Treatment of Advanced Malignancies with High-Dose Acetaminophen and N-Acetylcysteine Rescue

High-dose acetaminophen (HDAC) produces hepatocellular necrosis and cytotoxic changes in other tissues that express mixed-function-oxidase (MFO) activity. N-acetylcysteine (NAC), administered within 8 hr of HDAC exposure, replenishes reduced glutathione and prevents these effects. Numerous cell culture and animal studies have demonstrated that NAC may differentially protect normal cells compared with malignant cells from the toxic effects of chemotherapeutic agents and radiation. It was therefore proposed that HDAC with NAC rescue may be effective in malignancies that express MFO activity. To test this hypothesis, a phase I trial of HDAC with NA C rescue was conducted on 19 patients with advanced cancer. HDA C was escalated from 6 to 20 g/m² PO using a standard IV NAC rescue regimen. A total of 78 treatments were administered. Moderate fatigue, anorexia, and weight loss were the main toxicities observed. Transient grade 3 liver toxicity was noted following 1 treatment. Alopecia and renal and hematological toxicities were not observed. Responses after 4 courses administered weekly were as follows: response in at least 1 site—8 (partial 3, improved 3, mixed 2); stable disease—3; progressive disease—3; inevaluable—5. In conclusion, HDAC was tolerated with moderate fatigue, anorexia, and weight loss but few other effects using a standard IV NAC rescue regimen. A maximum tolerated dose was not reached at 20 g/m². A 3/19 (15.8%) partial response rate was observed.     

Vitamin A hepatotoxicity in multiple family members

Three of five family members experienced symptoms and biochemical evidence of hepatitis that could not be explained on the basis of infectious, metabolic or immunologic disorders of the liver. A history of prolonged ingestion of moderate amounts of vitamin A (20,000 to 45,000 IU per day for 7 to 10 years) was obtained in each of the three family members and was absent in the remaining two unaffected individuals. A liver biopsy performed in one family member confirmed the diagnosis of vitamin A toxicity. This report emphasizes the finding that even moderate amounts of vitamin A, when ingested over a prolonged period of time, can cause significant hepatocellular injury.     

A LIGHT AND ELECTRON MICROSCOPIC HISTOCHEMICAL STUDY ON THE MECHANISM OF DFP-INDUCED ACUTE AND SUBACUTE MYOPATHY

Tóth L., Karcsú S., Poberai M. & Sávay Gy. (1981) Neuropathology and Applied Neurobiology 7, 399–410
A light and electron microscopic histochemical study on the mechanism of DFP-induced acute and subacute myopathy
The histochemical changes occuring in association with the development of acute and subacute myopathy have been studied in the rat diaphragm 30 min-48 h after a single i.p. injection of 1–82 mg/kg of the irreversible cholinesterase inhibitor organophosphate, diisopropylfluorophosphate (DFP). In addition to a considerable inhibition of the AChE activity of the motor end-plates, accumulation of ionic Ca²⁺ and an increase in neutral protease activity in the subjunctional sarcoplasm have been demonstrated. A temporal and causal relationship has been established between the histochemical changes and the development of the ultrastructural signs of myopathy.     

Rare cause of vaginal bleeding in early puberty

STUDY OBJECTIVE: To document an unusual cause of vaginal bleeding in early puberty. DESIGN: Case Report. RESULTS: Clinical presentation with the aid of pelvic ultrasound pointed to the diagnosis of an endometrial polyp in this young adolescent prior to menarche. A hysteroscopy was deemed necessary to allay concerns for a serious pathology and confirm diagnosis. CONCLUSION: Endometrial polyps are infrequent in adolescents but should be included as a differential diagnosis of vaginal bleeding in this population.     

Causes and Differentialdiagnosis of Hematospermia

The authors examined the most frequent causes of hematospermia on their clinical material. They describe - in the order of importance - the examinations needed to discover pathological diagnostics. They call the attention to the importance of differentiation of "clear" hematospermia and hemato-pyospermia and review the possible ways of therapy.
Ursachen und Differentialdiagnose der Haematospermie

Zusammenfassung

Anhand eigener Beobachtungen wird zur Problematik der Haematospermie Stellung genommen. Dieses Symptom gelangt nicht so häufig zur Beobachtung, allerdings stellt die Haematospermie ein Symptom dar, das sehr ernst genommen werden muß. Die Autoren unterscheiden zwischen einer „klaren” Haematospermie und einer Pyo-Haematospermie, wenn es sich zusätzlich um eine eitrige Entzündung handelt. Die für die Differentialdiagnose wichtigen einschlägigen Untersuchungsmethoden werden beschrieben. Die wesentlichen Grundsätze der Therapie werden erläutert.     

去甲乌药碱对实验性心力衰竭的治疗作用

去甲乌药碱(DMC)是中药附子的有效成分之一。静脉滴注DMC2μg/kg/min共5min,使豚鼠正常心脏的收缩力明显加强,LVSP和LV dP/dt_max分别增加58±7和25±7%;心衰后,LVSP和LV dP/dt_max分别下降到心衰前的40±5和30.5±2.8%。DMC可使之恢复到79±14和75±9.9%,DMC也能加强离体豚鼠衰竭心脏的收缩力。DMC的强心作用与ISO相似,但前者作用较弱,作用维持时间较长,这可能与他们的作用机制不同有关。     

The Effects of Colectomy on Immediate–Early Proto-Oncogene Expression and Hepatic Regeneration in the Rat

The intact liver exists in a state of replicative quiescence. The factor(s) responsible for maintaining this state and their tissue sources have yet to be identified. Because the colon synthesizes and/or absorbs numerous agents that inhibit hepatocyte proliferation, the principle purpose of this study was to determine whether total colectomy would result in the conversion of quiescent livers to a state of replicative competence. Thus, adult, male Sprague-Dawley rats (250–300 g) were randomized to undergo either total colectomy with ileostomy or sham surgery. Thereafter, rats were sacrificed (N = 3–6/group) at times 15 and 30 min and 1, 2, 6, and 24 hr and the livers analyzed by Northern blot analyses for mRNA of the following immediate–early proto-oncogenes (IEP genes): c-fos, c-jun, and c-myc. Rats sacrificed at 24 hr also had hepatic regenerative activity documented by [³H]thymidine incorporation into hepatic DNA. The results of the study revealed that within 15 min, c-fos and c-jun mRNA expression increased in colectomized rats, with peak expression occurring at 30 and 60 min, respectively. c-myc mRNA expression was more delayed, with peak expression occurring at 6 hr postcolectomy. IEP gene expression also increased somewhat in sham-colectomy controls but the increases were not as prompt and, in general, were of lower magnitude than those in the colectomy group. Despite the differences in IEP gene expression between the two groups, [³H]thymidine incorporation at 24 hr was similar (mean ± SE: colectomy group, 17.2 ± 2.6 dpm/μ g DNA; sham-colectomy controls, 14.8 ± 1.4 dpm/μg DNA). To determine whether the increases in IEP gene expression expedite or augment the hepatic regenerative response to partial hepatectomy (PHx), rats that had undergone colectomy or sham colectomy 1 hr earlier and rats with no previous abdominal surgery then underwent a 70% PHx and were sacrificed at 8, 16, and 24 hr thereafter. At each time interval, [³H]thymidine incorporation was documented and found to be similar in the three groups. In conclusion, the results of this study indicate that total colectomy, and to a lesser extent abdominal surgery, induces the conversion of an intact, quiescent liver to a state of replicative competence. The results also suggest that, in addition to colectomy, the presence of mitogens and/or co-mitogens is required for further progression of hepatocytes through the cell cycle. Finally, a “primed” liver does not respond more promptly or vigorously to a regenerative stimulus than a “resting” liver.     

环丙沙星在预防酒精对肝细胞再生抑制中的作用

急性或慢性酒精中毒可不同程度抑制肝细胞ＤＮＡ合成和肝细胞再生。多数学者认为酒精抑制肝细胞再生与酒精抑制聚胺 (Ｐｏｌｙａｍｉｎｅ ,包括四甲烯二胺、精脒和精胍 )合成有关[1,2 ] 。实验证明 ,γ 氨基丁酸 (γ ａｍｉｎｏｂｕｔｙｒｉｃａｃｉｄ ,ＧＡＢＡ)是聚胺代谢的衍生物 ,是神经传递介质之一 ,是细胞增生调节中的抑制剂。Ｍｉｎｕｋ等[3 ] 指出 ,酒精中毒的实验动物血液中ＧＡＢＡ浓度升高 ,ＧＡＢＡ可能激活了肝脏ＧＡＢＡ受体 ,改变了细胞内环境。因此 ,酒精抑制肝脏合成聚胺可能是由于ＧＡＢＡ介导的结果。Ｄｉｅｈｌ[2 ] 认…     

Liver transplant outcomes in a Canadian First Nations population

BACKGROUND:

A higher incidence of autoimmune disorders may predispose First Nations (FN) individuals to higher rates and more severe episodes of rejection, graft loss and mortality following liver transplantation for advanced liver disease.

METHODS:

A retrospective review of patient outcomes in a single centre providing long-term follow-up care for FN and non-FN patients transplanted for advanced liver disease was conducted.

RESULTS:

A total of 20 FN and 129 non-FN charts were available for review. FN subjects were younger at transplantation (mean [± SD] age 32.4±4.1 years versus 46.3±1.4 years; P=0.00005), less often male (35% versus 58%; P=0.05), more commonly transplanted for autoimmune hepatitis (30% versus 4.7%; P=0.006), less often from urban residences (25% versus 74%; P=0.0001) and less compliant with medical care (20% versus 80%; P=0.007). After a mean follow-up period of 11.0±1.5 years and 8.4±0.5 years in FN and non-FN subjects, respectively, the incidence and severity of rejection, graft and patient survival were similar between cohorts.

CONCLUSION:

Although demographic profiles, nature of the underlying disease and compliance differed, the rates and severity of rejection, graft and patient survival were similar in FN and non-FN patients who underwent liver transplantation for advanced liver disease.