Coxofemoral luxation in a border collie as a complication of a Clostridium tetani infection.

A four-month-old male, entire, border collie was presented to the Queen Mother Hospital for Animals with a two day history of muscular spasms and "Risus sardonicus". Tetanus was diagnosed, and the dog was treated with tetanus antitoxin, antibiotics and supportive therapy. Coxofemoral luxation resulted as a complication of the tetanus and was successfully managed by performing a femoral head and neck excision. This is the first report of joint luxation associated with Clostridium tetani infection in a dog.

Hypertrophic osteopathy secondary to pulmonary sarcoma in a cat.

A case of hypertrophic osteopathy secondary to a pulmonary spindle cell sarcoma is described. The 9-year-old male cat presented with a 1-month history of decreased appetite, decreased activity and progressive lameness with swelling and pain of all four limbs. Thoracic radiographs showed a soft tissue opaque mass in the left caudal lung lobe. Radiographs of all limbs showed extensive periosteal new bone formation of uniform opacity demonstrating a 'palisading' pattern. The lung mass was removed at exploratory thoracotomy; histopathological examination diagnosed a low-grade spindle cell sarcoma. Prior to surgery, the cat had a non-specific conjunctivitis that resolved spontaneously following lobectomy raising the possibility of a paraneoplastic association. The lameness also resolved; six months after surgery, the periosteal palisading of new bone on the long bones had remodelled, and there was no evidence of pulmonary metastases.

Simultaneous pancreas and kidney transplant rejection: separate or synchronous events?

The results of simultaneous pancreas and kidney transplantation (SPK) cannot be matched by pancreas transplantation alone (PTA), in part because an independent diagnosis of pancreas graft rejection remains difficult. The relationship between rejection of the pancreas and rejection of the kidney is poorly understood, and it is not known whether simultaneous transplantation of both organs confers true protection to either graft. To study these questions, reliable canine allotransplant models of kidney transplantation alone (KTA), PTA, and SPK were established. Sixty-seven mongrel dogs received KTA (n=21), PTA (n=23), or SPK (n=23) with either no immunosuppression, low-dose cyclosporine (CsA)-based immunosuppression, or high-dose CsA-based immunosuppression. Needle core biopsy (NCB) and fine needle aspiration biopsy (FNAB) were performed at 0, 2, 4, 7, 9, 11, 14, 21, and 30 days or at the time of graft failure. Pancreas and kidney graft survival after SPK was significantly shorter in dogs given low-dose CsA than in dogs given high-dose CsA (pancreas, P<0.04; kidney, P<0.03). Concurrent NCBs and FNABs were performed on 227 occasions in pancreas grafts and 229 occasions in kidney grafts. The time to initial evidence of rejection by NCB was not different in any immunosuppressed group. Synchronous rejection occurred in 73% of immunosuppressed SPK biopsies. Kidney-only rejection occurred in 23% of biopsies and pancreas-only rejection occurred in only 3% after SPK. All markers of pancreas graft rejection were poor, with the most sensitive being NCB of the simultaneously transplanted kidney. In summary, recipients of SPK required more immunosuppression than recipients of PTA, and improved PTA survival should be achievable with more sensitive markers of rejection. Markers of kidney rejection were the most sensitive indicators of pancreas rejection, and independent pancreas rejection was uncommon after SPK.

Experimental hyperacute rejection in pancreas allotransplants.

A model of sensitization by intraperitoneal lymph node inoculation was developed to test the hypothesis that hyperacute rejection (HAR) could occur in sensitized recipients of vascularized pancreas allografts. Ten pairs of outbred mongrel dogs that were lymphocytotoxic cross-match assay negative were inoculated with homogenized lymph nodes on either three or four occasions at fortnightly intervals before renal transplantation. A renal allograft from the same donor was used to test the HAR response and to further enhance sensitization by rejection of a vascularized organ. Pancreas transplants were performed 2 weeks later, with biopsies of the graft and blood samples taken at 0, 10, 20, and 30 min and then at 30-min intervals until the grafts were no longer viable. All renal and pancreas grafts were rejected in a classical hyperacute pattern. Within 4 min of revascularization of the pancreas, central lobular hemorrhage and vascular congestion appeared, followed by general edema. Histology demonstrated parallel changes of edema, vascular congestion, necrosis, hemorrhage, and leukocytic infiltrate, which all preceded graft infarction. A sharp decline in both arterial and venous white blood cell count and platelets occurred within 10 min of revascularization with initial sequestration and subsequent release of platelets from the graft (P=0.02). In summary, HAR of the allografted pancreas can be observed by the surgeon within minutes of revascularization, with predictable macroscopic and microscopic changes. This study supports the use of routine lymphocytotoxic cross-match tests for all recipients of pancreas transplants and implies that particular care is warranted in regraft pancreas allograft recipients.

Interferon alfa for chronic active hepatitis B. Long term follow-up of 62 patients: outcomes and predictors of response.

