Esters of substituted benzoic acids as anti-thrombotic agents

Aliphatic esters of protocatechuic acid (PA,1), vanillic acid (VA,9) and gallic acid (GA,18) were prepared and their anti-thrombotic effects were evaluated in the mouse model of thrombosis. The aliphatic groups included methyl, ethyl,n-propyl,i-propyl,n-butyl,i-butyl,n-amyl and cyclohexyl.n-Amyl ester of PA (7), i-propyl and cyclohexyl esters of VA (13 and17 respectively) and ethyl ester of GA (20) treatment significantly lowered the death rate and increased the recovery from paralysis due to the thrombotic challenge. From the limited analogs available, it was tentatively concluded that the structural conformation, where carboxy oxygen (=O or-O^?) of the carboxyl group (COOH) at C₁ and the oxygen function at C₃ (either OH or OCH₃) are closely situated, is favorable for the esters of PA, VA and GA to be more antithrombotic.     

Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury.

A bilayer artificial skin composed of a temporary Silastic epidermis and a porous collagen-chondroitn 6-sulfate fibrillar dermis, which is not removed, has been used to physiologically close up to 60% of the body surface following prompt excision of burn wounds in ten patients whose total burn size covered 50--95% body surface area (BSA). Following grafting, the dermal portion is populated with fibroblasts and vessels from the wound bed. The anatomic structure of the artificial dermis resembles normal dermis and serves as a template for the synthesis of new connective tissue and the formation of a "neodermis," while it is slowly biodegraded. This artificial skin has physiologically closed excised burn wounds for periods of time up to 46 days before the Silastic epidermis was removed. At the time of election when donor sites are ready for reharvesting, the Silastic epidermis is removed from the vascularized artificial dermis and replaced with 0.004 autoepidermal graft in sheet or meshed form. Clinical and histologic experience in a relatively short follow-up period (2--16 months) indicates that "neodermis" retains some of the anatomic characteristics and behavior of normal dermis, thus promising improvement in the functional and cosmetic results, as well as providing physiologic function as a skin substitute. The artificial skin is easily sterilized and stored at room temperature, capable of large scale production, and immediately available for grafting, indicating its potential for easy and relatively economic use in the burn patient.     

Distortion-product and click-evoked otoacoustic emissions in healthy newborns.

Distortion-product otoacoustic emissions (DPOEs) are believed to provide frequency-specific information about cochlear function. The DPOEs have been reported in the adult population but have not been reported previously in the neonatal population. We recorded DPOEs from a group of healthy full-term newborn human subjects (35 ears) to establish the characteristics of these emissions in the newborn population. To our knowledge, this is the first study of DPOEs in newborns. The "DPOE audiograms" from the newborns tested revealed characteristics qualitatively similar to those seen in adults with normal hearing. This study demonstrates the feasibility of DPOE measurements among newborns and provides a normal baseline for this age group, thus fulfilling a necessary step toward the development of an objective, noninvasive frequency-specific test of cochlear function. Click-evoked otoacoustic emissions were also recorded from the newborn population and compared with click-evoked otoacoustic emissions from adults. The spectrum of the click-evoked emissions was variable and individualistic, similar to findings previously reported in adult subjects. The click-evoked otoacoustic emissions of the newborns had a higher overall level and contained stronger high-frequency (4.5 to 6 kHz) spectral components than those of the adults. We also found that the low-frequency components of the click stimulus spectrum were attenuated in the neonatal ears exhibiting a high-pass slope below about 2.5 kHz, whereas the stimulus spectrum was nearly flat in this frequency region in adult ears.     

Astrocytoma presenting with vasculitis.

A cerebral astrocytoma which had remained quiescent possibly for 12 years, presented with blackout, vasculitis and a lupus-like (L-E like) syndrome. The association between tumours and "L-E like" syndromes is reviewed briefly.     

Which programmable functions of pacemakers are available, and what is their clinical relevance?

