C16 and C17 substituted derivatives of pregnenolone and progesterone as inhibitors of 17alpha-hydroxylase-C17, 20-lyase: synthesis and biological evaluation

17 alpha-hydroxylase-C17, 20-lyase (P450 17, CYP 17) is a key enzyme in androgen biosynthesis and a target for the treatment of prostate cancer. In order to find novel inhibitors for this enzyme, several compounds bearing different moieties able to complex with the heme iron located in the active site of the enzyme were synthesized. The moieties were introduced into the 16-position of pregnenolone and progesterone. Their inhibitory activities toward human and rat CYP 17 were determined and compared to the activities of the corresponding 17-substituted compounds. It became apparent that the 16-substituted compounds were less active than the parent compounds: they were either moderate or poor inhibitors of the target enzyme. Tested for inhibition of human 5 alpha-reductase 1 and 2--a target for the treatment of benign prostatic hyperplasia (BPH)--the title compounds showed some inhibitory activity.     

Insight into illness and attitudes toward medications among inpatients with schizophrenia

This study assessed symptoms, severity of illness functional level, insight into illness, and attitudes toward medication in a sample of psychiatric patients who were newly admitted to a state hospital. The patients were evaluated before and after treatment with atypical, conventional, or mixed (atypical plus conventional) antipsychotic medication regimens with the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression, the Global Assessment of Functioning, the Scale to Assess Unawareness of Mental Disorder, and the Drug Attitude Inventory. Overall, the patients showed significant improvement in symptoms, severity of illness, functional level, and insight into their illness during the course of hospitalization. Their attitudes toward medications changed minimally during treatment. Only the patients who were treated with conventional antipsychotics showed significant improvement in their attitudes toward medication. However, the change was not large enough to differentiate the conventional antipsychotic treatment group from the other treatment groups.     

Pericardial diseases

Opinion statement Pericardial diseases have multiple clinical presentations with acute and chronic complications. Early diagnosis and prompt treatment markedly enhance the chance of complete resolution of the hemodynamic complications of pericardial disease. The treatment of patients with acute idiopathic pericarditis is mainly to alleviate symtoms of chest pain. A nonsteroidal anti-inflammatory agent such as indomethacin is our first drug of choice. Therapy is effective and symptoms resolve within 24 to 48 hours. In patients with chronic recurrent idiopathic pericarditis, we advise the use of colchicine at 1 mg/d. Constrictive pericarditis is a progressive disease and surgical pericardiectomy is the only definite treatment. It should be performed early in the disease process before myocardial fibrosis occurs. Cardiac tamponade is a cardiac emergency and patients should be treated promptly. We often start with volume expansion with intravenous fluid in preparation for transcutaneous pericardiocentesis. Echocardiographically guided, transcutaneous pericardiocentesis is the procedure of choice. Patients with asymptomatic pericardial effusion are followed with serial echocardiography, and reserve drainage for enlarging effusions if there are signs of cardiac compression.     

Internal hernia formation after laparoscopic Roux-en-Y gastric bypass for morbid obesity

There is mounting concern that internal hernia formation after laparoscopic Roux-en-Y gastric bypass (LRYGB) for morbid obesity remains unrecognized until complications develop. In this report we present our experience with this complication. Out of 100 patients who underwent LRYGB we identified five patients who were diagnosed with postoperative internal hernia formation. The medical records and operative details of these patients were reviewed. Of the five patients four were female and the average age was 36 years (range 30-43). All Roux limbs were placed in a retrocolic position. The average time interval to presentation was 104 days (range 4-305). All patients had abdominal pain and four patients experienced vomiting. One patient had obstipation. Only one patient had fever (38.1 degrees C) and the highest white cell count was 14,500. The average loss in body-mass index was 5.21 kg/m2 (range 2.5-14.8). Plain abdominal films revealed dilated bowel in the upper abdomen in three patients. Contrast bowel series was diagnostic in only one patient. One patient had a CT scan, which was diagnostic of small bowel obstruction. All patients underwent operative reduction of the internal hernia; two of these were completed laparoscopically. All hernias had occurred at the mesocolic window and were caused by sutures that had pulled through tissue at the dorsal and lateral aspect of the initial repair. One patient had a nonviable segment of small bowel. There were no deaths. Patients who undergo LRYGB are at a 5 per cent risk for developing small bowel obstruction secondary to internal hernia formation at the mesocolic window. Clinical evaluation and traditional study modalities may not be effective diagnostic tools. A high index of suspicion and low threshold to explore these patients may be the best way to avoid serious sequelae. Modification of operative techniques may reduce the occurrence of internal hernia formation.     

