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Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

This article reviews the persisting difficulty and the importance of the diagnosis of minor head trauma. The diagnosis has been complicated by pervasive disagreement regarding diagnostic criteria. This is primarily a result of the fact that evidence for actual injury is hard to obtain in minor cases because most symptoms tend to be subjective and have high base rates in the normal, uninjured population. At the same time, the diagnostic decision has important implications for patients in terms of treatment, expectancy for future function and lifestyle, and compensation for injuries. Decision theory leads us to the awareness of diagnostic errors. In addition to correct determination, the clinician can make an error of not diagnosing an injury when it has in fact occurred or making a positive diagnosis where there is no injury. The optimal strategy is to set the cutoff at the midpoint of these two error probabilities. The clinician may be willing to make one error rather than the other depending on the cost and bias involved. The second error is more likely to be made when the clinician stands as a strong advocate for the patient and willing to provide any help necessary to encourage treatment, give patients a rationale for understanding their symptoms, and help them obtain compensation for injuries. This can also lead to significant overdiagnosis of injury. The first error is more likely to be made when the clinician recognizes the potential for increasing costs to the health-care industry, the court system, and increasing personal injury claims. He or she may also recognize the vulnerability to the risk for symptom invalidity, the perpetuation of patient symptoms through suggestion, and the need for a biologic explanation for life stressors and preexisting emotional and personality constraints. It can be argued that the most objective diagnostic opinion, uninfluenced by the above biases, should ultimately be in the best interest of the patient, the clinician, legal consultants, and society. Based on the findings in this chapter, at least four symptom constellations can be identified. These have differing probabilities for residual symptoms of minor head trauma and include the following: 1. These patients' symptoms clearly meet the criteria from Table 2. This includes several findings from 1 to 10 of Table 1, together with abnormal neuropsychologic testing on the AIR, General Neuropsychological Deficit Scale, or other indicators of diminished cortical integrity. This group of patients shows a very strong probability of having experienced a brain injury and for showing residual symptoms of minor head trauma. 2. These patients have experienced concussional symptoms (e.g., headache, mild confusion, and balance and visual symptoms) that were documented at the time of injury but sustained no or brief (< 15 seconds) LOC or PTA and, therefore, do not qualify for the diagnosis in Table 2. They may still have several symptoms from Table 1, including objective findings from neuroscanning and variable neuropsychologic testing, especially in measures of attention and delayed recall. This group also shows a high probability for residual, unresolved concussional, and related symptoms. 3. These patients may have shown evidence of concussional symptoms at the time of injury, with no or brief LOC, PTA, or other symptoms from Table 1 (1-10). They continue to show persistent symptoms after 6 months to 1 year. With this group, there is a strong probability that emotional, motivational and premorbid personality factors are either causing or supporting these residual symptoms. 4. In these patients, clearly identifiable postconcussive symptoms at the time of injury are not easy to identify, and perhaps headache is the only reported symptom. There was no LOC or PTA, and virtually none of symptoms 1 to 10 in Table 1 are observed. These patients show strong evidence of symptom invalidity on MMPI-2 or other measures, and marked somatoform, depression, anx
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PMID:Minor head trauma. 977 99

Patients with severe asthma pose a dilemma to the physician since the treatment they need, namely high doses of oral steroids, has serious side effects, especially among the pediatric population. Deficiency in one or more of the IgG subclasses has been associated with abnormal pulmonary function, as well as with recurrent sinopulmonary infections in adults and children. In the last years attention has been focused on alternative therapies for these patients. One of these alternatives is the treatment with intravenous immunoglobulin (IVIG). We report an 11-year-old boy with severe asthma since the age of two years and multiple hospital admissions due to asthmatic crisis even more frequent and severe, to the point of needing, in the last year, daily treatment with high doses of oral steroids (20 mg). During six months the patient was given high doses of intravenous immunoglobulin. After one month of treatment a clinical and spirometric improvement was apparent allowing to taper down the oral steroids until their complete substitution by inhaled budesonide (1,600 microg/day). The only side effects noted were severe headaches after gammaglobulin infusions which responded well to oral paracetamol. This improvement was sustained throughout the treatment period, but few weeks after the IVIG was suspended the clinical and spirometric parameters started to worsen again.
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PMID:Severe steroid-dependent asthma with IgG-2 deficiency and recurrent sinusitis: response to treatment with high-dose intravenous immunoglobulin. 1043 Nov 2

Japanese-B virus encephalitis (JE) is considered a uniphasic illness with a variable outcome. Biphasic illness patterns have never been reported previously. From an endemic zone in India we observed six patients of JE (from 62 patients treated in 7 years) who had an early relapse resulting in the biphasic clinical course. Five had poor socio-economic status and three had laboratory evidence of nutritional deficiency. Two patients were adults and the other four were children. Fever, rigors, headaches, body aches, altered consciousness, rigidity and tremors predominated the first phase of illness. During the second phase, behavioural changes, dystonia, pen-oral dyskinesia, drooling, mutism and muscle wasting due to anterior horn cell involvement were the important features. Though the serial antibody titres against the JE virus showed a four-fold rise in the initial or late convalescent phases, there was no increase during the second phase of the illness as compared to the first phase. On MRI, fresh lesions appeared during the second phase at the sites known for their involvement in JE, suggesting recrudescence of the virus. One patient survived with major sequelae, two with minor sequelae and the other three had complete recovery. We conclude that some patients with JE may have an early relapse after partial recovery, giving rise to the biphasic illness pattern. A locally prevalent genetic variant of the virus or host factors may be responsible for the altered clinical course of the disease. Biphasic illness does not necessarily mean a bad prognosis.
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PMID:Biphasic illness pattern due to early relapse in Japanese-B virus encephalitis. 1116 88

Low levels of testosterone, determined by a blood test, were found to affect sexual interest, erections and orgasms. In a study conducted two years ago, male AIDS patients were administered testosterone replacement therapy. The patients enjoyed improved humor, energy, and sexual desire after four weeks of treatment. Future observations of testosterone therapy will include wasting syndrome, weight loss and reduction of muscle mass. Possible causes of low testosterone are illnesses of the pituitary or hypothalamus, use of certain medications, infection, tension or malnutrition. The study used intra-muscular injections of 200 mg initially, raised to 400 mg every two weeks. The injections continued for ten to fourteen days, with levels reaching over 1,000 mg. Adverse effects are rare (less than ten percent) but include hair loss, headaches, irritability and weight gain. An effect of testosterone injections is the body's inability to produce it on its own.
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PMID:[Testosterone Replacement Therapy: a recent innovation in the treatment of AIDS]. 1136 41

Cerebral sinus thrombosis (CST) is known to be related to a number of underlying aetiologies including otitis media, trauma, pregnancy, birth control pills, tumours, malnutrition, dehydration, haematologic disorders and malignancy (Fishman, 2000; Raizer and Abbott, 2000). We present the case of a patient with breast cancer receiving the antioestrogen drug tamoxifen who developed CST. A 40-year-old female presented as an emergency with a 10-day history of headache and left sided weakness. On questioning her past medical history included a diagnosis of breast cancer 3 years ago treated by radical mastectomy and tamoxifen 20 mg daily. At the time of admission, neurologic examination revealed a mild left sided hemiparesis and a present Babinksi sign. Non-contrast enhanced tomography was normal. Magnetic resonance imaging (MRI) showed thrombosis in the superior sagittal sinus, right lateral sinus and jugular vein in addition venous infarction in the right temporal lobe was present (Figs 1a and b). Routine haematology and biochemistry was normal. Anticoagulation tests, antithrombin III, protein S and C levels were also found to be normal. She was treated with anticoagulation therapy and her hemiparesis improved within 3 days. Control MRI showed the resorption of the venous infarction and resolution of the thrombosis (Fig. 1c).
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PMID:A case with cerebral thrombosis receiving tamoxifen treatment. 1178 61

The US Centers for Disease Control in 1982 listed conditions and infections then associated with AIDS. That case definition, used as a model for many countries, was designed primarily for epidemiologic surveillance and now includes more than 20 conditions. The definition, however, requires diagnostic and laboratory technologies which are not always available in developing countries. The World Health Organization (WHO) therefore published the Bangui definition in 1985 which uses clinical criteria alone. Many developing countries have adapted this definition to the types of pathogens they encounter domestically. According to the AIDS clinical definition, the presence of generalized Kaposi sarcoma or cryptococcal meningitis is sufficient for the diagnosis of AIDS. AIDS is also diagnosed if at least two major signs and one minor sign are present in the absence of known causes of immunosuppression such as malnutrition. Major signs are fever for more than one month, loss of more than 10% of body weight, and diarrhea for more than one month. Minor signs include cough for more than one month, generalized pruritic dermatitis, recurrent herpes zoster or shingles, oropharyngeal candidiasis or thrush, chronic or aggressive ulcerative herpes simplex, and persistent generalized lymphadenopathy. WHO has also developed criteria for diagnosing symptomatic HIV infection as an aid to individual case management. These criteria, however, are not intended to replace the Bangui AIDS case definitions developed for epidemiological purposes. The diagnosis of symptomatic HIV infection is made through physical examination and the taking of a very detailed case history. In so doing, there may be cardinal, characteristic, and/or associated findings. Cardinal findings of HIV infection are Kaposi sarcoma, oesophageal candidiasis, cytomegalovirus retinitis, Pneumocystis carinii pneumonia, and Toxoplasma encephalitis. Characteristic findings include oral thrush in a patient not taking antibiotics; hairy leukoplakia; cryptococcal meningitis; miliary, extrapulmonary,, or non-cavity pulmonary tuberculosis; current or past herpes zoster or shingles; severe prurigo; Kaposi sarcoma of a less than generalized or rapidly progressive nature; and high-grade B-cell extranodal lymphoma. Finally, associated findings in the absence of any other obvious cause of immunosuppression are recent and/or explained weight loss of more than 10% of body weight; fever for more than one month; diarrhea for more than one month; ulcers for more than one month; cough for more than one month; neurological complaints or findings, peripheral neuropathy, dementia, and progressively worsening headache; generalized lymphadenopathy; previously unseen drug reactions; and severe or recurrent skin infections. A person has symptomatic HIV infection if there are one or more cardinal findings, two or more characteristics findings, one characteristic finding and two or more associated findings, three or more associated findings together with any risk factors, or two associated findings together with a positive HIV test result. Malawi, Zambia, Thailand, and the English-speaking Caribbean are adapting these criteria for national use.
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PMID:Diagnosing symptomatic HIV infection and AIDS in adults. 1228 34

This discussion identifies some of the health problems experienced by rural women in Africa. The first of these health problems is malaria, which is not exclusively reserved for rural women. Yet, it is they who are most exposed to bites by the mosquitoes which abound more particularly in that country. So involved are they in their daily tasks, they often do not even feel these bites, and negligence and/or lack of information prevents them from taking antimalarial drugs. Only when fever or tenacious headaches occur do they decide to take a few nivaquine pills. Often they simply drink medicinal herb teas said to be "diuretic." Next on the list is malnutrition, with anemia as its corollary. It is caused by ignorance, or lack of information on what food should be eaten; dietary customs and taboos deeply anchored in some families and which deprive women of the nutrients required by their bodies, especially after childbirth; lack of time; and financial difficulties. The problems of malaria and malnutrition affect men and children as well as women, but others are specific to women. Closely spaced pregnancies, which used to be rare in villages, are now increasingly frequent in rural areas. Since planned parenthood is "unknown" in rural areas, most women bear a great many children -- 8-10 or more. Placenta previa is a frequent condition in such women, and often results in the mother's death, sinc the delivery was done in a poorly equipped center and the diagnosis was only made at the beginning of labor. Since women are constantly concerned with doing the most for their family and satisfying all of their needs, they never rest during the day, are excessively tired, and only sleep 5-6 hours a night. In addition to their own specific health problems, mothers often are obliged to spend their nights watching, alone, over 1 or more sick children. In sum, these are some of the everyday problems encountered in rural areas: the lack of information on health matters; the distance from health centers; limited financial resources in the rural population; and the precariousness of means of transportation, and the absence of an emergency transferral system.
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PMID:Health problems facing rural women. 1234 Jul 16

Normal ageing is associated with a decline in spontaneous growth hormone (GH) secretion, and although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of GH responsiveness on dynamic testing, there are few data available on the response to GH replacement in older subjects. We have studied the baseline characteristics of 295 patients (173 males and 122 females) aged >65 years of age who began GH replacement therapy at the time of entry into the KIMS program (Pfizer International Metabolic Database) and the effects of GH replacement in 125 patients who completed at least 12 months of GH replacement therapy. Data were compared with those of 2469 (1249 males and 1220 females) patients aged <65 years with adult-onset GH deficiency (GHD). The patients were selected using strict criteria in accordance with the recommendations from the Growth Hormone Research Society. There was a higher proportion of pituitary adenoma relative to craniopharyngioma in the older age group (P<0.001), but there was no difference between groups in the degree of hypopituitarism (number of additional hormone deficiencies). Blood pressure, cholesterol and low-density lipoprotein (LDL) cholesterol levels were positively correlated with age, and older patients had a predictably higher prevalence of diabetes mellitus, coronary heart disease, stroke and history of hypertension. Quality of life (Assessment of Growth Hormone Deficiency in Adults (AGHDA) score) was impaired in both groups before the start of GH therapy. GH replacement doses were lower in older patients with GHD as compared with patients <65 years old. After 12 months of GH replacement, significant improvements were evident in waist circumference, waist/hip ratio, lean body mass, diastolic blood pressure, total and LDL cholesterol levels and AGHDA scores in patients aged <65 years. Similar significant reductions were evidenced in patients >65 years old compared with those observed in younger patients. The total number of adverse events was similar in younger and older patients with GHD. However, younger patients had more fluid retention-related adverse events such as headache, oedema and arthralgia; whereas, older patients with GHD had more adverse events related to glucose metabolism, cardiovascular events and neoplasms. These data indicate a positive benefit from GH replacement in older patients with hypopituitarism - particularly in relation to quality of life - using a lower dose of GH for replacement and with appropriate age-related safety controls.
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PMID:Aspects of growth hormone deficiency and replacement in elderly hypopituitary adults. 1513 78

Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.
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PMID:Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. 1569 61


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