Massive haemoperitoneum complicating metastasis in the liver

The rare phenomenon of gross intra-abdominal bleeding due to hepatic metastasis was seen in a young male who a short time before had undergone orchiectomy because of embryonal cell carcinoma. Following laparotomy, 4 liters of fresh blood were drained from the peritoneal cavity and the left lobe of the liver, containing a single large metastasis, was removed. It is stressed that when no other cause of such haemorrhage can be found in a patient known to have had malignancy, the possibility of bleeding from a metastasis should be considered and appropriate measures taken.     

A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea synthesis that has been considered as a model for liver-directed gene therapy. Current treatment has failed to avert a high mortality or morbidity from hyperammonemic coma. Restoration of enzyme activity in the liver should suffice to normalize metabolism. An E1- and E4-deleted vector based on adenovirus type 5 and containing human OTC cDNA was infused into the right hepatic artery in adults with partial OTCD. Six cohorts of three or four subjects received 1/2 log-increasing doses of vector from 2 x 10(9) to 6 x 10(11) particles/kg. This paper describes the experience in all but the last subject, who experienced lethal complications. Adverse effects included a flu-like episode and a transient rise in temperature, hepatic transaminases, thrombocytopenia, and hypophosphatemia. Humoral responses to the vector were seen in all research subjects and a proliferative cellular response to the vector developed in apparently naive subjects. In situ hybridization studies showed transgene expression in hepatocytes of 7 of 17 subjects. Three of 11 subjects with symptoms related to OTCD showed modest increases in urea cycle metabolic activity that were not statistically significant. The low levels of gene transfer detected in this trial suggest that at the doses tested, significant metabolic correction did not occur.     

Familial varicocele.

Described are two families in each of which two young males had varicocele. HLA-A, B, C and D5R antigen studies were performed in one family but no genetic factors could be determined. In a review of several large series of patients with varicocele we found no mention of familial occurrence. Although the linkage between adolescent varicocele and spermatogenic dysfunction is still debatable, it is concluded from our experience that it is worthwhile examining other male members of families of affected adolescents or children but that expensive invasive studies are not warranted.     

The disposition of valpromide in rats and the isolated perfused rat liver

The pharmacokinetics and metabolism of valpromide (VPD) were investigated in intact rats and in the isolated perfused rat liver (IPL). The rats and the IPLs were divided into three groups. One was a control (untreated) group. The second consisted of intact rats and IPLs obtained from rats pretreated with phenobarbital. A third group of rats received VPD by oral administration. VPD was partially hydrolyzed to valproic acid (VPA) by the IPL following iv administration to intact rats. The fraction of the total body clearance of VPD which furnished VPA as a metabolite (fm) in the rats was 63%. The rate and extent of this conversion were greater in the phenobarbital-pretreated rats and in the IPLs than in the control group. Our studies showed that phenobarbital can induce the hydrolytic biotransformation of VPD to VPA. This is in addition to its known effect on oxidative metabolic pathways. In rats, as in humans and dogs, VPD is biotransformed to VPA in the liver. The complete oral bioavailability of VPD and the fact that the AUC of VPA obtained after oral administration of VPD was not higher than that obtained after the iv injection of VPD indicates that the gastrointestinal tract is not one of the metabolic sites of VPD to VPA conversion.     

Open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis.

Ten patients with relapsing-remitting multiple sclerosis were treated with intravenous immune globulin, 0.4 g/kg per day for 5 consecutive days, and then with additional booster doses of immune globulin of 0.4 g/kg, once every 2 months, for the next 12 months. Ten untreated patients with relapsing-remitting multiple sclerosis who were matched with the study patients for age, disease duration, and number of attacks per year served as controls. Immune globulin treatment was well tolerated, with no side effects. The exacerbation rate decreased from 3.7 +/- 1.2 exacerbations per year before treatment to 1.0 +/- 0.7 exacerbations per year during the treatment in the immune globulin-treated patients, while it remained unaltered in the controls. The posttreatment Kurtzke Expanded Disability Status Scale score decreased from a mean of 4.45 to 4.15, whereas in controls it increased from 3.55 to 3.75. The results suggest that immune globulin suppresses the ongoing pathologic process in multiple sclerosis and may be a promising treatment to prevent disease exacerbations.     

