Caprine mucopolysaccharidosis-IIID: clinical, biochemical, morphological and immunohistochemical characteristics

Laparoscopic antireflux surgery is rapidly replacing traditional operations for the treatment of medically refractory gastroesophageal reflux disease. These procedures are technically demanding. Troublesome side effects can be minimized by carefully selecting patients and using a meticulous and appropriate technique. Extensive follow-up data are now emerging and indicate that these procedures can offer long-term control of symptoms with few permanent side effects.     

Extended aromatic furan amidino derivatives as anti-Pneumocystis carinii agents

The syntheses of nine new derivatives of 2, 5-bis[4-(N-alkylamidino)phenyl]furans with extended aromatic systems are reported. The interaction of these dicationic furans with poly(dA)poly(dT) and with the duplex oligomers d(CGCGAATTCGCG)2 and d(GCGAATTCGC)2 was determined by Tm measurement, and the effectiveness of these compounds against the immunosuppressed rat model of Pneumocystis carinii was evaluated. At a screening dose of 10 micromol/kg, 4 of the 12 amidino furans described here are more active than the parent compound 1. In general, extension of the aromatic system in the absence of a substitution of the amidino nitrogens resulted in higher affinity for DNA than the parent compound as judged by the larger DeltaTm values and suggests enhanced van der Waals interactions in the amidino furan-DNA complex. Three of the compounds, 3, 5, and 11, yield cysts counts of less than 0.1% of control when administered at a dosage of 10 micromol/kg. Compound 3, which does not have an extended aromatic system, is the most active derivative. Although a direct correlation between anti-P. carinii activity and DNA binding affinity was not observed, all compounds which have significant activity have large DeltaTm values.     

Aspergillus laryngotracheobronchitis presenting as stridor in a patient with peripheral T cell lymphoma

Invasive aspergillosis is a serious opportunistic infection in immunocompromised patients. The case history is described of a 44 year old patient with peripheral T cell lymphoma who developed hoarseness and stridor after chemotherapy. Aspergillus fumigatus was isolated repeatedly from the sputum. Bronchoscopic examination showed symmetrical creamy-white exophytic lesions involving both vocal cords and the supraglottic area. There was diffuse tracheobronchitis with multiple raised cream-coloured plaques in the trachea which histologically consisted of numerous septate branching hyphae consistent with Aspergillus species. The lesions responded to systemic treatment with amphotericin B.     

Functional analysis of tumor necrosis factor (TNF) receptors in TNF-alpha-mediated insulin resistance in genetic obesity

Although obesity has become the most common metabolic disorder in the developed world and is highly associated with insulin resistance and noninsulin-dependent diabetes mellitus, the molecular mechanisms underlying these disorders are not clearly understood. Tumor necrosis factor-alpha (TNF-alpha) is overexpressed in obesity and is a candidate mediator of obesity-induced insulin resistance. Complete lack of TNF-alpha function through targeted mutations in TNF-alpha gene or both of its receptors results in significant improvement of insulin sensitivity in dietary, chemical, or genetic models of rodent obesity. In this study, we have analyzed the in vivo role of TNF signaling from p55 [TNF receptor (TNFR) 1] and p75 (TNFR 2) TNFR in the development of insulin resistance by generating genetically obese mice (ob/ob) lacking p55 or p75 TNFRs. In the ob/ob mice, the absence of p55 caused a significant improvement in insulin sensitivity. p75 deficiency alone did not affect insulin sensitivity but might potentiate the effects of p55 deficiency in animals lacking both TNFRs. These results indicate that TNF-alpha is a component of insulin resistance in the ob/ob model of murine obesity and p55 TNFR is the predominant receptor mediating its actions.     

Human mucopolysaccharidosis IIID: clinical, biochemical, morphological and immunohistochemical characteristics

Mucopolysaccharidosis IIID (MPS IIID) is one of the rarest of the MPS-III syndromes. To date, the clinical manifestations of 10 patients have been reported, the deficient N-acetylglucosamine 6-sulfatase (G6S) enzyme has been purified, and the G6S gene has been cloned, sequenced and localized. However, morphological manifestations of this condition have not been reported and the pathogenesis of the severe neurological deficits remains an enigma. In this paper we describe and correlate the clinical, biochemical and pathological observations for 2 cases of MPS IIID. We used monoclonal antibodies against heparan sulfate (HS) and GM2-ganglioside, thin layer chromatography, mass spectrometry, and morphological techniques to demonstrate the nature and the distribution of the uncatabolized substrates. The majority of the cells in various tissues showed morphological changes expected with lysosomal storage of HS. The central nervous system (CNS) was most severely affected because of the secondary storage of GM2 and GM3 gangliosides in addition to the primary accumulation of HS. The extent as well as the distribution of the diverse storage materials varied within and among different neurons as observed in MPS-III A, B, and C syndromes. This study supports the hypothesis that the neurological dysfunction and neurodegeneration common to the Sanfilippo syndromes is, in part, due to the secondary metabolic perturbations induced by HS accumulation.     

