Donald S. Karcher

Lymphoma and peripheral neuropathy: a clinical review.

Lymphoma occasionally affects the peripheral nervous system. When it does, the diagnosis can be elusive since many patients present without known lymphoma. Most peripheral nerve complications are due to non‐Hodgkins lymphoma (NHL), which infiltrates nerves causing axonal damage. This disorder can affect nerve roots and cranial nerves, often associated with lymphomatous meningitis. NHL may also infiltrate peripheral nerves and cause plexopathy, mononeuropathy, or generalized neuropathy. These neuropathies may resemble an asymmetric mononeuropathy multiplex or a generalized disorder such as chronic inflammatory demyelinating polyradiculoneuropathy. When NHL infiltrates diffusely, the term neurolymphomatosis is used. Hodgkins lymphoma (HL), by contrast, rarely infiltrates nerves. More often, HL causes immunological disorders of the peripheral nervous system such as inflammatory plexopathy or Guillain–Barré syndrome. Other rare lymphomas such as intravascular lymphoma and Waldenströms macroglobulinemia can also affect peripheral nerves in specific ways. In addition, other malignant and nonmalignant lymphoproliferative disorders enter into the differential diagnosis of lymphomatous neuropathy. This review discusses the multiple peripheral nerve presentations of lymphoma from the clinicians point of view and provides a guide to the evaluation and diagnosis of these uncommon, challenging disorders. Muscle Nerve, 2005

Bone marrow macrophage iron grade and survival of HIV-seropositive patients.

OBJECTIVE Increased iron stores predispose to certain microbial infections. This association might be especially important in patients whose immune system is impaired by HIV. This study examined the relationship between iron stores and the survival times of patients with HIV infection. DESIGN Retrospective analysis of iron stores, as determined directly in bone marrow aspirates, and of hospital records. SETTING The George Washington University Hospital, an urban academic tertiary care institution. PATIENTS Three hundred and forty-eight HIV-seropositive adults who had diagnostic bone marrow aspirates between January 1985 and June 1996. MEASUREMENTS Bone marrow macrophage iron stores were graded on a scale of 0 to 5. For analysis of the influence of iron stores on survival, we compared patients with grades 4-5 iron stores (markedly or massively increased; n = 188) to those with grades 0-2 iron stores (normal or decreased; n = 130). RESULTS Infections caused by Candida spp., Pneumocystis carinii, and Mycobacterium spp. were more common in patients with high macrophage iron grades than in patients with low or normal iron grades (P < or = 0.006). The adjusted estimated rate of death (hazards ratio) was higher in patients with high iron stores compared with patients with low or normal iron stores, both from the time of the bone marrow study (ratio of 2.1; 95% confidence interval 1.3-3.5; P = 0.003) and the determination of HIV-seropositivity (ratio of 2.8; 95% confidence interval 1.4-4.9; P = 0.001). CONCLUSION High iron stores, as determined by bone marrow macrophage iron grade, may be associated with shorter survival times in patients with HIV infection.

Human herpesvirus-8-associated body cavity-based lymphoma in human immunodeficiency virus-infected patients: a unique B-cell neoplasm.

Human immunodeficiency virus (HIV)-related body cavity-based lymphomas (BCBLs) are known to exhibit unusual clinical, immunophenotypic, and genotypic features, and have recently been found to harbor DNA sequences of a new human herpesvirus, designated Kaposis sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). The authors have encountered eight cases of HHV-8-associated BCBL in HIV-infected patients. A literature search revealed an additional 50 reported cases of HIV-related BCBL, as well as reports of several other disorders associated with HHV-8 DNA. Comprehensive analysis of the clinical and pathobiological features of all 58 known cases of HIV-related BCBL shows it to be a unique B-cell neoplasm with a strong propensity for body-cavity involvement without mass lesions and with little or no dissemination, poor prognosis, high grade usually immunoblastic morphology, late B-cell phenotype and genotype, no associated c-myc gene rearrangement, frequent presence of Epstein-Barr virus (EBV) genome, and uniform association with HHV-8 DNA. Considering these features in the context of other disorders associated with HHV-8 DNA, HHV-8 appears to play a causal role in BCBL, possibly in concert with EBV, and may induce this lymphoma through dysregulation of cytokines, particularly interleukin-6, or infection of an unusual B-cell subset. The characteristics of HHV-8-associated BCBL suggest a possible role for antiherpes or anticytokine agents in the treatment of this lymphoma.

