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Despite its unique pattern and intensity, cluster headache is frequently confused with other headache disorders, leading to unnecessary suffering and delays in adequate treatment. [ABSTRACT FROM AUTHOR]

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk., Purpose: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication., Methods: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture., Results: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk., Conclusions: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap., (© 2023. The Author(s).)

This study describes the development of a decision aid (DA), aimed at supporting patients in their decision whether to start anti-osteoporosis medication. People with recent fractures or osteoporosis and health professionals were supportive of the DA initiative. An experimental study been started to assess (cost-)effectiveness of the DA., Purpose: At fracture liaison services (FLS), patients with a recent fracture ánd osteoporosis or a prevalent vertebral fracture are advised to start anti-osteoporosis medication (AOM). This study describes the development of a decision aid (DA) to support patients and healthcare providers (HCPs) in their decision about whether to start AOM., Methods: The DA was developed according to International Patient Decision Aid Standards (IPDAS). A systematic procedure was chosen including scope, design, prototype development, and alpha testing. A previously developed DA for women with osteoporosis was used as a basis. Furthermore, input from literature searches, the Dutch guideline on management of osteoporosis, and from people with a fracture or osteoporosis was used. The updated DA was evaluated during alpha testing., Results: The DA facilitates the decision of patients whether to initiate AOM treatment and provides information on fractures and osteoporosis, general risk factors that increase the likelihood of a subsequent fracture, the role of lifestyle, personalized risk considerations of a subsequent fracture with and without AOM treatment, and AOM options and their characteristics in an option grid. Alpha testing with 15 patients revealed that patient preferences and needs were adequately presented, and several suggestions for improvement (e.g. adding more specific information, simplifying terminology, improving icon use) were accounted for. Participants from the alpha testing recommended use of the DA during outpatient visits., Conclusion: Professionals and persons with osteoporosis were supportive of the proposed DA and its usability. The DA could help in a shared decision-making process between patients and HCPs., (© 2023. The Author(s).)

The anti-common gamma chain (gammac) mAb CP.B8 is shown to inhibit interleukin 4 (IL-4)-dependent proliferation of phytohemagglutinin (PHA) activated T cells noncompetitively with respect to cytokine by blocking the IL-4-induced heterodimerization of IL-4Ralpha and gammac receptor chains. Affinities for the binding of IL-4 to Cos-7 cells transfected with huIL-4Ralpha, and to PHA blasts expressing both IL-4Ralpha and gammac, were used to estimate the affinity of the key interaction between gammac and the binary IL-4Ralpha.IL-4 complex on the cell surface. This affinity was defined in terms of the dimensionless ratio [IL-4Ralpha.IL-4.gammac]/[IL-4Ralpha.IL-4], which we designate KR. The results show that on PHA blasts this interaction is relatively weak; KR approximately 9, implying that approximately 10% of the limiting IL-4Ralpha chain remains free of gammac even at saturating concentrations of IL-4. This quantitative treatment establishes KR as a key measure of the coupling between ligand binding and receptor activation, providing a basis for functional distinctions between different receptors that are activated by ligand-induced receptor dimerization.

The IL receptor common gamma (gamma c) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how gamma c chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human gamma c chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-gamma c mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the gamma c chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on gamma c chain required for its association with multiple ligands.

There are several short-lived paroxysmal head pain syndromes, many of which are responsive to indomethacin, and some of which are potentially ominous. Included in this article are icepick headache, hypnic headache syndrome, chronic paroxysmal hemicrania, cough headache syndrome, coital headache, and thunderclap headache.

Women with migraine often experience a worsening of symptoms at menopause. Use of exogenous estrogens is not helpful and may even exacerbate the condition. Although initial pharmacologic management generally is focused on control of individual headaches, attempts to stabilize the underlying migraine mechanism through serotonin receptor downregulation are likely to provide a better outcome.

Headache-prone patients have many highly effective therapeutic options open to them. Used only at the time of headache, sumatriptan succinate by mouth or injection and dihydroergotamine nasal spray are novel choices now or soon to be available. The original migraine therapy, ergotamine, is highly effective in its rectal suppository formulation, when used at a subnauseating dosage. Valproate sodium is the latest addition to the many therapies available for long-term stabilization.

