Variability of neural activation during walking in humans: short heels and big calves.

People come in different shapes and sizes. In particular, calf muscle size in humans varies considerably. One possible cause for the different shapes of calf muscles is the inherent difference in neural signals sent to these muscles during walking. In sedentary adults, the variability in neural control of the calf muscles was examined with muscle size, walking kinematics and limb morphometrics. Half the subjects walked while activating their medial gastrocnemius (MG) muscles more strongly than their lateral gastrocnemius (LG) muscles during most walking speeds ('MG-biased'). The other subjects walked while activating their MG and LG muscles nearly equally ('unbiased'). Those who walked with an MG-biased recruitment pattern also had thicker MG muscles and shorter heel lengths, or MG muscle moment arms, than unbiased walkers, but were similar in height, weight, lower limb length, foot length, and exhibited similar walking kinematics. The relatively less plastic skeletal system may drive calf muscle size and motor recruitment patterns of walking in humans.

TERC telomerase subunit gene copy number in different disease stages of non-hodgkin lymphoma and in hepatitis C.

ABSTRACT Focal amplification of specific regions of the genome creates high copy number and expression of oncogenes in tumors. By applying fluorescence in situ hybridization (FISH) to leukocytes of hepatitis C (HCV) patients and non-Hodgkin lymphoma (NHL) patients, we estimated gene dosage of the TERC gene at 3q26.3. Higher TERC copy numbers were found in NHL at diagnosis compared to HCV patient groups. Higher TERC copy numbers were also observed in NHL patient at diagnosis and relapse compared to patients in remission. We believe that the TERC gene amplification is involved in the process of genetic instability leading to tumor genesis such as in NHL.

Telomere aggregates in non-Hodgkin lymphoma patients at different disease stages.

Telomeres of tumor nuclei tend to form aggregates (TA). The same phenomenon was also observed in premalignant states. The aim of this study was to estimate TA formation in leukocytes of patients with non-Hodgkin lymphoma (NHL) at different disease stages (diagnosis, treatment, relapse, and remission). The peptide nucleic acid Telomere Kit was used to evaluate TA formation, using two-dimensional fluorescence microscopy. A higher rate of TA was found in all the NHL stages (including remission) than in the control group. Significantly higher TA formation was also observed in the relapse group, compared to the diagnosis group. It may be possible that patients with higher TA numbers are prone to relapse. From our previous results involving replication pattern, random aneuploidy rate, and (recently) TA formation, it can be concluded that the patients in remission are at higher risk of developing relapse than the normal population throughout their life span. The genetic instability parameters remain in the cells of these patients, who must continue to be monitored throughout their life.

Hydroxyurea as a cause of drug fever.

We report on a patient with essential thrombocythemia treated with hydroxyurea who became febrile 3 weeks after the treatment was started. After drug withdrawal, the fever resolved but after rechallenge there was recurrence of the fever. Although hydroxyurea-induced fever is rare, this drug must be added to the list of drugs that produce fever and the physicians should be aware of this possibility.

Accelerated phase of chronic myeloid leukemia presenting with hypercalcemia and a mediastinal mass.

A patient with chronic myeloid leukemia developed hypercalcemia as a presenting sign of the accelerated phase of the disease. Ultrasound of the neck showed a large hypodense mass connected to the thyroid gland, which was thought to be a parathyroid tumor and the cause of the hypercalcemia. Histology of the surgically removed mass revealed a chloroma. The patient's course was complicated by respiratory failure and metastatic calcinosis of the lung, an unusual finding in hypercalcemia of short duration.

Treatment of Hodgkin's disease at a local hospital.

It is unclear whether patients with Hodgkin's disease can be adequately treated at local hospitals. From 1978 through 1991, 40 patients with Hodgkin's disease were treated at the Carmel Medical Center. Disease-free survival was 36/40 (90%) and 19/23 (83%) after 3 and 10 years follow-up, respectively. These results are comparable to those reported by tertiary cancer centers. We conclude that adequate treatment for patient's with Hodgkin's disease can be given at local hospitals. Further studies are warranted to determine if our results can be extrapolated to other local hospitals.

Fulminant bilateral cerebellar syndrome in a patient with chronic lymphocytic leukemia.

