Screw head plugs increase the fatigue strength of stainless steel, but not of titanium, locking plates.

OBJECTIVES: Screw plugs have been reported to increase the fatigue strength of stainless steel locking plates. The objective of this study was to examine and compare this effect between stainless steel and titanium locking plates. METHODS: Custom-designed locking plates with identical structures were fabricated from stainless steel and a titanium alloy. Three types of plates were compared: type I unplugged plates; type II plugged plates with a 4 Nm torque; and type III plugged plates with a 12 Nm torque. The stiffness, yield strength, and fatigue strength of the plates were investigated through a four-point bending test. Failure analyses were performed subsequently. RESULTS: For stainless steel, type II and type III plates had significantly higher fatigue strength than type I plates. For titanium, there were no significant differences between the fatigue strengths of the three types of plates. Failure analyses showed local plastic deformations at the threads of screw plugs in type II and type III stainless steel plates but not in titanium plates. CONCLUSION: The screw plugs could increase the fatigue strength of stainless steel plates but not of titanium plates. Therefore, leaving screw holes open around fracture sites is recommended in titanium plates.Cite this article: L-W. Hung, C-K. Chao, J-R. Huang, J. Lin. Screw head plugs increase the fatigue strength of stainless steel, but not of titanium, locking plates. Bone Joint Res 2018;7:629-635. DOI: 10.1302/2046-3758.712.BJR-2018-0083.R1.

Bioequivalence study of tramadol by intramuscular administration in healthy volunteers.

Tramadol hydrochloride (CAS 36282-47-0) is a centrally acting analgesic agent binding to mu opiate receptors. The bioavailability of a new tramadol hydrochloride injection (Limadol) was compared with a commercially available reference product by intramuscular administration in twelve healthy Chinese male volunteers by a standard two-way cross-over trial. Each volunteer received a single 100 mg injection of tramadol HCl in each phase. The bioavailability was compared using the area under the plasma concentration-time curve from time 0 to 30 h (AUC0-30), the area under the plasma concentration-time curve from time 0 to infinity (AUC0-infinity), peak plasma concentration (Cmax), and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the Tmax, Cmax, AUC0-30 and AUC0-infinity of the two preparations. It is concluded that test and reference formulations of tramadol hydrochloride are bioequivalent for both the extent and rate of absorption after a single intramuscular injection.

Treatment, outcomes, and prognostic factors of ear cancer.

Cancer of the ear is rare and a consensus has not been reached as to the most appropriate treatment. In this retrospective study, we examined the treatment modalities, prognostic factors, and outcomes of patients treated for ear cancer at the National Taiwan University Hospital during a 15-year period. The disease-free survival rates of patients with three different disease grades were compared using the log-rank test. The effects of prognostic factors on survival were examined with Cox's proportional hazard model. Of the 61 ear cancer patients treated from January 1982 through October 1996, 47 (36 men, 11 women; mean age, 54.6 yr) had complete records and were included in this study. The tumor originated from the middle ear in 29 (62%) patients and from the external ear canal in 18 (38%). A total of 37 patients underwent radical mastoidectomy to remove the gross tumor, while six underwent wide excision of the tumor. Concomitant parotidectomy or neck dissection was performed in seven patients. Thirty-eight patients received postoperative radiation therapy and five patients received chemotherapy for palliative treatment of recurrent or inoperable tumors. All but four (9%) of 43 patients developed facial nerve palsy postoperatively. There were no deaths directly related to surgery or other major complications, including cerebrospinal fluid leakage, meningitis, or hemiparesis. The 5-year disease-free survival rate was 53% overall (n = 47), but differed significantly among patients with different grades of disease (p = 0.038): 66% for grade I (n = 27), 44% for grade II (n = 17), and 0% for grade III (n = 3). Multivariate analysis revealed that cervical lymph node metastasis was a poor prognostic factor (relative hazard, 16.4; p < 0.001). These results suggest that mastoidectomy with postoperative radiation therapy can yield satisfactory outcomes, even in some cases of advanced (grade II) disease.

Determination of clindamycin in human plasma by liquid chromatography-electrospray tandem mass spectrometry: application to the bioequivalence study of clindamycin.

