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Inspiratory work and response times of a modified pediatric volume ventilator during synchronized intermittent mandatory ventilation and pressure support ventilation.

Volume ventilation by demand flow ventilators significantly increases work of breathing during inspiration. Although various ventilator modifications and different modes of ventilation have been developed, there have been few studies regarding imposed work of breathing in infants and children. This study was designed to evaluate several modifications of a commercially available demand flow ventilator designed to shorten response time (tr) and decrease the imposed work (Wi) involved in opening the demand valve. Minimum withdrawal volume (Vmin), maximum negative pressure (P mneg), and tr were measured. Wi was defined as the product of Vmin and P mneg. Seven Siemens Servo 900C ventilators were tested under 16 different trial conditions with four variables: 1) mode of ventilation (synchronized intermittent mandatory ventilation [SIMV] vs. pressure support ventilation [PSV]); 2) caliber of circuit tubing (adult vs. pediatric); 3) location of airway pressure monitor (distal vs. proximal); and 4) ventilator trigger sensitivity (0 cm H2O--high vs. -2 cm H2O--low). Vmin, Pmneg, and Wi were all decreased (P less than .05) while tr was unaffected by changing ventilator trigger sensitivity from low to high. Wi was decreased by pediatric tubing and proximal airway pressure monitoring only when low trigger sensitivity was used. PSV and proximal airway monitoring shortened tr. The authors conclude that the use of pediatric circuit tubing and proximal airway pressure monitoring with a Siemens Servo 900C ventilator significantly improved ventilator performance.

Adult↗

Laboratory diagnosis of heparin-induced thrombocytopenia: advantages of a functional flow cytometric test in comparison to the heparin-induced platelet-activation test.

Nearly one third of patients with heparin-induced thrombocytopenia (HIT) will progress to overt thrombosis. Owing to the severity of HIT, a reliable prompt diagnosis is mandatory. In this study 248 consecutive samples from patients referred to our laboratory for HIT diagnosis and 97 specimens from normal controls were prospectively evaluated in parallel using the heparin-induced platelet aggregation (HIPA) test and a flow cytometric (FC) test. The HIPA test resulted in 214 negative, 17 indeterminate and 17 positive samples of patients. The FC method detects activated platelets induced by heparin-immune complexes using the highly sensitive recombinant probe annexin V and pooled platelets from multiple donors. The criteria for positive FC test results included an increase in platelet activiation of at least 11% at 0.3 IU/mL heparin concentration in the tube, and a ratio of more than 1.5 between platelet activation at 0.3 and 200 IU/mL heparin. According to the cut-off level 17 patients who showed indeteminate HIPA test results had 14 negative and 3 indeterminate corresponding FC test results. Only one of these patients (HIPA test indeterminate, FC test indeterminate) had no other obvious medical cause for thrombocytopenia than HIT. Infections or inflammations did not show any association with the FC test results, whereas thromboembolic events displayed a significant patelet activation at pharmacological heparin concentration. Therefore the FC test is associated to the complications of HIT. In conclusion, the FC test, which is fast and practical, showed a good agreement with the HIPA test and may be an accurate and useful test for HIT.

Annexin A5↗

[Combined chemo-radiotherapy in non-operable cervico-facial neoplasms. Final results of an experience with non-selected patients].