A 55 year old patient with chronic lymphocytic leukemia (CLL) and long-standing excessive lymphocytosis developed a rapidly progressive neurological syndrome. Differential diagnosis focused on two rate neurological complications in this disease: direct brain infiltration by leukemic cells versus progressive multifocal leukoencephalopathy (PML). Tissue diagnosis was not available. Two cerebro-spinal fluid examinations performed during the presence of the acute neurological symptoms were normal. Computed tomography (CT) showed low density lesions without enhancement and no mass effect within the left cerebellum. Magnetic resonance imaging scan (MRI) demonstrated multiple hyperintense areas in the brain stem, right and left cerebellum and right capsula interna, suggestive of demyelinative process. In our opinion these findings were compatible with the diagnosis of PML, but biopsy was not performed. Because of the different therapeutic approach in these two conditions, we feel that tissue diagnosis is warranted in patients with CLL who develop a rapidly progressive central nervous system complication in the presence of normal CSF.

Fibromatosis (desmoid tumor) following radiation therapy for Hodgkin's disease.

Fibromatosis (desmoid tumor) can sometimes develop at sites of previous surgery or previous trauma, but it is very rarely detected at sites of prior irradiation. We report two cases of fibromatosis following radiotherapy for Hodgkin's disease. The fibromatoses, developing in the radiation fields, were detected at the posterior area of the neck 11 years after irradiation in one case and in the peritoneal cavity 3 years after laparotomy and irradiation in the second case. The tumors did not differ clinically or histologically from those seen in patients who did not undergo irradiation. Although rare, fibromatosis should enter the differential diagnosis of masses developing in irradiated fields in patients with treated Hodgkin's disease.

Soluble factors from peripheral blood T-cells of patients with polycythemia vera stimulate normal BFU-E.

T cells and monocytes from patients with polycythemia vera (PV) were isolated and grown in culture. The conditioned medium was tested for the presence of soluble factors that promote proliferation of erythroid colonies from the blood of healthy donors. We show that T cells from all 14 PV patients that were examined secrete factor/s that stimulate the proliferation of erythroid burst-forming units (BFU-E) in the absence of an external source of erythropoietin and BPA. Addition of cyclosporin A to the culture did not inhibit the production of this activity. The conditioned medium from monocytes of PV patients can also stimulate normal BFU-E but to a much lesser extent than T-cell conditioned medium. Such stimulation was not observed with control T cells or monocytes. We observed that the fraction of DR-positive T cells was significantly higher in PV patients comparing to normal. These results suggest that PV patients possess an abnormally high level of circulating activated T cells which may in turn be the source of the putative factor that facilitates uncontrolled erythroid differentiation.

High plasma fibronectin levels in multiple myeloma patients: possible mechanisms and clinical implications.

Fibronectin (FN) has been implicated in the formation of cryoprecipitates in rheumatic diseases and is present in tissues where, under pathological conditions, immune complexes are frequently deposited. We found elevated levels of FN in the plasma of 92% of multiple myeloma patients tested compared with a group of normal subjects, although the level of FN did not correlate with the level of the paraprotein. We then characterized the interacting fragments on both molecules and found that under physiological conditions of pH and ionic strength both heavy and light chain of all multiple myeloma and normal IgG showed affinity to FN; the active fragment on FN was found to be the aminoterminal heparin-binding domain. These findings raise the possibility that FN might be implicated in some of the clinical symptoms of multiple myeloma.

Increased spontaneous secretion of IL-6 from B cells of patients with B chronic lymphatic leukaemia (B-CLL) and autoimmunity.

We studied B cells from 18 patients with B-CLL, six of them with autoimmune haemolytic anaemia, for spontaneous secretion of IL-6. Our aim was to determine whether the increased incidence of autoimmune disease found in B-CLL patients is associated with enhanced spontaneous IL-6 secretion. IL-6 was measured by the effect of B cell supernatants on the proliferation of an IL-6 dependent plasmacytoma cell line T1165. The highest IL-6 values (7.4 +/- 1.8 U/ml) were measured in supernatants derived on day 3 of culture from lymphocytes of the six patients with B-CLL and concomitant autoimmune disease. The maximal IL-6 values for 10 patients with B-CLL only were 2.8 +/- 0.3 U/ml and for 10 age-matched controls, 0.8 +/- 0.3 U/ml (P less than 0.01, each group compared with the other). We conclude that there is an association between B-CLL, autoimmune disease and the spontaneous in vitro secretion of IL-6. Further studies are needed to determine whether the IL-6 secretion plays a role in the pathogenesis of autoimmune disease in patients with B-CLL.

Evidence for the existence of circulating monoclonal B-lymphocytes in multiple myeloma patients.

