bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroprevalence of parvovirus B19, cytomegalovirus, hepatitis A virus and hepatitis E virus antibodies in haemophiliacs treated exclusively with clotting‐factor concentrates considered safe against human immunodeficiency and hepatitis C viruses
Authors: FLORES G. , JUÁREZ J. C. , MONTORO J. B. , TUSELL J. M. , ALTISENT C. , JUSTE C. , JARDÍ R.
Published: June 2007

Clotting‐factor concentrates (CFC) are a potential source of transmission of blood‐borne viruses. Newer physical and chemical methods (pasteurization, wet‐heating, solvent/detergent treating) developed to inactivate viruses are effective against HIV, HBV and HCV. However, it is not clear if these methods protect against other pathogenic viruses such as parvovirus B19, cytomegalovirus (CMV), hepatitis A virus (HAV) and hepatitis E virus (HEV). To evaluate the safety of current CFC we have studied seroprevalence of parovirus B19, CMV, HAV and HEV antibodies in 22 HIV and HCV negative haemophiliacs who were treated exclusively with clotting‐factor concentrates considered safe with respect to HIV and HCV transmission, 22 healthy individuals served as controls. Neither HAV nor HEV antibodies were detected in haemophiliacs or controls.

Two controls and two haemophiliacs were seropositive for CMV. Five controls (32% prevalence) and 15 haemophiliacs (77%) were positive to parovirus B19. No statistical differences can be established for seropositivity with CMV, HAV and HEV between haemophilic patients and controls. In the case of parvovirus B19 the differences are statistically significant (P= 0.0128). The relative risk of parvovirus B19 is 2.4 in the case of haemophiliacs. CFC considered safe against HIV and HCV are not safe against parvovirus B19, although they seem to be safe against CMV, HAV and HEV.
Didanosine treatment of haemophilic patients infected with HIV
Authors: Wilde Jonathan T. , McKernan Angela , Hay Charles R. M.
Published: June 2007

Twenty‐six haemophilic patients with advanced HIV infection who had developed resistance or intolerance to zidovudine were treated with didanosine (ddI). 11 patients continue to take ddI at a median time of 14 months from commencement (range 7–18 months). Five of these patients showed an increase in CD4 lymphocyte count, reaching a maximum at a median time of 4 months. Four patients with HIV‐related symptoms improved clinically. In general, the CD4 count and clinical improvements were not sustained. 11 patients discontinued ddI after a median of 3 months (range 3 days to 10 months), most commonly due to gastrointestinal side‐effects. No case of pancreatitis or peripheral neuropathy was seen. Six patients, all with very advanced HIV disease, died. HIV‐infected haemophilic patients who become resistant or intolerant to zidovudine may derive benefit from ddI, although this is usually transient.
Communication about safer sex and serostatus disclosure in HIV‐positive adolescents with haemophilia
Authors: NUSS RACHELLE , Smith Peter S. , Cotton David , Kisker Thomas ,   the Hemophilia Behavioral Intervention Evaluation Project (HBIEP) Adolescent Elicitation Committee
Published: June 2007

Objectives. To assess the attitudes, beliefs and feelings of adolscents and young men with severe haemophilia with respect to discussing safer sex and disclosing their human immunodeficiency virus (HIV) seropositivity to potential sex partners.

Methods. Fifty‐nine males with haemophilia from throughout the US answered open‐ended questions.

Results. Talking about avoidance of transmitting AIDS and disclosing one's seropositivity was beneficial, moral and wise. Nevertheless, this was exceedingly, difficult, unpleasant, and fraught with fear of rejection and alienation. Communication was approved by family, friends, and health‐care providers. Facilitators of communication were: knowledge and an accepting attitude about persons with HIV, a supportive person to assist with discussion, and environmental cues.

Conclusion. This first report of HIV‐infected adolescents and young adults reveals that although they endorse discussing safer sex and disclosing their HIV seropositivity, they are painfully aware of the social and interpersonal risks of such extremely difficult communications.
A study to evaluate the effectiveness of ‘Air‐Stirrup’ splints as a means of reducing the frequency of ankle haemarthroses in children with haemophilia A and B
Authors: Buzzard Brenda M. , Heim Michael
Published: June 2007

With the introduction of readily available factor VIII and IX concentrates and programmes for home therapy and prophylaxis, most severe haemophilic arthropathies can be prevented. However, despite these programmes, bleeds into the ankle joints still occur during the years of growth. It is suggested that ankle haemarthroses may be caused by unrecognized inversion injuries by the patient. The history from a small child is not always accurate and when a child presents with a swollen ankle it is not uncommon for the medical team to make a diagnosis of haemarthrosis without really searching for the pathogenesis. This paper describes a clinical study using the ‘Air‐Stirrup’; (AS) ankle splint which is designed to restrict inversion. Children between the ages of 3 and 18 years with a history of recurrent ankle haemorrhages were entered into a 6‐month trial. Results showed a positive reduction in the number of ankle haemorrhages experienced by the children.
Obstetric management in von Willebrand's disease: a report of 24 pregnancies and a reivesw of the literature
Authors: RAMSAHOYE B. H. , DAVIES S. V. , DASANI H. , PEARSON J. F.
Published: June 2007

The case records of 13 patients (24 pregnancies) with von Willebrand's disease (vWD) were studies rettospectively. The overall incidence of primary and secondary post‐partum haemorrhage (PPH) was 15.8% and 25% respectively, all primary PPH occurring in tyre 2 discase (3/14 deliveries, 21.4%). The risk of primary PPH in type 2 patients who did not receive prophylactic factor VIII was 37.5% (3/8 deliveries).

