Sharon V. Medendorp

Prospective study of osseous, articular, and meniscal lesions in recent anterior cruciate ligament tears by magnetic resonance imaging and arthroscopy

Fifty-four patients with anterior cruciate ligament tears that were arthroscopically reconstructed within 3 months of initial injury were prospectively evaluated. Patients with grade 3 medial collateral ligament, lateral collateral ligament, or posterior cruciate ligament tears were excluded. Eighty percent of our patients had a bone bruise present on the magnetic resonance image, with 68% in the lateral femoral condyle. Two of the latter findings—an abnormal articular cartilage signal (P = 0.02) and a thin and impacted subchondral bone (P = 0.03)—had a significant relationship with injury to the overlying articular cartilage. Meniscal tears were found in 56% of the lateral menisci and 37% of the medial menisci. A significant association was present between bone bruising on the lateral femoral condyle and the lateral tibial plateau (P = 0.02). Results of our study support the concept that the common mechanism of injury to the anterior cruciate ligament involves severe anterior subluxation with im paction of the posterior tibia on the anterior femur. Determination of the significance of bone bruising, ar ticular cartilage injury, or meniscal tears will require a long-term followup that includes evaluation for arthritis, stability, and function. These 54 patients represent the first cohort evaluated in this ongoing prospective clinical study.

Endoscopic ultrasound cannot determine suitability for esophagectomy after aggressive chemoradiotherapy for esophageal cancer.

OBJECTIVE:Endoscopic ultrasound (EUS) provides important information in the initial staging of patients with esophageal cancer. With recent modifications in chemoradiotherapy protocols, a significant number of patients have no residual tumor at esophagectomy. The high surgical morbidity and mortality might be avoided if complete response to chemoradiotherapy could be predicted. Previously published clinical trials, with relatively small patient numbers, have suggested that EUS may accurately stage esophageal cancer after chemoradiotherapy. The aim of this study was to verify the accuracy of EUS in staging esophageal cancer after effective chemoradiotherapy.METHODS:EUS staging was performed before and after concurrent cisplatin, 5-fluorouracil, and hyperfractionated radiotherapy in 59 patients with newly diagnosed esophageal cancer. All patients underwent subsequent esophagectomy and pathological staging. The accuracy of preoperative, postchemoradiotherapy EUS was evaluated in a retrospective fashion by comparison to pathological staging.RESULTS:After chemoradiotherapy, 18 patients (31%) had no residual disease at pathological staging (T0N0). However, EUS correctly predicted complete response to chemoradiotherapy (T0N0) in only three patients (17%). The accuracy of postchemoradiotherapy EUS for pathological T stage was only 37%, and its sensitivity for N1 disease was only 38%. EUS was unable to distinguish postradiation fibrosis and inflammation from residual tumor.CONCLUSION:When aggressive preoperative chemoradiotherapy is provided to patients with esophageal cancer, the predictive value of postchemoradiotherapy EUS is inadequate for use in clinical decision making.

Zinc Gluconate Lozenges for Treating the Common Cold: A Randomized, Double-Blind, Placebo-Controlled Study

