Fulminant liver failure induced by hepatosplenic alphabeta T-cell lymphoma.

Since survival rates of fulminant liver failure are low, early consideration of liver transplantation in patients developing hepatic encephalopathy due to progressive liver failure is mandatory. Rapid diagnostic work-up is necessary to identify the underlying disease and to rule out contraindications to liver transplantation. We report the case of a 35-year-old patient presenting with fulminant hepatitis and a four-week history of biopsy-proven autoimmune hepatitis. Despite high-dose steroid-treatment liver function progressively worsened and hepatic encephalopathy rapidly developed. Histopathologic evaluation of a liver biopsy specimen revealed necrotizing hepatitis and rare atypical lymphocytes. Surgical biopsy specimens confirmed the suspicion of an aggressive hepatosplenic alphabeta T-cell lymphoma which represents a contraindication to liver transplantation.

Lesser curvature lymph node metastases with esophageal squamous cell carcinoma: implications for gastroplasty.

The creation of a gastric tube after subtotal esophagectomy includes resection of the lesser curvature and abdominal lymph nodes. The fundus rotation gastroplasty has been recently proposed as an alternative technique of reconstruction that preserves the vascular arcade of the lesser curvature. This study investigates the number of resected and metastatic lymph nodes associated with abdominal lymphadenectomy to assess the oncologic radicality of fundus rotation gastroplasty. In this prospective clinical trial a two-field lymphadenectomy was performed in 39 patients with squamous cell carcinoma of the esophagus. The abdominal lymphadenectomy included partial resection of compartment I (lymph node groups 1, 2, and 3) and compartment II (lymph node groups 7, 8, 9, and 11). A meticulous workup of the specimen allowed an exact classification of specific lymph node groups and their metastatic status. After two-field lymphadenectomy a total of 1170 lymph nodes (average 30.0) including 690 abdominal lymph nodes with an average of 17.7 per patient were resected. Metastatic disease was found in 27 of 39 patients (pN1 69.2%), with metastatic growth in 116 of 867 resected lymph nodes (13.4%). Of the 27 pN1 patients, 21 had abdominal lymph node metastases. Metastatic lymph nodes at the lesser curvature (groups 1, 3, and 7) were detected in 11.7%, 16.7%, and 29.7% of the resected lymph nodes, respectively. Of the 21 patients (85.7%) with abdominal lymph node metastases, 18 had positive lymph nodes at the lesser curvature. Squamous cell carcinoma of the esophagus is associated with a high rate of lymph node metastases at the lesser curvature and the left gastric artery. Therefore preservation of the lesser curvature and the left gastric artery for gastroplasty reduces the radicality regarding lymph node metastases.

[Volume selective 31P NMR spectroscopy for differentiation of graph rejection and acute tubular necrosis after kidney transplantation]. / Volumenselektive 31P NMR-Spektroskopie zur Differenzierung von Abstossungsrektionen und akuter Tubulusnektrose nach Nierentransplantation.

Volume-selective 31P-MR spectra were obtained from 37 patients using a whole-body MR scanner in combination with surface coils and a modified ISIS sequence. The quantitative evaluation took place by line fitting to the signal in the time domain using a non-linear procedure. The following signal intensities were determined: PME, PDE, Pi, gamma-, alpha-, beta-ATP and pH. 1024 excitations were averaged to achieve an adequate signal-to-noise ratio (10.0 +/- 3.3), measurements lasting 34 minutes on average. The mean measured volume was 174 +/- 52.4 ml. Contamination by muscle tissue could be excluded based on the absence of phosphocreatinine signal in the spectra. Contamination by fatty tissue was excluded by visualisation. A reduction in the value of the Pi/alpha-ATP ratio as a function of time was observed due to the regeneration process following reperfusion injury. In transplant rejection (n = 7) a significant rise in Pi/alpha-ATP ratio was seen compared to the control group (n = 20) (0.4 +/- 0.16 vs. 0.22 +/- 0.11, p < 0.01), the calculated difference in pH was significant as well. In cases of acute tubular necrosis a reduced value fore the PME/PDE ratio was observed (0.65 +/- 0.1 vs. 0.96 +/- 0.5, p < 0.04). Acute tubular necrosis could be differentiated from rejection by difference in pH (6.93 +/- 0.1 vs. 7.14 +/- 0.19, p < 0.04).

Formation of DNA adducts by cyproterone acetate and some structural analogues in primary cultures of human hepatocytes.

