The spectral signature method for the analysis of PET brain images

We introduce the concept of the metabolic centroid spectrum as the feature space to characterize the distribution of metabolic activity in three-dimensional brains. The method computes the metabolic centroid of a brain subvolume for each increment of metabolic activity occurring in the whole brain. The result is the metabolic spectral signature, a continuous three-dimensional curve whose shape reflects the distribution of metabolic rates in the brain. The method's sensitivity to metabolic distribution asymmetries is greatly increased over that of the metabolic centroid method, while retaining its advantages; it is almost invariant to head size, head positioning, photon scatter, and the positron emission tomography (PET) camera's full width at half-maximum. It does not require magnetic resonance, computed tomography, or x-ray images. To test the method we analyzed the metabolic PET images of 40 normal subjects and 20 schizophrenics. The results show a unification of several metabolic characteristics of schizophrenic brains, such as laterality, hypofrontality, cortical/subcortical abnormalities, and overall brain hypometabolism, which were identified by different laboratories in separate studies using differing methodologies. Here they are presented by a single automatic objective method.     

Value of a random single Doppler study of the umbilical artery for predicting perinatal outcome

A prospective blinded study was performed on 191 high-risk patients with pregnancies ranging from 25 to 42 weeks gestation to investigate the value of a single Doppler analysis of the umbilical artery blood flow waveform (systolic-to-diastolic ratio, S/D) for predicting poor perinatal outcome. This was defined as the presence of heavy meconium, delivery of a growth-retarded infant, an umbilical cord arterial pH less than 7.2, or a 5-minute Apgar score less than 7. The interval between Doppler examination and delivery ranged from 12 hours to 15 weeks. No clinical data were available to the examiner performing the Doppler study. Moreover, the Doppler measurements were unknown to the attending physicians. The sensitivity, specificity, and positive and negative predictive values of the Doppler study in predicting outcome were 30.4%, 92.9%, 36.8%, and 92.6%, respectively, with an adverse outcome prevalence of 12%. These results indicate that a single random S/D ratio from the umbilical artery is not an adequate screening test for the risk of perinatal complications.     

A method of repair for quadriceps tendon or patellar ligament (tendon) ruptures without cast immobilization. Preliminary report

The quadriceps tendon and patellar tendon (ligament) were repaired with a Dacron vascular graft used as a tension suture material. In cases of quadriceps tendon ruptures, the Dacron graft is passed transversely through the patellar ligament just below the patella and crossed transversely at the level of the musculotendinous junction with two loops applying tension to the tendon, which brings the tendon ends together by creating a solid structure. In cases of patellar ligament ruptures, the Dacron graft is passed through a hole in the tibia posteriorly to the tibial tuberosity instead of through the patellar ligament below the patella. This technique enables early mobilization on the first day after surgery. The technique was first tested on six dogs with severed quadriceps tendons and patellar ligaments that were repaired with this suture method. All of the animals recovered from surgery and walked and ran normally on the repaired legs within 27 days and with only mild limping after 17 days. The technique was then used on six patients, four with complete quadriceps tendon rupture and two with complete tear (avulsion) of the patellar ligament (tendon). In all of the patients, excellent surgical results were obtained and leg immobilization was virtually eliminated. Physical therapy was prescribed the first day after surgery. The rehabilitation period was significantly reduced.     

Bactericidal/permeability-increasing protein in host defense and its efficacy in the treatment of bacterial sepsis

The 55-kD bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived polypeptide belonging to a family of lipid and endotoxin binding proteins. BPI is composed of two functionally distinct structural domains: a potently antibacterial and antiendotoxin ∼ 20-kD aminoterminal half, and an opsonic carboxy-terminal portion. In multiple animal models, a recombinant amino-terminal fragment of BPI (rBPI₂₁) is nontoxic and protects against gram-negative bacteria and endotoxin. In humans, rBPI₂₁ is also nontoxic and nonimmunogenic and has undergone phase II/III clinical trials with apparent therapeutic benefit.     

Traumatic injuries associated with horseback riding.

BACKGROUND: According to the Center for Disease Control and Prevention (CDC), an estimated 30 million people ride horses each year in the United States. Horseback riding related injuries are common, with an estimated 50,000 emergency room visits annually. The popularity of recreational horseback riding has increased in South Florida and the incidence of associated traumatic injuries is a reflection of this. MATERIAL AND METHODS: Retrospective review of patients admitted to a state designated Level I trauma center that sustained horseback riding associated injuries between January 2000 and December 2003. Information extracted from the Trauma Center's data base included demographics, mechanism of injury and toxicology screening. RESULTS: During the review period, twenty-seven patients were identified. There were 12 men and 15 women. The average age was 36 years. The injuries occurred during pleasure riding in 23 patients and thoroughbred related activities in 4 patients. Multiple severe injuries were common and documented in 24 patients. All patients required hospitalization with an average stay of 5 days. Five patients had a positive toxicology screen on admission. No deaths were documented in this review. CONCLUSION: Horseback riding related injuries tends to be serious. Alcohol and recreational drugs may contribute to exacerbate the extent of these injuries. The use of proper protective equipment, instructions for safe riding, and discouraging drug and alcohol use during riding activities should be emphasized.     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

Production and characterization of high affinity monoclonal antibodies to cyclic anti-depressant molecules

A procedure is reported by which high levels of the tricyclic molecule desipramine was modified and conjugated at high density to the carrier molecules keyhole limpet hemocyanin and bovine serum albumin so that these could be used as immunogens in Balb/c mice. Such conjugates generated immune responses with high levels of antibody with specificity for the tricyclic. B cell hybridomas generated by fusion of immune Balb/c splenocytes to NS-1 cells which secreted monoclonal antibodies with specificity for the tricyclic were selected in a standard ELISA. In this report, we show that the binding constants of these monoclonal antibodies with various haptens can be assessed accurately by measuring fluorescence polarization, that a high degree of cross-reactivity between the monoclonals and various tricyclics exists, and that this procedure can be used to generate monoclonal antibodies of high binding constants.     

Parathyroid hormone decreases in vivo insulin effect on glucose utilization

Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulinmediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1–34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3±0.2 versus 9.9±0.1 mg/dl, P<0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166±4 versus 155±4 mg/dL, P<0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5±0.6 versus 5.6 ±0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205±13 versus 173±9; P<0.03). Also, calculated glucose disappearance rates (Kg) were decreased in the PTH-infused rats (4.05±0.3 versus 4.63±0.8; P=0.054), suggesting an impaired peripheral effect of insulin on glucose utilization. To gain insight into the potential contribution of the hypercalcemia or the PTH to these abnormalities, correlation evaluations were performed. Only in PTH-infused rats did plasma Ca correlate with plasma glucose at 0 and 20 minutes (r=0.6, P=0.02; r=0.7, P=0.01) and with the area under the glucose curve (r=0.6, P=0.03) during the glucose-insulin infusion. Also only in PTH-infused rats did PTH correlate with 0 (P=0.07) and 20-minute (P=0.02) plasma glucose levels. There was no correlation between either Ca or PTH and basal insulin levels or the area under the insulin curve in either group. Consequently, we suggest that in the rat, PTH infusion associated with hypercalcemia impairs insulin effect on glucose utilization in vivo and this defect may be induced by the Ca, PTH, or both.This study was presented in part at the 76th Annual Meeting of the Endocrine Society, Anaheim, CA, USA, June 1994.