Microprocessors incorporated into cardiac pacemakers enable a substantial number of programmable functions (Table 1), the clinical relevance of which is the subject of this overview. Stimulation mode: The mode of operation can be chosen as fixed-rate, triggered and inhibited stimulation. Rate: Rate-programmability enables optimal setting with respect to electrophysiologic and hemodynamic considerations. Impulse amplitude and width: With programmable impulse amplitude and width excessive stimulation energy can be avoided and the duration of the aggregate prolonged. In some pacemakers, the output current can be chosen as "unregulated or regulated" whereby with regulated current the magnitude of the output impulse remains constant until the battery is depleted. Functional impairment of the pacemaker through threshold elevation or muscle stimulation can be eliminated by reprogramming of the impulse amplitude or width. Sensitivity: Programmability of the input sensitivity enables noninvasive counteraction of detection disturbances (as undersensing especially with low-amplitude atrial signals and oversensing of interference signals with subsequent pacemaker inhibition; Figure 1). A new option, automatic sensitivity setting, regulates the registration of cardiac activity at the atrial and/or ventricular level within a safety margin of 2:1; even though somewhat problematic, undersensing is rare. Electrode polarity: Depending on the clinical situation, the unipolar or bipolar electrode may offer advantages. The programmability of the electrode polarity accordingly represents a clinically-relevant new development which provides a favourable combination of bipolar detection and unipolar stimulation. Some modern dual-chamber systems enable separate programming of the atrial and ventricular electrode configurations. Hysteresis: For single-chamber systems and, more recently, AV-sequential pacemakers, hysteresis is optionally available, that is, a programmable prolongation of the basic interval after detection of a spontaneous cardiac event. With further refinement, the so-called search hysteresis prolongs the stimulation interval after a constant number of continuous stimulation cycles to a programmed hysteresis interval to allow spontaneous cardiac activity; if this is detected during the prolonged interval, the pacemaker is inhibited, otherwise the pacemaker stimulates at the set rate. An AV-interval hysteresis - to date only available in one pacemaker system - prolongs the duration of the AV-interval in the following cycles to a programmed interval, if, within the programmed AV-interval, spontaneous AV-conduction is detected. Additionally, after a defined number of AV-cycles an AV-interval prolongation is chosen to assess the possibility of physiologic AV-conduction. AV-interval: Modern AV-sequential pacemakers incorporate integration of the differential and rate-adaptive AV-interval.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hans Bergers Entdeckung des Elektrenkephalogramms und seine ersten Befunde 1924–1931

Zusammenfassung Zum 50. Jahr seiner ersten EEG-Publikation werden Bergers frühe EEG-Ableitungen von 1924–1931 aus dem Freiburger Berger-Archiv besprochen und illustriert.Drei Arten der frühen Untersuchungen Bergers werden im einzelnen besprochen: 1. Saitengalvanometerableitungen von 1924–1926 vorwiegend bei Patienten mit Knochenlücken, die bei diesen Patienten mit Hirnerkrankungen verlangsamte Grundrhythmen von 6–8/s zeigten. 2. Die direkte Ableitung von Rinde und Mark eines trepanierten Patienten 1930, die den Ursprung des EEG in der Hirnrinde klar nachwies. 3. Typische unpublizierte EEG-Befunde bei Epilepsien 1930–1931 im Anfallsintervall und bei Absencen werden abgebildet.In Bergers ersten 6 Mitteilungen, die alle wesentlichen EEG-Befunde bei Hirnerkrankungen und die EEG-Veränderungen bei Aufmerksamkeit, Schlaf und Narkose beschreiben, fehlen diese in Abb. 4–7 illustrierten EEG-Kurven von Krampfpotentialen. Berger hat seine Epilepsie-Befunde zunächst zurückgehalten, weil er Bewegungsartefakte befürchtete und seine Kontrollen ähnliche Formen bei Lid- und Stirnbewegungen zeigten (Abb. 4a, b).Erst 1933, nachdem andere Untersuchungen über experimentelle Epilepsie bei Tieren das Vorkommen abnorm großer Krampfentladungen der Hirnrinde nachwiesen, wagte Berger in der 7. Mitteilung EEG-Ausschnitte eines Petit-mal-Anfalls und fokaler Anfälle bei Paralyse zu publizieren. In einer Synopsis des EEG 1938 illustrierte Berger den Beginn einer Absence mit großen 3/s-Wellen, die den von Gibbs und Lennox 1934 als spike and wave bezeichneten Formen entsprachen. Berger deutete 1933 die abnormen steilen und unregelmäßigen Hirnpotentialformen als Afallsbereitschaft des Großhirns und die Perioden großer 3/s-Wellen als corticale Begleiterscheinungen der Absencen.Die Arbeit wurde vom Sonderforschungsbereich Hirnforschung und Sinnesphysiologie (SFB 70) unterstützt.     

Tumor-M2-Pyruvatkinase beim Nierenzellkarzinom Untersuchungen im Plasma von Patienten

Tumor cell metabolism is characterized by a high rate of aerobic glycolysis. The metabolic differences require changes in glycolytic enzyme activities and isoenzyme patterns. The inactive form of the M2 pyruvate kinase (Tu M2-PK) is specifically expressed in tumor cells and has been detected immunohistochemically in tumor tissue but also in peripheral blood of patients with different malignant tumors. In this study, Tu M2-PK in the plasma of patients with renal cell carcinoma (RCC) was compared with healthy volunteers. Tu M2-PK was quantified with a commercially available enzyme linked immunosorbent assay (ELISA) kit. Using the ELISA kit, plasma probes of 57 healthy individuals were compared to 63 patients with RCC (51 patients with non-metastatic RCC, 12 patients with metastatic RCC). Statistical analysis was performed with the non-parametric ANOVA test according to Kruskal-Wallis. In patients with renal cell carcinoma, Tu M2-PK was significantly higher than in healthy volunteers. For organ-defined, non-metastatic tumors, sensitivity was only 27.5%, if the 95% reference values of the control group were used for discrimination. The differences were more pronounced in patients with metastatic disease. Tu M2-PK was significantly enhanced compared to healthy controls, but also to the group with non-metastatic disease, the sensitivity was 66.7%. Our data show that Tu M2-PK has no impact as an unspecific marker for the diagnosis of renal cell carcinoma. This is especially relevant to organ-defined, non-metastatic RCC. In advanced metastatic disease, a potential importance as a parameter for treatment control in palliative therapeutic approaches can be assumed, and warrants further investigations.     

