Chemotherapy for tumors: an analysis of the dynamics and a study of quadratic and linear optimal controls.

We investigate a mathematical model of tumor-immune interactions with chemotherapy, and strategies for optimally administering treatment. In this paper we analyze the dynamics of this model, characterize the optimal controls related to drug therapy, and discuss numerical results of the optimal strategies. The form of the model allows us to test and compare various optimal control strategies, including a quadratic control, a linear control, and a state-constraint. We establish the existence of the optimal control, and solve for the control in both the quadratic and linear case. In the linear control case, we show that we cannot rule out the possibility of a singular control. An interesting aspect of this paper is that we provide a graphical representation of regions on which the singular control is optimal.

A multi-centre study of Osseotite implants supporting mandibular restorations: a 3-year report.

This multi-centre study evaluated the performance of the Osseotite implant in the mandibular arch. Osseotite implants (n = 688) were placed in 172 patients; 43.5% were placed in the anterior mandible and 66.5% in the posterior mandible. Fifteen per cent of the implants were placed in soft bone, 56.9% in normal bone and 28.1% in dense bone. During placement, 49.9% of the implants were identified as having a tight fit, 48.6% a firm fit and 1.5% a loose fit. About one-third of the implants (32.4%) were short (10 mm in length or less). After 36 months, only 5 implants had been lost, for a cumulative survival rate of 99.3%. The 3-year results of this study indicate a high degree of predictability with placement of Osseotite implants in the mandibular arch.

Computing with DNA by operating on plasmids.

A new method of computing using DNA plasmids is introduced and the potential advantages are listed. The new method is illustrated by reporting a laboratory computation of an instance of the NP-complete algorithmic problem of computing the cardinal number of a maximal independent subset of the vertex set of a graph. A circular DNA plasmid, specifically designed for this method of molecular computing, was constructed. This computational plasmid contains a specially inserted series of DNA sequence segments, each of which is bordered by a characteristic pair of restriction enzyme sites. For the computation reported here, the DNA sequence segments of this series were used to represent the vertices of the graph being investigated. By applying a scheme of enzymatic treatments to the computational plasmids, modified plasmids were generated from which the solution of the computational problem was selected. This new method of computing is applicable to a wide variety of algorithmic problems. Further computations in this style are in progress.

The effect of hypotensive anesthesia on blood loss and operative time during Le Fort I osteotomies.

PURPOSE: The purpose of this prospective study was to compare the quality of the surgical field, blood loss, and operative time with either hypotensive or normotensive anesthesia during Le Fort I osteotomies. PATIENTS AND METHODS: Twenty-three patients were randomized into normotensive or hypotensive anesthesia treatment groups. The quality of the surgical field was assessed intraoperatively by direct observation and again postoperatively using video imaging. A standardized rating scale was applied at specific intervals by surgeons blinded to the anesthetic technique. The surgical time was measured on the videotape, and blood loss was measured by volumetric and gravimetric techniques. RESULTS: There was a statistically significant correlation (P < .0001) between the surgeon's perception of the quality of the surgical field and the blood pressure. There was also a statistically significant reduction (P < .01) in blood loss when using hypotensive anesthesia. However, there was no statistically significant reduction (P = .44) in operative time when using hypotensive anesthesia. CONCLUSIONS: It was concluded that hypotensive anesthesia is valuable in reducing blood loss and improving the quality of the surgical field during Le Fort I osteotomies, allowing for easier, more deliberate, and careful dissection. However, it does not reduce operative time.

Energy substrate metabolism during dual work rate exercise: effects of order.

