Perioperative circulatory side effects of topical 5% phenylephrine for mydriasis

PURPOSE: To study the systemic effects of topically applied 5% phenylephrine. To investigate intraoperative injection of epinephrine in the anterior chamber as an alternative. METHOD: 75 patients undergoing cataract surgery were randomized into three groups. In group 1, the pupil was dilated using topically 5% phenylephrine and 1% cyclopentolate, the patients blocked the lacrimal drainage system themselves by digital compression. Group 2 received the same drops, digital compression was performed by one of the investigators. In Group 3, no preoperative phenylephrine was used--instead, epinephrine 1:25,000 was injected in the anterior chamber at the beginning of surgery. Retrobulbar anesthesia was performed in a short narcosis with ketamine and propofol. RESULTS: Mean preoperative blood pressure values were higher than the day before. They fell during narcosis, to increase significantly after the injection of the local anesthetics. At the beginning of surgery they were back to prenarcotic values. Intraoperative blood pressure remained stable. Preoperative day values were found two hours postop. There was no significant difference in the circulatory behavior between the three groups. For mydriasis, intraoperative intracameral epinephrine was not as effective as preoperative phenylephrine. CONCLUSION: In normotonic or medically treated arterial hypertensive patients, preoperative mydriasis using 5% phenylephrine is safe--proceeding the way described above. Compression of the lacrimal drainage system can be performed by the patients effectively. Intraoperative intracameral epinephrine does not replace preoperative phenylephrine.     

Significance of wet autoclave pretreatment in immunohistochemistry

Until recently the only way to rescue masked epitopes in routinely processed surgical pathological material was enzymatic digestion. The use of heat for antigen retrieval, first by microwave irradiation, represents an important breakthrough in immunohistochemistry. With the acceptance of microwave oven pretreatment, various modified techniques and alternative heating methods have also been proposed. Wet autoclave pretreatment for tissue proteolysis is a highly reliable alternative to the microwave antigen retrieval technique. It provides uniform heating of the slides, hence an even enhancement of staining intensity in a variety of formalin-sensitive antigens, and it also offers consistent interlaboratory results. The method has been introduced in routine diagnostic immunohistochemistry for the detection of estrogen-and progesterone receptors, L26-, Ki-67- and bcl-2 antigens and variable types of cytokeratins (1/5/10/11, 8, 13, 19). Experimentally, wet autoclaving can be used very successfully for the immunophenotyping of p53 and mdm2 expression, for the detection of adhesion molecules (CD44, integrins) and some anti-inflammatory molecules (annexins), among others. It has produced a substantial improvement in the visualisation of silver-stained nucleolar organizer regionsassociated proteins (AgNORs) in routine paraffin sections and along with modified silver staining and standardized AgNOR parameters assessed by image analysis. Wet autoclaving-based AgNOR staining has been proposed by a European multicentric study group as the standardized method for AgNOR analysis in archival material.     

Proliferative (mib1, mdm2) versus anti-proliferative (p53) markers in head and neck cancer. An Immunohistochemical study

Formalin fixed and paraffin embedded samples from 36 squamous cell carcinomas of the larynx and the oral cavity (pT₂N₀M₀, R₀) surrounded by non-tumorous mucosa were studied immunohistochemically using a panel of four different anti-p53 antibodies (CM1, PAbl801, D07, PAb240), a monoclonal anti-mdm2 antibody and MIB1, following wet autoclave antigen retrieval. P53 immunoreactivity was detected in 11/14 laryngeal and in 9/22 oral carcinomas. All p53 positive oral, and all but one laryngeal tumors revealed mdm2 positivity as well, whereas in p53 negative tumors 4/12 and 1/3 mdm2 immunopositive cases were demonstrated, respectively. MIB1 labeling indices of the tumors ranged between 18% – 64% in p53 positive cases, and 10% – 53% in p53 negative ones. The difference was not statistically significant. Close spatial coexpression of p53, mdm2 and MIB1 immunoreactivity was observed at the invasive front of the carcinomas and in the basal and suprabasal layers of the non-tumorous epithelium in all p53 positive cases. However, the MIB1 expression was similarly increased at the invasive margins in carcinomas lacking immunohistochemically detectable p53 alterations. Our results strongly suggest that p53 overexpression does not necessarily correspond to increased rate of proliferation, but rather to mdm2 overexpression and is largely dependent on the anatomical site in case of small and localized squamous cell carcinomas of the head and neck region.     

Decreased HER-2 tyrosine kinase expression in rectal mucosa of FAP patients following low-dose sulindac chemoprevention

As a part of the mechanisms of action in reversing FAP adenomas by the low-dose sulindac maintenance therapy (2 x 25 mg/patient per day), the extent of HER-2 proto-oncogene expression in the rectal mucosa seems to be of interest. Immunocytochemical analyses were performed in plasma and in rectal tissue of sulindac-treated FAP patients during an 18 months follow-up and compared with rectal tissue of patients with FAP, Crohn's disease, or rectal cancer or with healthy volunteers. HER-2 was significantly reduced and maintained in tissue under sulindac chemoprevention below base line levels of healthy individuals, but not in plasma. Therefore, a direct or indirect effect of sulindac as a tyrosine kinase inhibitor may be implicated. During NSAID treatment HER-2 protein expression as a prognostic tool seems to be of little clinical relevance.     

