The inter-relationships between albuminuria, plasma albumin concentration and indices of glycaemic control in non-insulin-dependent diabetes mellitus. We studied the relationship between albuminuria (measured as albumin/creatinine ratio (alb/Cr) in a random urine sample) and measures of glycaemic control (fructosamine, HbA1 and glucose) in 470 patients with non-insulin-dependent diabetes mellitus (NIDDM). Albumin excretion was in the microalbuminuric range (alb/Cr ratio > 5.4-40.3) in 112 (23.8%) and in the macroalbuminuric range (alb/Cr ratio > 40.3 mg/mmol) in 89 patients (18.9%). Fourteen percent (n = 67) of patients had a normal plasma HbA1 (< or = 8.5%) while 27% (n = 127) had a normal plasma fructosamine concentration (< or = 2.2 mmol/l). Using stepwise multiple regression analysis, plasma fructosamine concentration was found to be independently and negatively associated with urine albumin/creatinine ratio (B = 0.24, P < 0.006) in the macroalbuminuric group. Further analysis of the relationship between plasma albumin concentration and indices of glycaemic control showed that plasma albumin concentration correlated negatively with random plasma glucose concentration in the normoalbuminuric patients (r = -0.16, P = 0.008) but not in microalbuminuric or macroalbuminuric groups. HbA1 was not correlated with plasma albumin concentration. Our results indicate that albuminuria has an effect on the plasma fructosamine concentration which is independent of plasma albumin concentration.


Intensive care management of acute hemorrhagic leukoencephalitis with favorable neurologic outcome. A 36-year-old woman who presented with acute hemorrhagic leukoencephalitis survived with favorable neurologic outcome. The patient underwent evacuation of a right temporal hematoma, with aggressive postoperative management in the neurosurgical intensive care unit. Aggressive surgical and medical therapy, including high-dose corticosteroid therapy and continuous intracranial pressure monitoring may yield favorable outcomes in an entity previously associated with dismal neurologic prognosis.


Development and validation of a robust specific enzyme mediated assay for phenylalanine in serum. The specificity of a phenylalanine dehydrogenase, particularly with respect to cross reactivity toward tyrosine, has been shown to be pH dependent, being minimal at high pH. The dehydrogenase step has been coupled to colorimetric detection of NADH using a tetrazolium salt. The assay shows no significant cross reactivity towards a range of amino acids or drugs and correlates well with an established HPLC technique.


Lipid peroxides in blood from patients with atherosclerosis of coronary and peripheral arteries. Lipid peroxides in plasma were determined in 100 patients with coronary artery disease, in 100 patients with peripheral artery disease and in 100 persons without any clinical symptoms of coronary or peripheral artery disease. The concentrations of lipid peroxides were significantly higher in patients with atherosclerosis (both coronary and peripheral arteries) than in controls. There was no difference between lipid peroxides in patients with coronary and peripheral artery disease. Lipid peroxides in plasma were similar in subgroups of patients with coronary artery disease without a history of myocardial infarct and those who had had myocardial infarct. In subgroups of patients with peripheral artery disease divided according to the severity of peripheral atherosclerosis a positive association between the concentration of lipid peroxides in plasma and the severity of disease was observed. In all groups there was a significant correlation between the age of examined persons and lipid peroxides in plasma; however, the concentration of lipid peroxides in plasma was statistically higher in patients with atherosclerosis than in the control age matched group. The correlation between lipid peroxides and total cholesterol as well as triglycerides were weak and not statistically significant in most of the examined groups. The results of this study provide clinical support for experimental data indicating that peroxidation of lipids is an important factor in the formation of atherosclerotic changes. They also indicate that determination of plasma lipid peroxides may give important supplementary information in monitoring patients with clinical symptoms of atherosclerosis.


High levels of nervous system-specific proteins in cerebrospinal fluid in patients with early stage Creutzfeldt-Jakob disease. Concentrations of several proteins that are characteristic of the nervous system were time-sequentially analyzed by radio- and enzyme-immunoassay in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD). We found abnormally high levels of several proteins, such as neuron-specific enolase (NSE), S-100b protein, brain-type isozyme of creatine kinase (CK-BB) and alpha subunit of GTP binding protein G0 (G0 alpha) in the early stage of the disease. Generally, these protein levels were far higher in CJD patients than in normal controls and other neurological patients in the early stage before the typical clinical manifestations were evident. These levels increased to maxima when the disease activity was most prominent and returned to normal or mildly elevated levels in the terminal stage. The results imply that these protein levels can serve as biochemical markers for the presence of an active destructive process in CJD brain and provide us with a useful indicator for early diagnosis of CJD.


Renin assay using a fluorogenic substrate and high performance liquid chromatography. Measurement of renin activity in human fluids using a fluorogenic substrate and high performance liquid chromatography (HPLC) is described. A nine amino acid peptide containing the fluorogenic residue, N-(2-pyridyl) glycine (Pg) is used as a substrate. The peptide sequence is homologous with the cleavage site of human angiotensinogen. This substrate is hydrolyzed by renin to generate fluorogenic and non-fluorogenic products. The amount of fluorogenic product is directly measured by reversed phase HPLC. Optimization of assay conditions and measurement of human serum renin levels are described. Assay results correlated well with those from radioimmunoassay. The method is simple, convenient, highly sensitive and can be used for routine clinical renin assays.


Isolation of acylcarnitines from urine: a comparison of methods and application to long-chain acyl-CoA dehydrogenase deficiency. Carnitine esters from acetylcarnitine (C2 acyl chain) to octadecanoylcarnitine (C18 acyl chain) can be extracted from urine with recoveries of greater than 80%. However, to obtain such recoveries, it is important to choose the method of extraction appropriate to the acylcarnitines of interest. For acylcarnitines with acyl chain length C2 to C8 (acetylcarnitine to octanoylcarnitine), an ion-exchange procedure is recommended. Acylcarnitines with acyl chain length C8 to C12 (octanoylcarnitine to dodecanoylcarnitine) are best isolated from carefully acidified urine by solvent extraction with butan-1-ol. For long-chain acylcarnitines, C10 to C18 (decanoylcarnitine to octadecanoylcarnitine), solvent extraction of unacidified urine with hexan-2-ol is particularly simple and effective.


Glycation of human tissue and serum creatine kinase. Human creatine kinase (CK) was demonstrated to be partly present as a glycated molecule. Sialic acid, galactose and sulfate were also found to be present on the molecule. The glycated forms were characterized by higher activation energies and were thermally unstable. Skeletal muscle CK showed lower relative binding towards the lectin concanavalin A (Con A) in comparison with the heart tissue forms. After skeletal muscle trauma, CK in serum was found to be less glycated than in tissue. After acute myocardial infarction (AMI), no glycated CK could be detected in serum. Following injury, it appears that the transfer from tissue to plasma is accompanied by a loss of glycated isoforms. High-voltage electrophoresis showed no differences in the distribution of CK isoforms between the glycated and non-glycated forms.


Serum apolipoproteins in heterozygous familial hypercholesterolemia. In order to characterize the abnormalities of the lipoprotein profile in familial hypercholesterolemia (FH), serum apolipoprotein AI, AII, B, CII, CIII, and E levels were determined by the turbidimetric immunoassay in 48 patients with heterozygous FH. Apolipoprotein B levels in FH were about 2.5 fold higher (203 +/- 48 mg/dl, mean +/- S.D.) than the 30 age-matched normolipidemic control subjects (84 +/- 13 mg/dl). Significant increments of apolipoprotein CII, CIII, and E levels were observed in FH (4.6 +/- 1.6, 11.0 +/- 3.6 and 6.4 +/- 1.7 mg/dl, respectively) as compared with those in normal subjects (3.0 +/- 0.9, 7.7 +/- 1.6 and 4.5 +/- 1.1 mg/dl, respectively). Apolipoprotein AI and AII levels in FH were 130 +/- 27 and 32 +/- 6.0 mg/dl, respectively, which were not significantly different from the levels in normal subjects (131 +/- 18 and 31 +/- 5.4 mg/dl, respectively). The ratio of low density lipoprotein (LDL) cholesterol to apolipoprotein B was significantly higher in FH (1.3 +/- 0.3) than that in normal subjects (1.2 +/- 0.1). This indicates that the LDL of FH was cholesterol-rich in comparison with that of normal subjects. The ratio of high density lipoprotein (HDL) cholesterol to apolipoprotein AI in FH (0.34 +/- 0.07) was significantly lower than that in normal subjects (0.39 +/- 0.05). This difference might possibly be produced by an abnormal HDL metabolism of FH patients, a topic which remains to be elucidated by further investigation.


De novo glomerulonephritis in patients during remission from Wegener's granulomatosis. In a cohort of 20 consecutive patients with Wegener's granulomatosis and biopsy-proven pauci-immune crescentic glomerulonephritis three patients were in remission, but developed again a nephritic sediment without signs of systemic disease or positive ANCA titers. The second renal biopsy showed de novo mesangial IgA deposits 6, 17 and 28 months following admission for systemic disease and institution of immunosuppressive treatment. All patients were male, HLA-DR-2 positive and exhibited repeated upper respiratory tract infections. A fourth patient was admitted in end-stage renal failure with high titers of C-ANCA of the IgG isotype and proteinase 3 ab without clinical evidence of systemic manifestations of WG. Renal biopsy showed chronic sclerosing GN with marked IgA deposits. De novo development of IgA-GN is observed in a remarkable proportion of patients with WG and must be distinguished from exacerbation of the systemic disease.


Kidney transplantation in Alport's syndrome: long-term outcome and allograft anti-GBM nephritis. Anti-glomerular basement membrane (anti-GBM) nephritis occurring in kidneys transplanted in patients with Alport's syndrome (AS) has been reported repeatedly. Therefore, we studied graft survival and course of renal function in all 30 AS patients grafted at Hannover Medical School and compared them with non-diabetic, age and sex matched patients, transplanted on the date closest to the transplantation of the AS patient. Serum creatinine, proteinuria, urinary sediment and anti-GBM antibodies were examined in all AS patients with functioning grafts. Cases of patient or graft loss in the AS group were analyzed retrospectively. One- and five-year patient survival was 100 and 91% in AS and 89 and 78% in controls (p > 0.05, respectively). One- and five-year first graft survival was 79 and 66% in both groups. Graft histology was available in 34 biopsies obtained from 21 kidneys in 15 AS patients. Anti-GBM nephritis was not detected in any of the biopsies. No graft was lost due to anti-GBM nephritis. Anti-GBM antibodies were detectable temporarily only in one AS patient. He also had linear IgG staining in his graft GBM, but no other signs of anti-GBM nephritis. We conclude that patient survival and graft survival in AS patients following kidney transplantation is not different from non-AS patients. Allograft anti-GBM nephritis is a rare complication in patients with Alport's syndrome.