Changes in workload are evident during many physical activities. The aim of this study was to assess total substrate metabolism when the temporal placement of a period of higher-intensity work (75% VO2max) was varied within a low-intensity exercise session (50% VO2max). One experimental trial (higher intensity first) comprised 5 min low-intensity work, followed by 15 min high-intensity work, followed by 40 min low-intensity work. The other trial (low intensity first) comprised 40 min low-intensity work, followed by 15 min high-intensity work, followed by 5 min low-intensity work. The trials were designed to achieve an identical total energy expenditure. Energy expenditure, fat and carbohydrate utilization were estimated by expired gas analysis and compared between conditions. Mean total energy expenditure during the higher-intensity phase was 1076 kJ and 1128 kJ in the high-intensity first and low-intensity first trials respectively (t6 = -3.76, P = 0.0047). Mean total energy expenditure for the whole trial was 3356 kJ and 3452 kJ in the high-intensity first and low-intensity first trials respectively (t6 = -3.48, P = 0.0065). Mean whole-trial fat utilization was 1753 kJ and 1857 kJ in the high-intensity first and low-intensity first trials respectively (t6 = -0.76, P = 0.24). Our findings suggest that changing the temporal placement of higher-intensity work within a low-intensity exercise session has a significant effect on total energy expenditure but not on the rate of fat oxidation.

Antibiotic prophylaxis in orthognathic surgery: a 1-day versus 5-day regimen.

PURPOSE: The effect on infection rates of 1-day and 5-day administration of prophylactic antibiotics in orthognathic surgical procedures was compared. PATIENTS AND METHODS: A prospective, randomized, double-blind clinical trial using placebo was conducted. Thirty patients were distributed equally between two groups. Each group received penicillin G, two million units intravenously, immediately preoperatively, and one million units intravenously every 3 hours intraoperatively and once postoperatively 3 hours after the last intraoperative dose. Group 1 then received penicillin G, one million units intravenously, every 6 hours for eight doses, followed by penicillin V suspension 300 mg orally every 6 hours for eight doses. Group 2 received placebo in a similar dosing schedule. The wounds were inspected on a regular schedule and evaluated for infection according to criteria established by the Centers for Disease Control. RESULTS: One of 15 patients in group 1 (6.7%) and 9 of 15 patients (60%) in group 2 became infected. The overall infection rate was 33.3%. There was a statistically significant difference in rates of infection between the two groups (P < .01). CONCLUSION: Antibiotic prophylaxis for orthognathic surgical procedures should continue beyond the immediate postoperative period. Five days of antibiotic administration appears to provide adequate coverage.

Dental extractions in patients on an oral anticoagulant: a survey of practices in North America.

PURPOSE: The World Health Organization (WHO) recommends the use of the International Normalized Ratio (INR) for reporting prothrombin time (PT) values. However, there are no scientifically based guidelines for performing dental extractions when using the INR. Oral and maxillofacial surgeons were surveyed to determine whether the INR is the method they use to monitor the level of anticoagulation and to determine what protocols are followed when anticoagulated patients require dental extractions. MATERIALS AND METHODS: A mail survey of academic oral and maxillofacial surgeons in North America was conducted to determine their choice of laboratory tests for assessing patients on oral anticoagulants and their protocol before proceeding to dental extractions. RESULTS: Fifty-three of 73 respondents (73%) routinely use the INR, but only 21% rely on this method alone. Twelve percent and 11% of respondents, respectively, also use the PT value and PT ratio. The level of anticoagulation at which surgeons would proceed with dental extractions was variable. For those using the INR, it was from 1.3 to 4.0, for those using PT ratios the perceived safe range was from 1.0 to 2.0, and for those using the PT value, the range was from 13 to 21 sec. CONCLUSIONS: Despite the support in the medical literature for use of the INR, many oral and maxillofacial surgeons still use the PT for monitoring oral anticoagulant therapy. There is no consensus on the INR interval at which dental extractions can be safely performed. Prospective studies are needed in this area.

Low-dose guanidine and pyridostigmine: relatively safe and effective long-term symptomatic therapy in Lambert-Eaton myasthenic syndrome.

