A protease-based biosensor for the detection of schistosome cercariae.

Parasitic diseases affect millions of people worldwide, causing debilitating illnesses and death. Rapid and cost-effective approaches to detect parasites are needed, especially in resource-limited settings. A common signature of parasitic diseases is the release of specific proteases by the parasites at multiple stages during their life cycles. To this end, we engineered several modular Escherichia coli and Bacillus subtilis whole-cell-based biosensors which incorporate an interchangeable protease recognition motif into their designs. Herein, we describe how several of our engineered biosensors have been applied to detect the presence and activity of elastase, an enzyme released by the cercarial larvae stage of Schistosoma mansoni. Collectively, S. mansoni and several other schistosomes are responsible for the infection of an estimated 200 million people worldwide. Since our biosensors are maintained in lyophilised cells, they could be applied for the detection of S. mansoni and other parasites in settings without reliable cold chain access.

Repeat urethrotomy and dilation for the treatment of urethral stricture are neither clinically effective nor cost-effective.

PURPOSE: We developed an algorithm for the management of urethral stricture based on cost-effectiveness. MATERIALS AND METHODS: United Kingdom medical and hospital costs associated with the current management of urethral stricture were calculated using private medical insurance schedules of reimbursement and clean intermittent self-catheterization supply costs. These costs were applied to 126 new patients treated endoscopically for urethral stricture in a general urological setting between January 1, 1991 and December 31, 1999. Treatment failure was defined as recurrent symptomatic stricture requiring further operative intervention following initial intervention. Mean followup available was 25 months (range 1 to 132). RESULTS: The costs were urethrotomy/urethral dilation 2,250.00 pounds sterling (3,375.00 dollars, ratio 1.00), simple 1-stage urethroplasty 5,015.00 pounds sterling (7,522.50 dollars, ratio 2.23), complex 1-stage urethroplasty 5,335.00 pounds sterling (8,002.50 dollars, ratio 2.37) and 2-stage urethroplasty 10,370 pounds sterling (15,555.00 dollars, ratio 4.61). Of the 126 patients assessed 60 (47.6%) required more than 1 endoscopic retreatments (mean 3.13 each), 50 performed biweekly clean intermittent self-catheterization and 7 underwent urethroplasty during followup. The total cost per patient for all 126 patients for stricture treatment during followup was 6,113 pounds sterling (9,170 dollars). This cost was calculated by multiplying procedure cost by the number of procedures performed. A strategy of urethrotomy or urethral dilation as first line treatment, followed by urethroplasty for recurrence yielded a total cost per patient of 5,866 pounds sterling (8,799 dollars). CONCLUSIONS: A strategy of initial urethrotomy or urethral dilation followed by urethroplasty in patients with recurrent stricture proves to be the most cost-effective strategy. This financially based strategy concurs with evidence based best practice for urethral stricture management.

Prolonged but reversible respiratory failure in a newborn with Prader-Willi syndrome.

A 29-week premature infant with severe central hypoventilation secondary to Prader-Willi syndrome required mechanical ventilation until 55 days of age. This disorder must be considered in the differential diagnosis of a premature infant who does not have primary lung disease but has significant hypotonia because the respiratory failure may require prolonged supportive care.

Identifying a new reality: zero vascular access recirculation using ultrasound dilution.

Access recirculation measurements by blood urea nitrogen (BUN) sampling methods have come under recent criticism regarding their reliability especially at low levels of recirculation. New methods have shown that the majority of patients have much less recirculation than previously suspected. However, some of these methods are prone to the same factors that limit BUN measurement accuracy. A new method, ultrasound dilution, was studied that avoids these problems and supports a new clinical reality--zero access recirculation. Information on the relationship of recirculation to access flow was also obtained which supports the assumption that patients with adequate vascular access flows have no recirculation.

Treatment of juvenile migraine with subcutaneous sumatriptan.

