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Biomedical subjects

R F Clark

Publications and source records attributed to R F Clark.

At least 55 records · Page 3Linked to original sources
PubMed1997

Affinity-purified, mixed monospecific crotalid antivenom ovine Fab for the treatment of crotalid venom poisoning.

SUBJECT OBJECTIVE: To test the efficacy and safety of a new antivenom, affinity-purified, mixed monospecific crotalid antivenom ovine Fab, in human subjects with minimal or moderate crotalid envenomation. METHODS: We conducted a prospective multicenter clinical trial of 11 patients 10 years or older with progressive manifestations after mild to moderate crotalid snakebite. After giving their consent, subjects received four to eight vials of study drug and were then repeatedly examined over 48 hours and at 7 and 14 days after discharge. Each patient's clinical condition was evaluated serially with the use of a validated severity score, as well as on the basis of the investigator's assessment. RESULTS: In all 11 subjects to the antivenom was judged by the investigator to have had a beneficial response. The severity score for each patient remained the same or decreased over the first 4 hours. However, two subjects demonstrated worsened condition 12 to 15 hours after antivenom administration. In no subject did an allergic reaction develop. CONCLUSION: In this patient group, affinity-purified, mixed monospecific crotalid antivenom ovine Fab was associated with a halt of progressive crotalid venom poisoning. Initial safety data are promising but must be addressed further in subsequent studies.

Adolescent↗
PubMed1997

Successful treatment of crotalid-induced neurotoxicity with a new polyspecific crotalid Fab antivenom.

STUDY OBJECTIVE: To report the effectiveness of a new polyvalent crotalid antivenom on neurotoxicity associated with North American rattlesnake envenomation. Two syndromes of crotalid-induced neurotoxicity have been reported. In severe envenomation by Crotalus scutulatus scutulatus (Mojave rattlesnake), weakness and fasciculations of various muscle groups, including those innervated by cranial nerves, may develop. Occasionally respiratory insufficiency develops. The second neurotoxic effects is myokymia, a type of fasciculation most frequently reported after bites by Crotalus horridus horridus (timber rattlesnake) and Crotalus atrox (Western diamondback rattlesnake). Conventional polyvalent antivenom is often ineffective in the treatment of venom-induced neurotoxicity. METHODS: We report a case series of three patients envenomated by North American rattlesnakes, one of which was identified as C scutulatus scutulatus. All three patients experienced neurotoxicity with weakness, paresthesias, and dramatic fasciculations, along with other signs and symptoms of crotalid venom poisoning. RESULTS: The administration of new polyspecific crotalid antivenom made of ovine Fab was successful in immediately and completely reversing neurotoxicity in each of these patients. CONCLUSION: We report the use of a new antivenom for North American crotalid envenomation that seems to have efficacy in reversing neurotoxicity associated with these bites.

Adult↗
PubMed1997

Association of rattlesnake bite location with severity of clinical manifestations.

STUDY OBJECTIVE: To examine an association between bite location in cases of North American crotalid envenomation and the severity of clinical manifestations. METHODS: We conducted a retrospective review of prospectively collected data for an experimental trial of crotalid antivenom. Our subjects were otherwise healthy individuals with minimal to moderate North American crotalid envenomation. We compared the severity of envenomation for patients with digit bites distal to the proximal interphalangeal joint and bites more proximal using a previously developed and validated snakebite severity score. RESULTS: Thirteen subjects were classified as having distal bites and 24 as having proximal bites. At baseline (before antivenom administration), the distal group had a mean severity score of 2.9 +/- 1.1, whereas the proximal group had a mean severity score of 5.0 +/- 2.2 (P = .0024). Patients in the proximal group tended to demonstrate a more rapid initial decline in severity score after receiving antivenom than did the distal group. CONCLUSION: In minimal to moderate North America crotalid envenomation, patients who sustained bites on distal aspects the digits tended to experience less severe clinical manifestations of envenomation. It is possible that an isolated bite to the distal aspect of a finger is an early marker of minimal envenomation.

Adolescent↗
PubMed1997

Drug-induced hyperthermia.

