Changes in resting connectivity during recovery from severe traumatic brain injury.

In the present study we investigate neural network changes after moderate and severe traumatic brain injury (TBI) through the use of resting state functional connectivity (RSFC) methods. Using blood oxygen level dependent functional MRI, we examined RSFC at 3 and 6 months following resolution of posttraumatic amnesia. The goal of this study was to examine how regional off-task connectivity changes during a critical period of recovery from significant neurological disruption. This was achieved by examining regional changes in the intrinsic, or "resting", BOLD fMRI signal in separate networks: 1) regions linked to goal-directed (or external-state) networks and 2) default mode (or internal-state) networks. Findings here demonstrate significantly increased resting connectivity internal-state networks in the TBI sample during the first 6 months following recovery. The most consistent finding was increased connectivity in both internal and external state networks to the insula and medial temporal regions during recovery. These findings were dissociable from repeat measurements in a matched healthy control sample.

Tumour lysis syndrome: an unusual presentation.

We report a case of spontaneous tumour lysis syndrome that developed postoperatively in a patient with undiagnosed Burkitt's lymphoma. The former diagnosis was made, unusually, following the development of white emulsion-like urine in the catheter bag whilst the patient was being managed in the intensive care unit. After laboratory analysis, the urine was found to contain large quantities of uric acid crystals which were the key to the prompt diagnosis. Spontaneous tumour lysis syndrome is rare and this case highlights the difficulties in making an early diagnosis when the presence of a predisposing tumour has not yet been identified. Untreated tumour lysis syndrome can be fatal due to severe biochemical disturbances causing cardiac dysfunction and multi-organ failure. Early recognition and treatment are crucial to prevent morbidity and mortality. The unusual presentation of this case in association with an undiagnosed Burkitt's lymphoma emphasises how vigilant anaesthetists and intensivists must be in recognising this potentially life-threatening condition. We believe that the triggering factor in this case was laparotomy and handling of the tumour.

Chlorproguanil-dapsone for treatment of drug-resistant falciparum malaria in Tanzania.

BACKGROUND: Resistance to the affordable malaria treatments chloroquine and pyrimethamine-sulfadoxine is seriously impeding malaria control through treatment in east Africa. We did an open, alternate drug allocation study to assess the efficacy of chlorproguanil-dapsone in the treatment of falciparum malaria clinically resistant to pyrimethamine-sulfadoxine. METHODS: Children younger than 5 years with non-severe falciparum malaria, attending Muheza district hospital in Tanzania, were treated with the standard regimen of pyrimethamine-sulfadoxine. Patients whose clinical symptoms resolved but who remained parasitaemic 7 days after pyrimethamine-sulfadoxine were followed up for 1 month. Clinical malaria episodes were retreated with either single dose pyrimethamine-sulfadoxine or a 3-day regimen of chlorproguanil-dapsone. Those with parasitaemia after 7 days were treated with chlorproguanil-dapsone. Parasite DNA was collected on day 7 after first treatment with pyrimethamine-sulfadoxine and we looked for point mutations in the genes encoding dihydrofolate reductase (dhfr) and dyhydropteroate synthetase (dhps). FINDINGS: 360 children were enrolled and treated with pyrimethamine-sulfadoxine. On day 7, 192 (55%) of 348 had cleared parasitaemia. Of the remaining 156 parasitaemic children, 140 (90%) were followed up to day 28, and 92 (66%) of 140 developed clinical malaria. These 92 patients were alternately retreated with either pyrimethamine-sulfadoxine (46) or chlorproguanil-dapsone (46). 28 (61%) of 46 children retreated with pyrimethamine-sulfadoxine were still parasitaemic at day 7, compared with three (7%) of 44 [corrected] children retreated with chlorproguanil-dapsone. Resistance to pyrimethamine-sulfadoxine increased from 45% (156/348) at the first treatment to 61% (28/46) after retreatment. 83 of 85 parasite isolates collected after the first pyrimethamine-sulfadoxine treatment, and before and after the second treatments with pyrimethamine-sulfadoxine and chlorproguanil-dapsone showed triple-mutant dhfr alleles, associated with a variety of dhps mutations. INTERPRETATION: Most patients treated with pyrimethamine-sulfadoxine, who remain parasitaemic at day 7, develop new malaria symptoms within 1 month. Chlorproguanil-dapsone was a practicable therapy under these circumstances. Analysis of parasite dhfr and dhps before and after treatment supports the view that pyrimethamine-sulfadoxine resistance in this part of Africa is primarily due to parasites with three mutations in the dhfr domain.

