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Biomedical subjects

F G Mullick

Publications and source records attributed to F G Mullick.

At least 19 recordsLinked to original sources

Microscopic pulmonary embolisation of an indwelling central venous catheter with granulomatous inflammatory response.

Indwelling catheters can disintegrate into tiny fragments and embolise. Once the fragments are detected radiographically, they can be removed using vascular intervention techniques. Rarely, indwelling catheters dwindle into inextricable pieces that embolise into minute pulmonary vessels and lymphatics, causing granulomatous changes microscopically. The present study reports a 54-yr-old female who had received several indwelling central lines during several abdominal surgeries over a 5-yr period. The patient developed a noncaseating granulomatous skin lesion followed by exertional dyspnoea a few months later. Chest radiographs and computed tomography showed diffuse interstitial infiltrates. Open lung biopsy showed two types of granulomas: 1) peri-lymphangitic and peri-bronchiolar non-necrotising granulomas consistent with sarcoidosis; and 2) distinct foreign body granulomas. In some of the foreign body granulomas, confocal Raman spectroscopy identified the presence of bisphenol-A-polycarbonate, a polymer commonly used in biomedical devices. The patient improved following treatment with prednisone followed by methotrexate. The present case illustrates an interesting combination of two causes of granulomatous disease, the importance of examining all biopsy specimens from sarcoidosis patients for foreign particles and the rare occurrence of microscopic embolisation of catheter fragments to the lung with foreign-body giant cell reaction to them.

Catheterization, Central Venous↗

Clinical evaluation of an international static image-based telepathology service.

Telepathology is the use of telecommunications technology as a means to facilitate transfer of image-rich pathology data between remote locations for the purposes of diagnosis, education, and research. Although varying levels of technology exist to accomplish this task, static image--based systems are currently the most widely used around the world. Field selection and image quality have often been identified as major impediments to the successful use of static images for diagnostic telepathology. Between November 1994 and July 1999, the Armed Forces Institute of Pathology (AFIP) performed electronic consultation on over 1,250 static image--based cases, recording a clinically significant concordance rate of 97.3% between telepathology and final diagnosis (in cases in which follow-up material was available). For the same subset of cases, an absolute concordance rate of 73.7% was attained. A review of the case flow and construction of the AFIP telepathology system is presented, as well as factors that have an impact on the diagnostic accuracy of static image-based telepathology sytems in general.

Diagnostic Errors↗

The surgical pathology and cytopathology of US Persian Gulf War military veterans.

BACKGROUND: Tens of thousands of Persian Gulf War veterans (GWVs) have presented with medical symptoms since Operation Desert Shield and Operation Desert Storm. The Kuwait Registry at the Armed Forces Institute of Pathology was established to act as a repository for surgical pathology, cytopathology, and autopsy material from GWVs. OBJECTIVE: To identify conditions known to be endemic to the theater of operations in our cohort of GWVs. METHODS: The Kuwait Registry database was searched by computer for listed conditions endemic to the Persian Gulf region included in the registry through December 31, 1997. RESULTS: Of the 2582 patients in this cohort, 1 patient with hepatitis B and 15 patients with hepatitis C were identified. Other known endemic conditions of the Persian Gulf region were not found. CONCLUSIONS: Viral hepatitis (B and C), which is prevalent in the US population, was the only listed endemic condition identified in surgical pathology or cytopathology specimens in our cohort of GWVs.

Adult↗

Ferrous sulfate toxicity: a review of autopsy findings.

Ferrous sulfate is the leading cause of accidental pediatric poisonings. Despite the requirement for child-resistant packaging for any oral iron product with 250 mg or more per container, the incidence has continued to increase. Although the clinical presentation of iron toxicity has been well described, pathologic findings in human tissue and correlation with clinical data are scant. We reviewed autopsies from the Armed Forces Institute of Pathology of 11 children who died from ferrous sulfate toxicity. Clinical data, morphologic changes, and iron levels in tissue were evaluated. The children's ages ranged from 11 to 36 mo. Prominent iron deposition in gastric and small intestinal mucosa was associated with necrosis, with some cases demonstrating prominent vascular iron deposition. The clinical courses were rapid and progressed from Stage I to Stage III. These observations were correlated with increased levels of iron in various tissues, as determined by analytical atomic absorption spectrophotometry. The morphologic and chemical analysis data provide information on the pathogenesis of ferrous sulfate poisoning; the vascular iron deposition may be related to subsequent hemorrhage. In the liver the periportal necrosis is probably a direct cytopathic effect of the highest levels of iron carried to these cells by the portal blood flow.