Endogenous activation of NMDA and non-NMDA glutamate receptors on respiratory neurones in cat medulla.

The aim of this study was to evaluate the involvement of dicarboxylic amino acid neurotransmission in the periodic discharges of respiratory neurones. Respiratory neurones of the ventral and dorsal respiratory groups in the medulla of the cat were subjected to iontophoretic applications of (1) N-methyl-D-aspartate (NMDA) and a blocker of the NMDA subtype of glutamate receptor, D-2-amino-7-phosphonoheptanoic acid (AP7) and (2) an agonist and an antagonist of the non-NMDA subtypes of receptor: quisqualate and 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. All five main types of respiratory neurones (all-, early- and late-inspiratory, transitional "off-switch", late expiratory) were excited by NMDA and quisqualate. Both agonists increased the peak firing rate but exerted different effects on the discharge pattern of respiratory neurones, within the respiratory cycle. Quisqualate induced discharges in the "silent" period of the neurone more readily than did NMDA which, in turn had a more pronounced effect during the burst period of the neurone. The effects of quisqualate and NMDA were suppressed by prior application of their selective antagonists, AP7 and DNQX. These antagonists decreased the spontaneous neuronal discharge of all cell types, throughout the entire firing phase, by a maximum of 24-63% with AP7 and by 30-50% with DNQX. The non-selective antagonist, gamma-D-glutamyl-glycine and the selective NMDA antagonists, CPP and MK-801, were also effective. It is concluded that respiratory neurones, of all types, within the medullary respiratory network are subjected to endogenous glutamate-like excitations, which may possibly shape the respiratory train of action potentials through the sequential activation of non-NMDA and NMDA subtypes of receptor.     

Das Tumorrezidiv am Hals nach papillarem Schilddrüsenkarzinom Eine statistische Analyse zur Rezidivwahrscheinlichkeit nach Radikaloperation

Zusammenfassung 308 Patienten mit papillärem Schilddrüsenkarzinom (82,6% des Gesamtkrankengutes, Operation 19522–1987), die postoperativ als tumorfrei eingestuft worden waren, wurden retrospektiv analysiert. Die Beobachtungszeit reicht von 1 Monat bis zu 29,4 Jahren (mediane Beobachtungszeit 4,58 Jahre). Bei 32 Patienten (10,4%) wurde ein Tumorrezidiv am Hals diagnostiziert (lokal und/oder regionär). 8 davon sind am Ende der Beobachtungszeit nicht tumorfrei, 6 sind am Tumor verstorben (tumorbedingte Todesrate 18,8%, relative Mortalität 66,7%, im Gesamtmaterial 2,9% bzw. 29,0%). Die kumulative Rezidivwahrscheinlichkeit beträgt 9,98% nach 5 und 16,98% nach 10 Jahren. Die statistische Analyse der Rezidivwahrscheinlichkeit erfolgte nur an Patienten, die mindestens 5 Jahre beobachtet wurden oder innerhalb dieses Zeitraumes verstarben. Als Einflußgrößen wurden neben Alter and Geschlecht, tumorstadium und histologische Kriterien des Tumors berücksichtigt. Als bestimmend für das Auftreten eines Rezidivs nach 5 Jahren Beobachtungszeit erweisen sich der Status der regiondren Lymphknoten, der Differenzierungsgrad des Tumors und das Geschlecht der Patienten. Zur Verbesserung der Rezidivrate wird eine abgestufte therapeutische Radikalität in Abhängigkeit von den Einflußgrößen empfohlen.

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Cervical tumour recurrence after papillary thyroid carcinoma. A statistical analysis on the recurrence after potentially curative surgery

Summary 308 cases of papillary thyroid carcinoma (82.6% of our patients operated on between 1952 and 1987) who had undergone potentially curative surgery were analysed postoperatively. The follow-up ranges from 1 month to 29.4 years (median 4.58 years). In 32 cases (10.4%) a cervical tumour recurrence (local recurrence and/or cervical lymph nodes) was found. 8 of these are not free of tumour at the end of the follow-up, 6 had died of thyroid carcinoma (case fatality rate 18.8%, mortality rate 66.7%, in the entire material 2.9% and 29.0% respectively). The cumulative recurrence rate is 9.98% after 5 years and 16.98% after 10 years. A statistical analysis of the probability of recurrence was carried out only for patients who could be followed at least 5 years or those who died within 5 years. Age, sex, stage of tumour and histological criteria were taken into account as statistical variables. The state of cervical lymph nodes, the differentiation of the tumour and the patients' sex turned out to be determining factors for tumour recurrence after 5 years. In order to improve the recurrence rate a differentiated surgical radicality, depending on the above mentioned variables, is recommended.