Tumour lysis syndrome during anaesthesia.

We describe a child who developed acidosis, hyperkalaemia and cyanosis while emerging from an otherwise uneventful anaesthetic. A diagnosis of tumour lysis syndrome was suspected and confirmed biochemically. Although this syndrome is usually associated with chemotherapy and has been described to occur spontaneously, it has not previously been reported as being associated with anaesthesia.

The association between Porphyromonas gingivalis-specific maternal serum IgG and low birth weight.

BACKGROUND: In Alabama, low birth weight (LBW) infants are about 20 times more likely to die before their first birthday compared to normal birth weight infants. While the rate of LBW has been consistently higher among African Americans compared to whites, there has been a gradual increase in LBW for both African Americans and whites over the last 15 years. In an attempt to identify modifiable risk factors for LBW, we have previously reported that a pregnant woman's poor periodontal health may be an independent risk factor for low birth weight. METHODS: A predominantly African American and socioeconomically homogeneous group of 448 women was followed from the second trimester of their first pregnancy. Thirty-nine LBW cases were observed at the end of follow-up. Using 17 preterm LBW cases and 63 randomly selected controls from the above cohort, the periodontal pathogen-specific maternal serum IgG levels during the second trimester of pregnancy were evaluated in relation to birth weight of the infant, while controlling for known risk factors for LBW. RESULTS: Porphyromonas gingivalis (P.g.)-specific maternal serum IgG levels were higher in the LBW group (mean 58.05, SE = 20.00 microg/ml) compared to the normal birth weight (NBW) group (mean 13.45, SE = 3.92 microg/ml; P= 0.004). Women with higher levels of P.g.-specific IgG had higher odds of giving birth to LBW infants (odds ratio [OR] = 4.1; 95% confidence interval [CI] for odds ratio = 1.3 to 12.8). This association remained significant after controlling for smoking, age, IgG levels against other selected periodontal pathogens, and race. CONCLUSIONS: Low birth weight deliveries were associated with a higher maternal serum antibody level against P. gingivalis at mid-trimester.

Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients.

OBJECT: This study was conducted to determine whether proton magnetic resonance spectroscopy (MRS) is a sensitive method for detecting diffuse axonal injury, which is a primary sequela of traumatic brain injury (TBI). Diffuse axonal injury is characterized by selective damage to white matter tracts that is caused in part by the severe inertial strain created by rotational acceleration and deceleration, which is often associated with motor vehicle accidents. This axonal injury is typically difficult to detect by using conventional imaging techniques because it is microscopic in nature. The splenium was selected because it is a site vulnerable to shearing forces that produce diffuse axonal injury. METHODS: The authors used proton MRS to evaluate the splenium, the posterior commissure of the corpus callosum, in normal control volunteers and in patients with TBI. Proton MRS provided an index of neuronal and axonal viability by measuring levels of N-acetyl aspartate (NAA). CONCLUSIONS: A majority of mildly brain injured patients, as well as those more severely injured, showed diminished NAA/creatine (Cr) levels in the splenium compared with normal control volunteers. The patients displaying lowered NAA/Cr in the splenium were also likely to exhibit lowered NAA/Cr in lobar white matter. Also, the levels of NAA/Cr in the splenium of normal volunteers were higher compared with those found in lobar white matter. Decreases in NAA/Cr levels in the splenium may be a marker for diffuse injury. A proton MRS examination may be particularly useful in evaluating mildly injured patients with unexplained neurological and cognitive deficits. It is concluded that MRS is a sensitive tool in detecting axonal injury.

The effect of character and array type on visual spatial search quality following traumatic brain injury.

Disorders of visuomotor function are common following traumatic brain injury (TBI), but spatially directed visual attention has received little study in this population. 'Cancellation' testing is a common bedside method for assessing directed attention, which can provide information on how task properties influence visual scanning and search following severe TBI. Groups of 20 individuals after severe TBI and 21 healthy control subjects were matched for age and education. Participants performed finger tapping tests to assess motor speed as well as four cancellation tests employing letter and geometric figure stimuli in random and structured arrays. Control and TBI groups differed significantly on measures of accuracy, task completion time, and search quality. There was no significant effect of stimulus or array type on accuracy or time. Figure targets in a higher search quality, suggesting a right hemispheric dominance effect on these tasks. The findings support a deficit in visuomotor scanning performance in TBI beyond a purely motor effect. Interactions between stimulus and array types suggest that hemispheric cooperation is required for the optimal performance of these tasks, and that interhemispheric communication may be preferentially compromised by TBI.

