A web-based review of global health programs in U.S. allopathic and osteopathic medical schools.

PURPOSE: There is no current centralized database of structured global health programs at U.S. medical schools and no published review in the past decade. This study aims to describe the prevalence, characteristics, and requirements of non-degree, longitudinal, structured global health programs in U.S. allopathic and osteopathic medical schools. MATERIALS AND METHODS: In July 2021, the authors performed a web-based review of existing structured global health programs for the 154 U.S. allopathic medical schools and 35 U.S. osteopathic medical schools established prior to 2019. RESULTS: Of 189 institutions examined, 74 (39%) had online information about a structured global health program. Forty-three (53%) programs reported coursework requirements, 44 (54%) required a global health experience, and one program required demonstration of language or cultural knowledge. More internally administered programs required experiential work, while more externally administered programs required didactic work. There were few differences in program requirements between allopathic and osteopathic medical schools. CONCLUSIONS: There has been a 75% increase over the past ten years in the number of U.S. allopathic medical schools with websites for structured global health programs. There appeared to be little standardization in their structure and requirements. The findings support the need for a web-based central repository for updated information regarding medical school global health curricula.

Cross-sectional structure of the central mitotic spindle of Diatoma vulgare. Evidence for specific interactions between antiparallel microtubules.

During the transition from prometaphase to metaphase, the cross-sectional area of the central spindle of Diatoma decreases by a factor of nearly two, both at the poles and at the region of overlapping microtubules (MTs) near the spindle equator. The density of spindle MT packing stays approximately constant throughout mitosis. Optical diffraction analysis of electron micrographs shows that the packing of the MTs at the poles at all stages of mitosis is similar to that expected for a two-dimensional liquid. Analysis of the region of overlap reveals more packing regularity: during prometaphase, a square packing emerges that displays sufficient organization by late metaphase to generate five orders of diffraction; during anaphase the packing in the overlap region shifts to hexagonal; at telophase, it returns to square. From the data provided by serial section reconstructions of the central spindle, it is possible to identify the polarity of almost every spindle MT, that is, to identify one pole with which the MT is associated. Near neighbor analyses of MTs in cross sections of the overlap region show that MTs prefer antiparallel near neighbors. These near neighbors are most often found at a spacing of approximately 40 nm center-to-center, while parallel near neighbors in the zone of overlap are spaced essentially at random. These results are evidence for a specific interaction between antiparallel MTs. In some sections definite bridges between MTs can be seen. Our findings show that certain necessary conditions for a sliding filament model of anaphase spindle elongation are met.

Three-dimensional structure of the central mitotic spindle of Diatoma vulgare.

Central mitotic spindles in Diatoma vulgare have been investigated using serial sections and electron microscopy. Spindles at both early stages (before metaphase) and later stages of mitosis (metaphase to telophase) have been analyzed. We have used computer graphics technology to facilitate the analysis and to produce stereo images of the central spindle reconstructed in three dimensions. We find that at prometaphase, when the nuclear envelope is dissassembling, the spindle is constructed from two sets of polar microtubules (MTs) that interdigitate to form a zone of overlap. As the chromosomes become organized into the metaphase configuration, the polar MTs, the spindle, and the zone of overlap all elongate, while the number of MTs in the central spindle decreases from greater than 700 to approximately 250. Most of the tubules lost are short ones that reside near the spindle poles. The previously described decrease in the length of the zone of overlap during anaphase central spindle elongation is clearly demonstrated in stereo images. In addition, we have used our three-dimensional data to determine the lengths of the spindle MTs at various times during mitotis. The distribution of lengths is bimodal during prometaphase, but the short tubules disappear and the long tubules elongate as mitosis proceeds. The distributions of MT lengths are compared to the length distributions of MTs polymerized in vitro, and a model is presented to account for our findings about both MT length changes and microtubule movements.

Induced muscle differentiation in an embryonal carcinoma cell line.

