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Biomedical subjects

P Farmer

Publications and source records attributed to P Farmer.

16 recordsLinked to original sources
PubMed1991

Fungal brain abscesses (aspergillosis/mucormycosis) in two immunosuppressed patients.

Although the mortality rate for fungal brain abscesses in immunosuppressed patients remains unacceptably high, this figure may be reduced if computed tomography or magnetic resonance imaging scans are performed more promptly in susceptible individuals with seemingly mild intracranial complaints. Earlier presumptive amphotericin B treatment and more timely surgical debridement may minimize neurological injury and enhance survival. These assumptions were only tentatively supported by the clinical courses of two patients, one an alert patient with promyelocytic leukemia and an aspergillosis brain abscess who survived, and the other, a comatose intravenous drug abuser with mucormycosis who died.

Adult↗
PubMed1991

Metabolic formation, synthesis and genotoxicity of the N-hydroxy derivative of the food mutagen 2-amino-1-methyl-6-phenylimidazo (4,5-b) pyridine (PhIP).

Hepatic microsomes from rats pretreated with PCB were found to metabolize the food mutagen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) to two major metabolites, one of which was identified as the N-hydroxy derivative, 2-hydroxy-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (N-OH-PhIP). This identification was based on mass spectral (MS), UV and HPLC data by comparison with N-OH-PhIP prepared by chemical synthesis, as well as the specific activity of the compound in the Ames Salmonella test. Synthetic N-OH-PhIP was prepared by catalytic reduction of the nitro derivative of PhIP, which was synthesized from PhIP by diazotization and reaction with sodium nitrite. N-OH-PhIP was mutagenic to Salmonella typhimurium TA98 without metabolic activation and had a specific mutagenic activity of 2700 revertants/nmol. N-OH-PhIP thus seems to be a proximate mutagenic metabolite of PhIP. Other direct acting mutagens were not detected in the microsomal incubation mixture after HPLC separation. N-OH-PhIP also induced sister chromatid exchange (SCE) in Chinese hamster ovary cells (CHO cells) without metabolic activation. The specific activity of N-OH-PhIP in this assay was approximately 3 times higher than the activity of PhIP with microsomal activation.

Animals↗
PubMed1991

Tuberculosis, poverty, and "compliance": lessons from rural Haiti.

Tuberculosis (TB) is the leading cause of death among rural Haitian adults, and TB control in Haiti is widely acknowledged to be a failure. The causes of both the endemicity of TB and the failure of attempts to address it are briefly reviewed before data from a study conducted in rural, central Haiti are presented. Members of one group of patients with active TB were given free medical care; members of a second group were given free care as well as financial aid, incentives to attend a monthly clinic, and aggressive home follow-up by trained village health workers. Comparing the two groups shows significant differences in mortality, sputum positivity after 6 months of treatment, persistent pulmonary symptoms after 1 year of treatment, average amount of weight gained, ability to return to work, and cure rate. The roles of human immunodeficiency virus and cultural factors are also examined. When adequate nutrition and access to free care were assured, drug-dependent and patient-dependent factors were shown to be of secondary importance in determining treatment outcome. Based on these data from a small, community-based TB-control project, the authors conclude that high cure rates can be achieved if the primacy of economic causes of TB is acknowledged and addressed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Characterization of the major metabolites of flavone acetic acid and comparison of their disposition in humans and mice.

