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Biomedical subjects

J Halter

Publications and source records attributed to J Halter.

At least 19 recordsLinked to original sources

Impact of high-resolution matching in allogeneic unrelated donor stem cell transplantation in Switzerland.

It is currently unknown what degree of human leukocyte antigen (HLA)-mismatching is acceptable in unrelated donor hematopoietic stem cell transplantation (UD-HSCT). Mismatches at some loci may be more permissive than others. We have analyzed the effect of high-resolution HLA-matching on outcome of all 214 consecutive recipients of UD-HSCT carried out in Switzerland. All typing was by the Swiss reference laboratory. Donor-recipient pairs were HLA-10/10 matched (n=130) or mismatched for either HLA-A/-B/-DRB1/multiple loci (n=33; (HLA-A/-B=10); (-DRB1=8); (multiple=15)); HLA-C (n=29) or HLA-DQ/-DRB3 (n=22; (DQ=16); (-DRB1=6)). The median follow-up was 32 months. Survival probabilities (+/-95% confidence interval) at 3 years were 57 (+/-10)% for recipients of HLA 10/10-matched transplants, 53 (+/-22)% for recipients of HLA-DQ/-DRB3-mismatched transplants, 44 (+/-20)% for recipients of HLA-C-mismatched transplants and 0% for recipients of transplants mismatched at HLA-A/-B/-DRB1/multiple loci (P<0.0001). In multivariate analyses, HLA compatibility was the variable most significantly associated with survival and treatment-related mortality. We found important differences in survival in recipients of UD-HSCT with best results for transplants from 10/10 matched donors. Single mismatches at HLA-DQ/-DRB3 were well tolerated, mismatches at HLA-C had intermediate results and mismatches at HLA-A/-B/-DRB1/multiple loci resulted in poor survival.

Adolescent↗

Pneumocystis carinii pneumonia in chronic lymphocytic leukaemia.

Pneumocystis carinii pneumonia in patients with chronic lymphocytic leukaemia (CLL) who have not been treated with fludarabin are rare, although clinically relevant CD4 T-cell depletion can occur in longstanding CLL without prior treatment with purine analogues. A 52 year old woman is reported who was on long term treatment with chlorambucil and taking a short course of prednisone for familial CLL before she developed progressive dyspnoea, and P carinii pneumonia was diagnosed in bronchoalveolar lavage fluid. Despite treatment with high dose co-trimoxazole the patient died.

Anti-Infective Agents↗

Contrast media triggering cutaneous graft-versus-host disease.

Adverse reactions to iodinated contrast media are varied and known to develop in patients with asthma and a history of allergy. We describe three successful allogeneic bone marrow transplantation (BMT) patients, who all developed dermal graft-versus-host disease (GVHD) after receiving contrast media. Cutaneous GVHD triggered by contrast media has not been reported to date and has implications for the assessment, monitoring and treatment of patients during the post-transplant period.

Acute Disease↗

Late G-CSF after allogeneic bone marrow or peripheral blood stem cell transplantation: a prospective controlled trial.

Granulocyte colony-stimulating factor (G-CSF) is widely used to accelerate neutrophil recovery after allogeneic BMT or PBSC transplantation. The optimal time to start G-CSF treatment is not known. Forty-two patients undergoing allogeneic BMT or PBSC transplantation for hematological malignancies received G-CSF either on day 6 or on day 9 post transplant. The time to hematological recovery was monitored and the two groups were compared with respect to peritransplant morbidity and mortality. Recovery of the neutrophil counts to >0.1 x 10(9)/l, > 0.5 x 10(9)/l and >1.0 x 10(9)/l were not significantly different in either group. There was no difference in recovery of red blood cell and platelet counts and no difference between the two groups with respect to the number of febrile days or number of days on antibiotic treatment. Documented bacterial, viral or fungal infections did not occur more often when G-CSF treatment was started on day 9. Delaying treatment with G-CSF resulted in a significant reduction in the length of treatment from 13 to 10 days (23.1% reduction). Reducing the length of the treatment by 3 days lowered the costs by 395.40 Euro per patient. Delaying G-CSF treatment and starting on day 9 after BMT or PBSC transplantation is safe and results in a clear economic benefit.

Adolescent↗

[Neonatal alloimmune thrombocytopenia due to a rare anti-HPA-1b antibody].

