Candidiasis-Endocrinopathy Syndrome with Progressive Myopathy

SUMMARY A women suffering from the candidiasis-endocrinopathy syndrome,developed severe myopathy in her fourth decade and died fromit at the age of 37 years. Associated conditions were hypoparathyroidism,vitiligo, chronic mucocutaneous candidiasis, short stature,intellectual disability, ovarian failure and alopecia totalis.Muscle biopsy findings were non-specific with focal atrophyof type 2 fibres. Serum immunoglobulin levels were normal. Theonly demonstrable abnormalities of her immune system were impairedT-cell function and antibody production by B-cells (detectableto smooth muscle, mitochondria and gastric parietal cells).The T-cell abnormality may have been part of a more generalizedcell defect, resulting from an unidentified genetic abnormality,whilst the circulating antibodies could have been a responseto tissue damage. There was no convincing evidence of primaryautoimmune damage.     

A hereditary immunoglobulin A abnormality: absence of light-heavy—chain assembly: Study of immunoglobulin synthesis in tonsillar cells

A new immunoglobulin A abnormality, absence of assembly of alpha-chain and light-chain, was found in an adult female suffering from recurrent upper respiratory infection and tonsillitis since childhood, but otherwise healthy. The IgA abnormality was manifest in her serum by the presence of free alpha-chains, in her saliva by the presence of alpha-chains bound to secretory piece, and in her urine by the presence of free alpha-chains and free light-chains. The serum IgG and IgM were found to be complete, containing both heavy-chains and light-chains.Evidence for this immunoglobulin A abnormality was also found in the proposita's mother and elder son, demonstrating it to be a hereditary disorder.Studies performed with patient's tonsillar cells in short-term culture, using amino acids-(14)C, revealed synthesis and secretion of both free alpha-chains and free light-chains, in addition to synthesis and secretion of normally assembled IgG and IgM.     

Temporary 6TH cranial nerve paralysis after accidental durotomy in endoscopic disc surgery

We present a unique case of 6th nerve palsy following accidental durotomy in endoscopic lumbar spine surgery, which has not been reported in the literature before. A 72- year-old female patient was admitted to our outpatient clinic complaining of right leg pain for 6 months. A 4/5 motor paresis was observed on her right toe with a positive Lasegue test at 45°. On her magnetic resonance imaging (MRI), a L5-S1 disc herniation was detected. The patient was planned for percutaneous endoscopic interlaminar disc surgery. The extruded disc was adherent to the dura. During removal, a dural tear was observed. She was relieved of her right leg pain immediately after surgery, but after 30 min postoperatively, she complained of double vision with left abducens nerve paralysis. On cranial MRI, no abnormality could be observed. Intravenous fluids were administered and the paralysis resolved on the postoperative 24th hour. The patient was discharged from the hospital and did not show any complaints on her follow-ups. A 6th nerve palsy can be caused due to alterations of intracranial pressure or mechanic injury. We believe that the durotomy following removing of the disc fragment caused a rapid drainage of CSF, leading to intracranial hypotension and injury of the abducens nerve. Intracranial pressure should be monitored perioperatively and brisk deteriorations has to result in immediate finishing of the surgery to avoid further secondary damage.     

一种新的血小板膜糖蛋白Ⅸ基因突变导致巨大血小板综合征

目的 对1例巨大血小板综合征（BSS）患者血小板异常和基因异常特征进行分析,探讨其发病机制。方法 光学显微镜与电子显微镜观察血小板形态与结构,比浊法测定血小板聚集。流式细胞仪检测血小板膜糖蛋白（GP）。PCR扩增与DNA序列分析确定基因异常。结果 该例BSS患者的血小板体积巨大而数量减少,瑞斯托霉素不能诱导血小板凝聚,血小板膜GPIb/Ⅸ复合物明显减少,GPⅨ跨膜区发生Ala139（GCC）→Thr（ACC）突变。结论 该例BSS患者的GPⅨ跨膜区Ala139(GCC）→Thr（ACC）突变为一种国际上尚未报道的新的基因突变。     

A serum inhibitor of immune regulation in patients with systemic lupus erythematosus.