The common cold is one of the most frequently occurring human illnesses in the world. More than 200 viruses can cause common colds in adults, including rhinoviruses (the most frequent cause), coronaviruses, adenoviruses, respiratory syncytial virus, and parainfluenza viruses. In the United States each year, adults develop an average of two to four colds and children develop an average of six to eight colds [1, 2]. The morbidity resulting from this disease and the subsequent financial loss in terms of working hours are substantial [3]. Many previously described treatments have not provided consistent or well-documented relief of symptoms. Even a treatment that is only partially effective in relieving cold symptoms could markedly reduce physical malaise and economic losses in a large population. The medical literature describes many possible mechanisms by which zinc may treat the common cold, and seven controlled trials have studied the use of zinc for this purpose. All seven were double-blind, placebo-controlled studies, but each used different formulations and dosages of zinc. Three of these studies showed that zinc had a beneficial effect [4-6] and four did not [7-10]. In the studies that examined virus shedding [5, 7], zinc treatment had no effect on this shedding. We designed a study similar to that of Godfrey and colleagues [6] and used the symptom score developed by these researchers. We emphasized starting treatment within 24 hours after the onset of symptoms, because Godfrey and colleagues found that early treatment was most effective. We used zinc gluconate lozenges, which appeared to be well tolerated and had the best bioavailability profile in previous studies. Other studies [4-7, 9] used lozenges containing 23 mg of zinc. To improve palatability, lozenges in our study contained 13.3 mg of zinc. This provided a local concentration of zinc ions of about 4.4 mmol/L, an amount greater than that necessary to suppress rhinovirus (0.1 mmol/L) [11, 12]. The placebo lozenge contained 5% calcium lactate so that it had a medicinal taste similar to that of the zinc gluconate lozenge. Ours was a pragmatic study designed to determine the efficacy of zinc gluconate lozenges in reducing clinical symptom scores under conditions that reflected usual medical care for the common cold [13, 14]. We did not seek to define the mechanism of any zinc effect. Although virus cultures or serologic tests might have been desirable, we decided not to do these tests because they are almost never done in the course of standard care. Methods Study Design We determined that a 50% reduction in the duration of symptoms (in days) would represent a significant clinical effect. A previous study of zinc gluconate given during the first day of cold symptoms suggested that the duration of illness was reduced from approximately 8 days to 4 days after treatment began [6]. Our previous research on patients with colds who were seen at the Cleveland Clinic suggested that the mean duration (SD) of cold symptoms was approximately 7 6 days [15, 16]. We chose a sample size of 100 patients so that we could detect a difference in the mean number of days of symptoms from 8 days in the placebo group to 4 days in the zinc group with a standard deviation of 6 days, a two-sided P value of 0.05, and an approximate power of 90%. Patients were recruited from among the Cleveland Clinic staff through announcements in internal Clinic publications and by word of mouth. One hundred volunteers were enrolled between 3 October and 4 November 1994. All patients who completed the study as specified by the protocol were enrolled in a raffle for one of two prizes: dinner for two or a trip for two to the Bahamas. The Institutional Review Board at the Cleveland Clinic Foundation approved the study, and participants gave informed consent at the time of enrollment. Participants were informed of the placebo-controlled, double-blind nature of the study. Patients who volunteered for the study were enrolled only if they had had cold symptoms for 24 hours or less. Patients must have had at least two of the following 10 symptoms: cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, or an oral temperature greater than 37.7 C. Patients were excluded if they were pregnant, had a known immune deficiency, or had had symptoms of the common cold for more than 24 hours. The zinc gluconate-glycine and placebo lozenges were supplied by the Quigley Corporation of Doylestown, Pennsylvania. The zinc lozenges consisted of a boiled hard-candy base prepared with approximately equal proportions of sucrose and corn syrup, zinc gluconate trihydrate (AKZO Chemie, Amersfoort, the Netherlands), a molar proportion of glycine (aminoacetic acid), and lemon and lime flavoring oils. The mixture was formed into lozenges that weighed 4.4 g and contained 13.3 mg of zinc. Placebo lozenges, also weighing 4.4 g, were prepared from the same flavored hard-candy base and contained 