Mycoplasma-pneumoniae-induced thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement. Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation. Recent data imply that all these different causes may induce the disease by decreasing the activity of the plasma von Willebrand factor-cleaving protease resulting in unusually large von Willebrand factor multimers that later on initiate the cascade of TTP. In this communication, we present a unique association between infection with Mycoplasma pneumoniae and TTP. We believe that the emergence of antibodies that cross-react with Mycoplasma and the protease might elucidate in this case the pathogenesis of TTP.     

Evaluation of the Glasgow coma scale score in critically Ill infectious disease patients

Summary In this prospective study the Glasgow Coma Scale (GCS) score was evaluated in 107 critically ill infectious disease (ID) patients admitted to the Intensive Care Unit (ICU) during a 1-year period. Patients were separated into two groups: those affected by central nervous system (CNS) infections and those affected by infections other than of the CNS. There were no apparent differences in the first ICU day GCS score values between the two groups (11±4 vs. 11±4, p=0.5318). Univariate logistic regression analysis confirmed a significant relationship between the first ICU day GCS score and the subsequent ICU mortality in the group of patients with CNS infections (r=0.3152, p=0.0015) but not in the group with infections not affecting the CNS (r=0.0919, p=0.1106). Our preliminary results suggest that the prognostic value of the GCS score is valid only in patients with CNS infections but not in other ID patients.

---

Evaluierung der Glasgow Coma Skala bei schwerkranken Patienten mit Infektionen

Zusammenfassung Die Glasgow Coma Scale (GCS) wurde bei 107 schwerkranken Patienten mit Infektionen im Rahmen einer prospektiven Studie evaluiert. Es handelte sich um Patienten, die während eines Jahres in der Intensivpflegestation behandelt wurde. Sie wurden nach dem Vorliegen oder nicht Vorliegen einer Infektion des Zentralnervensystems in zwei Gruppen eingeteilt. In den GCS-Scores am ersten Tag der Intensivpflegebehandlung wiesen die beiden Gruppen keine Unterschiede auf (11±4 und 11±4; p=0,5318). Die logistische Regressionsanalyse für eine Variable deckte eine signifikante Beziehung zwischen dem GCS Punktewert am ersten Tag und der folgenden Sterberate bei Patienten mit ZNS-Infektionen auf (r=0,3152; p=0,0015). Bei Patienten, deren Infektion das ZNS nicht betraf, war eine derartige Beziehung nicht zu erkennen (r=0,0919; p=0,1106). Diese vorläufigen Ergebnisse lassen darauf schließen, daß der Glasgow Coma Score nur bei Patienten mit ZNS-Infektionen eine valide Funktion hat, nicht aber bei Patienten mit anderen Infektionen.

     

Successful repair of a large aortic abscess causing apical displacement of the anterior mitral valve

Anatomic continuity between the anterior mitral leaflet and the aortic root may predispose those patients with aortic root pathology to functional changes of the mitral valve without any involvement of this valve. A 34-year-old man presented with aortic valve endocarditis. Transthoracic echocardiograpy showed severe aortic regurgitation with a large aortic root abscess. The anterior leaflet of the mitral valve was displaced towards the apex of the heart causing moderate mitral regurgitation. The patient underwent aortic valve replacement with reconstruction of the aortic annulus and ventriculoaortic continuity. This procedure alone restored the mitral valve structure and function without any need for intervention on the mitral valve. Aortic abscess is a serious complication of aortic valve endocarditis and may alter the function of other structures of the heart, especially the mitral valve. Restoration of aortic wall integrity and left ventricular – aortic continuity usually restores the mitral valve structure and function if the valve is unaffected by the infection. A decision on the mitral valve should be made following correction of the aortic pathology.     

Distinct behavior of mutant triosephosphate isomerase in hemolysate and in isolated form: molecular basis of enzyme deficiency.

In a Hungarian family with severe decrease in triosephosphate isomerase (TPI) activity, 2 germ line-identical but phenotypically differing compound heterozygote brothers inherited 2 independent (Phe240Leu and Glu145stop codon) mutations. The kinetic, thermodynamic, and associative properties of the recombinant human wild-type and Phe240Leu mutant enzymes were compared with those of TPIs in normal and deficient erythrocyte hemolysates. The specific activity of the recombinant mutant enzyme relative to the wild type was much higher (30%) than expected from the activity (3%) measured in hemolysates. Enhanced attachment of mutant TPI to erythrocyte inside-out vesicles and to microtubules of brain cells was found when the binding was measured with TPIs in hemolysate. In contrast, there was no difference between the binding of the recombinant wild-type and Phe240Leu mutant enzymes. These findings suggest that the missense mutation by itself is not enough to explain the low catalytic activity and "stickiness" of mutant TPI observed in hemolysate. The activity of the mutant TPI is further reduced by its attachment to inside-out vesicles or microtubules. Comparative studies of the hemolysate from a British patient with Glu104Asp homozygosity and with the platelet lysates from the Hungarian family suggest that the microcompartmentation of TPI is not unique for the hemolysates from the Hungarian TPI-deficient brothers. The possible role of cellular components, other than the mutant enzymes, in the distinct behavior of TPI in isolated form versus in hemolysates from the compound heterozygotes and the simple heterozygote family members is discussed.     

Problem-based learning in occupational therapy curriculum – implications and challenges

Purpose: Problem-based learning (PBL) is an educational method that fosters self-directed study in small groups. The purpose of this study was to describe the Tel Aviv University’s occupational therapy (OT) program and the challenges implementing such program. In addition, the study compared the PBL grades obtained by students who are native Hebrew speakers with those students who are native Arabic speakers; and, assessed the correlation between the grades in the PBL course and the grades in the clinical fieldwork studies.

