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Biomedical subjects

M Sadler

Publications and source records attributed to M Sadler.

At least 37 records · Page 2Linked to original sources

Management of intracerebral lesions in patients with HIV: a retrospective study with discussion of diagnostic problems.

A total of 95 patients who presented in 1994 and 1995 with focal brain lesions at a London HIV centre were studied retrospectively. Patients were allocated to "definite" or "presumed" diagnostic categories of toxoplasma encephalitis (TE), primary CNS lymphoma (PCNSL) or progressive multifocal leukoencephalopathy (PML), based on strict criteria. The number in each category was: TE, 20; PCNSL, 9; PML, 7; presumed TE, 12; presumed PCNSL, 8 and presumed PML, 17. There were 20 patients in whom a diagnosis could not be made, and there were three non-HIV diagnoses. Demographic data, features at presentation and routine CSF analysis were not discriminatory in making a diagnosis. Toxoplasma titres were a median of 1:256 in those with TE compared to 1:16 in all other groups (p < 0.001) and those with TE were less likely to be on toxoplasma prophylaxis compared to those with PCNSL (p < 0.002). Survival with TE (median of 446 days) was significantly longer than survival in all other groups. Survival with either confirmed or presumed PML was similar. The problems of diagnosis of focal brain lesions in HIV patients are discussed and a management flow chart for mass lesions is proposed.

AIDS-Related Opportunistic Infections↗

Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management.

Distal symmetrical peripheral neuropathy is a common adverse experience in persons with HIV infection. This condition, which presents as a pain, numbness. burning and/or dysaethesia initially in the feet, is often multi-factorial in its origin. Nucleoside analogue reverse transcriptase inhibitors represent an important contributor to peripheral neuropathy. Specifically, around 10% of patients receiving stavudine or zalcitabine and 1 to 2% of didanosine recipients may have to discontinue therapy with these agents due to neuropathy. Prompt withdrawal of these therapies enables gradual resolution of signs and symptoms in most patients, although a period of symptom intensification may occur shortly after withdrawal. Risk factors for developing peripheral neuropathy during nucleoside analogue therapy include low CD4+ cell count (<100 cells/mm3), a prior history of an AIDS defining illness or neoplasm, a history of peripheral neuropathy, use of other neurotoxic agents including high alcohol (ethanol) consumption and nutritional deficiencies such as low serum hydroxocobalamin levels. Thus, patients at increased risk of peripheral neuropathy should potentially avoid the use of the neurotoxic nucleoside analogues or be more carefully monitored during therapy. Management of this problem includes patient education. prompt withdrawal of the likely causative agent (giving consideration not to leave the patient on a sub-optimal therapy regimen) and simple analgesia. with augmentation with tricyclic antidepressants or anticonvulsant agents when pain is severe. New agents that may assist in managing this condition include levacecarnine (acetyl-L-carnitine) and nerve growth factors such as recombinant human nerve growth factor.

Clinical Trials, Phase I as Topic↗

Cross sensitivity of skin rashes with antiepileptic drugs.

BACKGROUND: Skin rashes are a well known complication of antiepileptic drug (AED) treatment. It has also been recognized that some patients will develop rashes from multiple AEDs (cross sensitivity). There are very few studies that have attempted to determine the frequency of cross sensitivity among AEDs. METHODS: Charts of all patients attending an epilepsy outpatient clinic were reviewed to determine AED exposure and the occurrence of a rash from AEDs. RESULTS: 633 patients had 1,875 exposures to 14 AEDs. Rashes occurred from carbamazepine (N = 27), phenytoin (N = 21), phenobarbital (N = 5) and lamotrigine (N = 1). A rash from 2 or more AEDs occurred in 14 patients and involved predominantly carbamazepine and phenytoin. Among the patients exposed to both phenytoin and carbamazepine 10/17 (58%) of patients with a rash from phenytoin also had a rash from carbamazepine; conversely 10/25 (40%) patients with a carbamazepine rash also had a rash from phenytoin. 4/5 patients with a phenobarbital rash were sensitive to carbamazepine and/or phenytoin. Amongst the other most commonly used AEDs no rashes occurred from valproic acid or clobazam. CONCLUSIONS: The cross sensitivity rate for rashes involving carbamazepine and phenytoin is 40-58%. If a rash develops from either of these AEDs, valproate or clobazam are safe alternatives.

