Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Iron overload presenting as exacerbation of hepatic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation has not been previously described. We report 6 patients with established hepatic GVHD in whom iron overload (median serum ferritin, 7231 mug/dL; median transferrin saturation, 77%) resulting from a lifetime median of 20 units of packed red blood cell transfusions was manifested by worsening of liver function. Liver biopsies performed in 4 patients confirmed severe iron overload and also hepatic GVHD. Analysis for the C282Y and H63D hemochromatosis gene mutation was negative for the homozygous state in all 6 patients. Erythropoietin-assisted phlebotomy resulted in normalization of liver function at a median of 7 months and of serum ferritin at a median of 11 months. Immunosuppressive therapy was successfully tapered in all 4 patients who completed the phlebotomy program, and this supported the impression that iron overload, rather than GVHD, was the principal cause of liver dysfunction. At a median follow-up of 50 months (range, 18-76 months) from the transplantation and 25 months (range, 5-36 months) from ferritin normalization, all 4 patients require maintenance phlebotomy. We conclude that iron overload can mimic GVHD exacerbation, thus resulting in unnecessary continuation or intensification of immunosuppressive therapy for GVHD, and that maintenance phlebotomy is necessary after successful iron-reduction therapy.     

Human hepatocellular carcinoma tumor xenografts

Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivostudies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice.     

Dostoevsky's epilepsy: A case report and comparison

The Russian writer Dostoevsky (1821–1881) suffered from a rare form of temporal lobe epilepsy termed “ec-static epilepsy.” Dostoevsky used his epileptic experiences to create Prince Myshkin, the protagonist of The Idiot. The recent case of a patient who experienced ecstatic epilepsy as a result of a temporal lobe brain tumor is presented and compared with that of Prince Myshkin. Reading Dostoevsky can give the contemporary physician an insight into the inner life of an epileptic patient — an example of how art can directly benefit medical practice.     

Phase II trial of 10 deaza-aminopterin in patients with bladder cancer

Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m² IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m² depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.     

Hernia through the foramen of Winslow: a complication of cholecystectomy. A case report

In 151 years since first described, there have been 112 reported cases of hernia through the foramen of Winslow (HFW). All thus far have described HFW as a primary entity. The case reported appears to be unique with HFW as a surgical complication. HFW is the least common of internal hernias. The primary symptom is pain referred from the herniated organ and the hepatoduodenal ligament. An interesting sign is that the patient is found curled up or stooped over for pain relief. Anatomic factors implicated in HFW are an enlarged epiploic foramen, a floppy cecum and ascending colon, or abnormal length of small bowel mesentery. Tension on these structures causes pain with the torso extended. Distention of bowel in the lesser sac mimics gastric obstruction. Organs herniated are: small bowel (63%); cecum, ascending colon, and terminal ileum (30%); and transverse colon (7%). Of 25 cases reported since 1966, cecal herniation comprised two-thirds. The diagnosis may be made radiologically and the treatment is surgical. The case and a review of the literature are presented with attention to the anatomy. Also provided are the signs and symptoms of this interesting and perplexing diagnosis.     

Direct observation in vitro of how neuroblasts migrate: medulla and cochleovestibular ganglion of the chick embryo

The hypothesis that neuroblasts migrate in the nervous system by a locomotory process was tested experimentally. An in vitro preparation permitted direct observation of postmitotic cells migrating from the rhombic lip of the medulla and the anlage of the cochleovestibular ganglion. Cell locomotion was not seen. Instead migration was produced by elongation of a leading process, followed by translocation of the nucleus (perikaryal translocation). On the basis of comparisons with previous observations in situ, we propose that this represents a common mode of migration in the developing nervous system. Cell clusters were explanted from the rhombic lip at the developmental stage when they migrate from the ventricular zone to the acoustico-vestibular anlage in the medulla. Cells from the cochleovestibular ganglion were explanted after migration from the otocyst, but before ganglionic differentiation. Each neuroblast's migration route was formed by an elongating leading process ending in a growth cone. The growth cone attached to other cells and processes or ended freely on an acellular substrate. Nonneuronal cells usually migrated as has been described for fibroblasts, yet with some of the features of perikaryal translocation, but some nonneuronal precursor cells may migrate the way neuroblasts do. Neuroblasts did not migrate preferentially on the processes of nonneuronal cells, although the reverse could be observed. In fact a variety of interactions between migratory cells, neuronal and nonneuronal, were observed. The advantage of the experimental system described here is that one can observe cells migrating spontaneously at the times in development when they normally do so, while preserving the cellular populations present in situ.