The clinical application of plasma Kaposi sarcoma herpesvirus viral load as a tumour biomarker: results from 704 patients.

OBJECTIVES: The aim of the study was to evaluate the role of plasma Kaposi sarcoma herpesvirus (KSHV) as a diagnostic and prognostic biomarker in people living with HIV (PLWH) and diagnosed with KSHV-associated diseases. METHODS: Using quantitative nested polymerase chain reaction (PCR) targeting the open reading frame-26 gene of KSHV, plasma levels of KSHV were measured in consecutive PLWH with KSHV-associated diseases or as part of the investigation of lymphadenopathy. RESULTS: Plasma KSHV assays were performed on samples from 684 PLWH and 20 HIV-seronegative people with KSHV-associated malignancies. In PLWH, plasma KSHV was detected in 39% of those with KS, 99% of those with multicentric Castleman disease (MCD), 9% of those with non-Hodgkin lymphoma (NHL), 2% of those with non-AIDS-defining malignancies and 0% of those with nonmalignant lymphadenopathy. There was no significant difference in plasma KSHV viral load among those with KS, MCD and KSHV-associated NHL. The 5-year overall survival rate from KS diagnosis of 335 PLWH was 95.2% (95% confidence interval 92.6-97.8%). Plasma KSHV viraemia did not predict overall survival in those with KS (P = 0.73), nor when those with T0 stage KS (P = 0.52) or T1 stage KS (P = 0.62) were analysed separately. CONCLUSIONS: Measuring the plasma levels of KSHV as a biomarker in KSHV-associated disease has a very limited value in either diagnosis or prognostication. The only potential role of clinical value is the suggestion that an undetectable plasma KSHV excludes a diagnosis of MCD in PLWH.

Morphometric analysis and roosting ecology of bat species Pteropus Medius in Mansehra, Khyber Pakhtunkhwa, Pakistan.

Morphometric measurement and roosting ecology of Pteropus medius were aimed to find out in Mansehra district of KP, Pakistan. Total 3149 numbers of bats were found in eight biological spots visited; Baffa Doraha, Darband, Dadar, Jallu, Hazara University, Garhi Habibullah Chattar Plain and Jabori, in total 299 numbers of different species of trees including; Morus alba, Pinus raxburghi, Eucalyptus camaldulensis, Morus nigra, Grevillea robusta, Brousonetia papyrifera, Platanus orientalis, Ailanthus altissima, Hevea brasiliensis and Populus nigra. Morphometric features were measured and found vary according to sex of the bats. The average wing span, wing`s length from tip of wing to neck, from thumb to tip of wing and the body`s length from head and claws were recorded to be 102.98 cm, 49.07cm, 28.7 cm and 22.78 cm respectively in males while 93.67 cm, 44.83cm, 24.78cm and 22.78 cm respectively in female bats. Mean circumference of the body including wings and without wing were measured as 22.78 cm and 17.29 cm in males and that of female were 20.07 cm and 16.9 cm. Average length of thumb 3.64 cm, ear`s length 3.1 cm, snout 5.62cm, eye length were 1.07 cm for both sexes and length between the feet in extended position were16.3 cm. Generally different measurement of males bodies were found to be greater than female such as mean body surface area, mass, volume and pressure were found to be 2691.79 cm2, 855.7gm,1236.4 ml and 295.77 dyne/ c m 3 for male and 2576.46 cm2, 852.71gm,1207 ml and 290.2 dyne/ c m 3 respectively for female. While weight and density for both males and females bats were same with mean of 8.59 newton and 0.701 g/m3. Findings of current reports can add valued information in literature about bats, which can be used for species identification and conservation.

Mood and motor effects of thalamic deep brain stimulation surgery for essential tremor.

PURPOSE: The aim of this study was to evaluate the effects of unilateral and bilateral ventralis intermedius (Vim) deep brain stimulation (DBS) on mood and motor function. METHODS: Thirty-one consecutive medication refractory patients with essential tremor who underwent unilateral or bilateral Vim DBS at University of Florida and returned for at least 6 -month follow-up completed the Visual Analog Mood (VAMS), the Beck Depression Inventory (BDI), and the Tremor Rating Scale (TRS) before and after surgery. We excluded all patients who were implanted at other institutions. RESULTS: The tense subscale of the VAMS improved significantly in both the unilateral and bilateral DBS groups (P < 0.001). On the VAMS afraid subscale, only the bilateral group trended toward improvement (P = 0.075). There were no significant changes for either group for the happy, confused, sad, angry, energetic or tired VAMS scores. TRS subscale scores all improved after unilateral and bilateral Vim DBS surgery (P < 0.001). CONCLUSIONS: Feelings of tenseness, tremor severity and ADLs improved following unilateral or bilateral Vim DBS for ET.

Brain penetration effects of microelectrodes and DBS leads in STN or GPi.

