Images in clinical medicine. Acute bacterial meningitis.
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Acute Disease↗
Biomedical subjects
J A Golden
Publications and source records attributed to J A Golden.
Development of the superior temporal neocortex is anomalous in trisomy 21.
Trisomy 21 (Down syndrome) is the most common inherited form of mental retardation in the United States, however, the basis of impaired cognition is unknown. We have used recently developed stereological cell counting techniques to quantitatively examine the pattern of neuronal migration and maturation in one neocortical area during gestation in normal development and in trisomy 21. Normal development of the cerebral cortex occurs in two general sequences: Beginning at approximately 7-8 weeks gestation, migration of cells destined to become neurons results in the accumulation of cells in the cortical mantle. This process is largely complete by 20-21 weeks. Over the next 7-10 weeks an "inside-out" differentiation into lamina of different neuronal densities occurs. Our data suggest that the second phase of cortical development, the emergence of lamination, is both delayed and disorganized in trisomy 21. The observed pattern of cortical maturation may reflect an abnormality in axonal and dendritic arborization that subsequently subserve the connectional and functional units underlying normal cognition.
Cell Movement↗
Pseudomonas stimulates interleukin-8 mRNA expression selectively in airway epithelium, in gland ducts, and in recruited neutrophils.
Neutrophils may play important roles in chronic airway diseases. Pseudomonas is a common pathogen in some chronic airway diseases, and expression of the neutrophil chemoattractant interleukin-8 (IL-8) is induced by Pseudomonas in various cells in vitro. Here we examine the localization of IL-8 mRNA expression after incubating human and dog bronchi with Pseudomonas supernatant in vitro. To examine IL-8 expression in recruited neutrophils, we also superfused the dog bypassed tracheal segment with Pseudomonas supernatant in vivo and measured neutrophil number and IL-8 concentration in luminal fluid; simultaneously, we introduced Pseudomonas supernatant by catheter in a peripheral airway. After 6 h, we analyzed IL-8 mRNA expression and localization in removed tissue. Unincubated bronchi showed no IL-8 mRNA expression, but incubation with Pseudomonas supernatant in vitro resulted in IL-8 mRNA expression in surface epithelial, gland duct, and a subpopulation of serous gland cells. In vivo, introduction of Pseudomonas supernatant into dog trachea and peripheral airways caused IL-8 mRNA expression in epithelial and gland duct cells but also in the recruited neutrophils. Pseudomonas lipopolysaccharide alone was without effect in vitro and in vivo. We conclude that Pseudomonas products, but not lipopolysaccharide, stimulate IL-8 expression in airways and that this expression occurs primarily in surface epithelial and gland duct cells, thus bringing the chemoattractant to the bacterial site. Furthermore, IL-8 expression in recruited neutrophils provides a potential mechanism for positive feedback of this protective antibacterial response.
Adult↗
Third ventricular xanthogranulomas clinically and radiologically mimicking colloid cysts. Report of two cases.
Two cases are reported of third ventricle masses that were clinically and radiographically indistinguishable from pure colloid cysts. A 21- and a 36-year-old man presented with a 5-year and 10-day histories of headache, respectively. Magnetic resonance (MR) imaging revealed smooth, homogeneous masses in the anterior third ventricle that were iso- to hyperintense on T1-weighted MR images and hyperintense on T2-weighted images. There was little enhancement with intravenous contrast material. In both patients, craniotomies were performed and histopathological examination revealed xanthogranulomas of the choroid plexus with only microscopic foci of colloid cyst-like structures. These cases illustrate that xanthogranulomas of the third ventricle may clinically and radiologically mimic pure colloid cysts, that a range of MR imaging signals can be seen, and that craniotomy rather than stereotactic aspiration is the indicated treatment.
Adult↗
The face-brain relationship: a case of the face not predicting the brain.
An infant with midline facial cleft and a severe brain malformation, not typical of holoprosencephaly, is reported. The CNF abnormalities suggested a malformation in the same category, but distinguishable from the various forms of holoprosencephaly sequence.
Brain↗
Intermittent pattern of neural tube closure in two strains of mice.
Development of the neural tube is often described as a continuous process that begins in the cervical region of the embryo and proceeds both rostrally and caudally. Examination of neural tube closure in the cranial region of LM/Bc and SWV/Bc mice revealed an intermittent pattern with four distinct areas of closure. Closure I begins at the level of somites 1-3 and proceeds bidirectionally. Closure II is initiated at the prosencephalic-mesencephalic border and also proceeds bidirectionally. Closure III is unidirectional, beginning adjacent to the stomodeum and proceeding caudally to meet closure II. Finally, closure IV takes place over the rhombencephalon where it meets closure II to complete rostral neural tube closure. In these two strains of mice anterior neural tube closure progressed as somite number increased. However, the SWV strain required a longer gestational time to develop equal numbers of somites and therefore to complete closure. In light of the intermittent pattern of closure observed in mice, the development of the rostral nervous system in other mammals, including humans, should be reconsidered.
