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Biomedical subjects

Jeffrey Miller

Publications and source records attributed to Jeffrey Miller.

6 recordsLinked to original sources

Efficacy of high-dose therapy and hematopoietic stem cell transplantation for mantle cell lymphoma.

Conventional treatment of mantle cell lymphoma (MCL) yields modest responses and short remissions. We report 30 hematopoietic stem cell transplants (HSCT) for MCL: 13 autologous, 10 allogeneic myeloablative, and 7 nonablative. After a median 1.2 years from diagnosis (range 0.5 to 4.7) and a median of 2 pre-HSCT chemotherapeutic regimens (range 1 to 5), their median age at HSCT was 52 years (range 37 to 67). Eleven patients (41%) were in first remission, 11 (41%) were in second remission, and 7 (25%) had resistant disease. Four died early. Nineteen achieved CR (83%) and 4 PR (17%). With median 2.7 years of follow-up, 5-year overall survival (OS) was 42% (95% CI 11-73%) after autologous versus allogeneic at 49% (95% CI 22-76%). Five-year progression-free survival (PFS) was 31% (95% CI 3-59%) and 50% (95% CI 24-76%) for autologous and allogeneic HSCT, respectively. Fourteen died: 3 from sepsis, 1 acute GVHD, 10 MCL. No autologous transplant-related deaths occurred. Allogeneic transplant-related mortality was 29% (95% CI 6-52%) at 1 and 5 years. HSCT for MCL can yield extended disease control and long-term survival.

Adult↗

Cutaneous cryptococcus in an elderly woman with chronic essential dermatitis.

Cryptococcus neoformans is a common cause of life-threatening infection. Cutaneous manifestations of Cryptococcus can be primary or secondary, most commonly from immunosuppression. With the global emergence of acquired immunodeficiency syndrome (AIDS), incidence of cryptococcosis is increasing and now represents a major life-threatening fungal infection in these patients. Nonspecific lesions may cause misdiagnosis. Disseminated Cryptocoocus requires early clinical diagnosis and effective management to decrease mortality. We review a case of cutaneous Cryptococcus as a complication of chronic essential dermatitis treated with long-term immunosuppressive agents and discuss updated guidelines on the treatment of Cryptococcus.

Antifungal Agents↗

A comparison of related donor peripheral blood and bone marrow transplants: importance of late-onset chronic graft-versus-host disease and infections.

Peripheral blood hematopoietic stem cell (PBSC) transplants have been shown to result in more rapid engraftment than standard bone marrow transplants (BMTs). Little comparative data exist regarding complications in patients receiving transplants using these stem cell sources. In our study, 97 adults with advanced hematologic malignancies who received allogeneic PBSC transplants were compared with 97 adults who received allogeneic BMTs using identical preparative regimens and support parameters. The incidence of systemic infections and other major complications occurring within the first year after transplantation were calculated in both groups. Proportional hazard analysis was used to examine risk factors for death and complications in both groups. Patients receiving PBSC transplants had more rapid neutrophil (17 days versus 24 days; P <.001) and platelet engraftment (28 days versus 47 days; P <.001) than BMT recipients. The survival rate at 2 years was 38% in PBSC transplant recipients and 28% in marrow recipients (P =.08). There was no difference in rates of grade II to IV acute graft-versus-host disease (GVHD) between groups (PBSC 46%, BMT 51%; P =.3). PBSC transplant recipients were more likely to develop chronic GVHD after 180 days (hazard ratio 2.2; P =.05). Accompanying this "late-onset chronic GVHD," a pattern of more frequent late systemic fungal and cytomegalovirus infections was observed in PBSC transplant recipients. In conclusion, although PBSC transplant recipients engraft more quickly than BMT recipients and have somewhat better 2-year survival rates, they develop more frequent late-onset chronic GVHD and may have more late fungal and cytomegalovirus infections than marrow recipients. Further studies must examine this late-onset chronic GVHD and better characterize immune reconstitution in PBSC transplant recipients to understand their effects on patient recovery.

Adolescent↗

Insights into the Holley- and Joseph- phenotypes.

BACKGROUND: The Dombrock blood group system consists of two antithetical antigens (Do(a) and Do(b)) and three high-incidence antigens (Gregory [Gy(a)], Holley [Hy], and Joseph [Jo(a)]). Hy and Jo(a) have an unusual phenotypic relationship. All Hy- RBCs are Jo(a-), but not all Jo(a-) RBCs are Hy-. The molecular background associated with Hy- and Jo(a-) phenotypes is reported. STUDY DESIGN AND METHODS: DNA from 18 probands with Gy(a+(w)) Hy- Jo(a-) RBCs (Hy- phenotype) and from 13 probands with Gy(a+) Hy+(w) Jo(a-) RBCs (Jo[a-] phenotype) was tested. RESULTS: Sequencing and PCR-RFLP revealed 323 G>T (Gly 108Val) and 378 T>C (silent mutation) changes on a DOB background (HY) associated with the Hy- samples. The sister of the original Hy- proband and the majority of samples had an additional mutation of 898 C>G (Leu300Val) (HY1); others had 898C (300Leu) (HY2). In the Jo(a-) phenotype, there is a 350 C>T (Thr1 17Ile) and a 378 C>T (silent mutation) change on a DOA background (JO). CONCLUSION: The results provide an explanation for the variation in typing results in antibody producers. The ablation of Jo(a) in the Hy- phenotype and the weakening of Hy in the Jo(a-) phenotype may be due to the close proximity of these antigens. The 898 C>G mutation, within the sequence motif for glycosylphosphatidylinositol linkage, may cause reduced efficiency of anchoring the protein to the RBC membrane, thereby weakening the expression of Gy(a) and Do(b).

Amino Acid Sequence↗

Thoughts of suicide among HIV-infected rural persons enrolled in a telephone-delivered mental health intervention.

This study characterized rates and predictors of suicidal thoughts among HIV-infected persons living in rural communities of eight U.S. states. Self-administered surveys were completed by 201 HIV-infected persons living in communities of 50,000 or fewer that were located at least 20 miles from a city of 100,000 or more. All participants were clients of rural AIDS service organizations and had recently enrolled into a randomized clinical trial of a telephone-delivered, coping improvement-group intervention designed specifically for HIV-infected rural persons. At baseline, participants reported on thoughts of suicide, psychological symptomatology, life-stressor burden, ways of coping, coping self-efficacy, social support, and barriers to health care and social services. Thirty-eight percent of HIV-infected rural persons had engaged in thoughts of suicide during the past week. A logistic regression analysis revealed that participants who endorsed thoughts of suicide also reported more depressive symptoms (odds ratio [OR] = 2.19; 95% confidence interval [CI] = 1.32-3.63, p < .002), less coping self-efficacy (OR = 0.70; 95% CI = 0.56-0.88, p < .002), more frequently worried about transmitting their HIV infection to others (OR = 1.66, 95% CI = 1.14-2.40, p < .008), and experienced more stress associated with AIDS-related stigma (OR = 1.58, 95% CI = 1.07-2.35, p < .03). As AIDS prevalence rates increase in rural areas, interventions that successfully identify and treat geographically isolated HIV-infected persons who experience more frequent or serious thoughts of suicide are urgently needed.

Adaptation, Psychological↗