Optimal therapy for pelvic recurrence after radical hysterectomy for early-stage cervical cancer

Forty-eight patients with pelvic recurrence after radical hysterectomy were evaluated. The influence of location of pelvic recurrence (sidewall versus central), histological grade, histological type, and interval from hysterectomy to recurrence had no influence upon curability by radiotherapy. Ten of twenty-eight patients treated by primary radiation therapy for recurrent disease remain without evidence of disease a minimum of 12 months post-therapy, with a projected 5-year disease-free survival in excess of 30%. No patient treated with adjuvant radiation after initial surgery was rendered disease free by subsequent treatment with radiotherapy. Eleven patients were explored for exenterative surgery. Three of six in whom exenteration was technically feasible remain alive without evidence of disease. None of 15 patients treated with chemotherapy remain free of disease. Radiation therapy remains the treatment of choice in post-radical hysterectomy recurrences confined to the pelvis. As exenterative therapy will result in the cure of a small number of patients with disease confined to the pelvis, exenteration should be considered in patients treated previously by radiotherapy. If these efforts fail, chemotherapy is unlikely to result in cure.     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.     

Role of endocervical curettage in colposcopy

Two-thousand three-hundred and four patients with abnormal cervical cytology were evaluated by colposcopy, cervical biopsy, and endocervical curettage. The endocervical curettage was more accurate than the cervical biopsy in 1.2% of patients with satisfactory colposcopic examinations, 15.7% of patients with unsatisfactory examinations, and 30.5% of patients with no lesions observed. The endocervical curettage contained neoplastic epithelium in all 15 of the patients with invasive cancer and in seven patients it was the only diagnostic parameter that indicated invasion. The information from the endocervical curettage, when correlated with the cervical cytology, colposcopic findings, and cervical biopsy, eliminated the need to do a diagnostic conization in 76% of patients with unsatisfactory examinations and 79% of patients with no lesion identified. It is recommended that the endocervical curettage be a part of every colposcopic examination.     

The role of percutaneous nephrostomy in gynecologic oncology

Percutaneous nephrostomy can provide rapid relief of renal failure due to ureteral obstruction by contiguous spread of cervical malignancy. A series of 26 percutaneous nephrostomies placed in 14 patients with cervical cancer, using only local anesthesia and ultrasound or fluoroscopic guidance is presented. Twelve patients experienced no complications, one developed pyelonephritis which cleared rapidly with antibiotics, and one suffered a hematoma managed by surgical nephrostomy. Three of six previously untreated patients and one of eight patients with recurrent disease survived over a year. A single exenterated patient was stented when anuria developed after surgery to correct a conduit leak. This patient survives at 1.5 years with no evidence of recurrence. Indications for percutaneous nephrostomy, anticipated benefits, and the decision-making process involved in determining who to stent is reviewed.     

Methylphenidate bioavailability from two extended-release formulations

OBJECTIVE: The objective of these studies was to compare the rate and extent of absorption of d,l-threo-methylphenidate (MPH) from two extended-release products--a capsule formulation containing coated beads and an OROS tablet formulation--in healthy male and female subjects under fasted conditions. MATERIALS: Metadate CD (methylphenidate HCl, USP) Extended-Release Capsules and Concerta (methylphenidate hydrochloride) Extended-Release Tablets. METHODS: Two studies were conducted: (1) A single dose, randomized, two-way crossover study in 36 adults comparing a 20 mg capsule and an 18 mg tablet, and (2) a single dose, randomized, four-way crossover study in 24 adults comparing 2 x 20 mg capsules, one 36 mg tablet, 3 x 20 mg capsules and one 54 mg tablet. Blood samples were collected over 24 hours and MPH plasma concentrations were used to calculate pharmacokinetic parameters for each treatment. Equivalence of pharmacokinetic parameters for comparable doses of the formulations was concluded if the 90% confidence intervals (CI) for the ratio between test and reference means were within the 80-125% equivalence criterion. RESULTS: Both formulations exhibited biphasic plasma concentration-time profiles and were equivalent in terms of total exposure (AUC(0-last) and AUC(0-infinity)). However, early exposure (AUC(0-4) and AUC(0-6), the first maximum measured plasma concentration (C(max-1), and early plasma MPH concentrations (1.5, 3 and 4 hours) were greater with the capsule formulation, while later plasma MPH concentrations (8, 10 and 12 hours) were greater with the tablet formulation (the CIs were outside the 80-125% required for equivalence and p < 0.001 for all). Similar results were obtained whether or not the data were normalized for the difference in total dose. CONCLUSIONS: The two formulations are not bioequivalent. The capsule fonnulation produces greater exposure to MPH and higher MPH concentrations during the first 6 hours following dosing. MPH is frequently used in school children, and this period would correspond to a major part of the school day.     

AGI-1067. AtheroGenics

AGI-1067 is an oral VCAM-1 (vascular cell adhesion molecule-1) gene expression inhibitor under development by AtheroGenics for the potential prevention of atherosclerosis (hypercholesterolemia) and restenosis. AGI-1067 was also being developed in collaboration with Schering-Plough; however, in October 2001, all rights to the drug were returned to AtheroGenics. In February 2001, dosing was completed in phase II trials for the potential treatment and prevention of restenosis and atherosclerosis following angioplasty. In December 2001, further phase II trials (CART-2) were initiated for the treatment of restenosis and atherosclerosis. Early-phase clinical trials are ongoing for the prevention of atherosclerosis. In January 2002, analysts at Adams, Harkness & Hill predicted that AGI-1067 would be launched in the second half of 2005, with sales of US $100 m in that year and US $540 m in 2006. It was also believed that AtheroGenics would look to sign a marketing partnership following the expected completion of the CART-2 trial in 2002.     