Guanidine hydrochloride is known to be highly effective in the symptomatic treatment of the Lambert-Eaton myasthenic syndrome (LEMS). However, because of its potentially dangerous side reactions of hematologic abnormalities and renal insufficiency, 3,4-diaminopyridine, which is not readily available in the United States, is recommended as the preferred drug for LEMS. We used low-dose guanidine and pyridostigmine combination therapy in 9 patients with LEMS and analyzed its long-term safety and effectiveness. In all patients, a liberal amount of pyridostigmine was used, while daily guanidine dose was kept below 1000 mg a day, and guanidine was given between pyridostigmine dosings. This combination therapy was used for 3-102 months (mean: 34.1 months) and improved clinical status in all patients. Although guanidine had to be discontinued due to severe gastrointestinal symptoms in 3 cases, no serious side reactions such as bone marrow suppressions or signs of renal insufficiency developed in any case. Thus, we conclude that low-dose guanidine therapy is relatively safe and effective for long-term symptomatic treatment of LEMS when it is combined with pyridostigmine.

What is the INR?

The World Health Organization (WHO), the International Committee for Thrombosis and Hemostasis, and the International Committee for Standardization in Hematology, have strongly suggested that INR (International Normalized Ratio) values should be used to report a patient's level of coagulation. This paper discusses the use of the INR to monitor a patient's coagulation level, and reviews the recommendations on the INR levels at which dental extractions and similar oral surgical procedures may be performed safely. Studies are needed to determine whether new local hemostatic agents are sufficient for the safe management of patients at higher INR levels, thereby avoiding the need for hospitalization and heparin therapy.

Peroneal nerve repetitive nerve stimulation test: its value in diagnosis of myasthenia gravis and Lambert-Eaton myasthenic syndrome.

We have developed a repetitive nerve stimulation (RNS) technique for the peroneal nerve. Normal limits for the decremental responses for the anterior tibialis and extensor digitorum brevis muscles are 6-21% at the low rate of stimulation and 44-70% at the high rate of stimulation. These values exceed the normal limits for other commonly tested muscles. This may be due to the lower safety factor for neuromuscular transmission for the anterior tibialis and extensor digitorum brevis muscles. We present 4 cases in which the peroneal nerve RNS test was crucial for the diagnosis of the limb-girdle form of MG or LEMS. Thus, we conclude that, in a small number of patients with neuromuscular transmission disorders, the peroneal nerve RNS test is needed for confirmation of disease.

Shifting the responsibility for payment for state hospital services to community mental health agencies.

OBJECTIVE: In 1990 the state of Arkansas shifted financial responsibility for state hospital services to community mental health centers; through a policy known as "bed buy-back," centers now authorize all state hospital admissions and prospectively purchase bed days for their patients. Characteristics of patients hospitalized before and after implementation of the policy were examined to determine how the policy affected hospital admission rates, types of patients admitted, and the amount of contact between CMHC and hospital staff about admitted patients, as well as how these elements were affected differently in rural and urban areas. METHODS: Changes in the types of patients admitted over the 13 months before and 14 months after the change in financing were studied through retrospective chart review of 648 patients. Administrative data were used to examine changes in numbers of admissions for 30 months before and 26 months afterward. Data were analyzed by piecewise regression, least-squares, and logistic regression analyses. RESULTS: After financial decentralization, state hospital use was reduced in both urban and rural areas, although the reduction in urban areas was proportionally greater. Contrary to expectation, admissions were not limited to the most severely ill, disruptive, or substance-abusing patients, nor were they more likely to be readmitted. For patients who were admitted, communication between the community and the state hospital was greater than before financial decentralization. CONCLUSIONS: Shifting financial responsibility for patient care significantly reduced state hospital use, did not affect patient mix, and apparently increased coordination of care between community and hospital. Whether bed buy-back has affected the kind or quality of services delivered in the community awaits further study.

Aneurysmal bone cyst of the mandible.

