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Biomedical subjects

J M Goldman

Publications and source records attributed to J M Goldman.

At least 19 recordsLinked to original sources
PubMed1992

Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) has a poor prognosis when treated with conventional chemotherapy. We analyzed the outcome of 67 HLA-identical sibling bone marrow transplants (BMTs) for Ph1-positive ALL reported to the International Bone Marrow Transplant Registry (IBMTR). Twenty-one of 67 (31%) transplant recipients survived in continuous complete remission more than 2 years after transplant. Two-year actuarial probabilities (95% confidence interval) of leukemia-free survival were 38% (23% to 55%) for 33 patients transplanted in first remission, 41% (23% to 61%) for 22 patients transplanted after relapse, and 25% (9% to 53%) for 12 patients failing to achieve remission with conventional chemotherapy. These data indicate that transplants are effective treatment for Ph1-positive ALL.

Adolescent↗
PubMed1992

Effect of inhaled methanol on pituitary and testicular hormones in chamber acclimated and non-acclimated rats.

Two experiments were conducted in which the acute effects of inhaled methanol on serum hormones associated with reproductive function in the male rat were evaluated. In the first experiment, rats exposed to methanol (0, 200, 5000 and 10,000 ppm) for 6 h were killed at the end of the exposure period (6 h) or the following morning (24 h). Also, because the process of exposure itself could modify neuroendocrine function, the effect of the handling associated with placing the rat in the exposure chamber was evaluated further by dividing the exposed animals into acclimated (2 weeks of prior handling) and non-acclimated groups. At 6 h, an effect of prior handling was noted in the sham-exposed rats, with serum luteinizing hormone (LH) of the non-acclimated group being greater than that of the acclimated group. Serum LH concentrations were altered by methanol exposure, but the direction of change and the exposure level at which an effect was noted differed between the acclimated and non-acclimated rats. Methanol (5000 ppm) reduced serum LH in the non-acclimated animals, while 10,000 ppm increased LH in the acclimated rats. Follicle stimulating hormone (FSH) and testosterone were unchanged by methanol in rats killed at 6 h. Thus, this experiment did not confirm earlier reports that exposure to 200 ppm for 6 h reduced serum testosterone. At 24 h, an effect of prior handling was still present in the hormonal measures, with serum and interstitial fluid testosterone concentrations being greater in the non-acclimated rats. Also, there was a dose x handling interaction with methanol exposure inducing an increase in serum testosterone in the non-acclimated rats (up to 5000 ppm) and a decrease in the acclimated rats (up to 10,000 ppm). In the second experiment, groups of acclimated and non-acclimated rats were exposed to 0 or 5000 ppm methanol for 1, 2 and 6 h and killed immediately after removal from the chamber. Serum LH, testosterone and FSH values were not different in sham- vs methanol-exposed rats at any time point. As in experiment 1, an effect of prior handling was noted. In general, the concentrations of these hormones and serum prolactin in the non-acclimated rats were greater than those observed for acclimated rats. Methanol exposure resulted in increased prolactin concentrations under both handling conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Acclimatization↗
PubMed1992

Graft vs. leukaemia reactions in chronic myeloid leukaemia.

A 39-year-old female relapsed 36 months after allogeneic bone marrow transplantation for chronic myeloid leukaemia. Infusion of peripheral blood leucocytes from her bone marrow donor resulted in complete remission, and she remains leukaemia-free 18 months later. This case provides direct evidence for a 'graft vs. leukaemia' (GVL) effect contributing to the eradication of leukaemia after marrow transplantation. Existing evidence for GVL and its possible mechanisms are reviewed.

Adult↗
PubMed1992

Simplifying the assessment of patients with chronic airflow limitation for home nebulizer therapy.

