Atypical mycobacterial spondylitis in HIV-negative patients identified by genotyping.

Non-tuberculous mycobacterial infections pose a significant diagnostic and therapeutic challenge. We report two cases of such infection of the spine in HIV-negative patients who presented with deformity and neurological deficit. The histopathological features in both specimens were diagnostic of tuberculosis. The isolates were identified as Mycobacterium intracellulare and M. fortuitum by genotyping (MicroSeq 16S rDNA Full Gene assay) and as M. tuberculosis and a mycobacterium other than tuberculosis, respectively, by culture. There is a growing need for molecular diagnostic tools that can differentiate accurately between M. tuberculosis and atypical mycobacteria, especially in regions of the developing world which are experiencing an increase in non-tuberculous mycobacterial infections.

p53 mutations in basal cell carcinomas arising in routine users of sunscreens.

Sun exposure histories were obtained from a series of patients age 35 or younger following diagnosis and removal of a basal cell carcinoma (BCC). The DNA was extracted from tumor biopsy samples derived from BCC of 10 patients who reported that they did not use sunscreens during youth (age 18 or younger) and 10 patients who routinely employed sunscreens during this age period. Exons 5-9 of the p53 gene were then amplified in three fragments from these samples using a nested polymerase chain reaction (PCR) approach and screened for mutations using an RNA heteroduplex assay. All PCR products displaying evidence of a mutation were sequenced. It was found that 6 of the 10 patients who were not routine sunscreen users displayed mutations in these p53 exons. All of the mutations were located at dipyrimidine sites, five of the six were C-->T transitions and one mutation was a tandem double mutation, consistent with a role for solar UVB in BCC formation. In contrast, only one p53 mutation was detected in the group of 10 patients who routinely employed sunscreens during childhood and adolescence. Hence, a significantly (P = 0.029) lower level of p53 mutations was detected in the BCC obtained from sunscreen users compared with tumors derived from nonusers. These findings suggest that the mechanisms involved in the etiology of skin carcinogenesis differ in sunscreen users compared with people who did not routinely employ sunscreens. These data are also indicative of a protective effect associated with sunscreen use against the formation of p53 mutations. It is possible that the patients who were diagnosed with BCC despite their use of sunscreens possessed a genetic susceptibility for skin cancer formation and developed BCC through a p53-independent pathway. Alternatively, solar UVA wavelengths, that were generally not blocked by the suncare products employed by the sunscreen users, may have played a significant role in BCC development through induction of a mutation(s) in an oncogene and/or a tumor suppressor gene, other than p53, for these patients.

Care of the skin at midlife: diagnosis of pigmented lesions.

Intrinsic skin changes with advancing years include dryness, decreasing elasticity, increasing skin fragility, and more prominent vasculature. Extrinsic skin aging, caused primarily by cigarette smoking and exposure to sunlight, includes mottled pigmentation and yellow discoloration, rough leathery textural changes, and wrinkling. Major premalignant and malignant neoplasms in photodamaged skin are actinic keratosis, basal cell carcinoma, squamous cell carcinoma, and melanoma. Nonmalignant lesions include solar lentigines and seborrheic keratoses. The A, B, C, D criteria can assist in the evaluation of pigmented nevi. Physicians play an important role in educating patients about the health risks associated with excessive sun exposure and about sun protection to prevent further skin damage.

Pustular and erythrodermic psoriasis complicated by acute respiratory distress syndrome.

BACKGROUND: The pustular and erythrodermic types of psoriasis have been associated with a number of systemic complications, including congestive heart failure and pneumonia. Acute respiratory distress syndrome (ARDS) refers to acute noncardiogenic pulmonary edema with hypoxemia of various causes and has been attributed to pulmonary capillary leak. Recently, 4 cases of generalized pustular or erythrodermic psoriasis have been described associated with a pulmonary capillary leak syndrome. OBSERVATIONS: We describe 2 additional patients, 1 with pustular and erythrodermic psoriasis and 1 with erythrodermic psoriasis; who developed ARDS. Radiographic findings, pulmonary capillary wedge pressures, echocardiograms, and, in one case, an open lung biopsy specimen, were consistent with the diagnosis of ARDS. In neither case could we document any of the common causes of acute respiratory failure. CONCLUSIONS: Generalized pustular and erythrodermic psoriasis may be complicated by ARDS. The pathogenesis of this complication is unclear, but proinflammatory cytokines may be involved.

Agonistic activity of a CD40-specific single-chain Fv constructed from the variable regions of mAb G28-5.