Drug-related causes of hyperthermia can often be overlooked in the setting of elevated body temperature. This article reviews the pathophysiology, presentation, and treatment of several drug-induced hyperthermia syndromes: malignant hyperthermia, neuroleptic malignant syndrome, sympathomimetic poisoning, and anticholinergic toxicity. Although the general approach is similar, specific management strategies may be required for each syndrome.

Cholinergic Antagonists↗
PubMed1996

Structure and alternative splicing of the presenilin-2 gene.

Missense mutations in the presenilin-1 (PS-1) and presenilin-2 (PS-2) genes have been shown to be causes of autosomal dominant Alzheimer's disease (the AD3 and AD4 loci, respectively). Alternative splicing has previously been reported in the PS-1 gene. In this study, elucidation of intron/exon boundary sequences revealed that PS-2 is encoded by 10 coding exons. In addition, PS-2 cDNA cloning and RT-PCR using RNA from a variety of normal tissues revealed the presence of alternatively spliced products. These products included species with in frame omissions of exon 8 and simultaneous omissions of exons 3 and 4.

Alternative Splicing↗
PubMed1996

Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease.

The presenilin 1 gene has recently been identified as the locus on chromosome 14 which is responsible for a large proportion of early onset, autosomal dominantly inherited Alzheimer's disease (AD). We have elucidated the intron/exon structure of the gene and designed intronic primers to enable direct sequencing of the entire coding region (10 exons) of the presenilin gene in a large number of families. This strategy has enabled us to find a further two novel mutations in the gene. We discuss the distribution of mutations and the proportions of autosomal dominant AD with a mean age of onset below 60 years caused by mutations in this gene.

Alzheimer Disease↗
PubMed1996

Alteration in brain presenilin 1 mRNA expression in early onset familial Alzheimer's disease.

The expression of the presenilin 1 (PS-1) gene has been investigated by in situ hybridization in early onset familial Alzheimer's disease (FAD), late onset Alzheimer's disease (AD) and normal control brain. Mutations in this gene are responsible for chromosome 14-linked FAD. We have found that presenilin 1 mRNA is present throughout the human brain with a distribution consistent with both a glial and neuronal localization. The in situ hybridization pattern was similar for the controls, the early onset FAD cases and the late onset AD cases. However, one of the two forms of the mRNA for PS-1, the long form (which contains a sequence encoding a four amino acid (VRSQ) insert at its 5' end) was significantly reduced in early onset FAD brain compared with late onset AD. We suggest that this long transcript may alter the normal pathway for processing of amyloid precursor protein, the protein which appears to be central in the pathogenesis of AD.

Adult↗
PubMed1996

The use of ondansetron in the treatment of nausea and vomiting associated with acetaminophen poisoning.

BACKGROUND: Nausea and vomiting associated with poisoning can complicate treatment and in some cases delay potential antidote administration. Side effect such as lowering the seizure threshold may at times discourage the use of traditional phenothiazine and butyrophenone antiemetics. METHODS: We performed a prospective, single arm, observational study examining the effectiveness of the 5HT3 receptor antagonist ondansetron in the management if nausea and vomiting associated with acetaminophen poisoning. Patients with a history or laboratory evidence of acetaminophen poisoning were eligible for inclusion in the study. Exclusion criteria included age less than 18 or greater than 65, use of other antiemetic therapy within the previous 12 hours, history of preexisting hepatic or hematologic disease, pregnancy, or significant ingestion of other substances. Upon meeting entry criteria, patients were administered 8 mg of intravenous ondansetron. Nausea was graded on a 100 mm scale with number of emetic episodes recorded before and after treatment. RESULTS: Six patients were entered in the study. All patients had nausea and at least one emetic episode prior to ondansetron and prior to administration of N-acetylcysteine. All patients reported relief of nausea after ondansetron. The degree of nausea decreased by an average of 52% at 30 min and 88% at 60 min following ondansetron administration. No significant vital sign changes were recorded in any patient, and there were no complications related to therapy. Three patients were administered N-acetylcysteine, and all tolerated this therapy without vomiting after ondansetron. CONCLUSIONS: Ondansetron appears to be a potentially useful adjunct in the management of nausea and vomiting associated with acetaminophen poisoning.