Cells of the teratocarcinoma-derived line P19S1801A1 (01A1) are pluripotent embryonal carcinoma cells and can be induced to differentiate when aggregated and exposed to dimethyl sulfoxide. Many nonneural cell types appear in dimethyl sulfoxide-treated cultures, cardiac and skeletal muscle being the most easily identified. We have used immunofluorescence procedures with monoclonal antibodies directed against muscle myosin to confirm and quantitate the number of muscle cells formed. A monoclonal antibody reactive with an embryonal carcinoma-specific surface antigen was used to confirm the disappearance of undifferentiated cells after dimethyl sulfoxide treatment. Cardiac muscle cells developed within 4 to 5 days of drug exposure, but skeletal muscle cells did not become evident until 7 to 8 days. We have isolated a mutant cell line (D3) which appears to be incapable of muscle development but which does form neurons and glial cells when exposed to high retinoic acid concentrations. We propose that this system will be useful for investigation of the means by which pluripotent cells become committed to development along the striated muscle lineages.

Magnetic resonance imaging. Clinical correlation in 64 patients with multiple sclerosis.

Sixty-four patients with possible, probable, or definite multiple sclerosis (McAlpine criteria) were clinically evaluated using the expanded disability status scale (EDSS) and Scripps neurologic rating scale (NRS). All were examined with a 0.15T magnetic resonance scanner using T2- and T1-weighted images. Correlations between EDSS and NRS scores and severity of disease detected on magnetic resonance imaging were determined. Significant correlations existed between EDSS and NRS with magnetic resonance ratings. Moderate correlations were observed in the motor, cerebellar, and brainstem subgroups of the clinical scales. Significant low correlations existed in the mood/mentation, vision (optic nerves), and bowel/bladder subgroups. Clinical and neuroimaging limitations may account for the lack of higher correlations. Significant correlations suggest the utility of magnetic resonance imaging in monitoring disease progression, and it may prove to be the technique of choice in following up patients with multiple sclerosis.

Brain-stem auditory evoked potential abnormalities with unilateral brain-stem lesions demonstrated by magnetic resonance imaging.

We correlated the brain-stem auditory evoked potential (BAEP) abnormalities in 24 patients with discrete unilateral brain-stem lesions demonstrated by magnetic resonance imaging. In 18 patients who had BAEP abnormalities either confined to or more severe on stimulation of one ear, the lesion on magnetic resonance imaging was in the brain stem ipsilateral to the corresponding ear. Mesencephalic lesions produced amplitude abnormalities of the IV/V complex while pontine lesions resulted in abnormalities of earlier components (wave II and/or III). Prolongation of the I-III interpeak latency tended to occur with pontine lesions and of the III-V interpeak latency with mesencephalic lesions. Unilateral brain-stem lesions, particularly at the mesencephalic level, often produced BAEP abnormalities on both ipsilateral and contralateral monaural stimulation.

HIPDM-SPECT in patients with medically intractable complex partial seizures. Ictal study.

Both interictal and ictal N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3,propanediamine -single photon emission computed tomography (HIPDM-SPECT) were performed in 16 patients with medically intractable complex partial seizures. Ictal HIPDM-SPECT localized epileptic foci in 13 of 14 patients with unilateral temporal focus and provided confirmative evidence of epileptic focus in 11 patients by demonstrating maximally increased regional cerebral perfusion (rCP) in epileptic foci that had shown decreased rCP in a previous interictal study. Ictal HIPDM-SPECT in two patients with bitemporal foci showed more complicated patterns consisting of slightly increased rCP in bilateral multifocal regions. Ictal HIPDM-SPECT was particularly useful for investigating epileptic foci, and correlation with simultaneously recorded ictal electroencephalograms provided further insight for localizing epileptic foci.

Magnetic resonance imaging in multiple sclerosis: analysis of correlations to peripheral blood and spinal fluid abnormalities.

MRI of the brain, peripheral blood (PB) T cell subsets and B cells, CSF T cell subsets, CSF IgG concentration and incidence of CSF oligoclonal bands (OB), and plasma cells were studied in 32 clinically suspected MS patients. The CSF in MS patients with MRI lesions showed increased IgG concentration and higher incidence of plasma cells and OB compared with those without MRI lesions. In PB, the percentage of kappa light-chain positive B cells was significantly increased in patients with abnormal MRI as compared with controls. The correlation of MRI of the head and immunologic studies in MS will be helpful in better understanding the pathogenesis and dynamics of the disease.