5.0% calcium lactate pentahydrate. Placebo and active lozenges were identical in weight, appearance, flavoring content, and texture. The zinc lozenges, however, were more astringent than the placebo lozenges. A statistical consultant prepared a computer-generated randomization code and the packages of medication. The packages were identical in appearance except for the randomization numbers. The study medication was distributed by the study nurse, who was masked to treatment assignments. Patients were given 120 lozenges and were asked to dissolve 1 lozenge in their mouths every 2 hours while awake for as long as they had cold symptoms. The study nurse administered the first lozenge to assess initial tolerability. Participants were asked to take no other cold preparations during the study period. Acetaminophen samples and oral digital thermometers were given to the patients at the time of enrollment. All patients were called on the second day of medication use to make sure that they were not developing a more serious illness and to assess the adequacy of the masking through responses to a questionnaire. By assessing the adequacy of the placebo on the second day of treatment rather than only at the end of treatment, we hoped to decrease the likelihood that a rapid cure would help patients in the zinc group correctly determine that they were receiving the active medication. This questionnaire was also administered at the end of treatment with the addition of questions about the occurrence of specific, previously described side effects of zinc therapy. Patients returned to the Clinic for the final visit within 1 day of noting that their cold symptoms had resolved. At this visit, they returned unused lozenges so that adherence to the protocol could be checked through lozenge counts, and the study nurse confirmed that cold symptoms had resolved. Patients were asked to complete a daily log documenting the severity of symptoms and the medications taken throughout the duration of their cold for as long as 18 days. Every day, patients graded each symptom as 0 for none, 1 for mild, 2 for moderate, or 3 for severe. Total symptom scores were calculated by summing the scores of the 10 symptoms for each day. Cold resolution was defined as resolution of all symptoms (a total symptom score of 0) or resolution of all but one mild symptom (a total symptom score of 1). Statistical Analysis The time to cold resolution was calculated as the number of days from study entry. Resolution rates were estimated using the Kaplan-Meier method, and resolution profiles were compared between groups using the log-rank test [17, 18]. We estimated median resolution times using the method suggested by Lee [19]. The effect of treatment on individual symptoms was examined by comparing the number of days with each symptom using the Wilcoxon rank-sum test. For analysis of treatment effect, we combined hoarseness, sore throat, and scratchy throat into a category called throat symptoms and nasal drainage and congestion into a category called nasal symptoms. Plots of individual patient symptoms give the percentage of the baseline total severity score (sum of symptom scores for all patients) by assignment group and study day. When appropriate, we used the Fisher exact test and the chi-square test to analyze associations between the side effects and assigned groups. Patient adherence was examined by comparing the total lozenge counts between the two groups using the Wilcoxon rank-sum test. These analyses were done using an intention-to-treat framework, regardless of patient adherence [20-22]. Before the randomization code was broken, patients who received antibiotic therapy or whose condition was diagnosed by a physician as an illness other than the common cold were considered nonadherent. Patients who wrote their diaries from memory were also considered nonadherent. Patients were considered adherent if they took an average of four or more lozenges per day for the first 4 days of the study (16 lozenges) and if they took no antibiotic agents. Results One hundred patients were enrolled in the study; 50 were assigned to the zinc group, and 50 were assigned to the placebo group. All patients were Cleveland Clinic employees older than 18 years of age. One patient in the zinc group withdrew from the study on the first day because she could not tolerate the lozenges; she did not complete the symptom diary. All other patients, as directly observed by the study nurse, indicated that they had good tolerance of the first lozenge. Demographic characteristics of the groups are given in Table 1. Table 1. Demographic Characteristics of 99 Volunteers Receiving Zinc or Placebo Lozenges for Treatment of the Common Cold The mean (SD) and median symptom scores at baseline (the first measurement) were 8.6 3.3 and 8 for the entire sample, 9.3 3.6 and 8 for the placebo group, and 7.9 2.8 and 8 for the zinc group. In practice, an increase in score

