A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region

Primary congenital glaucoma (gene symbol: GLC3) is an ocular disorder that occurs for 0.01-0.04% of blind people. In the majority of familial cases reported so far, this condition is inherited as an autosomal recessive trait. We have recently used a group of 17 GLC3 families with a minimum of two affected offspring and consanguinity in most of the parental generation and mapped the first GLC3 locus (GLC3A) to the 2p21 region. Six families did not show any linkage to the GLC3A locus and thus provided evidence for genetic heterogeneity of this disorder. A total of eight families unlinked to the 2p21 region were used to search for the chromosomal location of the second GLC3 locus. Herein, we describe mapping of a new locus (designated GLC3B) for primary congenital glaucoma to the short arm of chromosome 1 (1p36.2-36.1) that is situated centromeric to the neuroblastoma and Charcot-Marie-Tooth type 2A (CMT2A) loci. A total of 17 DNA markers were genotyped from this region of chromosome 1. Four families showed no recombination with the two markers D1S2834 and D1S402 with a maximum lod score of 4.510 and 4.157 respectively. Pairwise and multipoint linkage analysis and inspection of the haplotypes revealed that the remaining four families are not linked to this part of chromosome 1, thus providing further evidence that at least one more locus for the autosomal recessive form of GLC3 must exist in the genome. Based on the recombination events, the overall linkage map of this region is: tel-D1S1192-D1S1635-D1S1193 - (D1S1597/-D1S489/D1S228)- [GLC3B/D1S2834/D1S402] - (D1S1176/D1S507/D1S407) - D1S2728-(MFAP2/D1S170) - D1S1368 - D1S436- D1S1592-cen.      

Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis

Ultrasound scans of 51 consecutive patients with gallbladder wall thickening were reviewed, and specific sonographic features were correlated with surgical and clinical follow-up. Two patterns of thickening were identified as specific indicators of the presence or absence of acute cholecystitis. "Striated" wall thickening, consisting of several alternating, irregular, discontinuous, lucent and echogenic bands, was seen in eight of 13 patients (62%) with acute cholecystitis. This pattern was not encountered in any of the patients who did not have acute cholecystitis. Conversely, "three-layer" thickening, consisting of a single circumferential lucent zone between two relatively uniform echogenic layers, was seen in only one of 13 patients (8%) with acute cholecystitis but in 11 of 38 patients (29%) with other diagnoses. Other abnormalities, including the presence of intramural echogenic foci and wall irregularities, were more frequently seen in patients with acute cholecystitis but were not as helpful. Use of these features may suggest or help exclude a diagnosis of acute cholecystitis in those patients in whom the cause of gallbladder wall thickening is otherwise not apparent.     

Metastatic embryonal rhabdomyosarcoma of the breast: A case report and literature review

Rhabdomyosarcoma (RMS) is a common malignancy in children, but embryonal rhabdomyosarcoma (ERMS) deposits rarely occur in the breast in adults. Therefore, little is known about magnetic resonance imaging (MRI) features of breast metastases from RMS, especially the embryonal type. We reported a case of a 22-year-old woman who was diagnosed with ERMS at left foot 2 years ago and accepted operation and chemotherapy. She was confirmed to have breast metastases from the left foot. Successive imaging examinations were performed 3 months apart. Breast ultrasound indicated a benign lesion, and further examination did not reveal any bone metastases. However, predominant restricted diffusion and rim contrast enhancement on MRI combined with the patient's medical history suggested a malignancy of BI-RADS 5. After 3 months, breast ultrasound revealed masses detected last time became larger and lobulated. In addition, internal heterogeneous intensity and rim contrast enhancement with restricted diffusion were revealed on MRI. We speculated that typical MRI findings of breast metastases from RMS may include iso- to hypointensity on T1WI, heterogeneous hyperintensity on T2WI, and circular enhancement with restricted diffusion. Moreover, mild peritumoral edema, rapid expansion of necrosis, and ascending time-intensity curve detected on MRI may be features of the ERMS type.     

Is the IV obstructed or infiltrated? A simple clinical test

Objective. The objective of our study was to determine if clinical observation of pressure-flow relationships (PFR) can differentiate between partial external obstruction (obstruction) and infiltration as a cause of poor performance of gravity-fed infusions.Methods. A total of 24 patients with functional intravenous cannulae in situ had obstruction simulated by the application of a tourniquet proximal to the cannula. The change in flow (F) for a discrete change in pressure (P) was determined in each case by counting drop rates at two different elevations of the fluid reservoir level, 10 cm apart. The same process was repeated in 15 patients in whom the cannula was in an extra vascular location (infiltration). Three sizes of cannula—16-gauge, 18-gauge, and 20-gauge—were examined, with equal distribution of sizes in each group. The effect on flow rates of inflating a blood pressure (BP) cuff proximally on the cannulated limb was assessed. The ratio P/F is the total resistance of the infusion system, and by subtracting known values for resistance of infusion tubing and cannula, the venous or tissue resistance was calculated.Results. There was a statistically significant difference between the change in flow for obstructed compared with infiltrated cannulae for the same change in pressure for each cannula size. The mean venous resistance was 23 mm Hg/L/hr, while that of tissue was 280 mm Hg/L/hr, with no overlap between groups. There was no effect on flow rate with blood pressure cuff inflation in the infiltrated group whereas flow progressively fell in the obstructed group.Conclusions. Clinical observation of PFRs in poorly functioning gravity-fed IV infusions can assist in detecting infiltration as a cause. Inflation of a blood pressure cuff will further impair flow where the cannula is intravascular, but will have no effect in an extravascular location.     