Recently, we have shown that the therapeutically-used progestin and antiandrogen cyproterone acetate (CPA) causes the formation of high levels of DNA adducts in rat hepatocytes and rat liver [J. Topinka, U. Andrae, L.R. Schwarz, T. Wolff, Cyproterone acetate generates DNA adducts in rat liver and in primary rat hepatocyte cultures, Carcinogenesis 14 (1993) 423-427: J. Topinka, B. Binkova, L.R. Schwarz, T. Wolff, Cyproterone acetate is an integral part of hepatic DNA adducts induced by this steroidal drug, Carcinogenesis 17 (1996) 167-169; S. Werner, J. Topinka, T. Wolff, L.R. Schwarz, Accumulation and persistence of DNA adducts of the synthetic steroid cyproterone acetate in rat liver, Carcinogenesis 16 (1995) 2369-2372; J. Topinka, B. Binkova, H.K. Zhu, U. Andrae, I. Neumann, L.R. Schwarz, S. Werner, T. Wolff, DNA damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver, Carcinogenesis 16 (1995) 1483-1487]. Its structural analogues, chlormadinone acetate (CMA) and megestrol acetate (MGA) were much less active in this respect [J. Topinka, B. Binkova, H.K. Zhu, U. Andrae, I. Neumann, L.R. Schwarz, S. Werner, T. Wolff, DNA damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver, Carcinogenesis 16 (1995) 1483-1487]. In the present study we addressed the question whether these compounds and two further analogues, medroxyprogesterone acetate (MPA) and progesterone, induce the formation of DNA adducts in primary cultures of human hepatocytes. Incubation of CPA with human hepatocytes from two male and four female donors induced the formation of significant levels of CPA-DNA adducts detectable by 32P-postlabeling. The by far most prevalent DNA adduct is most likely identical with adduct A formed in CPA-treated rats. DNA binding was found even at 0.03 microM CPA, the lowest concentration used. The maximum effect occurred at about 10 microM in 5 of the 6 cell preparations. At this concentration 480 and 2690 adducts x 10(-9) nucleotides were detected in hepatocytes of the two male donors and 1072, 816, 613 and 659 adducts x 10(-9) nucleotides in the hepatocytes of the four female donors after an exposure of 6 h with CPA. Extending the incubation time to 20 h resulted in a roughly three-fold higher binding. CMA and MGA were assayed in two of the liver cell preparations from the female donors. At a concentration of 20 microM and an incubation time of 6 h, DNA adduct levels for CMA were 21 and 43% and for MGA 31 and 65% of the levels observed with 20 microM CPA. In contrast, DNA binding of MPA amounted to less than 1% of that observed with CPA and DNA binding of the natural occurring progestin progesterone was below the level of detection. The results point to a genotoxic risk associated with the therapeutic use of CPA and possibly of CMA and MGA. Furthermore, the findings suggest that the significant genotoxicity observed with CPA, MGA and CMA is associated with the presence of the double bond in position 6-7 of the steroid, which is absent in MPA and progesterone.

Duodenal microgastrinomas associated with Zollinger-Ellison syndrome.

This report describes 4 cases of duodenal microgastrinomas associated with a Zollinger-Ellison syndrome. All gastrinomas were solitary tumors located in the submucosal layer of the first (n = 3) or second portion (n = 1) of the duodenum. The tumor size ranged from 0.75 to 8 mm in diameter (mean 4.9 mm). All gastrinomas were classified as malignant with respect to the metastatic spread to regional lymphnodes (n = 4) and liver (n = 1). None of the gastrinomas was identified by the preoperative imaging studies. Three tumors were localized during the surgical exploration, one tumor (0.75 mm in diameter) by the histopathological work-up of the resected specimen. The surgical therapy included two local resections and two Whipple procedures. Except for the patient with hepatic metastases the postoperative serum gastrin was normal indicating complete tumor resection. No patient died because of recurrent or metastastic gastrinoma. In conclusion, microgastrinomas of the duodenum are rarely diagnosed preoperatively because of their small size but can be identified by careful surgical exploration. Considering the high malignancy rate of this tumor patient prognosis depends on radical surgical therapy.

[Fulminating malignant hyperthermia in swine--an alternative therapy concept]. / Die fulminante maligne Hyperthermie beim Schwein--Ein alternatives Therapiekonzept.

