Self-inflicted orbital and intracranial injury with a retained foreign body, associated with psychotic depression: Case report and review

Reports of intracranial self-multilation by psychotic individuals are associated with severe mental disorders, criminality, or both. We describe a psychotically depressed male who drove a ballpoint pen through his right medial canthus and into his intracranial compartment. The patient developed a cavernous sinus syndrome and a traumatic dissection of the cavernous portion of the carotid artery. The pen was removed intraoperatively. Postoperatively, the patient was placed on a course of broad-spectrum antibiotics, antidepressants, and antipsychotic medications, and he has received long-term psychiatric follow-up. The literature related to these unusual cases is reviewed, and relevant surgical, medical, and psychiatric aspects of treatment are discussed.     

Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer

10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a weekly x 3 schedule (35 patients) or a weekly schedule (27 patients). The dosage levels ranged from 5 to 120 mg/m2. The toxicity observed with 10-EDAM was qualitatively similar to that of methotrexate. Oral mucositis was the dose-limiting toxicity; diarrhea, skin rash, leukopenia, thrombocytopenia, and mild elevations of serum glutamic-oxaloacetic transaminase, prothrombin, and partial thromboplastin times were also observed, but were not dose limiting. A weekly dosage of 80 mg/m2 with escalation or attenuation in accordance with patient tolerance, or 100 mg/m2 weekly for 3 weeks, followed by a 2-week "rest period" are recommended for Phase II assessment. 10-EDAM produced partial remissions in three patients with non-small cell lung cancer and one patient with breast cancer lasting 6, 40+, 26+, and 15 months, respectively. Pharmacokinetic studies carried out at the 5, 30, and 100 mg/m2 dosage levels demonstrated the drug to have a triphasic disappearance from plasma. Elimination was independent of dose over the range tested, with mean plasma half-lives of: alpha = 12.9 min, beta = 1.5 h, and gamma = 11.9 h. Cumulative urinary excretion of the drug ranged from 13 to 55% of the administered dose (mean = 33%); 88% of the urinary drug appeared within the first 4 h following drug administration. The pharmacokinetic behavior of the first and second weekly dosages were consistent within a given patient. The metabolites 7-hydroxy-10-EDAM, and 10-ethyl-10-deaza-2,4-diamino-pteroic acid were demonstrated in the plasma and urine of treated patients. In studies of tissue homogenates from two patients with skin metastases, more extensive retention of the drug and of its polyglutamates was observed in the breast cancer metastases than in the metastases from a kidney cancer or in normal skin.     

Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome

Two siblings from a consanguineous family presented with a poikiloderma of limbs and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and neutrophil dysfunction with impairment of the respiratory burst and bacterial killing resulted in frequent respiratory tract infections. A bronchocentric granulomatous pneumonia was a fatal complication. The clinical presentation is consistent with Clericuzio type poikiloderma with neutropenia. Literature review identified several additional probable patients. Genetic linkage analysis excluded the locus of the RECQL4 gene, mutations in which have been described in some patients with the Rothmund-Thomson poikiloderma syndrome. This report confirms the clinical and genetic identity of the Clericuzio type of poikiloderma with neutropenia syndrome.     

Gamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy,non-mycobacterium bovis BCG-vaccinated Malawian young adults

We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-gamma) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. The M. tuberculosis antigens ESAT-6 and MPT64 and the M. bovis antigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded to M. tuberculosis PPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure to M. tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have antigens homologous to the M. leprae 35-kDa and 18-kDa antigens. M. tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M. tuberculosis antigens tested it provided the best indication of exposure to, or infection with, M. tuberculosis.     

A comparison of seasonal variation between suicide deaths and attempts in Hong Kong SAR