OBJECTIVE: To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)). BACKGROUND: Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified. METHODS: 47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout). RESULTS: Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar. CONCLUSION: This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.

Dynamics of follicular fluid in one-humped camel (Camelus dromedarius).

In the present study, ovarian follicular fluid and serum biochemical, hormonal, electrolytes and amino acids profiles in female dromedary camel (Camelus dromedarius), were investigated. Fluid from small (2-6 mm) and large follicles (7-20 mm) and blood samples were collected from 25 clinically healthy adult female camels. The concentrations of glucose, cholesterol, triglycerides, high-density lipoproteins, urea, total proteins, albumin, globulin, fibrinogen, alanine aminotransferase, aspartate aminotransferase and tri-iodothyronine were lower (p < or = 0.05) in large follicles when compared with the small follicles. However, the concentrations of low-density lipoproteins, uric acid, creatinine, alkaline phosphatase and acid phosphatase in small and large follicles did not differ. The concentrations of oestradiol 17-beta and progesterone were higher (p < or = 0.05) in large follicles. The serum concentrations of these hormones were many folds lower (p < or = 0.05) than those of follicular fluid. Among electrolytes, the concentration of phosphorus was higher (p < or = 0.05) in the large follicles, while that of potassium and chloride were lower (p < or = 0.05) in the small follicles. Serum concentrations of sodium, chloride, calcium and phosphorous were higher (p < or = 0.05), while that of potassium lower (p < or = 0.05) than corresponding concentrations in the follicular fluid. The concentrations of leucine and arginine were higher (p < or = 0.05) in follicular fluid when compared with serum concentrations, while the reverse was true for other amino acids. In conclusion, this study is indicative of either low or high concentrations of certain biochemical metabolites, hormones, electrolytes and amino acids in small and large follicles for the individual roles that they play in the growth and development of follicles in the one-humped she-camel.

Serum hormonal, electrolytes and trace element profiles in the rutting and non-rutting one-humped male camel (Camelus dromedarius).

The camel is known to be a seasonal breeder and, in the male camel, the breeding activity maximizes during the rutting period (winter and spring seasons). During the non-rutting period (summer and autumn), however, the breeding activity almost ceases completely. Serum steroid hormonal, electrolytes and trace element profiles were studied in 16 adult male camels aged 5-9 years, slaughtered during the rutting (n=8) and non-rutting periods (n=8). Moreover, testicular and epididymal tissue contents of electrolytes and trace elements were also studied during these two periods. Serum levels of testosterone, progesterone and T(4):T(3) ratio were higher in the rutting animals when compared to the non-rutting ones, while the reverse was true for serum T(3), T(4) and corticosterone levels (p<0.01). Among minerals, serum levels of sodium, calcium, copper and zinc were higher, while those of potassium were lower, in the rutting than non-rutting camels. In the testicular tissue, the levels of sodium, calcium, copper and iron were higher in the rutting group, while magnesium was higher in non-rutting one. In the epididymis, the tissue levels of chloride, iron and zinc were higher in the rutting than non-rutting period. These results demonstrate a clear evidence of the distribution of steroid hormones, electrolytes and trace elements forming and maintaining a certain level at two different physiological states in camels.

Is coronary risk an accurate surrogate for cardiovascular risk for treatment decisions in mild hypertension? A population validation.

OBJECTIVE: To examine the relationship between coronary (CHD) and cardiovascular (CVD) risk in patients with uncomplicated mild hypertension and to determine the accuracy of using CHD risk > or = 15% over 10 years to identify for antihypertensive treatment those patients with CVD risk > or = 20% over 10 years as advised in recent British guidelines. DESIGN: Comparison of decisions made using CHD risk > or = 15% over 10 years calculated by the Framingham risk function and estimated using a simple table with CVD risk > or = 20% over 10 years. SETTING: British population. SUBJECTS: People aged 35-64 years with uncomplicated mild systolic hypertension (SBP 140-159 mmHg, n = 624) from the 1995 Scottish Health Survey. MAIN OUTCOME MEASURES: Relationship between CHD and CVD risk. Sensitivity, specificity, positive and negative predictive values (PPV and NPV). RESULTS: CHD risk 15% over 10 years was equivalent to CVD risk 21% over 10 years. Exact CHD risk > or = 15% over 10 years had sensitivity 79%, specificity 98%, PPV 94% and NPV 93% in detecting CVD risk > or = 20% over 10 years. Use of the table to estimate CHD risk > or = 15% over 10 years gave sensitivity 88%, specificity 90%, PPV 76% and NPV 95%. CONCLUSION: CHD risk appears acceptably accurate for targeting treatment in mild hypertension. The risk assessment table, which slightly overestimates CHD risk, was more sensitive in identifying patients with CVD risk > or = 20% over 10 years and may be preferable to using exact CHD risk. European guidelines which suggest targeting treatment for mild hypertension at CHD risk > or = 20% over 10 years are over-conservative compared with British guidelines.

