Thermo-optical static and dynamic analysis of a digital optical switch based on amorphous silicon waveguide.

In this paper, static and dynamic thermo-optical numerical analysis of a Digital Optical Switch (DOS), based on amorphous silicon waveguide and operating at the infrared communications wavelength of 1550 nm, are presented. The aim of our design is to achieve good performances in terms of cross talk and switching time, considering relaxed requirements for the realization of device: large cross section single mode waveguides and an angle between the output branches not too small. Using a low temperature difference between the two output branches, an optical switching with a crosstalk of 25 dB and a response time of the order of ten microseconds are obtained. The device, designed for low-cost photonic applications, could be easily integrated in silicon optoelectronic circuits.

[The hospital medical director: his role and professional qualification in Modena (Italy) health care system]. / II Direttore di Presidio Ospedaliero: ruolo e requisiti professionali nell'esperienza dell'Azienda U.S.L. di Modena.

The development of health care system in Italy, from 1968, have changed the hospital medical director function and have put him in conflict with the desired physicians involvement in health care management. In Modena the health care system organisation, the self government and the responsibility decentralisation, promoted the achievement of an organisation model tempering every competence because the success of everyone's task depends on the other one's. Therefore, Italian laws are suitable of getting more efficiency and effectiveness in health care system without new rules, if the clinical governance becomes a way to involve the physicians in management and not an instrument to leave out managers and hospital medical directors.

Analysis and stability of the constituents of artichoke and St. John's wort tinctures by HPLC-DAD and HPLC-MS.

In continuing our investigations on tinctures, which represent both herbal drug preparations and herbal medicinal products, 40% and 60% v/v tinctures of artichoke and St. John's wort were investigated. Artichoke is largely used in hepatic disorders, while St. John's wort is an anti-inflammatory, antidepressant, and healing agent. Both herbal drugs contain various constituents, although the compounds responsible for the main effects have not yet been completely identified. However, caffeoylquinic acids and flavones seem to be of crucial importance for the activity of artichoke, as well as flavonoids, naphthodianthrones, and phloroglucinol derivatives for St. John's wort, and they are used as marker constituents. Thus, quantification of all these constituents was performed using high-performance liquid chromatography-diode array detection (HPLC-DAD) and HPLC--mass spectrometry (MS) analyses with rutin as external standard. In addition the stability of the constituents of these tinctures from accelerated and long-term testing was also evaluated. From the results it was evidenced that constituent content depends on the solvent used for the extraction. The stability was also shown to be very different and seems to be related to the water content of the tinctures.

Analysis of plant complex matrices by use of nuclear magnetic resonance spectroscopy: St. John's wort extract.

The efficiency of two-dimensional homonuclear (1)H--(1)H correlated spectroscopy and two-dimensional reverse heteronuclear shift correlation spectroscopy (i.e., heteronuclear multiple quantum correlation) in characterizing and evaluating the relative content of herbal extract constituents is demonstrated. These experiments are able to fully assign the proton and carbon resonances of all three classes of constituents present in dried commercial extract of St. John's wort, that is, flavonols, phloroglucinols, and naphthodianthrones, with particular regard to the very unstable phloroglucinols. In addition, shikimic and chlorogenic acids, sucrose, lipids, polyphenols, and traces of solvents of the extractive process (methanol) were also identified. These experiments can be considered to be a very simple and fast analytical method for determining the quality and stability of the titled commercial extract. They represent a generally applicable technique for a rapid screening and a specific measurement of other commercial phytochemicals or, in selected cases, an alternative to the classical analytical techniques such as high-performance thin-layer chromatography, high-performance liquid chromatography, capillary gas chromatography, and electrophoresis.

Evaluation of chemical stability of St. John's wort commercial extract and some preparations.