Preoperative risk prediction and intraoperative events in cardiac surgery.

OBJECTIVE: To examine the relationship between preoperative risk prediction and intraoperative events. METHODS: A total of 3118 patients operated in 1999 and 2000 at our institution were analysed, all of whom had their EuroSCORE collected prospectively. The intraoperative variables studied were consultant or trainee operating, long bypass time, long ischaemic time, return on bypass in theatre and use of intra-aortic balloon pump at the end of the procedure. The outcomes are reported as hospital mortality, prolonged length of stay in the intensive therapy unit (pLOS-ITU, >48 h) and death or pLOS-ITU. Risk models were constructed by logistic regression for predicting these three outcomes. RESULTS: With the exception of prolonged cross-clamp time, all variables analysed were independently predictive of a negative outcome. Trainee operating had an apparent protective effect. All risk models performed well. The area under the receiver operating characteristic (ROC) curve (95% CI) increased from 0.857 (0.81, 0.90) for EuroSCORE to 0.874 (0.83, 0.92) for the risk of death model. Similarly, the area under the ROC curve for the pLOS-ITU model increased from 0.687 (0.642, 0.732) to 0.734 (0.691, 0.777) and for the death or pLOS-ITU model from 0.717 (0.677, 0.756) to 0.757 (0.719, 0.795). CONCLUSIONS: Knowledge of adverse intraoperative events enhances preoperative risk prediction. This type of analysis could be used for identifying "near miss" outcomes in adult cardiac surgery.     

Nontraumatic osteonecrosis of the humeral head

The humeral head is the second most common site for nontraumatic osteonecrosis after the femoral head, yet it has attracted relatively little attention. Osteonecrosis is associated with many conditions, such as corticosteroid use, sickle-cell disease, alcoholism, dysbarism (or caisson disease), Gaucher's disease, and other systemic conditions. The diagnosis is a clinical and radiographic one, the latter forming the basis for its staging. Treatment depends on the chronicity and severity of symptoms, as well as the degree of clinical and radiographic progression. Surgical treatment includes arthroscopic debridement and core decompression for early osteonecrosis and hemiarthroplasty or total shoulder arthroplasty for more advanced disease. This report reviews osteonecrosis of the humeral head, with an emphasis on current treatment options.     

A comparison of two months pretreatment with GnRH agonists with or without an aromatase inhibitor in women with ultrasound-diagnosed ovarian endometriomas undergoing IVF

Research question

Does the addition of an aromatase inhibitor improve IVF outcomes in women with endometriomas when pretreating them with gonadotrophin-releasing hormone agonists?

A 2-year follow-up after rotoresection of the prostate: a prospective study

OBJECTIVE: To evaluate the success of rotoresection of the prostate for benign prostatic hyperplasia (BPH), after a follow-up of 24 months. PATIENTS AND METHODS: The 24 patients who were the subject of a previous report were followed for up to 24 months; only one patient was lost to follow-up. RESULTS: The mean (sd) American Urologic Association-7 score decreased from 20.5 (3.8) before surgery to 1.12 (1.56) at 24 months; the mean maximum urinary flow rate increased from 8.7 (2.1) to 21.8 (8.5) mL/s, and the mean total prostate volume decreased from 36.5 (12.9) to 21 (7.9) mL. Early complications were urinary tract infection in 10 patients and mild stress urinary incontinence in 11. One patient had a urethral stricture and another had a posterior urethral stone at 6 months; both were treated successfully with good urinary flow rates thereafter. At 24 months, 23 patients had sterile urine and were continent. CONCLUSION: Thus far, rotoresection of the prostate is a safe and effective method for treating BPH. The hospital stay was short and the functional results excellent at up to 24 months.