Molekulare Formen des prostataspezifischen Antigens und des humanen Kallikreins 2 als mögliche Indikatoren in der Prostatakarzinomdiagnostik

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and in the monitoring of patients with this diagnosis. Molecular forms of PSA and human kallikrein 2 (hK2) have been used to discriminate between benign prostatic hyperplasia and prostate cancer, as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to alpha 1-antichymotrypsin (ACT-PSA), and complexed PSA (cPSA) is given together with our own results. The ratio of fPSA/tPSA has been shown to improve both sensitivity and specificity of prostate cancer diagnosis based on tPSA measurements. The number of biopsies can be reduced in the total PSA range of 4-10 micrograms/l. Furthermore, carcinomas can be detected in patients with PSA values less than 4 micrograms/l. ACT-PSA or cPSA alone and the calculated derivatives are not superior in their discriminatory power compared with tPSA and the fPSA% value. The other molecular PSA forms and hK2 are still objects of research and their diagnostic significance needs to be evaluated in more extensive clinical trials.     

Clinical characteristics of patients with thyrotropin-secreting pituitary adenoma.

BACKGROUND AND PURPOSE: Thyroid-stimulating hormone (thyrotropin, TSH)-secreting pituitary adenoma is a very rare cause of hyperthyroidism. Diagnosis of this condition is often delayed due to lack of availability of TSH radioimmunoassay (RIA), the failure to recognize the utility of RIA and the incorrect attribution of the condition to other causes of thyrotoxicosis. This retrospective study analyzed the clinical characteristics of patients with this disorder treated from 1991 to 2002. METHODS: Seven patients (6 females, 1 male; mean age, 48 years; range, 33 to 72 years) with a diagnosis of TSHsecreting pituitary adenoma based on detectable TSH levels with high serum free thyroid hormone or triiodothyronine concentrations and pituitary lesions found on neuroimaging were included in this study. Patient records including clinical features, endocrine studies, immunohistochemistry studies, and response to treatment were reviewed. RESULTS: All 7 patients had hyperthyroidism, elevated free thyroxine or triiodothyronine levels, and unsuppressed levels of TSH. Imaging studies demonstrated a pituitary mass or lesion in all patients. Six patients had macroadenomas and 1 patient had a microadenoma. One of the patients had coexisting acromegalic features and hypersecretion of growth hormone was diagnosed. All of the patients had been treated with thionamides or thyroidectomy for presumed primary hyperthyroidism. Serum alpha-subunit level was uncharacteristically normal in 2 patients and elevated in 1 patient. Alpha-subunit/TSH molar ratios were elevated in 3 patients. Five patients underwent transsphenoidal adenomectomy but only one of them remained well-controlled at follow-up. Three patients received administration of somatostatin analogs and they achieved normalization of serum TSH and free thyroid hormones during the period of therapy. CONCLUSIONS: TSH immunoassay has an important role in the evaluation of hyperthyroid patients to determine the presence of inappropriate secretion. TSH-secreting pituitary adenoma exhibits heterogeneity in clinical presentation, hormonal expression and therapeutic response.     

The attitudes of cancer patients and their families toward the disclosure of terminal illness.

PURPOSE:To ascertain the attitude of cancer patients and their families toward disclosure of terminal illness to the patient. PATIENTS AND METHODS: We constructed a questionnaire that included demographic and clinical information and delivered it to 758 consecutive individuals (433 cancer patients and 325 families that have a relative with cancer) at seven university hospitals and one national cancer center in Korea. RESULTS: 380 cancer patients and one member from each of 281 families that have a relative with cancer completed the questionnaire. Cancer patients were more likely than family members to believe that patients should be informed of the terminal illness (96.1% v 76.9%; P <.001). Fifty percent of the family members and 78.3% of the patients thought that the doctor in charge should be the one who informs the patient. Additionally, 71.7% of the patients and 43.6% of the family members thought that patients should be informed immediately after the diagnosis. Stepwise multiple logistic regression indicated that the patient group was more likely than the family group to want the patient to be informed of the terminal illness (odds ratio [OR], 9.76; 95% CI, 4.31 to 22.14), by the doctor (OR, 4.00; 95% CI, 2.61 to 6.11), and immediately after the diagnosis (OR, 3.64; 95% CI, 2.45 to 5.41). CONCLUSION: Our findings indicated that most cancer patients want to be informed if their illness is terminal, and physicians should realize that the patient and the family unit may differ in their attitude toward such a disclosure. Our results also reflect the importance of how information is given to the patient.