Child, Preschool↗

Biologic response to passive dissolution of titanium craniofacial microplates.

The effect of anodization on passive dissolution of titanium was studied by measuring titanium levels in peritoneal leukocytes and tissues of laboratory animals with titanium plates implanted into the peritoneal cavity. Fifteen Sprague-Dawley rats were assigned randomly to three treatment groups of five animals. One group served as controls, the other two groups had an anodized or an unanodized implant placed in the left paracolic gutter. Peritoneal lavage samples and blood samples, organ tissues and tissue surrounding the implants, were removed for histologic examination and titanium levels. Titanium was not detected in any distant organs or in the peritoneal lavage fluid. The capsular tissues surrounding the implants contained titanium at levels ranging from 2610 to 16786 ng/g for unanodized plates, and 888-5933 ng/g for anodized plates. The titanium levels within the peritoneal leukocytes of animals with unanodized implants were significantly elevated (P = 0.01) over time, as compared with controls. The level of titanium in the peritoneal leukocytes of animals with anodized implants was not significantly elevated when compared with controls. Titanium levels in the trace range, as measured in the capsular tissues, are likely a result of corrosion. Surface treatment of titanium by anodization reduces passive dissolution.

Animals↗

Laser-Raman microprobe identification of inclusions in capsules associated with silicone gel breast implants.

Raman spectroscopy (the analysis of scattered photons after excitation with a monochromatic light source) provides a nondestructive method for identifying organic and inorganic materials on the basis of the molecule's characteristic spectrum of vibrational frequencies. Although the technique has been predominantly applied in sciences other than pathology, the recent advent of high-quality microscope optics coupled to optical Raman spectrometers (a variation known as a Raman microprobe) rendered this technique amenable to applications in human pathology. In the Raman microprobe, a laser beam is focused on a spot approximately 1 microm in diameter on the surface of the sample, e.g., tissue, and the scattered light is collected and analyzed. In this investigation, we used the Raman microprobe for the identification of foreign materials in breast implant capsular tissues. The characteristic silicone group frequencies associated with the silicon-oxygen stretch, the silicone-carbon stretch, the silicon-methyl and the methyl carbon-hydrogen stretch frequencies were used to identify polydimethylsiloxane and to define chemical differences among the various other implant-related inclusions. All of the inclusions were positively identified in a series of 44 capsules from silicone gel-filled implants: polydimethylsiloxane was found in 44 of 44 capsules surrounding silicone gel-filled implants; polyurethane was seen in 4 of 4 capsules around polyurethane foam-coated gel-filled implants; 4 of 4 capsules enveloping Dacron patch gel-filled implants revealed Dacron; and talc was identified in 8 of these 44 capsules. Raman microspectroscopy provides a rapid, accurate, and sensitive method for identifying inclusions associated with silicone and other implant materials in tissue.

Breast↗

Detection of titanium in human tissues after craniofacial surgery.

Generally, titanium fixation plates are not removed after osteosynthesis, because they have high biocompatability and high corrosion resistance characteristics. Experiments with laboratory animals, and limited studies of analyses of human tissues, have reported evidence of titanium release into local and distant tissues. This study summarizes our results of the analysis of soft tissues for titanium in four patients with titanium microfixation plates. Energy dispersive x-ray analysis, scanning electron microscopy, and electrothermal atomic absorption spectrophotometry were used to detect trace amounts of titanium in surrounding soft tissues. A single metal inclusion was detected by scanning electron microscopy and energy dispersive x-ray analysis in one patient, whereas, electrothermal atomic absorption spectrophotometry analyses revealed titanium present in three of four specimens in levels ranging from 7.92 to 31.8 micrograms/gm of dry tissue. Results from this study revealed trace amounts of titanium in tissues surrounding craniofacial plates. At the atomic level, electrothermal atomic absorption spectrophotometry appears to be a sensitive tool to quantitatively detect ultra-trace amounts of metal in human tissue.

Biocompatible Materials↗

Pathological and biophysical findings associated with silicone breast implants: a study of capsular tissues from 86 cases.

