Congenital hydrocephalus and L1 disease: a case report (2009: 7b)

L1 disease is the most common genetic cause of congenital hydrocephalus. Mutations in the L1CAM gene are associated with an overlapping clinical spectrum of four X-linked neurological conditions, characterized by hydrocephalus, mental retardation, lower limb spasticity and adducted thumbs. Brain anomalies are frequently present in L1 disease. We describe these anomalies by reporting a case of a male newborn presenting with congenital hydrocephalus along with corpus callosum agenesis and enlargement of the massa intermedia. These findings, in association with the presence of clasped thumbs, raised the suspicion of L1 disease, which was confirmed by the detection of a mutation in the L1CAM gene. In cases of congenital hydrocephalus, recognition of the brain anomalies associated with L1 disease may contribute to pursuing the genetic analysis needed for the diagnosis and genetic counseling.     

Local excision for ypT2 rectal cancer--much ado about something.

BACKGROUND: The role of local excision for pT2 distal rectal cancer has been challenged because of the observation of high rates of lymph node metastases and local failure. However, neoadjuvant chemoradiation therapy (CRT) has led to increased local disease control and significant tumor downstaging, possibly decreasing rates of lymph node metastases. In this setting, a possible role for local excision of ypT2 has been suggested. METHODS: A total of 401 patients with distal rectal cancer underwent neoadjuvant CRT. Tumor response assessment was performed after at least 8 weeks from CRT completion. One hundred and twelve patients with complete clinical response were not immediately operated on and were excluded from the study, and 289 patients with incomplete clinical response were managed by radical surgery. Patients with final pathological stage ypT2 were analyzed to determine the risk of unfavorable pathological features that could represent unacceptable risk for local failure after local excision. RESULTS: Eighty-eight (30%) patients had ypT2 rectal cancer. Final ypT status was not associated with pretreatment radiological staging (p = 0.62). ypT status was significantly associated with the risk of lymph node metastases, risk of perineural and vascular invasion, and recurrence (p = 0.001). Lymph node metastases were present in 19% of patients with ypT2 rectal cancer. The risk of lymph node metastases in ypT2 was associated with the presence of perineural invasion (47% vs 4%; p = <0.001), vascular invasion (59% vs 6%; p < 0.001), and decreased mean interval CRT surgery (12 vs 18 weeks; p < 0.001), but not with mean tumor size (3.2 vs 3.1 cm; p = 0.8). Disease-free and overall survival rates were significantly better for patients with ypT2N0 (p = 0.02 and 0.006, respectively). Fifty-five (63%) patients with ypT2 had at least one unfavorable pathological feature for local excision (lymph node metastases, vascular or perineural invasion, mucinous type or tumor size >3 cm). CONCLUSION: Lymph node metastases were present in 19% of patients with ypT2 and were significantly associated with poor overall and disease-free survival rates. The risk of lymph node metastases could not be predicted by radiological staging or tumor size. Radical surgery should be considered the standard treatment option for ypT2 rectal cancer after CRT.     

Agoraphobics 5 years after imipramine and exposure. Outcome and predictors

Five years after treatment in a controlled trial, in which all had received self-exposure homework, a group of 40 agoraphobic outpatients retained marked improvement in agoraphobia, mood, and free-floating anxiety. Frequency of spontaneous panics decreased as much in those who had placebo and self-exposure as in those who received imipramine and self-exposure. Few patients, however, were completely well at 5 years and over half had received further treatment for agoraphobia during the follow-up. Patients who were still highly phobic at the end of the clinical trial were more often prescribed psychotropic medication during follow-up and remained phobic at 5 years. Phobic improvement had generalized more in those patients with very low than in those with moderate pretreatment Hamilton depression scores. Frequency of initial spontaneous panics did not predict outcome. Improvement in agoraphobia was associated with improved marital adjustment. Those who began with the best marital, work, and social adjustment were more improved in their phobias 5 years later.     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

Temporal arteritis presenting with scalp ulceration

We report the case of a 75-year-old-woman who presented with bilateral scalp ulcerations and blindness, accompanied by severe headache and scalp tenderness, due to bilateral temporal arteritis without systemic involvement. A biopsy taken from the border of an ulceration showed evidence of giant cell arteritis. She was treated with oral prednisone, 60 mg per day. The ulcerations healed in a few weeks but the vision loss was irreversible. This case highlights for temporal arteritis the importance of accurate and timely diagnosis as well as the need for prompt therapy with systemic steroids in order to avoid major complications, namely loss of vision. It also demonstrates that scalp necrosis and ulcerations are skin signs associated with a poor prognosis.     

Pulmonary embolism.

Pulmonary embolism (PE) is an important health problem and often a major clinical challenge, not only because of the low specificity of its clinical manifestations but also because of the increasing number of medical circumstances that are risk factors for this illness and the importance of early identification, since prompt and appropriate treatment can decrease mortality from this disease by about 25%. In recent years research on PE has been extensive, directed mainly at trying to determine and characterize its risk factors, establish new clinical probability algorithms, develop new diagnostic methods and put existing ones into perspective, seek new therapeutic approaches (pharmacological and non-pharmacological), and above all establish protocols that can guide the clinician from the stage of clinical suspicion to measures to prevent recurrence. It was the authors' aim to review the most significant literature on this subject, in order to produce a text that reflects the state of the art concerning PE and that can be used as a guide in the clinical approach to this pathology.     

Ovarian and uterine findings in pelvic sonography: comparison between prepubertal girls, girls with isolated thelarche, and girls with central precocious puberty.

OBJECTIVE: To describe pelvic sonographic findings in girls as old as 7 years, to compare prepubertal girls with girls who had isolated thelarche or central precocious puberty, and to verify the accuracy of sonographic variables for distinguishing prepubertal girls from girls with central precocious puberty. METHODS: Ninety-six prepubertal girls and 2 reference groups (8 girls with isolated thelarche and 8 with idiopathic central precocious puberty) were included. Ovaries were classified morphologically as homogeneous, paucicystic, macrocystic, multicystic, and having isolated cysts. Receiver operating characteristic curves were used to choose the best cutoff points. RESULTS: Chronologic and bone age were correlated with uterine length, area, and volume and ovarian volume in prepubertal girls (P < .0001). Ovarian morphologic characteristics in prepubertal girls differed significantly from those of the reference groups (P < .0001). The best cutoff points were uterine length of 4.0 cm, uterine area of 4.5 cm2, uterine volume of 3.0 cm3, and ovarian volume of 1.0 cm3. CONCLUSIONS: Uterine and ovarian growth are proportional to age in prepubertal girls. Mean ovarian volume greater than 1 cm3 showed 100% sensitivity and specificity for discriminating between prepubertal girls and girls with central precocious puberty. Microcysts are common in prepubertal girls, but the presence of 6 or more follicles up to 10 mm in diameter may suggest central precocious puberty in girls younger than 8 years.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Cysticercosis of the brain. The value of computed tomography

Incidence and radiologic findings of neurocysticercosis were investigated in a series of 23,800 consecutive head examinations using computed tomography (CT). The condition was diagnosed in 168 cases (0.7%). The parenchymatous form was the most common presentation (96.3%), while the meningeal form corresponded to only 11.9 per cent of cases. These two forms coexisted in some cases. These findings reversed the knowledge on the condition based on conventional radiography. The different CT appearances in the brain are described and a new radiologic protocol for the CT evaluation of the condition is advocated, which includes a follow-up after a trial cure with Praziquantel in the presence of cysts not associated with suggestive brain calcifications. CT was more sensitive than conventional radiography in the differentiation between dead and living larvae, thus having an impact on the therapeutic management of the patients.