interfere with the local sympathetic-mediated veno-arteriolar reflex regulation of blood flow. Moreover, the vasoconstriction mediated by the veno-arteriolar reflex probably occurs in the larger arterioles (greater than 50-100 micron) or small arteries.

Vasoactive intestinal polypeptide concentration in human bladder neck smooth muscle and its influence on urodynamic parameters.

Three human studies were performed to evaluate the influence of vasoactive intestinal polypeptide (VIP) on bladder and urethral function. Bladder neck smooth muscle biopsies were obtained from nine men with functional bladder neck obstruction, from 10 men with medium sized benign prostatic hypertrophy and from four patients with a normal infravesical outlet. The biopsies were analysed for VIP by radioimmunoassay and by immunohistochemistry. No differences were found between the groups. Pressure-flow-EMG studies were performed in five men and urethrocystometry was performed in six women at rest, repeated coughing and at squeezing before, during and after VIP 3 micrograms/kg X h intravenously. No systematic changes developed in any of the urodynamic parameters.

Decreased distensibility of resistance vessels of the skin in type 1 (insulin-dependent) diabetic patients with microangiopathy.

The distensibility of the resistance vessels of the skin at the dorsum of the foot was determined in 11 long-term type 1 (insulin-dependent) diabetic patients with nephropathy and retinopathy, nine short-term type 1 diabetic patients without clinical microangiopathy and in nine healthy non-diabetic subjects. Blood flow was measured by the local 133Xe-xenon washout technique in a vascular bed locally paralysed by the injection of histamine. Blood flow was measured before, during and after a 40 mmHg increase of the vascular transmural pressure, induced by head-up tilt. The mean increase in blood flow during head-up tilt was only 24% in diabetic subjects with and 48% in diabetic patients without clinical microangiopathy, compared with 79% in normal non-diabetic subjects (P less than 0.0005 and P less than 0.05, respectively). An inverse correlation between microvascular distensibility and degree of hyalinosis of the terminal arterioles in biopsies from the skin was demonstrated (r = - 0.57, P less than 0.001). Our results suggest that terminal arteriolar hyalinosis reduces the microvascular distensibility and probably increases the minimal vascular resistance, thereby impeding hyperaemic responses.