Living-related liver transplantation for Crigler-Najjar syndrome in Saudi Arabia

OBJECTIVE: To analyse the outcome of six children with Crigler-Najjar syndrome type I (CNS-I) and report the first three living-related liver transplants for this syndrome in Saudi Arabia and the Middle East. SETTINGS: To review the medical records of six children suffering from CNS-I, three of whom underwent living-related liver transplantation (LRLT) between 22 November 1998 and January 2001. MAIN RESULTS: Living-related liver transplantation was performed in three children with a pre-transplant unconjugated bilirubin level of 362, 381 and 502 micromol/L, respectively, despite daily phototherapy of >or= 12 h. Two of the transplanted children developed acute hepatocellular rejection, which was successfully treated with methylprednisolone pulse therapy. One tested cytomegalovirus positive (using the PP65 method), but showed no signs of clinical infection and was treated with ganciclovir. One patient had a biliary leak at the cut surface of the graft which was surgically repaired. Post-operative bilirubin levels returned to normal in all three transplanted children and no further phototherapy was required. One patient, who was not transplanted but received phototherapy, developed severe neurological damage prior to the start of our living-related liver transplant programme with a bilirubin level of 450 micromol/L, her sister is still awaiting transplantation. A 14-yr-old child with a bilirubin level of 420 micromol/L is presently undergoing phototherapy whilst awaiting orthotopic liver transplantation because of the lack of a suitable living-related donor. Six siblings of the six children in our series were reported dead by the families. CONCLUSION: Crigler-Najjar syndrome type I is a relatively common disease in Saudi Arabia for which LRLT is a curative treatment when performed at an early age before the development of kernicterus and neurological deficiency. In countries where there is a severe shortage of cadaveric organs, as is the case in Saudi Arabia, LRLT is the optimum treatment modality for this syndrome.     

Short report: Crimean-Congo hemorrhagic fever outbreak in Rawalpindi, Pakistan, February 2002

A nosocomial outbreak of Crimean-Congo hemorrhagic fever occurred in Rawalpindi, Pakistan in February 2002. The identified index case died shortly after admission to a hospital. Two of the health care workers became secondary cases; one of them died on day 13 after coming in contact with the index case. The other secondary case was successfully treated with oral ribavirin.     

Circulating tuberculostearic acid in tuberculosis patients

Tuberculostearic acid (TBSA), a mycobacterial cell wall constituent, was measured in plasma samples using a highly sensitive high-performance liquid chromatography method. Plasma TBSA concentrations in patients with active tuberculosis (20 [0.5-347] nmol/l; n = 125) were higher than in patients with a variety of non-tuberculous pulmonary and extrapulmonary inflammatory conditions (0.1 [0-29] nmol/l; n = 116) and in healthy controls (0 [0-2] nmol/l; n = 102) (p = < 0.001). The calculated sensitivity, specificity, positive and negative predictive values for tuberculosis were 95.2%, 87.9%, 89.5% and 94.4%, respectively, indicating that assay of plasma TBSA might be a valuable complementary diagnostic tool.     

Perceptions of Pakistani medical students about drugs and alcohol: a questionnaire-based survey

Background  

Drug abuse is hazardous and known to be prevalent among young adults, warranting efforts to increase awareness about harmful effects and to change attitudes. This study was conducted to assess the perceptions of a group of medical students from Pakistan, a predominantly Muslim country, regarding four drugs namely heroin, charas, benzodiazepines and alcohol.     

Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.

PURPOSE: Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy. PATIENTS AND METHODS: Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death. RESULTS: With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195). CONCLUSION: Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.     