Factor VIII coagulant activity (VIII:C) and von Willebrand factor antigen (vWF:Ag) rose above bascline values by a factor of at least 1.5 during the pregnancy in most case. More severely affected patients were less likely to benefit significatntly. A baseline VIII:C of <15 iu/dl (4/14 cases) was predictive of a third trimester level of <15 iu/dl. Improvements in the von Willebrand factor activity were less marked. The baseline von Willebrand factor activity was <15 iu/dl in all patients with serial data, none of whom achieved a third‐trimester von Willebrand factor activity of >50 iu/dl. The bleeding times were unaltered significantly in all but one of the cases, reflecting a general failure of the primary haemostatic defect to improve with pregnancy.

The findings demonstrate that coagulation parameters do not universally improve in pregnancy in vWD, especially when preconception levels are low. The risk of primary PPH is generally higher in type 2 diseases. The level of factor VIII:C is not a good predictor of the risk of primary PPH in type 2 patients. Secondary PPH is a significatnt risk in both type 1 and type 2 patients.
A new approach to immunologic identification of factor VIII antibodies
Authors: SHURAFA MUHAMMAD , KITHIER KAREL
Published: June 2007

Summary We tested for antibodies against factor VIII by using monoclonal antibody‐purified factor VIII preparation as a source of antigen. The factor VIII was adsorbed on nitrocellulose membranes and stored in a refrigerator until later use. Plasma or serum was incubated with the factor VIII containing strip and the antibody was detected by another incubation with peroxidase‐labelled antihuman immunoglobulin antibodies. The test was efficient in detecting antibodies in haemophilic and normal subjects with acquired inhibitors to factor VIII. It also detected antibodies to the factor VIII protein in a haemophilic subject with no evidence of inhibitor. The technique is simple, readily applicable, and serves as a useful screening tool for detecting factor VIII antibodies. The stability of the antigen‐containing strips in a refrigerator is a practical advantage with potential commercial application.
Cytolytic activity against mycobacterial antigens: differences between haemophiliacs with and without HIV infection
Authors: PASI K. J. , EVANS J. A. , FORTE M. , KUMARARATNE D. S. , HILL F. G. H.
Published: June 2007

Summary Although asymptomatic haemophiliacs have been shown to have abnormalities of their immune response, independent of HIV, clinical evidence of significant immunosuppression is limited. The only clinical report has been an outbreak of M. tuberculosis in which a group of haemophilic boys appeared unduly susceptible to infection. These boys are now all HIV seropositive. Along with a group of HIV seronegative children with coagulation disorders and non‐haemophilic HIV seropositive men, these boys have been restudied to examine immune response to PPD. The HIV seropositive haemophilic boys that had had M. tuberculosis infection had reduced cytolytic response to PPD pulsed macrophages comparable to the non‐haemophilic HIV seropositive men. The HIV seronegative children with coagulation disorders showed a reduction in cytolytic activity at low effector:target ratios compared to normal controls. In vitro studies showed that exogenous factor VIII concentrate could inhibit cytolytic activity to PPD pulsed macrophages. The possible role of chronic blood‐borne virus infection and factor VIII concentrates in the original outbreak are discussed.
Seroprevalence of total antibodies to hepatitis A virus in haemophiliacs in the West of Scotland
Authors: CLARK PETER , CAMERON SHEILA O. , WALKER ISOBEL D. , LOWE GORDON D. O.
Published: June 2007

Summary Serum samples taken from 73 patients with haemophilia A were tested for the presence of total antibody against hepatitis A (antiHAV) by radiommunoassay. 29 (39.7%) were antiHAV positive and 44 (60.3%) were antiHAV negative. These figures are comparable with local prevalence figures for immunity (40.3%) and susceptibility (59.7%) to HAV in adults. 30 patients were subsequently exposed to Scottish National Blood Transfusion Service High‐Purity Factor VIII (SNBTS HPVIII). They were re‐tested for the presence of antiHAV at a median of 5 months after exposure. Of these, 25 (83.3%) were antiHAV negative and five (16.7%) were antiHAV positive. All five of these antiHAV‐positive patients were positive on samples taken prior to exposure. No cases of seroconversion to hepatitis A occurred.
Prevalence of inhibitor formation in a cohort of haemophilic children exposed to several products of various purities
Authors: ARONIS S. , PLATOKOUKI H. , KAPSIMALI Z. , ADAMTZIKI E. , KOLOKITHAS A. , MITSIKA A.
Published: June 2007

Summary. To evaluate the frequency and potency of inhibitor formation based on the product used, we retrospectively reviewed the records of 99 children with various types and severity of haemophilia (haemophilia A 82, severe 46; haemophilia B 10, severe 6; vWD 7) treated for the last 20 years. After a mean observation period of 8 years an overall of 23 patients (23.2′/0) developed an inhibitor (haernophilia A 26.8%; severe 4O%, moderate 20%, mild 3.8%). None of the haemophilia B patients presented with an inhibitor, and only one child with bevere vWD (1/7, 14.3%) showed a transient inhibitor under cryoprecipitate therapy. Inhibitor titre was low (< 5 BU) in most cases (91.3%) and in only two patients (8.75%) was 6 and 8 BU respectively. Antibodies to FVIII were transient (detected only once) in four (17.4%) and intermittent in 19 patients (82.6%). By the age of 12 years, 17/23 patients (73.9%) had demonstrated an inhibitor. The inhibitor detection seemed to be higher in the groups of patients exposed to monoclonal (3115, 20%), SID‐treated (10159, 16.9%) or H/T FVIII concentrates (6/41, 14.6%), compared to groups of patients who received cryo/plasma (9.5%) or unmodified concentrates (5.1%); nevertheless the differences were not statistically significant.

