Matrix metalloproteinases in the cerebrospinal fluid of patients with Lyme neuroborreliosis.

Neurologic manifestations of Lyme disease include meningitis, encephalopathy, and cranial and peripheral neuropathy. There are no sensitive markers for neuroborreliosis, and diagnosis is often based on clinical presentation and cerebrospinal fluid (CSF) abnormalities, including intrathecal antibody production. Matrix metalloproteinase (MMP) activity in CSF was compared in patients with neuroborreliosis, patients with diverse neurologic disorders, and healthy controls. The CSF of 17 of 18 healthy subjects and 33 of 37 patients with neurologic symptoms and normal CSF and imaging studies contained only MMP2. The CSF of several patients with neurologic disorders contained MMP2, MMP9, and gelatinolytic activity at 130 and 250 kDa. The 130-kDa MMP was found without the 92-kDa MMP9 in the CSF of 11 (79%) of 14 patients with neuroborreliosis and only 7 (6%) of 118 control patients (P < .001). This pattern of CSF gelatinase activity may be a useful marker for neuroborreliosis.

Analyses of 94 consecutive spinal cord injury patients using ASIA definition and modified Frankel score classification.

Serial neurological examinations were analysed on 94 consecutive spinal cord injury (SCI) patients admitted for rehabilitation to the Swiss Paraplegic Center at the Clinic Balgrist Zurich, Switzerland between 1987 and 1992. Patients' data were examined adopting ASIA and modified Frankel definitions in order to compare the two classifications in terms of consistency and prognostic value. The modified Frankel definition was subdivided into five categories (A, B, C, D and E). On admission (discharge) 43 (37) patients were classified as Frankel A, 23 (11) patients in group B, 26 (42) patients in group C, 2 (2) patients as Frankel D and 0 (2) patients in group E. A qualitative analysis of the results on the base of a maximal score of 100 points (A = 0, B = 25, C = 50, D = 75 and E = 100 points) suggested a mean score improvement from 21.5 (+/- 22.5) to 29.0 (+/- 26.3) or 7.5 (+/- 7.1), regarding all 94 patients during follow up (admission/discharge). The median improvement was one modified Frankel grade (A/B to B/C). No detailed assessments were yielded concerning motor and sensory functions. Using ASIA definition, a continuous numerical score of motor and sensory function was observed. Recovery during follow up was determined by detailed motor and sensory function. For all 94 patients (quadriplegics and tetraplegics), the average motor recovery according to the ASIA definition was 9.4 (+/- 9.6). The mean ASIA motor score improved from 52.2 (+/- 17.3) on admission to 61.6 (+/- 17.9) on discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

[Immunology and diagnostic test results in Lyme borreliosis]. / Immunologie und diagnostische Testverfahren bei der Lyme-Borreliose.

Borrelia burgdorferi (B. burgdorferi), the etiologic agent of Lyme borreliosis, shows both a variety of outer surface proteins with molecular weights between 16 and 100 kiloDalton (kD) and a 41 kD flagellar protein, which induce the immunologic response. Lipopolysaccharides, another constituent of the bacterial capsule, are responsible for the inflammatory reaction, constitutional symptoms and for the Jarisch-Herxheimer reaction. First a vigorous T-cell immune response develops, followed later by a more slowly evolving humoral B-cell immune response. The delayed onset of the humoral immune response may explain why antibodies against B. burgdorferi could not be detected early in the course of the disease. But the antibody titers increase with duration of the illness. The humoral response shows the usual pattern of IgM appearing first, followed by IgG and IgA. The IgM titer normalizes after recovery while the IgG titer could persist over years or decades. It is hardly possible to detect B. burgdorferi microscopically or by cultivation from blood, joint or cerebrospinal fluid. For routine diagnosis the fluorescent antibody staining and the ELISA methods are available which detect IgM or IgG antibodies against B. burgdorferi. But the sensitivity and specificity of these tests are still unsatisfactory. Other methods such as the ELISA-capture method, complement binding reaction, passive hemagglutination or the polymerase chain reaction are not yet established for routine purposes. Western blot analysis did not yield an essential diagnostic advantage but may be helpful in long term observation or in special cases. The measurement of the cellular immune response by T-cell proliferation tests remains controversial. First of all Lyme borreliosis has to be diagnosed by clinical findings and by elimination through differential diagnosis. An elevated antibody titer or a positive T-cell proliferation test may confirm the diagnosis but cannot prove it. Without consistent clinical findings they are of no practical significance. Some general guidelines for interpretation of laboratory results are given.

[Arrhythmia and swelling of all extremities]. / Herzrhythmusstörungen und Schwellungen an allen Extremitäten.