One-hundred nebulizer trials were performed in 98 adult patients with chronic airflow limitation who had remained symptomatic despite regular use of bronchodilators by metered dose or dry powder inhalation. Mean baseline FEV1 was 0.9 (SD = 0.41) 1, FVC -2.0 (0.74) 1 and PEFR 169 (77) 1 min-1. After laboratory measurements of reversibility to inhaled salbutamol (5 mg) and ipratropium bromide (0.5 mg), patients were supplied with a compressor and a peak flow meter to make twice daily measurements at home for 3 weeks. They nebulized normal saline, salbutamol (5 mg) and salbutamol (5 mg) ipratropium (0.5 mg) mixture 6-hourly, each for 1 week. A positive nebulizer trial was defined as a 15% increase in mean PEFR over a week on an active treatment compared to the week on saline. Twenty-eight patients had positive trials based on these criteria. Of these nine responded to both active treatments and 16 to the salbutamol/ipratropium mixture. Although no laboratory measurements predicted a positive domiciliary trial, the patients' subjective assessment of benefit had a 93% sensitivity and 87% negative predictive value. We conclude that an appropriate protocol for assessing the value of long-term nebulized bronchodilators is for patients to measure their PEFR during a week of nebulized saline and a week of nebulized beta-agonist/ipratropium mixture. Those with an increase of 15% in mean PEFR in the week on active treatment and who experienced subjective benefit should be supplied with a compressor. Had we conducted our 100 trials in this way we would have started 25 of our 98 patients on long-term home nebulized bronchodilators.

Adult↗
PubMed1992

Bone marrow transplantation for chronic myelogenous leukemia.

It is generally accepted that patients with chronic myelogenous leukemia in chronic phase under the age of 50 years who have HLA-identical siblings, should be offered bone marrow transplantation within the first year of diagnosis. The projected disease-free survival for these patients is 70% to 80% at 4 years, and most of these will prove to have been cured. Results of bone marrow transplantation for patients with more advanced disease are less promising. For transplant conditioning there is no important difference between cyclophosphamide plus total-body irradiation and busulphan plus cyclophosphamide. Nonenlarged spleens require neither splenectomy nor additional radiotherapy. The use of cyclosporine and methotrexate is currently the optimal approach to graft-versus-host disease prevention. Fewer good results are obtained with "matched" volunteer marrow donors. Use of the polymerase chain reaction to monitor residual BCR-ABL transcripts after bone marrow transplantation may prove useful in identifying patients at increased risk for relapse. Autografting may offer the prospect of prolonged life or even cure for patients without suitable allogeneic donors.

Bone Marrow Transplantation↗
PubMed1992

Evidence that umbilical cord blood contains a higher frequency of HLA class II-specific alloreactive T cells than adult peripheral blood. A limiting dilution analysis.

Umbilical cord blood has been used to effect hematological reconstitution and there are sufficient stem cells available in the cord blood obtainable from a single placenta to reconstitute an adult patient. Umbilical cord blood might therefore, have widespread potential use in the field of bone marrow transplantation. We compared alloreactivity of paired samples of adult and cord peripheral blood mononuclear cells, by measuring frequencies of both alloreactive T helper cells and cytotoxic T cell precursors (CTLp), using limiting dilution analysis. In addition we compared the phenotype of adult and neonatal PBMC, using monoclonal antibody staining. Cord PBMC in general showed higher frequencies of alloreactive Th than adult PBMC, with statistically significant differences in 6 out of 10 experiments. There was no statistically significant difference between adult and cord CTLp frequencies. Adult and cord PBMC surface phenotype was similar, except that cord blood contained fewer lymphocyte function-associated-3 (LFA-3) positive (memory) cells.

Adult↗
PubMed1992

A chronic pulmonary syndrome associated with graft-versus-host disease after allogeneic marrow transplantation.