The management of advanced inoperable head and neck cancer is often based on a combined chemo-radiotherapy approach. No definitive conclusions on the effectiveness of this combination can be drawn from clinical trials because these neoplasms are heterogeneous and treatment schedules vary. Many scientific trials test highly toxic combinations, whereas not only good results but also low toxicity are mandatory in the current practice. We report the results obtained in 90 consecutive patients affected with inoperable head and neck cancers in stages III-IV, or relapsed after surgery. Chemotherapy consisted of a cis-platinum/bleomycin induction phase, followed by weekly administrations of cis-platinum simultaneous with conventional irradiation. The objective remission rates, achieved at the end of the induction chemotherapy and the simultaneous chemo-radiotherapy phases, were respectively 55.5% and 84.5%. The tumor disappeared in 39% of cases, by the end of the whole treatment. With the Kaplan-Meier method, 3-year overall, progression-free and relapse-free survival rates were 21.20%, 22.25% and 38.75%, respectively. The overall survival rate, calculated with the "log-rank" test according to the stage and the site of the primary tumor, exhibited no significant differences. In contrast, significant differences (p < 0.05) were demonstrated, according to treatment intent (curative radical: 26%, vs palliative: 0%) and to the achievement of an objective response at the end of induction chemotherapy--i.e., 48% 3-year survival rate, vs 7% in chemotherapy resistant cancer patients. When limiting the analysis to 72 radically irradiated patients, however, the achievement of CR after induction chemotherapy lost its prognostic value. Toxicity was not substantially higher than with conventional irradiation. Our results are in agreement with literature data on this subject which, regarding survival, fail to prove such integrated treatments as ours better than irradiation alone. In contrast, the preliminary combination of chemotherapy and irradiation is clearly better for the patients waiting to receive radiation therapy, because tumor volume and related symptoms markedly decrease after induction chemotherapy. Currently the best survival rates (about 50% at 3 years) with chemo-radiotherapy are obtained, in this kind of cancer, by combining cis-platinum and continuous-infusion 5-fluorouracil, simultaneous with irradiation. However, frequent and severe toxicity is reported. Should such a modality be adopted in the current practice, patients should be selected according to their medical conditions.

Adult↗

Sensitization to thimerosal in atopic children.

Thimerosal is an organic mercurial compound widely used as a preservative in vaccines, eyedrops, and contact lens cleaning and storage solutions. 5 infants, 2 female and 3 male, ranging in age from 7 to 28 months and affected by atopic dermatitis (AD) diagnosed according to the Hanifin and Rajka criteria, experienced an exacerbation of their clinical condition 2-10 days after mandatory vaccinations with vaccines containing thimerosal. Cutaneous lesions of nummular eczema appeared on the trunk, limbs and face. All patients were patch tested with serial dilutions of thimerosal in petrolatum. A positive patch test reaction to thimerosal 0.1% pet. was observed in all 5 children. 3 of them also showed a positive reaction at 0.01% and 0.05% pet. Despite their thimerosal-hypersensitivity, all children completed the entire series of mandatory vaccinations, care being taken to use different needles for injection and aspiration of the vaccine. The 2-year follow-up did not reveal other episodes of exacerbation of the AD after vaccination. The present study confirms the high frequency of sensitization to thimerosal in atopic children and suggests that vaccination can cause clinical symptoms in sensitized children. Nevertheless, sensitization to thimerosal does not prevent children from continuing with mandatory vaccinations.

Child, Preschool↗

Recommended testing in diabetes research.

Diabetic disease is increasing rapidly and vast amounts of resources are spent in all countries. Thus, the screening of new compounds including plant extracts for antidiabetic effects is mandatory. In this review both simple assays [e.g., on blood glucose (after or without a glucose load), plasma insulin and extrapancreatic effects] are described as well as specific in vivo tests in diabetic animals and in vitro tests with respect to the mechanism of compounds. In total, approx. 30 selected tests are evaluated and references are given. Thus, the investigator is guided through the tests and is advised that measuring only one parameter such as glucose will not be sufficient. In the case that the financial resources are poor for the investigator, more than glucose still has to be measured. A balance is made by describing absolutely necessary investigations while concentrating on those at low cost. It has to be started with simple assays; to use one test only, however, means oversimplifying the diabetes disease; additionally antidiabetic effects may be missing. The investigator is guided through the advantages and limitations of diabetic animal models and is advised about specific in vitro tests to look at the mechanism of action. All investigators should profit from these details, not only the phytoresearchers.

Animals↗

Techniques for performing caesarean section.

In many countries caesarean section has become the mode of delivery in over a quarter of all births. Safety of the mother and cost are the two main areas of concern. Various studies on the techniques of performing a caesarean section have focused on reducing the operating time, blood loss, wound infection and cost. Given the fact that caesarean section is the most commonly performed operation in obstetrics, it is important that trainers and trainees are familiar with the basic surgical techniques and that best practice is followed. At the same time surgeons should take necessary precautions to reduce their risk of exposure to Hepatitis B and HIV. The skin incision and entry into abdominal cavity is best achieved by the modified Cohen's incision. The lower segment transverse uterine incision has stood the test of time over a period of 75 years and remains the best way to enter the uterus. Closure of the uterus in single layer appears to be acceptable, whenever technically possible. Placental delivery should be by controlled cord traction after spontaneous expulsion. Closure of the visceral and parietal layers of the peritoneum no longer seems to be necessary. Obliteration of space in the subcutaneous layer, either by suture or by suction, seems to reduce wound disruption. These issues are being considered in the CAESAR randomized controlled trial of surgical techniques currently underway in England.Prophylactic antibiotics are mandatory in preventing post-operative morbidity. Many of the above mentioned steps have been tested in randomized trials. Further studies are needed to examine a wide range of questions arising from this review, e.g. best position of the patient, the value of exteriorization of the uterus whilst repairing the uterus, and the use of agents to relax the uterus in difficult deliveries.

