The durability of virological success of tenofovir and didanosine dosed at either 400 or 250 mg once daily.

Tenofovir (TDF) co-administered with didanosine (ddI) 400 mg increases ddI plasma concentrations by up to 60%, raising concerns over toxicity. To limit this interaction, the dosage of ddI may be reduced to 250 mg once daily when co-prescribed with TDF. In this clinical cohort, highly active antiretroviral therapy regimens containing TDF and ddI 250 mg were significantly better tolerated than combinations with TDF and ddI at a dose of 400 mg. Low-dose ddI 250 mg once daily plus TDF as part of antiretroviral therapy was effective.

Diagnostic value of microtubule-associated protein-2 in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous carcinoma with neuroendocrine differentiation and a propensity for early spread to regional lymph nodes. Since surgical resection is the mainstay of treatment of MCC, differentiation of MCC from malignant lymphoma, metastatic small cell carcinoma, basal cell carcinoma, and malignant melanoma is very important and is sometimes challenging with routine histologic examination. Immunohistochemical studies may be required to differentiate MCC from other primary and metastatic skin neoplasms. Previously, the authors reported that microtubule-associated protein-2 (MAP-2) is a sensitive and specific marker for pulmonary neoplasms with neuroendocrine differentiation. Because MCC is also a neuroendocrine carcinoma, the authors hypothesized that MAP-2 may be expressed in MCC and therefore may be a useful marker in establishing an accurate diagnosis. MAP-2 staining was demonstrated in all 14 MCCs with diffuse (10 cases) to focal (4 cases) patterns of immunoreactivity. No MAP-2 immunoreactivity was observed in any lymphoma (14 cases), basal cell carcinoma (20 cases), or squamous cell carcinoma (14 cases). CK20 reactivity was present in 12 of 14 cases with focal (2 cases) to diffuse (10 cases) staining having the characteristic perinuclear dot-like pattern. NSE was positive in 13 of 14 cases, SYN was positive in all 14 cases, CHR was positive in 8 of 14 cases, CK7 was positive in 4 of 14 cases, and CD99 was focally positive in 2 cases and diffusely positive in 3 cases. MAP-2 showed a diffuse or focal staining of MCC with a +1 to +4 intensity in most cases. MAP-2 was positive in two cases of MCC that were negative for CK20 and CHR and negative or only slightly positive for SYN and NSE. Therefore, MAP-2 may be a valuable ancillary study in skin tumors suspicious for neuroendocrine origin with faint or negative staining with the antibodies traditionally used for diagnosing MCC. The authors believe this is the first study to demonstrate the utility of MAP-2 in the immunohistochemical workup of MCC. The authors recommend that MAP-2 be added to immunohistochemical panels to confirm the diagnosis of MCC.

Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in tumor growth and metastasis. We investigated the prognostic significance of VEGF overexpression, intratumoral microvessel density (MVD), and angiolymphatic invasion in stage Ia-b non-small cell lung cancer (NSCLC). METHODS: Eighty-five patients undergoing complete surgical resection of pathologic stage Ia-b NSCLC were evaluated. The mean and median clinical follow-up were 37.1 and 39.0 months (range, 30-44 months), respectively. Paraffin-embedded tumor specimens were stained with VEGF and CD31 (a specific endothelial marker) using immunohistochemical methods. VEGF staining was evaluated, by combining both percentage of positive tumor cells and staining intensity, as low (negative and < 20% of tumor cells showing weak positivity), or high (> 20% of tumor cells showing strong positivity). CD31 staining was expressed as MVD per high power field at 400x magnification. Angiolymphatic invasion was expressed as either presence or absence. RESULTS: Low VEGF expression was seen in 25 (29%) patients, and high VEGF expression was seen in 60 (71%) patients. The survival rate in patients with low VEGF expression was significantly higher (80%) than that in those with high VEGF expression (48%, P = .018). The mean MVD in the low VEGF group was 23.7 +/- 5.7 vs. 34.4 +/- 9.3 in the high VEGF group (P = .001). Patients with high MVD also had a significantly lower survival rate than did those with low MVD count (46% vs. 73%, P = .0053). Age, sex, tumor type, and tumor differentiation were not found to be associated with overall survival. The presence of angiolymphatic invasion and T2 stage (i.e., tumor size > 3 cm) were associated with decreased survival. High VEGF expression, tumor size, and angiolymphatic invasion emerged as three independent factors predicting worsening prognosis using multivariate analysis. CONCLUSION: High VEGF expression within stage I NSCLC is closely associated with high intratumoral angiogenesis and poor prognosis. Immunohistochemical evaluation of T stage and VEGF expression along with examination of angiolymphatic invasion perioperatively may aid in predicting prognosis. Adjuvant therapies aimed at retarding tumor angiogenesis may be considered for stage I NSCLC patients with high VEGF levels.

Is decompressive craniectomy for acute cerebral infarction of any benefit?