Surprisingly, none of the 52 patients who received a S/D + chromatography‐treated factor VIIl concentrate developed an inhibitor after a mean observation period of 1.7 years (range 0.2–2 years). The overall prevalence of inhibitor formation in previously untreated haemophiliacs was 14.3% (4/28), irrespective of the product used.

Our data indicate that a high proportion of our haemophilic children exposed to several products of various purities have developed a low‐titre inhibitor which in most cases was transient or intermittent. However, despite the presence of the antibody, none of the patients needed a change in the mode of treatment.
The impact of hepatitis C antibody screening of source plasma donors on hepatitis C virus RNA in factor VIII concentrates
Authors: BERNTORP ERIK , LETHAGEN STEFAN , NORDENFELT ERIK , MÅNSSON ANN‐SOFIE , MÅNSSON SIV , WIDELL ANDERS
Published: June 2007

Summary. We have used the polymerase chain reaction technique for the detection of hepatitis C RNA in nine different plasma‐derived factor VllI concentrates and in two factor IX concentrates. Four concentrates were investigated both prior to and after the introduction of donor screening for hepatitis C antibodies. A negative reaction was consistently found in the ultra‐pure factor VIII concentrates Octonativ‐M (Pharmacia) and Hemofil M (Baxter), both prepared by affinity purification with factor VI1I:C monoclonal antibodies and virus inacti‐ vated hy solvent/detergent procedures, as well as in both the low‐purity factor IX concentrates. I f produced from unscreened plasma, the other factor VIII concentrates manifested positive reactions irrespective of preparation procedure and type of virus inactivation or the temperature at which it was performed. We conclude that the preparation procedure of clotting factor concentrates, rather than type of virus inactivation, determines the degree of contamination by hepatitis C virus RNA, and that screening of source plasma seems effective in removing hepatitis C RNA from the final product as determined with a sensitive PCR method. I t is important to stress that the presence of viral RNA does not necessarily imply clinical infectivity.
Psychological status of men with haemophilia and HIV infection: two‐year follow‐up
Authors: MARSETTIN ELENA PASQUAL , CIAVARELLA NICOLA , LOBACCARO CATERINA , GHIRARDINI ALESSANDRO , BELLOCCO RINO , SCHINAIA NICOLA
Published: June 2007

This study aimed to assess the psychological status of men with haemophilia and HIV infection and to monitor changes in psychlogical status over time, in order to evaluate the need for psychological support. The study included 24 HIV seropositive men and a control group of 21 HIV seronegative men who attended the Haemophilia Centre in Bari (Italy). Subjects underwent psychological tests (STAl‐Y: State and Trait Anxiety Inventory; SDS: Self‐Rating Depression Scale) and completed a questionnaire on the emotional impact of AIDS. Assessment was repeated at 6‐monthly intervals over a 2‐year period. Contrary to expectation, HIV seronegative men with haemophilia had worse anxiety and depression scores, reported more confusion and fear, and had more reluctance towards the use of blood products (despite their present safety) than HIV seropositives. Possible reasons for these findings are considered, and their implications for clinical practice discussed.
Use of plasma‐derived factor VIIa in a child with inhibitors of FVIII for the placement of an implantable intravenous access device
Authors: TSUCHIYA HIROYUKI , IKEDA SHINJI , YOSHIOKA AKIRA
Published: June 2007

We treated a 20‐month‐old boy with severe haemophilia A who developed a high level factor VIII (FVIII) inhibitor. An implantable intravenous access device (IVAD) was safely placed on the lateral chest under anaesthesia using plasma‐derived factor VIIa (FVIIa). Implantation of an IVAD into a haemophilic child with an inhibitor requires considerable care, because the area of subdermal invasion is broader than in the implantation of a central venous line. However, placement of an IVAD provides very convenient access to the central venous line and is an appropriate tool for frequent injection, such as the induction of immunotolerance to FVIII.
Long‐term immunogenicity and safety of an inactivated hepatitis A vaccine in haemophilic patients
Authors: DENTICO PIETRO , CIAVARELLA NICOLA , SCARAGGI FRANCESCO A. , SCHIAVONI MARIO , VOLPE ANNA , FASANO ANTONIO , PERRICCI ANTONIA , BUONGIORNO ROSALBA
Published: June 2007

Summary. As a consequence of recent outbreaks of HAV infection by blood products, 91 patients, haemophiliacs and subjects with bleeding disorders (10 of whom were also anti‐HIV positive) susceptible to HAV infection received a formalin‐inactivated hepatitis A vaccine (HAVRIX 720 Elisa Units, SmithKline Beecham). Subcutaneous injections were given in the deltoid region at 0, 1 and 6 months. The seroconversion rates and litres, expressed in GMT IU/1, were determined at 1, 2, 6, 7, 12, 18 and 24 months. No adverse reactions to the vaccine were observed. The highest percentage of responders observed was 98.7% in anti‐HIV negative and 71.4% in anti‐HIV positive patients. The anti‐HAV GMT titres were higher in anti‐HIV negative than in anti‐HIV positive patients. The inactivated hepatitis A vaccine is safe, clinically well tolerated, and provides long‐term protection against HAV infection.
Development of a World Federation of Hemophilia External Quality Assessment Scheme: results of a pilot study
Authors: JENNINGS I. , KITCHEN S. , WOODS T. A. L. , PRESTON F. E.
Published: June 2007

