Perinatal outcomes in inflammatory bowel disease

Objective: To determine whether inflammatory bowel disease (IBD) is associated with increased risk for adverse perinatal outcome.

Methods: A case–control study of 116 singleton pregnancies with IBD compared to 56?398 singleton controls delivered between 1986 and 2001.

Results: Patients with IBD were slightly older (32.8 vs. 30.6 years, p <?0.001), more likely to be Caucasian or Asian than Black or Latino (92% vs. 57%, p <?0.001) and have private health insurance (33% vs. 3%, p <?0.001). IBD was associated with an increased risk for labor induction (32% vs. 24%, p?=?0.002), chorioamnionitis (7% vs. 3%, p?=?0.04) and Cesarean section (32% vs. 22%, p?=?0.007), but there were no differences in neonatal outcomes. Subgroup analysis demonstrated an increased risk for low birth weight (LBW) in the ulcerative colitis group vs. the Crohn's disease group (19% vs. 0%, p?=?0.002). Patients with prior surgery for IBD had a lower incidence of LBW (0% vs. 12%, p?=?0.03). Flares during pregnancy were associated with an increased risk for preterm delivery (27% vs. 8%, p?=?0.02) and LBW (32% vs. 3%, p?=?0.003).

Conclusion: IBD was an independent risk factor for Cesarean section but there was no increase in adverse perinatal outcome. Crohn's disease, prior IBD surgery and quiescent disease were associated with a lower risk for LBW.     

Femoral capital osteonecrosis: MR finding of diffuse marrow abnormalities without focal lesions

Six painful hips in five patients were examined with magnetic resonance (MR) imaging and were found to have diffuse signal abnormalities in the marrow of the femoral head and neck, which extended into the intertrochanteric area in five cases. The abnormal regions were low in signal intensity on images obtained with a short repetition time (TR) and a short echo time (TE) and were isointense or hyperintense on long TR/TE images--findings that have been attributed by others to bone marrow edema. Edema was also seen in marrow just above the acetabulum in two cases. No focal abnormalities characteristic of osteonecrosis were seen. Osteonecrosis was subsequently shown to be present in all six femoral heads at core biopsy (three cases) or by subsequent development of focal MR abnormalities reported to be highly specific for osteonecrosis (three cases). The affected hips had been radiographically normal or subtly osteopenic and had shown intense radionuclide uptake in the femoral head at scintigraphy, with lesser abnormality in the neck and intertrochanteric region. Follow-up MR examinations of five of the six femoral heads showed the diffuse abnormalities to have been transient. Although diffuse MR abnormalities in the proximal femur are not specific, they may indicate the presence of osteonecrosis of the femoral head.     

Endovascular management of isolated iliac artery aneurysms

OBJECTIVE: We reviewed our experience with endovascular treatment of isolated iliac artery aneurysms (IAAs). METHODS: Medical records for consecutive patients undergoing endovascular IAA repair from 1995 to 2004 were reviewed. Computed tomography (CT) angiograms were used to assess IAA location, size, and presence of endoleaks after endovascular repair. Rates of primary patency and freedom from secondary interventions were estimated using the Kaplan-Meier life-table method. RESULTS: From July 1995 to November 2004, 45 patients (42 men), with a mean age of 75 years, underwent endovascular repair of 61 isolated IAAs: 41 common iliac, 19 internal iliac, and one external iliac. Five patients (11%) were symptomatic, although none presented with acute rupture. The mean preoperative IAA diameter was 4.2 +/- 1.7 cm. Fifteen patients (33%) had prior open abdominal aortic aneurysm repair. Local or regional anesthesia was used in 28 cases (62%). Thirty-four patients (75%) were treated with unilateral iliac stent-grafts, eight (18%) with bifurcated aortic stent-grafts, and three (7%) with coil embolization alone. Perioperative major complications included one early graft thrombosis that eventually required conversion to open repair and one groin hematoma that required operative evacuation. On follow-up, late complications included one additional graft thrombosis and one late death after amputation. No late ruptures occurred after endovascular repair, with a mean follow-up of 22 months (range, 0 to 60 months). The mean postoperative length of stay was 1.3 +/- 1.0 days. On postoperative CT scans obtained at 1, 6, 12, 24, and 36 months, aneurysm shrinkage was noted in 18%, 29%, 57%, 67%, and 83% of IAAs, respectively, compared with the baseline diameter. One hypogastric aneurysm enlarged in the presence of a later identified type II endoleak. Five endoleaks were noted (4 type II, 1 indeterminate) at 1 month, with four other endoleaks (1 type II, 1 type III, 2 indeterminate) identified on later CT scans. At 2 years, primary patency was 95%, and freedom from secondary interventions was 88%. CONCLUSIONS: Endovascular repair of isolated IAAs appears safe and effective, with initial results similar to those after endovascular abdominal aortic aneurysm repair.     