A simple, sensitive and specific liquid chromatography-electrospray tandem mass spectrometry (LC-MS-MS) method for the determination of clindamycin (I) was developed. Both I and verapamil (II, internal standard) were analyzed using a C18 column with a mobile phase of 80% acetonitrile-0.01% trifluoroacetic acid. Column eluents were monitored by electrospray tandem mass spectrometry. Multiple reaction monitoring (MRM) using the parent to daughter combinations of m/z 425-->126 and 455-->165 was used to quantitate I. A limit of quantitation of 0.0500 microgram/ml was found. The assay exhibited a linear dynamic range of 0.0500-20.0 micrograms/ml and gave a correlation coefficient (r2) of 0.998 or better. The chromatographic run time was approximately 2 min. The intra-batch precision and accuracy of the quality controls (QCs, 0.0500, 0.150, 1.50, 15.0 and 20.0 micrograms/ml) were characterized by coefficients of variation (CVs) of 5.13 to 13.7% and relative errors (REs) of -4.34 to 4.58%, respectively. The inter-batch precision and accuracy of the QCs were characterized by CVs of 4.35 to 8.32% and REs of -10.8 to -4.17%, respectively. The method has successfully been applied to the analysis of samples taken up to 12 h after oral administration of 300 mg of I in healthy volunteers.

Topography of low skin resistance points (LSRP) in rats.

Based on the electrical properties of the skin, a method employing the unijunction transistor (UJT) relaxation oscillator for detecting low skin resistance points (LSRP) was developed in this study. By means of this instrumentation, the topography of the LSRP in Wistar rats was developed. All the LSRP in the rats were found to be bilaterally and symmetrically distributed except those points located on the dorsal midline (i.e., governor vessel, GV) and the ventral midline (i.e., conception vessel, CV). The resistances of the LSRP on these two major vessels, including 14 CV points and 17 GV points of six rats were experimentally determined to be in the ranges of 179.4 +/- 41.2 K omega and 152.5 +/- 32.2 K omega, respectively. The resistances of the GV points were found in general to be lower than those of the CV points. Most non-LSRP, on the other hand, exhibited resistances of greater than 420 K omega. It is noted that the resistances of most LSRP increased yet still retained a separate identity within thirty minutes after the death of the animals, but the low resistance properties of some LSRP gradually disappeared thereafter and could not be detected by the relaxation oscillator.

Studies of in vivo Gene Transfer by Electropulsation at the Low Skin Resistance Points (LSRPs).

Electropulsation has been proved to be a powerful technique for DNA transfection in vitro. This study was undertaken to assess the feasibility and evaluate the potential of applying this approach for facilitating gene transfer in vivo. The pCMVß plasmid, containing the Escherichia coli lacZ open reading frame under the cytomegalovirus early promoter, was complexed with poly-L-lysine (PLL) and injected directly into the livers of Wistar rats; electropulsation was then applied either at the low skin resistance points (LSRPs) of the skin, the non-LSRP, or directly at the liver by either a portable electrostimulator or an electropulsation unit. The locations of the LSRPs were detected by the unijunction transistor (UJT) relaxation oscillator. Seventy-two hours after gene transfer, the animals were sacrificed and the livers were excised, followed by examination of the transgene expression. The results obtained from X-gal staining, in situ hybridization, and Western blot analysis indicated that lacZ gene was expressed in the livers. Variations of the electropulsation parameters, including site of electropulsation, wave type, amplitude of the pulses, repetition rate, duty cycle, and duration of electropulsation treatment, do not reveal any statistically significant effects of differences of these variables on the transgene expression. Comparison of the results obtained from direct injection of PLL/pCMVß (1:1) followed by electropulsation at the LSRPs with that of direct PLL/pCMVß (1:1) injection, however, suggests that gene transfer by electropulsation achieved a higher transfection efficiency in vivo (p >. 05).

Medically inoperable stage I endometrial carcinoma: a few dilemmas in radiotherapeutic management.