A 54-year-old patient complained about palpitations secondary to ventricular arrhythmias over a period of several years and severe fatigue for months. Later on arthralgia of the left shoulder and diffuse swelling of both hands and feet appeared. An elevated B. burgdorferi antibody titer and later on in the course the characteristic cutaneous aspect of acrodermatitis chronica atrophicans supported the diagnosis of Lyme-Borreliosis with affection of multiple organs. Under intravenous antibiotic treatment with 2 g Ceftriaxone per day for two weeks the symptoms regressed completely. The clinical findings occurring in this patient are discussed.

[Rheumatic fever. Its current status based on 4 cases]. / Das Rheumatische Fieber. Eine Standortbestimmung anhand von 4 Fällen.

We report on 4 patients with rheumatic fever hospitalized and investigated in our clinics within a 12 month period between 1990 and 1991. In each case a clinically non-severe sore throat preceded the outbreak of rheumatic fever. In three cases diagnosis was according to the revised Jones criteria. Polyarthritis was the only major symptom in these cases. One patient suffered from monarthritis. Minor symptoms were fever, arthralgia, elevated blood sedimentation rates and elevated values for CRP and for antistreptolysin O. The joint symptoms were treated with nonsteroidal drugs and subsided. One of the patients had a recurrence 9 months after the first attack even though correct secondary prophylaxis with a 4-weekly intramuscular regimen of 1.2 million units of benzathine penicillin was carried out. We discuss some epidemiological aspects and diagnostic difficulties resulting from a changing clinical pattern of the disease, and emphasize the need for streptococcal sore throat treatment and continuous secondary prophylaxis to prevent recurrences.

Perhexiline maleate-induced hepatitis.

We report on a case of perhexiline maleate-induced hepatitis secondary to a long-term administration of recommended daily dosages of 300 mg. The patient had a spectacular weight loss of 29 kg. He developed hepatitis, which subsided after drug withdrawal. Our electron-microscopic findings with the typical inclusion bodies and impaired hydroxylation capacity point to an underlying metabolic disorder as the pathogenetic mechanism.

[Paresthesias]. / Parästhesien.

A 23-year-old patient suddenly experienced paresthesia in both legs which progressively ascended to the region of the umbilicus and finally also occurred in all fingers. The physical examination revealed a decreased sensation for touch, discrimination and vibration in all paresthetical regions and on the stem even up to dermatome C5. A mild elevation of the protein content, a mononuclear pleocytosis and oligoclonal bands were found in the cerebrospinal fluid. Magnetic resonance imaging of the cervical spinal cord showed a hyperintensive lesion in the region of the posterior tract at C6. With respect to these findings and after exclusion of other neurological affections, multiple sclerosis was diagnosed. The symptoms subsided spontaneously within five weeks, and the patient was discharged without any complaints. The diagnostic accuracy of the various findings is discussed.

[Laboratory chemical analysis in ascites]. / Laborchemische Untersuchungen im Aszites.

Chemical analysis of ascitic fluid may be helpful in determining the underlying disease. We discuss the diagnostic accuracy of the common and newer chemical parameters (protein, LDH, lactate, glucose, cholesterol, triglycerides, phospholipids, fibronectin, albumin gradient [value of serum minus value of ascites], ferritin, tumor markers, immunomodulators, leukocytes, bacterial and cytologic examinations). We also review the pathogenesis and clinical findings of the most frequent ascites forms (benign hepatic, infective, malignant ascites, ascites associated with liver metastases or hepatocellular carcinoma, cardiac and pancreatic ascites) and the most important diagnosis criteria. In the malignant ascites a high cholesterol, a narrow albumin gradient or a high ferritin value have high diagnostic accuracy, but diagnosis is by the finding of malignant cells. For the diagnosis of infective ascites, bacteriology is mandatory even though the results are negative in most cases, particularly in spontaneous bacterial peritonitis where diagnosis has to be established clinically, by a low pH or by a high leukocyte count. Benign hepatic ascites is diagnosed by demonstrating an underlying chronic liver disease and laboratory examinations of the peritoneal fluid to exclude other causes. The laboratory tests in ascites associated with liver metastases or with hepatocellular carcinoma were similar to those in benign hepatic ascites and the two ascites forms must be separated by other clinical and technical findings. Pancreatic ascites can easily be distinguished from the other forms by the high amylase and lipase content.

Complementary directed modifications of nucleic acids and oncogene-directed mutagenesis in vivo.