Animals↗
Clinical teratology counseling and consultation case report: two distinct anterior neural tube defects in a human fetus: evidence for an intermittent pattern of neural tube closure.
Human neural tube closure is believed to be a continuous process that begins in the cervical region and progresses both rostrally and caudally. In contrast, an intermittent pattern of anterior neural tube closure has been demonstrated in rodents. Based on individual case photographs, a similar pattern of anterior neural tube closure, with multiple sites of closure, may also exist in humans. We report a human fetus with two distinct anterior neural tube defects separated by a cutaneous and mesenchymal bridge. The two defects occurred within distinct closure sites predicted by the murine model, one falling within closure II and the second within closure IV. Although one defect had adherent amniotic bands, evidence is presented to support a primary dysraphy rather than disruption from an amniotic band. This case provides further evidence supporting an intermittent pattern of anterior neural tube closure in human embryogenesis.
Abortion, Therapeutic↗
Central nervous system malformations in trisomy 9.
Trisomy 21, 18 and 13 are the most common varieties of autosomal trisomy recognized at birth; most of the others lead to spontaneous abortions in the first trimester. Trisomy 9, a rare trisomy, is compatible with life, but, unlike trisomy 21, 18 and 13, the range of manifestations has not been well catalogued. Central nervous system abnormalities have been reported in the majority of cases, usually including a dilated fourth ventricle and malformed cerebellum. The posterior fossa malformation closely resembles the descriptions of the Dandy-Walker malformation leading some to suggest this designation, while others have suggested that the features are unique to trisomy 9. Two cases of trisomy 9 are presented in this report which extend the range of neuropathologic manifestations in this cytogenetic disorder. The first infant had cortical migration abnormalities, anomalous hippocampal formation, simplified inferior olivary nuclei, germinal matrix cysts, mild ventriculomegaly, syringomyelia, and a large myelomeningocele without a Chiari type II malformation. The fourth ventricle was normal in size and the cerebellum unremarkable. The second infant had a cystically dilated fourth ventricle and widely separated cerebellar hemispheres with an intact cerebellar vermis, the features of which we felt were compatible with the Dandy-Walker malformation. In addition, agenesis of the corpus callosum, anomalous hippocampal formation, subpial glial nodules and mild ventriculomegaly were present. These cases extend the range of malformations that may be associated with trisomy 9, and raise the differential diagnosis of trisomy 9 when these malformations are identified.(ABSTRACT TRUNCATED AT 250 WORDS)
Agenesis of Corpus Callosum↗
Upper and middle lobe bronchoalveolar lavage to diagnose Pneumocystis carinii pneumonia.
Pneumocystis carinii pneumonia (PCP) remains the most common lethal opportunistic pulmonary infection in patients infected with the human immunodeficiency virus (HIV). Although the use of prophylactic inhaled pentamidine has effectively reduced the frequency of primary and recurrent episodes of PCP, the aerosolization of pentamidine may have altered the localization of active PCP, resulting in more upper lobe disease. The distribution of disease may have also affected the diagnostic accuracy of standard bronchoalveolar lavage of the middle lobe, with a reduction in sensitivity from about 90 to 65%. In retrospective surveys of patients from our institution, Steiger and Fahy found that pooled multiple-lobe radiographic site-directed bronchoalveolar lavage resulted in diagnostic sensitivities of 91 and 100%, respectively. We performed a follow-up prospective study of 38 consecutive patients on aerosolized pentamidine in whom we lavaged both the middle lobe and an upper lobe. We found that bilobar lavage including routine lavage of an upper lobe increases the diagnostic sensitivity of bronchoalveolar lavage alone to 95% compared with 65% if lavage is performed only in the middle lobe (p < 0.05). Radiographic studies demonstrate a concordant increase in exclusive or predominant upper lobe disease in patients on aerosolized pentamidine, but our results indicate that PCP is recovered more frequently from the upper lobe regardless of the radiographic appearance. We conclude that all patients on prophylactic inhaled pentamidine should undergo bilobar lavage with the inclusion of an upper lobe in the initial evaluation of possible PCP. The diagnostic sensitivity of 95% makes bilobar bronchoalveolar lavage an acceptable sole initial diagnostic modality without the need for initial transbronchial lung biopsy.