Absence of linear subthreshold summation between red-green and luminance mechanisms over a wide range of spatio-temporal conditions

We have tested the independence of red-green chromatic and luminance mechanisms at detection threshold using a method of subthreshold summation. Stimuli were isoluminant red-green gratings and yellow-black luminance gratings that uniquely activate the red-green color and luminance mechanisms, respectively. Stimuli were Gaussian enveloped 0.25, 1 or 4 cpd sinewave gratings, counter-phase flickered at 0, 5 or 9 Hz. The threshold detection of red-green color contrast was measured in the presence of a subthreshold amount of luminance contrast, and vice versa. The results allow a model of linear summation between the color and luminance mechanisms to be rejected, but are well fitted by a model, assuming that these mechanisms are independent but combine to determine detection by probability summation, with a high summation index (median value = 4). We conclude that there are independent red-green chromatic mechanism and luminance detection mechanisms over this range of spatio-temporal conditions.     

A method of determining peritoneal penetration in gunshot wounds to the abdomen

BACKGROUND: It has previously been shown that 98% of gunshot wounds that penetrate the peritoneal cavity cause injuries that require surgical repair. Many gunshot wounds in the vicinity of the abdomen (GSWA) may actually be tangential and not penetrate the peritoneal cavity at all. Patients with such wounds may not require laparotomy. It is important to determine which patients with a potential tangential GSWA actually have penetration of the peritoneal cavity to minimize negative laparotomies. This study was undertaken to determine the sensitivity, specificity, and accuracy of diagnostic peritoneal lavage (DPL) in the determination of peritoneal penetration for patients who sustain GSWA. METHODS: DPL was performed for all patients who had sustained a GSWA in whom peritoneal penetration was unclear, i.e., patients whose GSWA appeared to be tangential, thoracoabdominal, or transpelvic and for whom a clear indication for laparotomy (shock, peritonitis, etc.) did not exist. Our threshold for a positive DPL was 10,000 red blood cells (RBC)/mm3. A prospective data base was kept with information on the location of the wound, DPL result, findings at laparotomy, and outcome. RESULTS: During a 4-year period, 429 consecutive DPLs were performed for GSWA at our urban Level I trauma center. One hundred fifty DPLs were positive, with more than 10,000 RBC/mm3. Six of these patients were found to have no peritoneal penetration at laparotomy (false-positive). The remaining 144 patients with positive DPLs were found to have operative injuries (true-positive). Of the 279 patients with DPL counts less than 10,000 RBC/mm3, 2 developed indications for laparotomy and were found to have intraperitoneal injuries (false-negative). The remaining 277 patients had no peritoneal injuries (true-negative). This was demonstrated either by laparotomy done for another indication (n = 7) or by uneventful inpatient observation for 24 hours (n = 270). The sensitivity, specificity, and accuracy of DPL in determining peritoneal penetration in GSWA is therefore 99, 98, and 98%, respectively. CONCLUSION: For patients who sustain GSWA for whom peritoneal penetration is unclear, DPL is a sensitive, specific, and accurate test to determine the need for laparotomy. It remains our test of choice when confronted with these patients.     

Immediate and simultaneous sensory reorganization at cortical and subcortical levels of the somatosensory system

The occurrence of cortical plasticity during adulthood has been demonstrated using many experimental paradigms. Whether this phenomenon is generated exclusively by changes in intrinsic cortical circuitry, or whether it involves concomitant cortical and subcortical reorganization, remains controversial. Here, we addressed this issue by simultaneously recording the extracellular activity of up to 135 neurons in the primary somatosensory cortex, ventral posterior medial nucleus of the thalamus, and trigeminal brainstem complex of adult rats, before and after a reversible sensory deactivation was produced by subcutaneous injections of lidocaine. Following the onset of the deactivation, immediate and simultaneous sensory reorganization was observed at all levels of the somatosensory system. No statistical difference was observed when the overall spatial extent of the cortical (9.1 +/- 1.2 whiskers, mean +/- SE) and the thalamic (6.1 +/- 1.6 whiskers) reorganization was compared. Likewise, no significant difference was found in the percentage of cortical (71.1 +/- 5.2%) and thalamic (66. 4 +/- 10.7%) neurons exhibiting unmasked sensory responses. Although unmasked cortical responses occurred at significantly higher latencies (19.6 +/- 0.3 ms, mean +/- SE) than thalamic responses (13. 1 +/- 0.6 ms), variations in neuronal latency induced by the sensory deafferentation occurred as often in the thalamus as in the cortex. These data clearly demonstrate that peripheral sensory deafferentation triggers a system-wide reorganization, and strongly suggest that the spatiotemporal attributes of cortical plasticity are paralleled by subcortical reorganization.