Dysplasia Epiphysealis Hemimelica/Trevor Disease: Report of a Lesion Solely Involving the Lunate Bone: A Case Report.

CASE: We describe the case of a dysplasia epiphysealis hemimelica (DEH) lesion affecting uniquely the lunate bone in a 16-year-old boy causing pain, stiffness, and decreased range of motion. Surgical excision was performed, leading to resolution of primary symptoms with residual limitations in terminal wrist extension. CONCLUSIONS: From our review of the literature, we believe this case to be the first report of a DEH lesion affecting solely the lunate bone. Although conservative and surgical management have both been described with DEH cases, we report a positive outcome following the excision of a symptomatic lesion.

Hip Arthroscopy for Femoral Acetabular Impingement: A Bird's-Eye/En Face Perspective With Ultrasound Guidance and 3-Dimensional Hip Printing.

Femoral acetabular impingement is a common hip disorder that may prove debilitating to many patients. Surgical management is indicated by way of hip arthroscopy for impinging CAM and pincer acetabular lesions. Traditionally, fluoroscopy has been used for the intraoperative assessment of bony resection; however, many disadvantages include radiation risks, equipment demands, and more. With ultrasound-guided arthroscopy, we describe the use of 1:1 3-dimensional hip printed models through various visual perspectives of impinging lesions. Given the low cost of 3-dimensional hip printing, lack of radiation exposure, and tactile multiangular views, we propose a safer and more reproducible intraoperative technique to conventional fluoroscopy to achieve better resection and outcomes after femoral acetabular impingement surgery.

A micellar cisplatin prodrug simultaneously eliminates both cancer cells and cancer stem cells in lung cancer.

Platinum-based chemotherapy as first-line treatment for lung cancers encounters insufficient selectivity, severe side effects and drug resistance in clinics. In this study, we developed an amphiphilic prodrug of cisplatin-poly(ethylene glycol)-block-polycaprolactone and demonstrated that the prodrug formed micellar nanoparticles, NPPt(IV), with an average diameter of ∼100 nm. NPPt(IV) released platinum in response to the intracellular acidic and reductive environment, and in turn induced significant anti-proliferative activity in lung cancer cells. More importantly, NPPt(IV) exhibited a prominent inhibitory effect on CD133+ lung cancer stem cells (CSCs) and suppressed tumor growth in vivo. Unlike cisplatin treatment which eventually enriches CSCs, NPPt(IV) treatment prevents the accumulation of CD133+ lung CSCs in tumors. Therefore, NPPt(IV) simutaneously targeting CSCs and non-CSCs might represent a superior strategy to improve conventional anticancer therapy directed predominantly to tumor bulk populations.

Depth versus subdural temporal electrodes revisited: Impact on surgical outcome after resective surgery for epilepsy.

OBJECTIVE: To study retrospectively the impact of electrode modality (subdural or depth electrodes) during presurgical assessment on surgical outcome after temporal lobectomy. METHODS: The study included 17 patients assessed with depth electrodes and 57 with bitemporal subdural strips. RESULTS: MRI showed a larger proportion of bilateral pathology in patients undergoing depth recordings (29.41% versus 3.5%, p=0.00069). Among the operated patients, those undergoing depth electrode recordings showed better outcome at one year after surgery (11/12 versus 22/33; p=0.046). This difference disappears at longest follow up (10/12 versus 22/33; p=0.138). Moreover, the probability of undergoing surgery and having good outcome after assessment with intracranial recordings is higher for the depth electrode group at one-year follow up (11/17 versus 22/57; p=0.029) but statistical differences decrease to a trend for the longest follow up (10/17 versus 22/57; p=0.069). No other statistical differences were noted between subdural and depth electrodes. Depth electrodes showed lower complication rates than subdural electrodes. CONCLUSION: Both depth and subdural electrodes are effective for presurgical assessment of temporal lobe epilepsy. SIGNIFICANCE: Assessment with depth electrodes is associated with slightly increased likelihood of surgery and marginally better surgical outcome at one year follow up which disappears for longer follow up periods. Initial assessment with depth electrodes would have avoided a second implantation in 15% of patients.