Breast implant capsular tissues from 86 cases were studied to characterize the relationship between capsular findings and the type of implant used. Tissues were examined by light microscopy, immunohistochemistry, scanning electron microscopy/energy dispersive x-ray analysis and Fourier transform infrared, and Raman microspectroscopy. Capsular pathology was influenced by the structure and composition of the implant. A pseudoepithelium at the inner capsular surface (synovial metaplasia) was noted with silicone gel-filled, saline-filled, and polyurethane-coated implants, and disproportionatelywith textured surface implants. Immunohistochemical studies of pseudoepithelium supported a macrophage/histiocyte cellular origin. Talc was identified intracellularly within macrophages in 42 cases. Capsular calcification was strongly associated with the presence of implant stabilization patch material. Infrared spectra were used to identify silicone, talc, Dacron, and two different types of polyurethane in capsular tissues. Micropapillary structures identified at the pseudoepithelial surface have, to the authors' knowledge, not been previously described.

Breast↗

Telemedicine and telepathology at the Armed Forces Institute of Pathology: history and current mission.

The Armed Forces Institute of Pathology uses telepathology and telemedicine programs to support its mission of providing pathology consultation, education, and research. The telepathology service is based on a static imaging or "store-and-forward" approach using both proprietary equipment and open systems through the Internet. Initiated in 1993, the service provides rapid expert consultation to pathologists globally. Diagnoses are provided by pathologists in 22 specialized departments. Educational programs are delivered through the World Wide Web. Category I continuing medical education credits can be obtained through Internet-based courses. Research activities are focused on forensic applications and the creation of image databases.

Computer Communication Networks↗

Calcium oxalate crystals in human pathology. Molecular analysis with the laser Raman microprobe.

OBJECTIVE: Calcium oxalate crystals in pathologic specimens were examined by the laser Raman microprobe, a nondestructive spectroscopic technique. Although research focused on the identification of calcium oxalate deposits in tissue sections, kidney stones were also studied to determine the in situ structural specificity of the technique. DESIGN: Paraffin-embedded tissue specimens were cut into sections of 2 to 6 microns. The unstained sections were placed on metal (aluminum)-plated slides and excited with the 514.5-nm line of an argon-ion laser, which was focused to a 1-micron spot size using a high-resolution optical microscope. MAIN OUTCOME MEASURE: The laser Raman microprobe technique generates spectra that differentiate the monohydrate (CaC2O4.H2O, whewellite) and the dihydrate (CaC2O4.2H2O, weddellite) forms of calcium oxalate inclusions in tissue sections. RESULTS: Characteristic spectra were generated and provided unequivocal evidence for the identification of the dihydrate oxalate form of calcium oxalate crystals in cases of oxalosis of the myocardium and for the monohydrate oxalate structure in a case of oxalosis of the pituitary. Finally, the combined occurrence of both oxalate structures was confirmed in kidney stone specimens. CONCLUSION: The results obtained in this investigation demonstrate the efficacy of the laser Raman microprobe as a useful adjunct in diagnostic pathology.

Calcium Oxalate↗

Characterization of acetaminophen: molecular microanalysis with Raman microprobe spectroscopy.

The in situ spectroscopic identification of acetaminophen in a fatal overdose case is described. Numerous techniques have been used to analyze acetaminophen in biological fluids, however, the use of nondestructive spectroscopic techniques has not been documented. In this investigation, the demonstration of the drug material was established by using the laser Raman microprobe technique, providing an accurate identification by virtue of the drug's molecular fingerprint characteristics. Material found on the deceased was collected and placed on metal (aluminum-coated) plated slides and excited with the 514.5 nm line of an argon ion laser, which was focused to a 1 micron spot size using a high-resolution optical microscope. Spectra of acetaminophen particles with an average size of 5 to 8 microns were obtained. The Raman spectrum of this drug contains characteristic group frequencies assigned to the C = O at 1649 cm-1, the N-H deformation mode at 1620 to 1612 cm-1, the bendstretch mode of the H-N-C = O at 1562 cm-1, the C-H bending mode at 1325 cm-1, and the phenyl ring stretch at 799 cm-1, respectively. The results reported here demonstrate the capability of laser Raman microprobe as a useful adjunct tool for the identification of foreign materials in forensic pathology.

Acetaminophen↗

The spectrum of pathological changes in the lung in children with the acquired immunodeficiency syndrome: an autopsy study of 36 cases.