High reactivity of the polyalkylating ss oligomers that were sense or antisense 30-200-mers containing sequences complementary to E1 oncogenes of simian adenovirus SA7 and one alkylating residue -CH2CH2N(C2H5OH) (CH2)3N(Ph-p-CH2OH)CH2CH2Cl per each 25 bases of oligomers was demonstrated in vitro by alkylation of ss DNA of recombinant M 13 mp8E1 and mp9E1 phages with inserted E1 sequences of adenovirus oncogene and then by followed complete and selective elimination of E1 sequences from recombinant ss DNA. Treatment of rodent cell cultures transformed by oncogenic SA7 with polyalkylating oligomers which are complementary to the long region of the minus or plus chains of E1 DNA of SA7 revealed a rather high extent of mutant cell clones formation. The cells formed were normalized; they had lost some properties of the transformed cells. Dividing cell clones inherited the new phenotypic properties: morphology, slower and more limited proliferation, and higher dependence on bovine serum growth factors. Some of the mutant cell DNAs demonstrated different mutations in the E1A sequences of the integrated proviral oncogene. There were exchanges G to C (leu to val) in the 525 and C to A (asp to tyr) in the 555 positions of E1A oncogene. Besides a deletions in the 1057-1477 E1A region or/and a mutation in the 1457-1477 of E1A were observed. Thus the inherited cell normalization observed is performed due to oncogene-directed mutagenesis in vivo.

[Persistent leg pain]. / Hartnäckige Beinschmerzen.

A 72 year old patient suddenly experienced severe lumbar pain irradiating into the right leg. Later on, weakness of the muscles thigh appeared. A thorough radiological investigation which showed degenerative alterations of the vertebral column did not supply an explanation. After a pathological titer against Borrelia burgdorferi was found in serum and radiculitis was detected on EMG, the diagnosis of Lyme-Borreliosis of the nervous system could be confirmed by analysis of the cerebrospinal fluid. Under intravenous antibiotic treatment with Ceftriaxone (2 to 4 g daily for three weeks) the symptoms regressed completely, and the pathological findings in the CSF regressed. The significance of some findings in CSF in relation to Borreliosis of the CNS.

[Abdominal actinomycosis--ileo-vaginal fistula as clinical manifestation. Case report and literature review]. / Abdominale Aktinomykose--ileo-vaginale Fistel als klinische Manifestation. Fallbericht und Literaturübersicht.

In 1985 sigmoid resection was performed in an 81-year-old patient with recurrent sigmoid diverticulitis. Due to adenomyosis uteri, hysterectomy was performed at the same time. Approximately one year after an uneventful recovery fetid leukorrhea occurred. Radiograms revealed a fistula between the terminal ileum and vagina. Adhesions between the terminal ileum and vaginal stump were surgically resolved and an ileum segment resection was performed. Postoperative recovery was uncomplicated and the patient has been symptom-free since. The histological findings of Actinomyces microorganisms, thread-like foreign material and detritus drew our attention to a rare instance of abdominal actinomycosis. Publications of purely historical interest dealing with therapeutic measures before the antibiotic era are not taken into consideration. The clinical picture, incidence and therapy of abdominal actinomycosis are described in the light of the literature.

[Diagnostic value of various laboratory parameters in acute pancreatitis]. / Diagnostischer Stellenwert verschiedener Laborparameter bei der akuten Pankreatitis.

In 427 samples of serum and urine, collected during their stay at hospital from 40 patients affected with acute pancreatitis, the sensitivity and the specifity of total amylase and lipase in serum, total amylase and pancreas isoamylase in urine, as well as the amylase-/creatinine clearance were determined. The pancreas isoamylase in serum was used as reference value. It appeared that the sensitivity of the lipase was next to that of the pancreas isoamylase in serum, even in limit ranges. Usually the lipase stayed pathological the longest and could therefore be used to identify in the best way even an easing-off pancreatitis. The diagnostic accuracy of the total amylase in serum and urine, of the pancreatic isoamylase in urine and of the amylase-/creatinine clearance was found to be obviously less reliable. The specifity of all examined tests was reduced in patients with renal insufficiency, liver disease, alcohol abuse and in patients with abdominal pains of non pancreatic origin. Concluding form our results and with regard to the expenditure of laboratory technique and to the time required by the methods of determination, we found that of all the examined parameters, the lipase was the most convenient for both emergency and routine diagnose of an acute pancreatitis.

[Semiquantitative lipase determination--a useful screening test for pancreatitis?]. / Die semiquantitative Bestimmung der Lipase--ein nützlicher Screeningtest für die Pankreatitis?

