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R B Lipton

Publications and source records attributed to R B Lipton.

At least 19 recordsLinked to original sources
PubMed1992

Autoimmunity and genetics contribute to the risk of insulin-dependent diabetes mellitus in families: islet cell antibodies and HLA DQ heterodimers.

The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody-negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies may be relatively common, it progresses only in those with variant HLA-DQ molecules.

Adolescent↗
PubMed1992

Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors.

OBJECTIVE: To describe the magnitude and distribution of the public health problem posed by migraine in the United States by examining migraine prevalence, attack frequency, and attack-related disability by gender, age, race, household income, geographic region, and urban vs rural residence. DESIGN: In 1989, a self-administered questionnaire was sent to a sample of 15,000 households. A designated member of each household initially responded to the questionnaire. Each household member with severe headache was asked to respond to detailed questions about symptoms, frequency, and severity of headaches. SETTING: A sample of households selected from a panel to be representative of the US population in terms of age, gender, household size, and geographic area. PARTICIPANTS: After a single mailing, 20,468 subjects (63.4% response rate) between 12 and 80 years of age responded to the survey. Respondents and non-respondents did not differ by gender, household income, region of the country, or urban vs rural status. Whites and the elderly were more likely to respond. Migraine headache cases were identified on the basis of reported symptoms using established diagnostic criteria. RESULTS: 17.6% of females and 5.7% of males were found to have one or more migraine headaches per year. The prevalence of migraine varied considerably by age and was highest in both men and women between the ages of 35 to 45 years. Migraine prevalence was strongly associated with household income; prevalence in the lowest income group (less than $10,000) was more than 60% higher than in the two highest income groups (greater than or equal to $30,000). The proportion of migraine sufferers who experienced moderate to severe disability was not related to gender, age, income, urban vs rural residence, or region of the country. In contrast, the frequency of headaches was lower in higher-income groups. Attack frequency was inversely related to disability. CONCLUSIONS: A projection to the US population suggests that 8.7 million females and 2.6 million males suffer from migraine headache with moderate to severe disability. Of these, 3.4 million females and 1.1 million males experience one or more attacks per month. Females between ages 30 to 49 years from lower-income households are at especially high risk of having migraines and are more likely than other groups to use emergency care services for their acute condition.

Adolescent↗
PubMed1992

Undiagnosed migraine headaches. A comparison of symptom-based and reported physician diagnosis.

BACKGROUND: Although migraine headaches are a common cause of temporary disability, many people with migraine have not been diagnosed. In a sample of the US population, we sought to determine the proportion of migraineurs diagnosed by a physician and to identify the headache characteristics and sociodemographic profiles associated with undiagnosed migraine. METHODS: A mail questionnaire survey was sent to 15,000 US households, selected from a panel to be representative of the US population. Of a total study base population of 23,611, excluding 3043 subjects less than 12 years of age and respondents with unreported gender, we analyzed data for 20,468 subjects aged 12 to 80 years. Migraine diagnoses were assigned on the basis of reported symptoms by means of operational diagnostic criteria. Physician diagnosis of migraine was ascertained on the basis of self-report. RESULTS: Forty-one percent of female and 29% of male migraineurs reported having been diagnosed by a physician. Diagnosis was more likely in females, in people with high income levels, and in individuals who reported migraine associated with aura, vomiting, or disability. Of the undiagnosed subjects, 80% experienced at least some headache-related disability. CONCLUSIONS: Results of this survey indicate that the majority of people with migraine in the United States do not report having been diagnosed by a physician. Given the high proportion of undiagnosed subjects with headache-related disability, efforts to improve the diagnosis and treatment of migraine are recommended.

Adolescent↗
PubMed1992

Genetic, immunological, and metabolic determinants of risk for type 1 diabetes mellitus in families.