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease. Atherosclerotic renovascular disease is an important cause of end-stage renal disease (ESRD). The exact incidence of ESRD and the rate of decline in glomerular filtration rate (GFR) in patients with this condition is unknown. We report the mortality, the rate of decline in renal function, and incidence of ESRD in 51 patients with bilateral atherosclerotic renovascular disease followed-up for a median period of 52 months. None of these patients had undergone any surgical or radiological intervention. Renal function was determined by serial measurements of serum creatinine. Bilateral atherosclerotic renovascular disease was associated with a high mortality rate; the crude mortality rate at 60 months was 45%. Assessment of renal function showed impaired renal function at time of angiography and a nonuniform and variable decline in renal function during the period of observation. The median GFR decreased from 39 mL/min (range, 15 to 80 mL/min) at time of angiography to 31 mL/min (range, 10 to 70 mL/min) and 24 mL/min (range, 10 to 40 mL/min) at 24 and 60 months, respectively (P < 0.05). The calculated mean rate of decline in GFR for all patients was 4 mL/min/yr (range, 1 to 16 mL/min/yr). Over the 5 years, there was a progressive increase in the incidence of ESRD. Of the original 51 patients who underwent angiography, six patients reached ESRD. The crude incidence of ESRD was, therefore, 12%. Patients who reached ESRD were characterized by advanced azotemia at the time of angiography (median GFR, 25 mL/min) and a rapid decline in GFR (8 mL/min) compared with patients who did not reach ESRD during the observation period (median GFR, 43 mL/min and an average rate of decline GFR of 3 mL/min).     

Radiotherapy for melanotic freckles

Five patients who received radiotherapy (RT) for 7 melanotic freckles (MF, also known as Hutchinson's freckles, lentigo maligna) were reviewed 8 to 37 months after their treatment by RT. Local control and a favourable cosmetic result occurred in all patients. Treatment toxicity was minimal. Few reports about the use of RT for MF exist. Many other treatments including observation alone have been associated with high rates of recurrence, and in some cases conversion to invasive melanoma has occurred. RT appears to be a safe and effective treatment for this condition, providing that doses equivalent to 44 Gy in 11 fractions or more are given.     

Mitoxantrone and cisplatin in recurrent and/or metastatic salivary gland malignancies

A phase II study was performed to assess the safety and efficacy of mitoxantrone and cisplatin in locally recurrent and/or metastatic carcinomas of the salivary glands. Between May 1997 and March 2001, a total of 14 patients were entered on this trial. All of them had previously undergone radical resection and 10 were subsequently treated with adjuvant radiation therapy with (n=3) or without (n=7) concomitant chemotherapy. Therapy according to the study protocol consisted of mitoxantrone given as i.v. bolus on day 1 at a dose of 12 mg/m2 and cisplatin given as 90-min infusion at a dose of 30 mg/m2 on days 1-3. We observed two partial responses (14.3%) and stabilization of disease in nine patients (64.3%); progression during therapy was noted in only three cases (21.4%). The median time to progression was 15 months (range 2-36) and the median survival time was 27 months (range 4-54). Myelosuppression was commonly observed. Leukocytopenia occurred in all patients, and was grade 3 or 4 in three (21%) and four (29%) patients. WHO grade 3 thrombocytopenia and anemia was seen in three (21%) and four (29%) patients, respectively. Non-hematologic toxicity was in general mild to moderate except for two cases (14%) of grade 3 nausea and vomiting; overall incidence rates were nausea and vomiting (n=14), stomatitis (n=6), diarrhea (n=3), alopecia (n=11), infection (n=7), increase of serum creatinine (n=3), and peripheral neuropathy (n=3). The combination of mitoxantrone and cisplatin seems to be an active and fairly well-tolerated regimen for the treatment of advanced salivary gland cancers. According to the observed high rate of abrogating progressive disease for a long duration, and the resulting promising progression-free and overall survival time, further investigation seems warranted.     