Childhood trauma and adult prostitution behavior in a multiethnic heterosexual drug-using population

A cross-sectional study of the association between severity of childhood trauma and adult prostitution behaviors was conducted among 676 heterosexual drug addicts in San Antonio, Texas. Three hundred and fifty eight women and 338 men taking part in a national multisite program for AIDS prevention research completed the Childhood Trauma Questionnaire as part of a comprehensive risk behavior assessment. Women addicts in the sample were less educated, more likely to be in a common-law relationship, living with someone of the opposite sex or separated, and had lower incomes in comparison to men addicts. Among male subjects,higher educational levels and older age were positively associated with prostitution activities. Single female subjects were three times more likely to engage in selling sex than married subjects. Single women with higher incomes were more likely to be prostituting than single women with lower incomes. Black women reporting severe degrees of emotional abuse, emotional neglect, or physical neglect were more likely to engage in prostitution behavior than Hispanic or white women with similar levels of trauma. Black men with a history of childhood physical abuse were more likely to use prostitutes than Hispanic or white men.     

Evaluation and management of toe fractures

Fractures of the toe are one of the most common lower extremity fractures diagnosed by family physicians. Toe fractures most frequently are caused by a crushing injury or axial force such as stubbing a toe. Joint hyperextension and stress fractures are less common. Most patients have point tenderness at the fracture site or pain with gentle axial loading of the digit. Anteroposterior and oblique radiographs generally are most useful for identifying fractures, determining displacement, and evaluating adjacent phalanges and digits. Referral is indicated in patients with circulatory compromise, open fractures, significant soft tissue injury, fracture-dislocations, displaced intra-articular fractures, or fractures of the first toe that are unstable or involve more than 25 percent of the joint surface. Most children with fractures of the physis should be referred, but children with selected nondisplaced Salter-Harris types I and II fractures may be treated by family physicians. Stable, nondisplaced toe fractures should be treated with buddy taping and a rigid-sole shoe to limit joint movement. Displaced fractures of the lesser toes should be treated with reduction and buddy taping. Patients with displaced fractures of the first toe often require referral for stabilization of the reduction.     

Pyrogenic reactions and hemorrhage associated with intrinsic exposure to endotoxin-contaminated intravenous solutions.

OBJECTIVE: An epidemiological investigation was conducted to determine risk factors for adverse reactions among patients in hospitals and the possibility of extrinsic or intrinsic contamination of intravenous solutions. DESIGN: A retrospective cohort study was conducted to identify solutions associated with adverse reactions. Implicated lots were cultured for bacteria, and endotoxin concentrations were measured. SETTING: Five hospitals in the state of Pernambuco, Brazil, were investigated from February through March 2002. PATIENTS: Surgical inpatients or outpatients receiving intravenous solutions during the study period. RESULTS: Of 355 surgical patients or outpatients treated at hospitals, 28 (8%) developed illness within a mean of 2.5 hours after exposure to intravenous solutions implicated in adverse reactions; 5 (17.9%) of the case patients died. Laboratory testing of bottles from the lots of Ringer's lactate solution implicated in deaths demonstrated a high mean endotoxin concentration of 88.3 endotoxin units (EU)/mL (range, 9.7-298.0 EU/mL), compared with the permitted limit in Brazil of <0.5 EU/mL. Testing of metronidazole implicated in adverse reactions at another hospital and produced by the same company that manufactured the lots Ringer's lactate solution also showed high endotoxin concentrations (mean level, 8.3 EU/mL [range, 5.0-58.3 EU/mL]). The outbreak was controlled after a national recall of the implicated brand of intravenous solutions. CONCLUSIONS: Case patient status was associated with use of Ringer's lactate solution and metronidazole from large bottles, both of which were produced by the same company. High endotoxin concentrations were demonstrated in unopened bottles of implicated products, which is consistent with intrinsic contamination. The high mortality rate may have been compounded by the fact that clinicians administered additional volumes of contaminated 0.9% isotonic sodium chloride solution in response to hypotension or bleeding to some surgical patients. No additional case patients were identified after a national recall of products, inspection, closure of the implicated company's manufacturing facility, and establishment of random quality-control testing of intravenous solutions.     

Preliminary experience with the Doppler ultrasound guided vascular access needle in paediatric patients

Percutaneous cannulation of the internal jugular vein (IJV) in infants and children may be technically difficult and can lead to complications. Various techniques exist to achieve successful cannulation and to reduce the rate of complications. We report the use of the Doppler ultrasound guided vascular access needle (the SMART needle) for IJV cannulation in 10 infants and young children (mean age 3.7 months) weighing less than 10 kg (mean weight 5.5 kg) who were to undergo cardiac surgery at Great Ormond Street Hospital for Children. Successful cannulation was achieved in six out of 10 patients with haematoma complicating the procedure in two patients. We believe this is the first reported use of this device for cannulation of the IJV in this patient group.