Endoscopic lumbar discectomy under local anesthesia may be an alternative to microdiscectomy: A single centre's experience using the far lateral approach.

OBJECTIVES: Since the turn of the century, minimally invasive surgery has become increasingly widespread. Discectomy surgery has evolved from wide open to microscopic and now endoscopic. This study aims to demonstrate that transforaminal endoscopic discectomy is an alternative and safe approach for degenerative disk surgery. PATIENTS AND METHODS: Two year retrospective assessments of patients who underwent transforaminal endoscopic discectomy at a tertiary neurosurgical center in the United Kingdom by a single surgeon. Under strict confidentiality, data was collected from online patient data and PACS systems. Patient feedback was achieved using phone call follow up and clinic appointments. Standard statistical analysis was performed. RESULTS: 201 patients had endoscopic discectomy and the mean age was 41 years. Male:female ratio was 1.3:1.0. Mean time of onset of symptoms was 5.5 months and the most common level was L4/5 (53%). All endoscopic discectomies were performed under local anesthesia. Theater time was on average 110 min. 10 patients were lost to follow up. 95% of patients were discharged within 7h post operatively. Visual acuity score of the pain dropped from an average of 7/10 pre-operatively to 0-1/10 in 95% of patients two weeks post operatively. 87% patients went back to their normal daily activities within two weeks. There were no cases of CSF leak, hematoma formation or wound infection. 1% of patients developed a nerve root injury. 6% of patients had recurrent herniation and require microdiscectomy. CONCLUSION: Endoscopic discectomy can be an alternative approach to microdiscectomy. While it can take more expertise to perform endoscopic discectomy, our data shows that the far lateral endoscopic discectomy using the TESSYS technique has comparable outcomes to microdiscectomy.

Validation of video-based skill assessment in carotid artery stenting.

OBJECTIVES: To develop weighted error-based, generic and procedure-specific rating scales, to validate these scales for video-based assessment during virtual carotid artery stent (CAS) procedures and correlate them with simulator-derived metrics. METHODS: A questionnaire was developed to assess the technique during live CAS procedures. Errors were rated from 1 (unimportant) to 5 (life-threatening) by 28 highly experienced CAS (>50 CAS) physicians. Virtual CAS procedure was performed by 21 interventionalists with varied CAS experience. Fluoroscopy screen and hand movements were video-taped, and simulator-derived metrics recorded. Experienced CAS practitioners then rated the video-taped performances using weighted error, generic and procedure-specific rating scales. RESULTS: Of the 23 errors assessed, 12 were regarded as moderate (score 3), six serious (score 4) and four life-threatening (score 5). The generic rating scale was able to detect significant differences in performance between inexperienced and experienced CAS operators (score 25 vs. 32 respectively, P<0.01). All scoring systems demonstrated good inter-rater reliability (alpha=0.61-0.87). Significant correlations were observed between simulator-derived and video-based scores: weighted error-based score (r: 0.76, P<0.01), generic (r: 0.62, P<0.01) and procedure-specific (r: 0.76, P<0.01) rating scales. CONCLUSIONS: The generic endovascular rating scale differentiated between levels of CAS experience among skilled interventionalists and correlated to simulator-based error scoring.

Potentiation of in vivo neuroprotection by BclX(L) and GDNF co-expression depends on post-lesion time in deafferentiated CNS neurons.

