In situ cell cycle kinetics in bone marrow biopsies following sequential infusions of IUdR/BrdU in patients with hematopoietic malignancies.

Examination of the proliferative characteristics of myeloblasts was undertaken in situ in bone marrow (BM) biopsies of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) following sequential infusions of iodo- (IUdR) and bromodeoxyuridine (BrdU). The ability to identify S-phase cells which have incorporated both or either one of the labels in vivo by using two monoclonal antibodies in vitro permitted the measurement of labeling index (LI) and durations of S-phase (Ts) and the total cell cycle (Tc) both from the BM aspirates and biopsies. While the LI is 2-3 times higher in biopsies, Ts and Tc are fairly comparable in the two samples in 8/10 cases (p = 0.02 and 0.003 respectively). Advantages associated with the determination of cell cycle parameters in BM biopsies have been discussed at length.     

The young pregnant teenager--why the poor outcome?

Studies have repeatedly emphasised the poor obstetric outcome in teenage pregnancies. This study examined 444 teenagers of 16 years and under and demonstrated little difference in the outcome between 14 years and under group and 15 to 16 year old. The poor pregnancy outcome, however, was predominantly related to the adequacy of antenatal care. The discussion emphasises the point that teenage pregnancy is not primarily a medical problem and much effort is required to create an awareness so that prenatal care is both accessible and acceptable to the pregnant teenager.     

The long-term success of fresh, small fragment osteochondral allografts used for intraarticular post-traumatic defects in the knee joint.

Ninety-two fresh osteochondral allografts were implanted in 91 patients with posttraumatic osteoarticular defects of the knee joint. These patients have been prospectively followed since 1972. An analysis of long-term survival of these grafts has been performed to determine their success rates: 75% at 5 years, 64% at 10 years, and 63% at 14 years. An evaluation was made between unipolar grafts, which involve only one surface of the compartment, and bipolar grafts, which involve both surfaces. The unipolar grafts had a lower failure rate at all time periods compared to bipolar grafts, with 76% survival at 5 years, 69% at 10 years, and 67% at 14 years. While investigating other factors that might affect the survival of the fresh osteochondral allografts, we calculated the influence of the anatomical location of the graft, patient sex, and patient age. There was no meaningful impact on allograft survival by either the location of the allograft or the sex of the patient. However, there was a significant effect on allograft longevity in terms of patient age, with patients under age 60 doing better. The best indication for the use of unipolar fresh osteochondral allografts is for posttraumatic defects in relatively young, active patients. Joint malalignment should be corrected to achieve best results.     

In-vitro antagonism by N-formimidoyl thienamycin and cefoxitin of second and third generation cephalosporins in Aeromonas hydrophila and Serratia marcescens

Antagonism of beta-lactam antibiotics by second and third generation cephalosporins was studied in 28 clinical strains of Serratia marcescens and Aeromonas hydrophila. Of the antibiotics tested, both cefoxitin and N-formimidoyl thienamycin (N-f-thienamycin) were capable of antagonism in Ser. marcescens (17 of 20) but in Aerom. hydrophila (7 of 8), only cefoxitin induced antagonism. Antagonism was observed to the greatest degree with cefotaxime and cefoperazone; intermediate with cefamandole and latamoxef (moxalactam) and essentially none with N-f-thienamycin. Inducible beta-lactamase was found in all strains of both genera which exhibited antagonism. The induced beta-lactamase showed enhanced inactivation for other antibiotics in only four strains with none occurring in Aeromonas.     

Determinants and outcomes of inpatient versus home based rehabilitation following elective hip and knee replacement

OBJECTIVE: There are large variations in practice patterns and costs of rehabilitation following total joint replacement (TJR). We evaluated the determinants of rehabilitation setting (home based vs inpatient) after TJR, and its influence on early functional outcomes. METHODS: We studied a retrospective cohort of 146 primary total hip and knee replacements. Ninety-six patients completed a mailed survey consisting of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), the Medical Outcomes Survey Short Form-36 (SF-36), and a satisfaction questionnaire. RESULTS: The mean age of the cohort was 66 years, 70% were women, and osteoarthritis was the primary diagnosis in 79%. Thirty-nine percent received home based rehabilitation. Determinants of home based rehabilitation included preference for home based rehabilitation, male sex, and knowledge regarding TJR. At a mean followup of 8 months post TJR, there were no significant differences between the inpatient and home based rehabilitation groups with respect to the WOMAC, SF-36, and satisfaction scores. CONCLUSION. These results support continued use of home based rehabilitation.     