AIDS-Related Opportunistic Infections↗
Appearance of a cavernous hemangioma in the cerebral cortex after a biopsy of a deeper lesion.
Cavernous hemangiomas are vascular malformations that can occur throughout the central nervous system. In certain patients, multiple lesions are known to occur. We present a patient with multiple cavernous hemangiomas who had a computed tomography-guided biopsy of a deep parieto-occipital lesion through a burr hole. Several passes of a biopsy needle were used. During a 5-year interval, the patient developed a new lesion directly under the burr hole on the cortical surface. The new lesion appears to have occurred from the implantation and growth of a cavernous hemangioma secondary to the biopsy.
Adult↗
Diagnosis of Pneumocystis carinii infection in HIV-seropositive patients by identification of P carinii in pleural fluid.
Pneumocystis carinii pneumonia (PCP) is the most common pulmonary complication of AIDS and is typically diagnosed by the identification of P carinii organisms in sputum, bronchoalveolar lavage fluid, or tissue obtained with transbronchial biopsy. We describe two HIV-seropositive patients with pleural effusions in whom the diagnosis of P carinii infection was made by examination of pleural fluid. Pleural effusions associated with PCP are very unusual but can provide a source of diagnostic material particularly in those HIV patients who have development of a spontaneous pneumothorax and require chest tube insertion.
AIDS-Related Opportunistic Infections↗
A randomized comparison of once-monthly or twice-monthly high-dose aerosolized pentamidine prophylaxis.
RESULTS: Ten of the 146 (7 percent) evaluable subjects developed PCP during the year study period, and there was no difference in the efficacy of the two regimens. Among patients receiving secondary prophylaxis, the attack rate of PCP at 1 year was 11 percent. This compares favorably with a 1-year attack rate of 19 percent in similar patients receiving standard dose (300 mg) prophylaxis and suggests, but does not prove, a dose-response effect. Concentrations of pentamidine in BAL fluid were not significantly different among the three lobes of the lung. Intrapulmonary pentamidine did not accumulate during the year of study. Aerosolized pentamidine was associated with a marginal but statistically significant increase in the residual volume, decreased flow rates, and increased airway reactivity. OBJECTIVE: The optimal regimen of aerosolized pentamidine in unknown. Published data suggest that there is a dose-response effect and that the occurrence of Pneumocystis carinii pneumonia (PCP) has been associated with prolongation of the interval between doses. The purpose of this study was to compare the efficacy, pharmacokinetics, and physiologic effects of two high-dose regimens of aerosolized pentamidine prophylaxis. DESIGN: Prospective, randomized study of 300 mg twice monthly vs 600 mg once monthly during a 1-year observation period. Pentamidine concentrations in plasma and bronchoalveolar lavage (BAL) fluid were measured and serial pulmonary function was measured. SETTING: A large teaching hospital in San Francisco. PATIENTS: One hundred fifty-one adult (age > 18 years) men with human immunodeficiency virus infection. Of 146 evaluable patients, prophylaxis was primary (no prior PCP) in 108 (75 percent) and secondary (one prior episode of PCP) in 38 (25 percent). MEASUREMENTS: Date and diagnosis of PCP, occurrence of drug toxicity, pulmonary function testing, and concentrations of pentamidine in BAL and plasma. CONCLUSIONS: The data suggest, but do not prove, that a dose-response effect has been demonstrated, and that high-dose aerosolized pentamidine may further reduce the attack rate of PCP. These preliminary observations should be confirmed in a double-blind trial comparing 300 mg with 600 mg administered once monthly. The clinical relevance of the adverse pulmonary effects is unclear and requires further investigation.
AIDS-Related Opportunistic Infections↗
An acidic fibroblast growth factor protein generated by alternate splicing acts like an antagonist.
Polymerase chain reaction amplification of cDNA for acidic fibroblast growth factor in several lines of cultured human cells revealed two forms of mRNA. The novel smaller mRNA lacks the entire second coding exon of the acidic fibroblast growth factor gene, whereas the previously identified mRNA consists of three coding exons. The truncated variant of acidic fibroblast growth factor (aFGF') is only 60 amino acids long with an apparent molecular mass of 6.7 kD on sodium dodecyl sulfate gels in contrast to 18 kD for the full-length acidic fibroblast growth factor. aFGF' elicits only minimal fibroblast proliferation and antagonizes the effects of acidic fibroblast growth factor when added exogenously to or when coexpressed with aFGF in BALB/c/3T3 fibroblasts. Thus, the truncated variant of acidic fibroblast growth factor may provide fibroblasts with a unique mechanism for endogenous regulation of their responses to acidic fibroblast growth factor.
