AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome.

Background: Joubert syndrome (JS) is an autosomal recessive disorder characterised by hypotonia, ataxia, mental retardation, altered respiratory pattern, abnormal eye movements, and a brain malformation known as the molar tooth sign (MTS) on cranial MRI. Four genetic loci have been mapped, with two genes identified (AHI1 and NPHP1).

Methods: We screened a cohort of 117 JS subjects for AHI1 mutations by a combination of haplotype analysis and sequencing of the gene, and for the homozygous NPHP1 deletion by sequencing and marker analysis.

Serum bilirubin levels and mortality after myeloablative allogeneic hematopoietic cell transplantation.

Many patients who undergo hematopoietic cell transplantation experience liver injury. We examined the association of serum bilirubin levels with nonrelapse mortality by day +200, testing the hypothesis that the duration of jaundice up to a given point in time provides more prognostic information than either the maximum bilirubin value or the value at that point in time. We studied 1,419 consecutive patients transplanted from allogeneic donors.

De novo generation of CD4 T cells against viruses present in the host during immune reconstitution.

T cells recognizing self-peptides are typically deleted in the thymus by negative selection. It is not known whether T cells against persistent viruses (eg, herpesviruses) are generated by the thymus (de novo) after the onset of the infection. Peptides from such viruses might be considered by the thymus as self-peptides, and T cells specific for these peptides might be deleted (negatively selected).

Death of an Arabian Jew.

A 69-year-old Judean man presents with chronic low-grade fever, pedal edema, and abdominal pain. His condition deteriorates over several weeks with the appearance of shortness and foulness of breath, pruritus, convulsions of every limb, and gangrene of the genitalia. Just before he dies, he orders dozens of the leading men of his kingdom imprisoned and instructs his sister to kill them all after he is gone.

A 21-year longitudinal analysis of the effects of prenatal alcohol exposure on young adult drinking.

Background: Prenatal alcohol exposure may be a risk factor for the development of alcohol problems in humans.

Methods: We use data beginning with interviews of women in prenatal care at midpregnancy to predict alcohol use and alcohol-related problems in their offspring now aged 21 years. Maternal drinking during pregnancy was assessed from November 4, 1974, through October 2, 1975, along with measures of maternal smoking, use of caffeine and other drugs, and demographic factors.

The current status of hematopoietic cell transplantation.

Hematopoietic cell transplantation is the preferred therapy for a substantial proportion of patients with life-threatening diseases of the lymphohematopoietic system. Recent advances in donor identification, disease eradication, and supportive care measures have broadened the application of transplantation and improved outcomes. This article provides a brief review of the major clinical principles of transplantation and results achieved to date.

Hematopoietic cell transplantation as a form of immunotherapy.

The association of graft-versus-host disease with diminished relapse rates following allogeneic hematopoietic cell transplantation, together with the dramatic responses sometimes seen following donor lymphocyte infusions, demonstrates the considerable power of the human immune system to eradicate hematological malignancies. The development of methods that reliably achieve complete engraftment of donor lymphohematopoiesis without subjecting patients to very-high-dose toxic chemoradiotherapy represents an important step in capitalizing on the allogeneic graft-versus-tumor effect. Nonmyeloablative hematopoietic cell transplantation can achieve complete chimerism in essentially all patients with HLA-matched siblings and the large majority of patients with matched unrelated donors.

Effect of hypergastrinemia on pancreatic carcinogenesis.

Background: Previous studies in our laboratory demonstrated that pancreatic carcinomas in rodents express receptors for the peptide hormone gastrin that are not present in normal adult pancreas. In view of an abundant literature suggesting that gastrin may promote growth of various gastrointestinal tissues and tumors, the effect of hypergastrinemia on the process of pancreatic carcinogenesis was evaluated.

Methods: Rats received subcutaneous injections of the pancreatic carcinogen azaserine at 19 and 26 days of age.

Management of hepatic sinusoidal obstruction syndrome following treatment with gemtuzumab ozogamicin (Mylotarg).

Gemtuzumab ozogamicin (Mylotarg) therapy may cause sinusoidal obstruction syndrome (SOS), the mechanism of which probably involves targeting of CD33+ cells in the sinusoids of the liver, activation of stellate cells, damage to sinusoidal endothelial cells, sinusoidal vasoconstriction, and ischemic hepatocyte necrosis. The clinical manifestations of this liver injury are hepatomegaly, weight gain, ascites, jaundice, and elevation of serum aminotransferase enzymes. An approach to patient management includes being certain that SOS is the correct diagnosis; ensuring that liver blood flow is optimized; and managing the accumulation of fluid in the peritoneal cavity, pleural spaces, and pulmonary interstitium.