Failure to detect unique reactivity to streptococcal streptokinase in either the sera or renal biopsy specimens of patients with acute poststreptococcal glomerulonephritis. Using purified group A streptokinase (SKA) as the antigen, ELISA assays were carried out on the sera of normal unaffected children, acute poststreptococcal glomerulonephritis patients (APSGN) and acute rheumatic fever patients (ARF). The results demonstrate that antibody titers to SKA increase with age in normal children and by age 8 years the vast majority of children have antibodies to SKA. APSGN patients did not demonstrate unique reactivity to SKA when compared to ARF patients either at time of onset of disease or during convalescence. Polyclonal and monoclonal antibodies to SKA which recognize both group A and C streptokinase failed to detect the presence of streptokinase in the biopsy sections obtained from ten well-documented APSGN patients. We conclude that there is no unique reactivity to group A streptokinase in the sera of APSGN patients. Furthermore, we failed to demonstrate the presence of streptokinase in the biopsy specimens of an early case of APSGN patients.


Subtypes of acute postinfectious glomerulonephritis: a clinico-pathological correlation. The case records and histopathology of 42 adults with the characteristic light and electron microscopic features of Acute Postinfectious Glomerulonephritis (APGN) were studied. The biopsies were divided into three subtypes depending on the form and distribution of subepithelial "humps" and other immune-complex deposits on electron microscopy (EM): the "starry sky", "garland" and "mesangial" patterns. There was no significant difference between the three subtypes with regard to age, hypertension, creatinine, anti-streptolysin 0 titer and low serum complement levels on presentation. The "garland" subtype had significantly more proteinuria than both the "starry sky" (p = 0.04) and "mesangial" (p = 0.003) subtypes. The "mesangial" pattern had a lesser degree of cellular proliferation and leukocytosis in the glomeruli than the other subtypes. The "starry sky" subtype was present in 4 of the 5 cases of crescentic nephritis and in 6 of the 7 patients with a chronic course. Our study suggests that the higher degree of proteinuria in the "garland" subtype and the chronic course of the "starry sky" subtype are the main clinical features that distinguish the three histological subtypes. Our patients, from a developing community with poor socio-economic conditions, had a poor prognosis.


Urinary Escherichia coli causing recurrent infections--a prospective follow-up of biochemical phenotypes. Twenty-three women with non-obstructive acute pyelonephritis due to Escherichia coli were prospectively studied during 880 patient months, mean observation time 38 months. Each patient had between 1 and 4 new episodes of E. coli bacteriuria during the study period (altogether 49 recurrencies). All E. coli isolates were typed by biochemical fingerprinting. Twenty-six of the recurrencies were caused by an E. coli strain identical to one of those that had previously appeared. Sixteen of these infections were caused by a strain identical to the one that gave rise to the original acute pyelonephritis. Ten further recurrencies were due to an E. coli strain that had previously caused symptomatic or asymptomatic bacteriuria during the observation period. Despite appropriate treatment and repeated negative urine cultures post-treatment, infections caused by identical E. coli strains occurred up to 35 months after the initial episode of acute pyelonephritis. We suggest that the infecting E. coli strain may survive in the fecal flora or is harboured in the patient's surroundings, and after recolonizing the patient, these strains may give rise to further urinary tract infections.


Caroli's disease and congenital hepatic fibrosis associated with polycystic kidney disease. A case presenting with acute focal bacterial nephritis. Congenital cystic dilatation of the intrahepatic biliary ducts (Caroli's disease), until recently, has been infrequently recognized. It is often associated with autosomal recessive polycystic kidney disease (ARPKD) and congenital hepatic fibrosis (CHF). We hereby report a case with Caroli's disease, polycystic kidney disease (PKD), and CHF: This 24-year-old female patient initially presented with acute bacterial nephritis (ABN). Renal ultrasonography revealed bilateral enlarged kidneys with multiple cysts. Because her parents showed no renal cyst on ultrasonographic examination, she received further studies. Abdominal ultrasonography showed cystic dilatation of the biliary tree. Computed tomography (CT) with meglumine lotroxinate (biliscopin) infusion study and hepatobiliary scintigraphy confirmed the diagnosis of Caroli's disease. Liver biopsy revealed CHF: The radiographic and scintigraphic pictures are hereby illustrated and CT with biliscopin infusion study is emphasized. We conclude that if radiologic evidence of renal cystic lesions is absent in the parents of patients with PKD, the coexistence of Caroli's disease and CHF should be considered. The clinical pictures of ABN in this patient are also discussed. As far as we know, this is the first reported case of ABN in a patient with PKD and Caroli's disease, and it showed good response to antibiotic therapy.


Effect of prostaglandin synthesis inhibition on glomerular filtration rate in renal transplant recipients. To determine the influence of prostaglandin (PG) synthesis inhibition on the renal function in renal transplant recipients, we carried out a crossover, double-blind, placebo controlled study of 18 ambulatory patients. Glomerular filtration rate (GFR) was measured using 51-Cr EDTA, before and after indomethacin (50 mgr. three times a day for three days), and placebo. Overnight urinary PGE excretion decreased 88.9 +/- SEM 4.81% after indomethacin, but remained unchanged following placebo. GFR decreased 15.3 +/- SEM 3.94% (p = 0.0139) after indomethacin. There was no correlation between PGE urinary excretion and GFR changes. Pre-existing renal functional impairment was not a significant risk factor. Caution should be exercised when using non-steroidal anti-inflammatory drugs in renal transplant patients.


Effects of indomethacin and misoprostol on renal function in healthy volunteers. We have examined the effects on renal function of indomethacin and misoprostol, alone and in combination. Eight healthy volunteers took indomethacin 50 mg tds for one week, and indomethacin plus misoprostol (a synthetic PGE1 analogue) 200 micrograms qds for one week in a crossover design. A separate group (n = 5) took misoprostol alone for one week. 51Cr EDTA GFR rose significantly from baseline after the combination of indomethacin and misoprostol (from mean +/- SD 117 +/- 7.1 to 123 +/- 8.0 mls/min/1.73 m2, p = 0.05). When indomethacin alone was given 51Cr EDTA GFR did not change significantly (120 +/- 9.0 to 117 +/- 9.0 mls/min/1.73 m2). However in 4 of these subjects 51Cr EDTA GFR fell (range 7-19 mls/min/1.73 m2); in each of these the reduction was reversed when the indomethacin was given together with misoprostol. In the whole group the change in 51Cr EDTA GFR, from baseline, after indomethacin plus misoprostol was significantly different from that after indomethacin alone (+6 +/- 8 vs -3 +/- 5 mls/min/1.73 m2 p = 0.05). Misoprostol alone had no effect on GFR. We conclude that misoprostol and indomethacin in combination increase GFR in healthy volunteers, and further studies are now warranted to determine whether misoprostol is beneficial in the prophylaxis and treatment of NSAID-induced renal impairment.


Seizures and fever: can we rule out meningitis on clinical grounds alone? A study was done of 309 children seen in two ERs with a first seizure and fever to assess whether meningitis could be recognized using readily available clinical information. Among these children, 23 (7%) cases of meningitis were diagnosed. A group of 69 children with seizures and fever but no meningitis served as controls. Signs from ER examinations that discriminated between children with and those without meningitis were: petechiae, nuchal rigidity, coma, persistent drowsiness, ongoing convulsions, and paresis or paralysis; 21 cases were thus identified. Two children with a suspicious history but none of these signs proved to have meningitis. Children whose seizures showed no complex features and whose febrile illness revealed no suspicious features did not have meningitis. Our results indicate that based on available clinical data, meningitis can be ruled out in children presenting with seizures and fever; thus, there is no need for routine investigation of cerebrospinal fluid.


A probability nomogram to predict rectal temperature in children. The relationship between rectal and peripheral-site temperature was investigated to achieve two objectives: 1) to evaluate a prevailing practice of intersite adjustment by use of an invariant temperature difference; and 2) to develop a statistical method for intersite temperature predictions in the individual child, especially for fever as defined by rectal measurement. Rectal, oral, axillary, left abdomen skin, and forehead skin temperatures (degrees F) were measured with an electronic thermometer in 257 children. Objective 1 was not achieved because a simple temperature difference between a peripheral site and the rectal site could not be used to predict rectal temperature reliably. For objective 2, intersite differences met three statistical criteria so that normal distribution theory could be used to derive the probabilities for occurrence of each difference. Accordingly, cumulative probability nomograms were constructed to estimate rectal-site fever from measurements at peripheral sites. This nomogram method produces a clinically reliable prediction of rectal-site fever from temperature measurement at peripheral sites, especially the oral and axillary sites. These predictions offer useful assessments of febrile illness severity when rectal temperature is not available.


A changing pattern of epiglottitis.

A changing pattern of epiglottitis. A case review of epiglottitis at Geisinger Medical Center over the past 12 years demonstrates a decrease in the number of pediatric patients with epiglottitis and an increase in the number of adults with epiglottitis. In the last five years, the number of epiglottitis patients younger than 10 years has fallen (0 cases), while the number of patients over 10 years of age has increased (6 cases). The cause of epiglottitis, Hemophilus influenzae type b, remains constant in the pediatric as well as in the adult population. There appears to be an increasing frequency of epiglottitis in adults and a decreasing frequency of epiglottitis in children.


Medical and developmental histories of maltreated children. This paper represents a first attempt at delineating and summarizing the issues in a child's medical and developmental history associated with the probability of suffering abuse. The sample consisted of 96 children between 5 and 10 years of age, 61 of whom had been maltreated and 35 of whom served as controls. There were 22 items about which the medical and developmental histories of the maltreated children revealed a significantly greater risk than those of the controls. A factor analysis revealed that 78% of the variance in these items can be represented by eight independent factors. None of these factors was dominant; rather, each accounted for a significant amount of the variation among the original items. The individual items tended to load on the four strongest factors in a coherent, interpretable manner: Factor 1 represented behavior problems; factor 2, neonatal issues and failure to thrive; factor 3, familial disruption, with the child suffering mental illness and/or head injury; and factor 4, a "difficult" temperament during the first year of life. We conclude there are numerous independent factors in the medical and developmental histories of maltreated children which should be considered by pediatricians involved in cases of child abuse and neglect.