Acetaminophen↗
PubMed1996

Hypermagnesemia following an acute ingestion of Epsom salt in a patient with normal renal function.

CASE REPORT: Hypermagnesemia is a rare condition that commonly follows excessive therapeutic administration of magnesium sulfate to treat eclampsia of pregnancy. Signs and symptoms of this condition include extreme muscle weakness, loss of deep tendon reflexes, mental status depression, and cardiac dysrhythmias. Clinically significant hypermagnesemia following oral or rectal administration of magnesium containing products in patients with normal renal function is rare. We report a case of hypermagnesemia following massive Epsom salt ingestion that resulted in extreme musculoskeletal weakness and altered mentation.

Central Nervous System Diseases↗
PubMed1996

The effect of hypertonic sodium bicarbonate on QRS duration in rats poisoned with chloroquine.

OBJECTIVE: To determine efficacy of hypertonic sodium bicarbonate in narrowing QRS prolongation produced by chloroquine. DESIGN: Randomized, controlled animal experiment using an accepted rat model of sodium channel blockade. METHODS: Hypotension and widening of QRS complexes (lead II) of the ECG were produced in 16 rats by administration of a total of 87 mg/kg chloroquine intravenously over 20 minutes. Eight rats were treated with 6 mL/kg 1 M sodium bicarbonate intravenously over two minutes beginning ten minutes into the chloroquine infusion. Serial measurements of QRS duration and systolic blood pressure were obtained for 30 minutes. RESULTS: QRS intervals narrowed more rapidly in animals receiving sodium bicarbonate (p = .045), although the difference in mean rate of narrowing between groups was modest at only .23 msec/min. Because of large variances, no statistically significant differences could be demonstrated in systolic blood pressure. CONCLUSIONS: Hypertonic sodium bicarbonate partially reversed sodium channel blockade and resultant QRS interval prolongation produced by chloroquine in rats. These data should be interpreted with caution, given the need to extrapolate to humans and the modest effect of sodium bicarbonate on QRS narrowing.

Amebicides↗
PubMed1996

Survey of illegal immigrants seen in an emergency department.

There is growing controversy regarding illegal immigrants and their use of social services, including health care, in this country. We surveyed undocumented persons presenting at our emergency department to investigate the reasons why they sought care in the United States. Overall, 227 visits (8.6%) were made in the emergency department by illegal immigrants, mostly Hispanics. Of 104 patients surveyed, all sought care in this country because they were here at the time, and 86 (83%) intended to remain permanently. Of the 104 persons, 83 (80%) cited lack of funding as a reason for seeking emergency department care. Undocumented Hispanics had a higher uninsured rate (64%) than both Hispanics (32%) and non-Hispanics (30%). Of the 104 patients, 38 (36%) had difficulty obtaining care elsewhere because of their status, 53 (51%) knew of no other sources of care, and 46 (44%) said that even if available, only the emergency department was acceptable. Many undocumented persons seek care in the United States because they reside here permanently, often using this emergency department as their source of care. These findings may be important in light of recent efforts to restrict services for this group.

Adolescent↗
PubMed1996

The role of presenilin 1 in the genetics of Alzheimer's disease.

Approximately 75% of AD patients have an onset of the disease after the age of 60 years, and 60% of AD patients have no family history of the disease. Some cases of EOAD are clearly inherited in an autosomal-dominant manner. The beta APP gene on chromosome 21, the PS-1 gene on chromosome 14, and the PS-2 gene on chromosome 1 have all been characterized as genes in which mutations lead to familial EOAD. For LOAD, the work on ApoE indicates that the epsilon 4 allele is a risk factor for developing AD. However, 35-50% of all AD patients do not have an epsilon 4 allele. Other loci contributing to LOAD remain to be mapped and characterized. As in other complex disorders, these additional loci may involve genetic interactions with the known AD loci. Identification of all susceptibility loci for AD is a major goal in resolving the pathogenesis of AD.