Effect of stimulus number, target-to-distractor ratio, and motor speed on visual spatial search quality following traumatic brain injury.

The object of this study was to investigate stimulus effects and motor limitations on visuospatial performance after traumatic brain injury (TBI). Previous findings have not fully explained the basis of attentional impairments after TBI. There has been little study of the spatial aspects of attention and information processing in this group. We studied 20 patients after severe TBI and 21 healthy controls. Four random-array letter cancellation tasks, varying in number of stimuli (50 and 100) and target-to-distractor ratio (1:4 and 1:9) were employed. Performance was calculated from the number and proportion of cancelled targets, as well as time to completion. TBI subjects were slower on finger tapping and achieved lower cancellation performance scores. Both TBI subjects and controls performed better on tasks with target-to-distractor (T/D) ratios of 1:4 than on those with 1:9. There was no effect of stimulus number. We conclude that there are both quantitative (speed) and qualitative contributors to impaired visuospatial ability following TBI. Motor impairments may slow the overall cancellation performance, but the differential effect of T/D ratio in the two populations suggests that TBI impairs quality of research. Accounting for both speed and accuracy suggests increased utility for the cancellation paradigm in clinical and research assessment of visuospatial attention.

Community treatment with ivermectin for onchocerciasis in the east Usambara mountains.

Ivermectin 150mcg/kg was given orally to 743 patients with positive skin snips for Onchocerca volvulus and to 697 residents in two villages in the Usambara mountains. 620 villagers attended for a second dose. On direct questioning, 98.7% patients with +ve skin snips and 91.8% villagers given mass chemotherapy admitted to adverse reactions. After a second dose, 16.6% had mild reactions. No serious problems were encountered. 167 of 170 repeat skin snips were negative. Repeated administration of ivermectin is well tolerated and offers a chance of reducing the burden of onchocerciasis in the Usambara mountains.

Hands across the equator: the Hereford-Muheza link eight years on.

Short elective sabbatical visits have been arranged between Herefordshire Health Authority in England and Muheza Health District in Tanzania over the past eight years. Any employee can apply, and the 64 who have participated include midwives, physiotherapists, engineers, and nurse tutors. The possibility of being chosen adds to the attractiveness of working in both districts, and costs have been small. The visits are believed to have led to new ideas and a willingness and confidence to consider change.

Rotating stations: an innovative approach to third-year medical student education in physical medicine and rehabilitation.

Education of medical students is an important component of physical medicine and rehabilitation training programs. A one-day combined lectures/rotating stations conference was designed to introduce physical medicine and rehabilitation to third year medical students during the academic years 1991 through 1993. Pre- and post-testing allowed objective measurement of student knowledge of physical medicine and rehabilitation. The lectures and rotating stations were evaluated, and the feedback was used to improve subsequent conferences. Pre- and post-tests indicated increased student knowledge, and interest in physical medicine and rehabilitation doubled in each class that participated. This instructional method increases third year medical student exposure to physical medicine and rehabilitation in a cost-effective and efficient manner.

Metabolic studies in kidney stone disease.

Patients with kidney stones (n = 59) and healthy controls (n = 31) collected a 24-hour urine sample and later underwent a 6-hour 'fast and load' test in which an oral calcium load was taken after 2 hours. In the 24-hour urine sample, mean calcium excretion was higher in patients than controls, while mean urate, oxalate and citrate levels were similar. The patients had higher levels of fasting plasma calcium, serum calcitriol and fasting urinary calcium, and lower levels of plasma phosphate than did the controls. Following the calcium load, plasma and urinary calcium increased similarly in both groups. Serum parathyroid hormone (PTH) levels were similar in both groups and decreased similarly following the calcium load. Multiple linear regression, relating the presence or absence of stone formation to all variables, found the only variables significantly related to stone formation to be plasma levels of calcium (p less than 0.001) and phosphate (p = 0.001) and fasting urinary urea (p less than 0.001), and 24-hour urinary calcium excretion (p less than 0.05). Urinary oxalate and citrate were not related to stone formation. The data do not support the hypothesis that primary stimulation by calcitriol produces a normal fasting plasma calcium level, with an exaggerated increase after an oral calcium load. The findings instead suggest an abnormality of parathyroid cell 'set point', such that PTH secretion continues until the plasma calcium level is a little higher and the phosphate a little lower than in controls.