Prospective studies of the relatives of people with Type 1 diabetes can provide insights into risk factors for processes leading to the ultimate destruction of the pancreatic islet B-cells. Relatives ascertained through the Children's Hospital of Pittsburgh diabetes registry were followed and rates of conversion to diabetes were determined. We studied the role of genetic and immunological markers, and used the oral glucose tolerance test (OGTT) to study metabolic disturbances among first-degree relatives. A group of siblings was serotyped for the HLA-A and -B antigens, and the degree of HLA haplotype sharing with the diabetic sibling was established. Later, islet cell antibody (ICA) assays were performed, and subjects were followed to determine the predictive value of ICA testing for the subsequent development of diabetes. The rate of conversion to diabetes among the siblings was 14 times greater than the rate observed in the general population from which they come. This is comparable to rates observed by other centres following relatives of people with Type 1 diabetes. Impaired glucose tolerance (by National Diabetes Data Group (USA) criteria) carried a three-fold greater risk for subsequent Type 1 diabetes than did a normal OGTT. Those relatives with detectable ICA were about 50 times more likely to convert to diabetes than were those without ICA. In a group of siblings in whom HLA haplotype sharing was determined, the prevalence of detectable ICA was greater among those who were HLA-identical to the diabetic sibling (9.9%) than among those who were haplo-identical (5.3%) or completely dissimilar (2.4%) at the HLA-A and -B regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Evaluation of chronic daily headache--comparison to criteria for chronic tension-type headache.

The purpose of this study was to evaluate the adequacy of the International Headache Society (IHS) criteria for chronic tension-type headache and, if appropriate, suggest modifications of the IHS classification. We evaluated 100 consecutive patients with chronic daily headache. Approximately two-thirds of our patients fulfilled the criteria for chronic tension-type headache. Most of the patients who failed to meet the criteria did so because they had more than one migrainous feature. Approximately 50% of patients took excessive amounts of analgesic medication. We conclude that the IHS criteria should be modified to include chronic daily headache evolving from migraine; subtypes with and without medication overuse should be distinguished.

Adolescent↗
PubMed1992

Chronic paroxysmal headache: two cases with cerebrovascular disease.

Paroxysmal headaches often occur in benign headache disorders such as episodic cluster headache, chronic paroxysmal hemicrania (CPH) and episodic paroxysmal hemicrania. We report 2 patients with paroxysmal headaches occurring in association with cerebrovascular disease. The first patient had paroxysmal headaches from an arteriovenous malformation which resolved following embolization. In the second patient, headache followed a cerebral infarction and responded to treatment with indomethacin. We suggest that vascular disease may cause paroxysmal headaches resembling CPH. Patients with an atypical presentation of CPH warrant a neuroimaging procedure.

Adult↗
PubMed1992

Medication use and disability among migraineurs: a national probability sample survey.

OBJECTIVE: To measure the use of prescription medication in treating migraine headache and the associations between medication use and sociodemographic factors, and headache characteristics. DESIGN: National sample survey using a mailed questionnaire to determine symptoms accompanying or preceding severe headaches; frequency, duration, and disability from severe attacks: use of medications to control pain; and medical-care use for severe headaches. SETTING: A stratified sample of United States households. PATIENTS: A sample of 20,468 respondents, aged 12 to 80 years, who responded to a survey on "severe" headaches during the prior year. MEASUREMENTS AND MAIN RESULTS: Overall, 20.2% of respondents reported severe headaches. Migraine was found in 17.6% of females and 5.7% of males. Of the migraineurs, 40.1% of female and 28.3% of male migraineurs reported using prescription drugs to control pain. Blacks were less likely than whites to report prescription use. Insignificant differences were seen in rates of prescription use among various income levels and regions of the country. Use of prescription medication varied considerably by symptoms and characteristics of migraine attacks. Vomiting and sensory aura were most frequently associated with medication use, as were severity and duration of attacks. Use of urgent-care services for severe headache attacks was associated with frequent use of prescription medications. Patients who reported a physician diagnosis of migraine were more likely to use prescription medication than other migraineurs. CONCLUSIONS: Most migraineurs in the United States are not being treated with prescription medications. Many active migraine patients would benefit from appropriate treatment if care was sought and diagnosis made.

