SARS-CoV-2 Related Ischemic Colitis in an Adolescent With Trisomy 21: Diagnostic Pitfalls and Considerations.

Millions of patients seek medical attention for diarrhea, vomiting, nausea, and abdominal pain. In the current environment, it is important to recognize that these symptoms may be the only manifestation or may precede more serious systemic complications of COVID-19. Herein, we describe the first case of ischemic colitis (IC) in a young adult who presented with diarrhea and highlight the laboratory pitfalls for patients with COVID-19 presenting with gastrointestinal (GI) symptoms.

A prospective multicenter phase II study of oral and i.v. vinorelbine plus trastuzumab as first-line therapy in HER2-overexpressing metastatic breast cancer.

BACKGROUND: To evaluate the efficacy and safety of oral and i.v. vinorelbine plus trastuzumab as first-line regimen in a patient-convenient application for human epidermal growth factor receptor 2 (HER2)-overexpressing patients with metastatic breast cancer. PATIENTS AND METHODS: Forty-two women were enrolled in a multicenter study. The patients received i.v. vinorelbine at a dose of 25 mg/m(2) on day 1 followed by oral vinorelbine at a dose of 60 mg/m(2) on days 8 and 15 in a 3-week cycle. Standard dose trastuzumab was given at 3-week intervals. RESULTS: Complete response was observed in 7 patients (18.9%) and partial response in 19 patients (51.4%), for an overall response rate of 70.3% [95% confidence interval (CI) 53.0-84.1]. The disease control rate reached 91.9% (95% CI 78.1-98.3). The median time to progression was 9.3 months, while median overall survival reached 35.6 months. Hematological and non-hematological toxic effects were acceptable with grade 3-4 leukopenia of 14% and neutropenia of 38%; cardiac toxicity did not reach the level of clinical relevance. CONCLUSION: The combination of i.v. and oral vinorelbine plus trastuzumab demonstrates high activity and good tolerability in first-line treatment of HER2-overexpressing metastatic breast cancer. In addition, it offers convenience for the patients with only one i.v. treatment every 3 weeks.

Neural correlates of rapid auditory processing are disrupted in children with developmental dyslexia and ameliorated with training: an fMRI study.

PURPOSE: Developmental dyslexia, characterized by unexpected difficulty in reading, may involve a fundamental deficit in processing rapid acoustic stimuli. Using functional magnetic resonance imaging (fMRI) we previously reported that adults with developmental dyslexia have a disruption in neural response to rapid acoustic stimuli in left prefrontal cortex. Here we examined the neural correlates of rapid auditory processing in children. METHODS: Whole-brain fMRI was performed on twenty-two children with developmental dyslexia and twenty-three typical-reading children while they listened to nonlinguistic acoustic stimuli, with either rapid or slow transitions, designed to mimic the spectro-temporal structure of consonant-vowel-consonant speech syllables. RESULTS: Typical-reading children showed activation for rapid compared to slow transitions in left prefrontal cortex. Children with developmental dyslexia did not show any differential response in these regions to rapid versus slow transitions. After eight weeks of remediation focused primarily on rapid auditory processing, phonological and linguistic training the children with developmental dyslexia showed significant improvements in language and reading skills, and exhibited activation for rapid relative to slow transitions in left prefrontal cortex. CONCLUSION: The presence of a disruption in the neural response to rapid stimuli in children with developmental dyslexia prior to remediation, coupled with significant improvement in language and reading scores and increased brain activation after remediation, gives further support to the importance of rapid auditory processing in reading development and disorders.

Composition dependence of vesicle morphology and mixing properties in a bacterial model membrane system.

We have determined the mixing properties and lamellar organization of bacterial membrane mimetics composed of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) and -phosphatidylglycerol (POPG) at various molar ratios applying differential scanning calorimetry, small and wide-angle X-ray scattering, as well as optical phase contrast microscopy. Combining the experimental thermodynamic data with a simulation of the liquidus and solidus lines, we were able to construct a phase diagram. Using this approach, we find that the lipids mix in all phases non-ideally in the thermodynamic sense. As expected, pure POPE assembles into multilamellar and pure POPG into unilamellar vesicles, respectively, which are stable within the studied temperature range. In contrast, mixtures of the two components form oligolamellar vesicles consisting of about three to five bilayers. The layers within these oligolamellar liposomes are positionally correlated within the gel phase, but become uncorrelated within the fluid phase exhibiting freely fluctuating bilayers, while the vesicles as a whole remain intact and do not break up into unilamellar forms. X-ray, as well as DSC data, respectively, reveal a miscibility gap due to a lateral phase segregation at POPG concentrations above about 70 mol%, similar to previously reported data on mixtures composed of disaturated PEs and PGs. Hence, the existence of a region of immiscibility is a general feature of PE/PG mixtures and the mixing properties are dominated by PE/PG headgroup interactions, but are largely independent of the composition of the hydrocarbon chains. This is in accordance with a recent theoretical prediction.