Antibiotic Prophylaxis↗

Ophthalmology resident surgical competency: a national survey.

PURPOSE: To describe the prevalence, management, and career outcomes of ophthalmology residents who struggle with surgical competency and to explore related educational issues. DESIGN: Fourteen-question written survey. PARTICIPANTS: Fifty-eight program directors at Accreditation Council on Graduate Medical Education-accredited, United States ophthalmology residency programs, representing a total of 2179 resident graduates, between 1991 and 2000. METHODS: Study participants completed a mailed, anonymous survey whose format combined multiple choice and free comment questions. MAIN OUTCOME MEASURES: Number of surgically challenged residents, types of problems identified, types of remediation, final departmental decision at the end of residency, known career outcomes, and residency program use of microsurgical skills laboratories and applicant screening tests. RESULTS: One hundred ninety-nine residents (9% overall; 10% mean per program) were labeled as having trouble mastering surgical skills. All of the programs except 2 had encountered such residents. The most frequently cited problems were poor hand-eye coordination (24%) and poor intraoperative judgment (22%). Most programs were supportive and used educational rather than punitive measures, the most common being extra practice-laboratory time (32%), scheduling cases with the best teaching surgeon (23%), and counseling (21%). Nearly one third (31%) of residents were believed to have overcome their difficulties before graduation. Other residents were encouraged to pursue medical ophthalmology (22%) or to obtain further surgical training through a fellowship (21%) or a supervised practice setting (12%); these residents were granted a departmental statement of satisfactory completion of residency for Board eligibility. Twelve percent were asked to leave residency. Of reported career outcomes, 92% of residents were practicing ophthalmology, 65% as surgical and 27% as medical ophthalmologists. Ninety-eight percent of residency programs had microsurgical practice facilities, 64% had a formal teaching course, and 36% had mandatory practice time. Most programs (76%) did not perform applicant vision or dexterity screening tests; questions existed about the legality and validity of such tests. CONCLUSIONS: The issue of ophthalmology residents who struggle to develop surgical competency appears common. Although many problems appear to be remediable with time, practice, and dedicated, patient teachers, more specific guidelines for a statement of surgical competency are likely necessary to standardize the Board certification process.

Career Choice↗

[A rheological method for the measurement of red cell deformability (author's transl)].

In a comparison of the filtration methods of Reid et al. and Schmid-Schönbein et al., the significance of other formed blood elements for the assessment of red cell deformability is established. The hydrodynamic measurements and the morphological inspection of the sieves show the interference of red cell pore passage by thrombozyte aggregates and white blood cells (which were not further identified). In light of these findings, which have since been corroborated by other groups, it is mandatory to remove all cellular blood elements exept the red cells in filtration test of the latter. Lowering the hematocrit improves the reliability of the test. The whole blood filtration test, popular because of its simplicity, cannot be standardized and yields results of questionable relevance.

Blood↗

The effect of an osteolytic tumor on the three-dimensional trabecular bone morphology in an animal model.