OBJECTIVE: To evaluate the response to treatment with interferon alfa and the long term outcome of patients with chronic active hepatitis B. METHODS: Sixty-two patients with chronic active hepatitis B (43 males, 19 females; age range, 10-67 years) who were treated with interferon alfa at Westmead Hospital between 1984 and 1992 were followed up (mean period of follow-up, 44 months). Thirty-nine patients were treated with interferon alfa-2a and 23 with interferon alfa-2b for a mean of 22.5 weeks. Interferon was given three times a week with a dose range of 3-21 million U. We evaluated pretreatment predictors of response (patient's age, sex, ethnic origin, presence of cirrhosis, serum levels of alanine aminotransferase [ALT] and hepatitis B virus DNA [HBV-DNA]) and the effect of dose and type of interferon. RESULTS: Nine patients had a complete response to treatment with interferon alfa (loss of hepatitis B surface antigen), 26 had a partial response (permanently HBV-DNA negative, hepatitis B e antigen to anti-hepatitis Be seroconversion), eight had a transient response and 19 had no response. All patients with a complete response had normal ALT levels at last follow-up. Histological evidence of hepatic inflammation was significantly reduced in responders. A high pretreatment ALT level and a low HBV-DNA titre were both positive predictors of a favourable response. We found no significant difference in the response to different types of interferon or to high or low dose regimens, or in the responses of patients with cirrhosis. CONCLUSION: Treatment with interferon alfa was associated with prolonged suppression of HBV replication in over half these patients and 14% appear to have been cured of the infection. Suppression of HBV replication is associated with sustained abatement of liver disease.

Coinfection with hepatitis B and C or B, C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment.

Chronic coinfection with the hepatitis B (HBV) and hepatitis delta (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-alpha 2b (IFN-alpha) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied; 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheuer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-alpha 2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and delta coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Rectal spirochaetosis in homosexual men: the association with sexual practices, HIV infection and enteric flora.

OBJECTIVE: To determine the prevalence of rectal spirochaetosis in homosexual men attending a sexually transmissible diseases clinic and investigate the association between their presence and sexual practices, HIV infection and enteric flora. DESIGN: The study included 144 male homosexual subjects who each completed a questionnaire, underwent physical examination, proctoscopy and investigations for STD and HIV screening, rectal biopsies and collection of faecal samples. SETTING: The Sexual Health Centre, Sydney Hospital, Sydney, Australia. RESULTS: Spirochaetes were detected in 39% of the rectal biopsies, using histological criteria. Logistic regression analysis showed that rectal spirochaetosis was significantly associated with: oral-anal contact. (P < 0.05, OR 3.45, 95% CI 1.48-8.05); detection of 3-5 different non-pathogenic protozoa in faeces (P < 0.01, OR 11.68, 95% C.I. 2.33-58) and a positive HIV antibody test (P < 0.01) OR 4.48, 95% C.I. 1.28-15.72). CONCLUSIONS: These findings indicate that rectal spirochaetosis is relatively common in homosexual men. The association with non-pathogenic protozoa is most likely attributable to the common mode of transmission viz oral-anal contact. However it is difficult to determine whether the association with HIV infection is cause or effect because of the limitations in the study design. Further information is required to determine the clinical significance of infection with these organisms.

Solid and papillary epithelial tumour of the pancreas: cytological case study with ultrastructural and flow cytometric evaluation.

An intraoperative cytological diagnosis of a rare solid and papillary epithelial tumor of the pancreas was made at laparotomy in a 15-year-old Indian female. The characteristic cytological features were the presence of numerous large branching papillary clusters with central vascular stalks lined by multiple layers of uniform bland cells. Perivascular metachromatic material was prominent on Romanovsky stain. Ultrastructural identification of endocrine and exocrine features supports a multipotential cell origin in small pancreatic ductules. DNA analysis, not previously reported for this tumour, demonstrated a diploid population of tumour cells with a low S-phase fraction (0.4%). This would explain the bland nuclear morphology and favourable prognosis with a high rate of surgical cure for this neoplasm.

A case of cholangitis glandularis proliferans and cholangiocarcinoma of the common bile duct.

A case of Cholangitis Glandularis Proliferans (CAGP) in association with a cholangiocarcinoma of the common bile duct as described. This is the eighth case of CAGP described and the second association with cholangiocarcinoma.

Nonspecific proctitis: association with human immunodeficiency virus infection in homosexual men.

In a cross-sectional study of 140 homosexual men attending a sexually transmissible diseases clinic, the association between the presence of antibody to the human immunodeficiency virus (HIV) and the presence of proctitis, as determined by histologic examination, as well as part or present exposure to other pathogens and details of sexual practices was analyzed. Significant associations with HIV seropositivity were found with the number of lifetime partners, positive treponemal serology, and evidence of previous infection with herpes simplex virus. However the major and unique finding was the strong and independent association between proctitis diagnosed by histologic criteria and seropositivity for HIV. Whether this is cause or effect awaits further elucidation.