The effects of adjuvant chemotherapy on cognition in women with breast cancer--preliminary results of an observational longitudinal study.

Several studies have reported that chemotherapy-treated patients have impaired cognition function relative to control groups. We are conducting a longitudinal study with cognitive assessments at baseline, 6 and 18 months. A planned preliminary analysis of data from 50 chemotherapy patients and 43 healthy controls at baseline and post-treatment found a significant group by time interaction on three measures of verbal and working memory. Chemotherapy patients were more likely to show cognitive decline than controls (OR 2.25). Patients were significantly more likely to have GHQ(12) scores indicative of possible psychological morbidity and showed significant increases in endocrine symptoms and fatigue post-treatment however neither GHQ(12) nor quality-of-life variables were related to cognitive performance.

A phase I study of letrazuril in AIDS-related cryptosporidiosis.

OBJECTIVE: The intestinal parasite Cryptosporidium is a common cause of chronic diarrhoea in AIDS patients and is responsible for significant morbidity and mortality. No effective treatment is currently available for this condition. Here we aim to determine the safety, tolerance, and clinical effect of letrazuril in the treatment of AIDS-related Cryptosporidiosis. DESIGN: A prospective, open-label study of letrazuril was performed. SETTING: The study was conducted at the Immune Deficiency Treatment Centre (IDTC) of Montreal General Hospital, a tertiary-care centre with inpatient and outpatient facilities. PARTICIPANTS: All HIV-positive patients presenting to the IDTC between November 1991 and January 1993 who had symptomatic intestinal Cryptosporidiosis were enrolled in this protocol. Sixteen participants entered the study and 15 were available for evaluation, having completed at least 2 weeks on the study medication. INTERVENTIONS: Patients received letrazuril daily in escalating doses of 50 to 100 mg orally for 6 weeks. Clinical and laboratory evaluations were performed weekly during the treatment phase, with a follow-up evaluation 4 weeks after the end of this phase, for a total study period of 10 weeks. MAIN OUTCOME MEASURES: Response to letrazuril was assessed by eradication of Cryptosporidial oocysts from the stool and symptomatic improvement in diarrhoea and abdominal pain. Haematological, biochemical, and electrocardiographic parameters were also studied to evaluate potential toxicities of the treatment. RESULTS: Fourteen evaluable patients had baseline CD4 lymphocyte counts ranging from 3 to 99 x 10(6)/l cells (mean, 30 x 10(6)/l cells). (The fifteenth evaluable patient had a CD4 count 235 x 10(6)/l.) Of these 14 patients, five showed a major response (symptomatic improvement and eradication of Cryptosporidial oocysts from the stool), two had a minor response (symptomatic improvement with persistence of oocysts in stool), and seven had no response to therapy with letrazuril. Seven patients developed a transient drug-related rash. CONCLUSION: Fifty per cent of the AIDS patients in this study experienced an improvement in their Cryptosporidial disease while receiving letrazuril. No serious dose-related toxicities were observed. Larger Phase II trials are needed to evaluate the safety and efficacy of letrazuril in AIDS-associated intestinal Cryptosporidiosis.

Frontal blood flow changes in recovery from coma.

Two-dimensional studies of cortical blood flow were conducted in 20 closed head injury patients in a comatose state and subsequently in 9 patients as they recovered to an awake and responding state. Comatose patients showed a reduction of frontal flow compared to the resting pattern observed in age matched normal volunteers. In most patients the normal anterior-to-posterior flow gradient was reversed. Increases in global flow, while in coma, tended to exaggerate this reversal. Patients who survived showed a normalization of the regional flow pattern as they regained consciousness. The marked reduction of frontal blood flow in the comatose state was independent of locus of injury as determined by computed tomography (CT) scan data. Combined with previous CBF studies of sensory and cognitive activation, these findings suggest that frontal reduction may be a nonspecific effect of any state or condition involving reduced directed mental activity. This, in turn, raises questions about recent interpretations offered for frontal CBF reduction in psychiatric disease.