In 233 sera, taken from 112 patients and 20 healthy blood-donors, we have compared RapiTex-Lipase, a semi quantitative immunochemical latex test for the determination of the lipase, with the conventional quantitative method of determination in order to establish its diagnostical value as a screening test for acute pancreatitis. It appeared that, with a positive result of the test increased values of lipase were found in 98% of the cases, but that a negative result of the test did not exclude an increased lipase. The sensitivity of the test as to the quantitative determination of the lipase depended directly on the activity of the lipase and turned out to be acceptable at 88% only with values 4 X higher than the upper limit of the normal range. With values 5 X higher and more, it reached 100%. Even if the test, due to its very high level of discrimination, did not show a reaction in every case of unspecific extrapancreatic hyperlipasemia, its organ-specificity for the pancreas was reduced and came to 80 to 96% in patients with renal insufficiency, diseases of the liver, abuse of alcohol and in various non-pancreatic intra- or extra-abdominal affections. In 16/18 patients with acute pancreatitis the test used for screening turned out positive (sensitivity 89%), two patients with values between 2 and 4 X the upper limit of the norm had a negative test.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antibiotic therapy of Lyme borreliosis]. / Die antibiotische Therapie der Lyme-Borreliose.

There are still no definite patterns for antibiotic therapy of Lyme borreliosis. Recent studies have shown that ceftriaxone or tetracyclines are superior to the conventional penicillin. Against erythema chronica migrans (stage I) oral therapy, preferably with tetracycline, is sufficient. In cases with stage II symptoms, such as arthritis or neurological affections, high dose parenteral treatment, preferably with ceftriaxone, is recommended, although its effect on the neurologic symptoms is not yet proven. Carditis also calls for high dose parenteral administration of antibiotics, even though there are no published studies on this treatment as yet. Opinion is divided on the cutaneous symptoms such as acrodermatitis chronica atrophicans, morphea, lichen sclerosus et atrophicus (acute inflammatory stage) and lymphadenitis cutis benigna. Even if oral penicillin or tetracycline can cure existing symptoms, in the absence of longterm observations, it remains an open question whether oral treatment can prevent further complications or evolution to chronicity (stage III). For these clinical pictures there is also a tendency to give high dose parenteral antibiotics, and ceftriaxone is likely to win favour. In stage II Lyme borreliosis, autoimmune processes occur which scarcely respond to antibiotics any longer. Nevertheless, parenteral administration of high dose antibiotics remains sensible as a means of eradicating pathogens from the tissues, CSF or synovial fluids, and to avoid further complications. Evaluation of the therapeutic effects of corticosteroids or other immunosuppressive agents would require prospective studies.

[Abdominal actinomycosis. Ileo-vaginal fistula as a clinical manifestation. Case report and review of the literature]. / Abdominale Aktinomykose. Ileo-vaginale Fistel als klinische Manifestation. Fallbericht und Literaturübersicht.

In 1985, a resection of the sigmoid colon was performed on an 81-year-old patient with recurrent and stenotic sigmoid diverticulitis. Vaginal hysterectomy was carried out at the same time for adenomycosis. After an uneventful recovery, approximately 1 year later the patient was presented with fetial leucorrhoea. Radiologically, a fistula was apparent between the terminal ileum and the vagina. Adhesions between the terminal ileum and the vaginal stump were surgically resolved and an ileum segment resection performed. Postoperative recovery was smooth and the patient has remained symptom-free since then. The histological findings of actinomyces spores, thread-like foreign material and detritus drew out attention to the rare manifestation of abdominal actinomycosis. The relevant literature was compiled as completely as possible. Not included are publications of historical interest on therapeutic measures before the antibiotic era. The clinical picture, frequency and therapy of abdominal actinomycosis are discussed on the basis of this review of the literature.

[Diagnostic possibilities and limitations in Lyme borreliosis]. / Diagnostische Möglichkeiten und Grenzen bei der Lyme-Borreliose.

In Switzerland 5-35% of Ixodes ricinus ticks are infested with Borrelia burgdorferi (B.b.). There is a high risk of transmission of this infectious agent from any tick bite and 4-5% of affected subjects subsequently contract evident Lyme borreliosis. However, both tick bite and erythema chronicum migrans are unreliable diagnostic pointers as they are not usually found in the history of Lyme borreliosis patients. Similarly, an increased titer of antibodies against B.b. is not evidence of Lyme borreliosis, since this increased titer is found in some 10% of the healthy population. Finally, even a negative antibody titer does not rule out the diagnosis. The special problems of diagnosis are investigated in 7 patients with articular Lyme borreliosis and 9 patients with CNS symptoms. Articular Lyme borreliosis must be diagnosed by elimination even where there is an increased titer of antibodies against B.b., since neither the clinical picture, nor laboratory analysis of the synovial fluid, nor histologic and radiologic investigations show specific findings. There is a wide spectrum of neurologic symptoms. Diagnosis is easiest in cases with typical clinical findings (meningopolyneuritis), but in all other cases it is still by elimination. Among laboratory tests, calculation of an antibody index has proven helpful. Nevertheless, it is not always possible to differentiate Lyme borreliosis from encephalomyelitis disseminata. Antibiotic treatment has been tried in doubtful cases.