Standard Setting Methods for Pass/Fail Decisions on High-Stakes Objective Structured Clinical Examinations: A Validity Study

Construct: Authentic standard setting methods will demonstrate high convergent validity evidence of their outcomes, that is, cutoff scores and pass/fail decisions, with most other methods when compared with each other. Background: The objective structured clinical examination (OSCE) was established for valid, reliable, and objective assessment of clinical skills in health professions education. Various standard setting methods have been proposed to identify objective, reliable, and valid cutoff scores on OSCEs. These methods may identify different cutoff scores for the same examinations. Identification of valid and reliable cutoff scores for OSCEs remains an important issue and a challenge. Approach: Thirty OSCE stations administered at least twice in the years 2010–2012 to 393 medical students in Years 2 and 3 at Aga Khan University are included. Psychometric properties of the scores are determined. Cutoff scores and pass/fail decisions of Wijnen, Cohen, Mean–1.5SD, Mean–1SD, Angoff, borderline group and borderline regression (BL-R) methods are compared with each other and with three variants of cluster analysis using repeated measures analysis of variance and Cohen's kappa. Results: The mean psychometric indices on the 30 OSCE stations are reliability coefficient = 0.76 (SD = 0.12); standard error of measurement = 5.66 (SD = 1.38); coefficient of determination = 0.47 (SD = 0.19), and intergrade discrimination = 7.19 (SD = 1.89). BL-R and Wijnen methods show the highest convergent validity evidence among other methods on the defined criteria. Angoff and Mean–1.5SD demonstrated least convergent validity evidence. The three cluster variants showed substantial convergent validity with borderline methods. Conclusions: Although there was a high level of convergent validity of Wijnen method, it lacks the theoretical strength to be used for competency-based assessments. The BL-R method is found to show the highest convergent validity evidences for OSCEs with other standard setting methods used in the present study. We also found that cluster analysis using mean method can be used for quality assurance of borderline methods. These findings should be further confirmed by studies in other settings.     

Controlled degradation of low-fouling poly(oligo(ethylene glycol)methyl ether methacrylate) hydrogels

Degradable low-fouling hydrogels are ideal vehicles for drug and cell delivery. For each application, hydrogel degradation rate must be re-optimized for maximum therapeutic benefit. We developed a method to rapidly and predictably tune degradation rates of low-fouling poly(oligo(ethylene glycol)methyl ether methacrylate) (P(EG)_xMA) hydrogels by modifying two interdependent variables: (1) base-catalysed crosslink degradation kinetics, dependent on crosslinker electronics (electron withdrawing groups (EWGs)); and, (2) polymer hydration, dependent on the molecular weight (M_W) of poly(ethylene glycol) (PEG) pendant groups. By controlling PEG M_W and EWG strength, P(EG)_xMA hydrogels were tuned to degrade over 6 to 52 d. A 6-member P(EG)_xMA copolymer library yielded slow and fast degrading low-fouling hydrogels suitable for short- and long-term delivery applications. The degradation mechanism was also applied to RGD-functionalized poly(carboxybetaine methacrylamide) (PCBMAA) hydrogels to achieve slow (∼50 d) and fast (∼13 d) degrading low-fouling, bioactive hydrogels.

To tune degradation rates of low-fouling hydrogels, a 6-member P(EG)_xMA copolymer library with different electronics and hydration levels was developed.     

Carcinoma of the Ampulla of Vater: Patterns of Failure Following Resection and Benefit of Chemoradiotherapy

Background

Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery.

Methods

A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan?CMeier method.

Results

A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n?=?43) or neoadjuvant (n?=?18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P?=?.03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8?years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P?=?.001) with trend toward 3-year DFS (66% vs 48%, P?=?.09) and OS (62% vs 46%, P?=?.074) benefit in patients receiving CRT.

Conclusions

Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.