Evidence for right-hemisphere involvement in recovery from aphasia.

Cortical evoked potentials and dichotic listening test scores were used to assess the extent of activation of the two cerebral hemispheres during various language tasks in a group of 21 recovering aphasics, 15 nonaphasic patients with right-hemisphere stroke, and 17 normal volunteers. In agreement with previous findings, both measures suggest greater right-hemisphere activation during language processing in the recovering aphasics than in nonaphasic patients and normal subjects. These data support the view that restitution of language entails reorganization of brain function with increased participation of the nondominant hemisphere.

Cerebral blood flow in severity-matched Alzheimer and multi-infarct patients.

Cerebral blood flow was studied in patients meeting research criteria for either Alzheimer's disease or multi-infarct dementia, matched for age and severity of dementia. In both groups, mean flow was less than in age-matched normal controls, but the Alzheimer patients also had significantly lower mean flow than the multi-infarct group. This result helps resolve discrepancies found in studies with inadequate control for severity. Either global flow or regional left parietal flow could be used to discriminate between these dementia categories with 87% accuracy.

Hemispheric asymmetries in arousal affect outcome of the intracarotid amobarbital test.

OBJECTIVE: To evaluate changes in arousal and their impact on memory performance during the intracarotid amobarbital test (IAT). METHODS: Along with memory measures, level of arousal was evaluated through clinical ratings and nonverbal self-ratings in epilepsy patients undergoing IAT before anterior temporal lobectomy. RESULTS: Irrespective of seizure focus, left-sided amobarbital injection resulted in decreased objective and subjective arousal more often than right-side injection. Impaired objective arousal was greater when the left hemisphere was injected second, because of the presumed additive effects of systemic amobarbital residual from the first injection. Decreased objective arousal was related to poorer performance on memory testing following left-hemisphere injection. CONCLUSIONS: The IAT, as practiced in most centers, is biased, so patients with right temporal lobe seizure focus are more likely to "pass" the test, whereas patients with left seizure focus are more likely to "fail" the test. The significant impact of changes in arousal on memory testing needs to be considered when using IAT results to select patients for temporal lobectomy.

Visuospatial tasks compared via activation of regional cerebral blood flow.

Regional cerebral blood flow was measured in 19 subjects during the performance of three tasks thought to primarily involve right hemisphere processing: judgement of line orientation, mental rotation of three-dimensional cube arrays, and a fragment puzzle task. Asymmetries in hemispheric flow (right side greater) were only observed in the line orientation and rotation conditions and were present in both sexes. The magnitude of the asymmetry was greater in the rotation task which also showed an asymmetry in parietal flow. Thus mental rotation placed the most asymmetric demand on cerebral resources. This provides a task that more reliably activates the right hemisphere than those previously reported and suggests a truly "mental manipulative" aspect to right hemisphere advantage in visuospatial performance.

CBF gradient changes elicited by visual stimulation and visual memory tasks.

Normal volunteers underwent three successive scans of regional cerebral blood flow (rCBF) using the 133Xe inhalation technique during visual stimulation, a recognition memory task and a resting state defined by high EEG alpha content. Since the stimulation was virtually identical in both non-rest conditions, we were able to separate the CBF pattern resulting from simple stimulation and that resulting from the cognitive (recognition memory) component alone. These turned out to have very nearly opposite effects on the normal anterior-to-posterior resting state gradient: the sensory component diminished the gradient, while the cognitive component exaggerated it. It is suggested that these normative data can be of clinical value in the study of cerebral recovery/reorganization following post-traumatic amnesia.

Regional stability of cerebral blood flow measured by repeated technetium-99m-HMPAO SPECT: implications for the study of state-dependent change.