Summary. A World Federation of Hemophilia External Quality Assessment Scheme has been established to promote high standards of laboratory performance in haemophilia centres worldwide. Twenty‐two International Haemophilia Training Centres (IHTCs) participated in a pilot study designed to assess between‐laboratory agreement and to establish target values for the prothrombin time, activated partial thromboplastin time, factor VIII:C, IX:C and von Willebrand factor assays. Although variations in results and clinical interpretations were observed between the centres, median results and assay precision were comparable to that seen in the United Kingdom National External Quality Assessment Scheme. IHTC‐generated median results were therefore considered appropriate target values against which to compare the performance of haemophilia centres in developing countries.
The fixed flexed and subluxed knee in the haemophilic child: what should be done?
Authors: HEIM MICHAEL , HOROSZOWSKI HENRI , VARON DAVID , SCHULMAN SAM , MARTINOWITZ URI
Published: June 2007

Summary. Knee haemarthroses are very common in the haemophiliac and often, despite infusion of the missing coagulation factor, synovitis develops. The warm swollen joint is maintained in the most comfortable position for the haemophiliac: flexion. Ambulation is achieved by planterflexion of the ankle joint and toewalking. As the chronic synovitis persists, the range of movement of the knee is affected, with loss of full extension. Development of radiological degenerative signs develop. The quadriceps muscle usually weaken due to disuse, but the hamstrings are active in maintaining the flexion of the joint. As the process continues, the tibia subluxes posteriorly on the condyles of the femur. The posterior capsule of the knee joint soon contracts, permanently limiting knee extension. A case is described on whom an Ilizarov device was used to gradually return the limb to a function position. This will allow the patient to complete his growth prior to a definitive orthopaedic procedure.
Abnormal immune parameters in HIV‐seronegative haemophilic patients
Authors: ALLERSMA D. P. , SMID W. M. , BRIËT E.
Published: June 2007

Summary. In HIV‐seronegative haemophiliac patients abnormal immune parameters have been demonstrated. In this review data on these abnormalities, their aetiology and clinical consequences are summarized and discussed. The data reviewed show abnormalities at different levels of the adaptive immune system. Most of the reported abnormalities regard lymphocyte subsets and their function, both in vivo and in vitro testing. Strong evidence has not been found for a causal relation between abnormalities and the consumption of factor VIII concentrates nor the purity of the concentrates. It seems likely that certain contaminants in the factor VIII concentrates have an inhibiting effect on lymphocytes and monocytes. Two clinical consequences of the abnormalities have been suggested: a higher susceptibility for infections and a greater risk to develop malignancies. Data on these consequences, however, are contradicting and not in agreement with the good results of long‐term treatment of HIV‐seronegative haemophiliac patients with factor VIII concentrates. The studies reviewed give no convincing evidence that more pure concentrates are advantageous in HIV‐negative haemophiliacs.
The use of intermediate‐purity clotting factor concentrates and HIV disease progression in men with haemophilia
Authors: SABIN C. A. , PASI J. , PHILLIPS A. N. , LILLEY P. , ELFORD J. , LEE C. A.
Published: June 2007

Summary. On the basis of evidence from the immune systems of patients with haemophilia infected with HIV, patients in the UK have been switched to high‐purity clotting factor concentrates. However, there is very little information currently available on the effect of intermediate‐purity clotting factor concentrates on progression of HIV disease. Among 99 HIV‐positive men with severe factor VIII deficiency registered at The Royal Free Hospital Haemophilia Centre, a 100 IU kg‐1 increase in the yearly amount of concentrate received did not appear to be associated with more rapid progression to AIDS, death or to a low CD4 count. However, the use of total concentrate usage may mask a more subtle effect of specific concentrate contaminants on the progression of HIV disease.
Detection and IgG subclass analysis of antibodies to factor VIII in multitransfused haemophiliacs and healthy individuals
Authors: GAUTIER Ph. , SULTAN Y. , PARQUET‐GERNEZ A. , MERIANE F. , GUEROIS C. , DERLON A.
Published: June 2007

Summary. Using a binding assay to immobilized factor VIII (F VIII) (ELISA) we measured the amount of IgG with binding capacity to FVIII, in the plasma of patients with an inhibitor to F VIII, in multitransfused haemophiliacs without inhibitor and in a control group of blood donors. It was shown that the amount of IgG bound to VIII was elevated in patients with an inhibitor although a weak correlation could be established between the inhibitor titre (BU) and the amount of bound IgG. In all haemophiliacs without inhibitor, IgG bound to F VIII were present. Although the mean value of IgG bound to F VIII was significantly lower than the amount detected in patients with F VIII inhibitors, a group of patients developed an equal amount of IgG recognizing the F VIII molecules to the amount of IgG measured in inhibitor patients. These results indicate that the presence of an inhibitor is not related to the amount of specific IgG bound to F VIII but more likely to the position of epitopes recognized by specific IgG. The presence of IgG bound to F VIII was detected in 92% of control blood donors and an inhibitor to F VIII ranging from 0.5 to 1.3 BU mL‐1 in 17% of them. The isotypes of bound immunoglobins were identified in patients and controls: IgG4 subclass was predominant only in patients with an inhibitor and usually associated with antibodies of one or more of the other subclasses. In noninhibitor patients, very few had antibodies of IgG4 subclass with binding capacity to F VIII. These results raised the question of the clinical significance of these antibodies in multitransfused patients. The study indicates that binding assay is a complementary test to be used in multitransfused patients but cannot be used instead of the coagulation tests for detection of inhibitors.
Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations
Authors: BERNTORP E. , EKMAN M. , GUNNARSSON M. , NILSSON I.M.
Published: June 2007

