One thousand cases of appendicitis seen from 1963 to 1973 were reviewed. The overall negative appendectomy rate was 20%, but in women between ages 20 and 40 it exceeded 40%. Two thirds of the negative appendectomies were due to nonsurgical lesions. Mesenteric adenitis, gastroenteritis, and abdominal pain of unknown cause accounted for one third of the errors in females and two thirds in males. These diseases were best distinguished from appendicitis on the basis of temperature and white blood cell count. The remainder of the errors in females were due to pelvic inflammatory disease or other gynecologic diagnoses and were best distinguished from appendicitis on the basis of history and physical findings. The rate of perforation was 21% overall. The incidence of wound infection was 8.5%. Use of systemic antibiotics did not affect the wound infection rate.

Appendicitis. A critical review of diagnosis and treatment in 1,000 cases.

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P=3.8610 25 ), establishing a novel phenotype for this genetic variant.

/pdf/reduced-neutrophil-count-in-people-of-african-descent-is-due-4978bs93wt.pdf

Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene

Antifibrinolytic drugs are widely used to reduce blood loss during surgery. One serious adverse effect of these drugs is convulsive seizures; however, the mechanisms underlying such seizures remain poorly understood. The antifibrinolytic drugs tranexamic acid (TXA) and e-aminocaproic acid (EACA) are structurally similar to the inhibitory neurotransmitter glycine. Since reduced function of glycine receptors causes seizures, we hypothesized that TXA and EACA inhibit the activity of glycine receptors. Here we demonstrate that TXA and EACA are competitive antagonists of glycine receptors in mice. We also showed that the general anesthetic isoflurane, and to a lesser extent propofol, reverses TXA inhibition of glycine receptor–mediated current, suggesting that these drugs could potentially be used to treat TXA-induced seizures. Finally, we measured the concentration of TXA in the cerebrospinal fluid (CSF) of patients undergoing major cardiovascular surgery. Surprisingly, peak TXA concentration in the CSF occurred after termination of drug infusion and in one patient coincided with the onset of seizures. Collectively, these results show that concentrations of TXA equivalent to those measured in the CSF of patients inhibited glycine receptors. Furthermore, isoflurane or propofol may prevent or reverse TXA-induced seizures.

/pdf/tranexamic-acid-concentrations-associated-with-human-7kfpnbotae.pdf

Tranexamic acid concentrations associated with human seizures inhibit glycine receptors

Appendicitis is a condition characterized by inflammation of the appendix. All cases require removal of the inflamed appendix, either by laparotomy or laparoscopy. Untreated, mortality is high, mainly because of peritonitis and shock.[1] Reginald Fitz first described acute and chronic appendicitis in 1886,[2] and it has been recognized as one of the most common causes of severe acute abdominal pain worldwide.

Appendicitis

Patient-controlled analgesia is a relatively new and investigational technique that permits patients to treat pain by directly activating doses of intravenous narcotics. The technique was developed in response to the undertreatment of pain in hospitalized patients. Continuous narcotic infusion and intraspinal narcotic administrations also have the potential to provide continuous, uninterrupted analgesia, but do not allow simple dose attentuation to avoid overdosage. Patient-controlled analgesia is used to treat postoperative and labor pain and pain associated with terminal illness; it delivers analgesic more effectively with fewer side effects than conventional parenteral narcotic therapies. The technique is also an ideal investigative instrument for studying equianalgesic states. Several foreign-made devices are now being used under investigational sanctions in this country, and it is anticipated that several American manufacturers will be seeking regulatory approval to market the devices.

/pdf/patient-controlled-analgesia-5c6dk9624e.pdf

Patient-controlled analgesia

AMINOCAPROIC acid is a useful agent in the management of hemophilia, particularly following extensive dental manipulations. The drug is widely used, in large measure because toxic reactions, including gastrointenstinal disturbances, dizziness, tinnitus, malaise, headache, rash, and conjunctival and nasal suffusion, are mild and rarely encountered. We report the case of a patient who experienced several of these side effects after aminocaproic acid infusion, then promptly progressed to a grand mal seizure, a toxic reaction not previously described. Report of a Case A 32-year-old man with mild hemophilia (factor VIII levels ranging from 10% to 15%) was admitted for dental scaling and prophylaxis. The patient's hemophilia had been identified two years prior to this admission, when he had bled excessively after dental extraction. At that time, von Willebrand's disease had been excluded by a normal bleeding time and ristocetin aggregation study. He had a long history of dental problems and had

Seizure after infusion of aminocaproic acid.

A 63-year-old man presented with fever, easy bruisability, splenomegaly and pancytopenia. Bone marrow aspiration was unsuccessful, and marrow biopsy revealed crowding by sheets of mononuclear cells; a diagnosis of leukemic reticuloendotheliosis (LRE) was made and the patient underwent splenectomy. There was no hematologic improvement, and the patient continued to have a significant requirement for erythrocytes and platelet transfusions. Within two months of beginning oxymetholone therapy (50 mg orally three times a day) the patient's platelet count had normalized, followed by improved erythrocyte and leukocyte counts. When the drug was discontinued, the peripheral blood counts deteriorated drastically; he again demonstrated hematologic improvement when oxymetholone therapy was reinstated. We feel that by demonstrating a hematologic response to oxymetholone, relapse when it was withdrawn, and another remission upon readministration, that we have provided stronger evidence than previously reported for the efficacy of this drug in LRE.

A case of leukemic reticuloendotheliosis responding to oxymetholone.

To the Editor— The tables in our article "Leukocytosis in Acute Appendicitis" (229:1630, 1974), incorrectly labeled "standard error of the mean," should read "mean and ± one standard deviation" Furthermore, recalculation from the raw data substantiates that the P value for total white blood cell counts is less than 01 rather than 001Although these corrections will not change the meaning of our observation, we believe they should be noted

Leukocytosis in Acute Appendicitis

To the Editor.— The statement by Alderman (229:1647, 1974) that "meperidine hydrochloride in parenterally administered doses of 75 mg provides effective analgesia of the same duration as does 10 mg of morphine sulphate" is counter to that of standard texts and journals of pharmacology 1-3 and is not consistent with our own experience. While it is accepted that the meperidine dose equivalent to 10 mg of morphine is 75 to 100 mg, duration of analgesia by meperidine may be as little as 50% that of morphine. This may not be observed when the pain of myocardial anoxia is fully or partially relieved during the first or second administration of analgesic, but in chronic or sustained pain, such as occurs in malignant invasion of bones or in sickle cell crisis, the difference is readily apparent to the alert physician and nurse. It has been suggested that physicians are undertreating patients in pain.

Meperidine vs Morphine

To determine if the relative neutropenia previously reported in healthy American, West Indian, and African blacks might also occur in patients with inflammatory disease, preoperative white blood cell (WBC) counts were compared among 112 cases of histologically proven acute appendicitis. Statistically significant lower WBC and neutrophil counts were found in black patients than in an identical group of whites. ( JAMA 229:1630-1631, 1974)

Leukocytosis in acute appendicitis. Observed racial difference.

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