Pharmacokinetics, metabolism and excretion of megazol, a new potent trypanocidal drug in animals.

The pharmacokinetics of megazol (CAS 19622-55-0) was investigated after intraperitoneal and oral administration of the drug (80 mg/kg) to mice. The plasma levels were significantly higher after oral administration of drug than after intraperitoneal route (33.8 micrograms/ml compared with 19.0 micrograms/ml for Cmax, 158714 micrograms.h/l compared with 96057 micrograms.h/l for AUC). When suramin (CAS 145-63-1) was administered 24 h before oral administration of megazol, megazol absorption was accelerated (2 h compared with 4 h for Tmax) but the amount absorbed was lower (19.9 micrograms/ml compared with 33.8 micrograms/ml for Cmax and 95547 micrograms.h/l vs 158714 micrograms.h/l for AUC). In the infected mice previously treated with suramin, all estimated pharmacokinetic parameters of plasma megazol were significantly modified, in particularly an increase in the apparent volume of distribution (5.6 l/kg compared with 0.9 l/kg) with a prolongation of the elimination half-life (3 h compared with 0.7 h) of megazol. Excretion of the total radioactivity of megazol was also evaluated after oral administration of 3H-megazol to rats. Total radioactivity was eliminated predominantly via the urinary route (80%) vs. 10.5% in the faeces, 9.5% remaining in the body 8 days after dosing. When unlabelled megazol was orally administered to rats with absence or presence of suramin, megazol recovered in urine and faeces 72 h dosing was: 55.7%/2% vs 20.6%/1.6%, respectively. In the urine, unchanged megazol was present as characterized by LC-MS/MS as well as 4 unknown metabolites. This study indicates that suramin significantly affects the pharmacokinetics of megazol and its elimination.     

Contribution of magnetic resonance imaging in sclerotic combined degeneration of the spinal cord due to vitamin B12 deficiency

Subacute combined degeneration (SCD) of the spinal cord is known to present histopathologically degenerative lesions in the spinal cord, but few studies on the neuroradiological findings have so far been reported. We present the interest of initial and follow-up MR findings in three cases of SCD. In the three cases, a causal event precipitated the onset of neurological symptoms: general anesthesia for the first and the third one and folic acid treatment for the second one. Clinical evolution was favorable after specific treatment with nearly total recovery. The initial MR study disclosed lesions predominantly involving the posterior columns of the spinal cord: high intensity on T2 weighted image was seen in the initial MR study and disappeared three months after treatment in correlation with good recovery, but with a delay. The recognition of this MR pattern suggests that MRI may be used in conjunction with clinical assessment to confirm the diagnosis and to monitor the efficacity of treatment in SCD.     

Dysfunctional regulation of alphaCaMKII and syntaxin 1B transcription after induction of LTP in the aged rat

Syntaxin 1B and alphaCaMKII are two genes that are upregulated after the induction of LTP and appear to underlie different mechanisms of synaptic plasticity. alphaCaMKII is directly implicated in strengthening the synapses that have been modified, whereas syntaxin 1B has been implicated in a mechanism for the propagation of synaptic plasticity within neural circuits. In these experiments we have investigated whether the regulation of these genes is altered after the induction of LTP in aged rats. We found, three hours after the induction of LTP in the dentate gyrus, that aged rats could be subgrouped into those in which LTP was maintained and those in which LTP had decayed back to basal levels. Both genes were upregulated in young adult rats, whereas there was a differential pattern of LTP-induced expression in the aged rats. Dendritic alphaCaMKII was upregulated in aged rats only when LTP was maintained. In contrast, regulation of syntaxin 1B and alphaCaMKII was absent in the granule cell bodies of the aged rats regardless of whether LTP was maintained or not. These results suggest that molecular mechanisms implicated in two aspects of hippocampal synaptic plasticity malfunction during normal ageing and therefore may have some contributory role in the decline in memory function routinely observed in ageing.     

O2-sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cells

Ventilatory responses to acute and long-term hypoxia are classically triggered by carotid chemoreceptors. The chemosensory inputs are carried within the carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brainstem neurons or secondarily via carotid body inputs, we tested the ventilatory responses to acute and long-term hypoxia in rats with bilaterally transected carotid sinus nerves and in sham-operated rats. Because brainstem catecholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyrosine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in situ hybridization and hypoxic ventilatory responses were measured in vivo by plethysmography. After long-term hypoxia, TH mRNA levels in the nucleus tractus solitarius and ventrolateral medulla increased similarly in chemodenervated and sham-operated rats. Ventilatory acclimatization to hypoxia developed in chemodenervated rats, but to a lesser extent than in sham-operated rats. Ventilatory response to acute hypoxia, which was initially low in chemodenervated rats, was fully restored within 21 days in long-term hypoxic rats, as well as in normoxic animals which do not overexpress TH. Therefore, activation of brainstem catecholaminergic neurons and ventilatory adjustments to hypoxia occurred independently of carotid chemosensory inputs. O2-sensing mechanisms unmasked by carotid chemodenervation triggered two ventilatory adjustments: (i) a partial acclimatization to long-term hypoxia associated with TH upregulation; (ii) a complete restoration of acute hypoxic responsivity independent of TH upregulation.