Foetal and neonatal alloimmune thrombocytopenia is caused by transplacental transfer of antibodies directed against platelet antigens and affects approximately 1 in 1000-2500 neonates. Clinically relevant complications are the intracranial haemorrhages that occur in 10-20% of cases. 20 platelet antigen systems are currently known. However, immunisation is most frequently seen against two of these (HPA-1a and HPA-5b). Treatment options include transfusion of compatible or, if these are not available while urgently needed, random donor platelets, intravenous immunoglobulin, and steroids. We report on a case of neonatal alloimmune thrombocytopenia due to an anti-HPA-1b antibody in the third pregnancy of a 31-year-old Caucasoid woman. The infant was treated with repeated maternal and random donor platelet transfusions and with a single dose of intravenous immunoglobulin.

Adult↗

Glucose transporter content and enzymes of metabolism in nerve-repair grafted muscle of aging Fischer 344 rats.

Aging and grafting are associated with decreased ability of muscle to sustain power, likely reflecting diminished fuel availability. To assess mechanisms that may contribute to availability of glucose, we studied GLUT-1 and GLUT-4 protein as well as mRNA contents and enzymes of glucose metabolism in grafted and control medial gastrocnemius (MG) muscles of 6-, 12-, and 24-mo-old male Fischer 344 rats. There was no effect of age or grafting on MG GLUT-4 content. There was both an age- and graft-associated increase in GLUT-1 content (P = 0.0044 and 0.0063, respectively). There was no effect of aging or grafting on hexokinase and phosphofructokinase activity or on protein and glycogen content. Muscle mass and citrate synthase activity were significantly diminished with grafting. Citrate synthase activity was significantly greater in the 12-mo-old compared with the 6- and 24-mo-old animals. Grafting in combination with aging had no impact on any of the parameters measured. We conclude that diminished glucose transporter expression cannot explain the decreased ability of aged muscle to sustain power. In addition, we conclude that the diminished ability of the grafted MG muscle to sustain power may be explained, in part, by a decrease in energy available from oxidative metabolism.

Aging↗

Variations in circulating catecholamines fail to alter human platelet alpha-2-adrenergic receptor number or affinity for [3H]yohimbine or [3H]dihydroergocryptine.

A series of studies were performed to determine the relationship between physiologic levels of circulating plasma norepinephrine and epinephrine and human platelet alpha-2 binding site number and the affinity (KD) of these sites for antagonist radioligands. In one study, alpha-2-adrenergic binding site number and affinity were compared using both [3H]yohimbine and [3H]dihydroergocryptine as radioligands. There was good absolute and relative comparison for binding site number, but only a relative relationship for KD. In 46 normal subjects, there was no significant relationship between site number or KD and age, plasma epinephrine, or plasma norepinephrine concentration. Even after plasma epinephrine was raised nearly 20-fold by means of an intravenous infusion for 4 h in seven normal subjects, neither sites (608 +/- 68 vs. 567 +/- 120 sites/platelet) nor KD (2.01 +/- 0.94 vs. 2.14 +/- 1.15 nM) were significantly changed. Similarly, neither sites (445 +/- 55 vs. 421 +/- 53 sites/platelet) nor KD (1.44 +/- 0.29 vs. 2.10 +/- 0.75 nM) were significantly changed in six normal subjects when plasma norepinephrine levels increased during oral administration of prazosin for 1 wk. Thus, in a cross-sectional analysis and after a change in plasma catecholamine concentrations, there was no relationship in normal subjects between platelet alpha-2 binding site number or affinity of these sites for antagonist radioligands and the circulating catecholamine levels to which the platelets were exposed. In a group (n = 7) of patients who lack epinephrine-induced platelet aggregation due to abnormal thrombopoiesis, binding site number was decreased (304 +/- 36 vs. 572 +/- 29 sites/platelet, P less than 0.001) and KD tended to be greater (8.69 +/- 2.44 vs. 5.40 +/- 0.31 nM, P = NS) than in normal subjects (n = 46), despite having similar plasma catecholamine levels. There was no difference in binding site number (491 +/- 116 sites/platelet) and KD (5.61 +/- 0.84 nM) in patients (n = 5) with autonomic insufficiency and low levels of upright plasma norepinephrine when compared with the normal subjects. Two patients were examined before and after the removal of a pheochromocytoma. Their binding site number and KD were normal before the operation and essentially unchanged after the tumor removal and fall of plasma catecholamines. Thus, this study demonstrates that within the physiologic and pathophysiologic range of plasma catecholamines (in men), there is no relationship between the circulating catecholamine concentration and either platelet alpha-2 adrenergic binding site number or the affinity of these sites for antagonist radioligands.

Adult↗

Neurophysiological assessment of electrode placement in the spinal cord.

