Idiopathic sclerosing peritonitis in a man

Idiopathic sclerosing peritonitis is a rare disease described in young adolescent women, characterized by fibrosis and adhesions of the peritoneum to loops of the small bowel. Here we describe a 35-year-old man who underwent exploratory laparotomy for repeated small bowel obstruction. Only partial resection of the terminal ileum was possible because of adhesions; recurrent abdominal infections and leakage from anastomosis required further resection, which ultimately resulted in short bowel syndrome and malabsorption. The clinical and pathological findings were characteristic for idiopathic sclerosing peritonitis. We review the relevant literature, to confirm, to the best of our knowledge, that this is the first report of a male patient who has developed this rare disease.     

Lupus refractory pleural effusion: transient response to intravenous immunoglobulins.

A patient with systemic lupus erythematosus complicated by refractory bilateral pleural effusions is described. High dose corticosteroids with azathioprine, as well as intrapleural instillation of corticosteroids, proved ineffective in management. As our patient remained severely symptomatic and required repeated thoracocentesis, a therapeutic trial of intravenous immunoglobulins (IVIG) was attempted. IVIG had a beneficial effect, although of a transient and partial nature. Despite the results achieved, it seems that IVIG has limited value in treating lupus pleural effusion.     

Cytokine storm in a mouse model of IgG-mediated hemolytic transfusion reactions

Cytokines are hypothesized to play a central role in the pathophysiology of IgG-mediated hemolytic transfusion reactions (HTRs), and deeper understanding is required for improving therapy for these events. After establishing well-defined mouse models of HTRs, we tested whether cytokines were involved. Red blood cells (RBCs) from human glycophorin A transgenic (hGPA-Tg) or wild-type (WT) mice were transfused into non-Tg recipients passively immunized with monoclonal antibodies (Mabs). Only transfusions of incompatible RBCs induced IgG-mediated HTRs, exemplified by rapid clearance and hemoglobinuria. Very high plasma levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), and lower levels of tumor necrosis factor- (TNF-), were induced after incompatible transfusion. No significant changes in IL-10, IL-12, or interferon- (IFN-) levels were observed. The proinflammatory cytokines elaborated in this in vivo mouse model are also implicated in the systemic inflammatory response syndrome (SIRS) and confirm the hypothesis that cytokine storm occurs as a result of HTRs.     

CASE REPORT: Recurrent maternal virilization during pregnancy associated with polycystic ovarian syndrome: a case report and review of the literature

Maternal virilization in pregnancy is associated, in most benigncases, with luteoma of pregnancy and hyperreactio luteinalis.Only a few reports relate this phenomenon to hyperthecosis orpolycystic ovarian syndrome (PCOS). A case of recurrent maternalvirilization during two consecutive pregnancies in a patientwith PCOS is presented. In both pregnancies, the deepening ofher voice, facial hirsutism and scalp hair loss began at theend of the first trimester and regressed 3–4 months post-partum.The patient underwent ovarian venous catheterization, and androgensecretion from both ovaries was found to be markedly high butsimilar, therefore ruling out an ovarian androgen-secretingtumour. Reviewing the English literature of similar cases, wefound reports of only seven cases of maternal virilization duringpregnancy associated with PCOS. Here, we present a case of recurrentmaternal virilization in pregnancy associated with PCOS.     

Nonaminergic striatal neurons convert exogenous l-dopa to dopamine in parkinsonism

In intact striatum, the enzyme dopa decarboxylase is localized predominantly in dopaminergic nerve terminals. In Parkinson disease, loss of dopaminergic neurons is associated with massive depletion of striatal decarboxylase activity. Nevertheless, efficacy of exogenous L-dopa in parkinsonism is generally believed to result from its enzymatic decarboxylation to dopamine in the corpus striatum. It has previously been suggested that, after degeneration of nigrostriatal pathways, decarboxylation of administered L-dopa may occur mainly at such striatal sites as surviving dopaminergic terminals, serotonergic neurons, or capillaries; but currently available data do not favor these hypotheses. Recent experimental studies indicate that a substantial amount of decarboxylase activity is localized in striatal interneurons or efferent neurons that may not normally synthesize monoamines. We propose that after depletion of dopaminergic terminals, these nonaminergic striatal neurons may contain a large fraction of residual dopa decarboxylase activity and may represent an important locus for conversion of administered dopa to functional dopamine in the parkinsonian corpus striatum.     