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin

Although clinical response to primary chemotherapy in stage II and III breast cancer is associated with a survival advantage, it is the degree of pathological response in the breast and ipsilateral axilla that best identifies patients with a good long-term outcome. A mathematical model of the initial response of 39 locally advanced tumours to anthracycline-based primary chemotherapy has been previously shown to predict subsequent clinical tumour size. This model allows for the possibility of primary resistant disease, the presence of which should therefore be associated with a worse outcome. This study reports the application of this model to an additional five patients with locally advanced breast cancer, as well as to 63 patients with operable breast cancer, and confirms the biological reality of the model parameters for these 100 breast cancers treated with primary anthracycline-based chemotherapy. The tumours that responded to chemotherapy had higher cell-kill (P < 0.0005), lower resistance (P < 0.0001) and slower tumour regrowth (P < 0.002). Furthermore, ER-negative tumours had higher cell-kill (P < 0.05), as compared with ER-positive tumours. All patients with a pathological complete response had zero resistance according to the model. Furthermore, the long-term implication of chemo-resistant disease was demonstrated by survival analysis of these two groups of patients. At a median follow-up of 3.7 years, there was a statistically significantly worse survival for the 37 patients with locally advanced breast cancer identified by the model to have more than 8% primary resistant tumour (P < 0.003). The specificity of this putative prognostic indicator was confirmed in the 63 patients presenting with operable disease where, at a median follow-up of 7.7 years, those women with a resistant fraction of greater than 8% had a significantly worse survival (P < 0.05). Application of this model to patients treated with neoadjuvant chemotherapy may allow earlier identification of clinically significant resistance and permit intervention with alternative non-cross-resistant therapies such as taxoids.     

The effects of adenoid hypertrophy and subsequent adenoidectomy on pediatric nasal airway resistance

To investigate how adenoid hypertrophy and subsequent adenoidectomy affect pediatric airway resistance, we developed a prospective controlled study. Fifty children, aged 3 to 12 years, diagnosed with adenoid hypertrophy and selected for adenoidectomy, preoperatively had their nasal airway resistance assessed by active anterior rhinomanometry. Twenty-five of these children were subsequently followed up postoperatively, undergoing nasal resistance evaluations at 1 month, 3 months, 6 months, and 12 months. Another 25 children, without chronic upper airway obstruction symptoms, were enrolled as a control group, and their airway resistance was assessed in the same fashion. We concluded that the children selected for adenoidectomy, compared to the control group and before surgery, had mean resistance values up to two- to threefold higher, in both untreated and decongested nose states. Surgery was found to dramatically reduce airway resistance, but only in children under the age of seven. However, the postoperative values still tended to remain higher than the control subjects results. If in a significant number of children the operation failed in completely resolving their complaints, no pre-operative rhinomanometric pattern could be found to specifically relate to a complete surgical success.     

The multi-institutional validation of the new screening index for physical child abuse

Background/Purpose

There is currently no evidence-based screening instrument to assist in the detection of physical child abuse patients. The screening index for physical child abuse (SIPCA) was previously developed as a potentially new tool for this need. It is a scale that assigns point values, on the basis of variable weights from logistic regression models, to age and patterns of injuries (including fracture of base or vault of skull, contusion of eye, rib fracture, intracranial bleeding, multiple burns), with higher scores indicating greater suspicion for abuse. The purpose of this study is to validate this new tool in another independent data set.

Methods

A cross-sectional hospital discharge database from 1961 hospitals in 17 states is used (n = 58558). Children aged 14 years or younger with International Classification of Diseases, Ninth Revision, Clinical Modification codes 800 to 959 are included for analysis. Child abuse cases are identified by E codes and certain International Classification of Diseases, Ninth Revision, Clinical Modification codes in the 995.5x range. Screening index for physical child abuse performance is evaluated by discrimination (receiver operating characteristic) and goodness of fit (pseudo r²).

Results

A total of 447 abused patients (0.76%) was identified. The receiver operating characteristic of SIPCA in this data set is 0.89 as compared with 0.86 in the development data set. The pseudo r² of SIPCA in this data set is 0.26 as compared with 0.28 in the development data set. A SIPCA score of 3 has a sensitivity of 86.6% and a specificity of 80.5% for detecting physical abuse; raising the threshold to a score of 4 improves the specificity to 93.1% but at a loss of sensitivity to 71.8%.

Conclusions

The validity of the new SIPCA instrument is supported by its performance in an independently derived data set. A score of 3 on SIPCA represents a balanced trade off in the sensitivity and specificity of the instrument in detecting physical abuse and is an optimal threshold above which to begin considering abuse in differential diagnosis. Application of the instrument could assist clinicians in detecting physical child abuse cases among pediatric trauma patients.