CD4+ suppressor cells of autoimmune encephalomyelitis respond to T cell receptor-associated determinants on effector cells by interleukin-4 secretion.

We have previously demonstrated that CD4+ suppressor T cells (Ts) inhibit the secretion of interferon (IFN)-gamma, but not interleukin (IL)-2, by effector cells of experimental autoimmune encephalomyelitis (EAE). Moreover, CD4+ Ts appear to regulate IFN-gamma by secretion of transforming growth factor-beta. We now show that CD4+ Ts produce a lymphokine with IL-4 activity in response to a determinant associated with EAE effector cells. CD4+ Ts do not proliferate or secrete IFN-gamma, IL-2, or IL-4 in response to myelin basic protein, nor do CD4+ Ts proliferate or secrete IL-2 when co-cultured with irradiated EAE effector cells. Rather, CD4+ Ts secrete IL-4 when co-cultured with either irradiated effector spleen cells or irradiated encephalitogenic line cells. CD4+ Ts do not secrete IL-4 in response to OVA-primed spleen cells, suggesting that the suppressor cells recognize a determinant specific to encephalitogenic T cells. Furthermore, CD4+ Ts secrete IL-4 when cultured with synthetic T cell receptor (TcR) V beta 8, but not TcR V beta 14 peptide, in the presence of antigen-presenting cells. This response is major histocompatibility complex class II restricted as demonstrated by inhibition of the response with anti-class II monoclonal antibody. These results suggest that CD4+ Ts recognize a determinant associated with TcR on the surface of EAE effector cells and respond by secreting IL-4, in a manner analogous to the Th2 lymphocyte subtype.     

Breast cancer detection: one versus two views

Mammographic examinations of 169 patients with 172 biopsy-proved carcinomas, and of 194 healthy subjects, were interpreted independently and retrospectively by three experienced mammographers, initially as single-view oblique examinations and 6 months later as two-view oblique-cephalocaudal examinations. For the single-view examinations of the cancer patients, 67% of the cancers were correctly recommended for biopsy, additional views were requested for 23%, and a "negative" interpretation was made for 10%. For the single-view examinations of healthy subjects, biopsy was recommended for 7% and additional views were recommended for 32%. For the two-view examinations of women with cancer, 80% of the cancers were correctly recommended for biopsy, additional views were requested for 4%, and a "negative" interpretation was made for 16%. For two-view examinations of healthy subjects, biopsy was recommended for 7% and additional views were requested for only 5%. The authors conclude that single-view screening should not be performed, because it would lead to an excessive number of "call-back" examinations of healthy patients, producing additional cost and anxiety that would outweigh any theoretical benefit.     

Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis

Ultrasound scans of 51 consecutive patients with gallbladder wall thickening were reviewed, and specific sonographic features were correlated with surgical and clinical follow-up. Two patterns of thickening were identified as specific indicators of the presence or absence of acute cholecystitis. "Striated" wall thickening, consisting of several alternating, irregular, discontinuous, lucent and echogenic bands, was seen in eight of 13 patients (62%) with acute cholecystitis. This pattern was not encountered in any of the patients who did not have acute cholecystitis. Conversely, "three-layer" thickening, consisting of a single circumferential lucent zone between two relatively uniform echogenic layers, was seen in only one of 13 patients (8%) with acute cholecystitis but in 11 of 38 patients (29%) with other diagnoses. Other abnormalities, including the presence of intramural echogenic foci and wall irregularities, were more frequently seen in patients with acute cholecystitis but were not as helpful. Use of these features may suggest or help exclude a diagnosis of acute cholecystitis in those patients in whom the cause of gallbladder wall thickening is otherwise not apparent.     

Substance P regulates natural killer cell interferon-gamma production and resistance to Pseudomonas aeruginosa infection

Studies have shown that after Pseudomonas aeruginosa (P. aeruginosa) corneal infection, BALB/c mice that are capable of resolving the disease, locally produce IFN-gamma. As T cells are not detected in the infected cornea of these mice, antibody depletion was used to test whether NK cells produce the cytokine. After depletion, decreased corneal IFN-gamma mRNA and increased disease severity, bacterial load, and PMN infiltrate resulted. Further work determined if substance P (SP), a pro-inflammatory neuropeptide, participated in regulation of this response. To this end, mice were treated with the SP antagonist, spantide I that blocks SP interaction with neurokinin-1, its major receptor. The treatment significantly decreased corneal IFN-gamma and IL-18 protein levels and corneal perforation resulted. In vitro experiments using isolated splenic NK cells confirmed their ability to respond to IL-18 and SP and to secrete IFN-gamma protein. We conclude: that for development of the BALB/c resistance response, NK cells are required to produce IFN-gamma; that the cells express the neurokinin-1 receptor; and that SP directly regulates IFN-gamma production through this receptor. The data suggest a unique link between the nervous system and development of innate immunity in the cornea.     

Are single fractions of radiotherapy suitable for plantar fasciitis?

The use of radiotherapy for plantar fasciitis has never been reported in Australasia and is scarcely found in the English language medical literature, but it is commonly used in Europe, especially in Germany. In Europe, treatment courses consisting of multiple small fractions have been associated with high levels of pain relief. In the present report, the use of single fractions or radiotherapy was evaluated by reviewing seven consecutive patients referred for treatment and by applying objective and subjective criteria for pain relief. One patient died of unrelated causes soon after treatment and one declined to receive radiotherapy. Four patients each received a single dose of 8 Gy resulting in complete pain relief. One patient was treated with 8 Gy and 12 weeks later was retreated achieving partial pain relief. A follow‐up interview was conducted after a mean of 15.6 months, ranging from 1.5 to 30 months. No acute or late effects occurred; however, the possibility that delayed effects may yet occur, particularly carcinogenesis, cannot be excluded. Radiotherapy for this common condition should be investigated further as it might be safer and more effective than other methods currently in use.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.     

Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia

We studied ten normal subjects and 20 patients with stable, untreated idiopathic thrombocytopenic purpura (ITP) and platelet counts in the range of 35,000 to 110,000/microL. The diagnosis was made by clinical criteria. Platelet-associated IgG was increased in all nine of the nine patients studied. Autologous platelets were labeled with chromium 51 and reinfused for measurement of mean cell life and platelet production rate. Mean cell life was calculated by two methods, weighted mean and multiple hit, with excellent agreement between the two. As expected, mean cell life was significantly reduced in ITP patients as compared to the normal subjects (2.9 days v. 8.0 days, P less than .001). However, mean platelet production rates in ITP patients and normal subjects, 3.5 and 3.8 X 10(9) platelets/k/d respectively, were not significantly different. Platelet production rate was above and below the normal range (2 to 5.6 X 10(9) platelets/k/d) in two and four patients, respectively. We conclude that the rate of platelet production is not increased in most patients with ITP who have platelet counts greater than 35,000/microL. We did find that platelet size was increased in eight of the 12 patients in whom it was measured, including two of the patients with low platelet production.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.