Thermal and photostability of a commercial dried extract and capsules of St. John's wort (Hypericum perforatum L.) were evaluated under the ICH test conditions. The extract was considered as drug substance and its preparations as drug products. In addition, capsules of different colours corresponding to different opaficient and pigment contents were also evaluated as primary package of drug product and the tests in the secondary pack were performed with amber containers, as well. A selective high-performance liquid chromatography (HPLC) for determination of stability of all the characteristic constituents, namely flavonols, hyperforins and hypericins, was carried out. Photostability testing showed all the constituents to be photosensitive in the tested conditions. However, different opaficients and pigments present in the capsules influenced the stability of the different classes of constituents. Amber containers suggested as secondary packages influenced only in part the photostability of the investigated constituents. Long-term thermal stability testing showed a very low (less than 4 months) hyperforins and hypericins t(90), even if ascorbic and citric acids were added to the formulation. From the results we have obtained it is clear that for St. John's wort preparations, a mere translation of the ICH guidelines to the field of herbal products, as suggested by the WPHMP of the EMEA, cannot be accepted. A revision and adaptation of the storage conditions should be elaborated.

Evaluation of the dissolution behaviour of some commercial herbal drugs and their preparations.

Dissolution rates are routinely performed with synthetic drugs, however, in the field of herbal drugs (HD), their preparations (HDP) and herbal medicinal products (HMP) this crucial property is generally not investigated. According to the European Pharmacopoeia, we have evaluated the dissolution behaviour of capsules containing various herbal drugs (Passira, Senna, Ginkgo) and some of their commercial dried extracts, manufactured with different methods, by analysis of their active components or marker constituents. Adequate dissolution behaviours of the flavonoids of Ginkgo were obtained for all preparations, while for both Passiflora and Senna only the extracts showed complete dissolution of the marker flavones and sennosides, respectively, in the investigated media.

[Observing an SSU Em 118 dispatch center for continuous quality improvement. The case of SSUEm 118 Varese]. / Una centrale operativa SSU Em 118 a giudizio per verifica e revisione di qualità. Il caso SSU Em 118 Varese.

The present paper highlights quality aspects of the management of an Emergency Health Service Center (SSUEm 118, Varese) in order to identify the corrective measures required in a service that is increasingly close to the citizens real needs and expectations. Data were collected retrospectively on a total 54,301 calls for assistance in the period October 1997-March 1999 from an area covering some 1,300 sq.km with a population of 1,150,000 residents. That resident population was dramatically increased on a daily basis by heavy vehicle traffic particularly on the motorways to the area's many factories and to the Intercontinental Airport Malpensa 2000. The survey employed 7 anaesthetists and resuscitation staff, 14 nurses and 8 Italian Red Cross works from the Emergency Center. The researchers analysed the following phases: call reception and telephone conversation: ambulance dispatch, patient transportation and the alerting of the hospital of destination. The ServFMEA method was used for Quality Control with appropriate dispatch and the conduct and timing of the ambulance service in the Varese SSUEm 118 area. The data collected allowed for a detailed analysis of the accuracy of the information provided over the telephone (over-triage 58%, undertriage 2%), the usefulness of the telephone filter, the colour coding (correct in 40% of cases), pick-up times (5'40" on average) which were related to problems inherent in the ambulance call-out and the way ambulances reached the emergency (BLS 99%, ALS 1%, Air rescue < 1%). It was concluded that Varese SSUEm 118 was effectively and efficiently run in its first 18 months and results were improved as far as they could be given the inadequate funding of the Italian Heatlh Service.

Identification by HPLC-DAD and HPLC-MS analyses and quantification of constituents of fennel teas and decoctions.

Qualitative and quantitative differences among the constituents in various fennel (Foeniculum vulgare Mill., family Apiaceae) teas prepared by classical infusion, microwave decoction, and dissolution are reported. Different commercial starting materials, such as fruit (unbroken and crushed), four herbal teas, and two instant herbal teas were evaluated. Chlorogenic acid (1), quercetin-3-O-beta-D-glucuronide (2), p-anisaldehyde (3), and trans-anethole (4) were identified by HPLC-DAD and HPLC-MS as constituents of fennel teas. No coumarins, which are characteristic constituents of plants of Apiaceae family, were found. Trans-anethole (4), the main constituent of the essential oil, was present in all teas. In addition p-anisaldehyde (3), a degradation product of trans-anethole, was also identified in all teas with the exception of two samples. Chlorogenic acid (1) and quercetin-3-O-beta-D-glucuronide (2) were also present in all teas. In addition, minor unidentified flavonol constituents were found in two teas. Quality, activity, and safety of the content of the investigated preparations are also discussed.

Hepatitis C virus risk: a hepatitis C virus related syndrome.

