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Pilocarpine for xerostomia after irradiation for cancer of head and neck
113 right time (in humans) and in mice will cause type I diabetes. These results open the possibility of a therapy based on blocking the action of alpha interferon. T Stewart t I ) Genentech Inca. South San Francisco. CA 94080, USA
Detection of cytokines in breast disease: the reverse haemolytic plaque assay. Solid tumours and their metastases comprise not only the malignant cell population but large numbers of tumour-infiltrating host inflammatory cells. Communication between these cells is mediated by the local release of a complex network of cytokines and growth factors. Many of these molecules are produced by more than one cell type and/or have overlapping biological activities; thus, bio- or immunoassays which measure their accumulated release can yield ambiguous results. As a result, the elucidation of the cytokine network of solid tumours is still in its infancy and the net effect of these signalling peptides on tumour growth is poorly understood. We have adapted a bioassay known as the reverse haemolytic plaque assay (RHPA) to detect the release of cytokines and growth factors from individual cells derived from breast tumour biopsies. Cytokine secretion is observed as an area of haemolysis around the central secreting cell. the phenotype of which is subsequently identified by immunocytochemical means. Thus, the RHPA has the potential not only to identify which cytokines are inherent to a given biological system eg the tumour microenvironment, but also to accurately define the cellular source of secretion. By way of this technique, we recently demonstrated that in a proportion of breast cancer patients, epidermal growth factor (EGF), a putative tumour growth factor, was released by normal host macrophages which had infiltrated the tumour. Hitherto, the accepted dogma had been that EGF was secreted by the breast cancer cells themselves, and in an autocrine fashion since it is upon these cells that the receptor for EFG has been located. Since over-expression of the EGF receptor in breast cancer is known to confer a poor prognosis, secretion of the mitogen by normal host inflammatory cells contradicts the purported defensive role of at least a proportion of tumour-infiltrating cells. C O’Sullivan (2) John Radcliffe Hospital, University of Oxford. Oxford OX3 9Dt.J. UK
Pilocarpine for xerostomia head and neck.
after irradiation
for cancer of
Patients with radiation-induced xerostomia have oral discomfort, increased susceptibility to dental carries, and difficulty in speaking, chewing, and swallowing. (I) Science (2) Lancer
1993; 260: 1942 1993; 342:148
The parasympathomimetic agent. Pilocarpine, stimulates the exocrine gland resulting in diaphoresis and salivation. This prospective randomized double-blind placebo-controlled trial studied 207 patients who had received greater than 4000 cGy of radiation to the head and neck. Patients were randomized to receive either placebo. Pilocarpine 5 mg. or Pilocarpine IO mg three times per day. Patients receiving Pilocarpine demonstrated an overall improvement when compared to the group receiving placebo. Improvement in comfort of the mouth, speaking ability and saliva production was also noted in the Pilocarpine groups. The primary adverse effect was sweating in addition to other minor cholinergic effects. Pilocarpine improved salivation and relieved symptoms of xerostomia. Side effects were minor and predominantly limited to diaphoresis. JT Johnson (3) University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. USA
Outpatient fever.