Adolescent↗
PubMed1992

Hemicrania continua: attacks may alternate sides.

Hemicrania continua (HC) is characterized by a continuous unilateral headache of moderate severity, occurring in 2 patterns; a continuous form in which headaches persist continuously without remission for years, and a remitting form, consisting of headache phases separated by periods of pain-free remission. The remitting form of HC must be distinguished from other cyclical headache disorders such as episodic paroxysmal hemicrania and episodic cluster headache. Characteristically, the headache of HC is unilateral and without sideshift. We now report a case of HC in which headaches alternate sides.

Aged↗
PubMed1992

Childhood onset cluster headaches.

Cluster headaches are rare in childhood. We identified 35 patients with cluster headaches starting at or before 18 years of age, including 7 patients with onset prior to age 10. All patients met the criteria of the International Headache Society for episodic or chronic cluster headaches. Patients experienced cluster headaches for as long as 20 years before seeking medical attention and required many medical contacts to establish the correct diagnosis. The clinical features of cluster headaches during childhood were similar to those which typically occur in adult life. Cluster headache patterns changed over 18 years of follow up. The frequency and duration of cluster periods increased in 14 subjects. The frequency of single headache attacks during cluster periods also increased in a similar number of subjects. We conclude that cluster headaches starting in childhood or adolescence closely resemble the adult form of the disease. In many patients, the frequency and duration of cluster periods and the frequency of the individual headache episodes increased over time. Cluster headache represent a treatable under-recognized cause of severe headaches in childhood and adolescence.

Adolescent↗
PubMed1992

Clinical features of chronic daily headache.

Patients with chronic daily headaches are commonly encountered in headache specialty centers but their clinical characteristics have rarely been documented. We studied 100 consecutive patients with chronic daily headache to determine their presenting characteristics and other associated features. Half of the patients described their headache as a steady ache but throbbing pain was reported in about one third. About half estimated the degree of pain as moderate but one third claimed the typical pain was severe. A consistently unilateral site was noted in only 2 percent. Associated features characteristic of migraine were often noted: Including photophobia (37 percent), photophobia (42 percent), and nausea (24 percent). Many also reported aggravating and ameliorating factors commonly associated with migraine. We conclude that the manifestations of chronic daily headache are extremely diverse, probably reflecting the heterogeneous mechanisms which underlie this condition.

Adolescent↗
PubMed1992

Amyloid angiopathy in diffuse Lewy body disease.

We determined the frequency of cerebral amyloid angiopathy (CAA) in 135 consecutive cases of diffuse Lewy body disease (DLBD) (N = 67), Alzheimer's disease (AD) (N = 34), and normal elderly controls (NECs) (N = 34). DLBD cases were subdivided into those with pathologic changes compatible with coexistent AD (DLBD/AD) and those without sufficient AD-type changes to warrant that diagnosis. In each case, we assessed the frequency, severity, and distribution of CAA on multiple thioflavin-S-stained sections of cerebral cortex examined with fluorescent microscopy. Based on immunocytochemistry with beta-amyloid antibodies, amyloid in all the brains was composed of beta/A4. CAA was present in the leptomeningeal vessels in 50% of the NECs and in 100% of AD cases. In DLBD without coexisting AD, the frequency of leptomeningeal CAA was 58%, whereas in DLBD/AD, the frequency was 85%. The frequency of CAA in parenchymal vessels was 38% for NECs, 97% for AD, 43% for DLBD, and 85% for DLBD/AD. There was no significant difference in the frequency or severity of CAA between NECs and DLBD, but CAA was significantly more severe, and comparable with CAA in AD, in the cases of DLBD/AD. Ten NECs had focal CAA without senile plaques (SPs), whereas all other cases with CAA had at least some SPs. Neither CAA nor SPs were present in 14 cases, including seven NECs and seven DLBD cases. We found cerebrovascular accidents in 50 cases (including nine without CAA) and leukoencephalopathy in 24 cases. These results suggest that CAA and other AD-type changes are not concomitant with DLBD but are related to coexisting AD or pathologic aging.