To elucidate effective and long-lasting neuroprotective strategies, we analysed a combination of mitochondrial protection and neurotrophic support in two well-defined animal models of neurodegeneration, traumatic lesion of optic nerve and complete 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal pathway. Neuroprotection by BclX(L), Glial cell line-derived neurotrophic factor (GDNF) or BclX(L) plus GDNF co-expression were studied at 2 weeks and at 6-8 weeks after lesions. In both lesion paradigms, the efficacy of this combination approach significantly differed depending on post-lesion time. We show that BclX(L) expression is more important for neuronal survival in the early phase after lesions, whereas GDNF-mediated neuroprotection becomes more prominent in the advanced state of neurodegeneration. BclX(L) expression was not sufficient to finally inhibit degeneration of deafferentiated central nervous system neurons. Long-lasting GDNF-mediated neuroprotection depended on BclX(L) co-expression in the traumatic lesion paradigm, but was independent of BclX(L) in the 6-OHDA lesion model. The results demonstrate that neuroprotection studies in animal models of neurodegenerative diseases should generally be performed over extended periods of time in order to reveal the actual potency of a therapeutic approach.

The Coronary Artery Revascularisation in Diabetes (CARDia) trial: background, aims, and design.

BACKGROUND: Patients with diabetes have an increased incidence and severity of ischemic heart disease, which leads to an increased requirement for coronary revascularization. Comparative information regarding mode of revascularization--coronary artery bypass graft surgery surgery (CABG) or percutaneous coronary intervention (PCI)--is limited, mainly confined to a subanalysis of the Bypass Angioplasty Revascularization (BARI) trial, suggesting a mortality benefit of CABG over PCI. No prospective trial has specifically compared these modes of revascularization in patients with diabetes. OBJECTIVE: The Coronary Artery Revascularisation in Diabetes (CARDia) trial is designed to address the hypothesis that optimal PCI is not inferior to modern CABG as a revascularization strategy for diabetics with multivessel or complex single-vessel coronary disease. The primary end point is a composite of death, nonfatal myocardial infarction, and cerebrovascular accident at 1 year. METHOD: A total of 600 patients with diabetes are to be randomized to either PCI or CABG, with few protocol restrictions on operative techniques or use of new technology. This gives a power of 80% to detect non-inferiority of PCI assuming that the PCI 1-year event rate is 9%. A cardiac surgeon and a cardiologist must agree that a patient is suitable for revascularization by either technique prior to recruitment into the study. Twenty-one centers in the United Kingdom and Ireland are recruiting patients. Data on cost effectiveness, quality of life, and neurocognitive function are being collected. Long-term (3-5 year) follow-up data will also be collected.

Distinct yet complementary mechanisms of heparin and glycoprotein IIb/IIIa inhibitors on platelet activation and aggregation: implications for restenosis during percutaneous coronary intervention.

OBJECTIVE: To study the effect of unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in combination with glycoprotein (Gp) IIb/IIIa blockers on platelet activation and aggregation. METHODS: Washed platelets were stimulated with thrombin in the presence or absence of UFH (monoparin), LMWH (enoxaparin), and a Gp IIb/IIIa blocker (abciximab, eptifibatide, or tirofiban). RESULTS: Although Gp IIb/IIIa antagonists blocked the final common pathway of thrombin induced platelet aggregation, UFH and LMWH were better at blocking upstream platelet activation. UFH was significantly more effective than LMWH at inhibiting P selectin expression (p = 0.001) and platelet derived growth factor release from thrombin activated platelets (p = 0.012). CONCLUSIONS: UFH and LMWH exert complementary effects to Gp IIb/IIIa blockers by inhibiting afferent pathways of platelet activation. Coadministration of heparin with Gp IIb/IIIa blockers provides improved protection against persistent platelet activation, thereby improving outcome after percutaneous coronary intervention. Judging from these data, UFH may be more effective in this regard than LMWH, at least in vitro. The use of LMWH in preference to UFH during percutaneous coronary intervention, although initially attractive, may inadequately protect against platelet activation despite the presence of Gp IIb/IIIa blockers.

Treatment options for von Hippel-Lindau's haemangioblastomatosis: the role of gamma knife stereotactic radiosurgery.