UNLABELLED: The replicability of resting state rCBF has implications for the analysis of cerebral activation protocols and the interpretation of rCBF in disease states. This study examined the stability of rCBF as measured by two resting state 99mTc-HMPAO brain SPECT scans with an emphasis on examining the contribution of specific cerebral regions to within and between subjects variance. METHODS: Nine normal, medically healthy subjects underwent two 99mTc-HMPAO brain SPECT scans under identical conditions separated by 48 hr. A reference system and semiautomated computer ROI method was used to enable accurate alignment and cortical analysis of the two scans. RESULTS: Mean within-subject difference between Scans 1 and 2 was 2.8% (range 0%-7.8%) for the 36 cortical ROIs. The mean between-subject coefficient of variation was 10% (range 7%-15%) for these ROIs. Correlation analysis of rCBF pattern replication for all slice levels yielded a highly significant overall consistency of pattern within subjects (Pearson r = 0.698, p = 0.0001). Variance component analysis revealed regional heterogeneity in between-subjects variance, with significantly greater variability found in frontal regions. The within-subject repeated measures variability was not significantly different across regions. CONCLUSION: Good within-subject 48-hr replicability indicates that individual resting state rCBF reflects fairly stable, subject-specific factors. This also justifies comparing state-dependent studies separated by a modest length of time. Although individual patterns of rCBF replicate well, the larger contribution of frontal regions to normal between-subjects variance makes evaluating the frontal effects of disease or activation more difficult.

Frontotemporal decreases in rCBF correlate with degree of dysnomia in primary progressive aphasia.

UNLABELLED: Primary progressive aphasia (PPA) is an uncommon degenerative dementia characterized by gradual impairment of language function with initial sparing of the memory domain. Using semiquantitative 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain SPECT as a measure of regional cerebral blood flow (rCBF), we investigated the relationship between reduced 99mTc-HMPAO uptake and the severity of dysnomia in PPA. METHODS: Seven right-handed patients with PPA had their dysnomia assessed by the Boston Naming Test (BNT), a subtest of the Boston Diagnostic Aphasia Examination. Neuroimaging studies, including 99mTc-HMPAO brain SPECT, CT, and MRI, were performed. Correlational analysis between reduced rCBF and BNT was performed. RESULTS: Brain SPECT showed a reduction in 99mTc-HMPAO uptake involving the frontal and temporal lobes in all 7 patients. CT and MRI showed mild to moderate cerebral atrophy in 4 patients. Low scores on the BNT correlated with low frontotemporal 99mTc-HMPAO (Spearman r = 0.97, P = 0.004) in the 5 patients with left-hemisphere involvement. CONCLUSION: Decreased rCBF to the frontotemporal region characterized the cerebral abnormalities associated with PPA. The finding of focal rCBF abnormalities in the right hemisphere of 2 right-handed women corroborates that PPA symptoms may arise from a "non-left-dominant"-hemisphere degenerative process. Our results support the usefulness of rCBF SPECT imaging as a diagnostic aid in PPA.

Psychogenic events presenting as parasomnia.

A 10-year-old child suddenly developed nocturnal enuresis and nocturnal behaviors similar to parasomnia that were occasionally violent. The child had no recollection of the events. Continuous video/electroencephalograph monitoring revealed the episodic nocturnal events with bizarre behaviors during what was perceived to be sleep, but in fact, the child was fully awake with his eyes closed, prior to and during the events. The attacks ceased with individual psychotherapy and family counseling.

Disrupted neural responses to phonological and orthographic processing in dyslexic children: an fMRI study.

Developmental dyslexia, characterized by difficulty in reading, has been associated with phonological and orthographic processing deficits. fMRI was performed on dyslexic and normal-reading children (8-12 years old) during phonological and orthographic tasks of rhyming and matching visually presented letter pairs. During letter rhyming, both normal and dyslexic reading children had activity in left frontal brain regions, whereas only normal-reading children had activity in left temporo-parietal cortex. During letter matching, normal-reading children showed activity throughout extrastriate cortex, especially in occipito-parietal regions, whereas dyslexic children had little activity in extrastriate cortex during this task. These results indicate dyslexia may be characterized in childhood by disruptions in the neural bases of both phonological and orthographic processes important for reading.

The treatment of periocular basal cell carcinomas by radiotherapy.

Experience in the treatment of periocular basal cell carcinoma is described. Excellent local control rates and minimal morbidity have been achieved in a series of 128 tumours occurring in 127 patients with a minimum 3 year follow-up.

The use of neoadjuvant CMF to avoid mastectomy.

