Intra-lesional injections of collagenase are ineffective in the treatment of keloid and hypertrophic scars.

The treatment of keloid and hypertrophic scars remains difficult. Enzymatic digestion of keloid scars has been previously proposed as an effective treatment strategy for reducing the volume of keloid scars. To test this, we administered intra-lesional injections of pure collagenase (between 600 and 4500 units for each scar) into the keloid and hypertrophic scars of seven human volunteers (five keloid and two hypertrophic scars). Five patients (three keloid and two hypertrophic) received more than one injection of collagenase. The treatment resulted in a temporary reduction in scar volume for three of the patients with keloid scars. However, scar volumes for these three patients returned to the same (or greater) levels after 6 months of follow-up. Treatment with collagenase produced no change in scar volume for the two patients with hypertrophic scar. Side effects were numerous and severe including; pain, swelling, blistering, ulceration and ecchymosis at the site of injection. One patient required admission to hospital for 48 h after the first injection. Maximum length of follow-up was 6 months. None of the seven patients completed the study and returned for final follow-up at 2 years. This pilot study suggests that treatment of keloid and hypertrophic scars with intra-lesional injections of collagenase is ineffective.     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Relationship between intracranial pressure and intracranial volume in craniosynostosis.

Premature fusion of cranial sutures in craniosynostosis has been thought to lead to craniostenosis, which in turn may lead to increased intracranial pressures. In 41 consecutive patients with craniosynostosis, intracranial pressure and intracranial volume were measured. Of the 41 patients, 38 (92.6%) had raised intracranial pressure but only 4 (9.7%) had a decreased skull volume. In the present study, there is no correlation between intracranial volume and intracranial pressure. This study confirms that the measurement of intracranial volume, a non invasive procedure, cannot be used to assess intracranial pressure and to avoid an invasive procedure.     

Cholate-dependent killing of Giardia lamblia by human milk.

We showed previously that nonimmune human milk (NHM) kills Giardia lamblia trophozoites in vitro and presented evidence that killing requires the bile salt-stimulated lipase of milk. Since this enzyme is activated by bile salts, killing should be dependent on the presence of bile salts. We now show that killing by fresh NHM or NHM stored at -70 degrees C is totally dependent on sodium cholate (a bile salt). With less than 0.4 mM cholate, no parasites were killed, whereas with 1 mM cholate, greater than 99.7% were killed by 5% NHM in 30 min. Moreover, killing activity was completely heat labile. The G. lamblia-killing activity of human milk was greatly altered by storage at -10 or -20 degrees C. In less than 23 days, the 50% lethal dose decreased, cholate dependence was lost, and killing activity became heat stable. In contrast, the activity of milk stored at -70 degrees C remained unchanged. Milk lipase activity, like killing activity, became cholate independent during storage at -10 or -20 degrees C. On the basis of these results, we hypothesize that killing of G. lamblia by fresh NHM or NHM stored at -70 degrees C depends on bile salt-stimulated lipase, which must be activated by bile salts. In contrast, NHM stored at -20 degrees C accumulated free fatty acids which kill G. lamblia. In support of this thesis, milk stored at -10 degrees C had a concentration of 18.7 mM free fatty acids compared with only 1.1 mM in an identical sample stored at -70 degrees C.