Haemangioblastomas secondary to von Hippel-Lindau (VHL) disease can be difficult to manage surgically, which has lead to an interest in the use of stereotactic radiosurgery. Retrospectively reviewed here are 30 tumours treated in 14 patients with a mean +/- SD follow-up of 34 +/- 24 months. During this time, three of the 14 patients (21%) died, two of generalized progressive disease. Before radiosurgery, the median time between interventions for cranial haemangioblastomas was 3 years (mean 3.9 +/- 5.0 years). After radiosurgery, the tendency for cranial disease progression was similar, 50% of patients developing further disease by 5 years. Local tumour control was achieved in the majority of cases and estimates of this are included. Radiosurgery is a useful palliative measure controlling the majority of haemangioblastomas, although its efficacy in these patients is limited by the tendency of further disease to develop or progress intracranially.

A prospective study of clinico-pathological features of epithelial ovarian cancer in Pakistan.

BACKGROUND: Although geographic and racial differences in the incidence of cancer are well recognized, information regarding any dissimilarity in clinico-pathological behavior of cancers is scarce. In particular, information from the developing countries regarding clinico-pathologic features of even some of the common cancers such as ovarian cancer is lacking. METHODS: Information was prospectively collected on all patients with epithelial ovarian cancer referred to the National Cancer Institute, Karachi, Pakistan between January 1, 1993 and June 30, 1998. Information was obtained directly from the patients and a close relative. Medical records were reviewed and radiologic and pathologic re-evaluation was done when necessary. RESULTS: Two hundred and eighty six patients were accrued. Mean age was 49.5 (+/- 13) years. Most of the well defined risk factors such as early menarche, late menopause, nulliparity, lack of lactation were uncommonly observed. Twenty percent of the patients had a positive family history of cancer. Most of these relatives were young (46.1 years), first degree (68%) and had breast or ovarian cancer. Clinical presentation, histologic features and stage of disease were similar to the North American or European women with epithelial ovarian cancer. CONCLUSION: Younger age at presentation and higher frequency of positive family history are two unusual features of Pakistani patients with epithelial ovarian cancer. This suggests a more significant role played by the genetic factors in these patients. Further work is needed.

Food fails to suppress ghrelin levels in obese humans.

UNLABELLED: Ghrelin is the first circulating hormone shown to stimulate feeding in humans following systemic administration. Food consumption decreases circulating ghrelin concentrations in lean subjects but the effects of feeding have not been studied in the obese. METHODS: We investigated the effects of a test meal on plasma ghrelin and leptin concentrations in 13 lean and 10 obese subjects. RESULTS: Fasting ghrelin was significantly higher in lean than in obese subjects (857 pmol/1 vs. 325 pmol/l, (p = 0.002) and fell by 39.5% thirty minutes after eating in the lean group before returning rapidly towards baseline values: (p = 0.003). There was no change in circulating ghrelin in the obese group. Circulating leptin concentration also fell acutely 15 minutes following food intake in lean but not obese subjects (p < 0.0001). CONCLUSIONS: Obese subjects do not exhibit the decline in plasma ghrelin and leptin seen after a meal in the lean. The role of the decline in leptin is unclear but given the orexigenic properties of ghrelin, the lack of suppression following a meal in obese subjects could lead to increased food consumption and suggest that ghrelin may be involved in the pathophysiology of obesity.

Clinico-pathological features of breast cancer in Pakistan.

OBJECTIVE: To obtain information about presenting features of women with breast cancer in Pakistan, to compare these data with information on patients with breast cancer in the United States and to highlight the differences. METHODS: Patients referred to the National Cancer Institute, Karachi, Pakistan between January 1, 1994 and February 28, 1999 who had been recently diagnosed with breast cancer were prospectively evaluated. A printed questionnaire was used as an interview guide. Information was obtained about demographic features/clinical characteristics, stage of the disease and previous therapy. RESULTS: Five-hundred sixty-six patients were evaluated. Mean age was 47.7 +/- 11.8 years. Risk factors for breast cancer were observed in a minority. Mean number of pregnancies was 4.4. Eighteen percent had positive family history mostly in first-degree (64%) relatives. The vast majority (93%) discovered the lump accidentally. Average size was 5.7 +/- 2.3 cm. Over half had used unconventional therapies before receiving standard medical care. Most patients had undergone modified radical mastectomy and only 5% had conservative surgery done. Almost one third had locally-advanced disease. Seventeen percent had metastases at the time of diagnosis. CONCLUSION: Despite significant advances made in cancer care in the United States, patients in Pakistan still present at an advanced stage. Antecedent use of unconventional therapies before seeking any medical advice is widespread. There is a great need for public education to enhance awareness about cancer and other health habits.