Human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus in organ transplant patients with immunosupression

Several recent studies have demonstrated Kaposis sarcoma‐associated herpes virus (KSHV), also known as putative human herpes virus‐8 (HHV‐8), DNA in various epidemiologic forms of Kaposis sarcoma (KS), including AIDS‐associated, classic, and endemic types. Risk of developing KS in non‐HIV‐infected immunosuppressed hosts, such as patients following solid organ transplantation, is also significantly higher compared to normal individuals. We have retrospectively evaluated 28 organ transplant patients with KS (23 cutaneous and five visceral) for the presence of KSHV genome by polymerase chain reaction (PCR) amplification of DNA isolated from formalin‐fixed, paraffin‐embedded archival tissue samples. 27/28 KS patients were positive for the presence of KSHV. In four KS patients, tissue samples with no histologic evidence of KS were also analysed for KSHV. No evidence of positivity in three samples was noted, but one patient had weak positive amplification products on DNA samples isolated from a gastric biopsy with chronic gastritis and lymph node with sinus histiocytosis. These data support the association of KSHV with KS developing in non‐HIV‐infected immunosuppressed patients, similar to other forms of KS, and suggest that KSHV may play a significant role in the development of all forms of KS.

Polymerase chain reaction detection of immunoglobulin gene rearrangement and bcl-2 translocation in archival glass slides of cytologic material.

Cytologic evaluation of lymph node fine-needle aspirates and serous effusions is a rapid and useful means for establishing the diagnosis of a variety of lymphoproliferative disorders. However, in some instances, cytologic findings are not sufficient to establish a diagnosis of lymphoma, thus necessitating the use of ancillary procedures, the most frequent of which is immunophenotyping. In this respect, the usefulness of molecular markers, such as clonal immunoglobulin gene rearrangements or chromosomal translocations, have been less well evaluated. Follicular lymphoma constitutes an interesting disease for such a study because these tumors possess characteristic histopathologic features and contain two potential molecular markers, that is, a clonal immunoglobulin gene rearrangement and a bcl-2 gene translocation [t(14;18)]. In the present study, we evaluated, retrospectively, the cytologic material from four lymph node fine-needle aspirates and one pleural effusion of five patients with biopsy-proven follicular lymphoma. In four of the cases, definitive diagnosis of lymphoma had not been possible solely from cytologic evaluation. DNA was isolated from archival air-dried samples present on glass slides and amplified by the polymerase chain reaction (PCR) for detection of either a clonal immunoglobulin heavy chain gene rearrangement or bcl-2 translocation (major breakpoint region). An immunoglobulin heavy chain gene rearrangement was detected in four of five patients, and two patients had the bcl-2 translocation by PCR. The effusion case was identical by gel electrophoresis with product amplified from a lymph node biopsy of the same patient and DNA extracted directly from fresh pleural effusion cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Findings in HIV-Positive Patients With Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease

Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus-8, is associated with 1 form of multicentric Castleman disease (MCD) and is the etiologic agent for most MCD in human immunodeficiency virus (HIV)-infected patients. Diagnosis is usually determined by lymph node biopsy. Bone marrow findings in KSHV-MCD are not well characterized. We conducted histomorphologic and immunohistochemical evaluation of bone marrow biopsy specimens in HIV-infected patients with KSHV-MCD, including evaluation for KSHV latency-associated nuclear antigen. Findings were correlated with clinical features and KSHV viral load. Reactive plasmacytosis was the predominant feature. Lymphoid aggregates were less common and not diagnostic of KSHV-MCD. Forty-eight percent of cases contained scattered KSHV-infected mononuclear cells. Although patients were generally cytopenic, bone marrow biopsy specimens were normocellular to hypercellular except in patients receiving hematotoxic therapy. Bone marrow biopsy specimens in KSHV-MCD patients recapitulate findings of interleukin-6 excess. In patients with HIV, unexplained cytopenias, and bone marrow plasmacytosis, evaluation for KSHV-MCD is warranted.