Alternative Splicing↗
PubMed1995

A mutation in Alzheimer's disease destroying a splice acceptor site in the presenilin-1 gene.

A series of mutations has been reported in the presenilin-1 (PS-1) gene which cause early onset Alzheimer's disease (AD). The mutations reported to date have encoded missense mutations which alter residues conserved between PS-1 and the presenilin-2 (PS-2) gene. We have recently determined the intron/exon structure of the PS-1 gene and this information has been used to identify a mutation in the splice acceptor site for exon 9 in a family with early onset AD. Amplification of cDNA from lymphoblasts of affected individuals revealed that the effect of the mutation was to cause splicing out of exon 9, however it does not change the open reading frame of the mRNA. The importance of this observation is discussed.

Age of Onset↗
PubMed1995

Raising the decontamination level for thyroid hormone ingestions.

Ninety-two pediatric cases (age < or = 6 years) of acute thyroid hormone ingestions that were reported over a 20-month period to one American Association of Poison Control Centers (AAPCC)-certified regional poison center were reviewed to determine whether significant toxicity in pediatric patients is associated with acute ingestions of < or = 5 mg levothyroxine (T4) equivalent of thyroid hormone and the highest-tolerated milligram-per-kilogram dose. Parameters evaluated included patient weight, amount ingested, drug preparation, treatment type, outcome, management site, and relevant comments. Eight patients had mild symptoms requiring no specific medical intervention and there was no correlation between the amount ingested and symptoms observed. The maximum T4 dose ingested without gastrointestinal decontamination was 0.13 mg/kg (2 mg). A literature review was also conducted. Only one case of moderate toxicity with a dose of less than 5 mg T4 equivalent was found in the literature review. Significant toxicity is not expected with ingestions of less than or equal to 5 mg T4 equivalent of thyroid hormone.

Child, Preschool↗
PubMed1995

Formic acid skin burns resulting in systemic toxicity.

Systemic toxicity developed in a 3-year-old girl burned by formic acid over 35% of her total body surface area. The patient presented with profound metabolic acidosis and a serum formate level of 400 micrograms/mL, the highest reported in the literature for poisoning by any route. The patient was successfully treated with hemodialysis, IV bicarbonate, and supportive measures. Reports of formic acid skin burns and systemic toxicity are limited. We discuss the pathophysiology and treatment of these cases.

Acidosis↗
PubMed1995

Contact dermatitis associated with capsaicin: Hunan hand syndrome.

"Hunan hand" is a contact dermatitis resulting from the direct handling of chili peppers containing capsaicin. Capsaicin also is found in an over-the-counter topical agent for treatment of postherpetic neuralgia, diabetic neuropathy, and arthritis. We present the case of a patient with capsaicin-induced dermatitis and discuss the pathophysiology, therapy, and current uses of capsaicin.

Adult↗
PubMed1995

Iron overdose and detection of gastrointestinal bleeding with the hemoccult and gastroccult assays.

STUDY OBJECTIVE: To determine the ability of the Hemoccult and Gastroccult tests (SmithKline Diagnostics) to detect blood in vitro in whole-bowel irrigation (WBI) solution. INTERVENTIONS: One tablet of ferrous gluconate 324 mg, ferrous sulfate 325 mg, or ascorbic acid 500 mg; or one Materna prenatal vitamin tablet (Lederle Laboratories) was dissolved in 30 mL of Colyte. Colyte alone and each test solution were tested with Hemoccult and Gastroccult slides, then retested at pH values of 3 and 8. Fresh solutions were then spiked with blood and tested with Gastroccult slides. Materna and ascorbic acid solutions were spiked with blood, then tested with Hemoccult slides. RESULTS: Positive results were difficult to detect on Gastroccult slides. Hemoccult slides were falsely positive for solutions containing only iron and falsely negative for blood-spiked samples containing ascorbic acid. CONCLUSION: Both the Hemoccult and Gastroccult tests may be unreliable in detecting GI bleeding in cases of iron overdose treated with WBI.

Ascorbic Acid↗