The value of cerebrospinal fluid α-synuclein and the tau/α-synuclein ratio for diagnosis of neurodegenerative disorders with Lewy pathology.

BACKGROUND AND PURPOSE: Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are three of the most common neurodegenerative disorders. Up to 20% of these patients have the wrong diagnosis, due to overlapping symptoms and shared pathologies. A cerebrospinal fluid (CSF) biomarker panel for AD is making its way into the clinic, but an equivalent panel for PD and DLB and for improved differential diagnoses is still lacking. Using well-defined, community-based cohorts and validated analytical methods, the diagnostic value of CSF total-α-synuclein (t-α-syn) alone and in combination with total tau (t-tau) in newly diagnosed patients with PD, DLB and AD was determined. METHODS: Cerebrospinal fluid concentrations of t-α-syn were assessed using our validated in-house enzyme-linked immunosorbent assay in 78 PD patients, 20 AD patients, 19 DLB patients and 32 controls. t-tau was measured using a commercial assay. Diagnostic performance was assessed by receiver operating characteristic curve analysis. RESULTS: Compared to controls (mean 517 pg/ml), significantly lower levels of CSF t-α-syn in patients with PD (434 pg/ml, 16% reduction, P = 0.036), DLB (398 pg/ml, 23% reduction, P = 0.009) and AD (383 pg/ml, 26% reduction, P = 0.014) were found. t-α-syn levels did not differ significantly between PD, DLB and AD. The t-tau/t-α-syn ratio showed an improved performance compared to the single markers. CONCLUSION: This is the first study to compare patients with PD, DLB and AD at the time of diagnosis. It was found that t-α-syn can contribute as a teammate with tau in a CSF biomarker panel for PD and DLB, and strengthen the existing biomarker panel for AD.

[Hyperbaric oxygen treatment for radiation reactions]. / Hyperbar oksygenbehandling ved strålereaksjoner.

BACKGROUND: A national hyperbaric centre was established in 1994 at Haukeland Hospital with responsibility for all hyperbaric oxygen (HBO) treatment in Norway. In hypoxic tissues with symptomatic radiation reactions, hyperbaric oxygen induces the formation of collagen and angiogenesis resulting in permanently improved local microcirculation. MATERIAL AND METHODS: 234 patients received elective HBO treatment at Haukeland Hospital in 1997 with a total of 4,048 treatments. All 47 patients treated for radiation reactions in the pelvic area in 1997 received a questionnaire 3-15 months after HBO therapy; 81% responded. RESULTS: Rectal bleeding and haematuria were reported as much improved in 61% and 55% respectively, while bladder incontinence was much improved in 46%. INTERPRETATION: This treatment modality may be an alternative in symptomatic radiation reactions of the urinary bladder and the bowel when conventional treatment has given unsatisfactory results.

Urinary tract infection. How has its management changed?

In patients with apparent urinary tract infection, clinical presentation and results of physical examination and a few simple laboratory studies can identify patients who need urine culture and/or imaging studies and can guide initial therapy. A wide variety of effective antibiotics are available for various causes, and local patterns of microbial sensitivity and cost-effectiveness help govern drug selection. Response to therapy governs further treatment and follow-up. Exclusion of complicated infection and particular risk factors permits simplified but effective management of symptomatic recurrent infections.

Internal medicine residency training at a crossroads.

The 1987 National Resident Matching Program resulted in a substantial number (18%) of vacant positions in internal medicine. Among the many factors inducing this change are: negative experiences in internal medicine training in medical school; lower compensation for cognitive versus procedural services; the shift of care from hospital to ambulatory settings inducing a decreased intensity of exposure; and the stringency and stress of internal medicine residencies. Various measures to address this problem are outlined.

Relationships between human blood groups, bacterial pathogens, and urinary tract infections.

Blood groups of 137 patients with acute pyelonephritis and chronic upper tract infection, cystitis, and asymptomatic bacteriuria were compared with those of a normal uninfected control population. In addition, the identified uropathogens were categorized according to the patient's blood group. There was a significant association between the diagnosis of chronic upper tract infection and blood group B as compared with controls (p = less than 0.05, chi 2). Analysis of the bacterial isolates showed that more patients with blood group B had infections with Pseudomonas sp., Klebsiella pneumoniae, and Proteus sp. than was expected; and fewer patients with blood group A had infections with Pseudomonas than predicted (p = less than 0.05, chi 2). There was an increased number of patients in blood group AB with infections caused by Escherichia coli and Klebsiella pneumoniae. These results suggest that an individual's blood group may be a significant factor in the host-response to bacterial invasion and influence the development of infection with certain gram-negative bacilli.

The treatment of urinary tract infections in women with diabetes mellitus.