The antimigraine efficacy of many drugs may be mediated less through their primary modes of action than through the common pathway of serotonergic transmission stabilization. Migraine treatment may be symptomatic, acute/abortive, or prophylactic. Because oral drug absorption is impaired during attacks, parenteral agents are more appropriate for acute therapy. Acute agents include ergots and ergotamine derivatives, narcotics, and sumatriptan succinate. Agents that activate the 5-HT3 receptors must be administered with an antiemetic. Sumatriptan succinate, a specific 5-HT1 receptor agonist, does not necessitate adjunctive antiemetics. Stabilization regimens, such as those using valproate, may favorably alter the natural history of migraine. Sumatriptan succinate is appropriate both for acute attacks and for symptomatic management during stabilization. beta-Blockers, tricyclic antidepressants, and calcium antagonists may be used prophylactically.

AIDS is a syndrome caused by HIV. The virus is spread by homosexual or heterosexual transmission and by infected blood or certain body fluids. Respiratory infections are the commonest cause of death, and diagnosis may be difficult. The fiberoptic bronchoscope (FOB) plays an essential role in diagnosing respiratory infections in AIDS and is important in minimizing the need for open lung biopsies. Various problems require thoracic surgical consultation and treatment. We do not consider it ethical to deny these patients help. There can be no "double standard" in the care of patients in the hospital or in the operating room since any of our patients may have HIV without our knowledge.

Rectal ergotamine and naproxen are the major candidates for the ad hoc treatment of migraine attacks; for particularly dramatic episodes, intravenous DHE with prochlorperazine is the author's preference. For long-term stabilization, after simpler measures fail, valproate appears to be a major addition to migraine therapy.

Slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus. There appear to be at least three pathophysiological mechanisms that cause this syndrome: 1) intermittent shunt malfunction; 2) intracranial hypotension; and 3) paroxysms of increased intracranial pressure in the presence of normal shunt function. To treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure, we successfully used antimigraine therapy rather than standard calvarial expansion procedures. None of these patients has required shunt revision or calvarial expansion during a mean follow-up period of 2 years. The symptoms of slit ventricle syndrome may be a form of "acquired" migraine in shunt patients. We suggest that, in clinically stable patients with normal shunt function, treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure. Such treatment may prevent unnecessary shunt revisions and/or calvarial expansion procedures.

August Bier, the father of spinal anesthesia, suffered and reported the first lumbar puncture (LP) headache. On August 24, 1898 his assistant, a Dr. Hildebrandt, attempted to administer a spinal anesthetic to Dr. Bier; it was never completed because the syringe did not fit the already implanted spinal needle. Bier himself suggested that continued leakage of cerebrospinal fluid (CSF) through the dural puncture site was the cause of headache, a theory that has been embraced by the medical community; however, the mechanism is probably more complex. Nearly 50 years ago, J. Lawrence Pool, using an endoscopic technique to visualize the surface of the spinal cord and the cauda equina, frequently observed large collections of epidural fluid two to four days following lumbar puncture in patients without headache. Evidence that will be presented below suggests that CSF volume alterations may be the signal closest to the headache mechanism.

Dependence upon a variety of drugs--ergotamine, analgesics, benzodiazepines, corticosteroids--is a major reason for patients to enter an intractable phase of their migrainous disorders. Repeated dosing of dihydroergotamine has proven to be remarkably effective in stabilizing the mechanism of migraine, allowing these patients to make the transition to a more reasonable as well as more specific form of therapy.

Stabilization of serotonergic neurotransmission by depressing the activity of serotonergic neurons may be the common mode of action of drugs effective in migraine. By serotonin receptor agonism, by prolonging the biologic half-life of serotonin in the synaptic cleft (through blockade of its re-uptake or metabolic degradation), by an increase in its synthesis, by inhibiting the release of serotonin, or by activation of cyclic AMP (fig), a unitary expression for the action of these drugs can be formulated which is corroborated, for many of the drugs, by direct measurement of serotonergic neuronal firing rates. However, there are at least three serotonin receptor sites in brain at which drugs would be effective, as assessed by differential responsiveness to agonists and antagonists and by different types of postsynaptic responses: presynaptically, postsynaptically, and at the autoreceptor itself. The locus of action for the antimigraine drugs may be primarily at the raphe, upon the serotonin neurons per se, but it will probably prove to be more complex as more data are generated.