Multiple myeloma is characterized by the proliferation of a single clone of plasma cells producing a homogeneous immunoglobulin fraction. In this disease, plasma cells home essentially in the bone marrow. However, controversy exists whether peripheral blood B-lymphocytes in patients with multiple myeloma (MM) are part of the malignant clone. We investigated clonal immunoglobulin gene rearrangement (IgGR) in T-cell-depleted peripheral blood mononuclear cells as well as in bone marrow of these patients. Seven out of 17 MM patients demonstrated an identical IgGR in bone marrow and peripheral mononuclear cells, these patients were in an active stage of the disease. In nine patients in plateau phase, clonal IgGR could not be detected in peripheral blood. Peripheral mononuclear cells from ten patients with monoclonal gammopathies of undetermined significance (MGUS) were also examined and no IgGR was detected. The existence of monoclonal B-lymphocytes in the circulation of patients with MM suggests a mechanism whereby the malignant clone homes in the bone marrow through peripheral blood. These findings may also be used for the evaluation of patients with active myeloma and the determination of plateau phase.

Multiple myeloma in the geriatric patient.

Consecutive patients with multiple myeloma were studied. The clinical characteristics and survival of 17 patients aged 75 years or more were compared to 42 patients younger than 75 years of age. Of the patients older than 75 years, 14/17 (82%) died in less than 12 months compared to only 11/42 (26%) of those under 75 years old (P less than 0.001). Multivariate analysis showed that both age and hemoglobin were significant predictors of survival (P less than 0.012 and P less than 0.002, respectively) explaining 34.6% of the variance (r = 0.588, P less than 0.000), whereas the extent of bone lesions, the presence of more than 50% plasma cells in the bone marrow, the amount of serum monoclonal protein, functional class, and the Salmon and Durie staging system did not significantly add to the analysis. We conclude that the factors that best predict prognosis are hemoglobin levels and age at presentation. Different approaches including more appropriate chemotherapeutic regimes and comprehensive geriatric assessment with improved supportive treatment need to be developed for the geriatric patient with multiple myeloma.

The effect of desmopressin on massive gastrointestinal bleeding in hereditary telangiectasia unresponsive to treatment with cryoprecipitate.

A patient with hereditary hemorrhagic telangiectasia and reduced levels of von Willebrand factor had severe recurrent gastrointestinal bleeding. Treatment with either desmopressin acetate or cryoprecipitate normalized both bleeding time and kaolin-activated partial thromboplastin time. Hematochezia (five episodes) continued, however, for a week despite daily treatment with cryoprecipitate, whereas treatment with desmopressin at the onset of three later episodes of hematochezia resulted in the prompt cessation of bleeding. After an episode of life-threatening gastrointestinal bleeding, desmopressin administration allowed a total colectomy without excessive bleeding. During the 3 years after colectomy, no further gastrointestinal bleeding occurred. In the past year, however, three episodes of severe epistaxis responded promptly to intravenous infusion of desmopressin. We conclude that desmopressin may be useful in the management of bleeding in patients with hereditary hemorrhagic telangiectasia with or without von Willebrand factor deficiency.

Antithrombin III levels in preeclampsia.

Antithrombin III (AT-III) activity was measured and compared in 29 patients with preeclampsia and 31 women with normal pregnancies. AT-III levels were 83 +/- 25% in preeclamptic patients with greater than 5 g/l proteinuria compared with 102 +/- 11% in the controls. Less severe proteinuria was not associated with decreased AT-III levels. Multivariate analysis revealed that the duration of pregnancy and the degree of proteinuria had an independent negative effect on AT-III levels. AT-III activity correlated poorly with platelet counts and blood pressure measurements. We conclude that urinary loss appears to be the major mechanisms of lower AT-III levels observed in our patients with preeclampsia.

Neutrophil chemotactic heterogeneity to N-formyl-methionyl-leucyl-phenylalanine detected by the under-agarose assay.

Human polymorphonuclear neutrophils (PMNs) are heterogeneous in their response to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). By using a computerized imaging method for analysis of agarose chemotaxis plates, the chemotactic sensitivity of the population of PMNs at the leading front to FMLP was greater than the mean sensitivity of all migrating PMNs. When PMNs were treated with the membrane-perturbing agent butanol at concentrations up to 0.25%, chemotaxis of the fastest PMN population in response to 10(-7) mmol/L FMLP was increased to 140% of control, whereas the mean of all populations was increased to only 110% of control. These data show that the PMN population at the leading front has a different chemotactic sensitivity to FMLP. Furthermore, the susceptibility to butanol treatment of the PMN population suggests that an alteration in membrane properties may partly account for this difference.