Normal mononuclear leukocytes were incubated with serum from patients with active systemic lupus erythematosus (SLE) and healthy subjects and then studied on lymphoproliferative tests. Serum from SLE patients that contained an autoantibody to a subpopulation of thymus-derived (T) lymphocytes inhibited suppressor T-cell activity induced with concanavalin A. These sera did not inhibit lymphoproliferative responses or suppression by monocytoid cells. Mitogen-activated suppressor cells were not inhibited with serum from SLE patients or healthy subjects lacking T-cell autoantibody. This abnormality may contribute to the altered immune response that occurs with SLE.     

Structurally abnormal insulin in a diabetic patient. Characterization of the mutant insulin A3 (Val----Leu) isolated from the pancreas.

We have recently identified a diabetic patient with marked fasting hyperinsulinemia. Family study revealed that the abnormality was an autosomal dominant trait. High-performance liquid chromatography (HPLC) profile of the patient's serum insulin showed that she had an abnormal insulin in addition to a normal insulin. We have purified her insulin(s) from the specimen of her pancreas, which was biopsied during an operation of cholelithiasis. Insulin was also immunologically purified from the serum of her portal vein. The reverse-phase HPLC analysis revealed that the ratios of normal to abnormal insulin in the pancreas, portal vein, and peripheral vein were 5:4, 4:5, and 1:7, respectively. Radioreceptor assay for insulin using guinea pig kidney membrane revealed that the binding activities of the normal component insulin, the abnormal component insulin and her pancreatic insulin containing both components were 100, 5, and 50% of standard human insulin, respectively. The biological activities of the normal component, the abnormal component and her pancreatic insulin to stimulate glucose oxidation in rat adipocytes were found to be 100, 8, and 60% of standard human insulin, respectively. Analysis of amino acid sequences of the abnormal insulin purified from her pancreas strongly suggested the substitution of leucine for valine at the third position of the A chain, A3 (Val----Leu).     

Liquefied petroleum gas cold burn sustained while refueling a car

There have been few cases of cold burn related to the exposure of liquid petroleum gas (LPG). We present the case of a young woman exposed to LPG while refueling her car who sustained partial thickness burns to the dorsum of her hand. Contact with LPG leaking from a pressurized system causes tissue damage because of cold injury. Immediate management of LPG is extrapolated from the management of frostbite. The increasing use of LPG mandates an awareness of prevention strategies and management principles in the setting of adverse events.     

Abnormal Plasminogen: A HEREDITARY MOLECULAR ABNORMALITY FOUND IN A PATIENT WITH RECURRENT THROMBOSIS

A patient who suffered a recurring thrombosis over the last 15 yr has been investigated. The only abnormality found in this patient was a significantly depressed level of plasminogen activity in plasma. In spite of the depressed plasminogen activity, the patient was found to have a normal level of plasminogen antigen concentration. It was calculated that the activity per milligram of plasminogen of the patient was approximately one-half the values of normal subjects. The same discrepancy between biological activity and antigen concentration was found in the other members of the kindred. A niece was found to have practically no plasminogen activity but possessed a normal concentration of plasminogen antigen. Both her parents were found to have approximately half the normal plasminogen activity and normal antigen levels. These studies suggested that the molecular abnormality was inherited as an autosomal characteristic, and the family members who had half the normal levels of activity with normal plasminogen antigen were heterozygotes whereas the one with practically no plasminogen activity was homozygote. Subsequent studies showed that the pattern of gel electrofocusing of purified plasminogen of the heterozygotes consisted of 10 normal bands and 10 additional abnormal bands, each of which had a slightly higher isoelectric point than each corresponding normal component. This indicates that plasminogen of the heterozygote is a mixture of normal and abnormal molecules in an approximately equal amount, which was substantiated by active site titration of purified plasminogen preparations obtained from the propositus and a normal individual. The gel electrofocusing pattern of the homozygote consisted of abnormal bands only. The defect is a hereditary abnormality of plasminogen.     

