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Biomedical subjects

L Rosen

Publications and source records attributed to L Rosen.

At least 55 records · Page 3Linked to original sources

Production of anti-erythrocyte antibodies by leukemic and nonleukemic B cells in chronic lymphocytic leukemia patients.

We have assessed the specificity of antibodies from the leukemic B cells of five patients with both chronic lymphocytic leukemia and autoimmune hemolytic anemia (CLL-AHA). Leukemic cells from one patient displayed surface immunoglobulin with heavy and light chain isotypes identical to that of the patient's anti-red blood cell (RBC) antibodies, and the leukemic cells secreted antibodies in vitro with anti-RBC activity. However, in the remaining patients, the leukemic cells displayed surface immunoglobulin with light chain isotypes different from that of the patient's anti-RBC antibodies and secreted antibodies in vitro with no detectable anti-RBC activity. Thus, there are two distinct classes of CLL-AHA patients, differentiated by the presence or absence of an anti-RBC antibody-producing leukemic B cell clone. The apparent heterogeneity in the source of pathogenic anti-RBC antibodies may impact the treatment response of the two classes of CLL-AHA patients.

Aged↗

Dengue hemorrhagic fever.

Dengue has been known for more than 200 years. The first dengue viruses were isolated about 50 years ago. Prior to the 1950's, dengue was considered a mild febrile disease, though rare hemorrhagic and fatal cases were known to occur. After that date, the first epidemics of dengue hemorrhagic fever (DHF) appeared in Southeast Asia, and DHF became the most important cause of childhood morbidity and mortality in the region. The emergence of DHF epidemics was first explained by mutations affecting dengue viruses, making them more virulent, but this hypothesis was not retained. Then, the "secondary infection" or "immune enhancement" theory was proposed to explain the increased virulence of dengue viruses when children had a secondary infection. This second hypothesis is still actually favoured. However, observations in Southeast Asia, some Pacific islands, and Americas do not agree with the "secondary infection" hypothesis, which consequently has been modified several times. Recent advances in molecular biology have led to the recognition that some viral strains are more virulent than others. Another hypothesis is the selection of more virulent dengue strains by the new vector Ae. aegypti, replacing the local vector Ae. albopictus, when urbanization and modern transportation increased in Southeast Asia after the last war. Comparisons between epidemics are very difficult, because of the distinction between DHF cases according to WHO criteria and dengue fever (DF) cases with hemorrhages. This distinction has no pathogenic or prognostic grounds, and makes the task of clinicians more difficult. The actual situation in countries facing dengue epidemics makes clear that this disease will continue to be a public health problem for some time to come.

Asia, Southeastern↗

Growth-restricted dengue virus mutants containing deletions in the 5' noncoding region of the RNA genome.

The dengue type 4 virus (DEN4) RNA genome contains a 101-nt 5' noncoding (NC) sequence which is predicted to form a stable secondary structure. DEN4 cDNA from which infectious RNA can be transcribed was used to engineer deletions in the 5' NC region for functional analysis of RNA structure and for isolation of DEN4 mutants that could be evaluated as candidates for use in a live attenuated vaccine. Eleven distinct deletions in the region of the DEN4 genome between nts 18 and 98 were constructed; each mutation was predicted to alter or disrupt the local base-parings in the 5' NC RNA structure. An infectious virus was not recovered from the RNA transcripts of five of these deletion mutants. Significantly, four of the five apparently lethal deletions were located in a 5- to 6-nt base-paired region of a predicted long stem or adjacent to it. In contrast, with one exception, mutants which yielded infectious virus had deletions which were located in a loop or short stem region. The effect of the deletions on the efficiency of translation of viral RNA transcripts was examined in vitro. The RNA transcripts of deletion constructs which did not yield viable virus were translated at an efficiency ranging from 40 to 160% that of wild-type virus transcripts. The translation efficiency of infectious RNA transcripts also varied. Deletion mutants recovered from RNA transcripts that exhibited low to moderate efficiency of translation had a small plaque morphology and exhibited reduced growth in simian LLC-MK2 and mosquito C6/36 cells compared to the wild-type virus. Among the 11 mutant constructs, deletion of nts 82-87 caused the greatest reduction in translation efficiency. Nevertheless, an infectious virus was recovered from LLC-MK2 cells transfected with the RNA transcripts of mutant d(82-87). The progeny of this mutant produced small plaques on LLC-MK2 cells and grew to low titer in these cells. Unlike wild-type DEN4 or other DEN4 deletion mutants tested, mutant d(82-87) failed to produce plaques on C6/36 cells and was also replication-defective in Aedes aegypti and Aedes albopictus following intrathoracic inoculation.