Multiple sclerosis: magnetic resonance imaging, evoked responses, and spinal fluid electrophoresis.

Magnetic resonance images (MRI), evoked responses (ER), and CSF findings were compared in 39 patients with possible, probable, or definite MS. MRI disclosed multiple lesions (72%) more often than ERs (55%) in the total group of patients. In possible MS, MRI showed multiple lesions in 71%, and ER abnormalities were found in 41%. MRI is the preferred test for patients with suspected MS, but ERs are useful when MRI is normal and in the evaluation of optic nerve or spinal cord lesions.

Single photon emission computed tomography (SPECT) brain imaging using N,N,N'-trimethyl-N'-(2 hydroxy-3-methyl-5-123I-iodobenzyl)-1,3-propanediamine 2 HCl (HIPDM): intractable complex partial seizures.

HIPDM-SPECT brain imaging was performed in four patients with intractable complex partial seizures (CPS). Three patients had an epileptogenic focus in one temporal lobe and underwent anterior temporal lobectomy. Interictal HIPDM-SPECT demonstrated decreased regional cerebral perfusion (rCP) in the epileptogenic area in only one patient, but ictal studies showed increased rCP in the epileptic foci of all three patients. In the fourth patient, interictal HIPDM-SPECT showed increased rCP in the area of epileptogenic focus; when antiepileptic medication was taken, rCP decreased. HIPDM-SPECT brain imaging is useful for localizing epileptogenic foci in CPS.

Girl with signs of Pelizaeus-Merzbacher disease heterozygous for a mutation in exon 2 of the proteolipid protein gene.

We studied a female infant with clinical signs of Pelizaeus-Merzbacher disease (PMD), who has a familial mutation (C41-->T) in exon 2 of the proteolipid protein gene (PLP), and selected relatives. While the carrier mother and grandmother of the proposita currently are neurologically normal and show normal T2 magnetic resonance imaging (MRI) of the brain, the infant has a neurological picture, MRIs, and brain auditory evoked response (BAER) consistent with that diagnosis. The data here presented show that PMD can occur in females carrying a mutation in the PLP gene. Our experience with the MRIs of this patient, her mother and grandmother, and those of a previously reported family [Pratt et al.: Am J Med Genet 38:136-139, 1991] show that molecular genetic analysis and not MRI is the appropriate means for carrier detection.

Foci of increased T2 signal intensity in MR images of healthy elderly subjects. A follow-up study.

An 18-month follow-up study was conducted on 26 healthy elderly subjects with and without foci of increased T2 signal intensity on MR imaging. The subjects did not differ with respect to health status or cognitive performance as measured by the Cognitive Subscale of the Cambridge Mental Disorders of the Elderly Examination and the Mini Mental State Examination at follow-up. There was a significant decline in performance on the Digit Symbol Substitution Test in subjects who had evidence of T2 foci compared to the performance of subjects without T2 foci. This may indicate that the presence of T2 foci is correlated with subtle difficulties in learning and memory.

Cerebral venous distention associated with cardiac failure in infants.

Three infants with congestive cardiac failure demonstrated dilated and hyperdense intracranial veins and sinuses on noncontrast cranial CT. Intracranial venous thrombosis and arteriovenous malformation were excluded in two infants by autopsy and in one infant by MR imaging. We believe the CT findings were secondary to an elevated central venous pressure caused by the cardiac failure. This CT pattern suggests venous congestive failure, and it should alert the clinician and radiologist to the risk of subsequent sinus thrombosis.

Cranial MR in spinal cord MS: diagnosing patients with isolated spinal cord symptoms.

MR brain scans, spinal fluid electrophoresis, and evoked responses were obtained in 10 adult patients with isolated spinal cord symptoms diagnosed as possible multiple sclerosis (MS) according to the McAlpine criteria. Typical lesions of MS were found on T2-weighted MR images in six patients. Spinal fluid abnormalities were found in four. Visual-evoked responses or brainstem auditory-evoked responses were abnormal in three. MR in conjunction with spinal fluid analysis supported the diagnosis of MS in eight of 10 patients. Evoked responses appeared less sensitive than MR in identifying subclinical lesions in this population.