B-cell, T-cell surface phenotypes and epitopes in autoimmune thyroid diseases]

Autoimmune thyroid diseases (AITD) are categorized as organ specific autoimmune diseases, including Graves' disease (GD), Hashimoto's thyroiditis and idiopathic myxoedema. In this article, B-, T-cell surface phenotypes and epitopes in AITD were reviewed. It has been reported that the proportion and absolute number of B and T lymphocyte subpopulation or CD4/8 ratio in peripheral blood from AITD was not different from normal subjects. Those of CD5+ B cells and gamma delta T cells known as autoreactive clones were, however, increased in peripheral blood from GD. In the thyroid tissue of AITD, B-cells with activated markers were predominantly infiltrated rather than T-cells. The CD4/8 ratio and the proportion of CD8+CD11b+ T (suppressor T) cells was decreased in contrast to the increase of CD8+CD11b- T (cytotoxic T) cells. The CD4+4B4+ T (helper/inducer) cells were more predominant than CD4+2H4+ T (suppressor/inducer) cells in thyroid tissue from GD. These abnormality might cause the cell destruction and the enhanced autoantibody production in the tissue of AITD. Thyroglobulin, thyroid peroxidase and thyroid stimulating hormone receptor are known as major autoantigens in AITD. Recently, B-cell and T-cell epitopes on these autoantigen molecules have been defined, using monoclonal antibodies, proteolytic or synthetic peptides with molecular gene engineering. These epitope analysis would be contributed to the autoimmune tolerance in AITD.     

Immune deficiency in CHARGE association

CHARGE association is the sporadic, non-random concurrence of Coloboma of the eye, Heart anomalies, choanal Atresia, Retardation of growth and development, Genitourinary anomalies, Ear anomalies and deafness (CHARGE association). Other abnormalities have also been reported in small numbers of patients with CHARGE association. The molecular basis of the CHARGE association is not clear. The spectrum of CHARGE association anomalies is wide and includes multiple systems. CHARGE association shares features with DiGeorge sequence, but no specific immune abnormalities are identified with the CHARGE association. The present study reports immune defects observed in three patients with CHARGE association. All patients presented with frequent upper and lower respiratory infections. The underlying immune abnormalities differ: one patient has impaired T-cell proliferation and poor antibody response to polysaccharide (pneumococcal) antigens; another has T-cell lymphopenia; and the third has a mild IgG2 subclass deficiency. Their course has so far been benign and they are all managed with prophylactic antibiotics. Although no single abnormality of the immune system is recognized in these patients, immune deficiency is considered among the occasional components of the CHARGE association.     

Biochemical markers in myocardial injury

Biochemical markers are substances that are detected in body fluids or tissues that may signify a disease or other abnormality. Biochemical markers have been used to help in the diagnosis of acute myocardial infarction since the 1950s. The major problem with these markers is that they lack specificity for cardiac muscle as they are also elevated in many disease states and after minor muscle damage.     

Spinal cord injury without radiographic abnormality in a 4-year-old child: hypoperfusion injury or direct trauma?

Spinal cord injury without radiographic abnormality is uncommon even in major paediatric trauma. A case is described of a 4-year-old girl sustaining multiple injuries from blunt trauma including spinal cord injury without radiographic abnormality. She was profoundly shocked with extensive thoracic, abdominal and pelvic injuries. An MRI performed 8 days after injury showed an ischaemic area from T8 to L2 consistent with hypoperfusion. Various possible aetiologies exist, including distraction, hyperflexion, hyperextension and ischaemic spinal cord damage. In this case the likely cause was spinal ischaemia. The anterior spinal and two posterior spinal arteries supply the spinal cord. The aorta feeds these superiorly via the subclavian and vertebral arteries, and inferiorly via the radicular arteries. Injury may tear these conduit arteries from the aorta causing cord ischaemia. This is important in the thoracolumbar area where the radicular artery of Adamkewicz supplies a large area of the spinal cord. The artery of Adamkewicz may have been interrupted directly by blunt trauma. The other cause of ischaemia is the systemic hypoperfusion sustained owing to profound hypovolaemia, which could also correlate with the child's reported transient blindness. Treatment and prognosis of spinal cord injury without radiographic abnormality are considered.     