New method to generate enzymatically deficient Clostridium difficile toxin B as an antigen for immunization

The family of the large clostridial cytotoxins, encompassing Clostridium difficile toxins A and B as well as the lethal and hemorrhagic toxins from Clostridium sordellii, monoglucosylate the Rho GTPases by transferring a glucose moiety from the cosubstrate UDP-glucose. Here we present a new detoxification procedure to block the enzyme activity by treatment with the reactive UDP-2', 3'-dialdehyde to result in alkylation of toxin A and B. Alkylation is likely to occur in the catalytic domain, because the native cosubstrate UDP-glucose completely protected the toxins from inactivation and the alkylated toxin competes with the native toxin at the cell receptor. Alkylated toxins are good antigens resulting in antibodies recognizing only the C-terminally located receptor binding domain, whereas formaldehyde treatment resulted in antibodies recognizing both the receptor binding domain and the catalytic domain, indicating that the catalytic domain is concealed under native conditions. Antibodies against the native catalytic domain (amino acids 1 through 546) and those holotoxin antibodies recognizing the catalytic domain inhibited enzyme activity. However, only antibodies against the receptor binding domain protected intact cells from the cytotoxic activity of toxin B, whereas antibodies against the catalytic domain were protective only when inside the cell.     

Erythropoietin receptor expression in human melanoma cells

Erythropoietin is well known for its role in the control of erythropoiesis, where it acts by binding to its cognate receptor (EpoR) on the surface of erythroid progenitor cells. Here we present the novel finding that the EpoR is also expressed in cells of the melanocytic lineage. It is expressed in transformed cell lines established from normal melanocytes and also in established human melanoma cell lines derived from melanoma metastases, but not in normal primary human melanocytes. The analysis of individual subclones isolated from spontaneously transformed melanocytes revealed that approximately 50% of all the clones examined expressed the EpoR. Further analysis of the individual growth characteristics of EpoR-positive and EpoR-negative clones indicated that, under standard cell culture conditions, expression of the receptor did not affect cell growth. Expression of this receptor is consequently most likely driven by an event that is associated with, but not absolutely required for, the transformed phenotype. While the definite function of this receptor in melanoma cells is still unknown and additional studies are required, our findings support the hypothesis that the EpoR may serve as a progression marker for human melanoma. This observation might be useful in the early diagnosis of melanoma.     

Frequency-dependent effects of phenytoin on frog junctional transmission: Presynaptic mechanisms

The action of the antiepileptic drug, phenytoin, on junctional transmission at various frequencies of synaptic activation was studied in frog nerve-muscle preparation. Intracellular recordings were made from muscle end-plates, and extracellular focal and subsendothelial recordings were obtained from motor nerve terminals and their parent axons, respectively. When the motor nerve was stimulated at 100-200 Hz, exposure to the drug (0.1-0.3 mM) induced intermittent failures of junctional transmission which appeared faster as the rate of stimulation was increased. At these and at lower stimulation frequencies (30-50 Hz), in which failures of transmission occurred only rarely, phenytoin markedly limited the buildup of end-plate potential amplitude during the period of repetitive nerve stimulation (tetanic potentiation). Several lines of evidence suggest that both drug effects are consequent to a frequency-dependent depression of the action potential at motor axons and terminals, which could lead to an intermittent conduction block at the higher rates of stimulation. The selective action of phenytoin on high frequency synaptic transmission may contribute to the specificity shown by this drug in suppressing epileptic seizures while sparing neuronal activity.