Summary. During treatment of a haemophilia A patient with a high‐responding inhibitor against factor VIII coagulant activity (VIII:C), we observed a difference in recovery of VIII:C depending upon which factor concentrate was infused. Inhibitor plasma samples or IgG fraction from seven patients were tested against a panel of seven different commercially available factor VIII concentrates of which five were plasma‐derived and two recombinant. In two of the plasma samples, inhibitor titres manifested a wide range of values depending upon which concentrate was used in the test system. Thus, inhibitor neutralization was less and VIII:C recovery greater when factor VIII concentrates containing large amounts of von Willebrand factor were used than when highly purified concentrates containing no von Willebrand factor or only trace amounts were used. In both of these two patients the inhibitor was directed against the light chain of factor VIII, and it is possible that the epitope of the light chain with which the inhibitor reacts is partly blocked by the von Willebrand factor.

We conclude that inhibitors may differ in their reactivity with factor VIII molecules contained in clotting factor concentrates, and that there is factor VIII epitope variation between different concentrates. These findings have implications for the selection of concentrates for the treatment of inhibitor patients and the haemostatic effect may be improved if a concentrate giving the lowest inhibitor titre is chosen. Thus, in vitro testing of inhibitor reactivity with a panel of concentrates is recommended when treatment of inhibitor patients with factor VIII concentrates is considered.
Beta interferon therapy for chronic hepatitis C in patients with haemophilia and other haemorrhagic disorders
Authors: HAGIWARA T. , FUKUE H. , KAWATA K. , YAMAGISHI T. , YAMAMOTO Y. , ARAI M. , FUKUTAKE K.
Published: June 2007

Summary. Beta interferon therapy was given to seven chronic hepatitis C patients with haemophilia or other haemorrhagic disorders who had received clotting factor replacement therapy. Serum alanine aminotransferase (ALT) levels ranged from 82 to 275 UL‐1 and hepatitis C virus (HCV)‐RNA ranged from 106 to 109 copies mL‐1. HCV‐genotypes were I+II in one patient, II in one, II+III in four and IV in one. Patients received 6 mega units (MU) daily of natural type beta interferon by intravenous infusion for 6 weeks. In three of seven patients, the protocol was modified to intermittent administration because neutrocytopenia (under 500 × 106 L‐1) developed in two patients and thrombocytopenia (under 50 × 109 L‐1) was observed in one during treatment. No modification was necessary with regard to daily and total dose. All patients received administration without any haemorrhagic complications. Six of seven patients showed improvement in serum ALT levels, and one of the patients showed normalization of ALT levels for 6 months after treatment. HCV‐RNA disappeared in four patients by the end of treatment, although no one remained negative 6 months after treatment. The results of our study were similar to those reported in previous papers which described the use of alpha interferon in haemophiliacs. The reason none of the patients showed sustained loss of HCV‐RNA after therapy might be associated with high HCV‐RNA levels, characteristics of the HCV‐genotype and prolonged duration of the disease.
Counselling for HIV‐positive haemophiliacs in Japan
Authors: YANAGA Y. , ONO O. , SHIRAHATA A.
Published: June 2007

Summary. This paper describes the current status of counselling for HIV‐positive haemophiliacs at a haemophilia centre in Japan. Clinical experience with 23 HIV‐infected haemophiliacs (all male, age range 16–56, mean 29.9 years), 22 family members (eight couples of parents, one grandmother, five siblings) and nine sexual partners (five wives and four girlfriends) between April 1990 and February 1994 is detailed. Methods of counselling consisted of individual counselling in 32, couple counselling in eight and family counselling in three cases. Indications for counselling consisted of fear of or shame of HIV infection in 37, concern for the family in 21, risk of transmitting HIV to sexual partners in 12, fear of death and dying in 12, future career and family life in seven, interest in treatment options in five, daily life style in 10, parents' feeling of guilt over the infection in five cases, lack of knowledge of haemophilia, HIV infection and AIDS in seven, and bereavement in two cases. A total of 200 counselling hours were provided. Consequently, pending disclosure of HIV infection was successfully completed in five, disclosure of HIV infection to the sexual partner by the patient was facilitated in two, the patient‐family relationship improved in nine, and smooth transition of care to the adult in‐hospital unit was achieved in two patients. Our experience in Japan clearly verifies the importance of psychoeducational counselling for HIV‐positive haemophiliacs and their family as well as sexual partners.
AIDS‐associated lymphomas and other cancers in individuals with haemophilia
Authors: RAGNI M. V.
Published: June 2007

Summary. Non‐Hodgkin's lymphoma is the most common malignancy in individuals with haemophilia and human immunodeficiency virus (HIV) infection. Among individuals with haemophilia, lymphoma accounts for 5% of primary AIDS diagnoses, and it is the sixth most common primary AID‐defining diagnosis in this group. At the time of AIDS‐lymphoma diagnosis, the median age in haemophiliacs is 32 years, the mean CD4 count is 116 μL−1, and the mean time from seroconversion to development of AIDS‐lymphoma is 8 years. The most common primary site of AIDS‐lymphomas in haemophiliacs is the gastrointestinal tract, and the most common histological type is large cell lymphoma. EBV has been detected at a molecular level in half of all haemophilia AIDS‐lymphomas and its presence is predictive of shorter survival than in those without detectable EBV. The median survival after diagnosis is 6 months, with or without treatment. An increasing proportion of these tumours are occurring as secondary AIDS diagnoses, associated with the longer duration of immunosuppression afforded by antiviral therapy. This paper reviews the natural history, immunological and viral features, clinical characteristics, and risk factors associated with AIDS‐lymphoma in the haemophilia population.
A study to assess the immunogenicity, reactogenicity and safety of hepatitis A vaccine administered subcutaneously to patients with congenital coagulation disorders
Authors: ZUCKERMAN J. N. , MOORE S. , SMITH J. , TYRRELL H. , BAXTER A. , LEE C. A.
Published: June 2007