treatment
for sickle cell patients
who have
For children with sickle cell disease (a common genetic disorder of the red blood cells), fever can signal a potentially fatal infection. Because of this risk, sickle cell patients have been routinely hospitalized for intravenous antibiotic therapy each time they have a fever. With the availability of longer acting antibiotics came the hope of outpatient treatment. However, critical questions remain to be answered. Would outpatient care be safe? Could children with an especially high risk of severe infection (sepsis) be identified in advance? To answer these questions, we began a study in which patients who had fever were evaluated in the emergency room, where they received an initial antibiotic injection. Children (86) who met the study’s risk criteria were assigned randomly to outpatient or impatient groups, while the “higher-risk” patients were all treated in the hospital. The study criteria succeeded in identifying patients for whom outpatient treatment might not be advisable. There were seven episodes of sepsis among the higherrisk patients but none in the other two groups. Equally important, outpatient treatment with a second antibiotic injection proved both safe and effective. Each instance of outpatient care saved an average of $ I, I95 in medical costs and was less disruptive to the lives of patients and parents. JA Wilimas (4) St Jude Children’s Research Hospital, Memphis, Tennessee, 38101-0318. USA
(3) N Engl J Med (4) N Engl J Med
1993; 1993;
329:390 329~472
Detection of cytokines in breast disease: the reverse haemolytic plaque assay. Solid tumours and their metastases comprise not only the malignant cell population but large numbers of tumour-infiltrating host inflammatory cells. Communication between these cells is mediated by the local release of a complex network of cytokines and growth factors. Many of these molecules are produced by more than one cell type and/or have overlapping biological activities; thus, bio- or immunoassays which measure their accumulated release can yield ambiguous results. As a result, the elucidation of the cytokine network of solid tumours is still in its infancy and the net effect of these signalling peptides on tumour growth is poorly understood. We have adapted a bioassay known as the reverse haemolytic plaque assay (RHPA) to detect the release of cytokines and growth factors from individual cells derived from breast tumour biopsies. Cytokine secretion is observed as an area of haemolysis around the central secreting cell. the phenotype of which is subsequently identified by immunocytochemical means. Thus, the RHPA has the potential not only to identify which cytokines are inherent to a given biological system eg the tumour microenvironment, but also to accurately define the cellular source of secretion. By way of this technique, we recently demonstrated that in a proportion of breast cancer patients, epidermal growth factor (EGF), a putative tumour growth factor, was released by normal host macrophages which had infiltrated the tumour. Hitherto, the accepted dogma had been that EGF was secreted by the breast cancer cells themselves, and in an autocrine fashion since it is upon these cells that the receptor for EFG has been located. Since over-expression of the EGF receptor in breast cancer is known to confer a poor prognosis, secretion of the mitogen by normal host inflammatory cells contradicts the purported defensive role of at least a proportion of tumour-infiltrating cells. C O’Sullivan (2) John Radcliffe Hospital, University of Oxford. Oxford OX3 9Dt.J. UK
Pilocarpine for xerostomia head and neck.
after irradiation
for cancer of
Patients with radiation-induced xerostomia have oral discomfort, increased susceptibility to dental carries, and difficulty in speaking, chewing, and swallowing. (I) Science (2) Lancer
1993; 260: 1942 1993; 342:148
The parasympathomimetic agent. Pilocarpine, stimulates the exocrine gland resulting in diaphoresis and salivation. This prospective randomized double-blind placebo-controlled trial studied 207 patients who had received greater than 4000 cGy of radiation to the head and neck. Patients were randomized to receive either placebo. Pilocarpine 5 mg. or Pilocarpine IO mg three times per day. Patients receiving Pilocarpine demonstrated an overall improvement when compared to the group receiving placebo. Improvement in comfort of the mouth, speaking ability and saliva production was also noted in the Pilocarpine groups. The primary adverse effect was sweating in addition to other minor cholinergic effects. Pilocarpine improved salivation and relieved symptoms of xerostomia. Side effects were minor and predominantly limited to diaphoresis. JT Johnson (3) University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. USA
Outpatient fever.
treatment
for sickle cell patients
who have
For children with sickle cell disease (a common genetic disorder of the red blood cells), fever can signal a potentially fatal infection. Because of this risk, sickle cell patients have been routinely hospitalized for intravenous antibiotic therapy each time they have a fever. With the availability of longer acting antibiotics came the hope of outpatient treatment. However, critical questions remain to be answered. Would outpatient care be safe? Could children with an especially high risk of severe infection (sepsis) be identified in advance? To answer these questions, we began a study in which patients who had fever were evaluated in the emergency room, where they received an initial antibiotic injection. Children (86) who met the study’s risk criteria were assigned randomly to outpatient or impatient groups, while the “higher-risk” patients were all treated in the hospital. The study criteria succeeded in identifying patients for whom outpatient treatment might not be advisable. There were seven episodes of sepsis among the higherrisk patients but none in the other two groups. Equally important, outpatient treatment with a second antibiotic injection proved both safe and effective. Each instance of outpatient care saved an average of $ I, I95 in medical costs and was less disruptive to the lives of patients and parents. JA Wilimas (4) St Jude Children’s Research Hospital, Memphis, Tennessee, 38101-0318. USA
(3) N Engl J Med (4) N Engl J Med
1993; 1993;
329:390 329~472