Intracavernous injection therapy: Analysis of results and complications

Experience with 100 patients who used intracavernous injection therapy with a combination of papaverine with or without phentolamine for 29 months is analyzed in detail. The largest group of patients had vasculogenic erectile failure (56%). At the end of followup 50% of the patients were no longer performing injection. Those who discontinued injection therapy were slightly older and had more vasculogenic erectile failure. The nonfibrotic complications were mild in all instances and did not result in discontinuation of injection therapy. These complications consisted of small hematomas in 20.9% of the patients, mild discomfort in 13.6% and mild liver enzyme abnormalities in 9.8%. No episode of priapism or infection occurred during therapy. Fibrotic complications consisted of nodules or plaques, and correlated significantly with the number of months on injection and the number of injections. At 12 months the fibrotic complication rate was 31 +/- 8.6%. Our study suggests caution regarding the long-term complication rate of intracavernous injection therapy with these compounds and underscores the importance of routine followup examinations. While injection therapy is an effective form of treatment for erectile failure, it is not a satisfactory alternative for many patients and is associated with a significant fibrotic complication rate.

The Decision to Breastfeed The Importance of Fathers' Approval

One hundred fifteen postpartum mothers who were within 24 hours of delivery completed a questionnaire to determine factors which may influence a mothers intention to breastfeed and to evaluate specifically the effect of working outside of the home. In our population of mostly middle-class married and insured women, working outside of the home was not significantly related to the decision to breastfeed (67.9% of working mothers, compared to 67.2% of those who did not plan to work postpartum, planned to at least partially breastfeed). The only factors that significantly related to breastfeeding intention pertained to the fathers level of education and to his approval of breastfeeding. Strong approval of breastfeeding by the father was associated with a high incidence of breastfeeding (98.1 %), compared to only 26.9% breastfeeding when the father was indifferent to feeding choice (P<0.001).

Transitional cell carcinoma of the prostate in cystoprostatectomy specimens removed for bladder cancer

Specimens from 84 radical cystectomies for bladder carcinoma performed between January 1984 and July 1986 were reviewed to characterize the involvement of the prostate with transitional cell carcinoma. Whole-mount sectioning of the prostate was performed at 4 mm. intervals and processed in the same manner as radical prostatectomy specimens. A total of 36 patients (43 per cent) had transitional cell carcinoma of the prostate: 94 per cent of these had prostatic urethra involvement and 6 per cent had a normal prostatic urethra but transitional cell carcinoma was present in the periurethral structures. In situ prostatic duct or acini, ejaculatory duct and seminal vesicle involvement occurred, respectively, in 67, 8 and 17 per cent of the patients with prostatic involvement. Of the patients with prostatic involvement 39 per cent had stromal invasion (22 per cent focal and 17 per cent diffuse invasion). The incidence of carcinoma in situ of the bladder neck or trigone (59 per cent), previous intravesical chemotherapy (59 per cent) and ureteral carcinoma (79 per cent) was significantly increased in patients with prostatic involvement. In patients with carcinoma in situ of the trigone or bladder neck, or in whom previous intravesical chemotherapy treatments have failed prostatic involvement should be suspected so that this disease can be detected before stromal invasion occurs.

Superficial esophageal carcinoma

BACKGROUND The detection of superficial esophageal carcinomas by surveillance endoscopy and the downstaging of advanced carcinomas to superficial carcinomas by induction therapy have increased the number of patients with these carcinomas undergoing resection. The natural history of these carcinomas is not well defined. METHODS To evaluate the results of surgical resection and identify predictors of improved survival, a retrospective review of (1) patients with superficial esophageal carcinoma at presentation (SECP) and (2) patients with advanced carcinomas that were downstaged to no residual carcinoma or superficial esophageal carcinoma after induction therapy (SECD) was conducted. RESULTS There were 54 patients with SECP (19 Tis and 35 T1). Survival was significantly better for patients with Tis carcinomas (85.3% at 5 years) and patients with intramucosal T1 carcinomas (79.4%) than for patients with submucosal T1 carcinomas (16.3%) (p = 0.007 and p = 0.045, respectively). Survival at 5 years for the 49 patients without regional lymph node metastases (N0) was 65.2%, whereas none of the 5 patients with regional lymph node metastases (N1) have survived more than 3 years (p = 0.054), and 3 died of recurrent disease. There were 21 patients with SECD (13 T0, 2 Tis, and 6 T1). Survival at 4 years was 58.2%. In this group, survival was not related to depth of tumor invasion (p = 0.76) or regional lymph node status (p = 0.68). CONCLUSIONS We conclude that (1) patients with Tis and intramucosal T1 SECP have a significantly better survival than those with submucosal T1 SECP, (2) patients with N0 SECP have a significantly better survival than those with N1 SECP, and (3) survival of patients with SECD is not related to depth of tumor invasion or regional lymph node status.