Summary. The objective was to compare the immunogenicity, reactogenicity and safety of an inactivated hepatitis A vaccine administered subcutaneously to patients with congenital coagulation disorders. Subjects, 97 patients with congenital coagulation disorders (67 men aged > 16 and 30 children aged ≤ 16 years), received hepatitis A vaccine administered at 1440 ELISA (enzyme linked immunosorbent assay) units (ELU) to the adult group and at 720 ELU to the child group at 0 and 6 months by the subcutaneous route. The vaccine was well tolerated, with the incidence of adverse events decreasing with subsequent administration of vaccine. Overall, 90% of subjects seroconverted 1 month after the booster (95% confidence interval 76–97%), with 100% seroconversion occurring in the child group compared with 85% in the adult group. There was a corresponding progressive rise in geometric mean titres in each group and no significant difference in the geometric mean titres was found between the two groups. Of the subjects, 29% were HIV positive, 3% of children compared with 40% of adults. A lower rate of seroconversion was observed in subjects with low CD4 counts. Administration of two doses of an inactivated hepatitis A vaccine at 1440 ELU in adults and 720 ELU in children is safe and highly immunogenic when given by the subcutaneous route.
De novo mutation causing sporadic type 2A von Willebrancd's disease: report of three cases
Authors: ENAYAT M. S. , THEOPHILUS B. D. M. , PASI K. J. , HILL F. G. H.
Published: June 2007

Summary. Chemical mismatch detection has been used to screen selectively part of the A2 domain of exon 28 of the von Willebrand factor gene of three unrelated patients with apparently sporadic type 2A von Willebrand disease (vWD) and their parents and siblings. Mismatches have been defined by DNA sequencing and mutations authenticated by restriction enzyme analysis. While a mutation was identified in all three patients, no evidence of mutation could be found in their asymptomatic/un‐affected parents or siblings, proving the disease to be truly sporadic in these cases. Of these, two with severe clinical bleeding had a serine 743 to leucine substitution while the third patient with clinically less severe bleeding had an arginine 834 to tryptophan substitution. The possible genetic mechanisms for sporadic type 2A vWD in these families are discussed.
Neisseria gonorrhoeae O‐linked pilin glycosylation: functional analyses define both the biosynthetic pathway and glycan structure
Authors: Aas Finn Erik , Vik Åshild , Vedde John , Koomey Michael , Egge‐Jacobsen Wolfgang
Published: June 2007

Neisseria gonorrhoeae expresses an O‐linked protein glycosylation pathway that targets PilE, the major pilin subunit protein of the Type IV pilus colonization factor. Efforts to define glycan structure and thus the functions of pilin glycosylation (Pgl) components at the molecular level have been hindered by the lack of sensitive methodologies. Here, we utilized a ‘top‐down’ mass spectrometric approach to characterize glycan status using intact pilin protein from isogenic mutants. These structural data enabled us to directly infer the function of six components required for pilin glycosylation and to define the glycan repertoire of strain N400. Additionally, we found that the N. gonorrhoeae pilin glycan is O‐acetylated, and identified an enzyme essential for this unique modification. We also identified the N. gonorrhoeae pilin oligosaccharyltransferase using bioinformatics and confirmed its role in pilin glycosylation by directed mutagenesis. Finally, we examined the effects of expressing the PglA glycosyltransferase from the Campylobacter jejuni N‐linked glycosylation system that adds N‐acetylgalactosamine onto undecaprenylpyrophosphate‐linked bacillosamine. The results indicate that the C. jejuni and N. gonorrhoeae pathways can interact in the synthesis of O‐linked di‐ and trisaccharides, and therefore provide the first experimental evidence that biosynthesis of the N. gonorrhoeae pilin glycan involves a lipid‐linked oligosaccharide precursor. Together, these findings underpin more detailed studies of pilin glycosylation biology in both N. gonorrhoeae and N. meningitidis, and demonstrate how components of bacterial O‐ and N‐linked pathways can be combined in novel glycoengineering strategies.
Die postnatale Entwicklung des Extremitätenskeletts bei Schaf und Ziege
Authors: Rajtová Viera
Published: June 2007

Postnatale Entwicklung dcs Extremitätenskeletts bei Sdiaf und Ziege

Bei der Ziege wadisen die langen Knochen gleichmäßiger und schließen sich die Epiphysenspalten früher als beim Sdiaf. Bei ihr ist audi der Geschlechtsdimorphismus ausgeprägter. Allgemein haben die Männchen längere und breitere Knochen, und einige Epiphysen können bei ihnen später als bei den Weibchen schließen. Zweimal fand sich bei der Ziege ein unpaares Os sesamoideum in der Ursprungssehne des lateralen M. gastrocnemius. Trächtige Tiere wiesen keine makroskopischen Veränderungen der Symphysis pelvis auf.

Postnatal development of the bones of the limbs in sheep and goat

The long bones of the goat grow more evenly, and the epiphyseal cartilages disappear sooner, than in the sheep. Sexual dimorphism is also more marked in the goat. The males generally have longer and wider bones and some epiphyseal cartilages may close later in the males than in the females. In the goat, a unilateral sesamoid bone was found twice in the origin of the lateral head of the gastrocnemius. Pregnant animals did not show any gross changes in the pelvic symphysis.