Mononuclear leukocytes from 151 patients with cancer of various organs and from 467 apparently cancer-free individuals were exposed, in vitro, to H2O2 (100 microM) and the effects of the exposure on the activity of adenosine diphosphate ribosyl transferase (ADPRT) were determined. First, the reproducibility of this test procedure was established as satisfactory, by comparing the results of assays performed independently by two investigators, and by measuring ADPRT in cells from two individuals over a 9-week period. The test data were analyzed by multiple linear regression, and the correlation of cancer diagnosis, age, sex and smoking habits with ADPRT values was determined. The strongest correlate was cancer diagnosis. We considered categorizing ADPRT values as high and low, with a cut-off value that would substantially distinguish cancer from cancer-free individuals. When a cut-off value of 1200 c.p.m. TCA ppt [3H]NAD+/5 x 10(5) cells was applied to the complete test material, it was found that ADPRT values from cancer patients were more frequently below the cut-off than values from disease-free individuals: the relative risk estimate (odds ratio) was 13.8. When a similar analysis was done on values from lung cancer patients and smoking disease-free individuals, the odds ratio was 73.5. However, a cut-off value of 2000 c.p.m. TCA ppt [3H]NAD+/5 x 10(5) cells was most effective in distinguishing lung cancer patients (the largest cancer group, n = 96) from smoking non-cancer individuals: that value provided better sensitivity (85%) and specificity (81%) than other cut-off values tested in the range 1200-2000 c.p.m. Further, in the case of lung cancer, possible effects of anatomical site, and of staging and pathology on ADPRT values was analyzed by the chi-squared test: no significant associations were found. These data support the value of the ADPRT test in detecting early stage lung cancer regardless of location or pathological type.

Large defects of the chest wall require stabilization of the remaining thorax to prevent paradoxical movement. A technique of fixation using rib grafts and compression plates is presented.

Lung cancer remains the greatest killing cancer in the United States with 149,000 new cases expected in 1987. The present expected mortality rate is 87 per cent. More women in the United States died of lung cancer than breast cancer in 1986. Asymptomatic, early and curable lung cancer in high risk individuals is usually found by routine chest X-ray. So-called Stage I lung cancer was reported to have a 83 per cent survival rate at three years by Martini and Beattie in 1977 and 70 per cent five year survival rate subsequently. When the more than 30,000 volunteer males were enrolled in the National Cancer Institute, national lung program for screening, 223 unsuspected lung cancers were found. 47 per cent were Stage I with a survival rate at five years of over 76 per cent. The PMI-Strang/Memorial Sloan Kettering Cancer Center study found 53 cancers in its first screen and 235 lung cancers over the next eight years of the study. Forty per cent were Stage I with a five year survival rate of 70 per cent. Sputum cytology as compared to chest X-ray was of little additional value. Studies (Martini) of Nl lung cancer was found to have a 49 per cent survival rate following resection. The N2 group of lung cancers where the mediastinal tumor was surgically removable and followed by external radiation therapy had a 27 per cent survival rate at five years. Those tumors with solitary brain metastases where the solitary brain metastasis could be resected and the primary tumor controlled, gave a 27 per cent survival rate at six years. The group of advanced N2 disease where the mediastinum could not be completely cleared were a serious group of cancers. A study of 100 patients treated from 1977 to 1980 with surgery plus internal radiotherapy followed by external radiotherapy had an overall 22 per cent survival rate for four to eight years with most of the deaths occurring because of metastases outside the chest. More recently chemotherapy has been used pre-operatively for those individuals with advanced lung cancer in the chest then followed by a combination of surgery, internal radiotherapy, external radiotherapy and more chemotherapy, if chemotherapy sensitive. This is the so-called multidisciplinary approach. In our present early studies it seems that those so treated who are chemotherapy sensitive have a 44 per cent, two year survival rate in a group of patients considered to have extremely poor prognosis.

For patients with chronic intractable headache, we compared a new treatment and a traditional one. Fifty-five patients (36 dependent on ergotamine, analgesics, diazepam, or corticosteroids) were given IV dihydroergotamine (DHE) and metoclopramide every 8 hours. Fifty-four age- and sex-matched patients (38 drug-dependent) were given diazepam intravenously every 8 hours. Forty-nine of the 55 DHE-treated patients became headache-free within 48 hours, and 39 of them sustained benefits in a mean follow-up of 16 months. In contrast, 7 diazepam-treated patients became free of headache within 3 to 6 days, and 31 had improved somewhat in 10 days. Repetitive IV DHE helps to terminate cycles of intractable migraine.

Genetic analysis of susceptibility to experimental allergic encephalomyelitis (EAE) was performed in guinea-pigs. The results indicate the existence of two Ir genes to EAE in susceptible strain 13 guinea-pigs. One gene is linked to the major histocompatibility complex (MHC) of this species, while the other one is located outside the MHC. The two genes segregate independently and both of them must be expressed to render the animal susceptible to EAE.