     

Treatment of severe sepsis in bone marrow transplant recipients with teicoplanin in combination with β-lactams and aminoglycosides

Summary We evaluated teicoplanin for suspected gram-positive infections after inadequate response to initial empiric beta-lactam and aminoglycoside combination therapy. All 20 patients included in this study received either an allogeneic (8 patients) or an autologous (12 patients) bone marrow transplant for acute myeloid leucaemia (AML), non-Hodgkin's-lymphoma (NHL, high grade) or other malignant diseases. All patients developing primary septicaemia of unknown origin (18 patients) or catheter-related septicaemia (2 patients) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g i.v., t.i.d.; netilmicin 400 mg once daily). All patients responded to therapy, 19 patients were clinically cured and one patient improved under therapy. The therapeutic regimen was well tolerated; only one adverse drug reaction was observed. We did not observe any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when our patients were compared to other bone marrow transplant patients (who did not receive this antimicrobial therapy). Our results suggest that teicoplanin is a potentially effective and well tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

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Teicoplanin in Kombination mit -Laktamen und Aminoglykosiden bei Knochenmarktransplantatempfängern mit schwerer Sepsis

Zusammenfassung Wir untersuchten Teicoplanin bei vermuteten grampositiven Infektionen nach ungenügendem Ansprechen auf die anfängliche Kombinationstherapie von -Laktam-Antibiotika und Aminoglykosiden. Alle 20 in dieser Studie erfaßten Patienten wurden entweder allogen (8 Patienten) oder autolog (12 Patienten) transplantiert mit folgenden Grundkrankheiten: akute myeloische Leukämie (AML), Non-Hodgkin-Lymphom (NHL) oder andere maligne Erkrankungen. Alle Patienten, die eine primäre Septikämie unbekannten Ursprungs entwickelten (18 Patienten) oder unter einer Katheter-bedingten Septikämie (2 Patienten) litten, wurden mit 400 mg Teicoplanin behandelt. Die Verabreichung von Teicoplanin erfolgte einmal täglich intravenös in Kombination mit einem Cephalosporin und einem Aminoglykosid (Ceftazidim 2 g i.v., 3 ×/die, Netilmicin 400 mg, 1 ×/die). Alle behandelten Patienten sprachen auf diese Therapie an. 19 Patienten wurden klinische geheilt, ein Patient besserte sich unter dieser Therapie. Die Kombinationstherapie wurde gut vertragen, unerwünschte Arzneimittelwirkungen traten während der Studie nicht auf. Wir beobachteten kein verzögertes Angehen des Knochenmarks oder eine Verlängerung der Thrombozytopenie unter dieser Behandlung im Vergleich zu anderen knochenmarktransplantierten Patienten, die diese antimikrobielle Behandlung nicht erhielten. Unsere Ergebnisse zeigen, daß Teicoplanin ein wirksames und gut verträgliches Antibiotikum für knochenmarktransplantierte Patienten ist, die primär nicht auf die Kombinationstherapie mit -Laktam-Antibiotika und Aminoglykosiden ansprechen.

     

Repair and mutagenesis of plasmid DNA modified by ultraviolet irradiation or N-acetoxy-N-2-acetylaminofluorene.

Plasmid DNA was modified in vitro to various extents with N-acetoxy-N-2-acetylaminofluorene or UV irradiation. The modified plasmid DNAs were then used to transform Escherichia coli strains having different repair capabilities. Both survival and mutagenesis frequencies of the plasmid were measured as a function of the number of lesions per plasmid molecule. The majority of N-2-acetylaminofluorene (AAF) adducts, like thymine dimers, were repaired by the excision (uvrA+-dependent) pathway. In rec+ strains, dose-dependent mutagenesis occurred in either AAF- or UV-modified plasmid DNA. This is in contrast with results obtained in recA- strains, in which only AAF adducts gave rise to a lower, but dose-dependent, mutagenesis frequency. In these recA- strains there was no UV mutagenesis. Unlike what is observed with phages, induction of the "SOS" functions by UV irradiation of the bacteria prior to transformation did not increase the survival or the mutagenesis of the plasmid.     

Swimming capacity of mice after prolonged treatment with psychostimulants

Swimming endurance and availability of metabolic substrates (blood glucose and nonesterified fatty acids [NEFA], liver and muscle glycogen, body fat) were studied in mice treated with 10 g/g methamphetamine/day for 6 weeks. At the end of the 6-week treatment, motor coordination of the methamphetamine-treated animals was much better than that of controls, and swimming capacity tended to increase. While swimming, mice treated with methamphetamine mobilized more glycogen from the hepatic stores and utilized glucose more effectively. Their NEFA levels in blood were higher than those of controls. There was no difference in the muscular glycogen content.