Alzheimer Disease↗
PubMed1992

Episodic paroxysmal hemicrania: two new cases and a literature review.

Episodic paroxysmal hemicrania (EPH) is a rare disorder characterized by discrete bouts of hemicranial headache separated by headache-free remissions. Although EPH resembles episodic cluster headache in the location and quality of pain as well as the pattern of associated autonomic features, it is distinguished by the greater frequency and shorter duration of individual headaches. Differentiation of these disorders is important because EPH almost invariably responds to treatment with indomethacin but not to standard cluster headache therapy.

Adult↗
PubMed1992

The persistent vegetative state: an analysis of clinical correlates and costs.

A review was compiled of 23 patients in the persistent vegetative state; a condition that developed while the patients were in an acute care hospital. Before the onset of the persistent vegetative state, eight patients had had dementia, 11 were functionally dependent, and seven had neurologic disorders that gradually led to the persistent vegetative state. For patients in the persistent vegetative state, three types of mechanical support--respirators, nasogastric or gastrotomy tubes, and intravenous lines--were utilized. All three were necessary in 43% of patients, two types in 52%, and one type in 4%. All patients in the persistent vegetative state required at least one type of mechanical assistance. Their course was complicated in all cases by incontinence, and in the majority, by decubiti, pneumonia, and urinary tract infection. Only one patient improved enough to be able to say a few words. These patients required active medical care and invasive procedures that were costly but futile. The hospital bills obtained for 13 patients averaged $170,000, and the length of stay for all patients averaged 197 days, the equivalent to a total number of bed-days of 12.5 bed-years. The poor outcomes, requirements for mechanical support, and frequency of complications--especially when neurologic impairments were present before the onset of the persistent vegetative state--should be considered when evaluating the cost in hospital bills and bed occupancy.

Adult↗
PubMed1991

Nerve growth factor prevents toxic neuropathy in mice.

Taxol is a promising new antitumor drug with therapeutic use that is limited by a toxic sensory neuropathy. Taxol is also cytotoxic to dorsal root ganglion neurons in vitro, but this effect is prevented by cotreatment with the trophic protein, nerve growth factor. We sought to develop an animal model and then to determine whether nerve growth factor can prevent taxol neuropathy in vivo. Administration of taxol to mice resulted in a profound sensory neuropathy characterized by decreases in dorsal root ganglion content of the peptide neurotransmitter, substance P, elevated threshold to thermally induced pain, and diminished amplitude of the compound action potential in the caudal nerve. Coadministration of nerve growth factor prevented all of these signs of neurotoxicity. These findings suggest that administration of nerve growth factor may prevent certain toxic sensory neuropathies.

Alkaloids↗
PubMed1991

Commentary: the affected sib-pair method in the context of an epidemiologic study design.

The purpose of this commentary is to provide a framework for using the well-known sib-pair methodology in the context of epidemiologic study designs. Using examples from the Pittsburgh family studies of insulin-dependent diabetes mellitus, we illustrate that the sib-pair method can be used in family-based epidemiologic studies. In a cohort study, unaffected relatives of probands ascertained from well-defined populations are followed for disease development. Disease risks are then stratified according to the number of alleles at one or more loci (0, 1, 2) that are identical by descent (ibd) with the proband. In the absence of linkage between the marker locus and the disease locus, disease risks are expected to be identical in the three groups. Measures of relative risk can be computed (with share-0 as baseline group). In a case-control study, relatives of probands that become affected (cases) are compared to a sample of relatives of probands that stay unaffected (controls) with respect to the number of alleles ibd with the proband. Measures of odds ratio can be computed (with share-0 as baseline group). In both cohort and case-control approaches, covariates including other genetic markers and environmental exposures can be evaluated in relation to disease risk and also for evidence of interaction with the specific marker of interest using stratified and multivariate analyses. Family-based epidemiologic studies allow investigators to study, in a single design, the role of environmental factors and specific gene loci in the etiology of diseases.

Alleles↗