BACKGROUND: The association between mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection has been recently described in many reports. OBJECTIVE: The aim of this study was to evaluate the long-term prognosis of hepatitis C virus-positive patients affected by mixed cryoglobulinemia with or without kidney involvement. PATIENTS: At total of 119 hepatitis C virus-positive patients affected by mixed cryoglobulinemia were divided in two groups. Group A: mixed cryoglobulinemia without kidney involvement (103 cases); group B: mixed cryoglobulinemia with glomerulonephritis (GN) (16 cases). A further 37 patients affected by mesangio-proliferative glomerulonephritis (MPGN) were evaluated as controls (group C). METHODS: Anti-hepatitis C virus antibodies were determined by commercial kits and hepatitis C virus-RNA was detected by polymerase chain reaction (PCR) amplification of the 5' untranslated region (5'UTR) of the virus. The hepatitis C virus genotype was determined according to Okamoto. Liver biopsy was performed in 62 patients, bone marrow biopsy in 65 patients, and kidney biopsy in all patients with proteinuria. RESULTS: In group A, 46 patients (45%) were affected by chronic liver disease (CLD), 21 (20%) by low-grade non-Hodgkin's lymphoma (NHL) and 16 (15%) by both diseases. All patients of group B were affected by type I membrano-proliferative glomerulonephritis, 3 (19%) by chronic liver disease, 6 (37%) by low-grade non-Hodgkin's lymphoma, and 7 (44%) by both diseases. Several genotypes of hepatitis C virus were found, but Type 1b was prevalent. In group C, no patient showed chronic liver disease or non-Hodgkin's lymphoma. Younger age, higher mean blood pressure, lower C4 serum level, and poorer survival significantly distinguished group B from group A. Survival rates at 5 years were: 87.4% for group A, 89.5% for group C, and 50.0% for group B. None of the patients of group B developed kidney failure requiring dialysis, whilst infections were the leading cause of death. CONCLUSIONS: In hepatitis C virus-positive patients, the presence of mixed cryoglobulinemia associated with kidney involvement seems to indicate a new syndrome characterized by immune system impairment, lack of progression to kidney failure, and poor survival (hepatitis C virus-Risk syndrome).

Interferon versus steroids in patients with hepatitis C virus-associated cryoglobulinaemic glomerulonephritis.

BACKGROUND/AIMS: The association between mixed cryoglobulinaemia, cryoglobulinaemic glomerulonephritis, and chronic hepatitis C virus infection has recently been described. The renal disease had usually been treated with immunosuppressive therapy, but, given the presence of viral infection, this therapy is no longer recommended. In this study, we compare steroid vs interferon therapy in a group of patients affected by hepatitis C virus-positive cryoglobulinaemic glomerulonephritis in the stationary phase. PATIENTS/METHODS: The diagnosis of cryoglobulinaemic glomerulonephritis was made bearing in mind standard criteria. Patients were randomly assigned to 2 groups receiving oral prednisone 0.2 mg/kg/die for 6 months (6 patients, group A) or lymphoblastoid interferon 3 MU, three times a week for 6 months [7 patients, group B). Hepatitis C virus-RNA was determined by reverse transcription-polymerase chain reaction and hepatitis C virus genotype according to Okamoto. Hepatitis C virus-RNA quantitation was performed by competitive polymerase chain reaction. RESULTS; The 2 groups were comparable in terms of age and severity of kidney failure. All genotypes of hepatitis C virus were found with a prevalence of Type 1b. In group A, 4 patients showed a partial response; in group B, 1 patient achieved complete remission, 4 a partial response, 2 patients in both groups showed no response. At the end of the treatment, all patients in both groups relapsed. Only 1 patient in group B became hepatitis C virus-RNA negative, and recovered from cryoglobulinaemic glomerulonephritis. CONCLUSIONS: Interferon seems to be an effective drug in the treatment of cryoglobulinaemic glomerulonephritis, but dosage and length of treatment still need to be addressed by large multicentre studies.

Plasma-exchange in chronic peripheral neurological disorders.

