Noninvasive measurement of regional blood flow in man

Regional blood flow in man is ideally measured by techniques that are noninvasive, accurate, and can measure flow repetitively with comparative ease. Although numerous noninvasive techniques are available, no single method records blood flow accurately in every location. The neophyte investigator is often faced with a confusing array of methods and can spend considerable time searching for the ideal one. This paper presents current methods available to the clinical or metabolic researcher and comments on the strengths and limitations of each method. It is hoped that this will allow more rapid selection of a flow measurement method that is tailored to each individual's need.     

A double blind clinical trial to assess the value of aprotinin in third molar surgery.

The bovine derived polypeptide, aprotinin, inhibits the activation of certain chemical mediators of acute inflammation. These mediators are responsible for causing pain and swelling in traumatised tissue. The properties of aprotinin were assessed in patients requiring surgical removal of third molars, a procedure which often results in considerable postoperative pain and swelling. A double blind clinical trial compared the effects of local infiltration of 1 ml of saline on one side of the mouth and aprotinin (10,000 international units) on the other, in patients requiring extraction of both mandibular third molars. Pain scores were assessed with a visual analogue scale, and swelling was subjectively assessed. The results, when analysed statistically, showed that aprotinin significantly reduced postoperative pain and swelling on the side of the mouth on which it was used, as compared to the control side (0.01% significance).     

The effect of an on-site radiology facility on radiologic utilization in family practice

Family physicians around the world are increasing their use of diagnostic x-ray examinations at a time of controversy about radiologic overutilization. To explore the role of accessibility in utilization, a study was undertaken testing the hypothesis that on-site radiology facilities are an important determinant of usage. Using a historical cohort design with chart review, rates in selected groups of patients were compared between two teaching family medicine centers, one with an on-site radiology service and one without. After controlling for confounding variables, patients with chest-related diagnoses were 2.4 times more likely (P less than .05) to have a chest film in the presence of on-site facilities. Rates for the off-site examination, upper gastrointestinal series, in patients with abdominal-related diagnoses were similar (relative risk 1.34, P greater than .5) at both centers. Higher usage brought no short-term clinical benefit. It was also observed that residents overinterpreted one quarter of chest films when compared with radiologists' reports.     

Molecular staging of head and neck squamous carcinoma

The staging system of head and neck cancer is a Tumor-Node-Metastases system that was developed by the American Joint Committee on Cancer. The stage of the head and neck cancer defines the extent of the lesion and is determined by physical examination, radiologic studies, and pathologic examination. Accurate staging of head and neck cancer is critical since it will determine the treatment modalities used to cure the disease. Recent advances in the field of molecular genetics have allowed clinicians to detect occult cancer cells previously missed by physical examination and standard histopathologic techniques. Molecular assays are 500 times more sensitive in identifying cancer cells than standard techniques and provide more objective analyses with fewer sampling errors. Consequently, these techniques are currently being used to perform molecular staging of head and neck cancer patients. Preliminary results show that molecular staging will accurately identify those patients at significantly increased risk for recurrence of their head and neck cancer.     

An automated multiplex oligonucleotide synthesizer: development of high-throughput, low-cost DNA synthesis.

An automated oligonucleotide synthesizer has been developed that can simultaneously and rapidly synthesize up to 96 different oligonucleotides in a 96-well microtiter format using phosphoramidite synthesis chemistry. A modified 96-well plate is positioned under reagent valve banks, and appropriate reagents are delivered into individual wells containing the growing oligonucleotide chain, which is bound to a solid support. Each well has a filter bottom that enables the removal of spent reagents while retaining the solid support matrix. A seal design is employed to control synthesis environment and the entire instrument is automated via computer control. Synthesis cycle times for 96 couplings are < 11 min, allowing a plate of 96 20-mers to be synthesized in < 5 hr. Oligonucleotide synthesis quality is comparable to commercial machines, with average coupling efficiencies routinely > 98% across the entire 96-well plate. No significant well-to-well variations in synthesis quality have been observed in > 6000 oligonucleotides synthesized to date. The reduced reagent usage and increased capacity allow the overall synthesis cost to drop by at least a factor of 10. With the development of this instrument, it is now practical and cost-effective to synthesize thousands to tens of thousands of oligonucleotides.     

Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution.

OBJECTIVE: To analyze treatment and survival of a large cohort of patients with retroperitoneal soft-tissue sarcomas (STS) treated and prospectively followed at a single institution. SUMMARY BACKGROUND DATA: Retroperitoneal STS are relatively uncommon and constitute a difficult management problem. Although surgical resection is often difficult or impossible, current chemotherapy is not effective and radiation is limited by toxicity to adjacent structures. Thus, complete surgical resection remains the most effective modality for selected primary and recurrent disease. METHODS: Five hundred patients with retroperitoneal STS were admitted and treated between July 1, 1982, and September 30, 1997, and prospectively followed. Patient, tumor, and treatment variables were analyzed for disease-specific and disease-free survival. Survival was determined with the Kaplan-Meier method. Statistical significance was evaluated using the logrank test for univariate influence and Cox model stepwise regression for multivariate influence. RESULTS: Two hundred seventy-eight patients (56%) had primary disease and 222 (44%) recurrent disease. Median follow-up was 28 months (range 1 to 172 months), 40 months for survivors. Median survival was 72 months for patients with primary disease, 28 months for those with local recurrence, and 10 months for those with metastasis. For patients with primary or locally recurrent tumors, unresectable disease, incomplete resection, and high-grade tumors significantly reduced survival time. CONCLUSIONS: In this study of patients with retroperitoneal STS, stage at presentation, high histologic grade, unresectable primary tumor, and positive gross margin are strongly associated with the tumor mortality rate. Patients approached with curative intent should undergo aggressive attempts at complete surgical resection. Incomplete resection should be undertaken only for symptom relief.     

A new bone/blood index in the study of labelled citrate metabolism in rat bones in fracture, deafferentation, rickets, and caries

A new bone/blood index has been developed which is calculated by dividing % of radionuclide inclusion in the bones by % of the inclusion in the serum. Graphic image of the index changes with time is significantly more demonstrative than digital tables and allows one not only easily measure distribution of the labelled compound between fractions diluted in the blood and sorbed on the bone but also specify a major direction of their transport between blood and bone. The index confirms the presence of biphasic primary fast but weak physical adsorption and secondary slow and strong chemisorption. This was established by the study of time course of the labelled citrate in intact rats of different age as well as in fracture and bone innervation defect, in rickets and dental caries. The proposed index can be applied in investigation of various diseases.     

Characteristics of protective immunity engendered by vaccination of mice with purified culture filtrate protein antigens of Mycobacterium tuberculosis.

In this study highly purified culture filtrate proteins obtained from Mycobacterium tuberculosis strains Erdman and H37Rv were tested for their capacity to stimulate immune T cells in vitro, and to immunize mice in vivo. Analysis of the culture filtrate antigen pool revealed a complex mixture of proteins; after separation of this pool into fractions of defined molecular size using an electrophoretic method, it was found that multiple fractions strongly stimulated interferon-gamma (IFN-gamma) secretion by immune CD4 T cells in vitro. In a further series of experiments mice were given multiple immunizations with the culture filtrate protein pool suspended in emulsions of incomplete Freund's adjuvant. Such mice were as resistant as mice given live bacillus Calmette-Guérin (BCG) vaccine to a low dose aerosol challenge infection with M. tuberculosis, but this resistance waned to low levels by 5 months post-vaccination. Furthermore, experiments using the filtrate antigens to boost or augment immunity induced by the BCG vaccination itself were unsuccessful. These data therefore support the hypothesis that the culture filtrate proteins of M. tuberculosis contain multiple antigens that are strongly recognized by T cells acquired during the initial expression of protective immunity to tuberculosis. Conventional immunization with these purified protein antigens can engender a strong degree of protective immunity, but this immunity is apparently not sustained at the same level as that induced by the live vaccine, perhaps suggesting a lack of suitable stimulation of memory immunity.