Urinary growth hormone and insulin-like growth factor I. Effects of growth-hormone injection schedule. Urinary growth hormone (GH) and insulin-like growth factor I (IGF-I) excretion profiles were compared in children receiving biosynthetic GH. Group 1 included 18 healthy controls. Group 2 included nine children given biosynthetic GH three times a week. Group 3 included 14 children given daily GH injections. Overnight urine samples were collected for three consecutive nights in all groups. No significant day-to-day variation in urinary GH output was observed in group 1. In group 2, urinary GH output was significantly higher on day one following injection than on days two and three. Urine GH outputs in group 2 were significantly lower on days two and three than the values observed on all days in group 3. Throughout the three-day study, subjects in group 3 excreted similar amounts of GH significantly higher than those of controls. Urinary IGF-I output (nmol/kg) was similar on all three study days in groups 1 and 3. Group 2 had significantly lower urinary IGF-I output on day three compared with day one. Urinary IGF-I output on day three was also significantly lower in group 2 than in group 3. We conclude that urinary GH and IGF-I outputs are influenced by the frequency of GH administration.


Review of mupirocin ointment in the treatment of impetigo. The introduction of mupirocin ointment gives the pediatrician a reliable topical alternative to oral antibiotic therapy for group A streptococcal and staphylococcal impetigo. It is as effective as oral antibiotics and is associated with fewer adverse effects. In superficial skin infections that are not widespread, mupirocin ointment offers several advantages. It is highly active against the most frequent skin pathogens, even those resistant to other antibiotics, and the topical route of administration allows delivery of high drug concentrations to the site of infection.


The newer radiographic contrast media.

The newer radiographic contrast media. The 1980s witnessed the development of many new contrast agents useful in radiographic and MRI to enhance the contrast discrimination between tissues and improve lesion conspicuity. In addition to improved efficacy, these agents are generally safer and cause less patient discomfort than older radiographic contrast media. The injection of any foreign material into the body always holds some risk, however, and it is the responsibility of clinicians and radiologists jointly to use these agents judiciously in the best interest of the patient.


Brain catecholamine concentrations in hyperosmolar diabetic and diabetic rats. The concentration of brain catecholamines were measured and compared in the experimentally made hyperosmolar diabetic, diabetic and normal control rats in order to clarify the metabolic changes of the brain in these states. Diabetes was induced with streptozotocin and hyperosmolarity was achieved through deprivation of water for 50 hours prior to experimentation. Dopamine, norepinephrine and epinephrine concentrations were measured in the left cerebral cortex, hypothalamic-thalamic area, cerebellum and medulla oblongata. Dopamine and norepinephrine concentrations were significantly elevated in the cerebral cortex, hypothalamic-thalamic area and cerebellum of the dehydrated hyperosmolar-diabetic rats relative to those of normal controls (p < 0.01-0.05). In diabetes with high blood sugar level, the norepinephrine concentration was significantly elevated in the cerebral cortex, cerebellum and medulla oblongata, and these changes generally paralleled the increase in fasting blood glucose. It was concluded that hyperosmolarity due to dehydration contributed these changes. The findings of this study further suggest that changes in brain catecholamines may be involved in the nervous system disturbances that occur in the dehydrated hyperosmolar-diabetes and severe diabetes.


Effects of thymosin and insulin on suppressor T cell in type 1 diabetes. In most studies the activity of suppressor T cells and the percentage of suppressor/cytotoxic T-lymphocyte subsets in type 1 diabetes have been found to be altered. To determine whether thymosin and insulin in vitro have a role in improving or normalizing these abnormalities, PBMC from 28 patients with type 1 diabetes of various durations were treated with thymosin or insulin and the activity and the percentage of suppressor T cells were detected by using the method of ConA-induced suppressor T cells and WuT8 (suppressor/cytotoxic) monoclonal antibody respectively. Both thymosin and insulin were found to have ability to improve and normalize the ConA-induced suppressor cell activity and the percentage of WuT8 cells in diabetic patients. Data have shown that the lower the activity and the percentage of suppressor T cells, the more intense the effects of both compounds. The strongest effects were found at the concentrations of 10 micrograms/ml thymosin and 10 ng/ml insulin. Thymosin was more effective than insulin. This experiment also suggested that the activated lymphocytes stimulated by mitogens (PHA or ConA) were required when insulin exerted a significant effect on suppressor T cells. We conclude that thymosin and insulin in vitro can exert immuno-regulatory or immunostimulating effects on suppressor T cells.


Blood and plasma viscosity in diabetes: possible contribution to late organ complications? It has been postulated that an increased whole blood and plasma viscosity contribute to diabetic organ complications. Blood viscosity was measured in 30 controls and four groups of insulin-dependent diabetic patients at three shear rates: 70 sec-1, 0.5 sec-1 and 0.05 sec-1. Results were compared before and after correction for a haematocrit of 0.45. Twenty-five patients without organ complications, 21 with microalbuminuria, 13 with overt nephropathy and 12 patients with leg ulcerations were studied. Blood and plasma viscosity were normal in the patients without organ complications and with microalbuminuria. Plasma viscosity was significantly elevated in the diabetic patient with nephropathy and leg ulceration. After correction for haematocrit blood viscosity was also higher in these two groups, although this was only significant in the group with leg ulceration. In conclusion blood and plasma viscosity were only elevated in the patients with major organ complications and not in the patients without or with early complications. Therefore it is unlikely that an elevation of blood or plasma viscosity contributes early in the pathogenesis of diabetic organ damage.


On the influence of metabolic state of parents at conception and pregnancy on incidence and age at onset of diabetes in the progeny of BB/OK rats. Thirty first and second litters of same parents of the BB/OK rat population were observed for diabetes occurrence up to an age of 200 days. The parents were nondiabetic at conception and pregnancy of their first litter (nd x nd) and either they remained nondiabetic up to an age of 200 days (nd x nd-->nd x nd) or the father (nd x nd-->d x nd) and the mother (nd x nd-->nd x d), respectively, were diabetic at conception of their second litter. There were no significant differences between first and second litters in incidence and age at onset of diabetes in the progeny, so that the genetic constitution of parents and not their metabolic state determines both traits. But, an influence of the maternal age on diabetes incidence of offspring was found. This influence, however, was not related to the metabolic state of mothers. This finding suggests that the age of mothers per se and not the metabolic state of mothers determines the diabetic disposition of the offspring in BB/OK rats.


Metabolic effects of aldose reductase inhibition in diabetic man. The metabolic effects of 52 weeks treatment with the aldose reductase inhibitor ponalrestat were examined in 32 diabetic patients (16 insulin treated) in a randomized, double-blind, placebo-controlled clinical trial. Twelve hour metabolic profiles were performed on two separate occasions in each patient (a) during a single-blind placebo run-in period and (b) after 52 weeks treatment with either ponalrestat 600 mg/day or matching placebo. No effects attributable to ponalrestat were evident in glucose, pyruvate, or alanine metabolism. A significant overall treatment effect was observed for lactate concentration (ponalrestat vs. placebo 12 h least square mean at 52 weeks: 1.35 vs. 1.65 mmol/l, p = 0.024). For glycerol (p = 0.018), non-esterified fatty acids (p = 0.003) and total ketone bodies (p = 0.045) there was evidence for a variation of treatment with time between the insulin treated and non-insulin treated patients, although no statistically significant overall treatment effects were observed for any metabolite. Fasting total ketone body concentration at 52 weeks was significantly elevated in the insulin-treated patients receiving ponalrestat (antilog LS mean: 0.12 vs. 0.01 mmol/l, p = 0.01). In conclusion, ponalrestat has no effect on glucose metabolism in diabetic patients. A potentially beneficial effect on lactate metabolism was accompanied by a minor ketogenic effect in insulin-treated patients.


Calcium antagonists and hormone release. VIII. Effects of verapamil infusion on C-peptide to insulin molar ratio in normal subjects and obese subjects with normal glucose tolerance. It is known that calcium-antagonist drugs can modify the insulin response to various secretagogues. In order to clarify whether calcium-antagonist effect was directed at the level of pancreatic insulin secretion or hepatic insulin extraction and further investigate the pathogenesis of hyperinsulinemia in obesity, an oral glucose tolerance test (OGTT) was performed in basal conditions and during a Verapamil infusion (VE, 5 mg/h x 3.5 h) in 12 normal subjects and 14 obese patients with normal glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cocaine: the historical aspects].

[Cocaine: the historical aspects]. The habitual use of drugs acting on the human mental faculties is very ancient. An overview on the history of cocaine, from the pre-Colombian populations of South-America to our days, is reported.


[The indications and need for diuretics in pregnancy]. The authors take into consideration specific cases of pregnancy with remarkable oedema caused by cardiac insufficiency, gestosis, pre-eclampsia and eclampsia. They emphasize that in these conditions and in other similar ones use of diuretics cannot be precluded. They report the case of a pregnant woman with severe cardiac insufficiency and considerable oedema observed at the Obstetric Clinical of Rome University. Thanks to diuretic therapy, the pregnancy could be followed through to full term.


[The use of interferon-beta in the treatment of essential mixed cryoglobulinemia]. The authors report two cases of essential mixed cryoglobulinemia (EMC) manifested by purpura, fatigue and arthralgia. After a corticosteroid treatment which proved a complete failure, beta-interferon therapy was started. This caused rapid improvement of the clinical picture without relevant side effects.


[Infective endocarditis].

[Infective endocarditis]. The authors underline the recent increase in the incidence of infective endocarditis (IE) involving the right side of the heart, because of instrumental procedures and, above all drug-addiction. They describe the epidemiology, congenital and acquired predisposing heart diseases, the most common portals of entry of the infective agents, etiology, pathogenesis, pathology, cardiac and extracardiac clinical manifestations and complications, clinical and instrumental diagnosis, medical and surgical therapy, prognosis and prevention of disease.


[A case of beriberi on the threshold of the year 2000]. The authors report a case of beriberi due to a deficit in thiamine, which became apparent in a young Chinese woman with polyneuropathy, distal oedema and epigastralgia. Parenteral administration of thiamine lead to the virtually complete resolution of symptoms.