We investigated 19 patients affected by chronic peripheral neurological disorders treated with therapeutic plasma exchange (TPE) to verify the efficacy of the therapeutic protocol used in these diseases. Every patient was clinically considered after 5 TPE. Those who showed an improvement started chemotherapy and continued TPE at the rate of 2 procedures/week for 2 weeks, then 1 procedure/week for 1 month and finally 1 procedure every 2 weeks for 2 months. Intravenous immunoglobulins (IVIg) were infused at the end of apheretic treatment in one of the patients affected by neurological disorders due to monoclonal gammopathy undetermined significance. HCV-positive patients with cryoglobulins were treated with alpha-interferon (alpha-IFN) for 6 months before TPE. Eleven patients (58%) had a symptomatic improvement, 2 (1.5%) stopped TPE treatment owing to side effects and 6 (31.5%) did not respond to apheretic therapy. In order to improve the advantages of TPE we suggest using IVIg at the end of apheretic therapy, while in HCV-positive patients, at least one year of alpha-IFN therapy is required before initiating TPE.

Technical-regulatory aspects of antiseptics and disinfectants in Italy.

The authors analyze Italian laws, in light of changes introduced with Legislative Act n. 178/91, which regulate products with antiseptic and disinfectant action. A new reclassification of medicinal, cosmetic and health products is considered and proposed. Particular attention is given to marketing criteria adopted by various producers with regard to the form of product presentation.

Recordando la fundación de la sociedad boliviana de pediatría: testimonio de una protagonista / Recalling the foundation of the Bolivian pediatrics society: testimony of one protagonist

Se presenta una rememoración de los principales acontecimientos que rodearon la fundación de la Sociedad Boliviana de Pediatría, ocurrida el 17 de abril de 1943. Recuperar la memoria histórica en torno a las instituciones y las personas que hicieron posible el desarrollo de la medicina en Bolivia, es fortalecer su proyección futura y ese es el objetivo y escencia del presente trabajo que vigoriza nuestro conocimiento sobre una de las sociedades cientificas fundamentales de la medicina boliviana.

Interferon therapy in HCV-positive mixed cryoglobulinaemia: viral and host factors contributing to efficacy of the therapy.

BACKGROUND: In a previous paper, we reported on the short-term efficacy of alpha-interferon in the treatment of hepatitis C virus positive mixed cryoglobulinaemia. AIMS: We investigated the long-term effects of therapy in a larger group of patients, and the viral and host factors able to influence the response to treatment. METHODS: In 27 females and 15 males (mean age 54.8 +/- 9.1 years) affected by mixed cryoglobulinaemia, bone marrow biopsy and phenotyping of marrow cells were performed before treatment and at the end of follow-up. A liver biopsy was obtained from patients showing biochemical signs of chronic liver disease. The presence of hepatitis C virus was assessed by detection of serum anti-hepatitis C virus antibodies, and hepatitis C virus-RNA. The treatment schedule was 3 million units of recombinant interferon alpha-2b three times a week for one year. Follow-up lasted for 1 year after the end of treatment. The response was classified as follows: 1) Complete response: Disappearance of the cryocrit (or reduction of more than 50%) and of all clinical manifestations of the disease. 2) Partial response: Disappearance of all clinical signs of the disease, but reduction of cryocrit of less than 50%. 3) Minor response: Reduction of cryocrit of less than 20% associated with the disappearance of one or more (but not all) signs of vasculitis. RESULTS: Anti-hepatitis C virus antibodies were present in 41 (95%) patients, and hepatitis C virus-RNA was detectable in all cases. Before therapy, marrow histology showed a massive monomorphous infiltration by plasmacytoid lymphocytes indicating the presence of low-grade non-Hodgkin lymphoma in 7 cases (16.6%). After therapy, 13 (31%) patients achieved a complete response, 23 patients (55%) a partial response, and 6 patients (14%) a minor response. Seven of the responders and all patients showing partial or minor responses relapsed a few months after withdrawal of therapy. At the end of the follow-up, only 6 patients had obtained complete remission. Bone marrow examination showed that B-lymphocytic monoclonal infiltrate had disappeared in 3 long-term responders. No difference was found between responders and non-responders/relapsers in terms of age, sex, duration of the disease, severity of symptoms, liver function tests, rheumatoid factor or complement levels, while the lack of response was associated with the presence of genotype 1b, liver cirrhosis, and high cryoglobulin level. CONCLUSIONS: Mixed cryoglobulinaemia is associated with a high prevalence of B-cell lymphomas. Alpha-Interferon is an effective agent for the treatment of this disease and seems able to determine regression of the lymphoproliferative disorder. The hepatitis C virus genotype and cryoglobulin level are the most important predictive factors of response to therapy.