Early and delayed neurotoxicity of Mitoxantrone and Doxorubicin following subarachnoid injection

Summary Doxorubicin (DXR) and Mitoxantrone (MXN) were administered into the subarachnoid space of mice or the ventricular system of rats. The maximal non-toxic systemic single dose (zero mortality=LDo) of DXR or MXN was used as reference for planning drug doses for CSF administration. LDo in mice were: 8 mg/kg DXR and 6 mg/kg MXN; in rats: 6 mg/kg DXR and 4.5 mg/kg MXN. Signs of neurotoxicity were remarkably similar in DXR or MXN treatment animals and included: head tremor, atactic-dystonic posture and circling behavior. The toxicity was dose dependent. Doses of ≥ 10% the LDo caused early appearance of clinical signs: a dose of 10% LDo caused neurotoxicity in 90% of DXR treated mice and in only 15% of MXN-treated animals. Treatment with 25% LDo MXN caused neurotoxicity in 30% of treated animals. Doses of ≤ 5% the LDo caused a delayed onset of DXR neurotoxicity in one third of treated mice (after 60–90 days). In rats, neurotoxicity was of an early onset and augmented severity following doses of ≥ 5% LDo. Abnormal histopathological findings were detected only in symptomatic animals with early toxicity and were usually restricted to superficial cortical layers in mice or the basal surface of the brainstem in rats. Brains of mice with delayed toxicity were unremarkable. The levels of monoamine neurotransmitters and their metabolites (DA, DOPAC, HVA, NE, 5HT) in the striatum, cortex and cerebellum of mice with early and delayed DXR neurotoxicity did not differ from normal brains. We conclude that DXR and MXN cause a similar dose-dependent early and delayed neurotixicity through a mechanism which is as yet unidentified.     

Diminished decarboxylation of l-dopa in rat striatum after intrastriatal injections of kainic acid

Injection of kainic acid into rat striatum reduced striatal DOPA decarboxylase activity by 20% as compared with that in control unlesioned sides. After administration of L-DOPA, concentrations of dopamine (but not DOPA) were lower (by 33%) in lesioned than in control striata indicating decreased in vivo formation of dopamine from exogenous DOPA after kainate lesions. These findings suggest that in the rat, a significant part of striatal DOPA decarboxylase activity i·s localized in neurons originating within the striatum (interneurons and/or efferents) whose perikaria are selectively destroyed by kainic acid.     

The tyrosine kinase inhibitors imatinib and AG957 reverse multidrug resistance in a chronic myelogenous leukemia cell line

The K562 cell line derived from a chronic myelogenous leukemia (CML) patient exhibits ATP-dependent exclusion of the multidrug resistance (MDR)-type drugs. The protein tyrosine kinases inhibitors, imatinib mesylate and AG957 allowed for increased doxorubicin and calcein-AM accumulation in these cells. Maximal modulation was achieved at 3 and 10 microM imatinib and AG957, respectively. This imatinib concentration is comparable to the plasma steady state levels observed in patients. Although the increase in cellular accumulation followed a time course similar to apoptotic manifestations induced by these drugs, the two phenomena seem independent. There was no correlation between the levels of MDR reversal and apoptosis in clones derived from the K562 cell line. Moreover, whereas protein kinase inhibitors induced apoptosis in only a fraction of the cells, the MDR reversal occurred in all of them. Inhibition of apoptosis by a non-specific inhibitor of caspases was not associated with MDR reversal. The consequence of these findings is that combination of tyrosine kinase inhibitors with antileukemic drugs is likely to have the added beneficial effect of allowing MDR-type drugs better access to cells.     

Transfusion of fresh murine red blood cells reverses adverse effects of older stored red blood cells

BACKGROUND: Although a subset of recent studies have suggested that red blood cell (RBC) storage length is associated with adverse patient outcomes, others have shown no such relationship. Adults may be transfused with RBC units of different storage lengths, and existing studies do not take into consideration that fresh RBCs may alter responses to concurrently transfused stored RBCs. To test this possibility, we utilized a murine model and investigated transfusion outcomes of fresh, stored, or fresh‐plus‐stored RBCs. STUDY DESIGN AND METHODS: Fresh, 14‐day‐stored or fresh plus 14‐day‐stored leukoreduced RBCs from HOD‐transgenic donors (with RBC‐specific expression of hen egg lysozyme, ovalbumin, and human Duffy^b) were transfused into naïve C57BL/6 recipients. Serum cytokines and anti‐HOD alloimmunization were evaluated after transfusion. RESULTS: In six of six experiments (n = 90 mice total), a proinflammatory serum cytokine storm of interleukin‐6, keratinocyte‐derived chemokine/CXCL1, and monocyte chemoattractant protein‐1 was observed in transfusion recipients of stored but not fresh RBCs, along with high degrees of anti‐HOD alloimmunization. However, concurrent transfusion of fresh HOD RBCs along with stored HOD RBCs significantly decreased these adverse outcomes (p < 0.05). CONCLUSIONS: These results are consistent with fresh murine HOD RBCs losing protective properties during storage, and introduce a previously unrecognized variable in RBC storage studies. If translatable to humans, uniform “old blood” groups may be needed in future clinical studies to more accurately investigate the biologic effects of older RBC units.