Percutaneous biopsy of bladder-drained pancreas transplants.

Percutaneous biopsy is a valuable investigation in the management of allograft rejection for all solid organs. Pancreas transplants have not been biopsed percutaneously, though open and percystoscopic biopsies have proved useful. We have compared percutaneous needle core biopsy with fine-needle aspiration cytology for the diagnosis of rejection in 18 patients receiving combined kidney and pancreas transplants and in one who was transplanted with the pancreas alone. Percutaneous needle core biopsy was successful in 37 of 40 attempts (93%), while fine-needle aspiration yielded diagnostic material on 33 of 47 attempts (70%). Transient hyperamylasemia occurred in 29%, returning to baseline in three days. One patient twice developed transient macroscopic hematuria. There was agreement between needle core biopsy and fine-needle aspiration on the diagnosis of rejection on six occasions and for the absence of rejection on 16. There was an 8% false-positive rate for fine-needle aspiration. In 13 instances of histologically proved renal rejection, concurrent pancreas biopsy revealed rejection in 69%. Pancreas rejection was not, however, seen in the absence of renal rejection. In this pilot study, percutaneous biopsy of the bladder-drained pancreas allograft was shown to be a practicable and valuable investigation without major complications.

Longitudinal histopathologic assessment of rejection after bladder-drained canine pancreas allograft transplantation.

In preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program, a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder-drained whole pancreas allografts. Edema, extravasation of polymorphs, and lymphocytes associated with focal parenchymal injury were early, invariable, and probably nonspecific findings. The initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred early and was progressive, whereas islets and ducts were relatively preserved, indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged. Functional rejection, determined by fasting urinary amylase levels, was at a stage of extensive and irreversible necrosis. Functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class II antigen staining of parenchymal cells.

Canine pancreas and kidney transplantation following total-lymphoid irradiation.

The effect of total-lymphoid irradiation on survival of canine pancreas and kidney allografts was studied. TLI had a marked immunosuppressive effect as measured by in vitro immune responses and reduced circulating leukocytes. Despite the changes, median graft survival times for animals treated with 800 cGy (9 days) or 1800 cGy (9.5 days) were not significantly different from untreated control animals (7 days). The addition of low-dose antithymocyte globulin (10 mg/kg/day) on post-transplant days 0, 2, 4, 6, 8, and 10 had no measurable synergistic effect. Similarly, median segmental pancreas allograft survival times after 1700-2200 cGy of TLI treatment (16.5 days) were only marginally longer than those of untreated controls (9 days). The only animal to maintain a graft for greater than 200 days was matched to the donor in mixed lymphocyte culture (MLC). This animal was able to reject a third-party skin graft after 8 days while a graft from the original donor was still surviving after 21 days when the pancreas graft failed from a chronic-type rejection. These results indicate that TLI alone or in combination with ATG will not be predictably effective as a method of prolonging allograft survival. The role of matching major histocompatibility complex antigens in TLI treatment requires clarification.

Randomised controlled trial of recombinant human interferon -alpha A for chronic active hepatitis B.

The efficacy of interferon treatment for Australian patients with chronic active hepatitis B (CAH-B) was assessed by a three-centre randomised controlled trial in Sydney and Brisbane. Thirty patients (29 with histologically-proven CAH-B with and without cirrhosis and one with chronic persistent hepatitis) were allocated to receive either thrice weekly intramuscular injections of recombinant human leucocyte interferon -alpha A (either 2.5, 5.0 or 10.0 million units/m2) for six months followed by 12 months of observation, or to be observed for 18 months without active treatment. Three of 23 treated patients but none of seven controls underwent clinical, biochemical and histological resolution of their disease with loss of HBsAg, HBeAg and HBV-DNA from serum. An additional six treated and two control patients underwent a sustained partial remission of their disease. This was characterised by resolution of symptoms and serum aminotransferase abnormalities in association with seroconversion from HBeAg positive to negative, loss of HBV-DNA from serum but persistent hepatitis B surface antigenaemia. In such patients, there was significant improvement in histological appearances but some necroinflammatory activity remained and fibrosis was unchanged. Although total response rates were similar in treated and control subjects, they appeared to occur earlier after interferon treatment. Treatment with interferon was associated with predictable but minor side effects that usually did not necessitate dose reduction and rarely compromised the patient's life style. Interferon is thus a feasible treatment for CAH-B. Complete responses occurred only in treated patients and partial responses appeared to occur earlier in treated than in untreated patients. However, differences in the partial response rate at 18 months were not significant and seroconversion from HBeAg positive to negative was not associated with complete histological resolution of disease activity. Hence, while interferon is a promising agent for treatment of CAH-B, efforts must continue to define more optimal treatment regimes and to identify those patients most likely to respond to this agent.