An open, prospective study was undertaken to assess the efficacy and safety of subcutaneous sumatriptan in 17 children, ages 6 to 16 years, with severe, recurrent migraine. A 6-mg dose was used in 15 patients and relieved headache within 1 hour in six and by 2 hours in five others. Two smaller children received a 3-mg dose and both were headache-free within 2 hours. Most also reported marked improvement in associated symptoms such as nausea and photophobia. Four subjects had no clinical improvement after a 6-mg dose. Side effects, such as neck pressure, were brief and mild. These findings suggest that subcutaneous sumatriptan can be both effective and safe as an abortive agent in juvenile migraine, but the appropriate dose in smaller children will need further investigation.

Vision despite tomographic absence of the occipital cortex.

A 14-month-old boy with developmental delay showed microcephaly, spastic diplegia, central visual fixation and an esotropia. A head tomographic scan disclosed absence of normal occipital cortex and electroencephalography showed markedly reduced voltages over the occipital region. Visual development in this patient may be related to heterotopic occipital cortex of a functioning non-striate system of visual processing. Visual function cannot be predicted when severe developmental anomalies of the occipital cortex are detected with computerized tomography.

Paroxysmal facial itch: a presenting sign of childhood brainstem glioma.

Two children with neurofibromatosis and a chief complaint of severe, episodic, unilateral facial itching were found to have brainstem glioma. Initial computerized tomography of the brain was thought to be normal, but the brainstem tumor was subsequently demonstrated on magnetic resonance imaging. The paroxysmal facial itching resolved in both cases after a course of radiation therapy. The pathophysiology of the attacks of facial itching is unknown but must be related to the brainstem glioma. This is the first report of paroxysmal, unilateral facial itching as a presenting sign of childhood brainstem tumor.

Childhood seizures. Individualized treatment based on type.

Seizures in children can have greatly differing prognosis and treatment, depending on the type of seizure, age at onset, and family and medical history. Treatment can vary from none at all (eg, in the child with a single febrile seizure) to the use of more than one drug and the ketogenic diet (eg, in poorly controlled atypical absence, atonic, and some myoclonic disorders). When drug therapy is required, an appropriate agent is started and the dosage increased as needed to control seizures. If seizures persist or toxicity occurs, another drug should be substituted. When the patient has been seizure-free for a year, the drug can be slowly decreased and eventually discontinued. Any recurrence is most likely to occur within the first year after anticonvulsive medication is stopped.

Ocular motor apraxia associated with intracranial lipoma.

Congenital ocular motor apraxia is rarely associated with brain tumors. A 10-month-old girl with normal vertical eye movements and head thrusting to initiate horizontal saccades is presented. CT brain scan revealed a midline posterior fossa mass and histopathology confirmed the clinical diagnosis of lipoma. Unlike previously described cases of posterior fossa brain tumors associated with congenital ocular motor apraxia, this patient showed persistent ocular motor apraxia despite complete resection of the tumor.

Comparison of self-hypnosis and propranolol in the treatment of juvenile classic migraine.

In a prospective study we compared propranolol, placebo, and self-hypnosis in the treatment of juvenile classic migraine. Children aged 6 to 12 years with classic migraine who had no previous specific treatment were randomized into propranolol (at 3 mg/kg/d) or placebo groups for a 3-month period and then crossed over for 3 months. After this 6-month period, each child was taught self-hypnosis and used it for 3 months. Twenty-eight patients completed the entire study. The mean number of headaches per child for 3 months during the placebo period was 13.3 compared with 14.9 during the propranolol period and 5.8 during the self-hypnosis period. Statistical analysis showed a significant association between decrease in headache frequency and self-hypnosis training (P = .045). There was no significant change in subjective or objective measures of headache severity with either therapy.

Childhood migraine. Differential diagnosis and treatment.

Migraine headaches may be confused with other types of headache, namely, those caused by tension and by organic disorders, but several features often set them apart. For one, migraines are often accompanied by other symptoms, such as nausea and vomiting. Also, they often are present in the family history. Treatment can involve such methods as biofeedback, diet, and limitation of exercise, and a number of medications are available for both treatment and prophylaxis. Studies of drug treatment of childhood migraine are few, so clinicians must tailor treatment to the individual case, watching for side effects and limiting the duration of treatment as much as possible.

Hearing loss following Hemophilus influenzae meningitis in infancy. Diagnosis by evoked response audiometry.