BACKGROUND: Acute occlusion of the major cerebral arteries results in ischaemic changes to the brain, without time for reperfusion by the collateral circulation. The subsequent cellular events lead to a breakdown of the blood-brain barrier, causing malignant cerebral edema manifested clinically by a rapid neurological deterioration. The aim of this study was to determine the value of surgical decompression in patients who present with acute cerebral infarction. METHODS: Retrospective review of patients with deteriorating consciousness level from massive cerebral ischemia and secondary edema, treated by decompressive craniectomy. RESULTSThere were 10 patients over a 2-year period from 1997-99, consisting of seven male and three female patients (mean age 47.56 years) with a mean preoperative Glasgow Coma Scale (GCS) score of 6/15. Three patients had dominant middle cerebral artery (MCA) infarction, four had nondominant MCA infarction, one had posterior cerebral artery infarction, and the remaining two had cerebellar infarction. At a mean follow-up period of 7 months, two patients had died (20% mortality), four patients (40%) were vegetative or severely disabled, and the remaining four patients (40%) had mild disability or good outcome. Favorable prognostic factors were younger age (less than 50 years) and good initial GCS score (14 or better). CONCLUSION: Decompressive craniectomy in the setting of acute brain swelling from cerebral infarction is a life-saving procedure and should be considered in younger patients who have a rapidly deteriorating neurologic status.

Golf buggy related head injuries.

Our department has recently managed three cases of serious head injuries resulting from falls from golf buggies. One of them sustained moderate head injury with a small cerebral contusion and skull fracture. Two of them sustained severe head injury with extensive cerebral contusions, extradural haematoma requiring craniotomy. Of the three patients, two made good recoveries whereas the third remained vegetative. We feel that instruction on the safe use of golf buggies is inadequate and should be intensified.

A study on the efficacy of intraventricular urokinase in the treatment of intraventricular haemorrhage.

Twenty-one patients with intraventricular haemorrhage were randomized to two treatment groups. Both groups had bilateral external ventricular drains inserted, but only the treatment group received 50,000 IU urokinase instilled into the ventricles. The clinical and radiological progress, and 1- and 6-month outcomes were compared. The group that received urokinase treatment was shown to have an improved outcome, with a lower mortality and a lower incidence of hydrocephalus requiring shunt insertion. No haemorrhagic complications were seen in either group, although the treatment group had a slightly increased rate of drain-related ventriculitis.

An unusual cause of dysphagia.

A case of dysphagia caused by anterior cervical osteophytes is presented. Although dysphagia and cervical spondylosis are common presenting problems, they are often unrelated to each other. The association between the two should, therefore, be accepted with caution; adequate investigation is necessary to avoid misdiagnosis. Review of the literature showed that this condition is relatively rare. The most likely mechanism of dysphagia is interference with swallowing at the pharyngo-oesophageal junction, although osteophytes in the lower cervical spine may also interfere with oesophageal peristalsis. Apart from the osteophytes of cervical spondylosis, those resulting from Forestier's disease, or Diffuse Idiopathic Skeletal Hyperostosis (DISH) have also been described to cause dysphagia.

Growing skull fractures.

Two recent cases of growing skull fractures are presented and the literature reviewed. Skull fractures in children which are at risk of enlarging should be recognised and followed up closely.

Role of marrow-derived monocytes and mesangial cells in removal of immune complexes from renal glomeruli.

Phagocytosis of intravenously administered immune complexes by cells in the mesangium was investigated. The model used was that of exchange marrow transplantation between Chediak-Higashi (CH) mice and syngeneic partners after X-irradiation. This model was chosen since marrow-derived macrophages could be differentiated from resident mesangial cells by the presence of the characteristic giant lysosomes in phagocytic cells of the CH mice. Injected immune complexes were cleared normally and localized in the glomerular mesangium in CH or C57BL/6J mice receiving either C57BL/6J or CH marrow. C57BL/6J mice with CH marrow injected with immune complexes prepared with reduced and alkylated antibodies accumulated many cells within the mesangium that contained both giant lysosomes and electron dense deposits. Deposits were not found in cells with subplasmalemmal microfilaments and perpheral dense bodies. Conversely, the cells in the mesangium of CH mice with C57BL/6J marrow that contained electron dense deposits were devoid of giant lysosomes. Based on these observations, we concluded that (a) marrow-derived monocytes contribute to mesangial hypercellularity after deposition of immune complexes and (b) phagocytosis of immune complexes localized in the glomerular mesangium was by marrow-derived monocytes rather than by mesangial cells.

Manifestations of systemic light chain deposition.

In two patients with terminal renal failure, manifestations of disease developed in multiple organ systems. One had a previous diagnosis of multiple myeloma with kappa light chain proteinemia and proteinuria. The other had idiopathic lobular glomerulonephritis. Hepatic and neurologic abnormalities developed in both; in the latter gastrointestinal, cardiac and endocrine disease developed as well. Clinical and pathologic correlations suggest that the retention and tissue deposition of light chains produced the organ dysfunction, inasmuch as free kappa light chain determinants were demonstrated histologically in the clinically affected organs. The deposition in these patients may be an extreme example of a common but previously unrecognized form of plasma cell dyscrasia.