Complicated infantile meningitis: evaluation by real-time sonography.

Real-time sonographic findings in 20 infants with bacterial meningitis are reported. The spectrum of features included normal scans, ventricular enlargement, focal areas of increased cortical echogenicity, ventricular bands, and cerebral abscess. Areas of increased cortical echogenicity on sonography representing meningoencephalitis corresponded to areas of contrast enhancement seen on computed tomography (CT). Excellent correlation was found between CT and sonography. Because of the advantage of obtaining sonographic scans at the bedside, it appears that sonography offers an attractive alternative to CT in the evaluation of infantile meningitis and meningoencephalitis.

Computed tomography of chiasmal optic neuritis.

Three cases of chiasmal optic neuritis are described with bitemporal visual field loss and enlargement of the optic chiasm as demonstrated by computed tomography (CT). Exploratory craniotomies were performed in two of the patients, but no tumor was found. After corticosteroid treatment, all three patients experienced virtually complete restoration of normal vision. Although the CT presentation in these patients was indistinguishable from that of a chiasmal glioma, the clinical presentation of acute visual loss in an older child or adult should suggest chiasmal optic neuritis. A period of observation, with or without a trial of corticosteroids, might permit the latter diagnosis and obviate exploratory craniotomy.

Foci of increased T2 signal intensity on brain MR scans of healthy elderly subjects.

Foci of increased T2 signal intensity were found on brain MR scans in 16 (59%) of 27 healthy elderly volunteer subjects, ages 63 to 86 years old. These foci were not related to cognitive function or cerebrovascular risk factors; instead, they were highly correlated to age, being present in 11 of 11 subjects aged 75 years and over.

Melanotic neuroectodermal tumor of infancy.

We present a case of malignant melanotic neuroectodermal tumor of infancy arising in the skull and secondarily invading brain. The central tumor was hyperintense to brain on T1-weighted images and hypointense to brain on T2-weighted images. This appearance corresponded to the surgical and histologic findings of melanin-containing tumor.

Gd-enhanced MR imaging of acute and chronic experimental demyelinating lesions.

Experimental allergic encephalomyelitis, a demyelinating disease with marked similarity to multiple sclerosis, was produced in two of 12 dogs. All dogs were studied with serial MR imaging. T1- and T2-weighted MR images were obtained both before and after IV Gd-DTPA. Multiple, new periventricular white matter demyelinating lesions were observed after each clinical episode of the disease. Like multiple sclerosis, the acute lesions of experimental allergic encephalomyelitis on T2-weighted MR images were indistinguishable from the older, more chronic lesions. However, after Gd-DTPA, there was bright paramagnetic enhancement of the acute lesions and, in one animal, no enhancement of the chronic lesions on T1-weighted MR images. At necropsy, the differences in the MR paramagnetic enhancement correlated well with the relative histologic age of the demyelinating lesions. Our results suggest that MR with Gd-DTPA may be used to differentiate acute, active demyelinating lesions from the more chronic, inactive lesions in this animal model.

Neuroimaging of disseminated germ cell neoplasms.

The purpose of this study was to determine the role of neuroimaging in the management of patients with metastatic germ cell tumors. Retrospective evaluation of 299 patients treated in 1986 and 1987 for initial presentation or recurrence of testicular, retroperitoneal, and mediastinal germ cell tumors was performed to determine indications for neuroimaging, frequency and site of CNS metastases, and occurrence of other CNS abnormalities. Sixty-six patients required CNS imaging with myelography, CT, or MR. Studies were normal in 24 patients. Twenty patients had CNS metastases including 11 with intracranial metastases, eight with spine lesions, and one with both brain and spine involvement. Sixteen had cerebral or cerebellar atrophy of unclear origin and functional significance. Two patients had ventriculomegaly without symptoms of hydrocephalus. Four patients had questionable lesions that were never confirmed. None of the 25 asymptomatic patients with elevated serum tumor markers had brain metastases. Fifteen of 17 patients with focal neurologic deficits and three of six patients with seizures had CNS metastases. CNS imaging to detect germ cell tumor metastases is most useful in the presence of neurologic deficits or seizures but is not useful in patients with unexplained elevation of serum tumor markers in the absence of neurologic deficits.