Hydrocephalus in coccidioidal meningitis: case report and review of the literature

OBJECTIVE AND IMPORTANCE: Coccidioidomycosis was once confined to the southwest United States and northern Mexico. It has become a larger concern because of the concentration of military bases in these areas, the increasing mobility of populations, and the rising population of immunocompromised persons. Outside endemic areas, the diagnosis is rarely considered. Patients with coccidioidomycosis may develop occult basilar meningitis progressing to communicating hydrocephalus and death. CLINICAL PRESENTATION: A 60-year-old white man presented with a 1-month history of vertigo, falls, and vomiting. Computed tomography of the head revealed mild hydrocephalus. Lumbar puncture results were remarkable for 1065 mg/dl protein; acid-fast bacillus stain, Gram's stain, and culture results were negative. Postgadolinium magnetic resonance imaging demonstrated enhancement of basilar and cervical meninges, suggesting inflammation, and communicating hydrocephalus. For 48 hours, the patient's level of consciousness decreased progressively. INTERVENTION: A ventriculoperitoneal shunt was placed, and antifungal agents were initiated on an emergent basis. CONCLUSION: Coccidioidomycosis should be considered in the differential diagnosis of occult basilar meningitis. The diagnosis is established by the discovery of a high (>1:2) titer of complement-fixing antibody in the cerebrospinal fluid. Communicating hydrocephalus is a common complication of untreated coccidioidal meningitis, and it may develop during appropriate treatment (oral fluconazole, 200-400 mg/d, continued indefinitely). Patients with hydrocephalus and evidence of increased intracranial pressure require a shunt.     

The nature of the myenteric infiltrate in achalasia: an immunohistochemical analysis

Achalasia is an esophageal motor disorder characterized by abnormal relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown the presence of myenteric inflammation to be a consistent and early pathologic change in patients with achalasia. Thus, the goal of this study was to determine the immunohistochemical characteristics of the inflammatory infiltrate within the myenteric plexus in patients with clinically early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the immunohistochemical features of the myenteric lymphocytes using antibodies that recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with clinically early achalasia who underwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine esophagomyotomy specimens was composed predominantly of T cells (CD3-positive), the majority of which also stained for CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal resection specimens, the myenteric infiltrate was composed predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there was a predominance of CD20-positive B cells, and in the remaining three cases there were relatively equal numbers of T and B cells. In eight of 13 cases, the majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and esophageal resection specimens studied, rare granzyme B-positive cells were detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also CD8-positive, although the relative percentage of such cells appears to decrease with disease progression. Furthermore, many of the CD3-positive/CD8-positive myenteric lymphocytes also express TIA-1, suggesting they are resting or activated cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a subpopulation of these cells supports the contention that achalasia is an immune-mediated disease, although the inciting antigen remains an enigma.     

Innervation of the digit on the forepaw of the raccoon

The innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin-gene related peptide, substance P, neuropeptide-Y, tyrosine hydroxylase, and neurofilament protein. The larger-caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine-caliber innervation terminates in the epidermis and on the microvasculature. The innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffini-like endings at the transition from the distal phalanx and unmyelinated innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine-caliber innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular innervation is peptidergic, whereas most of the unmyelinated epidermal innervation is nonpeptidergic.     

Disabled-1 is expressed in type AII amacrine cells in the mouse retina

The organization of several laminated structures in the brain is controlled by a signaling pathway activated by Reelin, a large glycoprotein secreted by pioneer neurons in the developing brain. Reelin binds to transmembrane receptors, including VLDLR and ApoER2, and stimulates tyrosine phosphorylation of Disabled-1 (Dab1), which associates with an NPxY motif present in the cytoplasmic domain of the receptors. Disruption of reelin, dab1, or both the vldr and apoer2 genes results in similar cell positioning defects in laminated brain regions including the cerebellum, hippocampus, and cerebral cortex. Although retinal ganglion cells express reelin during development, there is no obvious disruption of cell positioning in the retina of reeler mice. Here, we examine the expression pattern of Dab1 as a first step toward understanding the function of the Reelin signaling pathway in neural retina. Immunohistochemical analysis of the adult retina revealed that Dab1 is expressed in a specific type of amacrine cell. These cells display a narrow dendritic field and they project to two distinct sublaminae within the inner plexiform layer. Dab1 co-localizes with the high-affinity glycine transporter, indicating that these amacrine cells are glycinergic. Cells that express Dab1 are surrounded by dopaminergic fibers originating from wide-field amacrine cells. These features are characteristic of type AII amacrine cells described in other mammalian species. Analysis of the retina at several stages of development revealed that Dab1 is expressed shortly after birth during the time at which AII amacrine cells extend neurites and form synaptic connections in the inner retina. This raises the possibility that the Reelin/Dab1 signaling pathway contributes to formation of intraretinal circuitry in the neural retina.     