[Immunoglobulins in the treatment of herpes zoster]. We have treated 20 patients with Herpes Zoster with "hyperimmune anti-Zoster immunoglobulins" (Uman-VZIG) by intralesional administration, 20 patients with Uman-VZIG by intramuscular administration and 23 patients with acyclovir by intravenous administration. The results of treatment in both groups of patients treated with Uman-VZIG were clinically satisfactory with disappearance of fever, local pain and amelioration of cutaneous lesions after two days from the start of treatment and with a mean duration of disease of five days. In patients treated with acyclovir, signs and symptomatology of disease ameliorated slowly and we have observed a longer mean duration of disease (about 8 days). We concluded that Uman-VZIG, both by intralesional and intramuscular administration, is effective and safe in Herpes Zoster treatment.


[Intravenous immunoglobulins. General features and the main clinical applications]. Intravenous immunoglobulins are stable pooled human IgG preparations for therapeutic use. Intravenous immunoglobulins are used for replacement therapy for patients with primary or secondary antibody immunodeficiency, and they are also beneficial in the prevention and treatment of certain viral infections, such as cytomegalovirus pneumonia and Varicella-Zoster; they may also have a synergistic effect with antibiotics in some bacterial diseases. Intravenous immunoglobulins have also been used successfully in the treatment of idiopathic thrombocytopenic purpura, Kawasaki disease and other autoimmune diseases such as Graves ophthalmopathy. Disadvantages of intravenous immunoglobulins include some frequent (10%) but usually not serious side effects and high cost; rarely has transmission of viral infections been reported.


[Preliminary results of intravenous immunoglobulins in treating patients with vasculitis]. Four patients affected with vasculitis syndrome (1 systemic vasculitis, 3 cutaneous vasculitis) were treated with "intravenous immunoglobulin" (IVIG). Two patients (1 systemic vasculitis, 1 cutaneous vasculitis) presented an improvement of clinical syndrome, while the other 2 patients presented a stable remission; in all patients biochemical amelioration or normalization was observed too. These data confirm that IVIG may be useful in treatment of systemic vasculitis and, for the first time to our knowledge, suggest that IVIG may be an effective treatment in cutaneous vasculitis.


[Changes in markers of autoimmunity in patients with Hashimoto thyroiditis treated with intravenous immunoglobulins. Preliminary results]. We have evaluated the variations of thyroid function, of thyroid autoantibodies titer, of non-organ specific autoantibodies and of other autoimmunity indices in 3 patients affected with Hashimoto's thyroiditis treated with "high dose intravenous gammaglobulin" (IVIG) (400 mg/Kg/day for 3 cycles of 5 days and subsequently 9-12 cycles of 1 day every 21 days). Before the starting of IVIG treatment patient 1 presented clinically evident hypothyroidism while patients 2 and 3 presented a preclinical form of hypothyroidism. At the end of IVIG treatment patients presented no variation of thyroid function, while patients 2 and 3 presented a normalization of T3, T4 and TSH circulating levels. Before the starting of IVIG treatment thyroglobulin antibodies (TgAb) were positive in 3/3 patients, microsomal antibodies (MAb) were positive in 3/3 patients adt TRAb were positive in 2/3 patients and MAb titre was decreased or negative in 0/3 patients. At the end of IVIG treatment Tg Ab titre was decreased or negative in 2/3 patients and MAb titre was decreased or negative in 2/3 patients. Anti-nuclear antibodies (ANA) 1/3 patients before the titre and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA), anti-mitochondrial antibodies (AMA), C3, C4, CH50 and rheumatoid factors were negative or in the normal range in all the patients. In conclusion these data suggest that IVIG is effective in the treatment of preclinical hypothyroidism in patients with Hashimoto's thyroiditis and determine a stable immunosuppressive action on circulating thyroid and non organ specific autoantibodies.


[Autoimmune polyendocrine syndrome. Treatment with intravenous immunoglobulins]. We report the effect of "intravenous gamma-globulin treatment" (IVIG) in a patient with autoimmune polyglandular syndrome type II, with circulating organ specific autoantibodies, preclinical hypothyroidism, amenorrhea and Addison syndrome. During IVIG treatment we observed a normalization of thyroid function, the appearance of some non ovulatory menses, reduction of thyroglobulin, thyroidal microsomal, anti-parietal cell, adrenal and ovary antibodies. These data confirm that intravenous immunoglobulin may represent a new tool for treatment of autoimmune disorders and show, for the first time, an immunosuppressive effect of intravenous gammaglobulin treatment in immunological phenomena direct against ovary, adrenal and gastric mucosa.


[Parameters of organ-specific and non-specific autoimmunity in patients with Basedow's disease and Basedow's ophthalmopathy. Changes induced by IVIG treatment]. The aim of this study was to evaluate the variations of thyroid autoantibodies titre in a group of 15 patients affected with "Graves' disease" (G. D.) during the treatment with antithyroid drug (ATD) and "high dose intravenous immunoglobulin" (IVIG) for "Graves' ophthalmopathy". Before the starting of treatment thyroglobulin antibodies (TgAb) were positive in 10/15 patients, microsomal antibodies (MAb) were positive in 13/15 patients and TRAb were positive in 5/9 patients. At the end of treatment TgAb titre was decreased or negative in 7/10 patients, MAb titre was decreased or negative in 7/13 patients, TRAb titre was diminished or negativized in 5/5 patients. Anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were positive in 3/15 and 3/15 patients before the treatment and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA)m anti-mitochondrial antibodies (AMA) and rheumatoid factors were negative in all the patients. Also in the 3 patients not treated with ATD we have observed a reduction or a negativization of circulating thyroid autoantibodies. In conclusion these data suggest that the reduction of thyroid and non organ specific autoantibodies might be due to a stable immunosuppressive action of IVIG treatment in patients with Graves' disease.


[Liver function tests, hepatitis A, B, C markers and HIV antibodies in patients with Basedow's ophthalmopathy treated with intravenous immunoglobulins]. Recent reports of transmission by intravenous gamma-globulin preparations of A, B, C and non-A non-B hepatitis (NANBH), including several cases that progressed to severe liver damage and death, have raised concerns about the safety of intravenous gamma-globulins. To assess this issue 15 patients treated with high-dose "intravenous immunoglobulin" (IVIG) for Graves' Ophthalmopathy had serial determination of glutamic pyruvic transaminase (GPT), glutamic oxalacetic transaminase (GOT), gamma glutamyltranspeptidase (gamma-GT), alkaline phosphatase and bilirubin that were performed regularly at interval of 3 weeks during IVIG treatment and 6 months after the end of the treatment. Hepatitis A, B, C and HIV markers were determined before, during and 6 months after the end of the treatment. The standard dosage was 400 mg per Kg body weight IVIG (3 cycles of 5 days and 12 of 1 day, every 21 days). Transient minor elevations were observed for GPT, for GOT, for gamma-GT and alkaline phosphatase. None of the elevations were considered indicative of NANBH or of any chronic hepatic disease. Transient presence of hepatitis A, B and C antibodies were observed in 6 patients. All patients remained negative for hepatitis B antigens throughout the study. HIV antibodies resulted always negative in all patients. In conclusion this study suggests the hepatitis and HIV safety of IVIG.


[Intravenous immunoglobulins in hematologic therapy]. The use of intravenous immunoglobulin (IgIV) increased in the last ten years. IgIV are used in three different groups of haematologic pathologies. The first group is formed by the immunodeficiencies: primaries (those that started the use of IgIV) and secondaries (from immunosuppressive agents and from deficit accessories of Ig). The second group is that of autoimmunity of the blood corpuscular elements (ITP, autoimmune neutrocytopenia and autoimmune haemolytic anaemias). The third group is represented by thrombotic thrombocytopenic purpura. The right protocol and the optimal formulas of the dosages of IgIV are still to be tested. The same applies to its action mechanisms and its potential utilization in other diseases.


[The use of intravenous immunoglobulins in patients with severe burns]. The parenteral use of whole molecule immunoglobulins is an important instrument for immunotherapy which can be employed in a variety of morbid conditions characterized by immunodeficiency, and therefore also in the management of severe burns. In order to confirm this assumption, the effect of i.v. administration of immunoglobulins has been studied in a group of burn patients and has been compared with the results obtained in the same number of clinically homologous patients not submitted to this treatment. In view of the results obtained, i.v. immunoglobulins can be usefully employed for the control of inflammatory and septic phenomena with reduction of abnormal parameters and a positive influence on the recovery curve.


[Treatment of systemic lupus erythematosus with intravenous human immunoglobulins. Preliminary study]. Recently the availability of human immunoglobulin for intravenous use (IVIg) has been helpful in the treatment of some conditions characterized by autoimmune disorders and anecdotal reports have been suggested a favourable role in the therapy of SLE. We report our experience on 4 SLE patients in whom IVIg was administered. Our data suggest that IVIg may be considered an alternative regimen to treat selected patients affected by SLE.


Racemization of aspartic acid in human articular cartilage. The rate of racemization of aspartic acid was measured in young and aged human femoral head cartilage. Normal femoral heads were obtained at postmortem, osteoarthritic specimens at operations for total hip replacement. In order to distinguish between the aspartic acid racemization in collagen from that in proteoglycan (PG), in addition to native tissue, we tested cartilage specimens from which PG had been enzymatically removed. Preliminary results indicate that there is only a very slow collagen turnover in normal adult cartilage. The same is true of residual cartilage from osteoarthritic femoral heads, indicating no rapid repair except where osteophytes are formed. Native, PG-containing cartilage, whether normal or osteoarthritic was found to have unexpectedly high racemization rates.


Elastin synthesis and accumulation in irradiated smooth muscle cell cultures. Multilayer cultures of neonatal rat aortic smooth muscle cells, which were actively synthesizing elastin, were exposed to gamma-radiation. Elastin synthesis and accumulation was measured as a function of time after irradiation and compared to control (non-irradiated) cultures. Cells exposed to 50 Gy ceased to divide but continued to synthesize and accumulate elastin. The culture morphology suggested that the irradiated cells accumulated an extensive extracellular matrix between their cell layers. Interestingly, the amount of elastin accumulated in the irradiated cultures was nearly the same as in the controls despite the difference in cell number in the two cultures. Thus, on a per cell basis, the elastin accumulation was greater in the irradiated cultures than in the controls.


