Initial results from a randomized trial of cervical visual screening in rural south India

The impact of a single round of screening of visual inspection with acetic acid (VIA) on cervical cancer incidence and mortality was investigated in a cluster randomized trial in south India. Women 30-59 years of age in 113 clusters in Dindigul District were randomized to VIA screening (57 clusters, 48,225 women) by nurses and to a control group (56 clusters, 30,167 women). 30,577 eligible women were screened between May 2000 and April 2003; 2,939 (9.6%) screen-positive women were investigated with colposcopy by nurses and 2,777 (9.1%) women had biopsy. CIN 1 was diagnosed in 1,778 women, CIN 2-3 lesions were found in 222, and there were 69 screen detected invasive cervical cancers. The detection rates of lesions per 1,000 screened women were 58.2 for CIN 1, 7.3 for CIN 2-3, and 2.3 for invasive cancer. The detection rate of high-grade lesions in our study was 2-3-fold higher than those observed in repeatedly screened populations in developed countries. 71% of women with CIN 1 and 80% of those with CIN 2-3 lesions accepted cryotherapy provided by nurses and surgical treatment by mid-level clinicians. Overall, 97 and 34 incident cervical cancer cases were observed in the intervention and control arms, respectively. The intervention arm accrued 124,144 person years and the control arm accrued 90,172 during the study period. The age standardized cervical cancer incidence rates were 92.4/100,000 person-years in the intervention and 43.1/100,000 in the control arms. In the screened arm, 35.0% of cases were in Stage I as opposed to none in the control arm. The preliminary findings from our study indicate that not only is a VIA-based screening programme feasible, safe and acceptable to a population in rural settings, it also results in early detection of cervical neoplasia.     

In vivo efficacy of linezolid in combination with gentamicin for the treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus

Indifference or even antagonism has mainly been reported with combinations including linezolid. The presence of in vitro antagonism is not always correlated with in vivo failure. The purpose of this study was to evaluate the in vivo activity of linezolid combined with gentamicin using a methicillin-resistant Staphylococcus aureus (MRSA) endocarditis experimental model. A human-like pharmacokinetic simulation was used for linezolid and gentamicin to improve the extrapolation of the results to human therapy. Contrary to the antagonism previously described in vitro, linezolid combined with gentamicin exhibited bactericidal activity on the two strains with a decrease of at least 4 log(10)cfu/g of vegetation compared with controls. These data suggest that linezolid plus gentamicin could be an appropriate combination for the treatment of severe MRSA infections.     

Determination of the relative contribution of three genes-the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis

In the last 5 years, mutations in three genes, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the pancreatic secretory trypsin inhibitor (PSTI) gene, have been found to be associated with chronic pancreatitis (CP). In this study, using established mutation screening methods, we systematically analysed the entire coding sequences and all exon/intron junctions of the three genes in 39 patients with idiopathic CP (ICP), with a view to evaluating the relative contribution of each gene to the aetiology of the disease. Our results demonstrate that, firstly, 'gain-of-function' mutations in the PRSS1 gene may occasionally be found in an obvious ICP subject. Secondly, presumably 'loss-of-function' mutations in the PSTI gene appear to be frequent, with a detection rate of at least 10% in ICP and, finally, abnormal CFTR alleles are common: at least 20% of patients carried one of the most common CFTR mutations, and about 10% of patients were compound heterozygotes, having at least one 'mild' allele. Thus, in total, about 30% of ICP patients carried at least one abnormal allele in one of the three genes, and this is the most conservative estimate. Moreover, a trans-heterozygous state with sequence variations in the PSTI/CFTR genes was found in three patients. However, an association between the 5T allele in intron 8 of the CFTR gene and ICP remains unproven.     

Physiologic basis for the treatment of epiphrenic diverticulum

OBJECTIVE: To quantitate and characterize the motility abnormalities present in patients with epiphrenic diverticula and to assess the outcome of surgical treatment undertaken according to these abnormalities. SUMMARY BACKGROUND DATA: The concept that epiphrenic diverticula are complications of esophageal motility disorders rather than primary anatomic abnormalities is gradually becoming accepted. The inconsistency in identifying motility abnormalities in patients with epiphrenic diverticula is a major obstacle to the general acceptance of this concept. METHODS: The study population consisted of 21 consecutive patients with epiphrenic diverticula. All patients underwent videoesophagography, upper gastrointestinal endoscopy, and esophageal motility studies. The diverticula ranged in size from 3 to 10 cm and were predominantly right-sided. Seventeen patients underwent transthoracic diverticulectomy or diverticulopexy with esophageal myotomy and an antireflux procedure. The length of the myotomy was determined by the extent of the motility abnormality. Transhiatal esophagectomy was performed in one patient with multiple diverticula. Two patients declined surgical treatment and another patient died of aspiration before surgery. Symptomatic outcome was assessed via a questionnaire at a median of 24 months after surgery. RESULTS: The primary symptoms were dysphagia in 5 (24%) patients, dysphagia and regurgitation in 11 (52%) patients, and pulmonary symptoms in 5 (24%) patients. The median duration of the primary symptoms was 10 years. Esophageal motility abnormalities were identified in all patients. An esophageal motor disorder was diagnosed only by 24-hour ambulatory motility testing in one patient, and 24-hour ambulatory motility testing clarified the motility diagnosis in five other patients. The most common underlying disorder was achalasia, which was detected in nine (43%) patients. A hypertensive lower esophageal sphincter was diagnosed in three patients, diffuse esophageal spasm in five, "nutcracker" esophagus in two, and a nonspecific motor disorder in two patients. One patient had an intraoperative myocardial infarction and died. Two patients had persistent mild dysphagia after surgery. The remaining patients had complete relief of their primary symptoms. CONCLUSIONS: There is a high prevalence of named motility disorders in patients with epiphrenic diverticula, and this condition is associated with the potential for lethal aspiration. Twenty-four-hour ambulatory motility testing can be helpful if the results of the stationary examination are normal or indefinite. Resection of the diverticula and a surgical myotomy of the manometrically defined abnormal segment results in relief of symptoms and protection from aspiration.     