Implication of recent trials with b-hydroxy-b-methylglutaryl coenzyme A reductase inhibitors for hypertension management.

BACKGROUND: There is broad agreement that statin treatment should be targeted at absolute coronary heart disease (CHD) risk but no consensus on the level of risk to target. We have examined the implications of adopting three different treatment policies for the management of hypertensive patients in the UK using data from treated hypertensives aged 35-69 years included in the Health Survey for England (1993). METHODS: We calculated the proportion of hypertensive patients with existing atherosclerotic cardiovascular disease requiring statin treatment for secondary prevention of CHD. For those without atherosclerotic cardiovascular disease (primary prevention), we estimated CHD risk from the Framingham equation and examined the proportion with CHD risk exceeding thresholds of 4.5, 3 and 1.5% per year. RESULTS: Twenty-one percent of treated hypertensives would require statin treatment for secondary prevention of CHD. When the CHD event threshold for statin treatment was set at > or =4.5% per year [equivalent to a number needed to treat (NNT) in 5 years of 13] a further 0.6% of hypertensive patients were identified for treatment; at a threshold of 3.0% per year (NNT = 20) 5.5% of patients were identified for primary prevention; and at a threshold of 1.5% per year (NNT = 40) 28.5% of patients were identified for primary prevention. CONCLUSIONS: Those needing secondary prevention are first priority for statins and 21% of hypertensive patients will require treatment Formulation of guidelines for primary prevention should take into account the NNT; the proportion of patients targeted for treatment; the cost-effectiveness and the total cost of treatment. Current British guidance will entail treating an additional 5.5% of hypertensive patients for primary prevention and therefore 27% of hypertensive patients.

Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury.

The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

Prediction of coronary risk for primary prevention of coronary heart disease: a comparison of methods.

Most recent guidelines advise targeting of lipid lowering for primary prevention at those at high absolute coronary (CHD) risk. We compared the accuracy of five CHD risk assessment methods in identifying such patients: one based on total cholesterol > or = 6.5 mmol/l plus two risk factors, and four based on the Framingham risk function (the European Task Force chart and Sheffield table, both using total cholesterol and the New Zealand chart and modified Sheffield table, both using total: HDL cholesterol ratio) for predicting CHD event risk > or = 2% per year, calculated by an independent risk function, PROCAM, in 126 treated hypertensive men. Cholesterol threshold plus two risk factors had sensitivity 59% and specificity 63%, did not identify some very high-risk patients, and identified very low-risk patients. Framingham-based methods using total cholesterol alone had sensitivity 90-98% and specificity 37-43%, and identified high-risk patients well, but identified some patients at very low risk. Methods based on total: HDL cholesterol ratio had sensitivity 90-98% and specificity 60-63%, and did not identify incorrectly patients at very low CHD risk. Methods based on cholesterol threshold and counting of risk factors are too inaccurate for targeting drug therapy for primary prevention of CHD. Framingham-based methods should incorporate HDL-cholesterol as the total: HDL cholesterol ratio.

Is the Framingham risk function valid for northern European populations? A comparison of methods for estimating absolute coronary risk in high risk men.

OBJECTIVE: To examine the validity of estimates of coronary heart disease (CHD) risk by the Framingham risk function, for European populations. DESIGN: Comparison of CHD risk estimates for individuals derived from the Framingham, prospective cardiovascular Münster (PROCAM), Dundee, and British regional heart (BRHS) risk functions. SETTING: Sheffield Hypertension Clinic. Patients-206 consecutive hypertensive men aged 35-75 years without preexisting vascular disease. RESULTS: There was close agreement among the Framingham, PROCAM, and Dundee risk functions for average CHD risk. For individuals the best correlation was between Framingham and PROCAM, both of which use high density lipoprotein (HDL) cholesterol. When Framingham was used to target a CHD event rate > 3% per year, it identified men with mean CHD risk by PROCAM of 4.6% per year and all had CHD event risks > 1.5% per year. Men at lower risk by Framingham had a mean CHD risk by PROCAM of 1.5% per year, with 16% having a CHD event risk > 3.0% per year. BRHS risk function estimates of CHD risk were fourfold lower than those for the other three risk functions, but with moderate correlations, suggesting an important systematic error. CONCLUSION: There is close agreement between the Framingham, PROCAM, and Dundee risk functions as regards average CHD risk, and moderate agreement for estimates within individuals. Taking PROCAM as the external standard, the Framingham function separates high and low CHD risk groups and is acceptably accurate for northern European populations, at least in men.

Should cholesterol be measured in all hypertensives?