Portal vein thrombosis after hematopoietic cell transplantation: frequency, treatment and outcome.

Patients who develop veno-occlusive disease (VOD) of the liver may have low plasma levels of the natural anticoagulants protein C and antithrombin III, but large vessel thromboses are not commonly reported in these patients. We reviewed the records of 1847 consecutive patients for evidence of portal vein thrombosis. Eight patients (0.

First-stage palliation of complex univentricular cardiac anomalies in older infants.

Background: Poor outcomes have been reported for children older than 30 days of age with cardiac anomalies treated with first-stage palliation.

Methods: Our institution has offered first-stage palliation for all such patients regardless of age. The results of this policy were reviewed.

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987-1997: incidence, causes, and outcome.

Objective: Severe GI bleeding after hematopoietic cell transplantation is commonly due to lesions that are unusual in nontransplant patients. The frequency of GI bleeding appears to have decreased over the last decade, but the reasons have not been readily apparent. We sought to determine the incidence of severe bleeding during two time periods, to describe the causes and outcomes of bleeding, and to analyze the reasons behind an apparent decline in severe bleeding over the decade covered.

Chronic graft-versus-host disease of the liver: presentation as an acute hepatitis.

Chronic graft-versus-host disease (GVHD) of the liver usually presents as an indolent cholestatic disease in patients with skin, mouth, and eye involvement. We observed 14 patients in whom chronic GVHD of the liver presented with marked elevations of serum aminotransferases, clinically resembling acute viral hepatitis. Onset of liver dysfunction was at 294 days (range, 74-747 days) after allogeneic hematopoietic cell transplantation and coincided with a recent cessation or taper of immunosuppressive drugs.

Use of and attitudes about alternative and complementary therapies among outpatients and physicians at a municipal hospital.

Objectives: To survey outpatients and physicians about their use of, knowledge of, and interest in alternative therapies.

Design: Anonymous self-administered survey.

Settings/location: Outpatient clinics at a major municipal medical center.

Treatment of chronic myelomonocytic leukaemia by allogeneic marrow transplantation.

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) in 21 patients with chronic myelomonocytic leukaemia (CMML) who were treated at the Fred Hutchinson Cancer Research Center between 1990 and 1998. There were 11 male and 10 female patients with a median age of 47.4 years (range 1.

Bile duct apoptosis and cholestasis resembling acute graft-versus-host disease after autologous hematopoietic cell transplantation.

Background: Acute graft-versus-host disease (GVHD) of the liver is a frequent complication of allogeneic hematopoietic cell transplantation. This report describes hepatic GVHD following autologous transplantation.

Methods: We reviewed 116 consecutive autologous transplant recipients.

The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections.

Background: Children with gastrointestinal infections caused by Escherichia coli O157:H7 are at risk for the hemolytic-uremic syndrome. Whether antibiotics alter this risk is unknown.

Methods: We conducted a prospective cohort study of 71 children younger than 10 years of age who had diarrhea caused by E.

Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation.

Lymphopenia and immune deficiency are significant problems following allogeneic hematopoietic cell transplantation (HCT). It is largely assumed that delayed immune reconstruction is due to a profound decrease in thymus-dependent lymphopoiesis, especially in older patients, but apoptosis is also known to play a significant role in lymphocyte homeostasis. Peripheral T cells from patients who received HCT were studied for evidence of increased cell death.

Is there a best transplant conditioning regimen for acute myeloid leukemia?

The outcome of marrow transplantation is largely determined by the effectiveness of the transplant preparative regimen. Nonetheless, there have been startlingly few randomized trials attempting to identify optimal regimens for specific conditions and, at present, no single approach has emerged as superior for the treatment of acute myeloid leukemia (AML) in the few trials that have been performed. Newer approaches that appear encouraging in phase II studies include substituting etoposide for cyclophosphamide, adding thiotepa to the traditional cyclophosphamide plus total body irradiation combination in the setting of T cell depletion, and using antibody-based targeted radiotherapy as part of the transplant regimen.

Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate.

There are several competing models of stem cell involvement in acute myeloid leukemia (AML). At issue is whether the disease origin is in the pluripotent stem cell or whether it arises later in a more mature progenitor cell. The observation that the CD33 antigen is present on AML cells, and on normal and leukemic progenitors, suggested that one might be able to target these cells while sparing the normal stem cells.