An inexpensive therapeutic concept compared to the dantrolene-therapy to counter the malignant hyperthermia (MH) is to be discussed, using a case-study from swine-anaesthesia. Hyperventilating the animals (with O2), administering metamizol, beta-blocker, bicarbonate and sufficiently cooling the patient can, if the symptoms are recognized early enough, arrest the hypermetabolic cascade in its track. All the animals that were treated according to this scheme survived the (MH) crisis without any lasting post operative damage.

[Post-ischemia normal function of living related kidney transplants after preservation with HTK solution]. / Postischämische Normalfunktion von Verwandtennierentransplantaten nach Protektion mit HTK-Lösung.

This study reports on the first clinical use of HTK preservation solution devised by Bretschneider in renal transplantation. Using this HTK solution, nine living related donor kidneys subjected to cold ischemia for up to 4 h were consecutively transplanted between 1987 and 1989. The postoperative function of the donor and recipient kidneys is analyzed. The endogenous creatinine clearance and the plasma creatinine level are used as function parameters. Within 24-48 h after transplantation a postischemic normal graft function occurred. With triple drug therapy the transplanted kidneys showed an increase in renal function identical with that in the donor's single remaining kidney. Within 7 postoperative days no perfusion damage and no HTK or CyA nephrotoxicity was observed.

Gas-gangrene following arthroscopic surgery.

An arthroscopic anterior cruciate ligament repair was followed by gas-gangrene and the development of a compartment syndrome. Treatment consisted of extensive fasciotomy, debridement, and antibiotic therapy with penicillin G, cefotiam, and metronidazole. The patient was also treated with five sessions of hyperbaric oxygen in a pressure chamber for a duration of 2 h per session. This therapeutic regimen resulted in the preservation of a functionally intact extremity despite severe complication.

Use of ofloxacin in open fractures and in the treatment of post-traumatic osteomyelitis.

In two open prospective studies, the efficacy and tolerance of ofloxacin in the prevention of infection in patients with open fractures (n = 58) and in the treatment of chronic post-traumatic osteomyelitis (n = 115) were examined. In the study with open fractures, bone and/or soft tissue infection occurred in only four cases (6.5%). During an observation period of at least 12 months, post-traumatic osteomyelitis was seen in two patients with III degree open fractures (9%), while in the groups with I degree and II degree open fractures no bone infection could be found. Therefore, the rate of post-traumatic osteomyelitis related to all patients was 3.3%. In the second study with 115 patients suffering from chronic post-traumatic osteomyelitis 141 different Gram-positive and Gram-negative pathogens were isolated. 73% were Gram-positive cocci with Staphylococcus aureus in more than 50% of the cases. An elimination rate of more than 90% was found in the Gram-positive and Gram-negative bacteria, leading to a clinical cure in 85% and a recurrence of infection in 5% of the cases. The tolerability of ofloxacin was excellent. No drug-related allergic reactions were observed. Diarrhoea and headache occurred in less than 2% of patients. With adequate surgical treatment, ofloxacin proved to be a useful antimicrobial agent in the prevention and therapy of bone infection.

Significance of histamine formation and release in the development of endotoxic shock: proof of current concepts by randomized controlled studies in rats.

The significance of histamine in the initiation and progression of septic (endotoxic) shock is still uncertain. Increased new formation and increased release of histamine are the two hypotheses currently considered as the basis for a causal relationship. Both hypotheses were tested in a standardized rat model of endotoxic shock. Several randomized controlled studies were performed with inhibitors of histamine formation (histidine decarboxylase inhibitors) and of its action via receptors (H1 and H2 receptor antagonists). Two inhibitors of histamine formation (alpha-methylhistidine and alpha-fluoromethylhistidine) in a wide range of doses exerted no significant effects on survival curves for rats in endotoxic shock, despite enzyme inhibition in vitro and in homogenates of liver obtained from rats immediately after death. In addition, three H1 and three H2 receptor antagonists, which were selected on the basis of markedly different antihistaminic efficacies and of defined non-antihistaminic (nonspecific) efficacies, gave no indications of specific histamine-mediated effects on survival parameters in these studies when tested either singly or in various combinations. Thus, histamine cannot be shown to be a predominant factor in the lethal outcome of endotoxic shock in rats.

Effectiveness of imipenem in the treatment of chronic post-traumatic osteitis.

