Gaucher's disease associated with Hodgkin's disease.

A patient with chronic adult-onset Gaucher's disease is described. The diagnosis was based on the finding of typical Gaucher cells in the spleen, liver and bone marrow associated with deficiency of glucocerebrosidase. The patient also had Hodgkin's disease, nodular sclerosis type, stage III. The patient is alive and relatively well six years after presentation, having been treated with a combination of chemotherapeutic regimens. Previously reported cases of Gaucher's disease concurrent with Hodgkin's disease are reviewed.

Familial essential thrombocythemia.

Primary or essential thrombocythemia is rarely observed in childhood, and familial occurrence has been reported only once. In this study, essential thrombocythemia is documented in five members of both sexes from two to 62 years of age in three successive generations. The propositus had a persistent elevation of the platelet count, splenomegaly, a normal hemoglobin level, a normal white blood cell count, and abnormal platelet aggregation. Platelet arachidonic acid metabolites assayed by high-performance liquid chromatography and serum thrombopoietin levels were normal. Megakaryocytes were increased in number and size. Both mature and early immature megakaryocytes, but no atypical megakaryocytes, were identified by surface immunofluorescence. Bone marrow cultures showed normal myeloid and erythroid colony formation, and chromosome studies revealed a normal female karyotype. These findings support the concept that familial essential thrombocythemia is a myeloproliferative disorder that is transmitted by an autosomal dominant mode of inheritance, and that untreated young women and children with essential thrombocythemia have long survival.

An assessment of the validity of densitometric measures of striatal tyrosine hydroxylase-positive fibers: relationship to apomorphine-induced rotations in 6-hydroxydopamine lesioned rats.

The power of immunohistochemical staining as a tool for the study of the neurochemical anatomy of the brain would be greatly enhanced if quantitative measures of staining were to be developed. We have here assessed the reliability and validity of two population measures of extent of fiber innervation: percent area occupied by staining, and average optical density (AOD) of staining. We have evaluated these measures for tyrosine hydroxylase-positive staining of the striatum in relation to apomorphine-induced rotational behavior in 6-hydroxydopamine lesioned rats. We have found that inter-operator reliability for the area measure is high (r = 0.98). Apomorphine-induced rotations were observed when the area measured was reduced to 2% or less of the control side, and when the density measure was reduced to 15% or less. These results are similar to those obtained previously for biochemical assay of TH activity, which showed rotations at reductions to 10% or less. We conclude that these density measures provide valid relative indices of extent of fiber innervation on the same section. The AOD measure appears to be more sensitive at lower levels of innervation.

Attempted prevention of blast crisis in chronic myeloid leukemia by the use of pulsed doses of cytarabine and lomustine. A Cancer and Leukemia Group B study.

An attempt to prevent the blast crisis in chronic myeloid leukemia by the use of pulsed doses of (cytarabine cytosine arabinoside) and lomustine was attempted as a cooperative group study by Cancer and Leukemia Group B. The basis for this study was to delay the development of blast crisis by pulsing dose of drugs known to be effective against emerging "blast" cells. The experimental arm which consisted of cytarabine and lomustine did not produce overall results superior to conventional treatment with busulfan. This was related to the non-hematologic effects of the combination which produced significant gastrointestinal toxicity leading to relatively early discontinuation of the combination. Nevertheless, the trial design allowed relatively prompt discontinuation of experimental arm and cross-over to conventional treatment with either hydrea or busulfan. No evidence existed that the use of new drug combinations in CML prejudiced the patient's chance to response to conventional chemotherapy. Thus, a role model for future trials in this disease was developed. With the development of the interferons and other experimental forms of therapy this conceptual development may be of significance.

Unilateral hypoxic-ischemic injury in neonatal rat results in a persistent increase in the density of striatal tyrosine hydroxylase immunoperoxidase staining.

Little is known of the alterations in the neurochemical anatomy of the striatum following neonatal hypoxic-ischemic injury. In an experimental model in rodent, it has been shown that striatal biochemical markers of dopaminergic systems appear to be relatively spared. We sought to define the morphologic correlates of this finding by staining striatal tyrosine hydroxylase (TH)-positive fibers with the immunoperoxidase technique. Since this model is unilateral, it is possible to examine relative changes in the density of TH-positive staining of the striatum at the population level within the same section. We find that in immature animals (3-4 weeks) there is an increase in the relative density of striatal TH-positive staining on the injured side. There is also an increase in the relative density of staining in the nucleus accumbens, in the absence of shrinkage of that nucleus. There is no relationship between the degree of density increase in the striatum, and its degree of shrinkage. This increase in relative density is a persistent change, as it is also observed in adult rats (9-12 weeks). While the functional significance of these findings are unknown, they are compatible with a relative increase in the dopaminergic innervation of the hypoxia-ischemia injured striatum.