Aedes↗

Practice parameters for sigmoid diverticulitis. The Standards Task Force American Society of Colon and Rectal Surgeons.

It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.

Acute Disease↗

Exercise training and severe caloric restriction: effect on lean body mass in the obese.

The purpose of this study was to investigate the effects of exercise intensity on the body composition of obese subjects during severe caloric restriction. Forty obese subjects (33 women, 7 men; 41 +/- 7.7 years; 106 +/- 26kg; body fat > 25% men, > 30% women) on a commercially prepared OPTIFAST 420kcal/day supplemented fast were randomized into groups that exercised at target heart rates corresponding to 40% and 60% of the heart rate reserve (HRR) at the start of the program. Training volume was similar for both groups at approximately 300kcal per session three times per week for 12 weeks. Body weight, body fat, and lean weight were similar for both exercise intensity groups at week one. Overall, body weight decreased by 15.3 +/- 6.7 kg (p < or = .05), and body fat decreased by 14.9 +/- 5.0 kg (p < or = .05) for the 40 subjects, whereas lean weight remained unchanged. No significant differences in body weight, body fat, or lean weight were observed between the two groups. The results of the current study indicated that while on a supplemented 420-kcal/day fast, exercise at 40% and 60% of the HRR affected body composition similarly when total training volume was held constant at 900kcal/week. Lean weight remained unchanged and accompanied a 14.9 +/- 5.0-kg decrease in body fat, which may have resulted when the volume of exercise (ie, 900kcals/wk) was factored into the exercise prescriptions. These results suggest that exercising at 60% of the HRR offers no advantages for body composition changes over those obtained from exercising at 40% of HRR when the total volume of exercise training is controlled.

Adult↗

Multiple myeloma and chronic lymphocytic leukemia.

New insights into the molecular biology of both multiple myeloma and chronic lymphocytic leukemia can potentially lead to new treatment modalities. For myeloma, its lack of CD34 expression can lead to a functional but less contaminated autograft for stem cell transplantation. Single or even double transplants are being used to treat high-risk or even relapsed disease. Cytokines, such as interleukin-6, appear to play a role in tumor growth and bony complications as well. The bisphosphonate drugs are now known to decrease skeletal complications. For chronic lymphocytic leukemia, the nucleoside analogues have produced impressive response rates in many patients. Cell surface markers and cytogenetic abnormalities continue to identify patients with poor prognoses. Myeloablative therapy remains controversial for this disease.

Antineoplastic Agents↗

Molecular epidemiology of dengue-1 and dengue-4 viruses.

Genetic variation between geographically and temporally distinct isolates of dengue-1 (DEN-1) and dengue-4 (DEN-4) viruses was investigated. The nucleotide sequences of a fragment of the envelope protein gene encoding amino acids 28 to 87 of 35 DEN-1 isolates and 28 DEN-4 isolates were determined. Maximum nucleotide sequence variation was 6.9% and 4.9% for DEN-1 and DEN-4 viruses, respectively. Taking a divergence of 6% between the nucleotide sequences as the cut-off value, three genotype groups were defined for DEN-1 viruses, whereas only one was observed for DEN-4 viruses. Molecular analysis of isolates from the South Pacific permits the classification of the recent strains of DEN-1 (1988-1989 epidemics) into a genotype distinct from the genotype which comprises earlier strains. This observation suggests that the recent epidemics were due to the introduction of a new genotype rather than to the re-emergence of the earlier strain.

Animals↗

The relationship between alveolar bone height and age in the primary dentition. A retrospective longitudinal radiographic study.

The natural history of changes in attachment level in the primary dentition should be determined before considering diagnostic criteria for periodontal diseases in children. The present study was designed to describe longitudinal changes in the distance between the alveolar bone crest and the cementoenamel junction (ABC-CEJ) determined radiographically. Bite-wing radiographs were obtained from 33 children as part of a routine annual dental examination in a rural community. The ABC-CEJ distance of 1500 sites located at the mesial and distal aspects of primary molars and distal aspect of primary cuspids were measured. An analysis of variance model was used to assess the effect of age, sex, tooth, side of the mouth, jaw, site and patient on the ABC-CEJ measurements. The side of the mouth (left, right) and the site (mesial, distal) had no significant effect on the ABC-CEJ distance. ABC-CEJ distances in the upper jaw were greater than in the lower jaw, and different teeth exhibited different ABC-CEJ distances. Canines had the greatest distance and second molars the smallest. The most interesting relationship was between alveolar bone height and age. The overall ABC-CEJ distance seemed to increase with age; however, this was not a linear relationship but followed the pattern of facial growth, with two spurts separated by a period of minimal increase. The results indicate that different levels of ABC-CEJ distance might be considered as a cut-off value for radiographic diagnosis of alveolar bone loss at different ages, for different primary teeth and for different jaws.