PURPOSE: The aggressiveness of radiation therapy for patients with medically inoperable endometrial carcinoma is controversial. Patients may die of their underlining medical disease before succumbing to cancer. We try to identify certain subgroup of patients who might benefit most from an aggressive approach and also investigate the impact of residual tumor present in dilatation and curettage (D&C) specimen obtained in second intracavitary implant (ICI). METHODS AND MATERIALS: From 1965 to 1990, 101 patients were treated for clinical clinical Stage I endometrial carcinoma with RT alone due to medical problems. Ages ranged from 39 to 94 years (median 71 years). There were 18 patients with clinical Stage IA and 83 with clinical Stage IB disease. Histology included 44 well-differentiated, 37 moderately differentiated, and 20 poorly differentiated tumors. Radiation therapy consisted of external beam only in 3 patients, ICI alone in 26, whole pelvis plus ICI in 10, and whole pelvis plus split field plus ICI in 62. A second D&C was performed on 26 patients at the time of the second ICI. Minimum follow-up was 2 years (median, 6.3 years). RESULTS: The 5-year actuarial disease-free survival (DFS) for the studied cohort is comparable to the expected survival of an age-matched population. Pelvic control was 100% for Stage IA and 88% for Stage IB with 5-year disease-free survivals of 80 and 84%, respectively. We also observed a greater disassociation of DFS and overall survial among patients older than 75 years (84 and 55%, respectively) than in younger patients (84 and 78%, respectively). This is mainly because older patients succumbed to their medical illness. Well-differentiated disease demonstrated the trend toward a better outcome than moderately or poorly differentiated lesions in Stage IB patients (p = 0.05), but not in Stage IA patients. Aggressive radiation therapy approach showed the trend toward a better result in Stage IB patients 75 years of age or younger. There were two failures among 19 patients with no tumor found in the D&C specimen at the time of second implant. In contrast, seven patients with residual tumor seen in the endometrial sample at the time of second implant remain disease free. CONCLUSIONS: Radiation therapy alone is an effective treatment modality for medically inoperable Stage I endometrial carcinoma. Disease-free survival can be translated into longer overall survival in the younger age group, but not in older patients. The latter tend to die of their underlining medical illness. Tumor differentiation influenced the prognosis of Stage IB disease. No tumor seen in the endometrial sampling at the time of second implant did not correlate with a better disease control, and the treatment plan should not be modified on such information.

Secondary malignancy among seminoma patients treated with adjuvant radiation therapy.

PURPOSE: Early-stage testicular seminoma is among the most radiosensitive tumors, with an overall cure rate of over 90%. Among those cured of the disease by orchiectomy and postoperative irradiation, there is a risk of having a second malignancy. We conducted a study to determine the relative risk of the occurrence of secondary malignancy. METHODS AND MATERIALS: From 1964 through 1988, 128 patients with histologically confirmed early-stage seminoma of the testis underwent orchiectomy and postoperative irradiation at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, and affiliate hospitals. The follow-up periods ranged from 5 to 29 years, with a median of 11.7 years. The expected rate of developing a second cancer was computed by the standardized incidence ratio using the Connecticut Tumor Registry Database. The rate is based on the number of person-years at risk, taking into account age, gender, and race. RESULTS: Nine second nontesticular malignancies were found; the time of appearance in years is indicated in brackets: two squamous cell carcinomas of the lung [3, 11], one adenocarcinoma of the rectum [15], one chronic lymphocytic leukemia [2], one adenocarcinoma of the pancreas [14], one diffuse histiocytic lymphoma of the adrenal gland [7], one sarcoma of the pelvis [5], and two transitional cell carcinomas of the renal pelvis and ureter [14, 17]. One patient who developed a contralateral testicular tumor was excluded from risk assessment. The actuarial risk of second nontesticular cancer is 3%, 5%, and 20%, respectively, at 5, 10, and 15 years of follow-up. When compared with the general population, the overall risk of second nontesticular cancer in the study group did not reach the 0.05 significance level, with an observed/expected (O/E) ratio of 2.09 (95% confidence interval, 0.39-3.35). When analyzed by the latency period after radiation treatment, during the period of 11 to 15 years, the risk was higher (O/E ratio of 4.45, 95% confidence interval, 1.22-11.63) than expected. The median duration for developing a second cancer was 11 years for tumors arising from tissues outside the irradiated field and 14 years for those within or near the irradiated area. CONCLUSIONS: The overall observed incidence of second nontesticular malignancy among patients with early-stage testicular seminoma treated with adjuvant radiation therapy was not significantly increased in comparison with the expected incidence. Clinical implications are discussed.

Reirradiation of recurrent skin cancer of the face. A successful salvage modality.