Monoclonal antibody BRL 12 reacts with bone keratan sulphate proteoglycan. Our previous studies suggest that a monoclonal antibody, BRL 12, reacts with a specific product of differentiated cells of the osteoblastic lineage. In the present study, the bone constituent recognized by this antibody has been characterized by gel filtration, ion exchange chromatography, protein blotting and immunolocalization. Our findings show that the antibody reacts with an epitope associated with the core protein of rabbit keratan sulfate proteoglycan (KSPG), a molecule which shares considerable homology with the sialoprotein present in the bone tissue of other mammalian species.


Characterization of metalloproteinases and tissue inhibitors of metalloproteinases in human plasma. In this study, we have identified and characterized metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs) in human plasma. Treatment of plasma with trypsin or aminophenylmercuric acetate resulted in activation of latent gelatinolytic activity. Fractionation of plasma by gelatin Sepharose chromatography resulted in the isolation of 72 kDa and 92 kDa gelatinases/type IV collagenases. The 72 kDa gelatinase was purified by gel filtration chromatography. Stromelysin-1 was isolated from plasma by Matrex green A affinity chromatography. Immunoblotting of plasma fractions with antibodies to unique peptide regions of human gelatinases differentiated the 72 kDa gelatinase from the 92 kDa gelatinase. Antibodies to the amino terminal peptides of each enzyme were used to determine that plasma gelatinases circulate as latent proenzymes. Immunoblotting with antibodies directed against human stromelysin identified a 57 kDa stromelysin. TIMP-1 (28 kDa) and TIMP-2 (21 kDa) were also identified by immunoblotting of gelatin Sepharose bound plasma proteins using non-crossreacting antibodies to each protein.


Partial protein sequence of the globular domain of alpha 4(IV) collagen chain: sites of sequence variability and homology with alpha 2(IV). The globular domain (NC) of alpha 4(IV) collagen chain was partially sequenced and compared with the NC domain of other collagen IV chains. The alpha 4(IV) NC domain was found to be most closely related to alpha 2(IV) NC domain but distinct from the NC domain of alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 5(IV) collagen chains. Partial sequence, representing nearly one half of alpha 4(IV) NC domain, shows 56%, 69%, 51% and 54% identity with the corresponding NC domains of alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 5(IV) collagen chains, respectively. A short, highly polar, region of variable sequence is found near the carboxy terminus of alpha 4(IV) NC domain. This sequence corresponds to a non-conserved region among NC domains, suggesting functional specialization at this site. It exhibits high surface probability with predicted structural differences among NC domains. These results confirm uniqueness of alpha 4(IV) NC domain and indicate its structural relatedness to other NC domains of collagen IV.


Mycobacterium fortuitum keratitis. Clinicopathologic correlates and corticosteroid effects in an animal model. Mycobacterium fortuitum keratitis is an indolent infection of traumatized corneas in humans. To study this disorder in an animal model, 10(4) M fortuitum organisms (10 microliters) were inoculated into the stroma of both corneas of 16 New Zealand albino rabbits. Eight of the rabbits were also given bilateral subconjunctival injections of methylprednisolone acetate (20 mg in 0.5 ml) at the time of inoculation. Two corticosteroid-treated and two untreated rabbits were selected each week after inoculation for histopathological examination and quantitative cultures. Corneal lesions in corticosteroid-treated eyes were characterized clinically by indolent ulcerations and satellite lesions that slowly enlarged; on histopathologic examination at each week, acute inflammation and microorganisms were consistently present. Corneal lesions in untreated eyes were characterized clinically by small infiltrates that progressed little over time; at weeks 1 and 2, light microscopic examination showed intrastromal granulomatous and/or mixed acute and chronic inflammation with focal intrastromal necrosis, but at weeks 3 and 4 there was no evidence of active disease. Organisms could not be identified microscopically in corneas of any untreated rabbits. Mean values for quantitative cultures of corneas were higher in corticosteroid-treated rabbits after week 1, although standard deviations were large. These results suggest that M fortuitum keratitis in rabbits is made worse by corticosteroid use. Clinical and histopathologic changes were compared with human disease and found to be similar in corticosteroid-treated rabbits.


Mycobacterium fortuitum keratitis. A comparison of topical ciprofloxacin and amikacin in an animal model. The effect of topical amikacin or topical ciprofloxacin on Mycobacterium fortuitum keratitis was studied in a rabbit model. Two strains of M fortuitum were used: ATCC-6841 [for which mean inhibitory concentrations (MICs) indicated in vitro sensitivity to both drugs] and a cutaneous isolate from a human infection (for which MICs indicated relative in vitro resistance to amikacin but in vitro sensitivity to ciprofloxacin). Both drugs reduced the number of organisms in eyes infected with either strain (all p values < or = 0.01), but in no cases were organisms eliminated from eyes after 4 days of treatment. Amikacin was more effective in reducing the number of organisms in corneas infected with ATCC-6841 than in corneas infected with the patient isolate (p = 0.004), whereas ciprofloxacin was equally effective for treatment of both strains (p > 0.10). These results suggest that topical amikacin or ciprofloxacin may be useful in the treatment of M fortuitum keratitis. However, neither drug was shown to be more effective for treatment of either strain studied (all p values > 0.3).


HLA-DR alleles and sterile ulcerative keratitis. Human leukocyte antigen-DR typing was performed on 18 unrelated white patients with sterile ulcerative keratitis (SUK) to determine whether these patients share common immunogenetic susceptibility genes. There was no statistically significant increase in any DR allele among the entire group of SUK patients. There was a trend in the frequency of DR1 in the rheumatoid arthritis (RA) patients (5 of 8, 63%) versus the non-RA patients (1 of 10, 10%), which was not statistically significant, possibly due to the small number of patients in the study. Screening patients with RA without known SUK from our RA register revealed one DR1-positive patient with an inactive peripheral marginal melt. These findings suggest a possible relationship between DR1 and RA sterile corneal melting, which will need to be confirmed with a larger study.


Fluorophotometric assessment of tear turnover under rigid contact lenses. To examine the effect of rigid contact lens design on tear turnover the left and right eyes of 25 healthy volunteers were randomly fitted with either a spherical or an aspherical contact lens. Tear turnover is defined as the percentage of decrease of fluorescein concentration in the tear film per minute as a result of tear flow after instillation of fluorescein and can be determined with a fluorophotometer. A drop of fluorescein (1 microliter, 2%) was instilled in each contact lens-wearing eye, whereafter the decrease of the fluorescein was measured for about 30 min. The test was repeated without contact lenses. No statistically significant difference was found between the tear turnover in the spherical, the aspherical, and the non-contact lens-wearing eyes (mean values +/- SD: 15.2 +/- 4.9, 15.6 +/- 5.9, and 16.9 +/- 6.8%/min, p > 0.20).


Treatment of ocular surface disorders and dry eyes with high gas-permeable scleral lenses. Extreme corneal surface disorders and dry-eye conditions cannot be adequately treated with corneal contact lenses. For these cases a scleral lens with a diameter of between 21 and 25 mm could be prescribed. In this study, high oxygen-permeable scleral contact lenses were fitted onto 50 eyes, of which 32 had a deviant corneal topography and 18 had dry-eye syndrome. A significant improvement of visual acuity and good lens tolerance were found. The large lens successfully created a moist atmosphere in front of the cornea with dry-eye circumstances. No signs of oxygen shortage were recorded. In three dry eyes (16.7%) immediate failure in fitting was found, due to lens binding. The new scleral lens provides a physiological condition of the cornea, which allows a revival in the application of such lenses.


Corneal graft rejection after neodymium-yttrium-aluminum-garnet laser posterior capsulotomy. Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser capsulotomy was performed in three patients with corneal graft. Acute corneal graft rejection was noted in these patients 4 weeks to 4 months after posterior capsulotomy. In one patient, enlargement of the capsulotomy opening was followed by a second episode of corneal graft rejection. We discuss the complications of Nd-YAG laser capsulotomy, and its possible role as a cause for corneal graft rejection.


A new fluorocarbon for keratoprosthesis. Previous studies have demonstrated the potential use of microporous, biocompatible materials to improve the long-term stability of keratoprosthesis. To determine the factors that will influence corneal tissue ingrowth into biocompatible, microporous materials, we have compared three types of fluorocarbon polymers--Impra, Gore-Tex, and Proplast--after intrastromal implantation in rabbit corneas. Despite similar physicochemical structures, a great difference was observed in histologic and ultrastructural cross sections after 4- and 8-month follow-ups. For Gore-Tex, we observed extrusion of the implant and infiltration of necrotic and inflammatory cells. All implants of Proplast also led to significant corneal damage resulting in extrusion of the material. Through the use of electron and light microscopy and image analysis, this study demonstrates the presence of cell differentiation and collagen synthesis in the pores of the Impra implant. Apart from biocompatibility, this experiment demonstrates the influence of pore size, porous microorganization, and biomechanical factors on prosthetic corneal material. Only Impra offers satisfactory interface, allowing fibroblastic cells and neocollagen synthesis into its pores, and it can become transparent.


Topical cyclosporine A and corneal wound healing. The effect of 2% topical cyclosporine A (CsA) ointment on corneal epithelial and stromal wound healing was evaluated in a masked, placebo-controlled study in rabbits. The difference in epithelial would healing rate in the treatment and placebo group was not statistically significant. There was also no difference in the values of bursting strength of 2-mm central penetrating wounds and in the measurement of hydroxyproline content in the central corneal buttons from the wounded area in both the groups. Clinical evaluation of the quality of regenerating epithelium, stromal edema, haze, and iritis did not reveal a difference between the two groups. There was a significantly higher incidence of conjunctival injection in the CsA-treated group. We conclude that topical cyclosporine A 2% does not significantly inhibit epithelial or stromal corneal wound healing.


Histopathological variation in keratoconus. During examination of 131 penetrating keratoplasty specimens from patients with keratoconus obtained in an 11-year period, we observed two histopathologic variants based on the appearance of Bowman's layer and the corneal epithelium. "Typical" keratoconus specimens had multiple breaks in Bowman's layer and central epithelial thinning, whereas "atypical" corneas lacked breaks in Bowman's layer and had less thinning of the central epithelium. Ninety-five corneas were from patients who underwent grafting in only one eye. Seventy-six (80%) of these corneas were "typical" and 19 corneas (20%) were "atypical" in appearance. Both variants had similar degrees of central stromal thinning. Patients with "typical" and "atypical" corneas differed demographically by race only; 49% of "typical" and 95% of "atypical" corneas were from white individuals. Thirty-six corneas were from 18 patients who underwent bilateral penetrating keratoplasty. The histologic appearance of these corneal pairs was concordant in 13 patients and discordant (one "typical" and one "atypical" cornea) in five patients. Statistical analysis indicated that this distribution is not significantly different from that predicted by chance and suggests that "typical" and "atypical" corneas are manifestations of the same disease process.