AIMS: Large operable cancers have traditionally been treated surgically by mastectomy. More recently centres have investigated the use of neoadjuvant chemotherapy to allow breast-conserving surgery. Between 1991 and 1995, a prospective study into the response of large operable breast cancers to CMF neoadjuvant chemotherapy was performed. METHODS: Patients with cancers requiring mastectomy, and with or without clinically involved non-fixed lymph nodes, were offered neoadjuvant CMF chemotherapy. Patients declining neoadjuvant treatment underwent mastectomy and appropriate axillary surgery. Clinical response was assessed after two cycles in the neoadjuvant group. Subsequent surgical or non-surgical management was planned after this. RESULTS: Thirty-eight patients were suitable for neoadjuvant treatment. Twenty-two underwent two cycles of CMF and were then reassessed. Seventy-three per cent achieved a response [three (14%) complete remission, 13 (60%) partial remission]. Fifteen (68%) patients avoided mastectomy, with six (27%) requiring no surgery at all with no clinically detectable residual disease. Sixteen (42%) declined neoadjuvant chemotherapy and opted for immediate mastectomy, seven of whom accepted chemotherapy post-operatively. After 3 years' follow-up there is no statistical difference in local recurrence, distant recurrence or overall survival. CONCLUSION: Approximately 40% of patients offered neoadjuvant chemotherapy will demand prompt surgical treatment but will consider the use of adjuvant chemotherapy post-operatively. Sixty-eight per cent of patients receiving neoadjuvant CMF will successfully avoid mastectomy.

Innovative technique for Norplant implants removal.

This study evaluates a unique and completely different approach from the original removal technique. The main objective of this technique is to facilitate removal of widely-spaced, deeply-positioned, and misplaced Norplant capsules. A local anesthetic is injected deep and perpendicular to the long axis of the Norplant rods. The hypodermic needle is left in place underneath the six silicone rods for the entire removal procedure. One or two 3-4mm vertical incisions were made between the capsules over the needle. The Norplant rods were dissected free from the fibrous tissue and the skin with a #11 blade. A curved mosquito forceps was inserted between the skin and the Norplant rod, to hook and deliver the capsule through the incision, from where it can be easily removed. This method resulted in far less time, effort, and skill from the health care provider, no damage to the capsules, and much less trauma to the clients.

PIP: Between September 1993 and June 1994, 4 physicians in California removed 22 Norplant implants using an innovative and simple removal technique designed to remove misplaced capsules. They all had had experience with the original removal technique. They inserted a 2 inch, 21 gauge hypodermic needle perpendicular to the long axis of the Norplant capsules and left it under the capsules during the entire procedure. This served to lift, stabilize, and make the rods easier to palpate and to dissect a tract underneath the rods. They injected 2-3 ml of 2% xylocaine with epinephrine as they slowly advanced the needle. The physicians made one or two 3-4 mm vertical incisions between capsules 2 and 3 and between capsules 4 and 5 over the needle. The 2nd incision reduced trauma and scarring as well as the time, effort, and skill needed from the provider. In about 46% of cases, they were able to remove the rods through a single incision. They used a 11 blade to dissect the rods free. They inserted a small curved mosquito forceps to deliver the rod through the incision. The tip was either facing downwards, then rotated 180 degrees to deliver the rod, or facing upwards to deliver it. Another forceps was used to dissect the rod free from fibrous tissue and to remove it. After removal of the 6th rod, they removed the needle and applied Steri-strips. About 70% of all rods were visible and palpable. About 14% were higher than the other rods. Two women had rods that crossed. It took, on average, 12 minutes to remove all 6 capsules. 77% of the women returned for the follow-up visit (3-4 days postremoval). The physicians followed up with the remaining women by telephone. 64% experienced a minor hemorrhagic spot over the procedure site. The Steri-strips caused a blister in 1 client. At the postremoval visit, no one had removal-site hematomas or infections. This removal technique may increase acceptability and use of Norplant and reduce its cost.

Jejunal cirsoid aneurysm: a rare cause of massive lower gastrointestinal hemorrhage.

Diverticulosis and angiodysplasia are the most common causes of massive lower gastrointestinal hemorrhage. Lower gastrointestinal hemorrhage frequently resolves without determination of a definitive source. An uncommon cause of lower gastrointestinal tract hemorrhage is the small intestinal submucosal aneurysm. This poorly described entity, more commonly recognized as Dieulafoy's disease in the gastric mucosa, has been documented only rarely in the jejunum. We describe a case report of a 27-year-old man with a massive lower gastrointestinal hemorrhage. Diagnostic evaluation failed to identify the source on initial admission. The patient re-presented to the emergency room with recurrent bleeding, anemia, and hypotension. During a period of active bleeding, a number of diagnostic studies ultimately revealed the source to be the proximal jejunum. Inspection of the resected specimen identified a submucosal aneurysm on the mesenteric border. Histologic evaluation identified the pathologic entity as a cirsoid aneurysm.