Amino Acid Sequence↗
Microgranulomatous aspergillosis after shoveling wood chips: report of a fatal outcome in a patient with chronic granulomatous disease.
Chronic granulomatous disease is characterized by recurrent infections that result from an inability of phagocytes to kill organisms effectively. We describe a patient with this disease who developed aspergillus pneumonia after shoveling moldy cedar wood chips. Despite aggressive therapy, the patient's condition deteriorated and he died. At autopsy, the lungs revealed diffuse granulomas, all of the same age, with aspergillus organisms confined to the granulomas. We propose the term "microgranulomatous aspergillosis" for this response, which does not conform to the commonly described aspergillus syndromes. We conclude that susceptible immunosuppressed patients should be advised to avoid occupational situations where high spore concentrations are generated.
Adult↗
Recovery of Bordetella bronchiseptica from patients with AIDS.
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Acquired Immunodeficiency Syndrome↗
Cystic lung disease associated with eosinophilic granuloma and tuberous sclerosis: air trapping at dynamic ultrafast high-resolution CT.
Thin-walled lung cysts can occur in association with advanced pulmonary eosinophilic granuloma and lymphangioleimyomatosis (LAM). In LAM, cysts occur as an isolated abnormality or in association with tuberous sclerosis. The cause of these cysts is unclear, but some investigators have postulated that they result from air trapping. To determine if lung cysts in these two diseases are associated with air trapping, the authors performed dynamic ultrafast high-resolution computed tomography (DUHRCT) during forced expiration in two patients (one with eosinophilic granuloma and one with tuberous sclerosis) with lung cysts and correlated the results with results of pulmonary function tests. DUHRCT demonstrated focal and diffuse air trapping; in some lung regions, a less than normal increase in lung attenuation during forced exhalation was evident. These studies do not allow a conclusion regarding the mechanism of cyst formation in eosinophilic granuloma and LAM-tuberous sclerosis, but they confirm the association between lung cysts and morphologic findings of air trapping.
Adult↗
High-resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity.
To determine the prevalence of "nonobstructive" (impairment of gas transfer) emphysema in a select population of smokers with dyspnea, a retrospective study of patients with emphysema evident at high-resolution computed tomography (HRCT) was undertaken. Four hundred seventy HRCT studies were reviewed. In 47 cases, centrilobular emphysema was the dominant or sole parenchymal abnormality. Concomitant chest radiographs were available in 41 of these cases; 16 of the 41 lacked radiographic findings of emphysema. Among these 16 patients, pulmonary function testing revealed 10 to have normal flow rates (ratio of forced expiratory volume in 1 second to forced vital capacity and forced expiratory volume in 1 second greater than 80% predicted) and impaired gas transfer (single-breath carbon monoxide diffusing capacity [DLCOSB] less than 80% predicted). With the exclusion of one patient with congestive heart failure from the group of 10, the severity of emphysema at HRCT correlated inversely with DLCOSB (r = -.643). These results indicate that HRCT allows detection of emphysema in symptomatic patients when chest radiographs and pulmonary function tests are nondiagnostic.
Female↗
Treatment of pulmonary arteriovenous malformations by therapeutic embolization. Rest and exercise physiology in eight patients.
Pulmonary arteriovenous malformations (AVM) lead to chronic hypoxemia and systemic emboli. These lesions can now be treated by catheter embolization. In order to examine physiologic abnormalities during exercise in AVM patients, and to evaluate functional improvement after therapeutic embolization, eight patients underwent detailed physiologic studies at rest and during exercise before and after therapeutic embolization. Before treatment, six patients noted dyspnea on exertion and three had symptoms suggesting paradoxical embolism. Resting studies showed hypoxemia, abnormally increased shunt fractions, chronic alveolar hyperventilation, mild decreases in diffusing capacity, and abnormal wasted ventilation (VD). During exercise, oxygenation changed little from the resting values but VD increased markedly. Functional impairment was observed in most patients, and was correlated with shunt fraction. Obliteration of the AVM was accomplished by therapeutic embolization with placement of coils or balloons in the feeder vessels. This treatment resulted in immediate relief of dyspnea and improvement in resting PaO2 and shunt fraction. Exercise studies after embolization showed improvement in exercise capacity and gas exchange. However, chronic alveolar hyperventilation and reduced diffusing capacity remained unchanged. In summary, therapeutic embolization effectively reduces the degree of shunting, with improvement in respiratory symptoms, exercise capacity, and gas exchange at rest and during exercise. The abnormally decreased diffusing capacity and increased VD suggest the presence of a diffuse pulmonary vascular abnormality, of which further study is warranted.
Adult↗