OBJECTIVE: To investigate the application of micro-computed tomography (microCT) for the assessment of density differences and deterioration of three-dimensional architecture of trabecular bone in an experimental rat model for tumor-induced osteolytic defects. DESIGN AND MATERIALS: Walker carcinosarcoma 256 malignant breast cancer cells (W256) were surgically implanted into the medullary canal of the left femur of 15 4-month-old rats. Twenty-eight days after surgery all animals were killed and both femora from each rat were harvested. A total of 30 specimens (left and right femur) were scanned in a desktop microCT imaging system (microCT 20, Scanco Medical) to assess densitometric and architectural parameters. For each specimen a total of 200 micro-tomographic slices with a resolution of 30 microns in the distal metaphysis was taken. Bone mineral content (BMC) was analyzed for both cortical and trabecular bone (ctBMC), and for trabecular bone only (tBMC). Architectural indices (BV/TV, Tb.N, Tb.Th, Tb.Sp) according to standard definitions used in histomorphometry were calculated for trabecular bone. RESULTS: The quantitative analysis of density parameters revealed significantly (P < 0.001) lower values for ctBMC and tBMC in the tumor-bearing group (T) of 26% and 31%, respectively, compared with the contralateral control group. The quantitative analysis revealed significant (P < 0.001) changes in the architectural parameters in the tumor-bearing bones compared with the contralateral control group: BV/TV was 30% lower, Tb.N and BS/TV decreased by 24% and 21%, respectively, Tb.Th. decreased by 10% and Tb.Sp. increased by 94%. CONCLUSIONS: This study demonstrates that microCT is able to provide three-dimensional parameters of bone mass and trabecular structure in an animal model for tumor-induced bone loss. Recent advances in therapeutic approaches for skeletal diseases such as osteoporosis and metastatic bone diseasse rely on an understanding of the effects of the agents on the mechanical properties of bone. In order to quantify the structural changes of the affected bones the application of a non-destructive method is mandatory. The use of microCT seems to be a great advantage, since biomechanical tests and further histologic analysis can be done for the same specimens.

Animals↗

Does academic intervention impact ABS qualifying examination results?

OBJECTIVES: To assess the impact of a focused academic support program on American Board of Surgery In-Training Examination (ABSITE) scores and Qualifying Examination (QE) outcomes. METHODS: A mandatory intervention program was begun in April 2001 for residents with ABSITE Total Test (TT) percentiles <31. Program elements included: 1) individual faculty mentoring and personal learning plan 2) QE videotape review sessions 3) Surgical Education and Self-Assessment Program (SESAP) 4) monthly rotation evaluations, and 5) quarterly status feedback. A free medical evaluation was offered. Mock orals participation, educational psychologist consultation, and voluntary followup mentoring were added later. Study data were reviewed for 2003-2005 Chief Residents including ABSITE scores, QE results, conference attendance, rotation Overall Performance ratings, and resident surgeon case volumes. Results were compared for the academic intervention (AI) and no intervention (NI) groups. RESULTS: Fifteen residents graduated during the study period. Eight residents completed nine interventions; seven returned to TT percentiles >30 (7/8, 88%). First post-intervention ABSITE gains were large compared to NI and national peer groups. Standard Score (SS) TT gains were maintained until residency completion by four AI residents. Median AI PGY-5 TT percentile was 32 and three scores were <or=25. Six AI residents (6/8, 75%) and all NI residents (7/7, 100%) passed the QE on their first attempts. AI and NI groups were similar for conference attendance, rotation evaluations, and operative log totals. CONCLUSIONS: A focused academic support intervention for residents with marginal ABSITE TT percentiles can produce immediate substantial gains. Gains are variably maintained through remaining residency years. PGY-5 TT percentiles <or=25, seen with three AI residents (3/8, 38%), are associated with a 40% first QE failure rate. Therefore, our 75% QE first-time pass rate for AI residents argues for intervention success.

Curriculum↗

The experimental production of a persistent ductus arteriosus for testing catheter closure devices.

An experimental model was constructed to simulate a persistent ductus arteriosus (PDA) in infants. In 21 beagles (mean weight, 8.2 kg), a piece of subclavian artery was interposed between the main pulmonary artery and the aorta, thereby creating a large left-to-right shunt across the short, straight arterial pathway. There were no intraoperative complications. Three animals died postoperatively of stenosing tracheitis, pneumothorax, or bronchopneumonia. The model proved suitable for the serial testing of a new transvenous catheter closure procedure. Occlusion of the shunt was mandatory within a day after placement or severe heart failure would occur. Twelve animals with a released silicone double-balloon plug inside the vascular connection had a long-term follow-up of up to three years. Autopsy findings after the death of the animals at specified intervals revealed smooth ingrowth of the anastomoses and occlusion, by endothelialized fibrous tissue, of the pulmonary and aortic sides of the plugged experimental PDA within a month.

Animals↗

The electrocardiographic diagnosis of acute myocardial infarction in patients with ventricular paced rhythms.