Deficiency of vitamins E and A in cystic fibrosis is independent of pancreatic function and current enzyme and vitamin supplementation.

UNLABELLED: The aim of this study was to evaluate to what extent serum vitamins A and E cystic fibrosis are affected by the underlying disease, pancreatic sufficiency or insufficiency, meconium ileus, nutritional status, age and treatment (enzyme and vitamin supplementation). Serum vitamin A and E levels were determined by high performance liquid chromatography in 210 cystic fibrosis patients, subdivided according to clinical condition into four subgroups (unsupplemented pancreatic insufficiency, supplemented meconium ileus, pancreatic sufficiency, supplemented pancreatic insufficiency) and compared with 42 control subjects. Vitamin A and E levels were generally lower in cystic fibrosis patients than in controls (P < 0.002 and P < 0.001 respectively). Subjects with pancreatic insufficiency regularly receiving enzyme and vitamin supplementation had significantly lower vitamin A (P < 0.05) and vitamin E (P < 0.01) levels than controls. In subjects with pancreatic sufficiency only vitamin A was significantly lower than in controls (P < 0.01). Vitamin levels were not age-dependent in cystic fibrosis, and no significant correlation with standardized body weight (Z-score) was observed. CONCLUSION: Cystic fibrosis patients show a clear tendency to vitamin A and E deficiency, irrespective of pancreatic function, body weight and standardized supplementation with pancreatic extract and liposoluble vitamins. Since the clinical significance of this deficiency is still not clear, longitudinal studies of cystic fibrosis patients with and without adequate vitamin supplementation are required.

New marker of bone resorption: hydroxyproline-containing peptide. High-performance liquid chromatographic assay without hydrolysis as an alternative to hydroxyproline determination: a preliminary report.

A high-performance liquid chromatographic (HPLC) assay for a urinary hydroxyproline-containing peptide (hydroxy-proline peptide, HypP) is described. This peptide represents about 50% of urinary hydroxyproline-containing peptides. Its concentration and total 4-hydroxyproline (Hyp) concentration evaluated in 325 urine samples have been shown to be closely correlated (r = 0.972; y = 0.499 x -1.5), which may indicate that the two markers provide the same information. The HypP assay, similar to Hyp assay, is carried out without hydrolysis of urine samples. After the blocking of primary amino acids by o-phthaldialdehyde (OPA) and derivatization of secondary amino acids by 9-fluorenylmethyl chloroformate (FMOC-CI), the FMOC derivatives of HypP and 3,4-dehydroproline (internal standard) were separated on a strong anion-exchange column and detected fluorimetrically. HypP concentration was calculated by measurement of peak-area ratios of HypP and the hydroxyproline standard. The HypP/creatinine (mmol/mol) ratio in fasting urine samples from healthy adults was found to be 8.2 (S.D. = 1.6, n = 33) in 27-44-year-old premenopausal women and 6.9 (S.D. = 1.7, n = 21) in 28-49-year-old men.

Ira con neumonia en menores de dos meses: Reviciòn de 6 años / Acute respiratory infections pneumonia in children less of two months: review of 6 years

Se realizo un estudio retrospectivo en el Hospital del Niño Dr. Ovidio Aliaga Uria de la ciudad de La Paz, analizando los casos de IRA con neumonia en menores de dos meses desde enero de 1990 a diciembre de 1995. Se encontro que el 24,3 porciento de los casos de neumonia en menores de cinco años correspondiò al grupo etareo analizado. En este grupo el sexo masculino fue el màs suceptible, màs frecuente entre los 31 a 60 dìas de edad y durante los meses de abril a septiembre. La mortalidad encontrada fue del 8,9 porciento afectando principalmente a los niños entre 8 a 30 dìas de edad. El seguro de Maternidad y Ninez que esta vigente desde junio de 1996, mejorarà la cobertura de atenciòn a la madre y el niño menor de 5 años y creemos que mejorarà tanto la morbilidad materna como infantil

Systemic passive transfer studies using IgM monoclonal antibodies to sulfatide.

