A HIGH FREQUENCY OF INHERITED DEFICIENCY OF COMPLEMENT COMPONENT C4 IN DARWIN ABORIGINES

Abstract A high frequency of serum complement component C4A deficiency may explain the higher prevalence and greater severity of systemic lupus erythematosus reported in Australian Aborigines. Inherited deficiencies of serum complement components C4A, C4B, and C2 were examined in two Australian Aboriginal populations from Darwin and Alice Springs and compared with the prevalence of complement deficiencies in white Australian blood donors. The frequency of C4A deficiency alleles was 29% in Darwin Aborigines compared with 12% in Alice Springs and 17% in Canberra blood donors. Partial C4B deficiency was also higher in Darwin Aborigines than in the other populations. Inherited deficiency of serum complement component C2 was not observed.     

Shouldice hernia repair: results at a teaching institution

Authors with wide experience report that the Shouldice technique for repair of inguinal hernia is very effective. The technique has not gained widespread acceptance or notoriety. For example, the 13th edition of Textbook of Surgery, edited by Sabiston, devotes only one paragraph to this type of herniorrhaphy. Because of the excellent results reported by the Shouldice Clinic, this technique was adopted at the Augusta Veterans Administration Hospital, a teaching hospital of the Medical College of Georgia. Since 1976, a total of 604 Shouldice repairs have been performed by supervised house staff; 468 patients have been followed for up to 8 years and a recurrence rate of 1.3 per cent is reported. Although the follow-up is brief, the Shouldice hernia repair is widely applicable and good results are not dependent on wide experience alone.     

Immunotoxicology studies on octoxynol-9 and nonoxynol-9 in mice

In a double-blind study, mice were injected intraperitoneally with 0.2 ml 0.2% octoxynol-9 (O-9), 0.2 ml 0.2% nonoxynol-9 (N-9), or 0.2 ml saline (control) daily for 24 days. Another control group received no treatment. All mice were immunized twice with sheep red blood cells (SRBC) and bled by caudal incision. Mice receiving N-9 lost weight (P less than 0.02), had smaller livers (P less than 0.05), and showed enlarged spleens (P less than 0.05). The N-9-treated mice did not differ from either control group in the primary or secondary anti-SRBC responses, leukocyte (WBC) counts, or in the sizes of the kidneys, hearts, lungs, or thymuses. Mice receiving O-9 showed no significant differences from either control group in any of these tests. Serum immunoglobulin M (IgM) and immunoglobulin G (IgG) levels were similar in mice treated with O-9, N-9, or saline. All 3 groups had higher levels of both classes of immunoglobulins on day 16 than did untreated controls. This study shows that O-9, given to mice in doses 3 times that used by humans, is nontoxic, whereas the same dose of N-9 has minor deleterious effects.     

Nasal fractures in children

Summary A group of thirty children with nasal fractures was evaluated retrospectively by means of a questionnaire and hospital records. Age at the time of injury ranged from age 3 to 12 (mean = 8.6) years and mean follow-up period was 9 years. Eight patients reported some degree of nasal obstruction post reduction, but only one patient required submucous resection and two patients underwent septorhinoplasty for appearance. No patients reported class III malocclusion, or required orthodontic treatment or maxillofacial corrective surgery for maxillary hypoplasia. We concluded that a childhood nasal fracture treated by closed reduction does not have deleterious effects on facial or nasal growth.This work was supported in part by the Brigham Surgical Group Foundation, Inc., Boston, Massachusetts, USA     

Contradictory antitumor efficacies produced by the combination of DNA attacking drugs and polyamine antimetabolites

The antitumor effects of two polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), when combined with cis-diamminedichlroplatinum (CDDP) or mitomycin C (MMC), were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO 1000 mg/kg and MGBG 50 mg/kg were given intraperitoneally for 6 successive days, while CDDP 3 mg/kg or MMC 2 mg/kg was given every second day. Although DFMO and MGBG plus MMC did suppress the tumor growth, the combination with CDDP led to no suppression, and rapid growth occurred after the cessation of therapy. The inhibition of tumoral DNA biosynthesis and a decline in polyamine levels, were also not observed. The polyamine antimetabolites when used with CDDP did not produce the desired antitumor efficacy, even though the platinum concentration in the tumor tissue was high. On the contrary, however, DFMO and MGBG when combined with MMC did suppress tumor growth, inhibited DNA biosynthesis, and tissue polyamine levels were low. These results suggest that though CDDP and MMC belong to a similar category of DNA attacking, bifunctional alkylating agents, the findings of these two drugs are contradictory. Here, the mechanism of action no doubt plays a contributory role.     

Pharmacokinetics of ethylenediaminemalonatoplatinum(II) (JM-40) during phase I trial

Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin.     

Inborn errors of the urea cycle

Inborn errors of the urea cycle are an important cause of hyperammonaemia throughout childhood, and are associated with high morbidity and mortality rates. If they are diagnosed early and treated appropriately, the outcome for affected children is significantly improved.     

Polymorphonuclear leukocyte function in psoriasis vulgaris

Polymorphonuclear leukocyte (PMN) migration was assessed in vitro using the agarose plate method in patients with psoriasis vulgaris, and compared with an age- and sex-matched control group. No significant difference was found between the two groups in the PMN response to the chemotactic substances F-Met-Leu-Phe (FMLP) or zymosan activated serum (ZAS). Equally, the chemokinetic or chemotactic potential of psoriatic serum did not differ from control serum. Our results do not support a primary abnormality of PMN function in psoriasis.