Treatment of Paget's disease of bone with a combination of intranasal salmon calcitonin and oral calcium and thiazide.

The purpose of this study was to establish the smallest dose of nasally administered salmon calcitonin (SCT) which, if given in conjunction with a previously published calcium/thiazide treatment, would be as effective as parenteral SCT in the treatment of Paget's disease of bone. Forty patients suffering from symptomatic Paget's disease were treated with 0.5 g calcium three times daily, 10 mg/day clopamide, and 400 IU nasally administered salmon calcitonin given once or twice weekly. This regimen was given for 5 months, after which all treatment was ceased for 4 months. Parenteral SCT (100 IU) was then given three times weekly for 5 months to 25 of the patients. With the oral/nasal treatment, the plasma alkaline phosphatase level (AP) decreased by 30 +/- 15 (SD)% when the SCT was given once weekly and by 39 +/- 11% (P less than 0.05) when the SCT was given twice weekly. There were similar decreases in the fasting urinary hydroxyproline:creatinine ratios. The parenteral SCT reduced the AP by 33 +/- 23%. Though reduction in bone pain was similar with both treatments, most patients preferred the oral/nasal treatment. It is concluded that the oral/nasal treatment, when the SCT is given twice weekly, has similar efficacy to parenteral SCT, and is a well tolerated, effective initial treatment for Paget's disease of bone.

Bone death in hip fracture in the elderly.

We examined femoral head bone from 50 cadavers and from 21 patients who had suffered pathologic fracture of the femoral neck. We used a histochemical technique for lactate dehydrogenase (LDH) activity to demonstrate osteocyte viability. The femoral heads were removed within 36 hours of death or fracture, as LDH activity persists in the cytoplasm of viable cells for this time at 37 degrees after interruption of the blood supply. In the controls, there was an age-related reduction in mean osteocyte viability, from 88 +/- 7% (mean +/- SD) at age 10-29 years to 58 +/- 12% at age 70-89 years. In the hip fracture patients, mean osteocyte viability was 58 +/- 21% but there was much variability in both osteocyte viability and bone mass. In 5 fracture patients, there was extensive osteocyte death, suggesting that most of the femoral head bone was nonviable; these patients had little microfracture callus. Others had predominantly viable bone which was usually osteoporotic, and their bone frequently showed microfracture callus. Osteomalacia was not seen in any patient. It is suggested that bone death, in addition to osteoporosis, may sometimes contribute to hip fracture in the elderly.

Measurement of bone in the os calcis: a clinical evaluation.

Bone mineral content (BMC) was measured in the os calcis of 232 normal subjects aged 17-82 years. The mean reproducibility (coefficient of variation) of the measurement was 1.8%. Substantial bone loss occurred between the ages of 20 and 50 years, and in females the menopause was associated with additional bone loss. There was no significant difference in the rate of bone loss in females and males, but the mean BMC was greater at all ages in males than in females. We also compared os calcis BMC with spinal bone mineral density (BMD), measured by quantitative computed tomographic (CT) scanning, in 85 subjects: 33 were normal controls, 19 had osteoporosis defined by the presence of one or more pathological fractures, and in the remainder the CT examination was performed at the patient's request. Os calcis BMC correlated with spinal BMD in both females (r = 0.69, p less than 0.001) and males (r = 0.84, p less than 0.001). However, the os calcis BMC did not reliably predict spine values around the CT "fracture threshold" of 90-100 mg/cm3 and did not correlate with osteoporotic fracture as well as did spinal BMD. It is concluded that measurement of the os calcis BMC is of limited clinical usefulness for the early diagnosis of osteoporosis.

Disorders of calcium and bone metabolism.

Calcium levels in blood are maintained within narrow limits by parathyroid hormone, acting on kidney, bone and gut. Our understanding of the mechanisms of these actions has increased greatly in recent years, for example by identification of new hormones (eg 1,25 dihydroxy vitamin D) and by the study of isolated bone cells. Though most clinical disorders of calcium metabolism are now readily diagnosed and many are effectively treated, some serious problems still remain. Foremost amongst these are the early diagnosis of osteoporosis and the treatment of osteoporosis after fractures have occurred. Most disorders of calcium metabolism have ophthalmologic manifestations, sometimes troublesome to the patient, and sometimes diagnostically helpful.