The use of neurophysiological techniques in addition to radiographic methods to determine the location of electrodes to be introduced into the epidural space for spinal cord stimulation is beneficial. Information on the distribution of paresthesias and muscle twitches provides an indication of the level and lateral location in relation to the midline of the spinal cord. For electrodes placed posteriorly, the threshold currents necessary for sensation are lower than those for muscle responses. Somatosensory evoked potentials resulting from epidural stimulation demonstrate effective depolarization of ascending structures. Evoked potentials recorded from the electrodes in response to peripheral nerve or spinal cord stimulation at a distant segment illustrate the possibility of activation of underlying generators of the spinal cord.

Brain Injuries↗

Differential effect of isoproterenol on acute glucagon and insulin release in man.

In man, the infusion of arginine or isoproterenol elevates immunoreactive glucagon and insulin levels. Since arginine administered as a pulse stimulates the acute secretion of both hormones, and an insulin rise is observed after the bolus injection of isoproterenol, these findings probably represent a direct effect of arginine and isoproterenol on islet cells. To determine if there is an acute alpha-cell response to isoproterenol, we have administered this beta-adrenergic agonist as a bolus to healthy volunteers. Arginine administered as a pulse elicited both insulin and glucagon responses whereas pulses of isoproterenol, at half maximal and maximal insulin-stimulating doses, had little effect on glucagon levels. This relative insensitivity of the alpha cells to stimulation by isoproterenol suggests that endogenous beta-adrenergic tone may have a stronger influence on insulin than on glucagon secretion. Furthermore, these findings raise the possibility that beta-adrenergic regulation of plasma glucagon levels in vivo occurs by an indirect mechanism rather than a direct effect on the alpha cells.

Arginine↗

Circadian variation of plasma catecholamines in young and old men: relation to rapid eye movement and slow wave sleep.

Young and old healthy subjects with indwelling venous cannulae were found to undergo significant diurnal variations in plasma catecholamine levels. Both norepinephrine and epinephrine levels peaked in late morning and reached lowest values at night during sleep. Catecholamine levels were similar during slow wave and rapid eye movement sleep. While epinephrine levels were unaffected by age, norepinephrine levels were greater in older subjects by 28% during the day (at 1100 h; P less than 0.01) and by 75% at night (between 2200--0900 h; P less than 0.01). Older subjects slept less well; they had 90% less stage 4 sleep, 27% less rapid eye movement sleep, and twice as much wakefulness at night (P less than 0.05). These findings raise the possibility that this well known age effect on sleep may be related to increased sympathetic nervous system activity.

Adult↗

Nosocomial Legionnaires' disease: a continuing common-source epidemic at Wadsworth Medical Center.

Forty-nine cases of Legionnaires' disease were identified from May 1977 through July 1978 in patients and employees at Wadsworth Medical Center. Cases clustered in October and November 1977. Fifteen patients died. All Legionnaires' disease (LD) patients were in the hospital before onset of illness (median time from admission to onset, 17 days; range, 3 to 276 days). Twenty patients were immunosuppressed or compromised by malignancy. In 1977, six of 12 renal-homograft recipients acquired LD pneumonia in contrast to three of 22 during the preceding 3 years (P = 0.031, Fisher's exact test). In a prospective survey of 1658 consecutive hospital admissions, seven cases of Legionnaires' diseases occurred (0.4%), including six among 14 patients who seroconverted to the LD bacterium. Prevalence of a reciprocal titer of 128 or above in Wadsworth employees was significantly greater than in a nearby control population (P = 0.044, Fisher's exact test). Exposure to the external hospital environment may be an important factor, and soil may be a reservoir for the LD bacterium. Legionnaires' disease at Wadsworth may be a nosocomial pneumonia affecting a small group of patients with particular risk factors.

Antibodies, Bacterial↗

Gentamicin-resistant Pseudomonas aeruginosa and Serratia marcescens in a general hospital.

From Aug. 1, 1974, to July 31, 1975, inclusive, 19-1% of Pseudomonas aeruginosa and 50-0% of Serratia marcescens isolates from a general hospital were gentamicin resistant as determined by standardised disc testing; 80% of 118 different clinical isolates showed minimum inhibitory concentrations larger than or equal to 16 mug/ml of gentamicin in agar-dilution testing. All gentamicin-resistant S. marcescens and 79% of Ps. aeruginosa isolates were susceptible to amikacin, while tobramycin and sisomicin were shown to have little advantage over gentamicin. A wide variety of immunotypes was found for Ps. aeruginosa, but only two predominant types were found for S. marcescens. Most isolates originated from the urinary tract, but nine which came from urine or wounds were also isolated from blood. Resistant strains seemed to be as virulent as sensitive strains. A common source was not found. Clinical improvement was noted in 13 of 17 patients treated with amikacin. The high frequency of gentamicin resistance is a continuing problem in this hospital and soon may be in others.

Amikacin↗