Regional distribution of mammalian corneal aldehyde dehydrogenase and alcohol dehydrogenase. The regional distribution of mouse aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase activities in mouse ocular tissues was examined using spectrophotometric and agarose-isoelectric focusing techniques. The results established that these enzymes are predominantly localized in the cornea. Biochemical and histochemical analyses of the localization of these enzymes in the corneas of common domestic mammals (pigs, sheep, and cattle) and in baboons revealed species differences, with high levels being reported in corneal epithelium (pigs and baboons) and endothelium (sheep and cattle). The presence of these enzymes in the corneal epithelium is consistent with their proposed catalytic role in the detoxification of ultraviolet (UV)-induced peroxidic aldehydes, and with the proposed role for corneal ALDH in UVB absorption.


Albumin in the cornea is oxidized by hydrogen peroxide. The action of hydrogen peroxide on soluble proteins of the rat cornea has been evaluated. Two major corneal proteins are found to be oxidized by 10 mM hydrogen peroxide. Protein sequence and antibody recognition has shown one of the proteins to be albumin. Treatment of pure rat or human albumin with hydrogen peroxide oxidizes the protein and decreases its affinity for its antibody. Because albumin is a major protein in the cornea, its ready oxidation suggests that a role for albumin in this tissue may be to act as a native antioxidant, scavenging hydrogen peroxide and thus preventing more extensive damage by this toxin. These data are relevant to the evaluation of the safety of contact lens disinfectants containing hydrogen peroxide and suggest that further study of the action of this oxidant is warranted.


Indications and techniques of penetrating keratoplasties, 1985-1988. Indications and surgical techniques for penetrating keratoplasties (PKs) were evaluated to determine present trends and suggest future directions for PK. Analyses were based on 3,941 PK cases, with questionnaires completed at the time of surgery by 638 surgeons receiving tissue through Tissue Banks International, Inc. between July 1, 1985, and December 31, 1988. The leading indications for PK were pseudophakic corneal edema (PCE) (23%), graft failure (17%), Fuchs' corneal dystrophy (13%), kerataconus (13%), keratitis/scar (12%), and aphakic corneal edema (10%). Indications for PK varied by age and sex. Anterior chamber (AC) lenses accounted for the majority (56%) of PCE cases. Penetrating keratoplasty for PCE occurred within 5 years of cataract surgery for 81% of patients with PC lenses and only 52% of patients with AC lenses. Intraocular lens exchange was performed in most AC and iris-fixed lens PCE cases (65% and 77%, respectively), but less frequently in PC lens cases (17%). A PC lens was placed in 29% of all PCE lens exchange cases. These data have confirmed and expanded observations from smaller studies about leading indications and surgical techniques for PK. Therefore, eye bank data may be useful in describing and monitoring future indications and trends for PK because they provide a broader base of information than that obtained through a single institution.


Clinical and pathologic findings of aphakic peripheral corneal edema: Brown-McLean syndrome. Twenty-two patients (36 eyes) are reported with Brown-McLean syndrome, which consists of peripheral corneal edema associated with peripheral endothelial pigment deposits, usually after intracapsular cataract extraction. This group, the largest reported to date, had a spectrum of corneal alterations, those at the more severe end of the spectrum being both progressive and symptomatic. Some patients required medical and surgical treatment, including keratoplasty. Four corneas (two obtained surgically, two postmortem) were examined by light and electron microscopy (EM). Centrally, the corneas were relatively normal, but peripherally there were disintegrated endothelial cells with an abnormal posterior collagenous layer of Descemet's membrane. Scanning EM showed a somewhat distinct junction between the normal central endothelium and the diseased peripheral endothelium.


Multiple myeloma presenting as vortex crystalline keratopathy and complicated by endocapsular hematoma. The crystalline keratopathy of multiple myeloma may involve the corneal epithelium, but has not previously been described in a vortex epithelial distribution. Endocapsular hematomas have been described in the period immediately after extracapsular cataract extraction, but not later on or in association with systemic disease. We report a pseudophakic patient who developed a vortex epithelial crystalline keratopathy as a presenting sign of multiple myeloma, and who subsequently developed a spontaneous endocapsular hematoma.


Inadvertent corneal button inversion during penetrating keratoplasty. Inadvertent inversion of a corneal button during corneal transplantation for pseudophakic bullous keratopathy occurred with subsequent intense intraocular inflammation but a relatively compact graft. The diagnosis was made by a superficial corneal biopsy of Descemet's membrane, and a repeat corneal transplantation resulted in a clear graft and no evidence of epithelial downgrowth. Histology revealed the persistence of the donor epithelium on the inverted donor button but no residual endothelium on the externalized surface. Although laboratory attempts to duplicate an inversion of a corneal graft revealed that this occurs only with considerable difficulty, this operative complication may explain some of the unexpected primary graft failures reported in the literature.


Orbital cyst in a patient with Stevens-Johnson syndrome. A 10-year-old girl with ocular complications of Stevens-Johnson syndrome developed a large superior orbital cyst above the right eye. When the cyst recurred after needle aspiration, it was removed surgically and the superior conjunctival fornix was replaced with a buccal mucous membrane graft. Histopathologically the lesion proved to be a clear cyst lined by nonkeratinizing epithelium compatible with conjunctival epithelium with rare goblet cells. The patient did well postoperatively. An orbital cyst is a rare ocular complication of the Stevens-Johnson syndrome.


Corneal opacity in LCAT disease.

Corneal opacity in LCAT disease. Deficiency of lecithin:cholesterol acyltransferase, LCAT disease, is one of the dyslipoproteinemias with characteristic lipid deposits in the cornea. The present report documents the clinicopathologic abnormalities of one case in which a full-thickness corneal specimen was obtained at the time of corneal transplantation. The characteristic clinical abnormality was a progressive corneal opacification with a peripheral arcus that extended into the sclera. The pathologic abnormality consisted of vacuoles prevalent in the anterior corneal stroma by light microscopy and containing extracellular, membranous deposits by electron microscopy. These observations confirm and supplement the previous six pathologic reports of corneal changes in LCAT disease and demonstrate, for the first time, histopathologic evidence of unesterified cholesterol in the corneal stroma of LCAT disease.


Corneal endothelial irregularity with long-term contact lens wear. A case is presented of a 49-year-old woman who has worn hard contact lenses for 26 years. Specular microscopy of the central corneal endothelium revealed marked bilateral polymegethism and a large coefficient of variation in cell size. Of greater significance was the presence of clumps of small cells. This may be related to the way the corneal endothelium responds to long-term anoxia.


Aggression as a natural part of suicide bereavement. This article analyzes anger as a phase in the process of bereavement after suicide. Anger is generally very difficult for the survivors to recognize, accept, and express. At the beginning of the survivors' group meetings, anger is repressed and denied. After the group has become more structured and more cohesive, the aggression is first expressed indirectly (through dreams) and directed at different objects (the environment, the survivor him- or herself). In the final group sessions, when the members support each other emotionally, both the group atmosphere and the therapist help them to recognize their anger and to vent their aggression toward their relative who committed suicide. If the survivors do not go through this phase, the bereavement process should not be considered completed.


Double-blind comparison of etodolac SR and diclofenac SR in the treatment of patients with degenerative joint disease of the knee. An on-going multi-centre, double-blind, parallel-group study is being carried out to compare the efficacy and tolerability of sustained-release (SR) formulations of etodolac and diclofenac in patients with degenerative joint disease (osteoarthritis) of the knee. An interim analysis of the findings has been made for 64 patients from two centres which have now completed their part in the study. Thirty-two patients were randomly assigned to receive 600 mg etodolac SR once daily for 4 weeks; the remaining 32 patients received 100 mg diclofenac SR. Primary efficacy assessments rated on a 5-point categorical scale were patient and physician overall assessments of the patient's condition, night pain and pain intensity. Secondary efficacy parameters included weight-bearing pain, stiffness duration, joint tenderness on pressure, degree of swelling and erythema, degree of knee flexion and time to walk 15 metres. The results showed that for both etodolac SR and diclofenac SR treatment groups there was an improvement from baseline in all efficacy parameters at the last visit and no statistically significant difference was observed between treatments. However, although not statistically significant, the improvement rate in the patient's condition at Week 2 was slightly greater in the etodolac SR treatment group, suggesting that improvement may occur more rapidly with etodolac SR than with diclofenac SR. With regard to tolerability, 5 patients in the etodolac SR treatment group and 3 in the diclofenac SR group withdrew from the study because of adverse reactions. Two events (dyspepsia and mouth ulceration) in the etodolac SR group and 4 events (headache, glossitis, depression and insomnia) in the diclofenac SR group were considered to be definitely drug-related. Dyspepsia was reported by 3 patients (1 withdrawal) treated with etodolac SR and by 4 patients (2 withdrawals) treated with diclofenac SR. A statistically significant decrease was observed in haemoglobin and haematocrit values after 4 weeks of treatment in the diclofenac SR group, but this was not considered to be clinically important. In addition, there were no clinically significant changes in blood chemistry and urinalysis for either treatments. In conclusion, the results of the present study indicate that 600 mg etodolac SR once daily for 4 weeks is effective in the treatment of patients with degenerative joint disease of the knee, as is 100 mg diclofenac SR. In addition, both drugs have comparable tolerability profiles.


