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Biomedical subjects

M H Kramer

Publications and source records attributed to M H Kramer.

At least 37 records · Page 2Linked to original sources

Sick building syndrome in an office building formerly used by a pharmaceutical company: a case study.

In the past two decades, a group of health problems related to the indoor environment--generally termed sick building syndrome (SBS)--has emerged. We present an investigation of SBS in employees of a ministry working in a naturally ventilated office building that formerly had been used by a pharmaceutical company. A preceding environmental monitoring had failed to identify the cause(s) for the complaints. We conducted a questionnaire-based investigation and categorized the building sections and rooms according to their renovation status and their former use, respectively. The highest level of complaints was found among the employees working in rooms that in the past had been used for the production or storage of various pharmaceutical products suggesting that pharmaceutical odors may be a risk factor for SBS. Clinical laboratory tests did not show any unusual results. We conclude that the former use of a building for production and storage of pharmaceutical products should be considered as a possible risk factor for complaints about indoor air quality, e.g., when advising about or planning for renovations of buildings formerly used for production, handling, or storing of chemicals.

Adult↗

Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers.

Blotting, Southern↗

FISH identifies inv(16)(p13q22) masked by translocations in three cases of acute myeloid leukemia.

The inv(16)(p13q22) masked by different translocations was detected by fluorescence in situ hybridization (FISH) and confirmed by molecular analysis in three adult patients presenting with acute myeloid leukemia (AML)-M2 (cases 1 and 3) and M4Eo (case 2). Cytogenetic analysis revealed 47,XX,t(9;16)(p23;p13),+22 (case 1); 46,XX,t(1;16)(p32;p13) (case 2); and 46,XY,?del(16)(q22) (case 3). Using a panel of probes for chromosomes 1, 9, 16, and 20 as well as probes to detect inv(16), i.e., two cosmid contigs hybridizing proximally and distally to the 16p13 breakpoint, FISH demonstrated inv(16) involving the derivative 16 as well as reciprocal translocations between 16q22-qter and 9p24 (case 1), 1p32 (case 2), and 20q13 (case 3). In addition, a small interstitial del(16)(p13p13) proximal to the MYH11 breakpoint was detected in case 1. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis showed a CBFB-MYH11 fusion transcript and MYH11 rearrangement, respectively, in all three cases. We conclude that: 1) inv(16) can be masked by other structural abnormalities involving chromosome 16; 2) some of the so-called variant translocations not explored at the molecular level may in fact represent a masked inv(16); and 3) FISH, RT-PCR, and Southern blot analyses are reliable tools to detect masked inv(16) and should be applied in all AML cases with structural changes of chromosome 16.

Adult↗

First reported outbreak in the United States of cryptosporidiosis associated with a recreational lake.

In the summer of 1994, an outbreak of cryptosporidiosis occurred among visitors to a state park in New Jersey. We enrolled 185 persons in a cohort study, 38 (20.5%) of whom had laboratory-confirmed cryptosporidiosis or gastrointestinal illness that met our clinical case definition. Having any exposure to lake water (e.g., swimming) was strongly associated with illness (P < .001). The outbreak lasted 4 weeks and affected an estimated 2,070 persons. The most likely sources of the outbreak were contaminated runoff of rainwater and infected bathers. This outbreak of cryptosporidiosis is the first reported to be associated with recreational exposure to lake water. Our investigation shows that even a large and ongoing outbreak may not be detected for several weeks. Health professionals and persons at high risk for severe cryptosporidiosis should be aware that recreational water can be a source of cryptosporidium infection.

Adolescent↗

First reported outbreak of abdominal angiostrongyliasis.

Human abdominal angiostrongyliasis is a potentially fatal disease caused by Angiostrongylus costaricensis, a nematode found in the Americas. During the period of December 1994 through August 1995, an outbreak of this disease occurred in Guatemala. We identified 22 cases of abdominal angiostrongyliasis and conducted a matched case-control study to identify risk factors for illness. The median age of the 18 cases enrolled in the study was 37 years (range, 9-68 years), and 11 (61.1%) were male. Consumption of the following six raw food items was associated with angiostrongyliasis: mint (odds ratio [OR], 6.9; 95% confidence interval [CI], 1.5-66.0), shrimp (OR, infinite; 95% CI, 1.4 to infinite), and four kinds of ceviche that reportedly contained raw mint (OR for consumption of mint or ceviche that contained mint, 7.0; 95% CI, 1.0-315). We conclude that raw mint was the likely vehicle of infection for this outbreak. To our knowledge, this is the first reported outbreak of abdominal angiostrongyliasis and the first time that a specific food item has been epidemiologically linked to the disease.