In 61 patients the effectiveness of imipenem in the treatment of chronic post-traumatic osteitis was examined. The diagnosis of post-traumatic osteitis was based on clinical and radiological signs of infection, as well as a positive bone culture from a surgical specimen. The average duration of treatment was 10 days with a dosage 3 X 500 mg imipenem daily. The most commonly identified pathogen was Staphylococcus aureus. In 75% of the cases an infection with Gram-positive pathogens was found. The majority of Gram-negative infections was caused by Pseudomonas aeruginosa. The rate of elimination was greater than 90% for both Gram-positive and Gram-negative bacteria. A definite cure was achieved in 80% of the reported cases, only four patients (7%) showed a recurrence of the infection. Allergic reactions or other adverse effects were not observed except for diarrhoea in four patients. The high rate of therapeutic effectiveness as well as the excellent toleration justify the use of imipenem in the treatment of chronic post-traumatic osteitis.

Ofloxacin treatment in the management of chronic osteitis.

In an open prospective study, the efficacy and tolerability of ofloxacin in the treatment of chronic post-traumatic osteitis was examined in 83 patients. 103 different pathogens were isolated. More than 75% were Gram-positive bacteria with Staphylococcus aureus occurring in 61% of cases. After ofloxacin treatment bacteriological elimination was more than 90% for both Gram-positive and Gram-negative species, leading to a clinical cure in 85% of patients. Reinfection occurred in 5% of patients. These values were obtained from follow-up examinations which were carried out at least 6 months after the end of therapy. The tolerability of ofloxacin was excellent and no drug-related allergic reactions or side effects were observed. In conjunction with adequate surgical treatment, ofloxacin proved to be a useful antibacterial agent in the therapy of chronic bone infection.

Induced histidine decarboxylase in endotoxic shock: identification of the enzyme in rat liver and influence of its inhibitors on survival parameters.

The hypothesis of a causal relationship between a progressive and unrestrained increase of tissue histamine formation by activation of an inducible histidine decarboxylase (HDC) and lethality in endotoxic shock (Schayer's 'induced histamine concept') was tested in a standardized rat endotoxic shock model. Initial enzyme identification studies in the rat shock liver (8 hrs after endotoxin challenge) clearly demonstrate that the 'induced' histidine decarboxylase is an acid (specific) HDC. The succeeding randomized, controlled study with appropriate inhibitors of the enzyme, alpha-methyl-histidine (competitive inhibitor) and alpha-fluoromethyl-histidine (irreversible inhibitor) using doses of 2, 20 or 100 mg/kg showed no significant effect on the survival rate of rats in endotoxin shock. The survival rate of the non-treated endotoxin control group (NaCl) was 25%; all methylprednisolone treated rats (50 mg/kg) survived. Thus, the 'induced' histamine is not a predominant factor (necessary or sufficient determinant) for the lethal outcome in rat endotoxic shock. The protective effect of MP is not predominantly due to the inhibition of the 'induced' histidine decarboxylase. The use of HDC-inhibitors as the appropriate instruments for evaluation of the significance of this mechanism is discussed.

Kinetics of different 123I- and 14C-labelled fatty acids in normal and diabetic rat myocardium in vivo.

Terminally radioiodinated long-chain fatty acids (FA) or phenyl-FA have shown promise for external myocardial imaging and detection of metabolic disorders with changes like those seen with radiocarbon-labelled natural FA. Yet, questions remain about the correlation of these changes to the biochemical forms of radioiodine within the cell. We have measured the distribution of label from 123I-heptadecanoic acid (HA), 123I-para-phenyl- and ortho-phenylpentadecanoic acid (pPPA and oPPA), 1-14C-stearic acid (SA) and 1-14C-palmitic acid (PA) into complex lipids (CL) (i.e. triacylglycerols (TG) and phospholipids (PL)), aqueous phase (AP) and solid residue (SR) of myocardium of normal (N) and streptozotocin-diabetic (D) rats at 1,2, 3, 5 and 10 min after i.v. injection. For the total heart (TH) all FA have similar initial peak heights in % dose (pPPA highest) at 1 to 2 min in N and D. Tracer kinetics for CL, TG and PL were similar for PA and pPPA and for SA and HA. For PA and pPPA 2/3 of CL tracer were in TG and 1/3 in PL, whereas it was 1/2 in each for SA and HA. In D rats turnover of CL was enhanced and tracer uptake into TG reduced for all FA. Tracer kinetics in SR and AP were similar, with highest values for HA; relationship between peak times for CL and AP indicates rapid formation of catabolite and its early cell exit. Unlike pPPA, oPPA was little converted to TG or PL and equally in N and D rats showed rapid decline.