Adult↗

Serum total cholesterol and risk of hospitalization, and death from respiratory disease.

BACKGROUND: In earlier studies, serum total cholesterol was inversely associated with death due to respiratory diseases. METHODS: Relationships of cholesterol with risk of respiratory diseases were examined between 1978 and 1993 in a health maintenance organization in Northern California (48,188 men, 55,276 women, about 60% white, age range 25-89). Incident and fatal endpoints were ascertained using hospital discharge diagnostic codes and underlying cause of death, respectively. RESULTS: An inverse association of cholesterol level with pneumonia/influenza hospitalization was found among men and women except that, contrary to hypothesis, a positive association was seen in women under 55 years of age. Inconsistent inverse associations were found in men, but not women, between cholesterol level and hospitalization for chronic obstructive pulmonary disease (COPD). Hospitalization for asthma was unrelated to cholesterol level. An inverse association existed between cholesterol level and hospitalization for miscellaneous respiratory diseases among men, but not women. Exclusion of early hospitalizations tended to attenuate risk for cholesterol level below 4.14 mmol/l, but not the risk gradient across higher cholesterol levels. For deaths, cholesterol level was statistically significantly inversely associated only with COPD. CONCLUSIONS: Cholesterol had graded inverse associations with some respiratory diseases, but not others, tending to be stronger in men than in women, and in older than in younger participants. Associations varied for hospitalizations compared to deaths. More epidemiological and basic research is needed to elucidate the potential mechanisms underlying the observed associations.

Adult↗

Serum screening for Down's syndrome: how much do health professionals know?

OBJECTIVE: To assess knowledge about serum screening for Down's syndrome in health professionals involved in antenatal care. DESIGN: Postal questionnaire survey of knowledge of performance and interpretation of serum screening. SETTING: Portsmouth and South East Hampshire health district. POPULATION: All health professionals likely to be involved in antenatal care. METHODS: Questionnaires were sent to all general practitioners (n = 288), hospital midwives (n = 129), community midwives (n = 71), and obstetricians (n = 29) working in the district. MAIN OUTCOME MEASURES: Total number of correct responses given to eight factual questions and percentage of correct responses to each individual question. RESULTS: Responses were received from 434 health professionals (84%). Fifty-nine percent of health professionals correctly answered only a half or less of the factual questions on serum screening. Questions relating to the sensitivity, specificity, and positive predictive value were particularly poorly answered. Obstetricians scored most highly. General practitioners scored significantly less than the other groups. CONCLUSIONS: Women need accurate information to give informed consent to serum screening. Most health professionals likely to be involved in antenatal care in this district do not fully understand the test and are thus unlikely to provide such information. Changes in the provision of maternity services following Changing Childbirth may increase the input of midwives and general practitioners. Training of professionals about serum screening should be reviewed.

Down Syndrome↗

Progressive multifocal leukoencephalopathy in HIV.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by infection of oligodendrocytes by JC virus. As patients with HIV survive longer with severe immunodeficiency, the incidence of PML is rising. Diagnosis is not always easy and the gold standard remains histological confirmation of the characteristic lesions of PML which requires a brain biopsy. This is considered too invasive by many clinicians and patients alike and detection of JC virus DNA in the cerebrospinal fluid (CSF) using polymerase chain reaction (PCR) is used as an alternative to biopsy. JC virus subtype detection in brain, CSF and blood leukocytes may offer further diagnostic and prognostic possibilities. The aetiology, clinical features and diagnostic problems of PML are reviewed. At present the outlook for patients with confirmed PML is poor and there is currently no effective treatment. However, novel approaches to treatment are under investigation and show some promise.

AIDS-Related Opportunistic Infections↗

Historical vignette: cerebral cortical stimulation and surgery for epilepsy.

In 1909, in an isolated community hospital, on the northern tip of the Province of Newfoundland and Labrador, Canada, Dr. John Mason Little, Jr. performed electrical stimulation of the cerebral cortex, prior to cortical excision, as treatment of recurrent cerebral seizures in three patients. Extracts from Dr. Little's written records of the clinical features, the neurosurgical procedures and cerebral cortical stimulation are summarised. A brief review of the contemporaneous history of neurosurgical procedures for epilepsy provides a prospective of Dr. Little's remarkable surgical virtuosity.