Guidelines for the management of hypertension, and those for hyperlipidaemia, advocate measurement of cholesterol in all hypertensive subjects. It is suggested that knowledge of serum cholesterol should influence the choice of anti-hypertensive agent because thiazides and beta-blockers may influence lipids adversely. However, the changes in lipids associated with low-dose thiazides and beta-blockers are small, not sustained and do not appear to affect prognosis adversely. Some believe that knowledge of serum cholesterol may help target the treatment of mild hypertension more accurately by predicting an increased risk of vascular complications of hypertension. However, serum cholesterol does not predict the risk of cardiovascular complications in hypertensive women. It does predict coronary heart disease (but not stroke) in men, but coronary risk can be estimated satisfactorily without knowledge of serum cholesterol. Suggestions that cholesterol should be lowered in hypercholesterolaemic hypertensive patients to reduce the incidence of coronary heart disease are understandable. However, the diet recommended for this has no useful effect on serum cholesterol, and the benefit of lipid-lowering drugs for cholesterol reduction only exceeds the risk in patients at very high risk of coronary mortality, for example those who have had a myocardial infarction. Hypertension alone will not place individuals at high enough risk to warrant drug therapy for cholesterol reduction. We conclude that the current guidelines are incorrect, and that routine measurement of cholesterol in all hypertensive patients is not justified.

Might non-pharmacological treatment disadvantage patients with hypertension?

Weight reduction, moderate salt restriction and alcohol reduction are effective in lowering blood pressure (BP), and are feasible interventions for long-term management of hypertension. When used in combination these non-pharmacological measures are significantly inferior to drug therapy in anti-hypertensive effect. When they are implemented as a first step in the treatment of mild hypertension, resorting to drug therapy only if non-pharmacological measures fail, anti-hypertensive drugs can be avoided in about 40% of patients. However, BP control is again significantly inferior with this strategy compared with drug therapy without non-pharmacological advice. Those given advice on non-pharmacological measures may therefore have suboptimal protection against cardiovascular complications. This is particularly so when the threshold for drug treatment is set at a DBP of > or = 100 mmHg, as many patients will be left untreated with DBPs between 90 and 99 mm Hg as a result of non-pharmacological measures. Non-pharmacological treatment may thus stand between patients and anti-hypertensive drug therapy, which nowadays is simple, well-tolerated, safe and proven effective in preventing cardiovascular disease. The role of non-pharmacological therapy needs to be reconsidered.

Pakistan's maternal and child health policy: analysis, lessons and the way forward.

An estimated 400,000 infant and 16,500 maternal deaths occur annually in Pakistan. These translate into an infant mortality rate and maternal mortality ratio that should be unacceptable to any state. Disease states including communicable diseases and reproductive health (RH) problems, which are largely preventable account for over 50% of the disease burden. The analysis of Pakistan's maternal and child health (MCH) and family planning (FP) policy covers the period 1990-2002, and focuses on macroeconomic influences, priority programs and gaps, adequacy of resources, equity and organizational aspects, and the process of policy formulation. The overall MCH/FP policy is well directed. MCH/FP has been a priority in all policies; resource allocation, although unacceptably low, has substantially increased during the last decade; and there is a progressive shift from MCH to the reproductive health (RH) agenda. Areas in need of improvement include greater use of evidence as a basis for policy; increased priority to nutrition programs, measures to reduce neonatal and perinatal mortality, provision of emergency obstetric care, availability of skilled birth attendants, and a clear policy on integrated management of childhood illnesses. Enhanced planning capacity, development of a balanced human resource, improved governance to reduce staff absenteeism and frequent transfers, and a greater role of the private sector in the provision of services are some organizational aspects that need the governments' consideration. There are several lessons to be learnt: (i) Ministries of Health need sustained stewardship and well-documented evidence to protect cuts in resource allocation; (ii) frequent policy announcement sends inappropriate signals to managers and weakens on-going implementation; (iii) MCH/FP policies unless informed by evidence and participation of interest groups are unlikely to address gaps in programs; (iv) distributional and equity objectives of MCH/FP be addressed while setting overall national goals; (v) institutional capacity is a vital ingredient in translating MCH/FP policies into effective services. The suggested strategic directions emphasize, among others, the need for a comprehensive MCH/FP framework; strengthened stewardship in ministry of health, cost-effective strategies to address the gaps identified and doubling of the public sector resource allocation to MCH/FP over the next 5 years. The ability to ensure delivery of quality health services remains the biggest challenge in the Pakistani health sector. Unless sound policies are backed by well-functioning programs they are likely to become a victim of poor implementation.

Solitary fibrous tumour of the spinal cord.

We report an intramedullary primary solitary fibrous tumour of the cervical spinal cord in a 33-year-old man. The tumour predominantly consisted of monomorphic spindle cells with a storiform pattern. MRI demonstrated an inhomogeneously enhancing cervical intramedullary tumour. The patient was well without recurrence 18 months after surgery.