Distribution of homing protein on hemopoietic stromal and progenitor cells.

Homing receptor is a membrane lectin of 110 kd molecular weight that recognizes galactosyl and mannosyl residues of an as yet unknown glycoconjugate. It is responsible for recognition and selective homing of hemopoietic progenitor cells after these cells are transplanted intravenously. Consequently, it is present on the surface of hemopoietic progenitor cells. To determine the distribution of this receptor on other cell types we performed standard binding assays in many cell types using galactosyl and mannosyl residues covalently bound to bovine serum albumin (G-BSA and M-BSA) as an index of homing receptor. BSA moiety was then labeled with 125I. The three cloned hemopoietic cell lines B6Sut, FDCP-1, and FDCP-mix all showed combined binding of G-BSA and M-BSA, whereas the lymphoid cell line L1210 showed only M-BSA, not G-BSA binding and, therefore, was considered to lack homing receptors. Similarly, stromal cell lines D2X and GB1/6 as well as primary marrow stroma (progenitor cell-depleted) did not show homing receptors as evidenced by combined binding of G-BSA and M-BSA. Nor did the nonhemopoietic stromal cell line Swiss 3T3 show the presence of homing receptors by these criteria. We conclude that homing receptors are distributed narrowly and are present on hemopoietic progenitor cells, but absent on hemopoietic stroma.     

Reflex sympathetic dystrophy in brain-injured patients.

One-hundred consecutive patients were prospectively evaluated on admission to our Brain Injury Unit for signs and symptoms of reflex sympathetic dystrophy (RSD) in the upper extremity. Patients averaged 4 months postinjury and had an average age of 29 years. Thirteen patients had clinical signs and symptoms of RSD and were then evaluated with standard radiographs and 3-phase radionuclide scintigraphy. Twelve of 13 patients had 3-phase bone scans (TPBS) consistent with RSD (12% overall incidence). RSD was present exclusively in the spastic upper extremity. There were 9 patients with hemiparesis and 3 with quadraparesis. There was a significantly higher (P < 0.01) incidence of associated upper extremity injury in the group with RSD (75%). All patients had a mean Rancho Cognitive Level of V and initial Glasgow Coma Scores less than 8. Patients who developed RSD had lower Glasgow Coma Scores than the non-RSD patients. Brain-injured patients often display agitation, hyperalgesia, disuse or neglect of the RSD-involved extremity. In addition, these patients are often cognitively unable to vocalize complaints of pain. Undiagnosed RSD in these patients can result in a significant delay in rehabilitation and possible loss of the use of an otherwise functional upper extremity.     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Atypical retinitis in patients with the acquired immunodeficiency syndrome

We examined three patients with AIDS who had large, sharply demarcated areas of thinned retina consistent with inactive cytomegalovirus retinitis and who were not treated with ganciclovir. These lesions appeared identical to clinically inactive areas of cytomegalovirus retinitis after effective antiviral treatment. All patients were receiving azidothymidine or ribavirin, or both, which have activity against the human immunodeficiency virus and which may improve immune function. All patients also received oral acyclovir at doses ineffective against cytomegalovirus retinitis.     

A prospective, randomized, cross-over comparison of two methods of artificial insemination by donor on the incidence of conception: intracervical insemination by straw versus cervical cap

In a prospective, randomized study of insemination with donor semen, intracervical insemination by straw was compared with insemination using a cervical cap with an intracervical reservoir. A total of 91 patients completed 486 treatment cycles. There were no significant differences in age, parity, indication for insemination by donor, or method of cycle monitoring between women who became pregnant and those who did not conceive with either insemination method. In 236 standard intracervical insemination cycles, 14 patients became pregnant (5.9% per cycle), whereas 38 patients conceived in 250 cervical cap cycles (15.2% per cycle). Both the crude pregnancy rates and the cumulative pregnancy rates calculated by the Kaplan-Meier life-table method were significantly different (chi(2)-test, P < 0.001, and log-rank test, P < 0.005 respectively). Pregnancy rates in artificial insemination with cryopreserved donor semen may be improved by the use of a cervical cap when compared to cervical insemination by straw. The use of the cervical cap may prolong the exposure of the spermatozoa to the cervical mucus and prevent the backflow of semen into the vagina.      

Heat shock protein and high-dose aspirin: effects on random skin flap survival in a rat model.

The heat shock response is known to have a protective effect against flap ischemia. It has been shown that heat shock protein (hsp) expression can be augmented in vivo with the administration of high-dose aspirin before heat treatment. The authors hypothesized that administration of aspirin before hsp induction through heat stress would enhance further the protective effects of the heat shock response against skin flap ischemia. They used a random dorsal skin flap model in 32 rats divided into four groups (N = 8 each): control, heat shock, aspirin plus heat shock, and aspirin. Before surgery, rats in the two heat shock groups were placed in a 45 degrees C water bath until core body temperature measured 42 degrees C, and they were maintained at 42 degrees C for 15 minutes. Rats in the two aspirin groups received a single oral dose of aspirin (100 mg per kilogram) 1 hour before heat bath or surgery. Immunohistochemistry confirmed hsp expression in the two heat groups. Skin flap survival was improved significantly (p < 0.05) in the heat shock (55%), aspirin plus heat shock (58%), and aspirin (60%) groups when compared with controls (45%). Contrary to their hypothesis, aspirin combined with hsp induction did not offer greater protection from ischemia than hsp induction alone (p > 0.05). However, high-dose aspirin administration alone did improve skin flap survival when compared with controls. Future studies are needed to investigate further the role of pharmacological therapy combined with hsp induction in improving skin flap survival and to delineate the dose-response relationship between aspirin and hsp.