Comparison of meropenem with ceftazidime as monotherapy of cancer patients with chemotherapy induced febrile neutropenia.

BACKGROUND: Ceftazidime is commonly used as monotherapy of cancer patients with fever and neutropenia. Concern, however, has been raised regarding potential for drug resistance due to its widespread use. Meropenem is a new carbapenem with more extended antibacterial spectrum including anaerobes. It provides better coverage against gram positives. Hence, it may offer an advantage over ceftazidime. PATIENTS AND METHODS: We prospectively treated 49 patients hospitalized for fever (> 38 degrees C) and neutropenia (ANC < or = 500/cmm) with meropenem. We compared their outcome with 50 patients who consecutively received ceftazidime in the immediate past for the same indication. RESULTS: Comparison of demographic features between the 2 groups revealed no differences in age, gender, type of neoplasm, number of patients with prior antibiotic use, number of days since chemotherapy, absolute neutrophil count and number of patients previously or already hospitalized. Duration of fever, duration of neutropenia and number of patients with pyrexia of undetermined origin were also similar. Therapeutic outcome was same between the two groups. Eighty four percent of patients receiving meropenem and 79% receiving ceftazidime required no modification of the initially assigned therapeutic regimen. Two patients receiving meropenem died. Toxicity was minimal. CONCLUSION: We conclude that meropenem offers no significant advantage over ceftazidime in the management of neutropenic febrile patients.

Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis.

BACKGROUND: Previous studies have suggested that circulating concentrations of soluble adhesion molecules are useful predictors of risk of coronary heart disease (CHD). Larger studies are needed, however, to test this hypothesis. METHODS: We measured serum concentrations of four soluble cell adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], E-selectin, and P-selectin) in the stored baseline serum samples of 643 men with coronary heart disease and 1278 controls nested in a prospective sutdy of 5661 men who were monitored for 16 years. We also did a meta-analysis of previous relevant studies to place our findings in context. RESULTS: Concentrations of soluble adhesion molecules were significantly associated with one another, with other markers of inflammation, and with some classic coronary risk factors. For ICAM-1, the odds ratio for CHD was 1.68 (95% CI 1.32-2.14) in a comparison of men in the top third with those in the bottom third of baseline measurements after adjustments for age and town. This decreased to 1.11 (0.75-1.64) after adjustment for some classic coronary risk factors and indicators of socioeconomic status. For the three other cell adhesion molecules, the odds ratios for CHD, first adjusted for age and town only, and then additionally adjusted for other risk factors, were: VCAM-1: 1.26 (0.99-1.61) and 0.96 (0.66-1.40); E-selectin: 1.27 (1.00-1.61) and 1.13 (0.78-1.62); and P-selectin: 1.23 (0.96-1.56) and 1.20 (0.81-1.76). INTERPRETATION: The measurement of these adhesion molecules is unlikely to add much predictive information to that provided by more established risk factors.

Clinical characteristics and therapeutic outcome of patients with febrile neutropenia who present in shock: need for better strategies.