The electrocardiographic diagnosis of ischemic heart disease is more difficult in the setting of ventricular-paced rhythms (VPR). ST segment/T wave configurations are changed by the altered intraventricular conduction associated with ventricular pacing. The anticipated, or expected, morphology in patients with VPR is one of QRS complex-ST segment/T wave discordance. An awareness of the anticipated ST segment morphologies of VPR is mandatory for the emergency physician. This knowledge is not dependent on additional diagnostic testing, medical records, or expertise in pacemaker function. Two cases are presented in which an analysis of the electrocardiogram in the setting of VPR assisted the treating physicians in establishing the correct diagnosis of acute myocardial infarction and arranging for urgent revascularization.

Aged↗

Temporal and spatial patterns of the clinical surveillance of BSE in France, analysed from January 1991 to May 2002 through a vigilance index.

Between 1991 and mid 2000, the surveillance of Bovine Spongiform Encephalopathy (BSE) in France was based solely on clinical surveillance through a Mandatory Reporting System. Since 2000, the implementation of active surveillance programmes using rapid tests, as a complementary tool targeted at dead and slaughtered cattle has shown that part of the BSE cases were not detected with the clinical surveillance. In order to obtain a better knowledge of the strength of the clinical surveillance, we analysed a vigilance index defined as the ratio of negative clinical suspicions to the cattle population in the region and period of interest. The temporal analysis of the vigilance index showed that it did not vary much between 1991 and 1999, increased sharply since 2000, and then decreased partly in 2001. The geographical analysis of the variations of the vigilance index was performed at the department level by comparing the observed number of negative clinical suspicions per department to the expected number, computed on the basis of the national average index and standardised on the production type of the cattle - dairy versus beef suckling cattle. As assumed, the data followed a Poisson distribution. We observed a high geographical variation of the vigilance index: ten departments out of 91 presented a significantly higher vigilance index than the national one, and four a significantly lower vigilance index. The vigilance index showed that the clinical surveillance was heterogeneous during the past twelve years, both in time and geographic location, in a range of one to ten. So the apparent trend in the BSE epidemic during this period as well as the differences in the spatial incidence of BSE have to be analysed with caution.

Animals↗

Reactive arthritis: urogenital swab culture is the only useful diagnostic method for the detection of the arthritogenic infection in extra-articularly asymptomatic patients with undifferentiated oligoarthritis.

Reactive arthritis (ReA) is a seronegative oligoarthritis triggered by a preceding extra-articular infection. While evidence of a microbial infection is mandatory for establishing the diagnosis of ReA, the sensitivity of bacteriological and serological tests has not been determined in patients without symptoms of infection. In a retrospective study, we evaluated the usefulness of urogenital swab cultures, serology and stool culture to identify infections in 234 patients with undifferentiated oligoarthritis. One hundred and forty-four patients complaining about joint pain who had no sign or history of inflammatory arthritis served as controls. Urogenital swab cultures showed a microbial infection in 44% of the patients with oligoarthritis (15% Chlamydia, 14% Mycoplasma, 28% Ureaplasma), whereas in the control group only 26% had a positive result (4% Chlamydia, 7% Mycoplasma, 21% Ureaplasma) (P < 0.001). A Chlamydia IgG-antibody titre > or = 1:256 was found in 22% of the patients in the oligoarthritis group and in 9% of the controls (P < 0.01). However, for only half of Chlamydia IgG-positive patients could a Chlamydia infection be confirmed by urogenital swab culture. Twenty-one per cent of patients with oligoarthritis vs 23% of the controls had positive antibody titres for Salmonella (not significant), 15% vs 5% for Yersinia (P < 0.05) and 17% vs 3% for Borrelia IgG (P < 0.01). In two patients, stool cultures were positive for Campylobacter. Urogenital swab culture is a sensitive diagnostic method to identify the triggering infection in ReA. A single determination of antibodies against Chlamydia trachomatis is of limited value because of the high prevalence of positive results in the control group.

Adult↗

Invasive aspergillosis. Clinical features of 35 proven cases at a single institution.