Bacterial meningitis is a major cause of sensorineural hearing loss during childhood. This study compared the efficacy of auditory brain-stem evoked response (ABER) testing with conventional conditioned orienting response (COR) testing in the early diagnosis of postmeningitic deafness in 34 infants younger than 2 years of age, with a diagnosis of Hemophilus influenzae meningitis. In most of the children (62%), results of the two tests were in agreement. The use of ABER testing appeared to be more effective than COR audiometry for the testing of infants younger than 6 months of age, for older children with perceptual handicaps, and for the identification of small children with unilateral hearing loss.

Adrenoleukodystrophy: early frontal lobe involvement on computed tomography.

The computed tomographic (CT) findings in a teenage boy with adrenoleukodystrophy (ALD) are presented. Clinical presentation included the subacute onset of dementia and behavioral changes. Bilateral, isolated, symmetric low density areas were present in the frontal lobes on CT, without contrast enhancement. Minimal calcification was noted in the lesions. This unusual pattern of early frontal lobe demyelination in ALD is discussed.

Susceptibility of Pasteurella haemolytica to the bactericidal effects of serum, nasal secretions and bronchoalveolar washings from cattle.

Several isolates of logarithmic-phase organisms of Pasteurella haemolytica were shown to be sensitive to an antibody and complement-mediated killing mechanism in adult bovine serum. Data suggested that the classical complement pathway was important in the induction of bactericidal activity of serum. Sera from calves after colostrum feedings (post-colostral sera) killed only 30% of the bacteria in spite of the presence of high levels of antibodies against P. haemolytica. Addition of post-colostral serum to heat-inactivated adult bovine serum decreased the bactericidal capacity of the latter. It was speculated that this inhibition may have been caused by the presence of blocking antibodies (IgA) found in the post-colostral serum. Undiluted nasal secretions collected from adult cattle were not bactericidal to P. haemolytica. The results also suggest that the bronchoalveolar washings (BAW) from vaccinated calves, in spite of having a high antibody titer, were less bactericidal to P. haemolytica than BAW from sham-vaccinated calves (71.12% vs. 83.12%). The bactericidal factor(s) present in BAW from sham-vaccinated calves was heat stable, not complement dependent, and was not related to lysozyme concentration.

Intravenous glycerol and mannitol therapy in children with intracranial hypertension.

Acute intracranial hypertension may respond to intravenous mannitol, but frequent administration can cause cerebral edema or renal problems. We evaluated the use of 20% glycerol administered intravenously as an alternative to mannitol. Intravenous glycerol and mannitol were equally effective in lowering acute elevations of intracranial pressure. The duration of effect was similar for both agents. Side effects of intravenous glycerol were related to concentration, rate, and frequency of administration. In severe encephalopathies, such as Reye syndrome, we recommend infusions of 20% glycerol or 20% mannitol at a dose of 0.5-1.0 gm per kilogram. Glycerol should be administered in 0.45% or 0.9% saline, no faster than 1.5 ml (3.3 mOsm) per minute.

Acute hemiparesis in juvenile insulin-dependent diabetes mellitus (JIDDM).

Four episodes of acute left hemiparesis occurred in three pediatric-age, insulin-dependent diabetic patients. Each had a concomitant respiratory tract infection and headache, but no obvious signs of systemic hypoglycemia. No cerebral abnormalities were demonstrated by angiography or computerized tomography. The clinical course was benign, with slow but complete resolution of neurologic abnormalities within 8 to 24 hours of onset, and no further neurologic complaints in a 7- to 16-month follow-up.

Intrauterine chronic subdural hematoma.

We discuss a newborn delivered by elective cesarean section who had macrocephaly with severe anemia. The anemia was corrected by exchange transfusion, and the infant, at first, appeared stable but manifested poor feeding and seizures. Transillumination of the skull was negative, although the anterior fontanel was tense. Computerized tomography demonstrated mild hydrocephalus and suggested subdural fluid. Bilateral subdural taps yielded fluid typical for chronic subdural hematoma. To our knowledge, this is the first documented case of intrauterine subdural hematoma developing in the absence of trauma. An analogy is made to the pathogenesis of subdural hematoma after rapid decompression of the ventricular system by shunting procedures for obstructive hydrocephalus.