Comparison of the effects of etodolac SR and naproxen on gastro-intestinal blood loss. A single-blind, open-label controlled study was carried out in 30 healthy male volunteers to compare gastro-intestinal blood loss before, during and after treatment with a new, sustained-release formulation of the non-steroidal anti-inflammatory agent etodolac (etodolac SR) or with naproxen. Subjects remained at the study centre for 21 days and received placebo twice daily from Days 1 to 7 after which they were assigned at random to receive etodolac SR either as a single 600 mg or 1200 mg daily dose or naproxen (500 mg twice daily) for 7 days and then placebo again until the end of the study. There were 10 subjects in each of the three treatment groups. Gastro-intestinal blood loss was measured by the 51Cr-tagged erythrocyte method and was averaged for Days 4 to 7 (pre-treatment baseline), Days 11 to 14 (treatment period), and Days 17 to 20 (post-treatment period). The mean daily gastro-intestinal blood loss during the treatment period was significantly greater for the naproxen-treated group (1.20 ml/day) than for the 600 mg etodolac SR group (0.38 ml/day) and the 1200 mg etodolac SR group (0.45 ml/day). These results show that etodolac SR in doses of 600 mg and 1200 mg/day causes significantly less gastro-intestinal blood loss than does naproxen 500 mg twice daily.


A comparison of the efficacy of two ear drop preparations ('Audax' and 'Earex') in the softening and removal of impacted ear wax. Thirty-six patients with symptoms of impacted ear wax were recruited to an open, randomized, parallel group study of 'Audax' ear drops and 'Earex' ear drops. Patients had had their symptoms for several weeks and they were assessed on entry for the degree of impaction in each ear. After using the drops, morning and evening for 4 days, they were assessed on the fifth day for degree of impaction, ease of syringing, side-effects or discomfort, and the investigator's and patient's own global impression of efficacy of the ear drops. A trend was seen showing less impaction post-treatment in the 'Audax' group than in the 'Earex' group although the difference did not reach statistical significance. A significant difference was seen in favour of 'Audax' for the frequency and ease of syringing (p < 0.005). No patients in the 'Audax' group reported any side-effect or discomfort although 1 patient using 'Earex' reported slight irritation whilst another found the smell unacceptable. The results of the investigators' and patients' own global impression of efficacy were significantly in favour of 'Audax' ear drops (p < 0.01).


A single-blind, randomized study to compare the efficacy of two ear drop preparations ('Audax' and 'Cerumol') in the softening of ear wax. A parallel group, single-blind, randomized study was carried out in a general practice to compare the effectiveness and tolerability of two ear drop preparations ('Audax' and 'Cerumol') in the softening of ear wax in 50 adult patients with impacted or hardened ear wax. Assessments were made on entry of the amount, colour and consistency of the ear wax, symptoms, and objective hearing. Patients were then allocated at random to receive one or other preparation and instructed to use the drops, morning and evening, for 4 days after which they were reassessed. Details were recorded of any side-effects or discomfort caused by the study medication and both physician and patients were asked to give their overall opinion of treatment efficacy. Both treatments were shown to be effective in the softening of ear wax and were well tolerated, there being no significant difference between the two groups in these parameters. However, patients who had abnormal hearing before treatment had a significantly greater improvement in objective hearing after treatment with 'Audax' ear drops compared to those patients treated with 'Cerumol' ear drops. There were no between-treatment differences in either either the physician's or patient's overall assessments of effectiveness.


Amiodarone dosage in older patients with atrial fibrillation: an open, multi-centre study. An open, multi-centre study was carried out to assess the effectiveness and tolerability of amiodarone at a lower dose than routinely used in the clinical and symptomatic treatment of older patients with atrial fibrillation who were resistant to other therapy or in whom other therapy was either poorly tolerated or contraindicated. Suitable patients for dose adjustment were selected from a dosing survey population of those aged 60 years or over who were currently receiving amiodarone at a dosage of 200 mg or more daily. Periodic 100 mg dose reductions were made at 6-weekly intervals until there were signs of exacerbation or recurrence of the arrhythmia or until a daily dose of 100 mg was reached. Evaluation of the results from 167 patients showed that 156 (94%) were stabilized on a final dose of 100 mg daily and the remaining 11 (6%) on 200 mg daily. The majority of these patients were either in sinus rhythm or atrial fibrillation with a ventricular rate less than 100 beats per min. Twenty-one patients reported 22 adverse events. The majority of adverse events were not considered serious by the investigators, while approximately half were considered as 'probably unrelated' to amiodarone treatment. Six deaths were recorded during the treatment period but none was linked to amiodarone or 'probably related' to dose reduction.


The efficacy and tolerability of controlled-release dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hips. A double-blind, parallel group study was undertaken in general practice to compare the efficacy of and tolerability to controlled-release (CR) dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hip(s). Eighty-six patients were randomly allocated to receive either CR dihydrocodeine (60 mg) tablets (1 tablet twice daily to 2 tablets daily) or combination dextropropoxyphene (32.5 mg)/paracetamol (325 mg) tablets (2 tablets 3-times daily to 2 tablets 4-times daily) for a period of 2 weeks. Patients recorded in a diary card 4 times a day the severity of their pain and each morning whether or not they woke during the night due to pain in their hip(s). On entry to the study, after the first week's treatment and at the final visit another week later, the investigator assessed the patient's severity of pain on passive movement of the hip and also noted the severity of any volunteered symptoms or side-effects. After 2-weeks' treatment, pain on passive movement of the hip joint was statistically significantly less severe on CR dihydrocodeine than on dextropropoxyphene/paracetamol (p = 0.02). Nausea and vomiting were more pronounced in the dihydrocodeine than in the dextropropoxyphene/paracetamol group after the first week's treatment but by the end of the study there was no significant treatment difference in any of the volunteered side-effects. Patients on CR dihydrocodeine developed some constipation as expected and the dextropropoxyphene/paracetamol patients suffered from impaired concentration. More patients withdrew on CR dihydrocodeine than on dextropropoxyphene/paracetamol but these withdrawals tended to occur early in the trial just after initiating therapy. Tolerance in terms of withdrawals or side-effect profile did not appear to the dosage of each preparation administered. It is concluded that after 2-weeks' treatment CR dihydrocodeine provided superior analgesia to dextropropoxyphene/paracetamol with no difference in side-effects. Furthermore, CR dihydrocodeine has the advantage of twice rather than 3 or 4-times daily dosing.


Therapeutic synergism between hyaluronic acid and dexamethasone in the intra-articular treatment of osteoarthritis of the knee: a preliminary open study. In vitro studies on the effects of dexamethasone on human synovial cells have shown that with high concentrations of the steroid in the culture medium cellular activity was completely blocked whereas with low concentrations (10(-6)M), cellular density decreased but there was an increase in the synthesis of RNA, DNA, protein and hyaluronic acid. These data, coupled with clinical experience of using intra-articular hyaluronic acid to treat patients with osteoarthritis of the knee, prompted the investigators to carry out an open, randomized study of the use of very small doses of dexamethasone in association with hyaluronic acid in 40 osteoarthritic patients. Twenty patients received a weekly intra-articular injection of 20 mg sodium hyaluronate in 2 ml phosphate buffer for 5 weeks; the other 20 patients followed a similar treatment regimen, the only difference being the addition of 0.4 mg dexamethasone phosphate to the first injection. Clinical examination of the knee was made before each injection, 7 days after the fifth injection and 60 days after the start of the trial. Rating scale assessments were made at each visit of spontaneous pain, pain during the day, at night, weight bearing and whilst walking. The results showed that whilst a progressive decrease in all pain parameters was evident and persisted after the end of treatment in both patient groups, pain intensity decreased more rapidly and to lower levels in all but weight-bearing pain, as did improvement in joint mobility, in the combined treatment group. Local tolerance was good with both treatment regimens, with no untoward signs or symptoms at any time.(ABSTRACT TRUNCATED AT 250 WORDS)


Sulodexide and the microcirculatory component in microphlebopathies. A double-blind, placebo-controlled study was carried out in 36 patients, aged 30 to 50 years, to evaluate the effectiveness of oral sulodexide in the treatment of chronic venous insufficiency due to idiopathic varices. Patients were allocated at random to receive either oral sulodexide as 2 capsules (each containing 250 lipoproteinolipase releasing units) twice daily or 2 identical placebo capsules twice daily over a period of 45 days. Using strain gauge plethysmographic data, assessments were made of the microcirculatory effects of treatment by calculating the coefficient of capillary filtration from measurements made on both legs of each patient on entry and after 30 and 45 days of treatment. The coefficient is derived from the transmembranous flow values at the occlusive pressures of 60 and 40 mmHg, the difference between the two occlusive pressures examined and a corrective factor to calculate the capillary pressure based on the pressure in the venous circulation. Statistical analysis of the results showed that sulodexide produced a significant mean reduction from baseline values of the coefficient at both the 30 and 45 day examinations whereas the coefficient increased in the placebo group. The difference between the two groups was also statistically significant. These findings suggest that sulodexide has a positive influence on capillary permeability.


Perianal and intergluteal psoriasis.

Perianal and intergluteal psoriasis. Psoriasis of the perianal and intergluteal areas can cause pain and discomfort. Individualized therapeutic programs will reduce the morbidity. It is essential that optimal hygienic conditions be maintained in these regions to avoid itching and inflammation.


Mohs micrographic surgery for thin stage I malignant melanoma: rationale for a modern management strategy. Mohs micrographic surgery is presented as a rational surgical management approach for thin malignant melanoma. Advantages of the Mohs micrographic surgery fresh-tissue technique include tissue conservation, low local recurrence rates, and outpatient reconstruction. It is likely that in the future many physicians and patients will choose Mohs micrographic surgery for the surgical treatment of thin malignant melanoma.


Risk classification of life and health insurance applicants with atypical melanocytic hyperplasia or malignant melanoma in situ. Physicians may attempt to disguise malignant melanoma in situ from insurance companies by diagnosing atypical melanocytic hyperplasia instead. This study indicates that the insurance industry is not misled by atypical melanocytic hyperplasia and treats it equivalently to malignant melanoma in situ. In addition, physicians' failure to diagnose malignant melanoma in situ may result in underestimation of the incidence of malignant melanoma and may cause inadequate initial treatment and patient follow-up.


Photography for the early diagnosis of malignant melanoma in patients with atypical moles. Several articles have been published that carefully describe techniques for obtaining reliable photographic series of patients with the atypical mole syndrome. Four common methods of total body photography are described. Follow-up studies of the effectiveness of photodocumentation for patients with the atypical mole syndrome are reviewed.


The Texas peer education sun awareness project for children: primary prevention of malignant melanoma and nonmelanocytic skin cancers. Sixteen Texas elementary school students participated in a peer education sun awareness project. Upon completion of this program, student awareness about sun protection significantly improved. Peer education for elementary school students about skin cancer prevention may result in the primary prevention of future skin cancers.