Thirty-five patients with clinical features and histologically or microbiologically proven infection met predetermined stringent criteria for invasive aspergillosis over a 5-year period at our institution. Underlying conditions included hematologic malignancy, solid tumor, bone marrow and solid organ transplantation, and immunosuppressive therapy. The majority of patients (94%) presented with respiratory symptoms and abnormal pulmonary chest radiography; only 40% had neutropenia at time of infection. Invasive aspergillosis was suspected in only 21 cases (60%). Concomitant infections were present in 83% of patients. Half of patients had pathogenic or potentially pathogenic microorganisms other than Aspergillus spp. isolated from pulmonary specimens at time of aspergillosis. Aspergillus spp. were recovered from sputum in 75% of patients and from bronchoalveolar lavage in only 52%. Invasive aspergillosis is an unexpectedly unrecognized disease with poor outcome; overall mortality was 94% in our series. The lack of sensitivity of diagnostic procedures, together with the high frequency of concomitant infections, delays the time of diagnosis. Early diagnostic tests are needed, and presumptive antifungal therapy among high-risk patients is mandatory.

Adult↗

New strip immunoblot for the confirmation of HTLV-I/II infection.

In The Netherlands, anti-human T-cell lymphotropic virus type I (HTLV-I) blood donor screening became mandatory in January 1993. Donations reactive in the enzymelinked immunosorbent assay (ELISA) screening test are confirmed with Western blot analysis (WB). Only WB-positive or indeterminate blood donors are notified and retested by polymerase chain reaction (PCR) [1]. In accumulated data of the Dutch Blood Banks, only 2% of donors repeatedly positive in the anti-HTLV-I/II ELISA were WB-positive and all of these were also PCR-positive. However, 75% of the ELISA-positive blood donors have indeterminate WB results. In these cases the ELISA reactivities are nonspecific since all WB-indeterminate donors are negative in PCR [2]. Current WB confirmation thus leads to the notification and often to the deferral of many WB-indeterminate blood donors as well as to high costs for PCR testing, illustrating the need for a more specific serological confirmatory assay. The aim of our study was to evaluate a newly developed anti-HTLV-I/II Recombinant Immunoblot Assay (RIBA) to confirm samples reactive to screening tests with a special emphasis on the ability of this test to resolve WB-indeterminate results in blood donors, without compromising the sensitivity.

Blotting, Western↗

Measurement of free drug in phase I: is it useful?

Early investigation of protein binding of a new drug is mandatory. The following questions have to be answered: is unbound fraction constant over tested concentrations? Which proteins are involved? What are the binding parameters? Can the drug compete with other therapeutic agents for the binding sites or in other words can drug displacements be predicted? What is the interindividual variability in protein binding? Is the binding stereoselective? All this information is necessary in predicting the pharmacokinetic behaviour of the drug and in assisting in the design of future pharmacokinetic protocols in phases II and III. The use of free drug concentration should also be considered when comparing the bioavailability of regular vs sustained release dosage forms of drugs exhibiting concentration-dependent binding and when studying concentration-effect relationships.

Drug Evaluation↗

Biosynthesis of human blood group T-, N- and M-specific immunodeterminants on human erythrocyte antigens.

We synthesized on Tn erythrocytes with human sera, UDP-Gal, and activators T-specific haptenic structures in satisfactory yield. The specificity of this biosynthesis was ascertained by agglutination with human and animal anti-T, by specific absorption of human anti-T as well as by agglutination inhibition assays. With isolated human erythrocyte T antigen as substrate we synthesized N- and M-specific structures with sera from individual human donors in presence of CMP-sialic acid by incubation for 24 hr at 37 degrees C. Serology on the recovered product was carried out with nineteen monospecific human and animal sera under strictly standardized and controlled conditions with the mandatory tube assay. All M- as well as N-derived T antigens tested acquired N specificity with all transferase sera of all MN types. In contrast, M-activation of M- and N-drived T antigens tested acquired N specificity with all transferase sera of all MN types. In contrast, M-activation of M- and N-derived T antigens occurred only if the transferase donor had the M gene. The nine M transferase sera used all gave M-activation of MM- and NN-derived T antigens. None of twelve transferase sera from NN donors M-activated any T antigen. NN antigen was transformed to a M-specific one by all transferase sera from MM donors but by none from NN donors. We have not yet established the biochemical-genetic relation of M to N; N may be the immediate precursor of M or M may originate directly from T. The sialyltransferase responsible for M activation may be a N transferase 'modified' by the M gene product or an entirely different sialyltransferase.

ABO Blood-Group System↗