Canada↗

Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program.

BACKGROUND AND PURPOSE: Epidemiological studies indicate a higher incidence of intracerebral (but not subarachnoid) hemorrhagic stroke among persons with low total serum cholesterol levels. This report further examines the prospective relationship of total serum cholesterol with subsequent intracerebral hemorrhage in a large, well-defined population. METHODS: The cohort included 61756 enrollees in a health plan from the San Francisco-Oakland metropolitan area (46% men, 63% white), aged 40 to 89 years and free of cardiovascular disease at baseline. Sixteen-year incidence of combined nonfatal and fatal intracerebral hemorrhagic stroke (International Classification of Diseases [ICD], 8th revision, code 431, or ICD, 9th revision, codes 431 and 432) was investigated in relation to serum cholesterol measured in multiphasic health checkups made in 1977 through 1985. Intracerebral hemorrhagic events were ascertained using hospital discharge records and as underlying cause of death by the California Mortality Linkage Information System. RESULTS: From 1978 through 1993 (average of 10.7 years), there were 386 events (201 in men, 29% fatal; 185 in women, 42% fatal). By multivariate proportional hazards life-table regression analysis, serum cholesterol level below the sex-specific 10th percentile (< 4.62 mmol/L [178 mg/dL] in men), compared with higher cholesterol level, was associated with a significantly increased risk of intracerebral hemorrhage in men aged 65 years or older (relative risk, 2.7; 95% confidence interval, 1.4 to 5.0). An excess risk was also observed among elderly women at the lowest cholesterol range, but a chance finding could not be ruled out. No relationship was seen among men or women aged 40 to 64, and no statistical interaction of low serum cholesterol with hypertension was found in either sex. CONCLUSIONS: In these data, the association between low serum cholesterol level and intracerebral hemorrhage was confined to elderly men.

Adult↗

Changes in measurements of body fat distribution accompanying weight change.

The waist-to-hip circumference ratio (WHR), as an indicator of body fat distribution is related to several clinical diseases. Whether one can reduce this ratio with weight loss is still unconfirmed and may differ between sexes. The degree to which WHR changes with weight gain is also unclear. Changes in waist and hip circumferences and WHR accompanying changes in weight over 5 years were examined in 3,753 black and white men and women initially ages 18-30. Those who gained weight increased their WHR and in most cases those whose weight remained stable increased their WHR. Those who gained the most weight had the greatest increases in WHR. Men had greater increases in WHR per kg weight gain than women. In general, weight loss was accompanied by a decrease in the WHR. However, in those whose initial WHR was below the median, weight loss was associated with an increase in WHR. Smokers and black males also had increases in WHR with weight losses up to 4.9 kg.

Adipose Tissue↗

Health care use by frequent marijuana smokers who do not smoke tobacco.

Even though marijuana smoke contains carcinogens and more tar than tobacco smoke and marijuana intoxication has been implicated as a risk factor for injuries, relatively little epidemiologic evidence has identified marijuana use as a risk factor for ill health. This study is the first to examine the health effects of smoking marijuana by comparing the medical experience of "daily" marijuana smokers who never smoked tobacco (n = 452) with a demographically similar group of nonsmokers of either substance (n = 450). Marijuana smoking status was determined during multiphasic health checkups at Kaiser Permanente medical centers between July 1979 and December 1985. Medical records were reviewed for as long as 2 years after the checkups. Frequent marijuana smokers had small increased risks of outpatient visits for respiratory illnesses (relative risk [RR] = 1.19; 95% confidence interval [CI] = 1.01, 1.41), injuries (RR = 1.32; CI = 1.10, 1.57), and other types of illnesses (RR = 1.09; CI = 1.02, 1.16) compared with nonsmokers; their risk of being admitted to a hospital was elevated but not statistically significant (RR = 1.51; CI = 0.93, 2.46). Analyses were adjusted for sex, age, race, education, marital status, and alcohol consumption. Daily marijuana smoking, even in the absence of tobacco, appeared to be associated with an elevated risk of health care use for various health problems.

Adult↗