A single-chain Fv (sFv) was expressed from the variable regions of the CD40-specific mAb G28-5. The molecule bound CD40 with a high affinity (2.2 nM) and was a monomer in solution. Surprisingly, G28-5 sFv was a potent CD40 agonist that rapidly crosslinked CD40 on the cell surface but did not crosslink CD40-Ig in solution. G28-5 sFv was a more potent agonist than G28-5 IgG and was able to stimulate CD40 responses by B cells and monocytes. G28-5 IgG partially blocked, whereas G28-5 sFv augmented CD40 responses during stimulation with natural ligand (gp39-CD8 fusion protein). These results indicate that the functional activity of ligands built from the binding site of G28-5 is highly dependent upon the size and physical properties of the molecule both in solution and on the cell surfaces.

Efficacy of auditory brainstem response as a screening test for small acoustic neuromas.

Auditory brainstem response (ABR) has been advocated as a high sensitivity screening test for acoustic neuroma. With the advent of magnetic resonance imaging (MRI), smaller size acoustic neuromas are now detectable. A prospective trial was performed to determine the sensitivity of ABR in diagnosing small acoustic neuromas. One hundred five randomly selected patients with surgically proved acoustic neuromas underwent preoperative ABR tests within 2 months of their surgery. Patients with a histologic diagnosis other than acoustic neuroma were excluded from this study. A test was considered abnormal when the interaural wave I-V latency difference was greater than 0.2 ms, the absolute wave V latency was abnormally prolonged, or there was abnormal or absent waveform morphology. Of the 105 patients tested 92 (87.6%) had abnormal ABR test, and 13 (12.4%) had completely normal waveforms and wave latencies. Eighteen patients had tumors over 2 cm in total diameter. Of these, 12 were 2.5 cm or larger and 6 were between 2.1 and 2.4 cm. All of these 18 patients had abnormal ABR tests. Of the 29 patients with tumors 1.6-2.0 cm in size, 25 (86%) had abnormal ABRs. In the 1.0-1.5 cm diameter range there were 45 patients who underwent a preoperative ABR. Of these, 40 (89%) had abnormal ABRs. Of 13 patients with tumors 9 mm or smaller, only 9 (69%) had abnormal ABR test (p < .05). Thus, it appears that ABR sensitivity decreases with tumor size and is particularly inadequate for tumors of less than 1 cm in diameter. The authors conclude that ABR is not a good screening test for smaller acoustic neuromas and recommend MRI for patients with suspected acoustic neuroma.

Nonoperative management of upper thoracic spine fractures.

We attempted to determine if nonsurgical treatment could be successful in treating instability of upper thoracic spine fractures, which may receive some stabilization and splinting from the ribs. From 1966 to 1989, the records of all patients treated at Rancho Los Amigos Medical Center for fractures from T-1 to T-8 were reviewed. Penetrating injuries and malignant lesions were excluded. A total of 118 patients were admitted during this period; 49 patients had nonsurgical treatment. Complications included 1 patient with neurologic worsening, brace-related skin necrosis in 8 cases, and deep venous thrombosis in 12 patients. No failure of arthrodesis was noted. Rib fractures did not adversely affect late stability. We conclude that orthotic treatment of thoracic spine instability from T-1 to T-8 can be successful, especially in cases where early surgery is not possible.

Mutations in the gag gene of Moloney murine leukemia virus: effects on production of virions and reverse transcriptase.

We have constructed a series of deletion mutations in the p30 and p10 domains of the gag gene of Moloney murine leukemia virus. Mutants with deletions in P30 were completely defective in virion particle production even though an altered gag precursor protein is synthesized. This domain is apparently critical for particle formation. A mutant in P10 was able to release virion particles into the medium, and low levels of reverse transcriptase activity could be detected in these virions. To explore the effects of these mutations on the utilization of the gag-pol precursor, we have introduced these mutants into cells already releasing defective particles from an endogenous provirus which directs the synthesis of gag gene products and not pol gene products. The P10 mutant was capable of providing pol function as judged by the incorporation of high levels of reverse transcriptase into the particles and complete complementation for XC plaque formation. In contrast, the mutants in P30 were negative in this complementation test. Thus, those gag mutants which were unable on their own to assemble virion particles were also unable to contribute the gag-pol precursor to these particles. These mutations are the first to be mapped to the gag region which affect pol function, suggesting that the gag-pol precursor must be assembled before pol is functionally separated from the gag domain. The concordance of the effects of different mutations on both particle formation and gag-pol utilization suggests that similar domains of gag (namely, domains in the P30 region) are needed for these two processes.