OBJECTIVE: To study the frequency of neutropenic febrile patients who present in shock, to evaluate the influence of this presenting feature on response to antibiotic therapy, morbidity, and mortality and to identify discriminating demographic features and clinical characteristics of these individuals. METHODS: Prospectively collected data on all episodes of fever and neutropenia observed in cancer patients who were hospitalized for parenteral antibiotic therapy. RESULTS: Five hundred and seventy-six patients were evaluated; 22 (3.8%) presented in shock. This group of individuals was compared with the remainder. Patients presenting in shock were more likely to be older (P< 0.01) and have progressive unresponsive cancer (P< 0.01). They were also more likely to present with septic appearance (P< 0.01), dehydration (P< 0.01), diarrhoea (P< 0.01), altered mental status (P< 0.01) clinical bleeding (P= 0.02) and dyspnoea (P< 0.01). They more often had anaemia (P< 0.01), thrombocytopenia (P= 0.02) and abnormal liver function tests (P< 0.01). Eight of the 22 patients presenting in shock had documented bacteraemia. Non-bacteraemic microbiological infections were observed in three patients. Five patients had clinical evidence of infection and another five were severely dehydrated and volume depleted. One patient had cardiogenic shock. Three patients were managed with monotherapy, 19 received combination antibiotics as initial empirical therapy. Overall outcome of these patients was extremely poor, particularly those with infectious aetiology. Eighteen (82%) patients expired. CONCLUSION: Neutropenic febrile patients who present in shock have extremely poor outcomes irrespective of type of initial antibiotic therapy. Intense efforts are required to improve their outcome.

Altretamine is an effective palliative therapy of patients with recurrent epithelial ovarian cancer.

BACKGROUND: Management of patients with recurrent epithelial ovarian cancer is difficult. Although several agents are active, responses are short-lived and observed in only a small number of patients. Side effects of these drugs are substantial. There is a need for more effective and less toxic therapies. Altretamine is a well tolerated oral agent with minimal toxicity. There are only a few trials evaluating its efficacy as a single agent in recurrent epithelial ovarian cancer. METHODS: We prospectively studied patients with recurrent epithelial ovarian cancer who were able to take oral medication and had adequate bone marrow, liver and renal functions. All had been previously treated with at least one platinum-based chemotherapy regimen and had either relapsed or failed to achieve an adequate response. RESULTS: Seventeen patients were studied. The commonest histological subtype was serous adenocarcinoma. Seven patients had platinum refractory disease. The mean duration of therapy was 6.1 months. Six patients (35%) achieved complete or partial remission, time to progression was 6.0 months and mean overall survival was 15.1 months. Toxicity was primarily nausea, vomiting and asthenia and was easily manageable. CONCLUSION: Altretamine is an acceptable and apparently less toxic alternative to other cytotoxic drugs used for palliation of patients with recurrent epithelial ovarian cancer.

Morphological spectrum of ophthalmic tumors in northern Pakistan.

OBJECTIVE: The objective of the study was to assess the frequency and pattern of ophthalmic tumours in Northern Pakistan. METHODS: This study included all ophthalmic tumours diagnosed during a one year period (January to December 1992). RESULTS: One hundred and fourteen ophthalmic tumours were diagnosed at the Armed Forces Institute of Pathology (AFIP) and Pathology Department of the Army Medical College (AMC), Rawalpindi. Of these tumours, 70 were malignant (61.5%) and 44 were benign (38.5%). The age distribution of malignant ophthalmic tumours had two peaks. The first was seen in the paediatric age group and was mainly due to retinoblastoma. The second peak was seen above 50 years of age and was mainly due to conjunctival squamous cell carcinoma and malignant eyelid tumours which constituted 85% of the malignant ophthalmic tumours in paediatric age group. The average age at presentation of retinoblastoma was 3.8 years. The average age at presentation for squamous cell carcinoma was 56 years. Basal cell carcinoma was the most common malignant eyelid tumour (55%). The most common extraocular malignant orbital tumour was non-Hodgkin's lymphoma. Malignant melanoma of the uvea formed 22% of all melanomas diagnosed during this period. The most common benign tumours were naevi (33%), epidermal inclusion cysts (18%), choristomata (16%) and haemangioma (8%). The malignant ophthalmic tumours constituted 3% of all the malignant tumours diagnosed in Northern Pakistan during 1992 at AFIP and AMC, Rawalpindi. CONCLUSION: The ophthalmic tumours, both benign and malignant are not infrequent in clinical practice in Northern Pakistan.