Method: 166-second year OT undergraduate students participated. All completed three PBL courses and seven weeks of clinical fieldwork studies. Data collection included students’ grades in PBL course (based on PBL evaluation forms) and in clinical fieldwork studies (based on preceptor’s evaluation and a written assignment).

Results: Pearson correlations revealed significant correlations between PBL grades and clinical fieldwork studies grades. T-test analysis between students who are native Hebrew speakers and those who are native Arabic speakers revealed significant differences in PBL grades.

Conclusions: Findings imply partial congruence between students’ grades in the PBL course and their achievements in the fieldwork studies. Findings might suggest that adjustments should be made in order to assist students from minorities (challenged by language requirements) in gaining higher grades in the PBL program.

• Implications for Rehabilitation

• Problem-Based Learning (PBL) is an educational method, which fosters independent, self-directed study in small groups.

• PBL studies have the potential to prepare students for their clinical experience during studies.

• The PBL program should be adjusted for students from minorities (challenged by language requirements and different cultural backgrounds) in order to assist them in gaining more benefits from the program.

     

Dermatologic manifestations in lupus erythematosus

Various dermatologic manifestations are observed in the different lupus subsets. Lupus lesions are most frequently characterized by a dermoepidermal dermatitis. Other lesions, vascular or nonvascular, are essentially present in association with systemic lupus erythematosus. Acute, subacute and chronic lupus erythematosus are distinguishable according to their clinical aspects, pathological features and their evolution. Acute lesions are either localized to the midface or widespread. Subacute lesions may be annular or psoriasiform. Chronic lupus erythematosus includes localized or widespread discoid lupus, lupus tumidus, chilblain lupus and panniculitis. Therapy of cutaneous lupus is mainly based on antimalarials and avoidance of sun exposure. In refractory cutaneous lupus, no universal guidelines are available. Except for acrosyndromes and urticaria-like lesions, vascular lesions may be due to vasculitis or thrombosis. An accurate diagnosis is necessary, since therapeutic management is quite different in these two conditions. Nonvascular and nonlupus lesions are numerous and some of them require specific treatment, such as dapsone for bullous lupus.     

High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome

Forty-five patients with metastatic breast cancer without clinically evident disease were treated with thiotepa 750 mg/m2, mitoxantrone 40 mg/m2 and carboplatin 1000 mg/m2 followed by stem cell transplantation to determine the safety and efficacy of CD34+ selection of peripheral blood stem cells. Of these, 15 patients' (group I) stem cells were processed through Baxter Isolex 300 device for CD34+ selection, whereas 30 patients (group II) received unmanipulated stem cells. Toxicity, progression-free survival and survival were compared between these two groups. There was no difference in transfusion requirements, white cell count and platelet recovery and non-hematologic toxicity between the two groups. The survival of patients in group I was 27 months compared to 38 months in group II (P = 0.8). The progression-free survival was 12 months and 13.5 months for group I and group II patients, respectively (P = 0.6). Our results indicate that while there is no adverse effect, there is also no significant advantage of CD34+ selection in terms of progression-free survival and survival in patients with metastatic breast cancer without clinically evident disease. Bone Marrow Transplantation (2000).     

Primary amenorrhea associated with hirsutism, acanthosis nigricans, dermoid cysts of the ovaries and a new type of insulin resistance

We describe a 15 1/2 year old presenting with primary amenorrhea, hirsutism, acanthosis nigricans and insulin resistance. Ovarian vein catheterization studies revealed bilateral excess plasma testosterone and androstenedione secretion, and at surgery multiple dermoid cysts of both ovaries were found in association with polycystic ovaries. The suggestion that the dermoid cysts may be causative in the evolution of the polycystic ovarian disease has been made. The mechanism of the insulin resistance appears to be at the post receptor level. The acanthosis nigricans diminished following surgery with normalization of the plasma androgens.     

Why multiple small subunits (Y2 and Y4) for yeast ribonucleotide reductase? Toward understanding the role of Y4

Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides. Class I RNRs are composed of two homodimeric subunits: R1 and R2. R1 is directly involved in the reduction, and R2 contains the diferric-tyrosyl radical (Y*) cofactor essential for the initiation of reduction. Saccharomyces cerevisiae has two RNRs; Y1 and Y3 correspond to R1, whereas Y2 and Y4 correspond to R2. Y4 is essential for diferric-Y* formation in Y2 from apoY2, Fe(2+), and O(2). The actual function of Y4 is controversial. Y2 and Y4 have been further characterized in an effort to understand their respective roles in nucleotide reduction. (His)(6)-Y2, Y4, and (His)(6)-Y4 are homodimers, isolated largely in apo form. Their CD spectra reveal that they are predominantly helical. The concentrations of Y2 and Y4 in vivo are 0.5-2.3 microM, as determined by Western analysis. Incubation of Y2 and Y4 under physiological conditions generates apo Y2Y4 heterodimer, which can form a diferric-Y small middle dot when incubated with Fe(2+) and O(2). Holo Y2Y4 heterodimer contains 0.6-0.8 Y* and has a specific activity of 0.8-1.3 micromol.min.mg. Titration of Y2 with Y4 in the presence of Fe(2+) and O(2) gives maximal activity with one equivalent of Y4 per Y2. Models for the function of Y4 based on these data and the accompanying structure will be discussed.