Genotypic and phenotypic resistance: longitudinal and sequential analysis of hepatitis B virus polymerase mutations in patients with lamivudine resistance after liver transplantation

OBJECTIVE: Lamivudine-resistant strains appear in 27-62.5% of liver transplant recipients treated with lamivudine for hepatitis B virus (HBV) recurrence, and may lead to failure of antiviral therapy. In an extension of our previous study, we investigated the molecular events associated with the emergence of lamivudine-resistant mutants in this population. METHODS: Sequential serum samples from 10 consecutive patients with lamivudine resistance after liver transplantation were analyzed for viral genotype, precore mutants, and viral polymerase gene mutants (L528M, M552V, M552I) using restriction fragment length polymorphism. Quantitative analysis of HBV DNA was performed using hybridization assay and polymerase chain reaction. RESULTS: Eight patients (80%) were infected with genotype D and two (20%) with genotype C. Polymerase mutants (genotypic resistance) were identified in all the patients. Phenotypic resistance (rise in serum HBV DNA titers above the detection limit of the hybridization assay) developed in five patients (50%); of the remainder, three (30%) did not have phenotypic resistance, and two were primary nonresponders. Genotypic resistance was detected earlier than phenotypic resistance (median 285 days [range 42-510] vs median 387 days [range 320-420], p = 0.055). In five patients (50%), the emergence of the YMDD mutants took over the wild type; in three (30%), the YMDD mutant took over the wild type, but the wild type re-emerged during lamivudine therapy; and in two (20%), the YMDD mutants were detected in a mixture with the wild type (in different percentages). The mean pretreatment serum ALT level was significantly lower in the patients who did not develop phenotypic resistance (p = 0.0002). The M552I pure viral population was found mainly in these patients, and all retained stable graft function (median follow-up 33 months). A high pretreatment HBV DNA level (>50 x 10(6) copies/ml) was highly statistically significantly correlated with the rapid occurrence of phenotypic resistance (r = -0.90, p = 0.04). CONCLUSIONS: We reached the following conclusions: 1) In our area, liver transplant recipients who develop resistance to lamivudine given for recurrent HBV infection seem to be mainly infected with genotype D. 2) Re-emergence of the wild type can occur during lamivudine therapy. 3) Genotypic resistance precedes phenotypic resistance, although phenotypic resistance does not always follow genotypic resistance. 4) Quantitative determination of viremia and analysis of polymerase gene mutants are recommended for monitoring antiviral therapy of liver transplant patients with HBV reinfection in the graft.     

The use of advanced simulation in the training of anesthesiologists to treat chemical warfare casualties

Training anesthesiologists to treat nerve gas intoxication in a mass casualty scenario is a complicated task. The scenario is an unfamiliar medical situation involving the need to decontaminate patients before providing definitive medical treatment, and the need for physical protection to the medical team before decontamination. We describe the development of a simulation-based training program. In one site of a virtual hospital, anesthesiologists were trained in initial airway and breathing resuscitation before decontamination while wearing full protective gear. In another site, they were trained in the treatment of critically-ill patients with combined conventional and chemical injuries or severe intoxication. Intubation simulators of newborn, pediatric, and adult patients, advanced full-scale simulators, and actors simulating patients were used. Initial airway, breathing, and antidotal treatment were performed successfully, with or without full protective gear. The gas mask did not interfere with orotracheal intubation, but limited effective communication within the medical team. Chemical protective gloves were the limiting factor in the performance of medical tasks such as fixing the orotracheal tube. Twenty-two participants (88%) pointed out that the simulated cases represented realistic problems in this scenario, and all 25 participants found the simulated-based training superior to previous traditional training they had in this field. Using advanced simulation, we were able to train anesthesiologists to treat nerve gas intoxication casualties and to learn about the limitations of providing medical care in this setting. IMPLICATIONS: Advanced medical simulation can be used to train anesthesiologists to treat nonconventional warfare casualties. The limitations of medical performance in full protective gear can be learned from this training.     

Reliability and validity of a simulation-based acute care skills assessment for medical students and residents

BACKGROUND: Medical students and residents are expected to be able to manage a variety of critical events after training, but many of these individuals have limited clinical experiences in the diagnosis and treatment of these conditions. Life-sized mannequins that model critical events can be used to evaluate the skills required to manage and treat acute medical conditions. The purpose of this study was to develop and test simulation exercises and associated scoring methods that could be used to evaluate the acute care skills of final-year medical students and first-year residents. METHODS: The authors developed and tested 10 simulated acute care situations that clinical faculty at a major medical school expects graduating physicians to be able to recognize and treat at the conclusion of training. Forty medical students and residents participated in the evaluation of the exercises. Four faculty members scored the students/residents. RESULTS: The reliability of the simulation scores was moderate and was most strongly influenced by the choice and number of simulated encounters. The validity of the simulation scores was supported through comparisons of students'/residents' performances in relation to their clinical backgrounds and experience. CONCLUSION: Acute care skills can be validly and reliably measured using a simulation technology. However, multiple simulated encounters, covering a broad domain, are needed to effectively and accurately estimate student/resident abilities in acute care settings.     

Immunohistochemistry analysis of micrometastasis in pretreatment lymph nodes from patients with esophageal cancer

BACKGROUND: With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology. METHODS: Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53, an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed. RESULTS: 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series. CONCLUSIONS: Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.     

Radiofrequency Ablation Treatment in Proximity to the Gallbladder Without Subsequent Acute Cholecystitis

Initial reports have suggested that proximity of liver tumors to the gallbladder may increase the risk for cholecystitis after radiofrequency ablation. A colon adenocarcinoma metastasis to the liver in contact with the gallbladder was successfully treated with radiofrequency ablation without subsequent cholecystitis.