Squamous cell carcinoma of the paranasal sinuses: The cleveland clinic experience 1977–1986

Fifty‐four of 103 malignancies of the paranasal sinuses treated at the Cleveland Clinic Foundation between 1977 and 1986 were squamous cell carcinomas. Six arose from the ethmoid sinus and 48 from the maxillary sinus. Of the maxillary sinus patients, 11 presented with Tl or T2 lesions, 20 with T3, 16 with T4, and 7 of these had nodal disease. Treatment was surgery and/or radiation therapy. There was local recurrence in 25 of 48 maxillary sinus patients and in 1 of 6 ethmoid patients. Overall 5‐year survival was 38.2% in the maxillary sinus group: Tl, 100.0%; T2, 85.7%; T3, 31.8%; and T4, 6.7%. Three of six patients with ethmoid tumors were cured. There was a statistical trend for better prognosis in those patients presenting with ethmoid primaries, with early lesions, treated with both radiation and surgery, and with history of inverting papilloma. There were complications of treatment in 10 patients, four of which resulted in death. Local control was the major problem for these patients; therefore, early detection and aggressive local treatment are desirable.

Stage II esophageal carcinoma: The significance of T and N

OBJECTIVE Stage II esophageal carcinomas are a heterogeneous group of uncommon malignant tumors that include both node-negative (IIA; T2 N0 M0 and T3 N0 M0) and node-positive (IIB; T1 N1 M0 and T2 N1 M0) carcinomas. The purpose of this study was to evaluate this heterogeneity and to identify predictors of improved survival. RESULTS Ninety-four of 345 patients undergoing esophageal resection at the Cleveland Clinic Foundation between 1985 and 1994 had stage 11 carcinomas; 70 stage IIA (24 T2 N0 M0 and 46 T3 N0 M0) and 24 stage IIB (9 T1 N1 M0 and 15 T2 N1 M0). Pathologic stage and T and N status were the only identifiable predictors of survival. Stage IIA survival was significantly better than stage IIB (p = 0.01). T2 N0 M0 survival was not different from T1 N0 M0 survival (p = 0.83). T3 N0 M0 survival was significantly worse than T1 N0 M0 (p = 0.03) and intermediate between T2 N0 M0 survival (p = 0.06) and T1 N1 M0 and T2 N1 M0 survivals (p = 0.07). T1 N1 M0 and T2 N1 M0 survival was not significantly different from T3 N1 M0 survival (p = 0.63). CONCLUSIONS (1) N1 disease is the principal predictor of reduced survival and N1 is independent of T. Therefore the distinction between T1 N1 M0, T2 N1 M0, and T3 N1 M0 carcinomas is not warranted. (2) N0 disease is the principal predictor of improved survival but N0 is not independent of T. T1 N0 M0 and T2 N0 M0 survivals are similar and therefore distinction between these subgroups is not warranted. T3 N0 M0 survival is intermediate between T1 N0 M0 and T2 N0 M0 carcinomas and between T1 N1 M0, T2 N1 M0, and T3 N1 M0 carcinomas. Therefore stratification by T for N0 carcinomas is warranted.

Latent variable models for clustered ordinal data.

Existing methods for the analysis of clustered, ordinal data are inappropriate for certain applications. We propose latent variable models for clustered ordinal data which are derived as natural extensions of latent variable models for clustered binary data (Qu, Williams, Beck, and Medendorp, 1992. Biometrics 48, 1095-1102). These models can be applied to repeated measures data, familial data, longitudinal data, and data with both cluster specific and occasion specific covariates with a wide range of correlation structures.