Forty-five women with diabetes mellitus and urinary tract infections have been followed an average of 34 mo on treatment protocols based on localization of infection as determined by the presence or absence of antibody-coated bacteria (ACB). Treatment was usually, but not exclusively, trimethoprim-sulfamethoxazole. Two weeks of oral therapy was equally efficacious to 6 wk of treatment in asymptomatic women with antibody-coated bacteria (ACB)-positive infection in eradicating bacteriuria. Recurrences in all groups were predominantly reinfections with differing serotypes or species of microorganisms. The sustained remission rate (fractional extraction) after initial treatment was similar to other reported groups, but possibly less efficacious with recurrences. Suppressive therapy with trimethoprim-sulfamethoxazole for repeated recurrences effectively prevented infection but provided no posttreatment benefit. A high prevalence of underlying structural genitourinary tract abnormalities, usually detectable on pelvic examination, and which were not direct consequences of diabetes mellitus, were possible contributing factors to recurrent infection in this patient group. Progressive elevation in serum creatinine in seven patients with initial ACB-positive infections appeared to relate more closely to diabetic nephropathy rather than chronic pyelonephritis. ACB-positivity correlated well with elevated serum antibody titers and the presence of underlying anatomic abnormalities, but ACB categorization did not lead to improved therapeutic strategy or outcome and hence was of limited clinical usefulness.

Mannose-resistant hemagglutination and P receptor recognition of uropathogenic Escherichia coli isolated from adult patients.

Adhesions of 211 strains of uropathogenic Escherichia coli and 19 strains of normal fecal E. coli were characterized by patterns of agglutination with human erythrocytes, Saccharomyces cerevisiae, and horse erythrocytes coated with the P blood-group receptor (P). Mannose-resistant (MR) hemagglutination was significantly associated with P agglutination (P less than .001). E. coli expressing MR and/or P (MR/P) agglutinins concurrently with mannose-sensitive (MS) agglutinins predominated in all clinical categories. The highest percentage of E. coli demonstrating MR/P agglutinins, in the absence of MS agglutinins, was recovered from patients with acute pyelonephritis (35%) compared with percentages of patients with chronic pyelonephritis (13%), asymptomatic bacteriuria (16%), cystitis (11%), and normal fecal control E. coli (11%). Sixty-nine percent of E. coli isolates causing acute pyelonephritis agglutinated P-coated horse erythrocytes compared with only 11% of the fecal isolates. Strains expressing MR/P agglutinins (in the absence of MS agglutinins) isolated from patients with acute pyelonephritis, chronic pyelonephritis, and asymptomatic bacteriuria were significantly associated with the presence of antibody-coated bacteria in patients' urine sediments (P less than .010), an observation indicative of an immune response associated with bacterial invasion of host tissues.

Minimal-change lesion nephrotic syndrome with renal oncocytoma.

A renal mass was found in a 49-year-old man presenting with idiopathic nephrotic syndrome. The excised tumor was a well-encapsulated renal oncocytoma. Examination of the kidney revealed a minimal-change glomerular lesion and moderate arterionephrosclerosis. Nephrotic range proteinuria persisted through a postoperative course of prednisone therapy, but diminished and cleared within the subsequent two-year period. Renal function has remained stable and proteinuria has not recurred over a four-year follow-up. The clinical course suggests a previously unreported relationship between renal oncocytoma and minimal-change lesion nephrotic syndrome.

Antibody to kidney antigen in the urine of patients with urinary tract infections.

One hundred six urine specimens from 26 patients with acute and chronic pyelonephritis and cystitis were tested by radioimmunoassay to determine (1) whether antibody to normal human kidney antigen was present and (2) whether the presence or absence of this antibody correlated quantitatively with antibody to the patient's own infecting organism. Of the 106 urine specimens tested, 55 (52%) contained elevated antibody to human kidney antigen. For 80 (75%) of 106 urine specimens there was a correlation between the results of quantitative assays for antibody levels to kidney antigen and to the bacterial antigen. Indirect fluorescent antibody studies of thin sections of normal human kidneys and a patient's urine containing elevated levels of antibody to kidney antigen and to bacterial antigen demonstrated diffuse renal localization. Results indicate the occurrence of antibody to kidney antigen, particularly in urine specimens from patients with chronic pyelonephritis and from urine specimens containing elevated levels of antibody to bacterial antigen.

Bacteria-specific antibody in the urine of patients with acute pyelonephritis and cystitis.