Of 143 consecutive patients who survived at least 6 months after bone marrow transplantation (allogeneic [n = 131]; syngeneic [n = 5]; or autologous [n = 7]) and whose pulmonary function was evaluated before and on at least 2 occasions after BMT, 29 (20%) developed a chronic pulmonary syndrome without evidence for an infectious etiology. Twenty-eight (97%) presented with cough and 22 (76%) with dyspnea; abnormal chest signs were crackles in 23 (79%) and wheeze in 22 (76%). Chest roentgenogram showed pulmonary infiltrates in 15 (52%) cases but was normal in 14 (48%). All patients had major reductions in lung volumes (forced expiratory volume in 1 sec [FEV1]; relaxed vital capacity [VC]; and alveolar volume [VA]), and/or diffusing capacity (pulmonary diffusing capacity [TLCO] and single-breath carbon monoxide coefficient [KCO]). The obstructive component varied with only 18 (62%) patients developing overt airways obstruction (FEV1/VC < 75%), and in 6 of this group the fall in lung volumes preceded the onset of airways obstruction. Open lung biopsy (n = 4) showed both bronchiolitis obliterans and chronic patchy interstitial pneumonitis. The development of this syndrome was associated with acute (P < 0.001) and chronic (P < 0.0001) graft-versus-host disease of other organ systems. Twenty-four (83%) patients had a partial or complete response to immunosuppressive agents. Six (21%) have died, five (17%) of pulmonary complications. We suggest that this syndrome may be a manifestation of chronic GVHD involvement of the lung.

Adolescent↗
PubMed1992

Second transplants for patients with chronic myeloid leukaemia in relapse after original transplant with T-depleted donor marrow: feasibility of using busulphan alone for re-conditioning.

Between July 1986 and March 1991, 16 patients who had relapsed after T-lymphocyte depleted bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML) received a second transplant using unmanipulated marrow cells from the same HLA-identical sibling donor. The median numbers of days from first BMT to haematological relapse and to second BMT were 557 (range 273-1543) and 1211 (range 476-2310) respectively. 11 patients were in uncomplicated chronic phase at time of second BMT, and five had more advanced disease. As conditioning for second BMT, eight patients received various combinations of cytotoxic drugs, and eight received high-dose busulphan alone. Eight (50%) patients survive at a median of 424 d post-second BMT (range 158-1789) and all are free of leukaemia by conventional criteria: five had been conditioned with high-dose busulphan alone. Causes of death in the eight patients who died included relapse (n = 2), graft-versus-host disease (n = 2), interstitial pneumonitis (n = 2), and infection (n = 2). We conclude that patients relapsing into chronic phase after BMT with T-lymphocyte depleted donor marrow may be offered the option of second BMT with unmanipulated marrow from the original donor. Conditioning with high-dose busulphan alone may be safer than use of more intensive schedules.

Adolescent↗
PubMed1992

Lymphocytes from multi-transfused patients exhibit cytotoxicity against autologous cells.

We previously demonstrated that multitransfused patients with severe aplastic anaemia (SAA) exhibit high numbers of alloreactive cytotoxic T lymphocyte precursors directed against their HLA identical siblings. In this study a group of patients who had received multiple blood transfusions for SAA, other haematological diseases or acute blood loss were tested for autocytotoxicity and the results compared with those of untransfused controls. These controls consisted of normal individuals, patients with chronic myeloid leukaemia (CML) or untransfused patients with SAA. There was a significantly higher degree of autocytotoxicity in multitransfused patients, than in the untransfused controls, including untransfused patients with SAA (P = 0.0001). These results suggest that blood transfusion is responsible for inducing autoreactivity. In one patient, in whom both alloreactive anti-non-MHC and autoreactive cytotoxic T lymphocytes (CTL) had been detected, it was demonstrated that there was no crossreactivity between the alloreactive and autoreactive CTL responses. Inhibition studies using monoclonal antibodies revealed the effector cells to be T lymphocytes and the restricting determinants to be both HLA class I and II molecules.

Anemia, Aplastic↗
PubMed1992

Relapse into blast crisis following bone marrow transplantation for chronic phase chronic myeloid leukaemia: a report of five cases.

A proportion of patients receiving allogeneic bone marrow transplants (BMT) for chronic myeloid leukaemia (CML) in first chronic phase relapse; most of these relapses show features of chronic phase disease. We report here a series of five patients seen at a single institution over a 10 year period who developed blast crisis as the first sign of relapse after BMT for CML in chronic phase. The blast cells were myeloid in three cases and lymphoid in two. In one case the relapse may have occurred in cells of donor origin. The possible explanations for this unusual sequence of events include incipient transformation that was not detected before BMT, undetected relapse into chronic phase proceeding into transformation post-BMT, and transformation occurring de novo post-BMT in small numbers of residual leukaemic stem cells.