BACKGROUND: Seasonal variations in suicide deaths and attempted suicides have been reported for many countries. Recent research has suggested that seasonal patterns of suicide deaths have diminished considerably. The seasonality pattern between attempts and completed ones are not the same. This paper is the first one to examine seasonal variation between suicide deaths and attempts simultaneously. METHOD: Census and Statistics Department and the Hospital Authority provided mortality and morbidity data on suicides for the period 1997-2001 in Hong Kong SAR, respectively. Seasonal patterns of suicide deaths and attempts were examined by a harmonic analysis and a non-parametric chi-square test. RESULTS: A significant seasonal variation was detected in suicide attempts with a markedly bi-seasonal pattern was found amongst females with a peak in May and October; only a cyclic pattern was observed for males with a peak in summer. The female attempters who used non-violent suicide methods contributed to the second peak in October. On the other hand, there was no evidence of significant differences in the seasonal distribution among the suicide deaths for males and females. Only a mild pattern was found amongst females involving in violent suicide deaths, while others can be treated as a random event and no significantly pattern was observed in our study. Overall, a significant difference in seasonal variation existed between suicide deaths and attempts (p-value<0.01). CONCLUSIONS: This study reinforces the findings that seasonal variation in suicide appears to be diminishing. Also, suicide attempters and completed suicides in Hong Kong seem to arise from two non-identical but overlapping groups in the community.     

Apparent scarcity of glial fibrillary acidic protein expression in the brain of the pygmy shrew Sorex minutus as revealed by immunocytochemistry

We examined astroglial cells in the brain of the pygmy shrew Sorex minutus (Insectivora). For that purpose we labeled glial fibrillary acidic protein (GFAP) immunohistochemically in brain sections with a polyclonal antibody. Antigen retrieval experiments were performed to counteract formaldehyde fixation masking of GFAP epitopes. Our results showed remarkable paucity of GFAP-immunoreactive cells and fibers in the cerebral cortex and nuclei, as well as in the majority of the diencephalic and mesencephalic structures. In the forebrain, significant numbers of GFAP-containing astrocytes were found only in the ependyma and subventricular zones, superficial part of layer I of the cerebral cortex, and the majority of white matter structures. In the diencephalon, habenular nuclei were rich in GFAP-immunopositive astrocytes and labeled radial fibers were extended between median eminence and the third ventricle. A considerably higher density of labeled astrocytes was detected in the caudal brainstem and cerebellum. In contrast, in the mouse brain, immunoreactive astrocytes were present in large quantities in various structures. Staining of sections of the shrew brain against glutamine synthetase revealed abundance of immunofluorescent astrocytes in many areas, especially in the shrew cerebral cortex. It seems probable that in the shrew brain only a limited fraction of astroglia expresses GFAP, while other astroglial cells can be detected with different markers. It is possible that the rodent type of astroglial GFAP expression might not be common to insectivores and probably to some other mammalian orders.     

Acoustic startle response in the opossum Monodelphis domestica in comparison with the Wistar albino rat

The acoustic startle response (ASR) was studied in 20 gray short-tailed opossums (Monodelphis domestica) and its characteristics were compared with those obtained from responses of 20 Wistar albino rats. The animals were exposed to 10 ms, 110 dB white noise acoustic pulses in the Coulbourn apparatus. Amplitude of ASR was normalized to the weight of animals and then analyzed. The results show that probability of a freezing response is much higher in the opossums that generally respond with lower startle amplitudes in comparison to rats. These differences may reflect different emotional characteristics of the two species, different reactions to fear in opossum and/or different ecological specializations of the two species.     

Dental abnormalities in individuals with pathogenic germline variation in DICER1

Pathogenic germline variation in the microRNA processing gene DICER1 gives rise to an autosomal dominant, tumor‐predisposition disorder. Conditional deletion of Dicer1 in murine dental epithelium shows that it controls tooth patterning, size, number, and shape. The human dental phenotype of people with germline pathogenic variation in DICER1 is unknown. DICER1‐carriers (n = 57) and family controls (n = 55) were evaluated at the NIH Clinical Center dental clinic as part of a comprehensive medical evaluation. Digital panoramic radiographs, bite‐wing radiographs, and oral photographs were collected. A single observer, blind to DICER1 status, reviewed the dental records and determined the presence or absence of 11 dental characteristics as described in the clinic notes, radiographs, or oral photographs. Subjective phenotypes were reviewed on radiographs by two examiners (blind to DICER1 status) for the presence or absence of the dental characteristics to reduce inconsistencies. By simple association, bulbous crown, periodontitis, and taurodontism were all significant (p < .05). Logistic regression with chi‐square maximum likelihood estimates showed that bulbous crown and periodontitis remained significant. Recognition of these phenotypes may aid identification of individuals and families at risk for DICER1‐associated neoplasms. These findings may also guide dental care for individuals with germline DICER1 pathogenic variation.