Stimulation of ovine choriomammotrophin release, in vitro, by phospholipase C

Phospholipid metabolites have previously been implicated in receptor-mediated stimulation of protein hormone secretion. As the factors which regulate the release of choriomammotrophin remain to be elucidated, we investigated the potential involvement of phospholipase C-induced phospholipid metabolism in the release of this placental hormone. Phospholipase C (PLC) caused a dose-dependent release of choriomammotrophin from ovine placenta, incubated in vitro. At a concentration of 0.2 units/ml (0.25 microgram protein/ml), PLC caused the release of choriomammotrophin from placental tissue to approximately double that observed in control incubations (7.08 +/- 0.4 micrograms/50 mg/h and 3.26 +/- 0.3 micrograms/50 mg/h, respectively). PLC treatment did not significantly alter plasma membrane permeability, as indicated by the release of lactate dehydrogenase and protein. PLC-stimulated release of oCM was completely abolished by incubation in calcium-free medium or by preincubation with the inorganic calcium-channel blocking agents cobalt chloride (4 mM) and lanthanum chloride (1 mM). The effects of PLC treatment on ovine choriomammotrophin (oCM) release were also inhibited by preincubation of placental tissue with inhibitors of arachidonic acid metabolism: ibuprofen (10(-5) M), naproxen (10(-4) M) or nordihydroguaiaretic acid (NDGA) 5 X 10(-6) M). These results suggest that the effects of PLC on the release of choriomammotrophin are mediated via metabolites of arachidonic acid.     

Cerebroretinal vasculopathy. A new hereditary syndrome

A new hereditary syndrome characterized by a frontoparietal lobe pseudotumor and retinal capillary abnormalities is described. A pedigree is presented in which characteristic ophthalmic findings have been found in ten family members and are suspected in eight additional family members spanning a total of four generations. Typical retinal findings include perifoveal capillary obliteration, peripheral focal capillary occlusion, and microvascular abnormalities, particularly involving the posterior pole. Eight patients spanning three generations had a central nervous system pseudotumor with identical histopathology. Histopathologic analysis of brain tissue shows a characteristic pattern of an unusual vasculopathy without vasculitis characterized by fibrinoid necrosis and resulting in necrosis of white matter with sparing of cortical brain tissue. The pedigree shows an apparent autosomal dominant pattern of inheritance with delayed expression of abnormalities. Of note, two patients unrelated to the pedigree having similar neuropathologic and retinal findings also have been seen at the authors' institution.     

THE INTRARENAL PRESSURE DURING EXPERIMENTAL RENAL HYPERTENSION

The intrarenal interstitial pressure was measured during the course of experimental renal hypertension in dogs. In perinephritic hypertension, produced by wrapping the kidney in a cellophane bag, the intrarenal pressure rose slowly from the normal value of 25 mm. Hg to a final level of about 60 mm. Hg. Strong pressure pulsations were observed in the renal parenchyma during this type of hypertension. In the hypertension following partial occlusion of the renal artery, the intrarenal pressure remained approximately normal, except in malignant hypertension when it tended to decline to about 9 mm. Hg. The hypertension of perinephritis is interpreted as a consequence of renal ischemia, the high intrarenal pressure, produced by the constricting fibrotic hull, acting to reduce the effective perfusion pressure of the kidney. The two experimental hypertensions herein examined are considered as examples of influent resistance hypertensions and effluent resistance hypertensions, the former being due to renal arterial or arteriolar resistance and the latter due to renal venous resistance, specifically at the arcuate-interlobar junction. The application of this concept to renal hypertensive disease in man is discussed.     

Interpreting declines in HIV test positivity: an analysis of routine data from Zimbabwe's national sex work programme, 2009–2019

IntroductionEarly diagnosis of HIV is critical for epidemic control. To achieve this, successful testing programmes are essential and test positivity is often used as a marker of their performance. The aim of this study was to analyse trends and predictors of HIV test positivity over time and explore how an understanding of seroconversion rates could build on our interpretation of this indicator among female sex workers in Zimbabwe.MethodsWe analysed HIV test data from Zimbabwe''s nationally scaled sex work programme between 2009 and 2019. We defined test positivity as the proportion of all tests that were HIV positive and measured new diagnoses by estimating seroconversion rates among women with repeat tests, defined as an HIV‐positive test after at least one HIV‐negative test in the programme. We used logistic regression to analyse test positivity over three time‐periods: 2009–2013, 2014–2017 and 2018–2019, adjusting for potential confounding by demographic factors and the mediating effects of time since last HIV test. We calculated the seroconversion rates for the same time‐periods.ResultsDuring the 10‐year study period, 54,503 tests were recorded in 39,462 women. Between 2009 and 2013, 18% of tests were among women who reported testing in the previous 6 months. By 2018–2019, this had increased to 57%. Between 2018 and 2019, test positivity was 9.6%, compared to 47.9% for 2009–2013 (aOR 6.08 95% CI 5.52–6.70) and 18.8% for 2014–2017 (aOR 2.17 95% CI 2.06–2.28). Adjusting for time since last test reduced effect estimates for 2009–2013 (aOR 4.03 95% CI 3.64–4.45) and 2014–2017 (aOR 1.97 95% CI 1.86–2.09) compared to 2018–2019. Among 7573 women with an initial HIV‐negative test in the programme and at least one subsequent test, 464 tested HIV positive at a rate of 3.9 per 100 pyar (95% CI 3.5–4.2).ConclusionsTest positivity decreased among women testing through the programme over time, while seroconversion rates remained high. These declines were partly driven by changes in individual testing history, reflecting comprehensive coverage of testing services and greater knowledge of HIV status, but not necessarily declining rates of seroconversion. Understanding testing history and monitoring new HIV infections from repeat tests could strengthen the interpretation of test positivity and provide a better understanding of programme performance.