Abdomen↗

Gastric lymphomas compared with lymph node lymphomas in a population-based registry differ in stage distribution and dissemination patterns but not in patient survival.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) originating in mucosa-associated lymphoid tissue (MALT) is supposed to have different clinical behavior from lymph node NHL. To test this hypothesis, the authors compared data of gastric NHL patients with lymph node NHL patients in a population-based registry for differences in clinical presentation and prognosis. METHODS: Data from 1981-1989 on patients with primary gastric NHL (n = 109) and patients with primary lymph node NHL (n = 658) were retrieved from a Dutch population-based NHL registry. Patients were compared for stage distribution, involved sites, and survival. The prognostic value of grading lymphomas according to the malignancy grades of the Working Formulation for Clinical Usage was compared with the value of grading MALT NHLs as either low grade or high grade malignancies. RESULTS: Patients with gastric NHL presented more often with localized disease. Stage IV patients had a higher rate of dissemination to other non-lymph node sites but less frequent localization in the bone marrow. The restricted pattern of dissemination was reflected in a significantly lower recurrence rate for gastric NHL. Gastric NHL patients had significantly better disease free survival than lymph node NHL patients (80% and 44% at 5 years, respectively; P < 0.001). In contrast, overall survival did not significantly differ between the two groups, and it appeared to depend on disease stage. Grading MALT lymphoma as either low grade (26%) or high grade (70%) malignancies did not provide better prognostic information than grading according to the Working Formulation for Clinical Usage (low 8%, intermediate 75%, high 9%). CONCLUSIONS: Primary gastric NHL shows a restricted dissemination pattern, which gives support to the MALT lymphoma concept. Although this might explain the superior disease free survival observed for gastric NHL patients, it does not translate into better overall survival for these patients.

Adult↗

Kidney and liver transplants from a donor infected with Naegleria fowleri.

We describe the first reported case of organ transplantation from a boy who had died of undiagnosed Naegleria fowleri infection. While no subsequent amebic infections occurred in the three organ recipients, our report illustrates the need for an improved strategy for evaluating the benefits and risks of transplanting tissues from persons whose illness was likely caused by an infectious agent.

Amebiasis↗

Surveillance for waterborne-disease outbreaks--United States, 1993-1994.

PROBLEM/CONDITION: Since 1971, CDC and the U.S. Environmental Protection Agency have maintained a collaborative surveillance system for collecting and periodically reporting data that relate to occurrences and causes of waterborne-disease outbreaks (WBDOs). REPORTING PERIOD COVERED: This summary includes data for January 1993 through December 1994 and for previously unreported outbreaks in 1992. DESCRIPTION OF THE SYSTEM: The surveillance system includes data about outbreaks associated with water intended for drinking (i.e., drinking water) and those associated with recreational water. State, territorial, and local public health departments are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC on a standard form. RESULTS: For the 2-year period 1993-1994, 17 states and one territory reported a total of 30 outbreaks associated with drinking water. These outbreaks caused an estimated 405,366 persons to become ill, including 403,000 from an outbreak of cryptosporidiosis in Milwaukee, the largest WBDO ever documented in the United States, and 2,366 from the other 29 outbreaks. No etiologic agent was identified for five (16.7%) of the 30 outbreaks. The protozoan parasites Giardia lamblia and Cryptosporidium parvum caused 10 (40.0%) of the 25 outbreaks for which the etiologic agent was identified. Two outbreaks of cryptosporidiosis occurred in large metropolitan areas (i.e., Milwaukee and Las Vegas/Clark County) and were associated with deaths among immunocompromised persons. The waterborne nature of these two outbreaks was not recognized until at least 2 weeks after the onset of the Milwaukee outbreak and until after the end of the Las Vegas outbreak. Campylobacter jejuni was implicated for three outbreaks and the following pathogens for one outbreak each: Shigella sonnei, Shigella flexneri, non-O1 Vibrio cholerae (in a U.S. territory; the vehicle was commercially bottled water), and Salmonella serotype Typhimurium (the outbreak was associated with seven deaths). Eight outbreaks of chemical poisoning were reported: three were caused by lead (one case each), two by fluoride, two by nitrate and one by copper. Twenty (66.7%) of the 30 outbreaks were associated with a well-water source. Fourteen states reported a total of 26 outbreaks associated with recreational water, in which an estimated 1,714 persons became ill. Fourteen (53.8%) of these 26 were outbreaks of gastroenteritis. The etiologic agent in each of these 14 outbreaks was identified; 10 (71.4%) were caused by G. lamblia or C. parvum. Six of these 10 were associated with chlorinated, filtered pool water, and three with lake water. One of the latter was the first reported outbreak of cryptosporidiosis associated with the recreational use of lake water. Four outbreaks of lake water-associated bacterial gastroenteritis were reported, two caused by S. sonnei, one by S. flexneri, and one by Escherichia coli O157:H7. Nine outbreaks of hot tub- whirlpool-, or swimming pool-associated pseudomonas dermatitis were reported. Two outbreaks of swimming pool-associated dermatitis had a suspected chemical etiology. The child who had the one reported case of primary amebic meningoencephalitis, caused by infection with Naegleria fowleri, died. INTERPRETATION: The number of WBDOs reported annually has been similar for each year during 1987-1994, except for an increase in 1992. Protozoan parasites, especially C. parvum and G. lamblia, remain important etiologic agents of WBDOs. The outbreaks of cryptosporidiosis in Milwaukee and Las Vegas demonstrate that WBDOs can occur in large metropolitan areas. Surveillance methods are needed that expedite the detection of WBDOs and the institution of preventive measures (e.g., boil-water advisories). ACTIONS TAKEN: Surveillance data that identify the types of water systems, their deficiencies, and the etiologic agents associated with outbreaks are used to evaluate the adequacy of current technologies for prov