We present the pulmonary findings in 36 autopsies of children affected by the acquired immunodeficiency syndrome (AIDS). Twenty-three patients were male and 13 were female, ranging in age between 3 days and 13 years. Twenty children had human immunodeficiency virus (HIV)-positive parents or parents who were at high risk of exposure (intravenous drug abusers and prostitutes), five had a history of transfusion, and one had a history of renal transplantation and blood transfusion. Clinically, the patients presented with recurrent infections, failure to thrive, hepatosplenomegaly, fever, cough, and/or hemoptysis. Histologically, specific infectious processes were the most common finding (75% of cases), with Pneumocystis carinii pneumonia being the most prevalent type of infection, followed by bacterial pneumonia. Neoplastic conditions and lymphoid interstitial pneumonia were less frequent (approximately 10% of cases). In addition, in approximately 10% of the cases the pulmonary findings were non-specific (ie, pulmonary edema and atelectasis) and probably unrelated to HIV infection. Our findings suggest that specific infectious conditions constitute the most common type of pulmonary pathology in children with AIDS. However, because there is a small percentage of children with nonspecific findings, a transbronchial biopsy is important for proper evaluation before institution of therapy.

AIDS-Related Opportunistic Infections↗

Veno-occlusive disease of the liver induced by low-dose cyclophosphamide.

A 2-yr-old child with idiopathic pulmonary hemosiderosis and autoimmune thrombocytopenia developed hepatic veno-occlusive disease after being treated with long-term, low-dose cyclophosphamide. The authors believe that the injury was induced by cyclophosphamide. Although transplant dosages of cyclophosphamide alone or in conjunction with other drugs have been shown to induce hepatic venocclusive disease, this is the first case of hepatic venocclusive disease associated with nontransplant dosages of cyclophosphamide. Histopathologically, the injury was characterized by occlusive lesions of intrahepatic veins, both the terminal hepatic venules and portal veins branches, together with necrosis (predominately involving Zones 3 and 2) and hemorrhages. An added risk factor could have been release of platelet-derived growth factor that in turn activated and promoted proliferation of fibroblasts and smooth muscle cells in the vessels. Previously reported cases of cyclophosphamide-related injury are reviewed.

Child, Preschool↗

Geographical pathology profile of AIDS in Puerto Rico: the first decade.

Postmortem histopathological changes in 100 adult patients with AIDS who died in Puerto Rico from 1982 to 1991 were studied and tabulated. Modes of HIV transmission were reviewed. Patient ages ranged from 21 to 60 yr. Gender composition for the patient group was 83 men (average age, 35 yr) and 17 women (average age, 39 yr). Sixty-eight of the patients were injecting-drug users, 20 were homosexual and bisexual men, seven were women who had had heterosexual contact with men at risk for HIV, and one was a man who had had heterosexual contact with prostitutes. Only one case was linked to transfusions of blood. Twenty-seven men and seven women were serologically tested for antibodies and all were HIV seroreactive. The most common causes of infection and the frequency of each were as follows: Pneumocystis carinii in 49 patients; cytomegalovirus in 43; Toxoplasma gondii in 30; Candida species in 24; Histoplasma capsulatum in 18; Mycobacterium species in 14; Cryptococcus species in eight; and Strongyloides stercoralis in six patients. Infection by Schistosoma mansoni (10 patients) was considered incidental because this trematode is endemic in Puerto Rico. The lung was the organ most frequently infected by a single microorganism: Pneumocystis carinii affected 49 patients. However, Cryptococcus species was the microorganism that infected more body systems: 20 different organs in eight patients. Nineteen patients had microglial nodular encephalitis, 86 patients had lymphocyte depletion in the spleen, and 58 had lymphocyte depletion in lymph node tissue. Twenty-seven men had testicular maturation arrest and variable germ cell loss. Three patients had malignant lymphoma, and two had Kaposi's sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

Total parenteral nutrition: a histopathologic analysis of the liver changes in 20 children.

The histologic features of liver biopsies from 20 children treated with total parenteral nutrition (TPN) are presented. All the children received TPN for no less than 2 wk. Conditions that led clinicians to use this form of treatment included prematurity, sepsis, and gastrointestinal surgical procedures. Fourteen children had a history of prematurity; in nine the birth weight was between 640 and 1300 g. Gestational age and birth weight were not available in five and 11 children, respectively. Ten of the 20 children died. Our findings suggest that the morphologic features observed in the liver can be correlated with the duration of TPN. Thus, we propose a time table of hepatic histologic findings beginning with cholestasis and culminating in cirrhosis.

Cholestasis, Intrahepatic↗