Flavone acetic acid represents a novel chemical structure currently undergoing clinical investigation. Broad spectrum activity has been observed in preclinical animal screens, but at doses close to toxic in mice. Phase I clinical trials have established that equivalent plasma drug levels can be achieved in humans, but to date Phase II trials have not demonstrated significant activity in a range of tumor types. Little is known about the drug's biotransformation, although metabolites have been implicated in proposed mechanisms of action. In this paper, we have purified the two major human metabolites present in urine (also the only two metabolites detected in plasma) and characterized their structure, chemical properties, activity, and pharmacokinetics. Metabolite 1 (M1) was a glucuronide conjugated to the 8-acetic acid grouping (Mr 456), was chemically labile, and showed a strong tendency to undergo chemical rearrangement at mildly alkaline pH. Metabolite 2 (M2) was also a glucuronide (Mr 456) but appeared to be an unusual isomer of M1. Both were noncytotoxic. In patients, biotransformation represented the predominant mechanism of drug clearance with as much as 80% of a low dose (0.5 g/m2) recovered in urine as M1 and M2 after only 6 h. At high dose (4.8 to 8.6 g/m2, 1- to 6-h infusion) the appearance of peak concentrations of metabolites in plasma and urine was delayed, apparently due to saturation of glucuronidation pathways. This resulted in an overall reduction in drug clearance by 3- to 4-fold. Mice cleared flavone acetic acid much more slowly than patients (289 ml/h/m2 after 600 mg/m2 i.p. versus 2.3 liters/h/m2 after 4.8 g/m2-1-h i.v. infusion) without producing M1 or M2. A different metabolite, exhibiting characteristics of a conjugate, was detected at low concentrations in plasma, tissues, and tumor. Extensive metabolism to inactive products followed by their rapid clearance may contribute to the lack of activity so far seen in humans.

Animals↗
PubMed1986

The protective effect of profound hypothermia on the canine central nervous system during one hour of circulatory arrest.

Circulatory arrest during profound hypothermia is a safe technique of cardiac surgery when used in selected instances. Despite its proven safety, the degree of cerebral protection offered by this technique is still poorly defined. Ten dogs anesthetized with Pentothal (thiopental sodium) were surface cooled to 32 degrees C. They were placed on cardiopulmonary bypass, cooled to 13 degrees C (cerebral temperature), and then underwent one hour of circulatory arrest. At the end of the arrest period, the dogs were rewarmed, resuscitated, and successfully weaned from bypass. A control group of 6 dogs were subjected to the same protocol but without the one-hour period of circulatory arrest. There were no group differences in animal weight, duration of surface cooling, cardiopulmonary bypass, or rewarming, mean flow, or mean arterial pressure. After a 7-day observation period, the dogs were killed with rapid tissue fixation using formalin. No neurological deficits were noted in any of the dogs during the observation period. The fixed brains were examined by a neuropathologist. No gross or microscopic evidence of cerebral hypoxia was seen in any of the animals. We conclude that one hour of circulatory arrest under profoundly hypothermic temperatures produces no detectable neurological changes or histological evidence of cerebral hypoxia.

Animals↗
PubMed1986

Diagnosis of cerebral toxoplasmosis using fluorescein-labeled antitoxoplasma monoclonal antibodies.

The direct immunofluorescence technique using monoclonal antitoxoplasma antibodies was used to detect Toxoplasma organisms in 13 brain touch preparations and six smears of cerebrospinal fluid. For comparison, Giemsa-stained smears and histologic sections of the same cases were also studied. Positive results were obtained from two cases of acquired immunodeficiency syndrome (AIDS) with all three methods. Toxoplasma cysts, pseudocysts, and tachyzoites were easily identified by the immunofluorescence technique, and no false-positive results were encountered in nine cases of AIDS with different kinds of encephalitides. It was difficult to identify tachyzoites in histologic sections and time-consuming to search for pseudocysts and cysts. The parasite was even more difficult to recognize in Giemsa-stained brain touch preparations due to the easy distortion of the organisms. In the present study, immunofluorescence technique was more sensitive than hematoxylin--eosin or Giemsa staining in terms of the number and range of forms demonstrated in tissue. Therefore, immunofluorescence technique using monoclonal antibodies appears to be the preferred method for a rapid diagnosis of cerebral toxoplasmosis as compared to Giemsa staining and histology.