Adult↗
PubMed1992

Neuroendocrine responses to social regulation of puberty in the female house mouse.

First estrus is advanced in female house mice exposed to an adult male and delayed in those housed in groups. Experiments were conducted to explore possible mechanisms by which the hypothalamus integrates these puberty-regulating social signals. Female mice weaned at 21 days of age were placed in groups of 8 (G8JF), a juvenile female with a juvenile male (JFJM) or juvenile female with an adult male (JFAM). All females were ovariectomized on day 28 and sacrificed on day 29. There was no significant difference between treatments in the postovariectomy rise in LH. Next, female mice were weaned, assigned to G8JF, JFJM or JFAM treatments and ovariectomized on day 22. Females were sacrificed on day 29, 3 h after injection with either 1.0 micrograms of estradiol, or vehicle. Estradiol significantly suppressed LH in all three treatments, with no differences between treatments. Two-way ANOVA (social treatment x estradiol treatment) revealed no differences or interactions in brain catecholamines as a result of estradiol injection. The G8JF treatment significantly increased norepinephrine, (NE), dopamine (DA) and its metabolite 3,4-dihydroxy-phenylacetic acid in the mediobasal hypothalamus (MBH), and the 3-methoxy-4-hydroxy-phenylglycol/NE ratio in the preoptic area (POA). In the final experiments, isolate prepubertal female mice were treated with either water or male urine (MU) on the oronasal groove. Eight days of MU treatment resulted in significant uterine growth, however there were no differences in serum LH, POA or MBH catecholamines or POA and median eminence LHRH. One hour after application of MU, serum LH was significantly elevated, however, there were no differences in accessory olfactory bulb catecholamines. These results suggest that the mechanism by which male and grouped female exposure alters first estrus may not involve changes in sensitivity to estradiol negative feedback. Grouping may delay first estrus through the negative effects of DA on the LHRH system in the MBH. We observed no differences that might help to explain how male exposure causes LH release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Specific point mutations that activate v-abl are not found in Philadelphia-negative chronic myeloid leukaemia, Philadelphia-negative acute lymphoblastic leukaemia or blast transformation of chronic myeloid leukaemia.

The involvement of the BCRlABL fusion gene in patients with Philadelphia (Ph) chromosome positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL) is well characterised, but the molecular events underlying the cases of Ph-negative CML and ALL that lack BCR gene involvement and those that cause transformation of Ph-positive CML are unknown. The murine ABL gene can be activated by genetic events that do not involve the BCR gene, including the introduction of two specific point mutations in exons VII and XI respectively, as found in the homologous sequence of the v-abl oncogene. We therefore sought evidence for analogous point mutations in the ABL gene in patients with Ph-negative, BCR-negative CML (n = 25), Ph-negative ALL (n = 18) and in Ph-positive CML in transformation (n = 28). We used restriction fragment length polymorphism and single strand conformational polymorphism techniques to analyse DNA amplified fragments of selected ABL coding regions from leukaemia cells. We identified only normal wild-type DNA sequences. The absence of these transforming point mutations does not exclude the possibility that the ABL gene in such patients could be activated by other means.

Adult↗
PubMed1992

Use of autotransplants in chronic myeloid leukaemia.

Patients with newly diagnosed CML have Ph-negative stem cells in their marrow and peripheral blood. A minority can be restored to durable Ph-negative haemopoiesis by treatment with interferon-alpha but in general autografting with marrow collected after IFN treatment has not proved feasible. Some patients autografted with blood-derived stem cells collected in chronic phase have achieved durable Ph-negative haemopoiesis and selected patients autografted with 10-day incubated marrow cells have also achieved complete remission. An alternative approach involves collection and isolation of Ph-negative stem cells that may then be used for autografting. Different lines of evidence suggest that induction of remission for all patients with CML should be an attainable goal.

Blood Transfusion↗