Urine specimens from 65 adult patients with symptomatic urinary tract infections that involved 91 episodes of well-defined acute pyelonephritis or cystitis were tested for antibody-coated bacteria (ACB) by a fluorescent antibody assay, unbound bacteria-specific antibody by radioimmunoassay (RIA), and levels of total protein and IgG. Acute pyelonephritis was associated with positive tests for ACB (22 [69%] of 32), elevated levels of unbound antibody (28 [88%] of 32), and a mean RIA binding ratio of 9.4. Cystitis was associated with negative tests for ACB (56 [95%] of 59), low levels of antibody in urine (38 [64%] of 59), and a mean RIA binding ratio of 3.2. The results showed that a negative test for ACB may occur with elevated levels of unbound antibody in the urine because, although elevated, levels were still too low to result in detectable antibody coating of the bacteria. There was often, but not always, a correlation between RIA binding ratios and levels of urinary protein and IgG.

Immune response in urinary tract infection determined by radioimmunoassay and immunofluorescence: serum antibody levels against infecting bacterium and Enterobacteriaceae common antigen.

A solid-phase radioimmunoassay (RIA) procedure was compared with the indirect fluorescent antibody (IFA) test in a serological study of 76 female adults with urinary tract infections. Relative serum antibody activity was determined against patients' homologous infecting enterobacteria by RIA and IFA and against heterologous enterobacterial common antigen (Escherichia coli O14) by RIA. There was marked correlation between results of the IFA and RIA methods using the homologous system; 22 of 51 patients (43%) with pyelonephritis had significantly elevated serum antibody activity by both IFA (titers greater than or equal to 512) and RIA (binding ratio greater than or equal to 2.0) when compared with normal serum controls; three had significant antibody activity detectable by RIA only. Eighteen (72%) of 25 patients with pyelonephritis had RIA binding ratios of greater than or equal to 2.0 against their homologous bacterial isolates and the enterobacterial common antigen; an additional 6 patients had binding ratios of greater than or equal to 2.0 against the antigen only. All 25 patients with cystitis had low serum antibody levels by IFA and RIA when tested against their own isolate as well as enterobacterial common antigen. The RIA procedure was objective, quantitative, and less tedious to perform than IFA.

Urinary tract infections in patients with diabetes mellitus. Studies on antibody coating of bacteria.

The prevalence of urinary tract infection was determined in 333 patients attending a diabetes mellitus outpatient clinic during a one-year period. A total of 19% of the women and 2% of the men were found to have urinary tract infections. Antibody-coated bacteria, indicating parenchymal infection, were initially present in 43% of patients and rose to 79% within a mean pretreatment period of seven weeks. In those with recurrent infection following treatment, there were more reinfections than relapses, both in those with kidney infections (67%) and those with bladder infections (57%). The high prevalence of urinary tract infection among diabetic women and the evidence of rapid parenchymal involvement emphasizes the need for clinical awareness of the problem and clarification of its consequences.

Immunoglobulin levels and antibody-coated bacteria in urines from patients with urinary tract infections.

The presence of antibody-coated bacteria in urines from patients with urinary tract infections has previously been reported to correlate with renal infection as opposed to bladder infection. Urine specimens from 12 patients with pyelonephritis and 12 patients with cystitis were studied to determine whether the antibody coating the bacteria is associated with elevated urine levels of total protein or of particular classes of immunoglobulins. The classes of antibody bound to the infecting bacteria in urines from the patients with pyelonephritis were compared to the levels of unbound antibody in the urine. Each specimen was found to contain antibody-coated bacteria, but not all of the specimens had elevated levels of total protein or immunoglobulins. Thus, the occurrence of antibody-coated bacteria in pyelonephritis did not depend on marked elevations of total urinary protein or immunoglobulins. Studies of patients with cystitis showed that immunoglobulins and protein present in the urines, even in elevated quantities, did not react with the infecting bacteria in patients with bladder infections, as each of these patients had negative FA tests for antibody-coated bacteria.

Effect of hemodialysis and renal failure on serum and urine concentrations of cephapirin sodium.

Six patients undergoing chronic hemodialysis and 10 patients with chronic renal insufficiency hospitalized for nondialytic therapy received 1.0 g of cephapirin sodium by the intravenous route. The concentrations of cephapirin in arterial and venous plasma, dialysate, venous blood, and urine were measured during the ensuing 6 hr. The serum half-life of cephapirin was 105 to 108 min for the dialyzed patients and 95.9 min for the nondialyzed patients. Dialysis removed 22.8% of the administered dose. Nondialyzed patients excreted 19.5% of the administered dose in the urine. The concentration of cephapirin in the urine of all nondialyzed patients exceeded 50 mug/ml. The recovery of cephapirin in the urine collected for 6 hr after injection was from 34 to 770 mg (mean 195 mg). To maintain a concentration of cephapirin in the blood and urine which exceeds the minimal inhibitory concentration for most gram-positive and gram-negative microorganisms, nondialyzed patients should receive 15 to 18 mg of cephapirin per kg every 12 hr. Dialyzed patients should receive the same dose just prior to dialysis and every 12 hr thereafter.