Age Factors↗

Is simple fistula-in-ano simple?

PURPOSE: A study of 523 fistulas of cryptoglandular origin operated on between January 1985 and December 1991 at the Lehigh Valley Hospital was undertaken for the purpose of establishing whether the "so-called" simple fistula-in-ano has a favorable outcome. High transsphincteric fistulas with or without high blind tract, suprasphincteric, extrasphincteric, and horseshoe fistulas as well as fistulas associated with inflammatory bowel disease were excluded. METHODS: Four-hundred sixty-one patients with anal fistulas classified as simple fistulas-in-ano (uncomplicated transsphincteric, low and high blind track intersphincteric) were studied retrospectively. There were 310 males and 151 females with an average age of 42 years and mean follow-up of 34 months. RESULTS: Thirty (6.5 percent) patients developed recurrent fistulas: 16 (53.3 percent) because of missed internal openings at initial surgery, six (20 percent) attributed to missed secondary tracks, five (16.7 percent) because of premature fistulotomy wound closure, and three (10 percent) because of miscellaneous factors. CONCLUSION: All so-called simple fistulas-in-ano may not have readily detectable primary openings and may possess secondary tracks which preclude their behavior as simple fistulas.

Adult↗

Anorectal abscess-fistulae.

Anal abscess-fistulae have a tendency to recur based on variations in anatomic configuration and complexities of operative treatment and problematic postoperative healing. A classification of superficial, simple, complex, and recurrent fistulae was used to track outcome. Recurrence rates are substantially higher for those fistulae classified as complex. The reasons for this are discussed in this article.

Abscess↗

Molecular epidemiology of HTLV type I in Japan: evidence for two distinct ancestral lineages with a particular geographical distribution.

Japan is one of the highest endemic areas of the world for human T cell leukemia-lymphoma virus type I (HTLV-I). To gain new insight as to the origin of this virus in Japan and especially in the southern islands of the archipelago, we investigated the long terminal repeat (LTR) of 67 newly isolated HTLV-I proviral DNAs from peripheral blood mononuclear cells of HTLV-I-infected individuals for their restriction fragment length polymorphism (RFLP). The specimens were from Japanese living in different geographical areas (Hokkaido, Honshu, Kyushu, or the Ryukyu Islands) of Japan (59 cases) or Americans of Japanese ancestry living in Hawaii (8 cases). The analysis of the results, together with data for the 19 previously published LTR sequences, demonstrated the existence of 2 subtypes of HTLV-I in Japan. The first, which we propose to name Japanese subtype (previously named subtype III), is more frequent (67 of 86: 78%) than the second, the cosmopolitan subtype (previously named subtype II) (19 of 86: 22%). In parallel, a fragment of 413 base pairs of the U3/R region (nucleotide 22 to 434) was cloned and sequenced from 10 of the new Japanese samples. The alignment of these sequences and their comparison and phylogenetic analysis with previously published LTR HTLV-I sequences, demonstrated clearly the existence of the two distinct molecular subtypes of HTLV-I in Japan, diverging in this LTR region by about 1.6%. Furthermore, the study of the geographical distribution of the 2 subtypes among the 80 samples from patients whose place of residence in Japan was known showed an uneven distribution. While the Japanese subtype was present in all parts of Japan, the cosmopolitan subtype seemed to cluster in the southern islands of the archipelago (i.e., Kyushu and the Ryukyu Islands) as well as in immigrants from those areas who had lived in Hawaii for decades. These new molecular data raise questions and suggest hypotheses, discussed here, concerning the origin and means of dissemination of these human retrovirus subtypes in Japan.

Adult↗

Colorectal cancer.

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Colorectal Neoplasms↗

Outcome of delayed hemorrhage following surgical hemorrhoidectomy.

Delayed hemorrhage following surgical hemorrhoidectomy is a well-recognized complication. Emergency treatment may include suture ligation, anal packing, or other means of tamponade. At the Lehigh Valley Hospital, 27 patients were seen with the complication of delayed hemorrhage over an eight-year period from 1983 to 1990, for an incidence of 0.8 percent. Twenty-five patients (93 percent) underwent surgery primarily for hemorrhoidal disease; one patient had hemorrhoids removed in addition to a sphincterotomy for anal tissue, and the remaining patient had hemorrhoidectomy with fistulotomy. The mean interval from the operation to hemorrhage was six days. Treatment modalities included bedside anal packing in 20 patients (74 percent), observation alone in five patients (18 percent), and suture ligation in the operating room in two patients. Anal packing was successful in controlling postoperative hemorrhage in 20/20 patients, but late complications requiring reoperation developed in 15 percent.