BACKGROUND: The aim of this study was to assess the effectiveness of full doses of reirradiation to salvage previously irradiated recurrent skin cancer of the face. METHODS: As of December 1990, 17 patients at the Mallinckrodt Institute of Radiology were reirradiated for recurrent skin cancer in previously irradiated areas of the face. There were eight basal cell and nine squamous cell carcinomas. The interval between the two treatments ranged from 6 months to 15 years (median, 4 years). The dosimetry was reviewed, and the radiation doses were recomputed by the biologic effective dose (BED) formula. RESULTS: The accumulated BED from the two irradiation regimens ranged from 48.78 to 143.5 Gy on the skin surface (median, 103 Gy) and 80.93 to 160.68 Gy at 5 mm depth (median, 108 Gy). Local control was achieved in ten patients; two of them had skin defects that required reconstruction. Six of seven patients with persistent tumors had squamous cell carcinoma. Those patients with BED of previous treatment at 5 mm depth less than 55 Gy, and accumulated BED on skin surface of no more than 110 Gy had the best outcome. The residual damage of skin from previous treatment is a function of fraction size and total dose. CONCLUSIONS: Reirradiation is a feasible treatment alternative for recurrent skin cancer of the face when cosmesis is a concern.

Radiation therapy for primary orbital lymphoma.

PURPOSE: The influence of tumor size, grade, thoroughness of staging workup, and radiation dose on disease control, radiation-related complications, and incidence of systemic progression of primary orbital lymphoma is analyzed. METHODS AND MATERIALS: Twenty patients with Stage I primary orbital lymphoma were treated from August 1976 through August 1991 at Mallinckrodt Institute of Radiology. Staging workups included physical examination, chest x-ray, complete blood count (CBC), liver function test, and computerized tomography (CT) scan of the orbit, abdomen, and pelvis. Nineteen patients had bone marrow biopsy. The histological types based on the National Cancer Institute working formulation were 9 low-grade and 11 intermediate-grade, including five lymphocytic lymphomas of intermediate differentiation. The extension of disease and the volume of tumor were evaluated by CT scan of the orbit. The most commonly used radiation therapy technique was single anterior direct field with 4 MV or 6 MV photons. Lens was shielded or not treated in eight patients. Dose ranged from 20 to 43.2 Gy. Thirteen of 20 patients received 30 Gy. Minimum follow-up was 24 months (median, 4 years). RESULTS: Local control was achieved in all 20 patients. One patient with lymphocytic lymphoma with intermediate differentiation developed disseminated disease. Actuarial disease-free survival (DFS) was 100% and 90% at 2 and 5 years, respectively. No retinopathy was observed. Cataracts were noted in seven patients at 1 to 10 years following irradiation (median, 2 years). Three patients developed lacrimal function disorder; however, no corneal ulceration occurred. CONCLUSIONS: Thirty Gy in 15 fractions appears to be a sufficient dose for local control with acceptable morbidity, especially for low-grade, as well as certain types of intermediate-grade lymphomas, such as diffuse small cleaved cell and lymphocytic lymphoma of intermediate differentiation. Systemic dissemination is minimal, provided local control is achieved and initial staging workups are adequate.

Brachytherapy-related complications for medically inoperable stage I endometrial carcinoma.