Prevention of primary cutaneous malignant melanoma: increasing cure rate in the 1990's. This review focuses on the epidemiology, risk factors, early detection, and metastatic risk of thin primary cutaneous malignant melanoma. Primary prevention strategies and the results of screening programs and public education campaigns are discussed. Recent advances in the development of noninvasive diagnostic devices for primary cutaneous malignant melanoma are summarized.


Possible role of adjuvant therapy for thin malignant melanoma. Patients with thin (less than 0.75 mm) malignant melanoma generally have an excellent prognosis following adequate surgical resection. However, some patients will experience recurrent disease. Once features for a high risk of recurrence in patients with malignant melanoma can be reliably identified, adjuvant intervention will be offered. Two formidable challenges remain before this strategy is adopted: we cannot yet accurately predict the subgroup of patients with thin malignant melanoma who will experience disease progression and an effective, nontoxic adjuvant regimen for this subgroup is not currently available. Future prospects for the adjuvant management of thin malignant melanoma are reviewed.


Water-in-oil emollients as steroid-sparing adjunctive therapy in the treatment of psoriasis. An open label study of ninety-six patients with chronic plaque-type psoriasis demonstrated the efficacy of the addition of water-in-oil emollients to a topical corticosteroid regimen. Twice daily application of betamethasone dipropionate cream and once daily application of both betamethasone dipropionate cream and either a water-in-oil based moisturizing cream or lotion were equivalent in efficacy (p = 0.05). Once daily application of both betamethasone dipropionate cream and either a water-in-oil based cream or lotion was significantly better than once daily application of betamethasone dipropionate cream alone (p = 0.05). Water-in-oil emollients are useful in the therapy of chronic, plaque-type psoriasis and provide a steroid-sparing effect.


A seven-year follow-up study of 343 adults with bronchial asthma. A study of 343 urban adult outpatients with a history of bronchial asthma was initiated in 1981. Asthma was verified by a reversibility in airflow obstruction of at least 0.5 1 in forced expiratory volume (FEV1) (70%). The rest of the 343 patients was included because of diurnal variations of at least 100 l/min in peak expiratory flow (PEF) (22%), or because of a characteristic history of asthma (8%). In 1988, a follow-up study was performed. Two hundred-fourteen patients replied (80%), 100 women and 114 men. Fifty-four did not respond, but were known to be alive. Twenty-one had emigrated; of these, the fate of five was unknown. The mortality rate was significantly raised among the men (Standard mortality rate (SMR) = 1.55). In 19%, the cause of death was pulmonary. Seventeen percent were found dead. In these, no cause of death was obvious, and they may have died from an exacerbation of their pulmonary disease. One hundred and forty-four had non-allergic and 69 allergic asthma verified retrospectively by positive skin prick test in 1988. One was not tested and not classified. Seventy-five percent of the whole group were smokers. An annual decline of approximately 90 ml per year in FEV1 was found in both groups and was only partially explained by smoking and ageing. The remaining observed decline in lung function may be caused by asthma. Reversibility of 0.5 l in FEV1 was only maintained in the allergic group.(ABSTRACT TRUNCATED AT 250 WORDS)


Social context, social abstention, and problem recognition correlated with adult female urinary incontinence. The aim was to describe types of social contexts and abstention from social activity in women reporting urinary incontinence (UI); to identify social contexts and social abstention specifically associated with clinical UI subtypes; to relate clinical type of UI, social context and social abstention to individual problem perception. A self-administered postal questionnaire was sent to a random population sample comprising 3,114 women aged 30-59 in the Municipality of Aarhus, Denmark. RESPONDERS: A total of 2,631 women (84.5%) responded with a slight decrease in response rate by age. The present study group consists of 511 women (19.4% of the responders) who reported period prevalent UI for at least one of the years 1985-1987. Eighty-six percent of the study group members reported stress UI and 50% urge UI, so that 42% had both (mixed stress and urge UI) and 6% none of them (unspecific UI). Forty-six percent indicated the workplace and 66% the home as principal sites of UI occurrence. Thirty-one percent had experienced UI in specific situations such as during anxiety, sexual intercourse, or sleep. Nineteen percent had abstained from social activities, 17% from non-intimate social activity and 6% from sexual intercourse. Fourteen percent perceived UI as a social problem and 60% as a hygienic problem. Indicators of stress UI were associated with UI occurring at the work-place and during sexual intercourse which, in turn, both were correlates of abstention from non-intimate social activity. Urge UI was associated with episodes of UI occurring at home and in specific situations such as during anxiety and sleep. The experience of UI during sexual intercourse was related to all types of abstention. The perception of UI as a social or hygienic problem depended on the duration since first UI episode as well as social context and abstention. The everyday life consequences of UI are widespread and may cause serious relational problems for the individual. Stress UI manifests itself as a somatic condition leading to abstention from sport and other non-intimate social activities. Urge UI and the role of the experience of UI during sexual intercourse should be further investigated also from psycho-somatic and psycho-social coping points of view.


Thromboembolectomy in geriatric patients from long-stay wards. The results of arterial embolectomy with the Fogarty balloon catheter in patients over 70 years of age with acute ischaemia of the lower limbs were evaluated. Twenty-three geriatric patients from long-stay wards, median age 81 years, range 70-92, were compared with 45 independent patients, median age 81 years, range 70-91, living in their own homes. The period of ischaemic symptoms before admission was on average shorter for patients coming from long-stay wards, but the outcome was less successful. Recurrent occlusion during the first postoperative month took place in 12 patients (52%) from long-stay wards as compared to eight (18%) among independent patients (p < 0.01). The mortality was 35% and 18% respectively (p > 0.2). After six months, only 35% of patients from geriatric institutions were alive with a functional extremity as compared to 62% in the independent group (p > 0.01).


Hemophilus influenza infection of an implantable insulin-pump pocket. To increase awareness of adverse events associated with the use of implantable insulin pumps. A descriptive case report of a pump implant infection. This is a case report of one implanted insulin pump-pocket infection among a series of 15 patients. After exposure to a child with a respiratory infection on PID 30, V.L.C. (the patient) developed a fulminant pump-pocket infection. H. influenza was recovered from it. Despite aggressive antibiotic therapy, the infection could not be controlled. Insulin delivery ceased, and the pump was explanted. The pump-pocket infection rapidly resolved with pump removal, permitting later reimplantation. We have adopted the American Heart Association indications and antimicrobial prophylaxis regimens recommended for prevention of endocarditis in patients with prosthetic values for patients with implanted insulin pumps.


Microalbuminuria immunoassay based on antibodies covalently conjugated to Eupergit C-coated beads. To develop a reliable, simple, and sensitive assay for microalbuminuria, based on covalent attachment of anti-HSA to oxirane-bearing polymethylmethacrylate beads (Eupergit CB6200). Anti-HSA antibodies were coupled to CB6200 beads by reaction of their amino groups with the oxirane groups of the matrix. The capability of the beads to bind HSA from standard solutions or urine was evaluated and compared with the state of the art ELISA test. The new bead immunoassay is sensitive and linear in the range of 1-25 mg/L, which is considered the low microalbuminuria range. When HSA levels in urine were tested, the intra- and interassay CV values ranged between 2.7 and 3.9% and between 5.6 and 6.6%, respectively. The long-term storage stability of the antibodies covalently bound on the beads was higher than of the same antibodies adsorbed on ELISA plates. After 16 wk of storage, the CV was about 7.3% with the bead assay, compared with 14% obtained for the ELISA test under the same experimental conditions. A new procedure for microalbuminuria assay was developed, with Eupergit CB6200 beads as a solid support for covalent binding of the first antibody. Accuracy, sensitivity, reproducibility, and precision of the bead immunoassay were similar to those of commonly used immunoassays, as exemplified by the analysis of HSA in 53 clinical urine samples. The bead assay retains a low degree of variability over long storage periods, and the beads may be reapplied after a simple acid-washing procedure.


Family history of diabetes in relation to different types of obesity and change of obesity during 12-yr period. Results from prospective population study of women in Göteborg, Sweden. OBJECTIVE--To assess the relationship between family history and different types of obesity and change in obesity in a longitudinal population study. RESEARCH DESIGN AND METHODS--A longitudinal population study of 1462 randomly selected women (38-60 yr old) was conducted in Göteborg, Sweden, in 1968-69. The women were restudied after 12 yr. RESULTS--A family history of diabetes in mothers but not fathers showed, in univariate analysis, a significant positive association with obesity expressed as BMI. A family history of diabetes in the mothers was inversely related to body fat distribution expressed as WHR. No other association was observed between family history of diabetes and WHR. The association with BMI was independent of age, WHR, smoking habits, blood glucose, systolic blood pressure, serum cholesterol, serum triglycerides, maternal obesity, and the incidence of diabetes during the 12-yr follow-up period. Twelve years later, in 1980-1981, an independent association still existed between family history for diabetes and BMI measured at that examination, whereas there was no relationship with WHR. Women who had a family history of diabetes increased their BMI significantly more during the 12-yr follow-up compared with the women without a family history of diabetes, whereas there was no difference for the change of WHR. Family history of coronary heart disease and family history of cancer did not correlate to any kind of obesity. CONCLUSIONS--These findings indicate that family history of diabetes is related to overall obesity but not to abdominal adiposity per se.


Quality of life of pancreatic transplant recipients. To comprehensively assess and compare pancreas/kidney transplant recipients' quality of life. This quasi-experimental comparative study of 31 successful and 13 failed pancreas transplant recipients collected data from persons who had received pancreas and kidney transplants > or = 6 mo prior at a university tertiary care center. Physical and social function, symptoms, mental state, and sense of well-being of the recipients were assessed. Groups did not differ significantly regarding age, gender, marital status, onset or length of diabetes, comorbidity, type of prior dialysis, current kidney function, length of time since transplant, physical activity, symptom burden, emotional state, feelings of well-being, and present quality of life and health. A significant time by group interaction occurred for quality of life (P = 0.0013) and health (P = 0.0001). The successful group indicated that both quality of life and health were significantly better than in the past, and continued improvement was expected. The unsuccessful group did not have this perception. Members of the failed group were significantly more satisfied with their social support. The unsuccessful group's major concerns related to diabetes, not immunosuppression. Recipients of successful pancreas transplants perceived their improvement in health and quality of life to be significantly greater than the unsuccessful recipients.