Invasive Trichosporon cutaneum infection: an increasing problem in immunosuppressed patients.

Trichosporon cutaneum (syn. T. beigelii), a saprophytic fungal organism normally found in the soil, is increasingly being recognized as a cause of life-threatening systemic illness in immunosuppressed patients. Of 42 cases reported in the literature, 27 (64%) have died, including all four occurring after bone marrow transplantation. We report here a 44-year-old man who developed an invasive pulmonary infection and fungemia with T. cutaneum following bone marrow transplantation. The infection was manifest by severe respiratory distress and hypoxemia despite a clear chest X-ray, and was diagnosed by the identification of fungal hyphae on a percutaneous lung aspirate and by culture of the organism from the blood. Despite the previous reports indicating that there is a high mortality rate in this situation, the patient recovered following treatment with amphotericin B, miconazole and ketoconazole. T. cutaneum needs to be recognized as a potentially serious but treatable pathogen in severely immunosuppressed patients, including bone marrow transplant recipients.

Multiple endocrine neoplasm, type 1. Gastrinomas, pancreatic neoplasms, microcarcinoids, the Zollinger-Ellison syndrome, lymph nodes, and hepatic metastases.

OBJECTIVE: We reviewed the age of presentation, malignant potential, and outcome of gastrinomas and pancreatic tumors in patients with multiple endocrine neoplasm, type 1. DESIGN: Screening of one very large and one smaller, possibly related family on an island, including serum gastrin estimations and, when indicated, pancreatic ultrasound. SETTING AND PATIENTS: Over 2000 family members and their family physicians were advised on screening procedures. INTERVENTION: Data were collected and reviewed retrospectively and prospectively for all medical records, investigations, surgical procedures, and available tissue samples. OUTCOME MEASUREMENTS: Criteria for diagnosis were established for radiological, biochemical, and histological studies. RESULTS: Sixty-two patients had evidence of gastrinoma or pancreatic neoplasm. In 19 patients the diagnosis was based on demonstration of a tumor. In 21 patients the diagnosis was based on elevated serum gastrin concentration in the absence of demonstrable tumor. None of these patients required gastric surgery if they first underwent parathyroidectomy. In 18 patients the diagnosis was based on the combination of demonstrated pancreatic tumor plus elevated glucagon (two patients), gastrin (11 patients), or insulin (five patients) concentration. Peptic ulcer was difficult to control in seven of the 11 patients with elevated gastrin concentrations plus demonstrated tumor. Four patients had liver metastases that appeared to be secondary to the pancreatic gastrinoma. In patients with insulinomas, the first symptoms occurred before age 20 years. Elevated serum gastrin concentrations were not seen before age 24 years and were observed to occur for the first time in two patients after age 50 years.

Adrenal hypoplasia and pituitary agenesis in a normocephalic infant, with a review of the literature.

A case of adrenal hypoplasia and pituitary agenesis in a normocephalic female infant is described. Twenty-eight other cases from the world literature were reviewed. There were 18 females and 11 males. More than one affected infant was described in five families, suggesting autosomal recessive inheritance. The mode of presentation, subsequent course, pathology and possible pathogenesis are discussed.

Hypertension due to renal tuberculosis: assessment by renal vein renin sampling.

A 36-year-old man with asymptomatic hypertension was shown to have destruction of the right kidney due to renal tuberculosis. The peripheral renin level was normal, but renal vein renin sampling showed predominant renin secretion from the right kidney both in basal samples and after acute stimulation of renin release with intravenous diazoxide. Nephrectomy has resulted in marked reduction of blood pressure without treatment one year after operation. The findings support the predictive value of renal vein renin sampling when hypertension is associated with renal parenchymal disease, even when peripheral renin is normal.

Graft-versus-host disease in consecutive patients with acute myeloid leukaemia treated with blood cells from normal donors.