PURPOSE: The current study was conducted to investigate the incidence and risk factors for medical complications associated with low dose rate brachytherapy in patients with medically inoperable Stage I endometrial cancer treated with irradiation alone. METHODS AND MATERIALS: From 1965 through 1991 at Mallinckrodt Institute of Radiology, 150 implants were performed on 96 patients who were deemed medically unfit for hysterectomy because of advanced age, obesity, and various medical problems. The records of these patients were examined retrospectively to determine the incidence of medical complications that occurred in the first 30 days following the initiation of brachytherapy. The association of risk factors that precluded major surgery and the occurrence of brachytherapy-related complications was examined by logistic regression. RESULTS: Of these 96 patients, 40 patients were older than 75 years, and 31 patients were deemed morbidly obese. Medical problems included hypertension in 45 patients, and diabetes in 37; there was a history of congestive heart failure in 23, stroke in 11, myocardial infarction in 10, and thromboembolism in 8. There were concurrent malignancies in five patients. Implants were performed using intrauterine Simon-Heyman capsules, tandems, and vaginal ovoids in all patients. General anesthesia was used for 98 implants, spinal anesthesia for 26, local anesthesia for 25, and epidural anesthesia for 1. The duration of anesthesia ranged from 30 to 120 min (median, 60 min). The duration of radioisotope application ranged from 11 to 96 h (median, 46 h). Preventive measures included low dose subcutaneous heparin in 55 patients (since 1978), and intermittent pneumatic compression boots in 29 (since 1985). Four patients developed life-threatening complications including myocardial infarction (two patients), congestive heart failure (one patient), and pulmonary embolism (one patient). Two of these four patients died; one with a myocardial infarction and the other with pulmonary embolism. The morbidity rate was thus 4.2% (4 out of 96), and the mortality was 2.1% (2 out of 96). Although the four serious complications occurred within 30 days of the procedure, only one complication and one death occurred during treatment. There was no correlation between occurrence of complications and medical risk factors, type and duration of anesthesia, or type and duration of implant. CONCLUSIONS: There is a low incidence of complications associated with conventional low dose rate brachytherapy. The procedure is well tolerated in patients with medically inoperable Stage I endometrial cancer. In comparison to the predicted serious complication rate of surgery in these patients, the number of life-threatening complications from brachytherapy appears to be quite acceptable.

A multivariate analysis of prognostic factors in management of pineal tumor.

PURPOSE: A multivariate analysis of prognostic factors of treatment outcome of pineal tumor. METHODS AND MATERIALS: From February 1979 to June 1987, 25 patients with primary pineal tumors were treated in our department. Patients were treated with either AECL Co-60 unit or 10 MV linear accelerator to the primary tumor with an adequate margin or to the whole brain (median dose of 36 Gy) with or without a cone-down boost of 10 to 20 Gy. Craniospinal irradiation was performed in two patients with positive CSF cytology. Minimum follow-up was 40 months. Patients were further stratified according to tumor type. Group I consisted of seven patients with pineal germinoma. Group II included nine patients with nongerminoma, and Group III represented nine patients treated without a histological verification but clinical diagnosis. RESULTS: The relapse-free survival (RFS) of Group I patients was 100% and 86% at 2 and 5 years, respectively. Relapse-free survival was 55% and 21% at 2 and 5 years, respectively, for Group II patients. Six of 9 patients in Group II died of disease due to either local recurrence or tumor seeding. Eight of 9 patients in Group III remain no evidence of disease, and RFS was 89% at 2 and 5 years. Multivariate analysis revealed that tumor histology is the only significant prognosticator. Age, gender, type of surgical procedure, RT field, and tumor dose were not. Cox's regression model also failed to demonstrate a significant correlation of tumor seeding with the type of surgery. CONCLUSION: The type of tumors in the pineal region dictates the treatment outcome. Definitive radiation therapy is effective in controlling germinoma, whereas a more aggressive approach is needed to improve local control for nongerminoma. For a localized pineal lesion, we advocate that treatment can be tailored to the primary tumor with adequate margins. However, for locally advanced tumors whole brain or craniospinal irradiation should be considered. No definitive correlation between type of surgery and the probability of tumor seeding was identified.

Formation of trimethylamine from dietary choline by Streptococcus sanguis I, which colonizes the mouth.

Choline is a component of the normal diet, and when humans ingest large amounts they excrete trimethylamine (which can impart a fishy body odor). In the presence of nitrite, trimethylamine can be converted to dimethylnitrosamine, a potent carcinogen. Bacteria in the large intestine metabolize choline to form trimethylamine. We determined that a bacterium normally present in the oral cavity also has this capacity. Mixed bacterial flora cultured from dental plaque and saliva converted choline to trimethylamine. The only organism with trimethylamine-forming capability isolated from these mixed cultures was identified as Streptococcus sanguis I (a facultative anaerobe). The other products formed when choline was cleaved were ethanol and acetate. The formation of trimethylamine by S. sanguis I was enzyme-mediated. Activity was destroyed by heating at 100 degrees C, and obeyed Michaelis-Menten kinetics (K(apparent) for choline = 184 +/- 58 microM; V(max apparent) = 1.7 +/- 0.1 micromol/mg protein/h). Activity was maximal at pH 7.5 to 8.5, was membrane-bound, and required a divalent metal cation (cobalt or iron). More trimethylamine was produced by bacteria incubated under a nitrogen than under an aerobic atmosphere. Activity was inhibited by deanol, betaine aldehyde, hemicholinium-3, iodoacetate, semicarbazide, and 2,4-dinitrophenol, and was enhanced by sulfhydryl-reducing agents (glutathione, 2-mercaptoethanol, DL-dithiothreitol) and sodium bisulfite. The enzyme activity that we describe in S. sanguis I is similar to that previously described in the anaerobic bacteria isolated from intestinal flora.