The aneurysmal bone cyst (ABC) is a benign, solitary lesion of bone which is most commonly found in the long bones and vertebral column. Its occurrence in the mandible is uncommon. Because of its infrequent appearance, the ABC may be mistaken for neoplastic lesions. In the past, management has consisted of curettage, cryotherapy and local resection. In this publication we present a case of ABC of the mandible. We include a review of the literature, a discussion of the etiology, pathogenesis and management of this interesting lesion.

The effects of the helium-neon laser on postsurgical discomfort: a pilot study.

It has been postulated that low-energy lasers (soft lasers) have analgesic capabilities. European investigators who have worked with these lasers have tried to explain this phenomenon as an interference with the mediation of the pain message and/or the stimulation of endorphin production. There does not appear, however, to be much well-controlled research to support these claims. This study has examined the effect of the helium-neon laser on post-surgical discomfort. Fifteen patients who had surgical removal of bilaterally symmetrical mandibular third molars were evaluated. Laser therapy was applied to one side of each patient's mouth with the other side serving as the control. A similar technique of application, without activation of the laser beam, was utilized on the control side. This study has demonstrated that the helium-neon laser (632.8 nanometre (nm) at 10 milliwatt (mW), when applied to the surgical site for three minutes immediately following third molar surgery, reduced postoperative pain on the day of surgery and on the first postoperative day. This finding was statistically significant.

A clinical trial of intraligamentary anesthesia.

The effectiveness of the periodontal ligament injection in providing anesthesia for routine extractions and the possible mechanisms of action of the periodontal ligament injection in producing dental anesthesia were investigated in a clinical trial. Periodontal ligament injections were administered under strong pressure with lidocaine on 14 teeth, with epinephrine on seven teeth, and with normal saline on another seven teeth. The anesthesia attained was evaluated by: response of the teeth to an electric pulp tester, gingival probing around the teeth, and the ability for teeth to be extracted without pain. The results demonstrated that periodontal ligament injections with lidocaine were effective in providing adequate anesthesia for the performance of dental extractions. Lidocaine periodontal ligament injections were statistically and clinically more effective in attaining anesthesia than were epinephrine or saline injections. Epinephrine periodontal ligament injections resulted in a slight but statistically significant increase in the stimulus necessary to produce a patient response, when the teeth were stimulated with an electric pulp-tester. Saline injections produced no change in response to the stimulus tested. It appears, based on the results of the saline and epinephrine injections, that hydrostatic pressure had no direct effect on the production of anesthesia with the periodontal ligament injection.

The additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain.

In a double-blind, randomized, single-dose trial the analgesic contribution of acetaminophen, 1000 mg, and codeine, 60 mg, was determined. The study was a 2 X 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of: 1000 mg acetaminophen, 60 mg codeine, 1000 mg acetaminophen plus 60 mg codeine, or placebo. The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant (P less than 0.05) contribution to the analgesic effectiveness of the combination on all measures of efficacy (sum of pain intensity differences, largest pain intensity difference, total pain relief, largest pain relief, and time to remedication). The incidence of adverse effects did not appear to differ among the treatments, including placebo.

A comparative study of the effectiveness of metronidazole and penicillin V in eliminating anaerobes from postextraction bacteremias.

Recent reports have indicated the serious nature of anaerobic endocarditis and septicemia. As anaerobes can be isolated from postextraction bacteremias, this study was undertaken to evaluate the effectiveness of metronidazole and penicillin V in eliminating anaerobes from postextraction bacteremias. Twenty-five patients were randomly assigned to each of three groups--a placebo group, a metronidazole group, and a penicillin V group--for a total of seventy-five patients. Although penicillin V reduced the occurrence of anaerobes to a greater degree than did metronidazole, it was noted that gram-negative anaerobes were still detected in the blood of four patients in the penicillin V group. In the metronidazole group no gram-negative anaerobes were cultured. Because of the marked effectiveness of metronidazole against gram-negative anaerobes, the use of penicillin V and metronidazole in combination might be effective in the prevention of the sequelae of postextraction bacteremias. However, further studies, using a larger sample size, to investigate specifically gram-negative anaerobes are required.