Two consecutive patients with acute myeloid leukaemia (AML) developed severe probable graft-versus-host disease (GVHD) following transfusion of blood products from normal donors. In one patient the AML had arisen de novo, while in the other it occurred four years after the patient developed non-Hodgkin's lymphoma (NHL) and was treated with radiotherapy and combination cytotoxic chemotherapy. Both patients received anti-leukaemic treatment with doxorubicin and cytosine arabinoside and intensive haematological supportive care with transfusions of red cell, white cell and platelet concentrates obtained from normal donors. Clinically the GVHD in each patient was manifest by a severe erythematous rash, intractable diarrhoea and abnormalities in the liver function tests. On pathological examination the skin in each case showed the typical changes of GVHD. Both patients died. There have been few previous reports of GVHD occurring after accidental engraftment of immunosuppressed patients undergoing therapy for acute leukaemia. Our experience suggests that it may occur more often than has hitherto been recognised. At present there is controversy concerning the possible anti-leukaemic effects of granulocyte transfusions. Until the relative importance of the benefits and deleterious effects of cells with the potential for engraftment is determined by further studies, we recommend the routine irradiation of all cellular blood products intended for administration to acute leukaemia patients undergoing intensive cytoreductive chemotherapy.

Enteropancreatic malignancy associated with multiple endocrine neoplasia type 1: risk factors and pathogenesis.

BACKGROUND: Enteropancreatic malignancy is an important cause of morbidity and mortality associated with multiple endocrine neoplasia type 1 (MEN 1). However, the risk factors and mechanisms of the tumorigenesis of this malignancy are poorly understood. METHODS: The authors conducted a retrospective study of factors associated with the development of malignant enteropancreatic tumor in 69 patients with MEN 1 belonging to a single family. RESULTS: Metastatic enteropancreatic tumor and gastrinoma were identified in 20% and 36% of patients, respectively. Compared with MEN 1 patients who did not have an immediate family history of enteropancreatic malignancy, MEN 1 patients with a first-degree relative affected by enteropancreatic malignancy had an increased risk of developing disseminated tumor (odds ratio, 3.7; P < 0.05). In addition, hypergastrinemia and advanced age were both associated with a significant increase in the risk of enteropancreatic malignancy. Elevated serum glycoprotein alpha subunit levels were associated with enterochromaffin-like cell hyperplasia, gastric carcinoid formation, and disseminated enteropancreatic tumor in hypergastrinemic patients (P < 0.05). CONCLUSIONS: Disease modifier factors act in concert with the MEN 1 gene to modulate the development of enteropancreatic neoplasia. It is possible to identify MEN 1 patients at high risk for developing aggressive enteropancreatic tumors. Heritable disease modifier factor(s) affecting enteropancreatic malignancy appear to reside at loci distinct from that of the MEN 1 gene.

Transfusion-associated graft-versus-host disease: report of an occurrence following the administration of irradiated blood.

Patients who are heavily immunosuppressed, such as those undergoing intensive anti-cancer chemotherapy, are at risk for development of accidental engraftment and graft-versus-host disease when they undergo transfusion with cellular blood components, a condition known as transfusion-associated graft-versus-host disease (TA-GVHD). To prevent this complication, it is routine to irradiate such blood components prior to their transfusion, although the minimum irradiation dose required is uncertain. The development of probable TA-GVHD is reported in a 10-year-old child following transfusions of platelets and packed red cells that had been irradiated at a nominal dose of 15 Gy. The transfusions were given during treatment for relapse of acute myeloid leukemia. Although the child developed complications including exfoliative dermatitis, delayed bone marrow regeneration, renal failure requiring dialysis, and respiratory failure requiring assisted respiration, she recovered from the episode of TA-GVHD after treatment with high-dose methylprednisolone and antithymocyte globulin. However, her leukemia relapsed, and she died. This experience suggests that the irradiation of cellular blood components at a nominal dose of 15 Gy prior to their transfusion to heavily immunosuppressed patients may be insufficient to prevent TA-GVHD.