Uptake of choline by rat mammary-gland epithelial cells.

The neonatal mammal requires especially large amounts of choline to sustain growth. Much of this choline is derived from the newborn's only source of food, milk. The concentration of choline in rat milk [182 +/- 24 microM (S.E.M.)] was much higher than that in maternal serum (11.6 +/- 0.9 microM), suggesting that a mechanism capable of concentrating choline into milk must exist. We characterized choline uptake by mammary epithelial cells (the site of milk production) of the lactating rat. We observed two uptake processes, one saturable and obeying Michaelis-Menten kinetics, and the other non-saturable and linear. At physiological blood choline concentrations, the saturable component of choline uptake predominated. The saturable component had Kapp. = 35 +/- 16 microM, and Vmax. = 1.24 +/- 0.19 nmol/h per mg of protein. Saturable uptake of choline was inhibited by hemicholinium-3. Ca2+ was required for uptake, but Mg2+ was not. Replacement Na+ with K+, Li+ or sucrose inhibited transport. Ouabain did not inhibit choline uptake. Choline concentration in epithelial cells was 67.7 +/- 1.9 nmol/g wet wt. at the start of incubation at 37 degrees C and rose to 80.9 +/- 6.5 nmol/g wet wt. over 30 min. Much of the choline accumulated by the mammary gland (in the presence of endogenous concentrations of choline) remained in the form of choline (50 +/- 1.2%), phosphatidylcholine (12 +/- 2.3%), lysophosphatidylcholine (0.1 +/- 0.03%), betaine (7 +/- 0.3% and phosphocholine (6 +/- 0.5%). In addition, we isolated 25 +/- 1.2% of choline-derived radiolabel in an unidentified compound.

[Comparative study on the clinical effects and endometrial findings of IUD].

PIP: Clinical effects of IUD and its related endometrial changes in 418 women were studied. Typical subjects had their IUDs inserted in their mid to late 20s after 3 pregnancies and 2 child births. Major endometrial changes included leukocyte, endometrial hyperplasia, squamous metaplasia, but no malignant changes were noted. Of 418, 327 had CU-medicated IUDs (Group I) and 91 had non-medicated IUDs (Group II). Group I consisted of 259 users of Copper T-200, 35 users of multi load CU-250, 33 users of Nova T-200. Group II consisted of 54 users of Spira-ring and 37 users of Lippes loop. There was no significant difference between the 2 groups in duration of IUD use. 1/3 of all subjects had their IUDs removed within a year. 80% of CU-medicated IUDs were removed in 1 to 3 years. 20% of both groups removed IUDs because of excessive discharge; 60%, because of genital bleeding; 25%, because of pregnancy. 20% of both groups also complained of pain. The rate of removal due to side-effects was significantly lower in Group I than Group II (p0.001), although the removal due to side-effects took place earlier in Group I than Group II (P0.005). CU-medicated IUDs had lower rate of removal due to pregnancy than non-medicated group (p0.001). 8 cases of all subjects had inflammatory reaction within 2 years of insertion; 27 cases (6.5%), endometrial proliferative activity within 3 years. 7 cases of 259 Copper-T users had squamous metaplasia within two years of insertion. In conclusion, periodic pap smear test should be conducted on IUD users.^ieng

A dicentric iso (Y) chromosome in an infertile male.

A dicentric Y chromosome was detected in a 30-year-old azoospermic male patient who was found to be mosaic for 45,X/46,X,dic Y(qter----p11::p11----qter). The dicentric iso (Y) chromosome was identified conclusively with C-banding, G-banding and Q-banding techniques. The relationship of structural abnormalities of the Y chromosome and azoospermia is discussed.