Antibodies, Monoclonal↗
PubMed1979

Carcinoma of choroid plexus in a premature infant.

A histologically proven case of choroid plexus carcinoma in a 5-week-old infant is presented. Computed tomography showed invasion through the ventricular wall, suggesting its malignant nature.

Adenocarcinoma, Papillary↗
PubMed1979

Toxic substances in spinal cord injury.

Several investigators have implicated norepinephrine and other toxic substances released in the region of a spinal cord injury in the genesis of the progressive pathological and clinical changes that follow spinal trauma. To test this hypothesis, we subjected cats to T-10 to T-12 laminectomy and monitored epidural spinal evoked potentials from sciatic nerve stimulation. The spinal subarachnoid space was perfused with normal saline, with norepinephrine solution, or with heparinized autologous blood or the pial surface of the spinal cord was exposed to macerated gray matter taken from the upper cervical cord. During 1- to 2-hour exposure periods, we noted no significant changes in the base line spinal evoked potentials. In another series of cats, we have shown that norepinephrine perfused over the spinal cord in this manner diffuses rapidly into the subpial white matter. Therefore, its failure to affect spinal evoked potentials does not represent a failure to penetrate the spinal cord. Putative toxins must originate either in extravasated blood or damaged neural tissue in the region of the spinal cord injury. The failure of ascending spinal tracts to react to blood or cord tissue in our experiment suggests that toxins are not involved in the spinal cord dysfunction that occurs soon after injury.

Animals↗
PubMedDate not supplied

Multiple ischemic infarcts in a child with AIDS, varicella zoster infection, and cerebral vasculitis.

A 4 1/2-year-old girl with acquired immunodeficiency syndrome and prolonged varicella zoster virus skin infection developed multiple ischemic strokes and radiologic and histopathologic evidence of central nervous system vasculitis. Typical features of acquired immunodeficiency syndrome encephalitis were not present and there was no evidence of vasculitis outside the nervous system. Central nervous system vasculitis probably resulted from varicella zoster virus infection that persisted because of immunodeficiency. This acquired immunodeficiency syndrome complication has only rarely been described in adults and to our knowledge has not been described in children.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Prostaglandin synthesis inhibitors block alcohol-induced fetal hypoplasia.

Alcohol-induced growth retardation is a fetal effect consistently associated with maternal ethanol consumption. In humans, those infants whose mothers consume even a limited amount of ethanol during pregnancy have a significant incidence of growth inhibition. The molecular mechanism responsible for this growth deficiency is unknown, and prevention depends on maternal abstinence during pregnancy. The data reported here suggest that ethanol-mediated increases in tissue prostaglandin (PG) E levels (PGE1 plus PGE2) are correlated with the growth retardation. Further, simultaneous administration of PG synthesis inhibitors with the alcohol blocks the rise in tissue PG levels and protects against the alcohol-induced hypoplasia.

Animals↗
PubMedDate not supplied

Mechanical aids.

Explore the source record for details and available documents.

Back Pain↗
PubMedDate not supplied

Fat within the falx: MR demonstration of falcine bony metaplasia with marrow formation.

Falcine bony metaplasia frequently is incorrectly labeled "dense calcification" on brain CT and conventional radiography. Of 3,000 brain magnetic resonance (MR) scans reviewed, 12 demonstrated a central area of increased signal intensity on T1 and T2 weighted images with a smooth peripheral rim of diminished signal intensity within the region of the falx. The central area of increased signal intensity corresponded to fat in the medullary cavity and the peripheral area of low signal intensity corresponded to cortical bone. The CT scans, available in nine of 12 patients, were compared with the MR scans and revealed dense mineralization in the corresponding region of the falx. A postmortem specimen of densely "calcified" falx cerebri was examined that revealed cortical bone and a medullary cavity complete with bony trabeculae and marrow. The MR findings of falx ossification should not be confused with other entities of greater clinical significance.

Adipose Tissue↗