Relationship between human development and disappearance of unusually large von Willebrand factor multimers from plasma

von Willebrand factor (vWF) multimers were examined in fetal, umbilical cord, and neonatal platelet-poor plasma (PPP) specimens. Sixty-five of 65 (100%) fetal PPP samples aged less than 35 weeks and seven of ten (70%) fetal samples aged greater than 35 weeks had unusually large vWF (ULvWF) multimers. Thirty of 46 (65%) cord PPP samples from neonates ranging in gestational age from 34 to 41 weeks had ULvWF. There was no significant relationship between either gestational age at time of delivery or birth weight and likelihood of finding ULvWF multimers in cord PPP samples. No maternal PPP sample contained ULvWF multimers. Serial heelstick samples from 16 preterm and term neonates were analyzed for 8 weeks. ULvWF multimers disappeared from the PPP of ten of the neonates during this time. The PPP of four neonates had vWF patterns similar to those in normal adult PPP throughout the sampling period. The ULvWF multimeric forms of fetal and neonatal PPP samples were similar to those constitutively released from endothelial cells. They were not as slowly migrating in a very porous 0.5% agarose gel system as the ULvWF multimers released from Weibel-Palade bodies in response to the calcium ionophore A23187. A vWF protomer was present in 97% of fetal samples, 83% of cord blood specimens, and 11% of neonatal heelstick samples, but was not found in any maternal sample. These results indicate that control mechanisms operative in older children and adults to prevent circulation of ULvWF multimers and vWF protomeric forms are normally acquired late in uterine life or during the neonatal period. ULvWF multimers, which are normal components of fetal, most cord, and some neonatal plasma samples, may contribute to in utero and postnatal hemostasis.     

Gestational trophoblastic neoplasia: diagnosis with Doppler US

The sonographic appearance of gestational trophoblastic neoplasia is nonspecific and also seen in complete or partial hydatidiform mole, hydropic degeneration, degenerating fibroids, or ovarian dysgerminomas. Correlation with the serum human chorionic gonadotropin (hCG) level may be helpful since levels exceeding 100,000 IU/L are strongly suggestive of gestational trophoblastic neoplasia. However, low hCG levels may also be found in the presence of this disease. The authors studied six patients who were suspected of having gestational trophoblastic neoplasia. Three of the six proved to have incomplete abortions or molar degeneration. Doppler ultrasound (US) was used to record the signal in the uterine arteries of these patients. The signals were compared with those of three nongravid volunteers and three patients in the first trimester of pregnancy. Analysis of the signals in the uterine artery showed higher systolic and diastolic Doppler shifts in gestational trophoblastic neoplasia when compared with postabortal, gravid, and nongravid signals. These preliminary results indicate that Doppler US has the potential to be clinically useful in the diagnosis of gestational trophoblastic neoplasia.     

Granulated T cell lymphocytosis with neutropenia: malignant or benign chronic lymphoproliferative disorder?

The clinical, morphological, immunologic, and cytogenetic features of seven cases of chronic granulated T cell lymphocytosis with neutropenia were studied. The disorder was characterized by moderate blood and bone marrow lymphocytosis, neutropenia, polyclonal hypergammaglobulinemia, splenomegaly, absence of lymphadenopathy, and a chronic, relatively stable clinical course. The proliferative lymphocytes manifested a cytotoxic/suppressor T lymphocyte phenotype. In two of four cases studied, blood lymphocytes showed clonal chromosome abnormalities. One patient treated with pulse steroid therapy had reversal of lymphocytosis and severe neutropenia with subsequent resolution of an intractable infection. The lymphocytosis and neutropenia recurred when steroids were withdrawn. Six of the seven patients were living three months to 17 years from diagnosis; one died at 4.3 years of an unrelated cause. Five of the patients, including the two with lymphocyte chromosome abnormalities, had persistent lymphocytosis and neutropenia from three months to 13 years from diagnosis. In two patients, the disease appears to have undergone spontaneous regression. No differences in clinical presentation or the morphological or immunologic characteristics of the proliferative lymphocytes were apparent between those patients with lymphocyte chromosome abnormalities and persistent disease and those who had a spontaneous regression. The finding of clonal chromosome abnormalities in the blood lymphocytes of two of the patients in this study suggests a neoplastic origin for chronic granulated T cell lymphocytosis with neutropenia. However, apparent spontaneous regression in two patients, one after 11 years, lends support to a chronic reactive or immunoregulatory disorder as the etiology. It is probable that cases of granulated T cell lymphocytosis with neutropenia, although morphologically and immunologically similar, are biologically heterogeneous.     