[Tumor markers and immunomodulator substances in ascites--their value as screening and diagnosis parameters]. / Tumormarker und immunmodulatorische Substanzen im Aszites--Ihre Wertigkeit als Screening und Diagnoseparameter.

The object of this study was to determine the known laboratory parameters, tumor markers and immunomodulatory substances in 69 ascites of various etiology, and to test their diagnostic significance. The usual parameters such as protein content, LDH ratio, albumin quotient and albumin gradient, fibronectin, cholesterol and cell count did not reliably differentiate the etiology in each particular case, although the mean values of the various groups differed significantly. Even cytological investigation was negative in 6 out of 29 malignant ascites. Neither were the immunomodulatory substances such as neopterin, beta 2-microglobulin and interleukin-2 receptors suitable for differentiation. In patients with carcinoma of the prostate the values of prostate-specific antigen were significantly increased in ascites. The best separation between benign hepatic or cardiac ascites and malignant ascites was provided by ferritin (sensitivity 97%, specificity 100%). The values in benign hepatic or cardiac ascites were lower than 150 ng/ml and those in malignant ascites higher than 170 ng/ml.

[Diagnostic value of a diagnostic strip for determining urinary amylase]. / Diagnostische Wertigkeit eines Teststreifens für die Urinamylasebestimmung.

The semiquantitative determination of amylase in urine with a stick-method has produced controversial results as to its diagnostical significance. In our study we compared the result of the Rapignost-test with the simultaneously measures activity of enzymes (total amylase, pancreatic isoamylase in serum and urine and lipase) in 323 samples of serum and urine taken from 32 patients affected with acute pancreatitis. On the 1st day of hospitalization Rapignost was positive in only 17 out of 32 cases. Both sensitivity and specificity of the test depended of the values referred to. Near range limits and in cases with slight or average increase of the enzymes, the correspondence of Rapignost results were unsatisfactory. We found a good correspondence in cases with normal low and excessively high values of the enzymes. On the whole, Rapignost showed the best correspondence with the pancreas isoamylase in urine. The result of Rapignost was also positive in 5 out of 15 cases with extrapancreatic increased urinary amylase, which confirms its lack of organ specificity. From case to case, the -, and + + test results of Rapignost did not lead to any conclusions as to the absolute values of the enzymes in serum and urine. Our results show that Rapignost does not offer enough safety either to confirm or to exclude an acute pancreatitis, and especially it should not be used as a screening test in emergency diagnostics. The determination of the enzyme, in particular in serum, can not be eluded.

[Upper abdominal pain]. / Oberbauchschmerzen.

We report a female patient in whom the false diagnosis of acute pancreatitis was made, based on intensive epigastric pain and a four fold increase of amylase. The normal values for lipase and decreased values for the urinary amylase were suggestive of a constellation of macroamylasemia. Further investigations revealed a fresh ulcer in the bulbus duodeni as cause of the epigastric pain. With a therapy of cimetidine and antacids painlessness could be achieved within few days.

[Extrapancreatic hyperamylasemia. Diagnostic value of isoamylase and lipase determination]. / Extrapankreatische Hyperamylasämie. Diagnostische Wertigkeit der Isoamylasen- und der Lipasebestimmung.

The P- and S-isoamylase and lipase of 72 patients with extrapancreatic hyperamylasemia were determined and their diagnostic value checked to rule out a pancreatic origin. The hyperenzymemia was generally slight although extremely high values were observed in isolated cases. The increased serum amylase results were more often caused by P-, rather than S-isoamylase, while in 28% of cases lipase was also increased. In lung diseases, anorexia and disorders of the head organs only S-isoamylase was pathologically increased while P-isoamylase and lipase remained normal. In other entities such as liver, stomach and intestinal diseases, functional disorders, acidosis, infections, etc., the isoenzymes and lipase showed a variable tendency to increase. Thus, extrapancreatic hyperamylasemia could not always be identified by detection of isoamylases or with the aid of lipase determinations. Overall, however, lipase more often remained in the normal range and was therefore more useful than determination of the isoamylases in differentiating hyperenzymemia.