Développement postnatal du squelette des extrémités chez le Mouton et la Chèvre

Chez la Chèvre, la croissance des os longs est plus régulière et les épiphyses se soudent plus tôt que chez le Mouton; le dimorphisme sexuel est aussi, chez elle, plus accuse. En général, les mâles ont des os plus longs et plus larges et quelques épiphyses peuvent, chez eux, se souder plus tard que chez les femelles. Par deux fois, on a trouvé, chez la Chèvre, un Os sesamoideum impair dans le tendon d'origine du M. gastrocnemius latéral. Les sujets gestants n'ont présenté aucune modification macroscopique de la Symphysis pelvis.

Desarrollo postnatal del esqueleto de los miembros en oveja y cabra

En la cabra, los huesos largos crecen de una manera más uniforme que en la oveja y los cartílagos de conjunción desaparecen más temprano, siendo tambíen el dimorfismo sexual más destacado. En general, los machos tienen huesos más largos y anchos y algunas epífisis se unen a la diáfisis más tarde que en las hembras. Dos veces se encontró en la cabra un hueso sesamoideo impar el el tendón de origen del M. gastrocnemio lateral. Animales preñados no mostraron cambios macroscópicos en la sinfisis pelviana.
Relation between Fine Structure and Function of the Corpus luteum of Wild Ruminants
Authors: Kayanja F. I. B. , Gombe S.
Published: June 2007

Corpora lutea from 8 species of wild ruminants relatively abundant in East Africa were investigated. A comparison of the ultrastructure of luteal cells of the different species is recorded and discussed. The progesterone content was estimated in the corpora lutea of two species and related to the fine structure. A cell‐type having mitochondria as the predominant cytoplasmic organelle is described.

Die Beziehung zwischen Ultrastruktur und Funktion beim Corpus luteum von Wildwiederkäuern

Es wurden die Corpora lutea von 8 in Ostafrika relativ häufig vorkom‐menden Wildwiederkäuern untersucht. Die Ultrastruktur der Geldkörper‐zellen der verschiedenen Species wurde verglichen und diskutiert. Der Pro‐gesterongehalt wurde in den Corpora lutea zweier Species bestimmt und mit der Feinstruktur in Beziehung gebracht. Es wurde ein Zelltyp beschrieben, bei dem die Mitochondrien die vorherrschenden Zellorganellen darstellen.

La relation entre ultrastructure et fonction du Corpus luteum des ruminants sauvages

Des recherches sur les Corpora lutea de 8 species des ruminants sauvages qu'on trouve relativement souvant en Afrique de l'ouest ont été faites. On a comparé et discuté l'ultrastructure des cellules luteales de doux species differerants. La contenance du progesterone a été mesuré dans les corpora lutea de deux species, et on a fait une relation entre les corpora lutea st l'ultrastructure. On a décrit un type celluleux où les mitochondria prédominent.

Relaciones entre la estructura fina y la función del cuerpo luteo de rumiantes salvajes

Se estudiaron los cuerpos lúteos de 8 rumiantes salvajes que abundan en el Este del Africa. Se discute la ultra‐estructura de las células luteicas de las diferentes especies. En dos de las especies, se determinó el contenido en pro‐gesterona de los cuerpos lúteos, estableciéndose su relación con la ultra‐estructura. Se describe un tipo de célula, en el cual predominan las mito‐condrias.
Gonadal Ultrastructure and Steroids in Foetal Zebra
Authors: Kayanja F. I. B. , Gombe S. , Rumney G.
Published: June 2007

The presence of progestins and androgens in the foetal gonad of the zebra and the absence of these hormons in the foetal horse reflect perhaps a significant species difference.

Feinstruktur der Gonaden und Steroidhormone beim fetalen Zebra

Die fetalen Gonaden des Zebras enthalten Progestine und Androgene. Das ist beim Pferd nicht so. Der Unterschied beruht moglicherweise auf einem Artunterschied.
Fine Structure and Peroxidase Activity of the Bovine Mandibular Gland Cells
Authors: Bloom Gunnar D. , Carlsöö Bengt
Published: June 2007

The acini of the bovine mandibular gland consist of mucous and demilunar seromucous cells. The mucous cells contain electron‐lucid mucigen droplets or mucoid masses, only rarely delimited by membranes. The cisternae of the RER communicate freely. Mitochondria are scarce. The seromucous demilunar cells contain considerably more granules, and perigranular membranes are far more common. Many granules have characteristic alternating electron opaque and less electron dense areas. The prominent RER appears to be associated with a peculiar labyrinth of interconnecting tubules. Mitochondria are numerous. Numerous myoepithelial cells are observed. The cuboidal cells of the intercalated ducts lack signs of secretory activity. The columnar cells of the striated ducts have extensive infoldings of the basal plasma membrane, associated with mitochondria. The cell apex contains many granulated vesicles.

Endogenous lactoperoxidase activity could be demonstrated only in the demilunar cells, within the secretory granules, the RER, including the perinuclear cisternae, as well as the labyrinth mentioned above. A positive reaction could be observed over acinar lumina and in intercellular canaliculi. The possible role of peroxidase as a component of a bactericidal system of the bovine saliva is discussed.
Le développement de l' activité des estérases carboxyliques et de la phosphatase alcaline dans l' oesophage, le réseau, le rumen et le f euillet du boeuf1
Authors: Lauwers H. , Sebruyns M. , Vos N. de
Published: June 2007

Les réAservoirs gastriques et l' oesophage de 8 boeufs adultes, de 6 veaux gras, d' un veau de 4 jours et de 4 foetus furent examinés quant à leur activité en estérases et phosphatase alcaline.