Histochemical demonstration of terminal deoxynucleotidyl transferase in leukemia

White blood cells from 22 patients with leukemia and lymphoma were studied for the presence of terminal deoxynucleotidyl transferase with a peroxidase-antiperoxidase method. The enzyme was detected in leukemic cells of 5 patients with acute lymphoblastic leukemia and 1 patient with chronic myelogenous leukemia, whereas 16 patients with different forms of leukemia or lymphoma were negative for this enzyme. Comparative studies using a biochemical and an indirect immunofluorescence assay revealed complete concordance between these three methods.     

LAPAROSCOPIC SURGERY

The speed of adoption and popularity of laparoscopic cholecystectomy is without precedence in modern surgical history. This has resulted in therapeutic and diagnostic laparoscopy being attempted in almost every field of surgery to substitute open surgical procedures. The list is endless. It will take time to evaluate the safety and advantages of many of these procedures as reports of controlled studies and long term follow up results are awaited. While certain procedures like gall bladder surgery and appendicectomy will establish their many fold advantages over open surgery, many other procedures like repair of hernias, radical resection of bowel for malignancy etc may fail to do so once the initial enthusiasm wanes away. Any way the concept of minimally invasive surgery is going to be a dominant factor in the surgery of this decade and one should prepare to face this fascinating challenge. Further developments in laparoscopic instruments, optical system and video imaging techniques will add to the progress and safety of laparoscopic surgical procedures in the days ahead.KEY WORDS: Laparoscopic Surgery     

Frequent occurrence of identical heavy and light chain Ig rearrangements

Single-cell PCR analyses of expressed Ig H and L chain sequences presented here show that certain rearrangements occur repeatedly and account for a major segment of the well-studied repertoire of B-1 cell autoantibodies that mediate the lysis of bromelain-treated mouse erythrocytes, i.e. antibodies reactive with phosphatldyicholine (PtC). We repeatedly isolated at least 10 different types of VH region rearrangements, involving three distinct germline genes, among FACS- sorted PtC-binding B-1 cells from three strains of mice (C57BL/6J, BALB/c and C.B-17). The predominant rearrangement, VH11-DSP-JH1 (VH11 type 1), has been previously found in anti-PtC hybridomas in several studies. We show that within each of six mice from two strains (C57BL/6J and BALB/c), unique instances of IgH/IgL pairing arose either from different B cell progenitors prior to IgH rearrangement or from pre-B cells which expanded after IgH rearrangement but prior to IgL rearrangement. Together with other recurrent rearrangements described here, our findings demonstrate that clonal expansion of mature B cells cannot account for all repeated rearrangements. As suggested by initial studies of dominant idiotype expression, these findings confirm that clonal expansion is only one of the mechanisms contributing to the establishment of recurrent rearrangements.      

Early acute otitis media and siblings' attendance at nursery

To assess the relation between early acute otitis media and exposure to respiratory pathogens mediated by siblings and other children, a prospective cohort of 3754 Norwegian children born in 1992-3 was followed up from birth to 12 months. Of these, 25% had one or more episodes of acute otitis media during the first year. Results from multiple logistic regression analysis adjusted for confounding showed that siblings' attendance at daycare is the most important risk factor for early acute otitis media (adjusted odds ratio, ORadj = 1.9). The total number of children in the daycare setting is another determinant for early acute otitis media (ORadj = 2.0 in groups of four or more other children and ORadj = 1.3 in groups of one to three other children, as compared to those who are cared for alone). Having siblings in daycare outside the home and the number of children in the daycare setting are the most important determinants for early acute otitis media.