We present a patient with benign IgM-gamma anti-Sulfatide (SUL) whose neuropathy was transferred in newborn rabbits. The patient's clinico-pathological picture of anti-SUL-associated demyelinating neuropathy is reported. The monoclonal IgM antibodies prepared by Tatum's method, that retained their biological activity, were passively transferred to newborn rabbits. The passive transfer produced demyelinating nerve lesions very similar to the donor antibody neuropathy. In experimental lesions we observed the human IgM anti-SUL antibodies binding to Schmidt-Lanterman incisures and nodes of Ranvier. We postulate that the myelin-specific and complement-dependent lesions observed in the peripheral nerve support the potential demyelinating role of anti-SUL antibodies. Moreover, the pattern of the antibody binding to the perineuronal sheath of satellite cells in dorsal root ganglia strengthen the hypothesis that anti-SUL antibodies may have a pathogenetic role in this sensorimotor syndrome.

HCV and lymphoproliferative diseases.

METHODS: Genomic and replicative forms of HCV-RNA in B lymphocytes were detected by RT-PCR, and HCV genotyping was performed using universal and type-specific primers for the core region. Immunoglobulin gene rearrangement was detected by RT-PCR. RESULTS: The presence of genomic and replicative forms of HCV-RNA in the 5'NC region was investigated on total RNA extracted from subpopulations of PBMC. The frequency of HCV-RNA was higher in the B lymphocytes than in other PBMC. In two patients a larger sized band was present in the B lymphocytes and PMN; this band could represent either another form of HCV-RNA or a cross-reaction between cellular RNA and HCV primers. HCV-RNA detected using primers for the core region was negative in the patients examined. Immunoglobulin monoclonal gene rearrangement was present on the cDNA in all of the HCV and type II cryoglobulinemia positive samples except two; in contrast, it was absent in the HCV positive and cryoglobulinemia negative samples. The analysis of immunoglobulin monoclonal gene rearrangement on DNA showed the presence of new positive samples among the HCV positive, type II cryoglobulinemia negative patients, who had been negative when PCR was performed on cDNA. Denaturing sequencing gel showed clearer results than agarose gel. CONCLUSIONS: The early detection of immunoglobulin monoclonal gene rearrangement and expression is very important because it could provide evidence of the possible lymphoproliferative evolution of HCV infection. In addition, these investigations together with PCR product sequencing could show us the steps in the clonal selection of B lymphocytes towards malignant transformation, in which HCV plays a direct and/or indirect role.

HCV genotypes and cryoglobulinemia.

OBJECTIVE: To evaluate the HCV genotype distribution in subjects affected by cryoglobulinemia in order to verify its possible role in the pathogenesis of the disease and to provide the clinician with a useful datum for therapy. METHODS: Nested PCR with universal and type-specific primers was used for the genotyping. RESULTS: Genotype I (1a) was never present in cryoglobulinemia, while it was present in 7 (4.3%) patients with chronic hepatopathy and in 4 (10.8%) asymptomatic patients. Type II (1b) was present in 28 (58.3%) and in 8 (47.1%) cryoglobulinemic patients with and without hepatopathy, respectively, in 106 (64.6%) patients with chronic hepatitis; in one patient with acute hepatitis; and in 14 (37.9%) asymptomatic patients. Type III (2a) was present in 2 (4.2%) and 2 (11.8%) cryoglobulinemic patients with and without hepatopathy, respectively; in 1 (0.6%) patient with chronic hepatopathy; and in 2 (5.4%) asymptomatic subjects. Type IV (2b) was present in 1 (2.1%) and in 2 (11.8%) cryoglobulinemic patients with and without hepatopathy, respectively; in 5 (3%) patients with chronic hepatopathy; and in 1 (2.7%) asymptomatic subject. Coinfections were present in 42 cases: 6 (12.5%) cryoglobulinemia with hepatopathy, 4 (23.5%) cryoglobulinemia without hepatopathy, 25 (15.3%) chronic hepatopathy, and in 7 (18.9%) asymptomatic subjects. For 41 (15.4%) strains typing was not possible. Eight of the "untypable" strains and 3 strains from patients with coinfection proved to belong to a new genotype. CONCLUSIONS: Genotype II (1b) was the most frequent in patients with and without cryoglobulinemia; genotype I (1a) was absent in all 65 patients with cryoglobulinemia, in whom, however, as in the subjects without cryoglobulinemia, all the other genotypes could be found. An interferon-resistant genotype characterized by an elevated homology with Simmonds' type 2c (rare genotype) was present.