Animals↗

Mantle-cell lymphoma: a population-based clinical study.

PURPOSE: From a population-based non-Hodgkin's lymphoma (NHL) registry, 41 patients with mantle cell lymphoma (MCL) -- a recently defined distinct B-cell NHL -- were selected and compared with patients with low- or intermediate-grade NHL from the same registry. PATIENTS AND METHODS: The incidence and behavior of MCL in the area of the Comprehensive Cancer Center West (CCCW) from 1981 to 1989 were analyzed. Age, performance, tumor bulk, extranodal localization, stage, response to therapy, and survival were registered. Expression of cyclin D1 protein and Ki-67 were measured in 29 patients. RESULTS: MCL made up 3.7% of NHLs. The median age was 68 years, and the male-to-female ratio was 1.6:1. Seventy-eight percent presented with stage IV, with the majority having bone marrow involvement. The complete response (CR) rate was 32% (13 of 41), with a median duration of 25 months. The median overall survival time was 31.5 months. The International Prognostic Index identified five patients with a low-risk score and a median survival time of 93+ months. In 23 of 29 patients, cyclin D1 overexpression was present, without any relation to overall or disease-free survival. In contrast, a proliferative index less than 10% was significantly related to a better overall survival time (50 v 24 months). CONCLUSION: MCL is a disease of the elderly, who present with widespread disease and with a poor response to therapy. Although it harbors features of an indolent NHL, it behaves clinically as an aggressive NHL with a short overall survival time.

Aged↗

Clinical significance of bcl2 and p53 protein expression in diffuse large B-cell lymphoma: a population-based study.

PURPOSE: We studied the prognostic significance of bcl2 and p53 protein expression in relation to clinical and pathologic characteristics in patients with diffuse large B-cell lymphoma (LCL). PATIENTS AND METHODS: Three hundred seventy-two patients with LCL were retrieved from a population-based registry for non-Hodgkin's lymphoma (NHL). bcl2 and p53 protein expression was studied on paraffin-embedded tumor tissue by immunohistochemistry in relation to clinical factors. Response to therapy and survival were analyzed in 165 patients who were uniformly staged and treated and for whom all prognostic data were available according to the International Prognostic Index (IPI). RESULTS: Forty-five percent of tumors showed strong expression of the bcl2 protein (bcl2++), with a higher frequency in patients with primary nodal involvement. Disease-free survival (DFS) was significantly better in bcl2-negative/intermediate (bcl2-/+) cases as compared with bcl2++ cases (P = .0011). At 5 years, bcl2-/+ patients showed a DFS rate of 74%, in contrast to bcl2++ patients with a DFS rate of 41% (P = .002). Bcl2 was the strongest independent prognostic value in a multivariate analysis, with a relative risk (RR) of 3.0 in comparison to p53 expression and the clinical factors of the IPI. Overall survival (OS) was not significantly influenced by bcl2 protein expression. p53 protein expression was found in 13% of cases, with a higher frequency in patients with extensive disease. p53 expression did not influence the chance to achieve complete remission (CR) and survival. CONCLUSION: bcl2 protein is frequently expressed in LCL and is a strong independent prognostic factor for DFS. p53 expression is related with high tumor burden, but is not an independent risk factor for CR and survival.

Adult↗

Respiratory symptoms and subcutaneous granuloma caused by mesocercariae: a case report.