Human herpesvirus-8-positive body cavity-based lymphoma involving the atria of the heart: a case report.

We describe an unusual case of a body cavity-based lymphoma, otherwise termed primary effusion lymphoma (PEL), involving the atria of the heart of an HIV-seropositive patient. This is the first reported case of the involvement of the heart by this rare lymphoma. This HIV-related lymphoma represents a distinct B-cell malignancy associated with human herpesvirus-8 (HHV-8) infection. It is characterized by involvement of body cavities, with infrequent evidence of organ or bone marrow infiltration. The tumor cells are large, nucleolated with an immunoblastic or anaplastic appearance, positive for activation markers, such as CD30, and negative for B-cell and T-cell immunophenotypic markers. Integration of HHV-8 DNA sequences is considered the hallmark of PEL. The tumor demonstrates frequent association with Epstein-Barr virus (EBV) and uniform absence of c-myc oncogene rearrangement, unlike most other HIV-related lymphomas.

Utility of Repeat Testing of Critical Values: A Q-Probes Analysis of 86 Clinical Laboratories

CONTEXT A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result. OBJECTIVES To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test. DESIGN Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing. RESULTS Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care. CONCLUSION Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.

Is it a safe practice to administer oxygen during uncomplicated delivery: a randomized controlled trial?

BACKGROUND Newborns exposed to oxygen suffer from an oxidative stress with significant alterations in the concentrations of superoxide dismutase (SOD) and glutathione (GSSG). OBJECTIVE To investigate the biological and clinical effects of oxygen administration to delivering mothers. METHODS We conducted a randomized, double-blinded, controlled trial on a cohort of delivering women (n=56) with an uncomplicated term pregnancy. Women were randomly assigned to one of two groups: Oxygen group or Room Air group. The Oxygen group received 100% oxygen (2l/min) via nasal cannula for at least 30 min before delivery. Subjects in the Room Air group were connected to a nasal cannula while on room air. Concentrations of SOD (μg/g of Hb) and GSSG (μM/ml) were measured in maternal and umbilical cord blood. Bivariate and multivariate analyses were used to compare the two groups using the SAS system. RESULTS Maternal SOD and GSSG did not differ between the two groups at baseline or after delivery. Concentrations of SOD and GSSG in umbilical cord blood did not differ between groups. More infants in Oxygen Group required delivery room resuscitation (20% vs. 0%, P=0.03). This difference could not be explained by mode of delivery, infant sex, or other confounders. CONCLUSIONS Maternal exposure to oxygen during delivery is not associated with changes in umbilical cord SOD or GSSG. Further studies are needed to explore mechanisms responsible for the need of resuscitation in the oxygen group.

Fifteen years' experience of a College of American Pathologists program for continuous monitoring and improvement.

CONTEXT The Q-Tracks program, created in 1999, is a quality monitoring subscription service offered by the College of American Pathologists. OBJECTIVE To establish benchmarks in quality metrics, monitor changes in performance over time, and identify practice characteristics associated with better performance. DESIGN The Q-Tracks program provides ongoing study of multiple metrics offered in most laboratory disciplines. The design enables measuring the effects of process changes and comparisons with other participating laboratories. Each laboratory Q-Tracks monitor has a primary quality indicator and additional secondary indicators. RESULTS To date, 19 Q-Tracks monitors have been offered, with 12 currently active monitors. Q-Tracks are primarily conducted in hospital-based laboratories in the United States, Canada, and 21 other countries. Common to most Q-Tracks monitors is a demonstration of performance improvement by subscribers with long-term participation. This finding was seen in preanalytic, turnaround time, and postanalytic measures. Q-Tracks monitors contribute to the overall demonstration and improvement of laboratory and hospital quality because they address core quality measures for the College of American Pathologists Laboratory Accreditation Program and multiple Joint Commission National Patient Safety Goals. CONCLUSIONS The Q-Tracks program has established multiple benchmarks in most disciplines of the laboratory and has demonstrated significant performance improvement in benchmarks and individual laboratories over time.