Demonstration of a medial to lateral gradient in the density of cholinergic neuropil in the rat striatum.

The striatum is anatomically organized into both distinctly bounded compartments (striosomes) and gradients of neuronal markers. Biochemical markers of striatal cholinergic systems are distributed in increasing amounts laterally. We have investigated the morphologic basis of this gradient by quantitative analysis of neuronal somata and neuropil stained immunocytochemically for choline acetyltransferase (ChAT). We found in both immature and adult rats that there was no difference in the density (neurons mm2) of somata in the medial and lateral compartments. In both age groups, however, there was a clear increase in ChAT-positive neuropil laterally. This medial to lateral gradient was present in all striatal planes examined. This gradient corresponds to the distribution of some other, non-cholinergic, striatal biochemical markers, and is likely to represent an important organizational feature of striatal anatomy, with functional implications.

Neurologic problems associated with chronic nitrous oxide abuse in a non-healthcare worker.

Chronic exposure to nitrous oxide (N2O) is known to be associated with hematologic and neurologic abnormalities. When this syndrome occurs, it is generally seen in health care workers, especially dentists and anesthesiologists, who have access to nitrous oxide. Here, however, we report a case of a 55-year-old non-healthcare worker who presented with multiple neurological abnormalities. His serum vitamin B12 level was low but his Shilling test was normal. His neurologic symptoms improved after cessation of inhaling nitrous oxide and starting vitamin B12 therapy. Physicians should consider nitrous oxide abuse in non-healthcare workers presenting with neurologic symptom of unclear cause.

Quantitative morphological analysis of striatal cholinergic neurons in perinatal asphyxia.

Although the static encephalopathies of childhood are common, little is known of the underlying alterations in the neurochemical anatomy of the brain. Using quantitative morphological techniques, we examined the effect of perinatal hypoxia-ischemia on the number and distribution of cholinergic (ACh) neurons in a unilateral experimental striatal lesion in rats. The striatal pathology simulates status marmoratus, a recognized correlate of human dystonic cerebral palsy. We found that striatal injury results in a mean 22% decrease in the number of ACh neurons at the age of 3 to 4 weeks. The loss of neurons was relatively less than the volume loss, resulting in a mean 16% increase in neuron density. This effect was not uniform throughout the striatum; it was more pronounced caudally, resulting in a mean 52% increase in density in the most caudal striatal plane. These changes in immature rats were also seen in adult rats, indicating that there were lasting alterations in striatal cholinergic morphology. Hypoxic-ischemic injury to the striatum also resulted in a persistent decrease in the mean area of ACh neurons. The increased density of these neurons may imply that they are relatively resistant to hypoxic-ischemic injury. These findings may be relevant to the observation that anticholinergic drugs are among the most effective for treating dystonias, including those observed in static encephalopathies.

Receptors for immunoglobulin isotype on T and B lymphocytes from untreated patients with chronic lymphocytic leukaemia.

Peripheral blood lymphocytes from eighteen untreated patients with chronic lymphocytic leukaemia (CLL) were analysed for the proportions of T and B lymphocytes with receptors for IgM, IgG or IgA. T lymphocytes with Fc receptors for IgM (T mu cells) or IgA (T alpha) cells were found in proportions comparable to those found in the controls. However, the proportion of T lymphocytes with receptors for IgG (T gamma cells) was significantly increased (P < 0.001) resulting in an abnormally low ratio of T mu/T gamma (P < 0.001), when compared with normal controls. The proportion of B cells bearing Fc receptors for IgM, IgG or IgA was determined simultaneously. No significant differences were found between the normal controls and the patients with CLL. In vitro treatment of the purified T and B lymphocyte preparations with human leucocyte interferon, did not alter the proportions of the lymphocytes expressing Fc receptors for various immunoglobulin isotypes. The significance of these findings is discussed.

Transient agranulocytosis associated with non-A, non-B hepatitis.

A 44-yr-old woman with non-A, non-B hepatitis developed agranulocytosis and absence of marrow granulocyte precursor cells with only mild involvement of other blood elements. The agranulocytosis was complicated by gram-negative septicemia, successfully treated with antibiotic therapy. Marrow recovery followed 2 wk of supportive therapy. Before reversal of the agranulocytosis, a future bone marrow transplant was a consideration, making the use of therapeutic granulocyte transfusions, with their ability to sensitize the recipient, potentially harmful. Experience in this case indicates that agranulocytosis associated with non-A, non-B hepatitis may be reversible, and supports the use of supportive care including appropriate antibiotics, and if necessary, granulocyte transfusions, pending marrow recovery.