Adult↗

Hemorrhage following colonoscopic polypectomy.

Clinically significant hemorrhage following colonoscopic polypectomy may occur primarily as the polyp is removed or manifest itself days to weeks later secondary to clot dissolution. The rate of hemorrhage following colonoscopic polypectomy ranges widely from 0.3 to 6.1 percent, depending on whether the data are derived from studies using the number of patients or number of polypectomies. A retrospective study was performed in our institution to study 4,721 patients who underwent polypectomy between January 1987 and December 1991. Twenty (0.4 percent) of these patients required hospital admission because of 9 primary and 11 delayed hemorrhages. Fifty-four polyps were removed from these patients: 11 in the right colon, 7 in the transverse colon, 17 in the descending colon, and 19 in the sigmoid colon. Eight polyps were 2 cm or larger, 10 were pedunculated, and 44 were sessile. Six patients underwent cauterization or resnaring of the bleeding polyp site, one patient underwent subtotal colectomy, and the remainder of the patients stopped bleeding spontaneously. Factors that could be associated with the outcome of hemorrhage include patient age, size, location, number and morphology of polyps (i.e., sessile or thick stalk), and use of anticoagulants. An experienced endoscopist with knowledge of electrosurgical and technical principles may be the most important factor for prevention of postpolypectomy bleeding.

Adult↗

Genetic determinants of dengue type 4 virus neurovirulence for mice.

Mouse-adapted dengue type 4 virus (DEN4) strain H241 is highly neurovirulent for mice, whereas its non-mouse-adapted parent is rarely neurovirulent. The genetic basis for the neurovirulence of the mouse-adapted mutant was studied by comparing intratypic chimeric viruses that contained the three structural protein genes from the parental virus or the neurovirulent mutant in the background sequence of nonneurovirulent DEN4 strain 814669. The chimera that contained the three structural protein genes from mouse neurovirulent DEN4 strain H241 proved to be highly neurovirulent in mice, whereas the chimera that contained the corresponding genes from its non-mouse-adapted parent was not neurovirulent. This finding indicates that most of the genetic loci for the neurovirulence of the DEN4 mutant lie within the structural protein genes. A comparison of the amino acid sequences of the parent and its mouse neurovirulent mutant proteins revealed that there were only five amino acid differences in the structural protein region, and three of these were located in the envelope (E) glycoprotein. Analysis of chimeras which contained one or two of the variant amino acids of the mutant E sequence substituting for the corresponding sequence of the parental virus identified two of these amino acid changes as important determinants of mouse neurovirulence. First, the single substitution of Ile for Thr-155 which ablated one of the two conserved glycosylation sites in parental E yielded a virus that was almost as neurovirulent as the mouse-adapted mutant. Thus, the loss of an E glycosylation site appears to play a role in DEN4 neurovirulence. Second, the substitution of Leu for Phe-401 also yielded a neurovirulent virus, but it was less neurovirulent than the glycosylation mutant. These findings indicate that at least two of the genetic loci responsible for DEN4 mouse neurovirulence map within the structural protein genes.

Amino Acid Sequence↗

Concordance of familial characteristics in Crohn's disease and ulcerative colitis.

The diagnosis of inflammatory bowel disease (IBD) in a proband increases the probability of a parallel IBD diagnosis in a family member. In this study, we were able to confirm the IBD diagnosis in 35 (9.9 percent) of the relatives of 352 registry probands. To confirm a proband's report of a positive family history of IBD, efforts were made to directly contact all first-degree relatives regardless of their IBD status (parents, siblings, and children). Consent to contact family members was obtained from the proband, who furnished the registry personnel with names, addresses, and phone numbers. We then attempted to contact each identified relative by phone. After verbal consent was obtained, family members were asked if they had been diagnosed with IBD. This diagnosis was confirmed by contacting the relative's physician. A McNemar (chi 2 Mc) matched-pair analysis was used to analyze concordance between the proband and the affected family member. Within the CD/CD (Crohn's disease) concordant pairs, sex was a significant risk factor. Sex was not a significant risk factor within the UC/UC (ulcerative colitis) concordant pairs. In the concordant surgery pairs, no surgical procedure was a significant risk factor for the prediction of a similar surgical procedure for the affected relative. In concordant extraintestinal complications, only the appearance of a skin rash was significantly related to the appearance of a skin rash in the affected relative.

Colitis, Ulcerative↗

Practice parameters for the management of anal fissure. The Standards Task Force American Society of Colon and Rectal Surgeons.

It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.

Fissure in Ano↗