A 38-year-old man with no history of pulmonary disease developed intermittent hives and bronchospasms shortly after returning from a hunting trip. Approximately one year later, examination of an excised subcutaneous nodule demonstrated infection with a mesocercaria (larval trematode). The morphology of the parasite was consistent with infection with a parasite of the Alaria spp. or Strigea spp. Eating undercooked wild goose meat during the hunting trip was the most likely source of infection. This appears to be the first report of human infection with mesocercariae acquired through the ingestion of wild goose meat.

Adult↗

International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades.

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

Aged↗

Differentiation of follicular lymphoma cells after autologous bone marrow transplantation and haematopoietic growth factor treatment.

A patient with follicular lymphoma developed a striking but transient plasmacytosis in blood and bone marrow with paraproteinaemia after treatment by autologous bone marrow transplantation and interleukin-3 (IL-3). By immunophenotyping, cytogenetics and Southern blotting, we proved that the plasma cells were clonally related to the original lymphoma cells. This event was preceded by fever accompanied by high IL-6 concentrations. The patient recovered spontaneously and had a long-lasting remission. We speculate that the bone marrow-derived malignant B cells were stimulated by IL-3 and IL-6 into terminally differentiated plasma cells.

Adult↗

Histological conversion of follicular lymphoma with structural alterations of t(14;18) and immunoglobin genes.

About half of the patients with follicular lymphoma will develop an aggressive B cell lymphoma with morphological changes in growth pattern and cellular morphology. Changes of the immunophenotype, especially of the expression of immunoglobulin (Ig) have been documented less frequently. Multiple tumor samples of two patients with follicular lymphoma who developed tumor progression, were studied by Southern blot analysis for rearrangements of the Ig genes and the oncogenes BCL2 and MYC. In both patients, the general pattern of Ig gene rearrangements, especially of the Ig light-chain genes, and the structure of the t(14;18) breakpoint as assessed by the polymerase chain reaction (PRC) and fine restriction mapping, remained unaltered with time. However, both within the functional Ig heavy-chain allele and around the t(14;18) breakpoint, extensive secondary alterations took place. This indicates clonal evolution rather than the appearance of an independent lymphoma. In the first case with progression from follicular lymphoma to Burkitt's lymphoma 3 years after diagnosis, alterations were especially present 3' of the t(14;18) breakpoint. In the second patient with a change from follicular to diffuse centroblastic lymphoma 4 years after diagnosis, subsequent class switches from IgM to IgG and to defective IgH expression were accompanied by deletion of C mu sequences and a rearrangement of the MYC gene, respectively. Additionally, in both patients alterations in individual restriction sites occurred, which most likely were due to somatic mutations within both the functional IgH and translocated allele. Our data indicate that complex alterations of both the functional and non-functional IgH allele may accompany tumor progression and may erroneously suggest the appearance of independent clones by Southern blot analysis. It remains to be established whether these alterations are causative events or the consequence of genetic instability and clonal evolution.

Adult↗

Legionellosis: ecological factors of an environmentally 'new' disease.

This review paper discusses environmental factors influencing multiplication, persistence and virulence of Legionella. The differing modes of transmission of legionellosis are discussed in relation to the epidemiology and clinical manifestations of the disease. Characteristics of pathogenicity of Legionella are compared to other pathogens. Implications for prevention are presented, and areas where further research is needed are discussed.

Amoeba↗

Essential differences in oncogene involvement between primary nodal and extranodal large cell lymphoma.

Large cell lymphomas (LCLs) are heterogeneous in morphology, clinical presentation, and behavior. We studied 52 de novo LCLs of B-cell type for rearrangements of the bcl-2 and c-myc oncogenes by Southern blot analysis and related these data to the primary site of presentation, stage, and cytomorphology. Thirteen tumors had comigrating rearrangements of JH and bcl-2, indicative of a t(14;18). Far more primary nodal lymphomas than extranodal lymphomas carried a t(14;18) (40% v less than 5%). Additionally, almost all lymphomas with a t(14;18) versus 41% of the tumors without a bcl-2 rearrangement presented with lymphadenopathy. c-myc rearrangements were seen in 35% of the extranodal lymphomas and 5% of the nodal lymphomas. No differences were observed in bone marrow involvement and staging according to Ann Arbor. bcl-2 rearrangements were found in 50% of the LCLs with cleaved nuclei, whereas c-myc rearrangements were relatively frequent (25%) in the noncleaved subtype. Our data support the hypothesis that primary nodal and extranodal lymphomas have a different genetic origin.

Blotting, Southern↗