Dans les réservoirs gastriques la localisation et l' intensityé des ces enzymes dépendent de l' âge de l' animal. Chez les foetus et le veau de quatre jours les estérases sont limitées aux couches profondes de l' épithélium. Chez les veaux gras et les boeufs adultes le stratum corneum et le stratum transitionale sont devenus trés positifs. La phosphatase alcaline est absente dans l' épithélium des foetus. Une ligne d' activité se developpe au niveau du stratum transitionale chez le veau de quatre jours et chez les boeufs adultes les cellules supérieures du stratum spinosum et toutes les cellules du stratum transitionale et corneum sont positives.

Dans l' oesophage la présence de ces enzymes ne change presque pas avec l'âge. Les estérases restent limitées aux couches épithéliales profondes et la phosphatase alcaline n'apparait pas dans l'épithélium.

La localisation et l'activité de ces enzymes est mise en relation avec le processus de kératinisation et surtout avec la résorption dans les réservoirs gastriques du boeuf adulte.
Biology of the Rice Rat (Oryzomys palustris natator) in a Laboratory Environment
Authors: Park A. Wallace , Nowosielski‐Slepowron B. J. A.
Published: June 2007

The pattern of body growth ranging from weaning to old age has been examined by means of parameters of weight and head‐body length from 370 rice rats. The differences between the sexes were found to emerge after 20 days until clear demarkation existed in both weight and length by 30 days. Weight was found to have a greater rate of increase relative to length. The males were found to continue to increase weight until 20 months old while length had ceased by 16 months. The females were found to increase weight and length until 14 and 12 months respectively. Since the onset of maturity, both sexual and in body, begins earlier in the female than the male, the cessation of such processes would occur earlier and later respectively. These growth periods occupy the earlier months and are regarded as representatives of growth in length whereas the later increases cannot be placed in the same category.
Etude cytologique de ľhypophyse de la barbotte brune (Pisces, Ictalurus nebulosus, Le Sueur, 1819)
Authors: LE Dlscorde D.
Published: June 2007

Ľhypophyse &dcar;Ictalurus nebulosus présente 3 lobes qui s'emboitent con‐centriquement les uns dans les autres. Les 2 lobes, périphérique et moyen, con‐tiennent les 7 cellules hypophysiotropes toutes individualisées par leurs affinityés tinctoriales histologiques. Elle est pédiculisée sur ľhypothalamus par ľin‐termédiaire du lobe nerveux, qui invagine dans le lobe moyen et infiltre des faisceaux nerveux dans ce dernier.

Zur Zytologie der Hypophyse der Aalraupe (Pisces, Ictalurus nebulosus, Le Sueur 1819)

Die Hyophyse von Ictalurus nebulosus besteht aus 3 Lappen, die ein‐ander konzentrisch umgeben. Der periphere und mittlere Lappen enthält 7 hypophysiotrope Zellarten, die an ihrer histologischen Färbbarkeit erkennbar sind. Der dritte, nervöse Lappen sitzt mit seinem Mittelteil gestielt auf dem Hypothalamus und buchtet sich gegen den mittleren Lappen vor, letzteren mit Nervenbündeln infiltrierend.

On the cytology of the hypophysis of Ictalurus nebulosus (Le Sueur 1819)

The hypophysis of Ictalurus nebulosus consists of three lobes which surround each other concentrically. The peripheral and the middle lobes contain seven hypophysiotropic cell types, which can be differentiated by histological stains. The third, neurohypophyseal lobe is attached, with its stalklike central part, to the hypothalamus and bulges into the middle lobe, infiltrating the latter with nerve bundles.

La citología de la hipófisis de ïctalurus nebulosus (Le Sueur, 1819)

La hipófisis de Ictalurus nebulosus se compone de tres 1óbulos concén‐tricos. Los 1óbulos perférico y mediano contienen 7 tipos de células hipofisio‐tropas que se distinguen por su coloración histológica. El tercer 1óbulo, el nervioso, se fija con su tallo mediano en el hipotálamo, evaginándose hacia el 1óbulo medio, al cual infiltra con haces nerviosos.
On the Fine Structure and Mucosubstances in the Bulbourethral Gland in the Domestic Boar
Authors: Nielsen Ellen Holm , Sørensen Vibeke Wang , Björkman Nils
Published: June 2007

The purpose was to study the fine structure of the cells and the histochemistry of the mucosubstances of the porcine bulbourethral gland. The material comprised adult boars from the Danish Landrace, two for electron microscopy and 10 for ordinary histology and histochemistry. The methods included histology, electron microscopy and histochemical tests on mucosubstances. The fine structure of the cells and the histochemistry of the mucosubstances of the secretory granules were described. The functional aspects of the findings were discussed.
Intercellular Junctions in the Developing Mammalian Thymus*
Authors: Harrison Bettina H.
Published: June 2007

Lymphopoiesis in fetal thymuses of mice and rabbits was studied to try to correlate heterogeneity of lymphocytes with heterogeneity of embryonic origin. The thymuses of fetal mice of 11 to 14 days gestation and of fetal rabbits of 18 and 19 days gestation were examined by electron microscopy. At the time of earliest appearance of lymphoid cells in both species desmosomes were seen on both epithelial and lymphoid cells. These desmosomes persisted for several days, then disappeared from completely differentiated lymphocytes in both species. The similarity between epithelial and lymphoid cells in their earliest developmental stages suggests a common precursor cell for both.