A request for an abortion

How to manage to abortion request by a hypothetical 30-year old married woman who states the she fears a deformed child because of taking an antibiotic combination, cotrimoxazole, containing trimethoprim is discussed by 3 physicians. The 1st doctor would confirm pregnancy with an exam and a laboratory test, schedule another consultation for counseling, and schedule a pelvic ultrasound if she decides to carry the pregnancy. If she wants an abortion, the physician would counsel her at length about her marriage and the emotional consequences of abortion. The 2nd physician would advise her that fetal abnormality from trimethoprim has not been reported in women. Since this doctor is personally opposed to abortion, she would refer the patient to another doctor to make the arrangements, and counsel her again afterward. The 3rd physician added the advice that 1-2% of all U.K. births are abnormal in some way. He would take steps to establish the precise gestational date, recommend an ultrasound scan at 18 weeks to cover himself legally and suggest that the patient's husband join in the counseling session to help bring out feelings about the marriage and the pregnancy.     

Prolonged course of a cutaneous T-cell lymphoma with late systemic involvement

The clinical course of cutaneous T-cell lymphomas is known to be extremely variable. The disease may be present for up to 50 years, although it has a median survival of four to ten years. Clinical manifestations may range from cutaneous involvement alone to widespread systemic involvement. Described here is a patient with an unusually prolonged course of a cutaneous T-cell lymphoma with systemic involvement which reappeared ten and 18 years after the initial presentation. The patient developed Sj?gren's syndrome, bone marrow and peripheral nerve involvement late in the course of her disease.     

Continuous proliferation of murine antigen-specific helper T lymphocytes in culture.

Murine helper T cells activated to sheep or horse erythrocyte antigens in vivo have been established as continuous cell lines in culture. T cells require the presence of a T-cell growth factor (TCGF) for continuous proliferation. TCGF purified from murine, rat, or human sources all stimulate murine T-cell growth. The T-cell mitogens concanavalin A and phytohemagglutinin do not stimulate cell proliferation in continuous T-cell lines. All cells that grow in the presence of TCGF express Thy-1 antigens. Helper activity of T-cell lines is both antigen specific and effective for syngeneic or F1 B cells. Supernates from T-cell lines do not contain antigen-specific or nonspecific helper factors. Although several T-cell lines have shown stable helper activity for greater than 50 wk in culture, other cell lines have shown a gradual decline in effector function. The procedure used to establish and maintain proliferation of T cells in culture should be suitable for the selection and growth of antigen-specific effector T cells from each subclass.     

Epstein Barr virus-specific immune defects in patients with persistent symptoms following infectious mononucleosis

In a number of patients recovery from infectious mononucleosis (IM) following primary Epstein Barr virus (EBV) infection, is complicated by the persistence of symptoms for months or years. Normally recovery from infectious mononucleosis is associated with the development of EBV-specific antibodies and memory cytotoxic T-cells, which are present in the peripheral blood of all normal seropositive individuals. We studied four patients who had persistent symptoms for more than two years after infectious mononucleosis to determine if this abnormality was associated with a defect in EBV-specific or non-specific immune responses. All four patients had normal immunoglobulin concentrations, T- and B-cell numbers, T-cell proliferative responses and natural killer cell activity. However three of the four had reduced or absent antibodies to the EBV nuclear antigen (EBNA) although other EBV-specific antibody titres were normal. All four also had reduced EBV-specific cytotoxic T-cell activity as measured by the EBV regression assay. This defect was probably EBV-specific as alloreactive cytotoxic T-cell responses were normal. In addition, three of three patients tested had reduced in vitro antibody synthesis following pokeweed mitogen stimulation. These studies indicate that the syndrome of persistent symptoms following EBV mononucleosis may be associated with a defect in EBV-specific immunity, and thus suggest a possible immunological basis for the syndrome.     

An abnormality of the gene that encodes neutrophil Fc receptor III in a patient with systemic lupus erythematosus.

In the course of examining the structure and function of Fc receptors on peripheral blood cells of patients with systemic lupus erythematosus, we identified a patient whose neutrophils did not react with either monoclonal or polyclonal antibodies to Fc receptor III. However, neutrophils from the patient were comparable to neutrophils from healthy controls with respect to their expression of Fc receptor II, complement receptor 1, complement receptor 3, and the phosphatidylinositol-linked, complement regulatory protein, decay-accelerating factor. The abnormality of expression of Fc receptor III was limited to the patient's neutrophils (her natural killer cells reacted normally with anti-Fc receptor III antibodies), and was associated with abnormal recognition and binding of IgG-coated erythrocytes. Analysis of genomic DNA revealed evidence that failure of the patient's neutrophils to express Fc receptor III was most likely due to an abnormality of the gene that encodes this receptor.     

