SYMPTOMATIC COLITIS AS THE INITIAL PRESENTATION OF WEGENER'S GRANULOMATOSIS

SUMMARY Wegener's granulomatosis is a multisystem disorder which rarely presents with gastrointestinal involvement. We report a case in which colitis was the reason for hospital admission. Diagnosis may be difficult unless clinical, serological and histopathological features are all considered.     

The pharmacology of a new pasteurized antihemophilic factor concentrate derived from human blood plasma

The pharmacology of a new pasteurized factor VIII (FVIII) concentrate derived from human blood plasma was studied in 23 adults with hemophilia A. In Part 1 of the study involving six nonbleeding subjects, the mean increase in FVIII activity was 1.43 +/- 0.34 U per ml 10 minutes after an intravenous dose of 50 U per kg. The intravascular survival kinetics in these six patients showed a biphasic decay curve with an initial mean half-life of 5.1 +/- 1.2 hours probably representing early redistribution, and a late half-life of 13.3 +/- 4.9 hours. In Part 2 of the study, the activity at 10 minutes was measured in another 17 patients, as well as in one patient already studied in Part 1. The mean increase in activity with the 24 observations was 1.13 +/- 0.37 U per ml with a mean FVIII dosage of 51.0 +/- 2.6 U per kg of body weight. Only one patient had an allergic reaction, which did not recur when the patient was given a second lot.     

Percutaneous umbilical blood sampling and umbilical vein transfusions. Rapid serologic differentiation of fetal blood from maternal blood

Percutaneous umbilical blood samples (PUBS), obtained under ultrasound guidance, are used for prenatal diagnosis and management of hemolytic disease of the newborn (HDN) and other fetal disorders. Rapid testing at the time of sampling is vital to distinguish fetal from maternal blood. Blood typing was performed by slide technique in the treatment room during 38 procedures on 25 patients. Anti-I was used to test 50 presumed PUBS; venous I-positive maternal blood was tested in parallel. Because anti-I cannot detect fetal blood after umbilical vein transfusion (UVT) of I-positive donor blood, ABO and Rh blood typing reagents were used to test 29 samples when maternal and fetal or donor blood groups differed. Monoclonal reagents were used for optimal detection of weak AB antigens in fetal blood. Avid, chemically modified anti-D was used for Rh typing. Blood typing showed 27 (34%) of 79 samples to be maternal blood. Fetal blood was obtained in 8 of 10 cases investigated for fetal disorder and in 16 cases of potential HDN (anti-D, 5; -CD, 5; -cE, 2; -K, 2; -c; -E). The absence of HDN (antigen-negative fetus) was determined in 4 cases. UVT afforded live birth of 9 of 10 infants with HDN and was not indicated in two cases.     

Comparison between published clinical success of direct resin composite restorations in vital posterior teeth in 1995–2005 and 2006–2016 periods

Composites are increasing in popularity as restorative materials. This growing role indicates the necessity of studies on their clinical outcome. In this study, clinical studies published on the performance of posterior composite restorations were included except those of less than a 24‐month assessment period. Results of non‐vital, anterior or primary teeth and cervical single‐surface restorations were also excluded. Records about composite type, number of final recall restorations, failure/survival rate, assessment period and failure reasons were analysed for each decade. Overall survival/failure rates for studies in 1995–2005 were 89.41%/10.59% and for 2006–2016 were 86.87%/13.13%, respectively. In 1995–2005, the reasons for failure were secondary caries (29.47%) and composite fracture (28.84%) with low tooth fracture (3.45%) compared with reasons of failure in 2006–2016, which were secondary caries (25.68%), composite fracture (39.07%), and tooth fracture (23.76%). An increase in incidence of composite fracture, tooth fracture and need for endodontic treatment as failure reasons was noted in the latter decade in addition to a decrease in secondary caries, postoperative sensitivity, unsatisfactory marginal adaptation and wear. The overall rates of failure showed little difference, but the causes showed a notable change. This is believed to be a reflection of increased use of composites for larger restorations and possibly changes of material characteristics.     

Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency

Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3- tetrahydrofolate and five patients with defects in the synthesis of CH3- Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.     

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

An approach to post‐radical trachelectomy vaginal‐isthmus cytology

Radical trachelectomy (RT) is the surgical amputation of the uterine cervix with paracervical lymphadenectomy, performed in reproductive age women to treat invasive squamous‐cell carcinoma or endocervical adenocarcinoma while preserving the uterine corpus for potential child bearing. Post‐RT patient monitoring includes isthmic‐vaginal cytology. This study reviews our experience with liquid based preparation of post‐RT cytology samples. Fifty‐four post‐RT vaginal‐isthmic cytology specimens were reviewed from nine patients, seven with adenocarcinoma, and two with squamous‐cell carcinoma. Five patients had normal (NILM) or normal with reactive changes on all cytology samples. Two patients had isolated squamous abnormalities (atypical squamous‐cells of uncertain significance (ASC‐US) and low‐grade squamous intraepithelial lesion (LSIL)); both follow‐up biopsies were negative. Two patients had repeatedly abnormal specimens interpreted as atypical glandular cells (AGC), one of whom also had a concurrent ASC‐US. Only one sample was tested for high risk human papilloma virus (hrHPV), with negative results. All patients with abnormal cytology went on to have biopsies which were interpreted as benign. The cytology specimens most often interpreted as AGC contained many groups of hyperchromatic crowded glandular cells and/or stromal cells derived from direct sampling of the lower uterine segment. The crowding often limits visualization of all the cells in a group, plus sampled endometrium may harbor mitoses, adding to the atypical appearance. Cytologists should become familiar with the spectrum of changes in the post‐RT cytology. Testing for hrHPV should be considered for use in the management of abnormal cytology results. Post RT cytology should be compared with presurgical cytology since one would anticipate similarities in post‐RT true positive cases. In particular, a primary diagnosis of adenocarcinoma makes differentiating benign reactive glandular cells from recurrence a critical issue. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura

An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane.