Drivers of solar radiation variability in the McMurdo Dry Valleys, Antarctica.

Annually averaged solar radiation in the McMurdo Dry Valleys, Antarctica has varied by over 20 W m-2 during the past three decades; however, the drivers of this variability are unknown. Because small differences in radiation are important to water availability and ecosystem functioning in polar deserts, determining the causes are important to predictions of future desert processes. We examine the potential drivers of solar variability and systematically eliminate all but stratospheric sulfur dioxide. We argue that increases in stratospheric sulfur dioxide increase stratospheric aerosol optical depth and decrease solar intensity. Because of the polar location of the McMurdo Dry Valleys (77-78°S) and relatively long solar ray path through the stratosphere, terrestrial solar intensity is sensitive to small differences in stratospheric transmissivity. Important sources of sulfur dioxide include natural (wildfires and volcanic eruptions) and anthropogenic emission.

Listerial brainstem encephalitis--treatable, but easily missed.

Listerial brainstem encephalitis (LBE) is an uncommon form of listerial central nervous system infection that progresses rapidly and is invariably fatal unless detected and treated early. We report on six adult patients with LBE, of whom five were managed or co-managed by our unit during the period January - June 2012. All presented with a short prodromal illness followed by a combination of brainstem signs, including multiple cranial nerve palsies with emphasis on the lower cranial nerves, ataxia, motor and sensory long-tract signs, a depressed level of consciousness and apnoea. In two cases the diagnosis was delayed with adverse outcomes. LBE may be difficult to diagnose: clinicians may not be aware of this condition, the brainstem location may not be recognised readily, general markers of inflammation such as the erythrocyte sedimentation rate, C-reactive protein level or white cell count may be normal, and the cerebrospinal fluid is typically normal or there are only mild and nonspecific findings. Serological tests are unreliable, and diagnosis is achieved through blood cultures, magnetic resonance imaging and clinical recognition.

Plasmodium genetic loci linked to host cytokine and chemokine responses.

Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1ß, IP-10, IFN-γ, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1ß, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection.

Epilepsy in South Africa.

Since its first democratic elections in 1994, South Africa has undertaken a massive social reconstruction program that has included major healthcare reform. The state healthcare system aims to provide a unitary service, based on a primary healthcare approach, to the 85% of the population who depend on it. Although the burden of epilepsy is largely unknown, it is likely to be large, with a study of children in a large rural community, for example, demonstrating an active prevalence of 6.7/1000. Common causes of epilepsy are likely to include infectious diseases, such as neurocysticercosis and HIV/AIDS, trauma and alcohol consumption. Limited evidence suggests the existence of a large treatment gap in some areas. The management and treatment of epilepsy are also greatly influenced by cultural attitudes and beliefs, which vary widely. South Africa thus provides a microcosm of issues affecting the management of epilepsy worldwide.

High-dose immunosuppressive therapy in generalised myasthenia gravis--a 2-year follow-up study.

BACKGROUND: Immunosuppressive (IS) therapy is increasingly advocated in the treatment of myasthenia gravis (MG). This study assessed whether early 'high-dose' IS therapy in new patients with generalised MG (GMG) altered the outcome and reduced the morbidity of GMG. METHODS: Patients with GMG were treated with 'high-dose' IS therapy (prednisone < or = 1 mg/kg, azathioprine 2-3 mg/kg) and followed up for 2 years. Prednisone and azathioprine were initiated on diagnosis. Outcome measures were compared with those of controls previously treated at our clinic with 'low-dose' IS therapy. The primary outcome measure was the number of patients in remission at 1 and 2 years. Secondary outcomes included the MG scores (MGS) after 1 and 2 years, as well as the number of plasma exchanges (P/E), hospital and intensive care unit (ICU) admissions required for decompensated MG. FINDINGS: At 1 and 2 years there were significant improvements in the MGS of patients treated with 'high-dose' IS therapy compared with those of controls; 50% of these patients were in remission after 2 years compared with less than 16% of controls. The number of hospital and ICU admissions had also dropped significantly in the first year of patients receiving 'high-dose' IS treatment. CONCLUSION: Early 'high-dose' IS therapy using azathioprine and prednisone in GMG resulted in a significant increase in the number of patients in remission and reduced morbidity at 1 and 2 years.

Early detection of undiagnosed diabetes mellitus: a US perspective.

Undiagnosed Type 2 diabetes has become a common condition in the US, comprising one-third of all cases of the disease. We believe that screening for and detection of undiagnosed Type 2 diabetes is an important endeavor. In this review we provide evidence that diabetes is a condition that is appropriate for population screening and detection. This includes evidence that: 1. Type 2 diabetes is a significant health problem. It affects more than 16 million adults in the US and places these individuals at high risk for serious complications of the eyes, nerves, kidneys, and cardiovascular system. 2. There is a latent phase before diagnosis of Type 2 diabetes. During this period of undiagnosed disease, risk factors for diabetic micro- and macrovascular complications are markedly elevated and diabetic complications are developing. 3. Diagnostic criteria for diabetes have been established and are based on plasma glucose values. These criteria define a group of individuals with significant hyperglycemia who also have a high frequency of risk factors for micro- and macrovascular disease. 4. The natural history of Type 2 diabetes is understood. In most patients, diabetes proceeds inexorably from genetic predisposition, through the stage of insulin resistance and hyperinsulinemia, to beta cell failure and overt clinical disease. 5. There are effective and acceptable therapies available for Type 2 diabetes and its complications. Treating hyperglycemia to prevent complications is more effective than treating these complications after they have developed. Furthermore, guidelines for treatment to prevent cardiovascular disease in people known to have diabetes are more stringent than in those individuals who are not known to have diabetes. 6. There is a suitable test for screening for undiagnosed Type 2 diabetes that has high sensitivity and specificity - measurement of fasting plasma glucose. Guidelines for identifying persons at high risk for diabetes have been established.

Human immunodeficiency virus-associated pure motor lumbosacral polyradiculopathy.

BACKGROUND: Neuromuscular disease is a common manifestation of human immunodeficiency virus infection and acquired immunodeficiency syndrome, but isolated and severe pathology confined to the motor roots or anterior horn cells are not a recognized clinical entity. OBJECTIVE: To describe the novel clinical presentation of human immunodeficiency virus-related polyradiculopathy manifesting as isolated severe motor symptoms confined to the legs. DESIGN: A case series comprising 4 patients identified prospectively during a 6-month period. SETTING: Patients were seen in the Department of Neurology, Groote Schuur Hospital, Cape Town, South Africa. This is an 800-bed teaching hospital, with approximately 5000 patients seen annually in the Department of Neurology. PATIENTS: Patients were identified by their unique presentation with a severe isolated motor neuropathy in the lower limbs. All were Xhosa-speaking African women. RESULT: Early human immunodeficiency virus infection may be associated with pure motor lumbosacral polyradiculopathy. CONCLUSION: It remains unclear whether this clinical syndrome should be regarded as a variant of the Guillain-Barre syndrome or whether it represents a unique disorder associated with early human immunodeficiency virus infection.

The GlucoWatch biographer: a frequent automatic and noninvasive glucose monitor.

The GlucoWatch (Cygnus, Inc, Redwood City, CA, USA) biographer provides automatic, frequent and noninvasive blood glucose measurements for up to 12 h. The device extracts glucose through intact skin where it is measured by an amperometric biosensor. Clinical trials in a variety of environments have shown that the biographer provides accurate and precise glucose measurements when compared with serial fingerstick blood glucose measurements. Mean difference between these measurements was 0.26 mmol/L in the home environment (r = 0.80). Over 94% of biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low glucose levels. Biographer precision, as measured by coefficient of variation (CV)%, is approximately 10%. The low glucose alert function of the biographer was able to detect up to 75% of hypoglycaemic episodes with a low false alert level. Skin irritation, characterized by erythema and oedema was either nonexistent or mild in over 87% of subjects and resolved in virtually all subjects without treatment in several days. The GlucoWatch biographer has been shown to be a safe and effective method to track glucose level trends and patterns, which should enable improved glycaemic control for many patients.

Prevention and treatment of microvascular and neuropathic complications of diabetes.

The most important factors that influence development of the eye, kidney, and nerve complications of diabetes are the duration and degree of exposure to hyperglycemia. Hypertension is also very important. The risk of complications appears to be similar for all patients with diabetes; differences in complication rates between patients with type 1 and type 2 diabetes are largely due to differences in duration of diabetes and glycemic control. The benefits of lowering blood sugar are also similar for patients with diabetes, regardless of the type. Significant reductions in complications can be seen with relatively short-term treatment of hyperglycemia.

Racial and ethnic differences in glycemic control of adults with type 2 diabetes.

OBJECTIVE: To evaluate glycemic control in a representative sample of U.S. adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged > or = 20 years. Information on medical history and treatment of diabetes was obtained to determine those who had been diagnosed with type 2 diabetes by a physician before the survey (n = 1,480). Fasting plasma glucose and HbA1c were measured, and the frequencies of sociodemographic and clinical variables related to glycemic control were determined. RESULTS: A higher proportion of non-Hispanic blacks were treated with insulin and a higher proportion of Mexican Americans were treated with oral agents compared with non-Hispanic whites, but the majority of adults in each racial or ethnic group (71-83%) used pharmacologic treatment for diabetes. Use of multiple daily insulin injections was more common in whites. Blood glucose self-monitoring was less common in Mexican Americans, but most patients had never self-monitored. HbA1c values in the nondiabetic range were found in 26% of non-Hispanic whites, 17% of non-Hispanic blacks, and 20% of Mexican Americans. Poor glycemic control (HbA1c > 8%) was more common in non-Hispanic black women (50%) and Mexican-American men (45%) compared with the other groups (35-38%), but HbA1c for both sexes and for all racial and ethnic groups was substantially higher than normal levels. Those with HbA1c > 8% included 52% of insulin-treated patients and 42% of those taking oral agents. There was no relationship of glycemic control to socioeconomic status or access to medical care in any racial or ethnic group. CONCLUSIONS: These data indicate that many patients with type 2 diabetes in the U.S. have poor glycemic control, placing them at high risk of diabetic complications. Non-Hispanic black women, Mexican-American men, and patients treated with insulin and oral agents were disproportionately represented among those in poor glycemic control. Clinical, public health, and research efforts should focus on more effective methods to control blood glucose in patients with diabetes.

The effects of treatment on the direct costs of diabetes.

Treatment of diabetic complications consumes health care resources. Intensive therapy was shown by the Diabetes Control and Complications Trial (DCCT) to avert complications. Economic analyses and models have been used to evaluate the cost-effectiveness of intensive therapy for people with type 1 and type 2 diabetes. An economic analysis of the DCCT estimated the cost of intensive therapy to be two to three times greater than that of conventional therapy. In contrast, an economic model predicts that intensive therapy, as compared with conventional therapy, could reduce blindness from 34 to 20% or by 41%, end-stage renal disease from 24 to 7% or by 71%, and lower-extremity amputations from 7 to 4% or by 43%. Although intensive therapy is more expensive, when the costs of complications are factored in, it becomes cost-effective for treatment of type 1 diabetes. Similarly, a model to evaluate the cost-effectiveness of intensive therapy for people with type 2 diabetes found that the lifetime costs of general and diabetes-related medical care would be approximately two times greater. However, the reduction in lifetime costs of complications, which would produce substantial reductions in costs of treatment, largely offsets the difference. Intensive therapy for type 1 and type 2 diabetes may be more expensive than conventional therapy, but from an economic perspective, it is comparable in cost to pharmacological therapies for people with hypertension and hypercholesterolemia. From a health system viewpoint, intensive therapy represents a fruitful long-term financial investment.

Sonography of gallbladder abnormalities in acromegaly patients following octreotide and ursodiol therapy: incidence and time course.

PURPOSE: We studied the effects of octreotide and ursodiol on the gallbladders of patients with acromegaly. METHODS: We performed gallbladder sonography in patients with acromegaly at various intervals during treatment. Group I (18 patients) was treated with subcutaneous injections of the somatostatin analogue octreotide. Group II (10 patients) was treated with ursodiol while receiving octreotide therapy. RESULTS: Seventy-eight percent of patients receiving octreotide developed gallbladder abnormalities: sludge in 72% (13/18) and calculi in 39% (7/18). Ursodiol reversed the gallbladder abnormalities in 7 of 10 patients. CONCLUSIONS: A majority of patients receiving octreotide develop gallbladder abnormalities. Ursodiol appears to reverse the abnormalities in most cases.

Comparison of diabetes diagnostic categories in the U.S. population according to the 1997 American Diabetes Association and 1980-1985 World Health Organization diagnostic criteria.

OBJECTIVE: To compare the 1997 American Diabetes Association (ADA) and the 1980-1985 World Health Organization (WHO) diagnostic criteria in categorization of the diabetes diagnostic status of adults in the U.S. RESEARCH DESIGN AND METHODS: Analyses are based on a probability sample of the U.S. population age 40-74 years in the 1988-1994 Third National Health and Nutrition Examination Survey (NHANES III). People with diabetes diagnosed before the survey were identified by questionnaire. For 2,844 people without diagnosed diabetes, fasting plasma glucose was obtained after an overnight 9 to < 24-h fast, HbA1c was measured, and a 2-h oral glucose tolerance test was administered. RESULTS: Prevalence of diagnosed diabetes in this age-group is 7.9%. Prevalence of undiagnosed diabetes is 4.4% by ADA criteria and 6.4% by WHO criteria. The net change of -2.0% occurs because 1.0% are classified as having undiagnosed diabetes by ADA criteria but have impaired or normal glucose tolerance by WHO criteria, and 3.0% are classified as having impaired fasting glucose or normal fasting glucose by ADA criteria but have undiagnosed diabetes by WHO criteria. Prevalence of impaired fasting glucose is 10.1% (ADA), compared with 15.6% for impaired glucose tolerance (WHO). For those with undiagnosed diabetes by ADA criteria, 62.1% are above the normal range for HbA1c compared with 47.1% by WHO criteria. Mean HbA1c is 7.07% for undiagnosed diabetes by ADA criteria and 6.58% by WHO criteria. CONCLUSIONS: The number of people with undiagnosed diabetes by ADA criteria is lower than that by WHO criteria. However, those individuals classified by ADA criteria are more hyperglycemic, with higher HbA1c values and a greater proportion of values above the normal range. This fact, together with the simplicity of obtaining a fasting plasma glucose value, may result in the detection of a greater proportion of people with undiagnosed diabetes in clinical practice using the new ADA diagnostic criteria.

The cost-effectiveness of intensive therapy for diabetes mellitus.

Although persons with diabetes constitute only 3.1% of the US population, costs for their care account for 11.9% of total US health care expenditures. Approximately half of the expenditures for medical care for diabetes are for treatment of the metabolic condition and half for the treatment of chronic complications. Intensive therapy for persons with diabetes uses more resources and is more expensive than conventional therapy. On the other hand, intensive therapy is associated with a lower incidence of costly chronic complications. Formal economic analyses have demonstrated that intensive therapy is cost-effective for the treatment of diabetes. In IDDM, intensive therapy costs approximately $20,000 per QALY gained; in NIDDM, it costs approximately $16,000 per QALY gained. From an economic perspective, intensive therapy for persons with diabetes compares favorably with pharmacologic therapy for high-risk individuals with hypertension and hypercholesterolemia. Health policy should foster the use of such therapy for persons with diabetes mellitus.