Splenorenal shunt: an ideal procedure in the Pacific

HYPOTHESIS: Splenorenal shunt, an accepted treatment to prevent recurrent variceal bleeding, is an ideal procedure for patients with psychosocial issues or limited access to tertiary medical centers. METHODS: We retrospectively reviewed the medical records of 34 patients (32 distal splenorenal shunts and 2 central splenorenal shunts) treated from January 1, 1995, through December 31, 2001, for demographic data, substance abuse status, psychosocial factors, previous treatments, Child class, length of hospital stay, operative transfusions, complications, and outcome. RESULTS: Of the 34 patients, 17 were from surrounding Pacific islands (as many as 3800 miles away from Honolulu, Hawaii). Sixteen patients were Child class A, and 18 were Child class B. Twenty-four patients were either homeless, actively involved in substance abuse, or being treated for psychiatric problems, and 20 patients were either uninsured or insured by third-party payers that did not cover liver transplantation. Four patients underwent distal splenorenal shunt for a failed transjugular intrahepatic portosystemic shunt. Patients received a mean of 1.3 U of packed red blood cells (range, 0-5 U), and 15 received no blood transfusions. Mean length of hospital stay was 12.7 days (9 days postoperatively). Perioperative mortality was 8.8%. Three patients rebled postoperatively, 2 because of gastric ulcers and 1 because of an inadequate shunt. The 1-year survival rate was 95% in the 20 patients for whom data were available. CONCLUSIONS: Splenorenal shunt is an important treatment for noncompliant patients or patients living in remote areas where access to specialized treatments, such as endoscopy, transjugular intrahepatic portosystemic shunt, ultrasonography, and liver transplantation, is limited. We can achieve acceptable morbidity and mortality in this group of patients, although follow-up can be difficult.     

Patellar fracture after total knee arthroplasty

BACKGROUND: Patellar fracture can occur as a complication following total knee arthroplasty. The purpose of this study was to evaluate a large series of patellar fractures to determine the results of different forms of treatment of specific fracture types. METHODS: A retrospective review identified eighty-five fractures (in seventy-seven patients) following 12,464 consecutive total knee arthroplasties performed between 1985 and 1998. Seventy-eight fractures occurred after primary total knee arthroplasty and seven, after revision total knee arthroplasty. Five fractures were treated elsewhere, and two others were lost to follow-up. The results of treatment of the remaining seventy-eight fractures were reviewed. Fractures were classified according to three main criteria: integrity of the extensor mechanism, fixation status of the patellar implant, and quality of the remaining bone stock. The mean duration of follow-up was 3.6 years. RESULTS: The prevalence of patellar fracture after total knee arthroplasty was 0.68%; fractures were significantly more prevalent among men (1.01%) than among women (0.40%) (p = 0.0004). Thirty-eight fractured patellae had a stable implant and an intact extensor mechanism (Type I). All but one were treated nonoperatively, and there was only one late failure of nonoperative treatment, which required operative intervention. Twelve fractures were associated with disruption of the extensor mechanism (Type II). Eleven were treated operatively; six knees had complications and five had a reoperation. Twenty-eight fractures occurred in association with a loose patellar component (Type III). Twenty were treated operatively; nine knees had complications, and four had a reoperation. CONCLUSIONS: Patellar fractures after total knee arthroplasty are infrequent. Treatment can be guided by three main criteria: integrity of the extensor mechanism, fixation status of the patellar implant, and quality of the remaining bone. Fractures associated with a stable implant and an intact extensor mechanism were usually treated successfully with nonoperative means, with minimal complications. When operative treatment was required, it was associated with a high rate of complications and reoperations.     

Enhanced expression of NGF receptors in multiple sclerosis lesions

The receptor for nerve growth factor (NGF) comprises a 75-kDa (NGFRp75) and a tyrosine kinase A (TrkA) subunit. In view of conflicting opinions on the identity of glial targets of NGF in human central nervous system (CNS), we examined the cellular distribution of both NGF receptor subunits in normal CNS and in chronic multiple sclerosis (MS) lesions. For this, we compared the pattern of recognition of 2 monoclonal antibodies (mAbs) and a polyclonal antiserum to NGFRp75. Only the 2 mAbs specifically recognized NGFRp75, while the polyclonal antiserum showed widespread reactivity. In normal CNS and silent MS lesions, immunohistochemistry with anti-NGFRp75 mAbs and for TrkA revealed perivascular cell reactivity. At the edge of chronic active MS lesions, selective NGFRp75 staining was prominent on reactive astrocytes, while throughout the lesion, NGFRp75 was expressed on microglia/macrophages. The vast majority of mature or precursor oligodendrocytes did not express NGFRp75. Both NGF receptors were co-expressed on a subset of inflammatory cells. Immunoreactivity for NGFRp75 on glial and immune cells did not correlate with the distribution of apoptotic figures, as detected by TUNEL. Thus, expression of NGF receptors in active MS lesions suggests a role for NGF in regulating the autoimmune response at both immune and glial cell levels.