Epstein-Barr virus-associated T-cell lymphoma in solid organ transplant recipients.

Post-transplantation lymphoproliferative diseases (PTLDs) are a heterogenous group of lymphoid proliferative disorders occurring in transplant patients. Most PTLDs are B-cell in origin; T-cell PTLDs are seldom reported, and EBV-associated T-cell PTLDs are rare. The first case of a T-cell, non-EBV-associated PTLD was first described in a renal allograft recipient in 1987. A total of 40 cases of T-cell PTLDs in solid organ transplant recipients have been reported. However, so far only 16 cases of EBV-associated T-cell PTLDs have been reported in the literature. The sites of occurrence of EBV-associated T-cell PTLDs were in the gastrointestinal tract, lungs, bone marrow, skin, liver and spleen. The pathogenesis of EBV-associated T-cell PTLD is uncertain; it is speculated that the EBV may infect a subset of T-cells that express the CD21 receptor. The present treatment of EBV-associated T-cell PTLD consists of surgical removal, reduction or withdrawal of immunosuppression and/or radiotherapy and chemotherapy. The prognosis is uncertain, and the 1-year survival for patients who were followed up for 1 year was 50%.     

Transfusion-associated graft-versus-host disease in patients with Hodgkin''s disease and T cell lymphoma

Two patients, one with Hodgkin's disease and one with peripheral T cell lymphoma, developed transfusion-associated graft-versus-host disease 16 and 8 days after transfusion of red cell and platelet concentrates. Fever and skin rash were followed rapidly by an elevation of liver enzymes and the onset of diarrhoea and pancytopenia. Despite treatment with high-dose methylprednisolone and anti-lymphocyte globulin, commenced within 7 and 2 days of the onset of rash, grade IV GvHD persisted and both patients died with severe pancytopenia. HLA types of peripheral lymphocytes of the patient with Hodgkin's disease were inconsistent with those of her parents and siblings, but HLA typing of her fibroblasts revealed that her true type was consistent with those of her parents and that her circulating lymphocytes were not genetically her own. The HLA types of the patient with T-cell lymphoma were inconsistent with those of her siblings which suggests, but, in the absence of other evidence, does not prove, chimaerism.     

再生障碍性贫血患者T细胞亚群检测的临床意义

本研究探讨再生障碍性贫血(AA)患者外周血T细胞亚群的变化及其与AA发病、免疫抑制治疗之间的关系;为AA患者合理选择治疗方案提供依据。以88例临床确诊为AA、并分别接受常规和常规联合免疫抑制治疗的患者为对象,采用三色免疫荧光抗体标记法和流式细胞术检测外周血T淋巴细胞亚群及CD4 和CD8 比值,参考正常对照组水平将患者分为比值正常型、比值倒置型和比值超高型3个免疫亚型,分析和比较各亚型与病情、疗效之间的关系。结果表明:CD4 /CD8 比值正常型占39.8%、比值倒置型占44.3%、比值超高型占15.9%。免疫亚型、治疗方法与总有效率的关系为:单独常规治疗时,3个亚型组之间疗效无明显差异;当联合免疫抑制治疗时,比值正常型患者的总有效率与常规治疗相比无显著改变,而比值倒置型及免疫异常型(比值倒置型 比值超高型)患者有效率较同组常规治疗疗效均显著提高(84.2%vs45.5%及82.6%vs42.8%,p值均<0.05),也显著高于比值正常型患者(84.2%及82.6%vs52.6%,p值均<0.05)。结论:大多数AA患者存在严重的CD4 和CD8 比值失调,CD4 /CD8 异常既可表现为降低,也可以是异常增高,AA发病机制与免疫异常有密切相关性;T细胞亚群检测对临床了解病情和发病机制、合理选择治疗方案、提高诊断和治疗水平具有重要价值。